WO2003070714A1 - Fluorous acetylation - Google Patents

Abstract

The present invention relates to a method for the synthesis of highly fluorinated compounds and to novel highly fluorinated compounds. In particular, the present invention relates to the synthesis of highly fluorinated acetals and ketals and their thio analogues and to novel highly fluorinated acetals and ketals and their thio analogues.

Description

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  Technical Field 
The present invention relates to a method for the synthesis of highly fluorinated compounds and to novel highly fluorinated compounds. In particular, the present invention relates to the synthesis of highly fluorinated acetals and ketals and their   1 hie   analogues and to novel highly fluorinated acetals and ketals and their thio analogues. 



  Background   Pluorous   chemistry is emerging as a powerful adjunct to traditional solution and solid phase methods   of parallel and combinatorial synthesis. Fluorous techniques are   highly applicable to new drug discovery programs that are being actively pursued worldwide. Further development of this important field presents new challenges to chemists and those interested in solution phase pharmaceutical development. 



  Introduction to Fluorous Chemnistry 
Fluorous chemistry is a young science. Whilst there are sporadic reports of chemistry in fluorous solvents in older literature, the systematic study of fluorous chemistry began in 1994,   2   and has spanned fluorous   biphasic     catalysis2a°   and conventional organic   synthesis 2 h   shown promise as an adjunct to solid phase and template methods   of combinatorial synthesis, 3   and has provided new separation techniques. 4 The following is a brief outline of the concept and of its current status. 



   Several highly fluorinated solvents are commercially available and they readily solubilise fluorinated compounds but not purely organic or polar inorganic compounds. 



  The fluorous solvents are therefore immiscible in many conventional organic solvents and water, and indeed a mixture of the three separates into three phases. Organic materials are partitioned between the three phases depending upon their polarity and degree   offtuonnation. This permits organic   substrates to be treated in organic solvents with fluorinated reagents and then to have excess reagent or reagent   byproducts   removed by   washing with a fluorinated solvent. Conversely, if the   reagent introduces fluorine into the organic substrate, then substrates can be transported into the fluorinated solvent leaving unchanged material in the purely organic solvent The physical operation of solvent extraction is very easy to perform, is amenable to large scale synthesis, and is technically non-demanding. 



   Many of the requirements for useful separations using the technique have been delineated, 3, 4 and high yields and improved separation efficiencies have been achieved by using various fluorous-phase strategies in which very different chemistry is involved. Synthetic strategies have included the use of highly   fluorinated phosphorus   

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 ligands,   5     triaJkyltin and tiialkylsilicon   reagents, 7   meditation   of reactants through introduction of highly fluorinated   trialkylsilicon   appendages,   8   and derivatisation of products   with highly fluorxnated trialkylsilicon groups   to achieve high yields and excellent separation characteristics.

   4 These examples convincingly demonstrate the power of doing chemistry in the fluorous phase. 



   It should be noted that a key element in these separation strategies is that expensive   perSuorinated   solvents need not be used during reactions. Instead, an inexpensive hybrid solvent, such as supercritical   GO9   or   trifluoromethylbenzene   (benzotrifluoride, BTF), 10 can be used for   ffuorous and organic reactants. Reactions   can be performed in BTF, or in   BTF-organic   solvent combinations, and separations effected at a later stage by partitioning the products between an organic solvent, typically dichloromethane   (and H20   if necessary), and a fluorous solvent, e. g. FC-7211 (an expensive but recyclable, low boiling fluorinated solvent).

   Alternatively, reactions in   supercritical   C02 can be diluted with PC-72, the   COz   allowed to evaporate, and   non-fluorous   products precipitated from the fluorous solution, 
A more recent advance has been the discovery that   less Yluorousv substances,   that need not be fully partitioned into a fluorous solvent nor be completely insoluble, can be retained on fluorous reverse phase silica gel   RPS)   in water or polar to moderately polar organic solvents. 6c,12 This development permits another mode of separation, called solid phase extraction (SPE) to be   used. The SPE   process is akin to chromatography but is performed more like filtration. It has become valuable for cleanup of products in conventional   combinatorial   synthesis.

   In its fluorous modification, mixtures are filtered through a bed of the   fiuorous   gel to remove non- fluorous material. The fluorous component is then recovered by washing the gel with a fluorophilic solvent, such as BTF or ether. this goes beyond existing applications in which SPE is used to remove unwanted   byproducts.   It also has advantages over purely solid phase techniques, which rely heavily upon filtration, because the fluorous tag does not need to be removed to   resolubilise   the product. 



   Despite the very significant progress in modern fluorous chemistry, advances have been made with relatively few reagent types. Mention has already been made of   fluorous phosphines   as ligands for catalysts, and of trialkyltin and trialkylsilicon compounds for stoichiometric and sub-stoichiometric reagent and scavenging (repêrcher13) use. However, beyond this, few useful fluorous molecular types have been reported, and a call has been made3 for the design of new fluorous reagents that might allow the field of fluorous chemistry to develop to its full potential. 

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   The acetal, ketal,   thioacetal   and   thioketal   classes of compounds have found widespread use in organic synthesis, both as useful intermediates and as protected forms of otherwise reactive functional groups. For example, acetals (derived from aldehydes) and ketals (derived from ketones) are commonly used as protecting groups for diols   (typically acetonides)   and ketones or aldehydes   (dioxolanes,   dioxanes or analogous   acyclic     compounds), 14, 15 and   there has been much interest in their asymmetric cleavage to generate useful intermediates.   16     Similarly, dithiolanes and     dithianes arc conunon protecting groups for   ketones and aldehydes.

   14,15However, cabanions obtained from   1, 3-difhianc or   aldehyde-derived   dithianes will also react   with electrophiles to give more complex intermediates that can be cleaved to their carbonyl equivalents through hydrolysis or oxidation or to methylene derivatives under reducing conditions 17   A   search of the chemical literature has indicated that highly fluorinated (containing more than 4   fully   fluorinated sp3 carbons) acetals and ketals have not been reported.   Whatsmore,   very few molecules that could be used to prepare acetals or ketals by any of the standard methods   of acetal and ketal formation   have been described and none has been used in this way.

   Those polyfluorinated reactants that have been described have all been 2-polyfluoroalkylated 1,3-propanediols18-21 Disclosure of Invention 
The present invention relates (a) to the synthesis of highly fluorinated acetals and ketals and their analogues through (i) reaction   ofpolyfluorinated alkanediols   and polyfluorinated alkanedithiols and polyfluorinated 1,2-dithiacyloalkanes with carbonyl compounds, especially aldehydes and ketones,   and their synthetic equivalents, and (ii)   reaction   of alkanediols and alkanedithiols with polyfluorinated carbonyl compounds,   especially highly fluorinated aldehydes and ketones, (b) the highly fluorinated diol dithiol and   1, 2-dithiacycloalkane reactants   in these syntheses, and (c)

   the resulting highly fluorinated acetals and ketals that are the products of these syntheses, some of which we believe to be novel in themselves. 



   In a first aspect, the present invention provides method for producing a compound of formula III as shown in reaction   Scheme 1 :   

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 EMI4.1 
 
Scheme 1 wherein each X is independently selected from O or S; n = 0-2 ;
R to   ta   which may be the same or different, are independently selected from the group consisting of H, optionally substituted straight or branchede alkyl, 
CF3, optionally substituted aryl optionally substituted aralkyl, optionally substituted   aralkylene,   optionally substituted straight or branched alkene, optionally substituted, bridged or non-bridged 3-to   8-membered   saturated or unsaturated carbocylic or heterocyclic ring and- (CH2) mZR11, in which   m   = 0-3,   Z   is   0,   S or is absent,

   or 
7 and   h   together form a substituted or unsubstituted   3-to     8-membered   ring 
R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one substituent R'to R8 is the group- (CH2)mZR11;   R.''is   selected from a single   covalent bond between X groups   (when X = S), H, 
SiR103 or C (O)   R10,   wherein   Rlo   is optionally substituted alkyl ; and 
Y is O or (OR10)3. 



   The present invention also extends to compounds produced by the method of the first aspect of the invention. 



   The method of the invention may be carried out in the presence of an acid catalyst. Example of suitable catalysts include, but are not limited to H2SO4, CH3SO3H, CF3SO3H, CH3C6H4SO3H, pyridinium p-toluenesulfonate, Me3SiCl, Me3SiO3SCF3,   SnCl4,   TiCl3, HgCl2, or various lanthanide alkylsulfoante salts, in a non-hydroxylic solvent such as toluene, cyclohexane, or BTF, or in the absence of solvent at elevated temperature with continuous removal of volatailes. 



   In a second aspect, the invention provides compound of formula   I :   
 EMI4.2 
 
I wherein each X is independently selected from 0 or S; 

 <Desc/Clms Page number 5> 

   n-0-2   ; 
R1 to R6, which may be the same or different, are independently selected from the group H, optionally substituted straight or branched alkyl,   CF3   or a gorup -(CH2)mZR11 in which m = 0-3, Z is O, S or is absent, and   t1 is   a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one of R1 to R6 is the group -(CH2)mZR11;

   and 
R9 is selected from a single covalent bond between   X   groups (when   X   is   S),   H, SiR103 or C(O)R10 wherein R10 is substituted or unsubstituted alkyl, provided that when each   X   is 0, n   = 1, one   or both of R3 and   R4   are-   (CEt m   which m =   0-3   and R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, and at least one of R1, R2, R5, R6 or R9 is other that   H.   



   It will be recognized that in some cases compounds of formula I can exist in isomeric forms. This aspect of the invention includes all such possible isomeric forms of the   compounds, including diastereomers, enantiomeric forms   and mixtures of the isomers. 



   Compounds of formula I may be produced by techniques known to those skilled in the art. For example, compounds of formula I (X   =     0     ;     n     = 1 or   2) can be prepared through, for example, the addition of   organometallic   reagents, especially   Grignard   reagents, in excess on substituted   malonate or succinate (including tartrate) esters and   through the reduction of substituted malonate and   suceinate (including tartrate) esters   with hydride reducing agents, especially lithium aluminium hydride.

   Compounds of formula I (X = O; n =   0)   can be prepared through symmetrical or cross reductive coupling of aldehydes and ketones R1R2C=O and R5R6C=O using reagents such as zero valent titanium Or magnesium. They can also be synthesised by methods such as from alpha-hydroxy carboxylic acids and esters, for example,   RlR2C     (l) 02Et through the   addition of excess   organometallic   reagents, especially   ignard   reagents, and hydride reducing agents such as lithium aluminium hydride. 



   Compounds of formula I (X   =   O; R9 = SiR103 ; n = 0-2) can be prepared from the corresponding alcohols by reaction with   trialkylsilylating   agents including silyl halides and silyl sulfonates, Compounds of formula I   (X     =   S; n = 0-2) can be prepared from the corresponding alcohols by way of their sulfonate esters or from the corresponding halides (formula 1 ; Cl, Br or   I)   by treatment with sulfur reagents such as   NaSH,   R12SNa   (in   which R12 is alkyl or aryl),   HSCH2COaIH   or NaSC(O)CH3. 

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   These methods of synthesis are representative and should not be implied or   construed a. s being limiting.   



   In a third aspect, the present invention provides a compound of formula   III :   
 EMI6.1 
 wherein each X is selected independently from 0, S or   C*   ; n = 0-2 ; 
R to R8, which may be the same or different, are independently selected   from   the group consisting of , optionally substituted branched or straight chained alkyl optionally interrupted by one or more heteroatom (s), optionally substituted straight or branched alkene optionally interrupted by heteroatoms,   CFa,   optionally substituted aryl, optionally substituted aralkyl, optionally substituted arallcylene,, optionally substituted 3-to 8-membered saturated or unsaturated carbocyclic ring, optionally substituted 3-to   8-membered   saturated or unsaturated   heterocyclic   ring,

   optionally substituted 3-to 8-membered,   heteroaromatic   ring   and- (CH2) mZR",   in which m = 0-3,   Z   is   0,     S   or is absent, or when n is 1 or   2,   at least one of the pairs Rl and R2, R3 and   Ruz   R5 and   R   or 
R7 and R8 optionally from a substituted or unsubstituted   3-to     7-membered   ring optionally containing one or more heteroatom (s) or an oxo   (=O)   group or, when n=0, at least one of the pairs R1 and R2, R2 and   R   or   R   and   RS optionally   form a substituted or unsubstituted 3-to   7-membered   ring optionally containing one or more heteroatom (s)

   or an oxo   (=0)   group ; and   R11 is   a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one substituent   Rto     f   is the group- (CH2)mZR11. 



   It will again be recognized that in some cases compounds of formula III can exist in isomeric   fbrms. This aspect of   the invention includes all such possible isomeric forms of the compounds, including diastereomers, enantiomeric forms and mixtures of the isomers. 

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   In a fourth aspect, the present invention provides the use of a compound in accordance with the invention as a solvent. 



   In a fifth aspect, the present invention provides a composition of matter including a compound in accordance with the present invention. 



  In another aspect, the invention provides a compound of formula I 
 EMI7.1 
 wherein the R1R2(R9X) C group taken together and the R1R2 (R9X) C group taken together are individually or separately a nitrile (-CN), an ester (-CO2R12), a thionoester (-C(S)OR12), a thiolester (-C(O)SR12), an amide (-CONR12R13) or a thioamide (-   CSNR12R13) and   n = 1-2;   3   to   R,   which may be the same or different are independently selected from the group H, CH3, CF3 or a group- (CH2)mZR11 in which m = 0-3, Z =   0,   S or is absent, and R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one of R3 or R4 is the group -(CH2)mZR11. 



   It will be recognized that in some cases compounds of formula I can exist in isomeric forms. This aspect of the invention includes all such possible isomeric forms of the compounds,   including diastereomers,. enantiomeric forms   and mixtures of the isomers. 



   In another aspect, the invention provides a compound of formula   I   
 EMI7.2 
 wherein the R1R2(R9X)C gorup taken together is a nitrile (-CN), an   ester (-   CO2R12), a thionoester (-C(S)OR12), a thiolester (-C(O)SR12), an amide (-CONR12R13) or a thioamide (-CSNR12R13) and taken individually, X = O or   S   ; n-0-2 ; 
Ri to R6, which may be the same or different, are independently selected from the group H, CH3,   CF3   or a group- (CH2)mZR11 in which m = 0-3, Z = O, S or is absent, 

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   and R"is   a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one of R1 to R6 is the group- (CH2)mZR11;

   and   R.   ! is selected from a single covalent bond between X groups (when X = S), H, SiR103 or C(O)R10 wherein R10 is alkyl, provided that when   X   = 0, n = 1, one or both of   R   and   R   are -(CH2)mR11 in which m   =     0-3   and R11 is a fully fluorinatede straight or branched alkyl chain of 4 to 12 carbons in length, at least one of R1, R2, R5, R6 or R9 is other that H. 



   It will be recognized that in some cases compounds of formula I can exist in isomeric forms. This aspect of the invention includes all such possible isomeric forms of the compounds, including diastereomers,   enantiomeric     fonns   and mixtures of the isomers. 



   In yet another aspect, the invention provides a compound of formula I 
 EMI8.1 
 wherein the R1R2(R9X)C group taken together is a branched or straight chain alkyl, aryl, alkaryl polyether or polyamine group that is hydrophobic, hydrophilic or fluorophilic ; and taken individually,   X = 0   or S ;    n = 0-2 ;     1t3   to R6, which may be the same or differnet, are independently selected from the   group H, CH3, CF3   or a group-   (CH2)   mZR11 in which m = 0-3,Z = O, S or is absent, and R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one of R1 to R6 is the group -(CH2)mZR11;

   and 
R9 is selected from a single covalent bond between X groups (when X = S), H, 
SiR103 or C (O) R10 wherein R10 is alkyl, provided that when   X   =   0,   n =   1,   one or both of   ruz   and R4 are-   dCH2) in   which m = 0-3 and R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length. 



   It will be recognized that in some cases compounds of formula I can exist in isomeric forms. This aspect of the invention includes all such possible isomeric forms of the compounds, including diastereomers, enantiomeric forms and mixtures of the isomers. 



   In another aspect, the present invention provides a compound of formula III 

 <Desc/Clms Page number 9> 

 
 EMI9.1 
 wherein X =   4   or S; n = 0-2; 
R1-R6, which may be the same or different, are individually selected from the group consisting of H, CH3, CF3 or a group- (CH2)mZR11 in which m = 0-3, Z = O, S or is absent, and   A11 is   a   fully fluorinated straight or   branched   alky !   chain of 4 to 12 carbons in length, provided that at least one of the   substituents   R1-R6 is the group- (CH2)mZR11;

   and 
The R7R8C gorup when taken together is a carbonyl (C=O),   thiocarbonyl   (C=S), iminyl (C=NR11), borane (BR15), or borate   (BOR15), in which R"is   H or CH3, or   a   branched or straight chain alkyl, aryl, aralkyl, polyether or   polyamine   group of 2-12 atoms in length that is hydrophobic, hydrophilic or fluorophilic 
It will again be recognized that in some cases compounds of formula   m   can exist in isomeric forms. This aspect   of the invention includes al !   such possible isomeric   forms   of the compounds, including diastereomers,   enantiomeric   forms and mixtures of the isomers. 



   In a yet another aspect, the present invention provides a compound of formula III 
 EMI9.2 
 
III wherein one X =   0   or   S ;   the second X = CH2, CR16R17, or a carbonyl group ; n=0-2 ; 
R1-R8, R17, R18 which may be the same or different, are individually selected from the group consisting of H, CH3, CF3 or a group- (CH2)mZR11 in which m =   0-3,   Z = O, S or is absent, and R11 is a fully fluorinated straight or branched alkyl chain of 4 to 

 <Desc/Clms Page number 10> 

 12 carbons in length, provided that at least one of the   substituents     Rt   is the group- (CH2)mZR11. 



   It will again be recognized that in some cases compounds of formula   M can   exist in isomeric forms. This aspect of the invention includes all such possible isomeric forms of the compounds, including diastereomers,   enantiomeric forms and mixtures of   the isomers. 



  The present invention also provides a method for producing   a   chemical product, the method comprising the steps : (a) performing the method of any one of claims   1   to 17 to produce a tagged acetal or ketal of formula III ; (b) chemically transforming the tagged acetal or ketal of step (a) into   a   modified tagged acetal or ketal of formula   If ;   (c) chemically transforming the modified tagged acetal or ketal of step (b) to form   a   product. 



   Step (b) may repeated 2 or more times. 



   The term"optionally substituted"as used herein includes a group that may or may not be further   substituted'with one or more groups   selected from alkyl, optionally   bridged cycloalkyl, alkenyl, alkynyl,   halo,   haloalkyl, haloalkynyl,- (CH2) RIl (where   n,   Z   and   Roi are   defined above), oxo   (=0),   hydroxy, COOK alkoxy,   alkenyloxy,   aryloxy, haloalkoxy, haloalkenloxy, nitro, cyano, amino, nitroalkyl, nitroalkenyl,   nitroalkynyl,   nitroheterocyclyl alkylamino, dialkylamino, alkenylamine, alkynylamino, hydrazone, CHO, acyl, alkenacyl, alkynylacyl, acylamino,   diacylamino,   acyloxy,   alkylsulphonyloxy,     heterocyclyl,     heterocycloxy,

     heterocyclamino, haloheterocyclyl,    alkylsulphenyl, carboalkoxy, alkylthio, acylthio, phosphorous-containing groups such   as phosphono and phosphinyl, or a residue of   a     compound   of formula III or a residue of compound   of formula IH and   an associated linking group. 



   The term "alkyl" includes straight chain or branched C1-6 alkyl groups. Non- limiting examples include methyl, ethyl, propyl, isopropyl and the like. 



   The   term"alkoxy"includes   straight chain or branched alkoxy. Non-limiting examples include methoxy, ethoxy,   n-propoxy,     isopropoxy   and the different butoxy isomers. 



   The   term"alkenyl"includes groups formed from straight chain, branched or   mono-or poly-cyclic alkenes including ethylenically mono-or poly-unsaturated alkyl or cycloalkyl groups Non-limiting examples of alkenyl include vinyl, allyl, 1- methylvinyl, butenyl iso-butenyl,   3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl,   1- 

 <Desc/Clms Page number 11> 

   methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl, 1-heptenyl, 3-heptenyl, 1-   octenyl,   cyclooctenyl,     1-nonenyl,     2-nonenyl,   3-nonenyl,   1-decenyl,   3-decenyl, 1, 3- butadienyl, 1-4,   pentadienyl,     1,   3-cyclopentadienyl, 1, 3-hexadienyl, 1, 4-hexadienyl, 1,3-   cyclohexadienyl,   1, 4-cyclohexadienyl, 1,3-cycloheptadienyl,

   1,3,5-cycloheptatrienyl, 1,3,   5,   7-cyclooctatetraenyl. 



   The term"aryl"as used herein includes an aromatic substituent containing a single aromatic ring or multiple aromatic rings that are fused together, linked   covalently,   or linked to a   common   group such as a methylene or ethylene moiety. The common linking group may also be a carbonyl as in benzophenone, an oxygen atom as in diphenylether, an alkylether or a nitrogen atom as in   diphenylamine.   



   The term "aralkyl" refers to an alkyl group with an aryl substituent, and the term   "aralkylene"refers   to an alkylen group with an aryl substituent ; the term"alkaryl" refers to an aryl group that has an alkyl substituent, and the term "alkarylene" refers to an   arylene   group with an alkyl substituent. 



   The term "acyl" used either alone or in compound words such   as"acyloxy",   "acylthio", "acylamino" or diacylamino" denotes carbamoyl, aliphatic acyl group and acyl group containing a   heterocyclio   ring which is referred to as heterocyclic acyl, preferably   Cl-10 acyl.

   Examples   of acyl include carbamoyl ; straight chain or branched alkanol, such as formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl; alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, t-   pentyloxycarbonyl or heptyloxycarbonyl   ;   cycloalkylcarbonyl   such as cyclopropylcarbonyl   cyclobutyloarbonyl,     cyclopentylcarbonyl   or cyclohexylcarbonyl ; alkylsulfonyl, such as methylsulfonyl or ethylsulfonyl ;   alkoxysulfonyl,   such as   methoxysulfonyl   or ethoxysulfonyl ;   heterocyclylcarbonyl ;

   heterocyclylalkanoyl, such   as   pyrrolidinylacetyl,   pyrrolidinylpropanoyl,   pyrrolidinylbutanoyl,   pyrrolidinylpentanoyl, pyrrolidinylhexanoyl   or thiazolidinylacetyl ;     heterocyclylalkenoyl,   such as heterocyclylpropenoyl,   heterocydylbutenoyl,     heterocyclylpentenoyl   or   heterocyclylhexenoyl   ; or heterocyclylglyoxyloyl, such as,   thiazolidinylglyoxyloyl   or pyrrolidinylglyoxyloyl. 



   The   term"alkoxy"as   used alone or in combination herein refers to a straight or branched chain alkyl group covalently bonded to the parent molecule through an-0- linkage containing from one to ten carbon atoms and the   terms"C 1-6 alkoxy"and   "lower   alkoxy"refer   to such groups containing from one to six carbon atoms, such as methoxy, ethoxy,   propoxy, isopropoxy, butoxy, tbutoxy   and the like. 

 <Desc/Clms Page number 12> 

 



   The   term"heteroaromatic"group   as used herein refers to a stable, aromatic   monocyclic   or polycyclic ring system containing carbon atoms and other atoms selected from nitrogen, sulfur   and/or   oxygen. For example, the heteroaromatic group may be a 5 or   6-membered     monocyclic   ring (optionally   benzofused)   or   an 8-11     membered   bicyclic ring which consists of carbon atoms and contains one, two, or three heteroatoms selected from nitrogen, oxygen and/or sulfur.

   The term "optionally   substituted"as   it refers   to"heteroaromatic"herein   indicates that the   heteroaromatic   group may be substituted at one or more substitutable ring positions by one or more groups independently selected form alkyl (eg lower alkyl), alkoxy (eg lower alkoxy), nitro, monoalkylamino (eg   a   lower alkylamino), dialkylamino (eg a di [lower]   alkylamino,     cyano,   halo, haloalkyl (eg   trifluoromethyl),   alkanol, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, alkyl amido (preferably lower alkyl amido), alkoxyalkyl (eg a lower alkoxy [lower] alkyl), alkoxycarbonyl (eg a lower alkoxycarbonyl), alkylcabonyloxy (eg a lower   alkylcarbonyloxy)   and aryl (eg phenyl),

   said aryl being optionally substituted by halo, lower allyl and lower alkoxy groups. Examples of such beteroaromatic groups are   isoxazolyl, imidazolyl, thiazolyl, isothiazolyl, pyridyl, furyl, pyrimidinyl, pyrazolyl,   pyridazinyl,   furazanyl   and thienyl. The heteroaryl group may be attached to the parent structure through a carbon atom or through any heteroatom of the heteroaryl that results in a stable structure. 



   The   terms"halo"and"halogen"as   used herein to identify substituent moieties, represent fluorine, chlorine, bromine or iodine, preferably chlorine or   fluorine.   



   The term"cycloalkylene",   includes   divalent cyclic   Cs. io alkyi groups. Non-   limiting examples include cyclopropyl, cyclobutyl, cyclopentyl and cycloheptyl. The term includes fused rings and bridged rings. 



   The term"heterocyclyl"as used alone or in compound names such as   "alk3rleneheterocyclyl"denotes   3-to   8-membered heterocyclic rings. Examples   of 5 or 6 membered   heterocyclic   rings include   pyrrolidine,   imidazolidine, pyrazolidine, thiazolidine,   isothiazolidine, oxazolidine, piperidine   and piperazin 
The term"tag"refers to a substituent comprising a polyfluor alkyl group. 



  Methods for carrying out the invention 
The invention is further described in and illustrated by the following examples.. 



  These examples are not to be construed as limiting the invention in any way. 



  1, Examples of methods for the preparation of polyfluorinated diol reagents 

 <Desc/Clms Page number 13> 

 
 EMI13.1 
 1 2 3 
 EMI13.2 
 
1. 4 5 6   2- (3,   3,4, 4,   5,     5,   6,6,7,7,8,8,8-Tridecafluorooctyl)-1,3-propanediol 1 A solution of diethyl 2-(3, 3, 4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-propanedioate   (1.   956   g,   3.9 mmol) in dry   Et, 20   (20   rnL)   was added to a suspension of LiAlH4 (0.340   g mmol)   in dry   Et20     (20   mL) at such a rate as to maintain reflux. The mixture was stirred at ambient temperature for 20 h then quenched by careful addition of 10% aq. solution (20 mL). The mixture was filtered under suction through a pad of filter aid.

   The pad was washed with fresh Etc0 (2 x 20mL), the combined filtrate and washings separated and the aqueous layer extracted with more Et20 (2 x   15mL) The   organic layers were combined and evaporated under vacuum to afford a white solid (1.522 g). Thorough extraction of the solid with light petroleum and   recrystallization   of the remaining white solid from CH2Cl2 afforded 2-(3, 3,4, 4,   5,     5,     6,     6, 7, 7, 8, 8, 8-   tridecafluorooctyl)-1, 3-propanediol 1 as white flakes (1. 323 g, 81%)   ni.     p   72-74 C (Found : C, 31.24; H, 2.88 C11H11F13O2 requires: C, 31.   29   ;

   H, 2.63%). 1H NMR (300 MHz) :   3   1. 67, m, (H1')2 ; 1. 78, m, H2; 1.99, s, 2-OH; 2.17, br m, (H2')2', 3. 72, dd, J 10. 6, 6.0 Hz, Hal and Ha3; 3.85, dd,   J   10, 6, 3.8   S   Hb1 and Hb3. 13C NMR (75.6   MHz): # 18,   4, t, J 4.0 Hz, C1'; 28.7, t, J 22.5 Hz, C2'; 41.2, C2 ; 65.0, Cl and   C3. Mass   spectrum :   ? nlz   422   (M,   absent), 374 (15%), 169 (5), 119 (12), 105 (18), 77 (18), 69   (31), 57   (70), 55   (100).   



    2, 2-Bis (3, 3,   4,   4,   5,5,6,6, 7, 7,8,8,8-tridecafluorooctyl)-1,3-propanediol 2 (a)   A.   solution. of diethyl 2,   2-bis (3,   3,4, 4, 5,5,6,6,7, 7, 8,8,8-   tndecafluorooctyl)     propanedioate   (0.   697 g, 0. 82   mmol) in dry Et2O (6 mL) was added dropwise to a suspension of LiAlH4 (0.080 g, 2.11 mmol) in dry Et2O (6 mL). This mixture was stirred at ambient temperature for   24   h, then quenched by careful addition 

 <Desc/Clms Page number 14> 

 of   10%   aq. KOH solution (5 mL). The mixture was filtered under suction through a pad of filter aid. The pad was washed with fresh Et2O   (2x20mL).

   The   combined filtrate and washings were separated and the aqueous layer extracted with more   EtoO   (2x15 mL). 



  The organic phases were combined and evaporated under vacuum to afford white solid (0.605 g). The white solid was   recrystallized   from CHCl3 to afford 2, 2- bis (3, 3,4,4,5,5, 6,6, 7, 7,8,8,8-tridecafluorooctyl)-1,3-propanediol 2 as white needles (0.   572 g,   91%)   m.   p. 73-75 C (lit.18 m p.   77-77,   5 C) (Found : C,   30.   06;   H,   1.   97.   



  C19H14F26O2 requires: C, 29.70; H, 1.84%). 1H NMR (300   MHz): # 1.    66, m,   tel') 2   and (H1") 2 ; 1.90,   s7 2-OH ;   2. 13, br m, (H2')2 and (H2")2; 3. 61, s,   (Hl)   2 and (H3)2. 13C NMR   (75.   6 MHz) :   ##1#C1' and C1"; 25.1, t, J22.2 Hz, C2' and C2";    40. 0, C2 ; 66. 8, Cl and C3. Mass spectrum :   mlz     768     nez   absent), 721   (201/o),   413   (6),   401   (62),   375   (9),   327   (5),   169   (20),   131 (25), 119 (45), 95 (33), 77 (50). 



   (b) (i) A mixture   of3, 3, 4, 4, 5, S,   6, 6,7,7,8,8,8-tridecafluoroctyl iodide (10. 653 g, 22. 47 mmol), ethyl   cyanoacetate     (J.   232 g, 10. 89 mmol), anhydrous K2CO3 solid (3.323 g,   24.   08 mmol) and dry DMF (15 mL) was stirred together in a flame-dried flask for 20 h under argon. The resulting reaction mixture was poured into water and filtered to remove the red precipitate. The precipitate was dissolved in Et2O (50   mL)   and the solution was   decolourized   by addition of charcoal.

   The solution was filtered and then evaporated to dryness to give some pale solid that was   recrystallized   from light petroleum to afford ethyl 2,2-bis(3,3,4,4,5,5,6,6,7, 7, 8,8,8- tridecafluorooctyl)cyanoacetate 71 as white needles   (6.   516 g, 74%) m. p. 66-67 C 
 EMI14.1 
 (Found: C, 31.26 ; H,   1. 5S   ; N, 1. 84.

   C21H13F26NO2 requires: C, 31.32; H, 1.63 ; N, 1.74%). vmax 1744,   1320, 1240, 1190, 1141, 1043, 699. 1H NMR (300 MHz): # 1.36, t,   J 7. 0 Hz, CO2CH2CH3; 2. 17,   m,   (H1') 2 and H1")2 ; 2. 31, br m, (H2')2 and (H2")2, 4. 37, q, J 7. 2 HA CO2CH2CH3. 13C NMR (75. 6 MHz) :   #13.8, CO2CH2CH3   ; 27.   3,     t, J 2Z   5 Hz, C2' and C2"; 28.1, C1' and C1"; 47.5, C2; 63.8, CO2CH2CH3; 116.8, CN; 166. 7, CO2CH2CH3.Mass specturm: m/z 806 (M+1, 2%), 733 (25), 508 (12),   428     (72),   400 (100), 327 (11), 169 (20), 131 (30),   119 (38),   77 (53), 69   (82).   



  (ii) Conc. H2SO4 (5 mL) was slowly added to a solution of ethyl 2,2- bis (3,   3,   4, 4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)cyanoacetate 71   (5.   370   g,     6.   67   rnmol)   in n-BuOH (50 mL), and the mixture heated at reflux for 3 days. The brown solution was cooled,   fizz   (50 mL) and   EtO (50 mL)   were added, and the resulting mixture was 

 <Desc/Clms Page number 15> 

 separated and the aqueous layer was extracted with more   Et20     (2   x 25 mL).

   The organic phases were combined and evaporated under vacuum to afford brown solid   (5.     922     g   which was chromatographed on silica gel (40   g).   The first   fraction, eluted   with 4 : 96   EtzO/light   petroleum was combined and evaporated to dryness to give largely di-n-butyl 2, 2-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-triedcafluorooctyl)propanedioate as a yellow oil   (1.     872     g).   The second fraction from 4:96 Et2O/light petroleum was recrystallized ±rom light petroleum to give n-butyl 2,2-bis(3,3,4,4,5,5,6,6,7,7,8,8,8tridecafluorooctyl)cyanoacetate 72 as white Hakes (3.039 g   55%)   m. p. 66-67 C 
 EMI15.1 
 (Found: C, 33.07; H, 2.18; N, 1.59.

   C21H13F26NO2 requires: C, 33. 15 ; H, 2. 06; N,   1.68%). #max    1732,   1321,     1240, 1189, 1139, 1044, 699, 658. 1H NMR (300 MHz): #   0. 96, t J 7.3 Hz, CO2CH2CH2CH2CH3; 1. 42, m, J 7. 4 Hz, CO2CH2CH2CH2CH3; 1.70, m, J 7.2 HzCO2CH2CH2CH2CH3; 2.16, m, (Hl')2 and (Hl")2; 2.31, br   m,   (H2')   2   and (H2")   2 ;   4. 30, t, J   6.     6     Hz,     CO2CH2CH2CH2CH3. 13C NMR (75.6 MHz): #13.2,   CO2CH2CH2CH2CH3; 18.8, CO2CH2CH2CH2CH3; 27.4, t, J 22.5 Hz, C2' and C2";   ?-S.     I,     t,   J 4.4   Hz,   Cl'and Cl 30.   2,     C02CH2CH2CH2CH3   ; 47. 6, C2; 67. 6, CO2CH2CH2CH2CH3; 116. 7, CN;

   166.8, CO2CH2CH2CH2CH3. Mass spectrum: m/z 833   (M",   absent),   733     (15 /0,   508 (7), 414 (3), 400   (58),   386   (3),     327     (5),   169   (5),   130   (8), 119 (10), 84 (17), 77 (26), 69 (36), 57 (100).   



  (iii) A solution of the first fraction from part (ii), a yellow oil (1. 872   g),   in dry Et2O   (15   mL) was added dropwise to a suspension of   LiAIH4 (0. 235 g, 6. 16 mmol)   in dry Et2O   (8     mL) This mixture was stirred   at ambient temperature for 24 h, then quenched by careful addition of 10% aq.   KOH   solution (20 mL). The mixture was   faltered   under suction through a pad of filter aid. The pad was washed with fresh Et2O (3   x     20mL).   



  The combined filtrate and washings were separated and the aqueous layer extracted with more   Et20   (2   x   20 mL). The organic phases were combined and evaporated under vacuum to afford a   white gel (1.   656 g). The white gel was then chromatographed on silica gel (20   g).   The first fraction, eluted with 20: 80 Et2O/light petroleum was combined and evaporated, and the residue was distilled to give 2, 2- bis(3,3,4,4,5,5,6,6,7,7,8,8,8-triedcafluoroctyl)-l-ethanol 49 as a colouless oil (0.766 g, 16%) 160 C (oven)/1.0 mmHg 

 <Desc/Clms Page number 16> 

 
 EMI16.1 
    49   (Found: C, 29. 41 ;   l   1, 71.

   C18H12F26O requires : C,   29. 29   ; H,   1. 64%). 1H NMR   (300   MHz): #1.   41, s, OH; 1.66, m, (H1')2, (H1") 2 and   H2 ; 2, br X   and (H2")2; 3.64, s, (H1)2. 13C NMR (75.6   MHz)     : Q21. 4, Cl'and Cl" ; 28.   4, t, J 22.2 Hz, C2' and C2"; 38.9 C2; 64.   2,   Cl. Mass spectrum : m/z 738 (M+, absent), 706   (1),   686   (2),   401   (3),   169 (12), 131   (15), 119 (32),   91 (13), 77 (53),   69     (100),     55     (69).

   The second fraction from   50 ;50 Et2O/light petroleum was combined, evaporated and   recrystallized ftom CHCla   to afford 2, 2-bis (3,3, 4,4,5,5,6,6, 7, 7,8,8,8-tridecafluorooctyl)-1,3-propanediol 2 as white needles (0, 774 g, 15%). 



  Cone.   H SO4 (4 5 mL)   was slowly added to a solution of ethyl   2, 2-   bis (3,   3,   4, 4, 5,5,6,6,7,7,8,8,8-tridecafluorooctyl)cyanoacetate 71 (4.80 g, 5. 96 mmol) in n-BuOH (45 mL), and the solution heated at reflux for 7 d. The brown solution was cooled,   lI20     (50     mL)   and   EtzO     (50   mL) were added, the resulting mixture was separated, and the aqueous layer was extracted with more Et2O (2   x   25 mL). The organic phases were combined, dried and evaporated under vacuum to afford the crude dibutyl diester as a brown oil (5.02 g). 



  (iii) The oil   (5.     02 g)   was dissolved in dry   EtO (30 mL) and   added dropwise to a suspension   of LiAIH4 (0. 50 g, 13.   16 mmol) in dry Et20 (20 mL). The mixture was stirred at ambient temperature for   24     h,   then quenched by careful addition of 10% aq. 



  KOH solution (20 mL). The mixture was filtered under suction through a pad of filter aid, and the pad washed with fresh   Et2O     (3   x 20 mL). The combined filtrate and washings were separated and the aqueous layer extracted with more   EtO (2 x 20 mL).   



  The organic phases were combined and evaporated under vacuum to afford a brown oil (4.37 g), which was chromatographed on silica gel   (50   g). The first fraction, eluted with 20 ; 80 Et2O : light petroleum, was combined and evaporated, and the residue was distilled to give 2,2-bis(3,3,4,4,5,5,6,6,m 7, 7,8,8,8-tridecafluorooctyl)-1-ethanol 49 as a colourless oil (1.45 g, 34%) The second fraction, from 50 : 50 EtwO :

   light petroleum, was combined, evaporated and recrystallized from   CHOIS   to afford   2, 2-   bis   (3,     3,   4,4,5, 5,6, 6, 7,7,8,8,8-tridecafluorooctyl)-1,3-propanediol 2 as white needles   (1.   89 g, 44%). 

 <Desc/Clms Page number 17> 

 l, 1-Bis (3,3, 4,4,   5,   5, 6, 6,7,7,8,8,8-tridecafluorooctyl)-2,2-dimethyl-1,3-propanediol 3 (i)   3,     3,   4,4,5,5,6,6,7, 7,8,   8,   8-Tridecafluorooctyl iodide (0.903 g, 1.91 mmol) was added to a suspension of Mg powder   (0.   636 g, 26.   20   mmol) in dry Et2O (15   mL)   under argon. 



  The mixture was sonicated for 30 min then more   3, 3,   4, 4,   5,     5,     6,   6,7,7,8,8, 8- tridecafluorooctyl iodide (9. 074 g,   19.   14 mmol), in dry   EtsO     (20     mL),   was added dropwise over 60 min at such a rate that gentle reflux was maintained. Upon complete addition, the mixture was stirred at reflux for a further 90 min then cooled to room temperature and a solution of diethyl dimethylmalonate (1. 671 g,   S. 88 mmol) in dry   Et2O (4   mL)   was added slowly. The mixture was stirred for a iurther 2 d at ambient temperature then quenched carefully by dropwise addition of sat.   aq.   CI solution. 



  The aqueous layer was extracted with Et2O (3 x 20 mL) and the original organic layer and the extracts were combined, dried over anhydrous Na2SO4, and evaporated to dryness to give a yellow oil (7.847 g) that was column chromatographed on silica gel. 



  The forera from light petroleum gave   1,   4-bis (perfluorohexyl) butane as a white solid   (1.   093 g, 7%) The   major fraction, eluted   with 3: 97   EtxOllight petroleum,   was evaporated to dryness and the residue wa distilled ot give ethyl 3,3,-bis(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-2,2-dimethyl-3-hydroxypropionate 73 as a colourless oil (5. 970 g, 80%) b.   p   120 C (oven)/04. mmHg 
 EMI17.1 
   (Found :   C, 32. 89; H, 2.53.   C23H20F26O3 requires: C, 32.95;

   H, 2.40%), #max 3452,     2990,   1743, 1698, 1475,.   1367,   1203,   1059,     847,   811, 735, 708 cm-1. 1H NMR (300   MHz, CDCl3): #1,   27, s,   2-CH3     ; 1. 30,   t, J 7.2 Hz, CO2CH2CH3 ; 1.   57-1. 89,   br m, (H1')   2   and (H1")2 ;   2. 00-2. 40,   br   m,   9H2')2 and (H2")2; 4. 20, q, J 7. 2 Hz,   C02CH2CH3,   4.   48,   s,   OH¯13C NMR (75.6 MHz): # 13.7,CO2CH2CH3;    20.9,   2xCH3     ; 26.   1, t, J21.8 Hz, C2' and C2"; 26.7, C1' and Cl"; 50.4, C2; 61.6, CO2CH2CH3; 73.7, C3; 178.7, 
CO2CH2CH3.

   Mass spectrum; m/z 838 (M+, absent), 703   (15%), 551 (5), 491 (40), 453     (35),   417 (30), 389   (45),   375 (95),   327     (25),   263 (25), 213 (25), 169 (28), 131 (50), 116    (100), 88 (95), 70 (92).   



   (ii) A solution of   ester 73 (1. 611 g, 1.   92 mmol) in dry Et2O (12 mL) was added dropwise to a suspension of LiAlH4 (0. 193 g,   5,   07 imnol) in dry   Eut20   (5 mL). This mixture was stirred at   ambient   temperature for 24 h then quenched by careful addition   of 10%   aq. KOH solution (5 mL). The phases were separated and the aqueous layer 

 <Desc/Clms Page number 18> 

 was extracted with Et2O (2 x 15 mL). The organic phases were combined, evaporated and the residue was distilled to ¯ afford 1.1-bis(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-2,2-dimethyl-1,3-propanediol 3 as a colourless oil (1. 486 g, 97%) b.   p.     140 C   (oven)/0.3 mmHg (Found: C,   31.   91 ; H, 2.25.

   C21H18F26O2 requires : C, 31. 67; H, 2.   28%). #max 3370,    2973,   2891,     1475,   1366,   1318,   1209, 1146, 1057,   114   NMR   (300 MHz): #0.99,    s, 2-CH3 ;   1.   71, dt, J 12. 8,   3. 8 Hz, (HII) 2 ; 1. 98,   dt, J 13. 6, 3. 8    Hz, (H1") 2; 2.14, s, CH2OH; 2.16, m, (H2')2; 2.33, m, (H2")2; 3.69, d, J 3.8 Hz, H3 ; 3.95, s, (C6F13CH2CH2)2COH, 13C NMR (75.6 MHz); #20.8, 2xCH3; 26.1, Cl' and   Cl" ; 26. 4, t, J 11.8 Hz, C2' and C2''; 41. 9,   C2 ;   71. 5, C3 ;   75. 3, Cl.

   Mass spectrum   :   mlz     796     (M-,   absent), 761 (18%)l, 723 (18), 449 (65), 431 (58), 375   (95),   327   (22),     263     (18),   169   (30),   119 (45), 77 (68), 69   (100).     l,   1-Bis(3,3,4,4,5,5,6,6.7,7.8,8,8-tridecafluorooctyl)-1,2-ethanediol 5 (i)   Reaction of (3, 3, 4,   4,5,   5,     6,   6,   7,   7, 8,   8,   8-tridecafluorooctyl) magnesium iodide with diethyl oxalate A portion   of 3,   3,4, 4,5,   5,   6,   6,   7,7,   8,   8, 8-tridecafluorooctyl iodide (0. 933   g,     1.

   97 mmol)   was added to a suspension of Mg powder   (0.   731 g, 4.13 mmol) in dry Et2O   (10     mL)   under argon. The mixture was sonicated for 30 min then a solution of 3,3, 4, 4, 5, 5,6, 6,7, 7,8,   8,   8-tridecafluorooctyl iodide (8. 726 g, 18. 41 mmol) in dry Et2O (25 nL) was added dropwise over 60 min. Upon complete addition, the mixture was stirred at   reflux   for a further 90 min then cooled to room temperature and a solution of diethyl oxalate (1. 247 g, 8.53 mmol) in dry Et2O (5   mL) was added slowly. The   mixture was stirred for a further   2   d at ambient temperature then quenched carefully by dropwise addition of sat.   aq.   NH4Cl solution.

   The aqueous layer was separated and extracted with Et2O   (3   x 20 mL). The original organic layer and extracts were combined, dried over   anhydrous   Na2SO4 and evaporated to dryness to give a yellow oil (6.400 g) that was column chromatographed on silica gel. The faction from light petroleum gave   1,   4-bis(perfluorohexyl)butane as a white solid (1.230 g,   8%).   The major fraction, eluted with 5:95 Et2O/light petroleum, was evaporated to dryness and then distilled to give ethyl 2,   2-bis     (3,   3,   ,   4,5,5,6,6,7, 7, 8, 8, 8-tridecafluorooctyl)-2- 
 EMI18.1 
 hydroxyacetate 74 as a colourless oil (2. 119 g, 31%) b. p. 120 C (oven)/0. 4 mmHg .

   F13
O2Ho 
C, H 
I H 6F, 3 

 <Desc/Clms Page number 19> 

   (Found :   C, 30. 20 ; H,   1.     80.   C21H18F26O2 requires : C, 30. 17;   H,   1. 77%). 1H NMR (300   MHz,)   :   #1.32, t, J7.2 Hz, CO2CH2CH3; 1.86, br m, (H2')2;    1. 95-2. 12, br m, (H1')2 and (H1'')2; 2.30, br m, (H2'')2; 3.38, s, OH ; 4.   32,   q, J7.2 Hz, CO2CH2CH3. 13C NMR (75.   6     Nfffz)   :   #13.9, CO2CH2CH3   ; 25. 6,   t,   J 22. 5 Hz, C2' and C2''; 29.4, C1' and C1''; 63. 0, C2; 74.8, CO2CH2CH3; 174. 9, CO2CH2CH3.

   Mass spectrum; m/z 796 (M+, absent), 779   (5%),   723   (92),   703   (52), 683 (12),   449 (20), 403 (33), 375 (100), 327 (84), 169 (47),   119 (53),   69 (91). The fraction from 10 : 90 Et2O : light petroleum was distilled to afford ethyl 2-hydroxy-2-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)acetate 75 as   a     colourless oil (1. 512 g, 39%) b. p. 120 C (oven)/l. 0 mmHg   
 EMI19.1 
 (Found : C,   32.   04; H, 2, 54.

   C12H11F13O3   requires: C, 32.02; H, 2.54%). #max 3471,   2988, 1740, 1455, 1367, 1240,   1145, 1121, 1096,   1076, 1021, 707, 1H NMR (300   MHz): #1.32,    t, J 7.2 Hz, CO2CH2CH3 ;   1.     92,     m,   Ha1'; 2.12, m, Hb1'; 2.15-2.35, br m, (H2')   z     ; 2. 87, d, J   4.9 Hz, OH ; 4. 22, m, H2 ; 4.26, dq,   J   10. 9, 7.2 Hz, CO2CHaHbCH3; 4. 31,   1, dq, J 10.9, 7.2 Hz, CO2CHaHbCH3. 13C NMR (75.6 MHz): #14.0, CO2CH2CH3;   25.0,   t,   J4.0 Hz, C1'; 26.   7,   t, J 22.5 Hz, C2'; 62.1, CHOH; 68.9, CO2CH2CH3 ; 174.0, CO2CH2CH3.

   Mass spectrum : mlz 451   %),   377 (100), 357   (52),   337   (9),   309 (12), 289 (15), 245 (12), 239 (13), 169 (8), 131 (15), 119 (22), 69 (67). 



  (ii) A solution of ester 75 (1. 212 g 2 mmol) in dry   Bt2O     (5     mL)   was added dropwise to a suspension of LiAlH4 (0.160 g, 4. 22 mmol) in dry   Et20     (20   mL). This mixture was stirred at ambient temperature for   20   h, then quenched by careful addition of   10%     aq.   



  KOH solution (10 mL). The phases were separated and the aqueous layer was extracted   with Et2O (4 X 15 nnL) The   organic phases were combined and evaporated to give a colourless oil (1.   332     g)   that solidified when it stood overnight at room temperature. The white solid was recrystallized from CH2Cl2 to give 1,1-bis(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-1,2-ethanediol 5 as white needles   (1.   114g,   97%)     mp. S4-85 C   (Found C, 28. 68; H, 1. 69.

   C18H12F26O2 requires; C, 28.66 ;   H,     1.60%). #max    3344,   1319,   1235, 1208, 1189, 1145, 1122,1070,   699. 1H NMR (300 MHz): #1.   80,   m,   2-OH,   (Hl')   2 and (H1'') 2; 2.20, br m, 1-OH, (H2')2 and   (H2") : ; 3. 55,   d, J 4.1   Hz,     (H2)   2.   13c   NMR (75.   6     MHz): #25.3,    t,   J 22.   7 Hz, C2'and   C2" ; 26.   7, t,   J   3.6   Hz,   C1' and C1''; 66.   9,   C2 ; 71.8, C1.

   Mass spectrum: m/z 754 (M+, absent), 723 (58%), 703 (22), 467   (8),     407   07 (95), 389 (35), 375 (65), 327 (33), 169 (32), 119 (52), 69 (100). 

 <Desc/Clms Page number 20> 

 l, l-Bis (3, 3, 4,   4,   5,   5, 6, 6, 7, 7,   8,8, 8-tridecafluorooctyl)-1,4-butanediol 6 (i) A portion of 3, 3,   4,     4,   5,   5,     6,     6,   7, 7, 8,8,8-tridecafluorooctyl iodide (0. 592 g, 1.25 mmol) was added to a suspension of Mg powder   (0.     375 g, 15.   42 mmol) in dry Et20   (10 mL)   under argon.

   The mixture was   sonicated   for   30   min then a solution of 3,   3,   4,   4,   5,   5,     6,     6,   7,   7,   8,8,8-tridecafluorooctyl iodide (4. 561 g, 9. 62 mmol) in dry   Et20   (20 mL) was added dropwise over 60 min. Upon complete addition, the mixture was stirred at reflux for a further 90 min then cooled to room temperature and a solution of diethyl succinate (2.010 g, 11.54 mmol) in dry   Et7O     (4   mL) was added slowly. The mixture was stirred for a further 2 d at ambient temperature then quenched carefully by dropwise addition of sat. aq.   NH4Cl   solution. The aqueous layer was separated and extracted with Et2O (3 x 20 mL).

   The original organic layer and extracts were combined, dried over anhydrous Na2SO4 and evaporated to dryness to give a yellow oil (4. 786   g)   that was column chromatographed on silica gel. The fraction from light petroleum gave   1, 4-bis (perfluorohexyl) butane   as a white solid   (0.   629 g,   8%).   Diethyl   succinate   (1.267g, 63%) was recovered from the fraction eluted with   10 :   90 Et2O : light petroleum.

   The major traction, eluted with 40 : 60   EtO : light petroleum, wa. s   evaporated to dryness and distilled to give 4,4-bis(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)butyrolactone 76 as a colourless oil that solidified after standing overnight at ambient temperature (1.760 g,   21%)   b. p. 170 C (oven)/0. 6 mmHg m.p. 54- 54.   5 C   
 EMI20.1 
 (Found : C, 30.99; H, 1. 52.

   C20H12F26O2 requires: C, 30.87 ; H,   1.55%). #max 2722,   
1776, 1246,   1203, 1189, 1144, 1071, 1031, 699. 1H NMR (300 MHz): #1.97,    m,   (Hl')     2   and (H1'')2 ;   2   13,   t,     l   8. 7 Hz, (H4)   2 ; 2. 16, br m, (H2') 2 and (H2") 2   ; 2. 68, t,   I   8. 5   Ha,     (H3) 2. 13C NMR (75.6 MHz): #25.5, t, J22.5 Hz, C2' and C2''; 28.2, C3; 28.7, C1' and   Cl"   ; 30. 5, C4   ; 84.5, C5; 174.8, C2.

   Mass spectrum: m/z 778 (M+, absent), 703 (7%), 375 (5), 327   (3), 169 (3),   147   (28),   103 (74),   73     (100).     NMR. spectroscopic assignments   were confirmed by 1H-1H COSY and 1H-13C HMQC experiments. 



  (ii) A solution of lactone 76 (1.345 g, 1.73 mmol) in dry Et (8 mL) was added dropwise to a suspension of LiAlH4 (0.152 g, 4.00 mmol) in dry Et2O (8 mL). This mixture was stirred at ambient temperature for 20 h, then quenched by careful addition of 10% KOH solution   (10   mL). The phases were separated and the aqueous layer was extracted with Et2O   (4   x 15 mL).

   The organic phases were combined and evaporated to give a colourless oil (1.332 g) that solidified when it stood overnight at room 

 <Desc/Clms Page number 21> 

 temperature.   The white solid was then recrystallized from CH2Clz   to give 1,1- bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,4-butanediol 6 as white needles (1. 328 g, 93%) m. p. 65-66 C   (Found : C, 30. 54   ;   H,   2.   06.   C20H16F26O2 requires: C, 30. 71;

   H, 2. 06%).   vt     3368,     1319,   1241, 1208, 1145, 1038, 697. 1H NMR (300 MHz):   #    1. 65, br   s,     (H2)     2   and (H3) 2; 1.75, m, (H1')2 and (H1'') 2; 2.17, br m,   (142')     2     and (H2") 2 ;   3. 74, s, (H4)   2   13C NMR (75.6   MHz): #25.   4, t, J 22.2 Hz, C2' and C2''; 25. 9, C3;   29.     1,   Cl'and Cl" ; 36.0, C2; 62. 7, C4 ; 71. 2, Cl. Mass spectrum : m/z 782 (M+, absent), 723 (22%), 703   (7),   435   (5),   417 (65),   375   (30), 327 (7),   169     (5),   69   (33), 42 (100).   



  Synthesis of polyfluorinated diol trimethylsilyl ethers 1,1-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-bis(trimethylsilyloxy)-2,2- dimethylpropane 77 
 EMI21.1 
 
77 Diol 3 (0. 791 g, 0.99   mmol),   1,   1,   1,3,3,3-hexamethyldisilazane (2. 830 g, 17.53 mmol) and iodine (0. 043 g 0. 17 mmol) were refluxed overnight in   CH2C12     (30   mL). The solution was cooled and finely   ground Na2Sz03 powder   (0.   210 g, 1. 33 mmol)   was added and the resulting mixture was stirred for another 1 h.

   The CH2Cl2 solution was filtered and the residue was   washed with Et20 (2   x 20   mol).   The original filtrate and washings were combined and evaporated. under vacuum to afford a   colourtess   oil (0.874 g) that was column chromatographed on silica gel. The fraction eluted with 3 : 97   Et20   : light petroleum was distilled to give   J.   1-bis(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-1,3-bis(trimethylsilyloxy)-2,2-dimethylpropane 77 as   a   colourless oil (0.435 g, 47%) b. p.   120 C     (oven)/0.   4 mmHg (Found: C, 34.47; H, 3. 57. 



  C27H34F26O2Si2 requires : C,   34.   7; H, 3. 64%). Vmax 2962, 2905, 2885, 1479, 1366,   1318,   1240, 1203, 1145, 1088, 873, 841. 1H NMR (300 MHz) :   #0.   08,   s,     3-0si (CR,,) 3 ;   0.15, s, 1-OSi   (CH3)     3 ; 0. 90,   s, 2xCH3 ; 1. 94, br m, (H1')2 and (H1'')2; 2. 13, br m, (H2')   2   and   (H2")     2   ; 3. 39, s, (H3)2. 13C NMR (75. 6 MHz) :   #-1.    1,   3-OSi     (CH3)   3; 2.5, 1- OSi (CH3) 3; 21. 7, 2xCH3 ; 26.1, C1' and C1''; 26.8, t, J 21.5 Hz, C2' and C2''; 44.1, C2; 68. 3, C3; 81.1, C1.

   Mass spectrum: m/z 940 (M+, absent), 795 (8%), 703 (6), 375 (5), 149 (5),   147 (28),   103   (82),   73 (100). 



  1. Examples of methods used for   acetalation   
Use of polyfluorinated diol   1   (formula I : X = O; n = 1; R1 = R2 = R4 = R5 = R6 =   R9   =   H   ; R3 = -CH2CH2C6F13)18 in the preparation of acetals and ketals 7-12. 

 <Desc/Clms Page number 22> 

 



     (a)   Method   1 : Diol   1   and carbonyl compound (1, 1 mol equiv)   were dissolved together in toluene (20 L per mol). p-Toluenesulfonic   acid monohydrate (0. 1 mol   equiv) was added and the mixture refluxed in a Dean-Stark apparatus for   20   h under argon. The solution was cooled, washed with 10% aqueous   KxCOs   solution, dried, evaporated under vacuum. The resulting solid was normally chromatographed on silica gel using a gradient   of Et20/light   petroleum and the major product recrystallized. 



   (b) Method 2 : Diol 1 and carbonyl compound (1. 1 mol equiv) were dissolved together in toluene (20 L per   mol).     Pyridinium p-toluenesulfonate (PPTS) (0. 1   mol equiv) was added and the mixture refluxes a Dean-Stark apparatus for 20 h under argon The solution was cooled, washed with 10% aqueous K2CO3 solution, dried, evaporated under vacuum. The resulting solid was normally chromatographed on silica gel using a gradient of Et2O/light petroleum and the major product   recrystallized.   



     (c)   Method 3: Diol 1 and carbonyl compound (1.0 mol equiv) were dissolved   together in BTF   (20 L per mol) and Amberlyst 15 resin (126 g per mol) and 4A molecular sieves (4.2 kg per mol) were added and the mixture stirred for 20 h at room temperature. The resulting mixture was filtered and the residue of molecular sieves was washed well with   Et2O.   The filtrates were combined and evaporated under vacuum, and the resulting solid chromatographed on silica gel using a gradient of Et2O/light petroleum and the major product recrystallized. 



   (d)   Method 4 : Diet 1   and carbonyl compound (1.0 mol equiv) were dissolved together in cyclohexane   (20   L per mol) andp-toluenesulfonic acid   monohydrate   (0.7 mol equiv.) and 4A molecular sieves (4. 2 kg per mol) were added. The mixture was stirred for 20 h at room temperature then filtered and the residue of molecular sieves washed well with Et2O. The filtrates were combined, washed with   10% aqueous KzCOs   solution, dried and evaporated under vacuum, and the resulting solid chromatographed on silica gel using a gradient of   St2 (;)/light petroleuin   and the major product   recrystallized.   



   It has been noted that aldehydes react more readily than ketones. Methods 1 and 2 proceed to completion with aldehydes and ketones. Method 4 proceeds well with aldehydes but less well with ketones while Method 3 is satisfactory for both aldehydes and ketones. 



  The same four methods are suitable for use in the   preparation ofacetals and keta ! s from     a   wide range of polyfluorinated diols, including   2   (formula   I   : X = O; n = 1; R1 = R2 = R 5 = R6 = R9 = H; R3 = R4 = -CH2CH2C6F13), 3 (formula 1 : X =   0   ; n   =   1 ; R'= R2 = R9   = H; R3 = R4 = CH3; R5 = R6 = -CH2CH2C6F13), 5 (formula @:    X =   0 ; ri   = 0; R1 = R2 = 

 <Desc/Clms Page number 23> 

 R9 = H; R5 = R6 = -CH2CH2C6F13), and 6 (formula   1   :   X     =   O; n = 2; R1 = R2 = R3 = R4 = R9 = H; R5 = R6 = -CH2CH2C6F13). 



    2.   Examples of   highlw fluorinated derivatives   
The following acetals and ketals are representative of those capable of formation by Methods 1-4, Neither the compounds themselves nor the methods by which they are prepared should be construed as limiting the invention in any way. 



  Derivatives prepared from polyfluorinated diol 1 (formula I: X = O; n = 1; R1 = R2 = R4 = R5 = R6 = R9 = H; R3 = -CH2CH2C6F13)18 5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane-2-spirocyclopentane 7 
 EMI23.1 
 
Prepared from diol 1 and cyclopentanone by Method 1 as an oil in   70%   yield b. p. 100 C/0. 07 mmHg (Found : C,   39.   78; H, 3.79.

   C16H17F13O2 requires : C,   39. 36   ; R   3.51%). 1H NMR (300 MHz, CDCl3): # 1.58, m, (H1')2   ; 1. 66, m, (H2'')2 and (H3")   2   ; 1.   81,   m, H5; 1.88, m, (H1'')2 and (H4'')2; 2.07, br m, (H2')2; 3.55, dd, J 12.   1,     8.     3 Hz,     Ha4   and Ha6; 3. 93,   dd,   J 12.1, 7.9   Hz,     H, 4 and H, 6.   



  Trans- and cis-2-phenyl-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoroocytl)-1,3-dioxane 8 
 EMI23.2 
 
Prepared from   diol µ   and benzaldehyde as a 58: 42 mixture of   trahis   and cis diastereoisomers in   95%   yield by Method   2   using toluene as solvent and 80% yield by Method 4.

   Chromatography gave trans-2-phenyl-5-(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-1,3-dioxane 8 m.p. 77-79 C (Found: C, 42.24; H, 3.32.   CisHisFuO2   requires : C,   42.37; H, 2.96%). 1H NMR (300 MHz, CDCl3): #    1.45, m,   (Hl')     2 ; 2,   05, br m, (H2')2 ; 2. 16, m, H5 ;   3.     59,   dd, J 11.3, 11.3 Hz, Hax4 and Hax6; 4. 27, dd, J 11.7, 4. 5 Hz,   He@4 and Heq6; 5,43, s, H2   ; 7. 35, m, 3 ArH; 7. 47, m, 2 ArH''. 13C NMR (75.   6     NIH7,   CDCl3) :   0     18.   8, Cl' ; 28. 1   C2';   33.   5,   C5 ; 71. 7, C4 and C6 ; 101.6, C2 ; 125.9, C2'' and C6"or C3"and C5''; 128.2, C3'' and C5'' or C2'' and C6''; 128.9, C4'' ;

     138.     0,   Cl". 

 <Desc/Clms Page number 24> 

 



  Mass spectrum : m/z 510 (M+, 4%), 509 (M-1, 8), 433 (2), 107 (38), 105 (100), 79 (19), 77   (34),   55 (14). The cis isomer could not be fully separated from its trans isomer. 



   2-methyl-2-phenyl-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 9 
 EMI24.1 
 
Prepared   Sont   diol   J   and acetophenone as a   67 :   37 mixture of   t s and cis     diastereoisomers m 84% yield by Method 1 with toluene   as solvent and as a 59; 41 mixture of the same isomers in 74% yield by Method 3. The mixture was chromatographed on silica gel to give in-order of elution   r-2-methyl-2-phenyl-c-5-     (3,   3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane trans-9 as white flakes m. p. 



  92-93. 5 C (petroleum) (Found : C, 43. 60 ; H,   3.   30. C18H17F13O2 requires: C, 43.52; H, 3. 27%). 1H NMR (300 MHz, CDCl3) :   #      1.   22, m, (H1')2 ; 1.52, s, 2-CH3; 1.99, br m, (H2')   ; 2.. 08, m, HS   ; 3.40,   dd,   J   11.   3,11. 3   Hz,   Hax4 and Hax6 ; 3.   s     dd,   J   11.   3,4.   5   Hz, Heq4 and Heq6; 7.33, m, 1   ArH ;   7. 38-7.44, m, 4   ArR."C NMR (75.   6   MHz,     CDCl3): #   18.8, C1'; 27. 9, C2'; 32.0, C1''; 33. 6, C5 ; 65.8, C4 and   C6   ;   100.   6,   C2 ; 126.   6,   C2"'and   C6''' or C3''' and C5''';

   127.7, C4'''; 128. 7, C3"'and C5''' or C2''' and C6'''; 140. 4,   Cl'".   



  Mass spectrum : mlz   512 (M, absent), 509 (5%),   447 (4),   149   (6),   121 (12),   105 (100), 91   (7), 77 (28),   69 (21), 43 (37); and r-2-methyl-2-phenyl-t-5-(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-1,3-dioxane cis-9; which could not be fully separated from   the irans     isomer. 1H NMR (300 MHz, CDCl3): # 1.32, m, H5   ; 1.51, s, 2-CH3; 2.07-2.20, m, (H1') 2; 2.15-2.32, br m, (H2')2; 3.69, dm, J   11.   7 Hz, Hax4 and Hax6 ; 3. 94, dm, J 11. 7   Hz,   Hcq4 and Heq6; 7.31, m, 1 ArH; 7.37-7.46, m, 4 ArH. 13C NMR (75.6 MHz,   CDCl3): #    20.   1,   Cl' ; 28. 2,   C2' ;   31.   6,   Cl" ; 33.2, C5 ; 64.0, C4 and   C6   ; 100. 8, C2;

   126.5, C2''' and C6''' or C3''' and C5'''; 127. 7, C4'''; 128.6, C3''' and C5''' or C2''' and C6'''; 140.   7,   C1'''. 



  2, 2-diphenyl-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 10 
 EMI24.2 
 

 <Desc/Clms Page number 25> 

 
Prepared from diol   1   and benzophenone in 64% yield by Method 1 using toluene as solvent. White flakes m.p. 70.   5-72 C   (petroleum)   (Found :   C, 48. 86; H, 3.56. 



  C24H19F13O2 requires: C, 49.16   ; H, 3.27%). 1H NMR (300 MHz, CDCl3): # 1.62, m,     (Hl')     2   ; 1. 96,   r,   H5; 2.09, br m, (H2')2; 3.70, dd, J 11.7, 7.9 Hz, Hax4 and Hax6; 4.09, dd, J 11.7, 4.1 Hz, Heq4 and Heq6; 7.20-7.39, m, 6 ArH; 7.50, m, H2'', H2''', H6'' and   H6'"."C     NMR     NMR (75.6 MHz, CDCl3): # 19.3, C1'; 28.   2, t, J22. 5Hz, C2'; 33.6, C5 ; 65. 5, C4 and C6;   101.   2, C2 ;   126.   0 and 126.7, C2'' and C6'' and C2''' and C6''' or C3"and C5'' and   C3'"and C5"   ; 127.   8   and 127. 9, C4"and C4'''; 128.2 and   128. 5, C2"and   C6"and C2''' and C6''' or C3'' and C5'' and C3''' and C5'''; 142.5, C1'' or C1'''.

   Mass spectrum:   7nez   626   (MF,   absent),   510 (10 ro),   509   (55),     182 (25),   165   (10),   154   (8),   123   (8),   105   (100),   77 (65), 55 (15). 



  2, 2-diethyl-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 11 
 EMI25.1 
 
Prepared from diol 1 and 3-pentanone in 73% yield by Method 3 as solvent. 



  Colourless oil b. p. 100 C/0. 1 mmHg (Found: C, 39. 15; H, 4,25. C16H19F13O2 requires : C,   39.   20; H, 3. 91%). 1H NMR (300   zu     CDCl3: # 0.87, t, 2-CH2CH3; 1.55-1.80, m,     (H1')   2, H5, 2-CH2CH3 ; 2. 05, br m, (H2')2 ; 3.   58,   dd, J 11.7, 4.5 Hz, Heq4 and Heq6; 3.92,   dd,   J 11. 7,7. 5 Hz, Hax4 and Hax6. 13C NMR (75. 6   MHz, CDCl3): # 7.3, Cax2'';   7.4, Ceq2'''; 19.4, t, J4.4, 3   :   6. Hz, C1'; 24.4, Cax1''; 26.9, Ceq1'''; 28.2, t, J22.5 Hz, C2'; 33.4, C5; 63. 2, C4 and C6; 101.   2,   C2.

   Mass spectrum : mlz 490   Oe,   absent), 461 (20%), 169   (2),   127 (3), 87   (20),     69     (10),   57 (100), 55 (8), 41 (10). 



  2-(3-hydroxylphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 12 
 EMI25.2 
 
Prepared from diol 1 and   3-hydroxybenzaldehyde   as a   63     37   mixture of trans- and cis-diastereoisomers in 83% yield by Method 2 and as a 93:7 mixture of the same isomers in   83%   yield by Method 4. White flakes m.   p.   118-119 C (petroleum) (Found;   C,   40.95; H, 2.82.

   C18H15F13O3 requires: C, 41.08 ;   H,   2.   87%). 1H NMR (300 MHz): #   1.   42, m, (m') 2 ;   2. 06,   m,   (H2')2 2   ; 2. 14,   m, H5; 3.   58,     dd,     J   11. 3, 11.3 Hz, Hax4 and Hax6; 

 <Desc/Clms Page number 26> 

 4.   26,   dd, J11.7, 4.5 Hz, Heq4 and Heq6 ; 4. 87, br   s,   OH; 5.38, s, H2; 6.82, dd, J7.9, 2. 3 Hz, H4''; 6.   96,   S, H2' ; 7.02, d, J7.5 Hz, H6''; 7.22, dd, J7.9, 7. 5 Hz, H5''. 13C NMR   (75. 6 M)   :   ci   18.8, C1'; 28.0, t, J22. 9 Hz,   C2' ; 3 3. 5, C5 ; 71.   7, C4 and C6; 101. 1, C2; 112.9, C2''; 115. 9, C4''; 118. 4, C6''; 129.6, C5'' ; 139. 6, C1'';

   155. 5,   C3".   Mass spectrum : m/z 526 (M+, 4%), 509 (2), 123 (18), 122 (71), 121   (100),   94 (30), 77   (20),   9 (33), 65   (37),   55   (48).   



  Derivatives prepared from polyfluorinated diol 2   (formule     1   :   X     = 0   ; n = 1 ;   R1     ruz   =   R   = R4 = -CH2CH2C6F13). 
 EMI26.1 
 



  5, 5-E,'is (3, ', 4, V, 5, 5, d, Ï, i', 7, 8, 3, 8-decaflvorooc4blJ-2-et1-', 3^ xXe 13 
CeF13zZ 2eft3 
6 r"") 4 6Cm4 o A - : XH 1 
Ill. 



   I Diol 2 and   propionaldehyde   were treated by Method 3 to give 2-ethyl-5,5- bis (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 61 as a colourless oil (0.   187   g, 96%). vmax 2948, 2851, 2774, 2726, 2665, 1728, 1474, 1461, 1366, 1317, 1240, 1196, 1146, 1122, 1070, 708. 1H NMR (300 MHz) :   q   94, t, J7.5 Hz, CH2CH3 ;   1.     36,   m, CH2CH3; 1. 64, m, (H2')2; 1.99, m, (H1')2 and (H1'')2; 2.16, br m, (H2'')2; 3.50, d, J11.3 Hz, Hax4 and Hax6; 3. 79, d, J11.7 Hz, Heq4 and Heq6 ; 4.   40,   t, J4. 9 Hz, H2. 
 EMI26.2 
 



  , 8, 8, 8-trid--cajyuoroociyl)-2-phenyl-1. 3- & oxan 14 
C6F3) T
1'"", wJ 1 
6 () 4 
7. 0 
0" 
14   (i) Diol   2 and benzaldehyde were treated by Method   2   to give a yellow   oiJ   that was column chromatographed on silica gel   and recrystallized from   light petroleum to give 5,5-bis(3,3,4,4,5,5, 6, 6, 7,7,8,8,8-tridecafluorooctyl)-2-phenyl-1,3-dioxane 14 as white needles   (70%)   m. p.   60-6I C (Found : C, 36. 36   ;   II,   2. 20.

   C26H18F26O2 requires : C, 36. 47 ;   H,   2. 12%). 1H NMR (300 MHz) :   #1.45, m, (H1')2; 2.05, m, (H2')2; 2.11, m, (H1'')2;   2.17,   ni,   (H2'')   2 ; 3.   74,   d, J   11.   7   Hz, Hax4 and Hax6; 3.96, d, J 11.7 Hz, Heq4 and Heq6; 5,44, s, H2; 7.39, m, H2''', H4''' and H6'''; 7.45,   m,   H3''' and H5'''. 13C NMR (75. 6 

 <Desc/Clms Page number 27> 

   MHz): #    21.7,   Cl" ; 22.   9, C1'; 24. 3, t, J22.9 Hz, C2'; 25. 7, t, J22.2 Hz, C2''; 33.4, C5; 74.1, C4 and C6 ; 102.2, C2; 126.0, C3''' and C5'''; 128. 3,   C2'"and   C6'''; 129.1, C4'''; 137.5, C1'''.

   Mass spectrum: m/z 855   (M-', 40/o),   401 (5),   373   (2), 327   (2),     149   (5), 131   (6),     123     (17),   105   (100),     97 (20), 91 (32), 79 (35), 77 (45), 69 (72).   



     (ii)   Diol 2 and benzaldehyde were treated by Method 3 to afford 5, 5- bis(3,3,4,4,5,5,6,6,7, 7, 8, 8,8-tridecafluorooctyl)-2-phenyl-1,3-dioxane 14 in 89% yield. 



  Derivatives prepared from polyfluorinated diol 3 (formula I : X = O; n = 1; R1 = R2 = R9 = H; R3 = R4 = CH3; R5 = R6 = -CH2CH2C6F13) 5,5-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-(3-hydroxyphenyl)-1,3-dioxane 
 EMI27.1 
 Diol.   2   and   3-hydroxybenzaldehyde   were treated by Method 2 to afford 5, 5-   bis (3)   3, 4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-(3-hydroxyphenyl)-1,3-dioxane 15 as white   ilakes   (0, 432 g, 91%) m. p. 106-108 C (Found : C,   35. 90   ; H, 2. 13.

   C26H18F26O3 requires   : C,   35. 80; H, 2.08%). 1H NMR (300 MHz) :   LI   1.45, m, (H1')2; 1.98, M, (H2')2; 2. 07, m, (H1'')2 2 ; 2. 20, m, (H2'')2; 3.72, d, J11. 7   Hz,   Hax4 and Hax6; 3. 95, d, J 11.   7     Hz,   Heq4 and Heq6; 4.86, br   s,     OH ;   5, 39, s, H2; 6.83, dd, J 7.   9,   2.6 Hz,   H4'" ;   6.94, dd,   J2.     3,   1. 5 Hz,   H2"' ; 7. 02,   d,   J 7.   5 Hz, H6'''; 7.   25,   dd, J7. 9, 7.5 Hz,   H5'"."C NMR   (75.   6     NIEZ)   :   O   21.   b,   C1''; 22.   8,   Cl' ; 24.3, t, J22.2 Hz, C2';

   25.6, t, J21.1 Hz, C2''; 33. 4,   C5   ; 74.   1,   C4 and C6   ; 101. 8,   C2;   112.     9,   C2''' ; 116. 1,   C4'" ; 118.   5,   C6"µ   ;   129.     7,   C5'''; 139.   1,   C1'''; 155. 5,   C3"'.   Mass spectrum :   Dilz   872 (M+, 3%), 871 (4), 855   (2),   779 (1), 401 (3), 373 (3), 327 (2), 219 (5), 167 (8), 149 (30), 123 (63), 122 (100), 121   (94),   95 (35), 81   (51), 69 (90).   



  4,4-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-5,5-dimethyl-2-ethyl-1,3-dioxane   16   
 EMI27.2 
 

 <Desc/Clms Page number 28> 

   Diol 3   and   propionaldehyde   were treated by Method   3   to   give 4-   bis (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-5,5-dimethyl-2-ethyl-1,3-dioxane 16 as a colourless oil   (94%),     #max 2972, 2884,    1471, 1398,   1367,   1317, 1240, 1196, 1145,   1053,     707. 1H NMR (300 MHz): # 0.77, s, (CH3)ax; 0.91, t, J7.5 Hz, CH2CH3;    1. 22, s,   (CR)   eq ; 1.63, m, CH2CH3; 1.63, 1.79 and 2. 46,   in,   (H1')2 and (H1'')2 ;   Z.   12, br m, (H2')2 and   (H2")   ;

   3.36, d, J11.7 Hz, Hax6; 3.79, d, J12.1 Hz, Heq6; 4.52, t, J4.9 Hz, H2. 13C NMR   (75.6 MHz, CDCl3): #7.8, CH2CH3; 20.2, (CH3)ax; 20.9, C1'; 22.9, (CH3)eq; 24.6,   t, J21.8 Hz, C2'; 24.   9, Cl" ;   26.   7,   t, J22. 2 Hz, C2''; 27.9, CH2CH3 ;   36. 2, C5   ; 74.   Z C6   ; 77.0, C4 ;   99.     4,   C2. Mass spectrum ; m/z 836 (M+, absent), 761 (5%), 489 (2),   431 (8),   387   (6),   375 (12), 119 (3), 85 (15), 69   (8),   57   (39),   56   (100).   



    -   4,4-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-5,5-dimethyl-2-phenyl-1,3-dioxane 17 
 EMI28.1 
 (i) Diol 3 and benzaldehyde were treated by Method 2 to give a mixture of white solid and colourless oil   (0.   269 g) that was adsorbed on to fluorous reverse phase silica geld and the gel loaded on to a chromatography column. The column was flushed with 70:30 MeOH/H2O then light petroleum. The fraction from light petroleum was column chromatographed on silica gel to yield 4,4-bis(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-5,5-dimethyl-2-phenyl-1,3-dioxane 17 as a colourless oil   (85%)   b. p. 



    175 C     (oven)/0.   4 mmHg (Found: C,   38. 32   ; H, 2.70 C28H22F26O2 requires: C, 38.03 ; H, 2.51%). vmax 3071, 3038, 2865, 1474, 1397, 1316, 1240, 1196, 1145,   1101,     1019,   746, 735, 708, 698. 1H NMR (300 MHz) :   00.     86,     s,   (CH3) ax; 1.36, s, (CH3)eq; 1.78, m, Ha1';   1.   89,   ni,   (H1'')   2   ;   2. 20,   br m, (H2')2 and (H2'')2; 2. 63, m,   Bol ;   3. 54, d, J12.1 Hz, Hax6; 4.   02,   d, J12. 1 Hz, Heq6 ; 5,54, s, H2; 7. 40, m, 5xArH. 13C NMR (75. 6   MHz): # 20.4,   (CH3) ax ;   20.   8,   Cl'     ;   23.0, (CH3) eq;

   24.8, t, J20.3 Hz, C2'; 25. 1, C ; 26.3, t, J21.8 Hz, C2"   ; 36.   2, C5; 74.   7,   C6; 78.   4,   C4 ; 95. 5,   C2 ;   125. 9, C3''' and C5'''; 128.3, C2''' and C6''';   129.   1, C4'''; 138. 0,   Cl"'.   Mass spectrum :   m/z   884 (M+, 2%), 761 (2), 431 (4), 375 (4), 162 (5), 149   (6), 123   (8), 107   zoo),   105 (27),   56     (34).   



  (ii) Diol 3 and benzaldehyde were treated by Method 3 to, give acetal 17 in 88% yield. 



  4,4-Bis(3,3, 4,   4,     5,     5,     6,   6,7,7,8,8,8-tridecafluorooctyl)-2-phenyl-2,5,5-trimethyl-1,3- dioxane 18 

 <Desc/Clms Page number 29> 

 
 EMI29.1 
 Diol 3 (0.241 g, 0.30 mmol) and acetophenone (0. 046 g, 0. 38 mmol) were treated by Method 2 with PPTS (0.   013 g,   0.05 mmol) as catalyst to give a colourless oil   (0.   271   g)   that was separated on silica gel.

   The fraction from 5: 95 Et20/light petroleum was evaporated to afford crude 4,4-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2- phenyl-2,5,5-trimethyl-1,3-dioxane 18 as a colourless oil   (0.   034 g,   12%).'H NMR   (300 MHz) :   Q0.   83, s, (CH3)ax; 1. 24, s, (CH3) eq; 1.54, s, CH3, 1.80-2,27, br m, (H1'')2, (H1')2, (H2')2 and (H2'') 2;   3.     48,     d J 11.   7   Hx,     tE   ; 3.92, d, J 11.7 HA   Hzq6   ; 7.   30,     m,   3xArH 7. 42, m, 2xArH. 



  4,4-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-5,5-dimethyl-2-(3-hydroxyphenyl)-   J,     3-dioxine   19 
 EMI29.2 
   9g   
Diol 3 and 3-hydroxybenzaldehyde were treated by Method   2 to afford 4, {-   bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-5,5-dimethyl-2-(3-hydroxyphenyl)-1,3-   dioxane 19 as   white flakes (91%) m. p. 73-74 C (light petroleum) (Found: C, 37. 38 ; H,    
2. 51.

   C28H22F26O3 requires: C, 37.35; H, 2.465). 1H NMR (300 MHz): #0.85, s,   (CH3)ax; 1.35, s, (CH3)eq ;   1.   78, ddd,   J   15.   1,   10.   2,   4.   9     Hz,   Ha1'; 1.89, t, J8.6 Hz, (H1'')2; 
2,   0     38,   m,   (H2') 2   and (H2'')2; 2.61, ddd, J15. 4,11. 6, 4.5 Hz,   1-1l'   ; 3.53, d, J11. 7 
Hz, Hax6; 4.00, d, J 11.7   °     I-L,,   ; 4, 84, br   s,   OH, 5.49, s, H2 ; 6. 83, dd, J7.9, 1.9 Hz, 
H4''' ;   6.   94, d, J 2.3 Hz, H2'''; 6.97, d, J7. 9 Hz, H6'''; 7. 25,   dd,   J7.9, 7. 9 Hz, H5'''. 13C 
NMR (75. 6 MHz) :   D   20. 4, (CH3)ax; 20.7, C1'; 23.0, (CH3)eq;

   24.8, t, J 22.   2   Hz, C2';   25.     1,   C1"; 26. 3, t, J22.5 Hz, C2''; 36.2, C5 ; 74. 6, C6; 78.5, C4; 95.1, C2; 112.8, C2'''; 
116.1, C5'''; 118.4, C6'''; 129.7, C4'''; 139.7, C1'''; 155.6, C3'''. Mass spectrum : m/z 901   (M-M, trace),   415 (11%), 375 (7), 139 (12), 123 (45), 122 (100),   121   (41), 95 (13), 69    (25).   

 <Desc/Clms Page number 30> 

 



  Derivatives prepared from polyfluorinated diol 5   (formula I :   X = O; n =   0   ;   R-R-R   =   H     ;   R5 = R6 = -CH2CH2C6F13) 
 EMI30.1 
 4 4-Bis (3, 3, 4, 4, 5,. 5, 6, 6, 7, 7, 8, 8, 8-t-deca c 
S 6F13 z, 
2 &commat;S)
S 
2"' 
CH- 
20 (i) Diol 5 and benzaldehyde were treated by Method 2 to give 4,4- bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-phenyl-1,3-dioxolane 20 as a colourless oil (70%)   b.   p, 165 C (oven)/0.5 mmHg (Found: C, 35.70 ;   R     1.   97. 



  C25H16F26O2 requires: C, 35.   65   ;   R   1.91%). vmax 3041, 2960, 2878, 1456, 1366, 1317, 1240, 1209, 1145, 1069, 732,   708,   699. 1H NMR (300   MHz): # 2.00,    br M, (H1')2 and (H1'')2 ; 2. 22,   br m, (H2') 2   and (H2'')2; 3.86, d, J 8. 7   Hz,   Ha5 ; 4. 02,   d,     J   9.   0   Hz, Hb5 ; 5. 90, s, H2; 7.40, m, 5xArH. 13C NMR (75.   6     MHz): #25.   8, t, J22.2 Hz, C2' and C2'';   27.   5, Cl' ; 27. 7, Cl" ; 73. 6, C5 ; 80.4, C4 ; 104.   1,   C2 ; 126.1, C2"'and C6'''; 128. 4, C3''' and C5'''; 129.5, C4'''; 136.5, C1'''.

   Mass spectrum: m/z 842 (M+, 13%), 720 (4),   495     (18),     401     (19),   375   (10),     327 (3),   131   (4),   123 (30), 107 (66), 105 (100), 91   (29),   78 (69). Unreacted 1,2-diol 5 (28%) was recovered as white solid. 



   (ii) Diol 5 and benzaldehyde were treated by Method 3 to give 4,4- bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-phenyl-1,3-dioxalane 20 as a colourless oil (95%), which by GC was of 98% purity.   a,   4-Bis(3,3,4,4,5,5,6,6, 7,   7,   8,   8,   8-tridecafluorooctyl)-2-methyl-2-phenyl-1,3-dioxolane 21 
 EMI30.2 
 (i) Diol 5 and acetophenone were treated by Method 2 to give 4, bis(3,3,4,4,5,5,6,6,7, 7, 8,8,8-tridecafluorooctyl)-2-methyl-2-phenyl-1,3-dioxolane 21 as a colourless oil (11%) b. p.   170"C   (oven)/0, 8 mmHg (Found: C,   36. 61 ; H, 2. 08.   



  C26H18F26O2 requires: C, 36.47 ;   H,   2. 12%). vmax 2723, 1319,   1247,   1203, 1145, 1071,   1044,   697, 655. 1H NMR (300   MHz): # 1.    53-1. 73, m, (H1')2; 1.63, s,   Chia   ;   1.   75-2.   00,     m,   (H1'')2; 1.98, m, (H2')2 ; 2.   29,     m,   (H2'') 2 ; 3.   60,   d, J9.1 Hz, Ha5; 3.92, d,   J 9   

 <Desc/Clms Page number 31> 

 Hb5 ; 7.34, m, H2''', H4''' and H6'''; 7. 43, m, H3''' and H5'''. 13C NMR (75.6 MHz):   #25      8,   C2'; 26.   0,   C2" ; 27.5, C1'; 28.1, C1"; 28.8, CH3; 72. 7,   C5   ; 81.1, C4; 110.5, C2 ; 124. 7, C2''' and C6'''; 128. 0, C4'''; 128.3, C3''' and C5''';

   143.   4,     Cl'".   Mass sectrum; m/z 856   (M+,   absent), 841 (5%), 779 (1), 509 (3), 375 (3), 133   (17),   123 (22), 105 (100), 77   (18).   



     Unreacted 1, 2-diol 5 (87%)   was recovered as a white solid. 



  (ii) Diol 5 and acetophenone were treated by Method 3 for   2   days to give 4,4- bis   (3,   3,4,4,5,5, 6, 6,7,7,8,8,8-tridecafluorooctyl)-2-methyl-2-phenyl-1,3-dioxolane 21 as a colourless oil (54%), and   1,     2-diol S (37%)-was recovered as   a white solid. 



  4,4 Bis (3, 3,   4,   4, 5,   5,   6, 6,7,7,8,8,8-tridecafluorooctl)-2-(3-hydroxyphenyl)-1,3-dioxolane 22 
 EMI31.1 
 
Diol 5 and   3-hydroxybenzaldehyde   were treated by Method   2   to give 4 bis (3, 3, 4, 4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-(3-hydroxyphenyl)-1,3-dioxolane 22 as a colourless oil (92%) b.p. 200 C (oven)/0.4mmHg (Found: C2 35.11; H, 1. 95. 



   C25H16F26O3 requires : C, 34:   98; H, 1.88%). 1H NMR (300 MHz): # 2.00, br m, (H1')2   and   (Hl")     2 ;   2.   22,   br m, (H2')2 and (H2")2 ; 3.   86,     d,   J   8.   7 Hz, Hu5; 4.00, d, J 8.7 Hz, Hb5; 4.   91,   s, OH; 5.85, s, H2; 6.83, ddd, J 7. 9,   2.   6,   1.   1 Hz, H4'''; 6.   91,   dd, J2. 2.2, 1.5   Hz,     H2'" ;   7. 01,   d,   J 7.5 Hz, H6'''; 7. 26, dd, J-7. 9,7.   5     ha   H5'''. 13C NMR (75. 6 MHz) :   #25.8,    t, J 22.2 Hz, C2' and C2''; 27.4, t, J 3. 6 Hz, C1'; 27.   7,   t, .   J3. 2144 Cl" ; 73 ;   5, C5 ;

     80. 5, C4 ; 103.   7, C2; 113.0, C2'''; 116.4, C4'''; 118.5, C6'''; 129.8, C5'''; 138. 5,   Cl'" ;   155.7, C3"'. Mass Spectrum; m/z 858 (M+, 0.9%), 857 (M-1+,1), 511 (3),   375 (4), 169   (3),1 39 (14), 121 (51), 94 (100), 77 (16), 65 (13). 



  Derivatives prepared from polyfluorinated diol   6   (formula   f   : X=O; n=2; R1=R2=R3   =   R4=R9=H; R5=R6= -CH2CH2C6F13) 4, 4-bis(3,3,4,4,5,5,6,6,7, 7,   8,     8   8-tridecafluorooctyl)-2-phenyl-1,3-dioxepane 23 

 <Desc/Clms Page number 32> 

    5   10    15   20 25 
 EMI32.1 
 (i) Diol   6   and benzaldehyde   were   treated by Method 2 to give 2, 2bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoroocty)tetrahydrofuran 78 as a colourless oil 
 EMI32.2 
 (25%) b. p. 1 lOaC (oven)/0. 5 i3 
5S
5 
0 \-C6Fi3 
78 (Found : C, 31. 56 ;   H,   1.97.

   C20H14F26O requires : C, 31.43; H, 1.85%). vmax 2964, 2874,   1456,   1317,   1196,     1071,     847,     813,   746, 730, 708. 1H NMR (300 MHz) :   #1.   83,   m,     at)   2, (H1')2 and (H1'')2; 1.98, m, J 7.2 Hz, (H4)2; 2.   16,   br m, (H2')2 and (H2")2 ; 3.88, t, J 6.   8 Hz, (H5)2. 13C NMR 975.6 MHz): #26.   4,   t,     J   22.2   Hz,   C2'and   C2" ;   26.4, C4 ; 28.9, C1' and C1"; 35.3, C3 ; 68.4, C5 ;   82.   3, C2.

   Mass   spectrum : mlz 764 (MF, absent),     723   (5%), 4 18 (10), 417 (100), 375 (34), 327 (5), 263 (5), 169 (6), 131 (8), 97 (24), 69 925)   ;   and 4,4-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-phenyl-1,3-dioxepane 23 as a colourless oil (8%) b. p.   170 C     (oven)/0. 3mmHg (Found   : C, 37.16 ;   H,   2. 08. 



    C27H2O.   requires : C, 37.26 ; H, 2. 32%). vmax 3069,   3036,   2958, 1456, 1366,   1316,   1190,   1114,     1056,   980,   812, 746, 697. 1H NMR (300 MHz); #1.   78-2.   40,   m,   (H5)   2. 



  (H6) 2, (H1')2, (H1")2, (H2')2 and (H2")2; 3.65, ddd, J 12.1, 10.2, 2.6 Hz, Hax7 ; 4. 16, ddd,   712. 1, 3.   8,3. 4   Hz,     H. q7   ; 5,66,   s, H2   ; 7. 30-7, 40, m, 5xArH. 13C   NMR. (75.   6 MHz):   #25.7, t,    J22. 5 Hz, C2" ; 25.9, t, J 22. 5   Hz,     C2' ; 26. 2, Cl' ; 27.   9, C1" or C6; 28.0, C6 or C1"; 37. 4,   C5 ;   70.   5,     C7 ;   77.7,   C4 ; 97. 9, C2   ; 125.6, C2''' and C6'''; 128. 2, C3''' and C5'''; 128. 4, C4''' ; 139.6, C1'''. Mass spectrum : m/z 868 (M+, absent), 747   (4%), 4g3 (4,   417 (100), 375 (32), 147 (96), 119 (13), 105 (94), 77 (58). 



  Unreacted 1, 4-diol 6   (61%)   was recovered. 



   (ii) Diol   6   and benzaldehyde were treated by Method 3 to   give 4, d-   bis(3,3,4,4,5,5,6,6, 7,7, 8,   8,   8-tridecafluorooctyl) 2-phenyl-1,3-dioxepane 23 as colourless oil (25%) and   unreacted     1,     4-diol   6 as   a white solid (73%).   



  3. Example of a method used for thioacetalation 
Use of polyfluorinated disulfide 24 (formula I: X = S ; n = 1 ; R1=R2 = R4=R5 = R6 =H;R3=CH2CH2C6F13; R9= single covalent bond between   X   groups) in the preparation of dithioacetal 25. 

 <Desc/Clms Page number 33> 

 
 EMI33.1 
 



   25 
A solution   ofBF3'OEt2 (0. 10 mL,   0.   6     nimol)   and glacial   AcOB   (0.2   nL)   in 
CHCl3 (1 mL) was stireed under reflux in an argon atmosphere for 15 min. A solution or 4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,2-dithiacyclopentane 24 (280 mg, 
0.6 mmol) and   dimethoxymethane     (0.   054 mL, 0.61 mmol) in CHCl3   (1.   5   mL)   was added over 15 min and the mixture refluxed for another 6   h.   The reaction mixture was cooled)   20   (10   mL)   added, the organic layer separated and the aqueous layer reextracted with Et20 (2   x mL).

   The organic extracts were combined, washed with   10% KOH (10   mL)   and dried (Na2SO4). Removal of the solvent and chromatography of the resulting yellow oil   (23 0 mg) afforded from   the 1% Et2O in light petroleum fraction, unreacted disulfide 24 (75 mg, 27%), and from the 5-10% Et2O in light petroleum fraction, 5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dithiane 25 as (54 mg, 19%) m. p. 68-70 C (ligh petrole) (Found : C,   30.   95; H,   2.     35.     Ci2HjiFj3S2   requires :

   C,   30.91, H, 2.38%). 1H NMR (300 MHz, CDCl3): #1.70-1.   85 (2H,   m,   RFCH2CH2),1.90-2.00 (1H, m,-H2), 2.00 - 2.25 (2H, m, RFCH2CH2), 2.57 (1H, d, J    13.9 Hz, -CH2), 2.60 (1H, d, J 14.3 Hz, -CH2), 2.85 (2H, d, J 14.3 Hz, -CH2-), 3.60 (1H, d, J 13.9 Hz, -CH2-), and 3.82 (1H, d, J 13.9 Hz, -CH2-). 13C NMR (75.5 MHz,   (1H, d, J 13.9 HZ, -CH2-), and 3. 82 (1H, d, J 13. 9 Hz, -CH2-). 13C NMR (75. 5   Mus,     CDCl3): #    25.11 (RFCH2CH2), 28. 02 (RFCH2CH2), 31.57 (-CH2-), 34.39 (-CH-) and 34.55 (2x -CH2-). Mass spectrum : m/z 466 (M+, 90%), 433 (8), 419 (20), 401 (10), 387 (15) and   375 (18).   



  4. Method for preparation of reactant 24 (formula I: X = S; n=1; R1=R2=R4=R5= R6=H; R3=CH2CH2C6F13; R9 =   smg ! e covalent   bond between X groups) (i) Synthesis of 2-(3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl)prpopane-1,3-diol 
 EMI33.2 
 dimesylate 26 '6F 13 
5 
OMsOMs    26   
2- (3,3,4,4,5,5,6,6,7,7,8, 8, 8-Tridecafluorooctyl)propane-1,3-diol 1 (1.   00 g,   2. 36 mmol) and methanesulfonic anhydride (1.65 g, 9.44 mmol) were heated together at 

 <Desc/Clms Page number 34> 

 100 C until they became miscible, whereupon conc H2SO4 (1 drop) was added and the mixture heated at the same temperature for   2   h. The reaction mixture was cooled, diluted with ice-water   (25   mL) and extracted with Et2O (4 x 50 mL).

   The combined organic extracts were dried   (Na2SO4)   and evaporated to dryness to give a tan solid   (1.   00 g) that was   recrystallized   from Et2O to give 2-(3,3,4, 4, 5, 5, 6,6,7,7,8,8,8- tridecafluorooctyl)-1,3-propanediol dimesylate 26 sas colourless flakes (937 mg, 72%) (Found : C, 27. 08; H, 2.   39.   C13H15F13O6S requires: C, 27. 00 ;

   H, 2.61%). 1H NMR (300 MHz,   CDCII) : 0   1.   70-1.     90   92H, m, RFRCH2CH2), 2.   10-2.   30 (3H, m, RFCH2CH2, -CH), 3.06   (6H,   s, 2   x   CH3), 4.20-4.40 (4H, m, -CH2). 13C NMR (CDCl3, 75.   5     MHz): #    18.   18   (RFCH2CH2), 27.99 (RFCH2CH2), 37.39 (2   x   CH3), 37.62 (C2), 67. 14 (2 x -CH2-). Mass spectrum : mlz 403   (23%),   367 (5), 205 (5), 175 (85), 135 (10), 111 (65), 97 (80), 79 (100) and 55 (60). 



    (ii)   Synthesis of 2-(3,3,4,4,5,5,6,6,7, 7,   8,     8-tridecaSuorooctylpropane-1, 3-dithiol   diacetate 27 
 EMI34.1 
 
27 
Potassium   thioacetate (59.   7 mg, 0.52 mmol) was added to a solution of 2- (3, 3, 4, 4,   5,   5, 6, 6, 7,7,   8,     8,   8-tridecafluorooctyl)-1,.3-propanediol dimesylate 26 (100 mg,   0.   17 mol) in DMF (2 mL) under argon and the mixture heated   at 100-C for   20 h. The reaction mixture was cooled, the solvent removed under reduced pressure, the residue diluted with CHCl3, and the mixture filtered. The solid was   washed several times with   more   CHC13,   and the combined CHCl3 solutions washed with H2O (20 mL) and dried (Na2SO4).

   Removal of the solvent under vacuum gave an oil (100 mg), which was flash chromatographed. Elution with 40% Et2O in light petroleum gave 2-   (3,   3, 4,   4,   5,   5,   6,   6,     7,   7,8,8-tridecafluorooctyl)propane-1,3-dithiol diacetate 27 as an orange oil (80   mg,   86 %) (Found: C, 33.50   ;     H,     2.   86. C15H15F13S2O2 requires: C, 33.46,   H, 2.81%).

   IR: #max 2930, 1694 (C=O), 1456, 424, 1354 cm-1. 1H NMR (300 MHz,     CDC13)   :   0   1.   60-1.   80   (2H,   m, RFCH2CH2), 1.80-2.00 (1H, m,-H2), 2.00 - 2. 25 (2H,   ni,   RFCH2CH2), 2. 35 (6H,   s,   2 x   CH3COO),   2. 80-3, 10   (4E,   m, -2 x CH2). 13C NMR (75.5   M     CDCl3): # 22.    74 9RFCH2CH2), 28. 31 (RFCH2CH2), 30.44 (2 x CH3CO), 31.93 ( Z x S-CH2-), 38.13 (-CH-) and 194.92 (-CH3-C=O). Mass spectrum : m/z 538 (M+, 5%), 495   (100),   453   (92),   419   (40),     3 87 (8), 149 (20).   



    (iii)   Synthesis of 4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,2-dithiacyclopentane 24 

 <Desc/Clms Page number 35> 

 
 EMI35.1 
 
Sodium sulfide nonahydrate   (166     mg,     0.   66 mmol) and sulfur (22   mg,   0.69 mmol) were added to   dimesylate   26 (200 mg, 0.34 mmol) in dry DMF (10   mL)   and the mixture heated at   1 00"C   for 3   d.   The reaction mixture was cooled and ice-water   (15   mL) was added. The mixture was acidified with cone.   HCl   and   extracted with EtsO (2   x 50 mL). The combined organic extracts were dried (Na2SO4), and the solvent removed in vacuum to give a yellow oil (143 mg).

   The oil was dissolved in Et2o (5   mL)   and the solution added dropwise to a suspension of LiAlH4 (26 mg, 0. 69 mmol) in   Etz4     (5     ml)   under argon, and the mixture stirred for a further 48 h. The reaction mixture was cooled to 0 C and H2O (10 mL) and then   10% H2S04 (20 mL)   added sequentially. The mixture was filtered through filter aid and the residue washed with Et20 (50 mL). The organic layer was separated and the aqueous layer extracted with more   Et20 (50 mL).   The combined organic extracts were washed with   H20     (25   mL) and dried   (Na2SO4).   



  Evaporation of the solvent gave a yellow oil (110 mg) which was subjected to repeated flash chromatography. Elution with 1% Et2O in light petroleum afforded   4-   (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,2-dithiacyclopentane 24 as a yellow wax (45 mg, 29 %) (Found: C, 29. 46;   H,   2.05. C11H9F13S2 requires: C, 29.22, H. 2.01%). 1H NMR   (300 MHz, CDCl3): # 1.79-1.90 (2h, m, RFCH2CH2), 2.00-2.30 (2H, m,   RFCH2CH2), 2.55-2 70   (1H,   m, H2),   2,   75-2.90 (2H, m, CH2), 3. 20-3. 40   (ZR     E-CH2-)-     13c   NMR (75.   5 MHz, CDCl3); #    24.27 (RFCH2CH2),   29.     64   9RFCH2CH2), 43.62 (2 x CH2), 46. 28 (C2).

   Mass spectrum : m/z 452 (M+, 100%), 387 (33), 367 (8), 327   (8),     119     (5),     103     (2),   73 (38). 



  Examples of selectivity in acetal/ketal formation Reactions of 2,2-bis (3,3,   4,     4,     5,     S,   6, 6,7,7,8,8,8-tridecafluorooctyl)-1,3-propanediol 2 (a) with 1S-(endo,endo)-3-acetyl-bicyclo[2.2.1]hept-5-en-2-ylcarboxaldehyde [Aldehyde versus ketone] 

 <Desc/Clms Page number 36> 

 
 EMI36.1 
   (i)     Diol 2   (0.   227   g, 0. 30 mmol) and 1S-(endo,endo)-3-acetylbicyclo[2.2.1]hept-5-en-2-   ylcarboxaldehyde-3-acetyl (0. 023 g,   0.14 mmol) were treated together by Method 2 with PPTS   (0.   004 g, 0. 02 mmol) as catalyst to give a pale solid (0.   257   g) that was column chromatographed on silica gel.

   Elution with   10 : 90 Et20/light   petroleum gave 1S-(endo,endo)-2-(5,5-bis(3,3,4,4,5,5,6,6,7, 7,   $,   8, 8-tridecafluorooctyl)-1,3-dioxan-2- yl)-3-(2-methyl-5,5-bis(3,3,4,4,5,5,6,6, 7, 7, 8, 8, 8-tridecafluorooctyl)-1,3-dioxan-2- yl)bicyclo[2. 2. 1]hept-5-ene 28 as a white flakes (0. 108 g, 46%) m.p. 95-96 C (EtOH) (Found. C, 34.66 ; H, 1.98.

   C48H36F52O4 requires: C, 34.   63   ; H, 2.18%). 1H NMR (300   MHz): #1.   24, d,   J 8.   7   Hz,   H a7 ; 1.   33,   m, (H1")2 or (H1v)2; 1. 44, s, CH3; 1. 45, m, IM and   (Hl")     2   or (H1")2; 1.78, d, J 7. 9 Hz, Hb7; 1.86-2.   20,   br   ni,   (H1''')   2   (H1vi) 2, (H2")2, (H2''')2, (H2v)2 and (H2vi)2; 2.29, m, H6; 2.91, br s, HI ; 3. 00, br   s,   H4; 3,   39, d, J 12. 1   Hz, Hax4' and Hax6'; 3.49, d, J 11.3 Hz, Hax4iv or HaX6iv; 3. 53, d, J 11.3 Hz, Hax6iv or Hax4iv; 3.72, d, J 11.3 Hz, Hcq4iv and Hcq6iv; 3. 77,   d,   J 12. 1   Hz,   heq4' and Hcq6'; 4.04, d,   J   6.4   Hz, H2' ;

   6.   07, dd, J 5.3, 2. 6 Hz,   H2   ; 6.20, dd, J   5. 3,   3.4 Hz, H3. 13C NMR (75.6 MHz) :   0   17. 1, CH3; 20.9, 218, 22.5, 22.9, Cl", Cl''', clv and Clvi; 24. 2,24. 3, 25. 4, 25. 7, C2", C2''', C2v and C2vi ; 33.1,   C5'or C5" ; 33.   4, Ctiv or C5'; 43.6, Cl; 44.2, C4; 45.3, C6; 46. 7, C7 ;   51.   2, C5; 66.3 and 66.8, C4iv and C6iv ; 73. 8, C4'and C61; 100. 7, C2iv; 106. 1, C2'; 136. 0, C2 ;   137.   9,   C3.   



  Further elution with 10 : 90 Et2O : light petroleum gave 1S-(endo,endo)-3-acetyl-2- (5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxan-2- yl)bicyclo[2.2.1]hept-5-ene 29 as a white solid   (0.     034     g, 26%)   that was   recrystallized     Som   light petroleum as white flakes m.p. 117-117.5 C (Found: C, 37. 81 ; H, 2. 50. 



  C92H24F25O3 requires: C, 38.09 ;   R   2. 65%). vmax 2728, 1699, 1321, 1247, 1209, 1185, 1140, 1119, 1062, 733, 698, HE (300   MHz): #1.35, m, Ha7    ; 1. 45,   m,   (H1")2 ; 1.52, m, Hb7; 2.05, m, (H2") 2; 2. 11, m, (H1''')2; 2.15, d, J 3. 4   Hz,   H5 ; 2.   17,     zu,   (H2''')2;   2.   23,   s,   COCU, 2.   56, m,   H6,2. 94, br s, H1 and   H4   ; 3.   40,   d, J 11.   7     Hz,   Hax4' and Hax6''; 3.77, d,   J     11.   7 Hz, Heq4' and Heq6'; 3.87, d, J 7.9 Hz, H2'; 6.09, dd, J 5.3, 2.6 Hz,   m   ; 6. 22,   dd, J 5.6, 3.4, Hz, H3. 13C NMR (75.6 MHZ): # 21.7, Cl''';

      22. 9, Cl"; 24. 3, t,   J   

 <Desc/Clms Page number 37> 

 22. 5   Hz,   C2"; 25.6, t, J 22.2 Hz, C2'''; 29.7, COCH3; 33. 4, C5' ;   43. 5, Cl or C4   ;   46. 2,   C4 or Cl ; 46. 8, C7 ; 47. 4, C6 ; 53. 8, C5; 73, 5 and 73.7, C4'and C6' ; 105. 8, C2'; 135.7,   C2 ; 136.   9, C3; 209.7, COCH3. Mass spectrum : mlz 914 (M+, absent), 805 (1%), 779   (1),     373     (1), 135 (9),   109 (12), 97 (25), 83 (36), 81 (49), 69   (100),   57 (65), 43 (73). 



  Initial diol 2   (0.   089 g,   39%)   was recovered from the pure Et2O fraction. 



  NMR spectra were assigned through 1H-1H COSY, 1H-13C HMQC and dept   135   experiments. 



  (ii) Diol 2   (0-353 g, 0,   46 mmol) and 1S-   (endo,   endo)-3-aceytl-bicyclo [2.2. 1] hept-5-en-   2-ylcarboxaldehyde   (0. 078   87     0. 47 tnmol)   were treated by Method 2 with PPTS   (0. 012     s   0.05 mmol) as catalyst to give 1S-(endo,endo)-2-(5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8tridecafluorooctyl)-1,3-dioxan-2-yl)-3-(2-methyl-5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8tridecafluorooctyl)-1,3-dioxan-2-yl)bicyclo[2.2.1]he[pt-5-ene 28 as a white soild   (0. 327   g, 78%).   The H spectrum of this substance   was identical to that from part ere was no measurable signal Rom compound 29. 



    (b)   with 3,4, 8,8a-tetrahydro-8a-methyl-1, 6 (2H, 7H)naphthalenedione (Wieland- 
 EMI37.1 
 Miescher ketone) etone versus unsaturated ketone] 
C6FI3-V 6F13 
9 fu oW 30 Diol 2   (0. a 10 g,   0.14 mmol) and Wieland-Miescher ketone (0.027 g, 0. 15 mmol) were treated by Method   2   with PPTS (0.004 g,   0.   02 mmol) as catalyst to give a pale solid 
0, 1   g)   that was loaded on to   FRY-SAPE   cartridge. The cartridge was flushed with 70:30 MeOH/H2O then light petroleum. The fraction from light petroleum was evaporated under vacuum to afford   a   yellow oil (0. 250 g) that was column chromatographed on silica gel.

   The faction from   20   : 80 Et2O : light petroelum was combined and distilled under vacuum to give product 30 as a colourless oil (0. 068 g, 51%)   13C NMR (75.6 MHz): # 21.7; 22.6; 24.9, t J 22.2 Hz;    24.   9 ; 25.   0, t J 22. 5   Hz   ; 27, 2;   29. 9   ; 33.   6 ;   35.   5 ; 38.   6; 46.9 ; 66. 4; 66.7 ; 98.   6   ;   122. 0 ; 138. 1 ;   214.4. 



  Initial diol 2   (0.   028 g, 25%) was recovered from the pure Et2O fraction. 

 <Desc/Clms Page number 38> 

 
 EMI38.1 
 (d) with 4-formylacetophenone [AMehyde /'. N/ ketone) 
06FI3 I-, bfla 
11" 
0 31 
O  . 1 Diol 2   (0.   502 g, 0. 65 mmol) and 4-formylacetophenone (0.102 g, 0.69 mmol) were treated by method   1   in toluene (30 mL) with PPTS (0.018   zu   0.07 mmol) as catalyst to give a pale solid (0.566 g) that was column chromatographed on silica gel. The major fraction, eluted with 3 : 97   Et20-light   petroleum, was evaporated to dryness to give   5,   5- bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-(4-ethanoylphenyl)-1,3-dioxane 31 as a white solid (0.   488   g, 83%).

   The solid was recrystallized from light petroleum to give white needles m. p.   83-84 C   (Found : C, 37. 24; H, 1.95. C28H20F26O3 requires: C, 37. 43; H,   2.24%). 1H NMR (300 MHz): #1.44, m, (H1')2; 2.05, m, (H2')2   ;   2.   10, m, (Hl")2 ; 2.   18,   m, (H2")2; 2.60, s, COCH3; 3.75, d, J 11.7 Hz, Hax4 and Hax6; 3.98, d,, J   11.   7 Hz, Heq4 and Heq6 ; 5. 48, s, H2 ; 7.   US,   d,   J 8.   3 Hz, hand H6'''; 7.97, d, J 8.7 Hz, H3'''a nd   tit,   13C   NMR (75.6 MHz): #21.7, C1"; 22.8, C1'; 24.3 t, J 22.5 Hz, C2'; 25.6, t, J   22.2 Hz,   C2"     ; 26.   6, COCH3; 33.5, C5 ; 74.2, C4 and   C6,   ; 101.3, C2; 126.3, C2''' and   C6"'     ;

   128.   3,   C3.. and C5"' ; 137.   6, C4'''; 142.0, C1'''; 197.6, COCH3. Mass spectrum :   mlz     898     (M+,     1%),     883   (1),   855 (1),   779   (1), 401 (5),   165   (15),   149   (100),     133     (52), 104     (31), 69 (43).   



    Initial diol 2 (0.   083 g,   17%)   was recovered from the pure Et2O fraction. 



  5,5-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-(2-phenyl-(E)-ethenyl)-1,3-   dioxane 3 ?,   
 EMI38.2 
 

 <Desc/Clms Page number 39> 

 Diol 2 (0. 625 g, 0.81 mmol) and cinnamaldehyde (0.169 g, 1.28 mmol) were treated by method I with PPTS   (0.   028 g, 0.   09   mmol) as catalyst to give a pale gel (0.774   g)   that was loaded on to a Silica gel column. The fluorous column was eluted with 70 : 30 MeOH :   Hz0   then light petroleum.

   The fraction from light petroleum was recrystallized from light petroleum to give 5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-(2- phenyl-(E)-ethenyl)-1,3-dioxane 32 as white flakes (0.   704     8%     98%)   m.   p.     78-79'C   (Found: C, 38. 05; H, 2.35.

   C28H20F26O2 requires: C,   38.   11 ; H, 2.28%). 1H NMR (300   MHz): #    1. 41, m, (H1')2; 2.02, br m, (H2')2 ; 2.05,   m,   (H1'') 2; 2.15, m, (H2'')2; 3. 63,   d,   J 
11.7   Hz,   Hax4 and Hax6; 3.89, d,   J     11.   7 Hz, Heq4 and Heq6; 5.   07,     d,   J 4.9 Hz, H2; 6.18, dd, J 16.2, 4.   9   Hz, H1'''; 6.78, d, J 16. 2 Hz, H2'''; 7. 32, m, 3xArH ; 7.39, m, 2xArH. 13C NMR (75.   6     MHz): #21.7, C1''; 22.9, C1'; 24.3, t, J 22.5 Hz, C2';    25.6, t, J 21. 8 Hz,   C2";   33.4,   C   ;   73. 8, C4 and C6   ;   101.   4, CZ ; 124.5, C1'''; 126.8, C2iv and C6iv;

   128. 3,   C4iV   ; 128.5, C3iv and C5iv; 134. 0, C2'''; 135.7, C1iv. Mass spectrum: m/z 882 (M+, 6%), 387 (3),   256     (2), 149 (16), 133 (31),   132 (35), 131   (75), 107 (36),   104   (100),   81 (29), 69 (83). 
 EMI39.1 
 



  (d) with terephthalaldehyde [single versuv two-fold reaction with a dialdehyde] 
CeFis--y. eFl3 r, 1"' , 4'
GF3A., sFi3 ia 6FI3 4 
O" ... v. F, 1 
X4 X 
H in . d4l 6 
Ils 
33 34   (i)   Diol 2   (0.   113 g, 0. 15   mrnol)   and terephthalaldehyde (0. 042 g, 0.31   nimol)   were treated by Method 2 with PPTS (0.004 g, 0. 02 mol) as catalyst to give an off-white solid (0. 108 g) that was adsorbed on to a column of FRP-silica gel. The fluorous column was eluted sequentially with 70 : 30 MeOH/H2O, MeOH and Et2O. The fraction from MeOH gave 4-[5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3- dioxane]benzaldehyde 33 as a white solid (0. 019 g,   15%)   that was recrystallized from light petroleum as a white powder   m.   p.

   (Found :   C,   36.73 ;   R     1.   97. C27H18F26O3 requires : C, 36.67 ;   R,   2.05%). vmax 1706, 1240, 1208, 1143, 1076, 710. 1H NMR (300   MHz): #1.44, m, (H1')2; 2.05, m, (H2')2; 2.09, m, (H1'')2;    2.20, m, (H2'')   2   ; 3.76, d, J 11.7 Hz, Hax4 and Hax6; 3.99, d, J 11. 7 Hz,   Hm4   and Heq6; 5.50,   s,   H2 ; 7.   64,   d, J 7. 9 

 <Desc/Clms Page number 40> 

 Hz,   H2'"and H6'" ;   7.91,   d,   J   8.   3 Hz, H3'''and H5'''; 10. 04, s, CHO. 13C NMR (75.6 MHz)   : #21.7, C1''; 22.   7,   Cl'     ; 24.   3, t, J 22.9 Hz, C2'; 25.6, t, J 22.5 Hz, C2''; 33. 5,   C5   ;

     69.     8,   C1iv; 74.2, C4 and C6 ; 101. 1, C2; 126. 7, C2'''and C6'''; J 29. 7, C3'''and C5'''; 
136.8, C4'''; 143. 3,   Cl'" ; 191. 8, CHO. Mass spectrum   : m/z 884 (M+, 2%), 401 (8),   373     . (4),   167 (9),   149   (31), 135 (100), 133 (66), 105 (23), 69 (88), 55 (54). 



  Elution of the column with Et2O gave 1,4-bis[5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-1,3-dioxane]benzene 34 as a white solid   (0.     08z, 34%)   that was recrystallized from   F-TOH   to give white flakes m.p. 115-116 C (Found: C, 33. 57 ; H,   1.   58.

   C46H30F52O4 requires: C, 33.80 ; H, 1. .85%). vmax 1323, 1240, 1189, 1120, 1073,   1025,   704, 648. 1H NMR (300   MHz): #1.    45,   m,   (H1'') 2 and (H1vi)2 ;   1.   98, m, (H2'')2 and (H2vi)2; 2. 04, m,   (Hl'")     2   and (H1v)2; 2. 17,   ri   (H2'") 2 and (H2v)2 ; 3. 73,   d,     J     11.   3 Hz, Hax4', Hax6', Hax4iv and Hax6iv; 3.96, d, J 11.3 Hz, Heq4', Heq6', Heq4iv and Heq6iv; 5.44, s,   H2'and   H2iv ; 7. 48,   s, H2,   H3, H5 and   H     13C NMR (75.6 MHz): # 21.7, C1'', C1''',   
C1v and C1vi ; 25.   7,     C2",     C2"',   C2v and C2vi; 33. 4, C5' and C5iv;

   74.1, C4', C6', C4iv and   C6'v ; 10 1.   7,   C2'and C2'" ; 126.   0, C2, C3, C5   and C6 ; 13S.   4, CI and C4. 



   (ii) Diol 2 (0.   684   g, 0.   89   mmol) and   terephthalaldehyde (0. 125 g,   0.93   mmol) were   treated by Method 3 with Amberlyst 15 (0.219 g) as catalyst in BTF (10   mL)   to give an off-white solid (0.795 g) that was subjected to chromatography on FRP-silica gel. The fluorous column was eluted sequentially with 70 : 30 MeOH : H2O, MeOH and Et2O. 



  The fraction from   MeOH   gave 4-[5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-   1,     3-dioxcmeJbenzaldehyde   33 as a white solid (0.260   g, 33%). Elution with EtaO   gave 
1 ,4-bis[5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane]benzene 34 as a white solid   (0.   435 g, 30%). The 1H NMR and 13C NMR spectra of this substance were identical to those from part (i). 



     (iii)   Diol 2 (0.684 g, 0.89 mmol) and terephthalaldehyde (0.125 g. 0.93 mmol) were treated by Method 3 with Amberlyst 15 (0.219 g) as catalyst in BTF   (10 mL)   to give an   off-white solid 0. 795 g) that was chromatographed   on FRP-silica gel. The fluorous column was eluted sequentially with 70 : 30 MeOH : H2O, MeOH and Et2O. The fraction from MeOH gave 5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-(4-    formylphenyl)-1,3-dioxane 33 as a white solid (0. 0.260 g, 82%). The elution from Et2O   gave 1,4-bis[5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane]benzene 34 as a white solid (0.435 g, 6%).

   The 1H NMR and 13C NMR spectra of this substance were identical to those from part (i), Reaction of 1,1-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2,2-dimethyl-1,3- propanediol 3 (a) with cinnamaldehyde [1,2- versus 1,4-addition] 

 <Desc/Clms Page number 41> 

 
 EMI41.1 
 (i) Diol   3   (0. 902 g, 1.13 mmol) and cinnamaldehyde (0.189 g, 1.43 mol) were treated by Method 2 with   PPTS (0.   041 g,   0. 15 mmol) as catalyst   to give a pale gel (1.   047   g)   that was column chromatographed on silica gel, The major fraction, eluted   with   5 :   95 Et2O :

   light petroleum, was recrystallized from light petroleum to give 4,4- bis(3,3,4,4,5,5,6,6,7, 7, 8, 8, 8-tridecafluorooctyl)-5,5-dimethyl-2-(2-phenyl-(E)-ethenyl)-   1,   3-dioxane 35 as white flakes (0.971 g, 95%) m. p.   74-75 C   (Found: C, 39.38; H, 2. 76. 



  C30H24F26O2 requires : C, 39. 58; H,   2.   66%). vmax 1691, 1241, 1203, 1142, 1115. 1H NMR   (300 MHz): #    0. 82, s, (CH3)ax; 1.30, s, (CH3)eq; 1.74, m, (H1')1; 1.86, m, (H1'')2; 2.16, br m, (H2')2 and (H2'')2; 2.   54,     m,   (H1')   1 ;   3.47,   d,     J   12.   liez   Hua 6; 3.79, d, J 12.1 Hz, Heq6; 5.16, d, J 4. 9 Hz,   H2   ; 6.15, dd, J 15. 8,4. 9 Hz, H1'''; 6.   78,   d, J 16.2Hz, H2'''; 7. 32,   m,   3xArH; 7.39, m, 2xArH. 13C NMR (75. 6   MHz); #20.4, (CH3)ax; 20.9, C1';   23.0, (CH3)eq; 24.8, t,   J 17.   8   Hz,   C2' ; 25. 0, C1''; 26. 2, t, J 22.2 Hz, C2''; 36.2, C5; 74. 4, C6; 78.0, C4; 94. 9, C2; 125.1, C1''';

   126.8, C2iv and C6iv; 128.3, C4iv; 128.5, C3iv and C5iv ; 133. 5, C2'''; 135.7,   CliV.   Mass spectrum :   mlz     910   (M+, 5%), 761 (7), 563 (5), 431   (8),   401   (12),   387   (11), 150 (27), 131 (97),   104   (100), 69 (65).   



  (ii) Diol 3 (0.180 g, 0, 23 mmol) and   cinnajnaldehyde   (0.033 g,   0.   25 mmol) were treated by method 2 with Amberlyst 15 (0. 033   g)   as catalyst in BTF (5 mL) to give acetal   35   as white flakes (0. 175 g, 85%) m.p. 74-75 C. The 1H NMR and 13C NMR spectra of this substance were identical to those of the product from method 1 (part (i)). 



  Applications of fluorous acetals 
 EMI41.2 
 (a) Protection during catalytic hydrogenation 
F13
7,
6 
6 13 
0 06Fl3 
2" 
36 Solid   10%     Pd/C     (0,   034 g) was added to a solution of unsaturated acetal 35 (0.121 g, 0.13   mmot)   in EtOAc (10 mL) under argon. The mixture was stirred vigorously under 

 <Desc/Clms Page number 42> 

   I2 for   24   h   at room temperature, then filtered and the filtrate was evaporated to dryness to afford 4,4-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-5,5-dimethyl-2-(2- phenylethyl)-1,3-dioxane 36 as   a   colourless oil   (O. H5 g, 94%)   b. p. 170 C (oven)/0. 6 mmHg (Found : C, 39.50; H, 2.92.

   C30H26F26O2 requires: C,   39.   49; H,   2. 87%).   The oil comprised two   diastereomeric   components, which were evident in a ratio of 92 :   8   in the   H NMR spectrum through   the appearance   of (H6)2 signals at #3.   40, 3. 79 and   3. 56,   4.02, respectively. vmax 3030, 2966, 2863, 1605, 1474, 1367,   1318,   1240, 1202, 1145, 
1037,   707. 1H NMR (300 MHz, major isomer): #0.   77, s, (CH3)ax; 1.24, s, (CH3) eq; 
1. 64, m, Ha1'; 1.   7$,   m, (H1'') z ; 1.   96,     m,   (H1''')2; 2. 00-2. 28, br m, (H2')2 and (H2'')2; 2.39, m, Hb1'; 2. 70, t, J 8.1 Hz, (H2''')2 ; 3.   40,     d, J   11.7 Hz, Hax6;

   3.79, d, J 11.7 Hz, Heq6; 
4.61, t, J 4.7 Hz, H2; 7.20, 3xArH; 7. 26, 2xArH. 13C NMR (75.6 MHz, major isomer) ;   #20.   3,   (CH3)   ax ; 21.0, C1'; 22.9, (CH3)eq; 24. 7, t, J 21.8 Hz, C2; 24. 8, C1''; 26.2, t, J 21.8 Hz, C2''; 29.7, C2''', 36. 2, CS and C1'''; 74. 2, C6; 76.9, C4; 94.8, C2;   125. 9, C4'   
128. 1,   C2iV   and C6iv; 128.3, C3iv and C5iv; 141. 2, C1iv. Mass spectrum: m/z 912 (M+,   1%),   761 (5),   431 (4), 415   (15),   375     (6),   134 (100),   107   (22),   105   (38), 92 (54), 69 (28). 



  (b) Protection during epoxidation 
 EMI42.1 
 Unsaturated acetal 35   (0.   082   zu   0. 09 mmol) in CH2Cl2   (6     mL)   was added m-   cbloroperoxybenzoic   acid   (O.   068 g, 0.39 mmol) at room temperature. The mixture was stirred at ambient temperature for 24   h,   then evaporated under vacuum to dryness and column chromatographed on   Fry-silica   gel (5 g). The column was flushed with 70 : 30 MeOH/H2O then light petroleum. The fraction from light petroleum was evaporated to dryness to give 4,4-bis(3,3,4,4,5,5,6,6, 7, 7,8,8,8-tridecafluorooctyl)-5,5-dimethyl-2-(2- phenyloxiranyl)-1,3-dioxane 37 as a colourless oil (0.077 g, 93%), which by GC analysis was of 87% purity.

   The oil comprised two   diastereomeric   components, which were evident in the'H NMR spectrum in a ratio of 62: 38 through integration of the signals at 0   4.   54 and 4. 64, respectively. (Found: FAB-HRMS m/z 949.1258. 



  C30H24F26O3Na (M+Na) requires m/z 949. 1208). vmax 2970, 2867, 1730, 1478, 1366,
1317,   1240,   1202, 1145,   1110, 1050,   707,   698. 1H NMR (300 MHz) (major isomer): #   0.80, s, (CH3)ax; 3.82, s, (CH3)eq ; 1.   72,   1.85, 2.46, m, (H1')2 and (H1'')2; 2.   16,   br m, (H2')2 2 (H2'')2 ;   3.   16, m, H1'''; 3. 47, dd, J 11. 7,9. 8 Hz, Hax6; 3. 85, dd,   J   12. 1, 3.   8     Hz,   

 <Desc/Clms Page number 43> 

   Sq6   ; 3.   81 and 3. 89,   d, 1. 9 Hz, H2'''; 4. 54 and 4.64, d, 4.   3 Hz,   H2;   7.     28,     m,   2xArH; 7.32,   ni,     3xArH. 13C NMR (75.6 MHz) (major isomer):

   #20.    3, (CH3)ax; 20.4, C1'; 22. 8, (CH3) eq; 24.6, t, J 21.4 Hz, C2'; 24.8, C1''; 26.2, t, J 22.2 Hz, C2''; 36. 4 and 36. 5, C5 ; 55.1 and 55.   2,     CZ"     ; 61.   1, C6; 74.1,   C4 ;   78.0 and 78.   2,   C1'''; 125.6, C4''', C6''' and C8''';   128.   4, C5"'and   C7"' ;   135.9 and   136.   0, C3'''. 
 EMI43.1 
 



  (c) Protection during reaction with organometallic reagents sFs 
C6F 1
SK 
6So4 
H '. ", H 
OH Methyl iodide   (0.   04   mL,   0.64 mmol) was added to a suspension of Mg powder   (0.   022 g,   0.   93 mmol) in dry   Et20   (5   mL)   under argon. The mixture was   sonicated   for 15 min, stirred at reflux for a further 10 min then cooled to room temperature.   A   solution of   4-   [5,   5-bis   (3, 3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane]benzaldehyde 33 (0.160   zu   0. 18 mmol) in dry Et2O (10 mL) was added slowly. The mixture was stirred overnight at ambient temperature then quenched carefully by dropwise addition of saturated aq. NH4Cl solution.

   The aqueous layer was separated and extracted with Et20 (3 x 20   mL).   The original organic layer and extracts were combined, dried over anhydrous Na2S04, and evaporated to dryness to give 5, 5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-2-[4-(1-hydroxyethyl)phenyl]-1,3-dioxane 38 as a colourless oil   (0.   160 g, 98%) which solidified after standing overnight at room temperature. The white solid was recrystallized from light petroleum to give a white powder m. p. 65-   66 C   (Found: C, 37. 20 ; H,   2.   20.

   C28H22F26O3 requires: C,   37.   35; H, 2. 46%). vmax 2722,   1670,     1305,   1169,   723. 1H NMR (300 MHz): #1.   44, m, (H1') 2; 1. 47,   d,   J 6. 4 Hz, (H2iv)3; 1.79, d, J 3.0 Hz, OH; 2.05, m, (H2')2; 2. 09, m, (H1'')   2 ;   2.20, m,   (H2") 2   ; 3. 73, d, J   11.   3   Hz,     ES   and Hax6; 3.96, d, J 11. 3 Hz, Heq4 and Heq6 ; 4. 92, qq, J 6. 4,2. 6 Hz, H1iv; 5.43, s, H2; 7.   39, d,   J 8. 3 Hz, H2'"and H6'" ; 7. 45, d, J 8.3 Hz, H3''' and H5'''. 13C NMR.

   (75. 6 MHz)   : #21.    6, C1''; 22.8, C1'; 24.3, C2'; 25.1, C2iv ;   25.   6, C2''; 33. 4, C5; 70. 1, C1iv; 74.2, C4 and C6; 102.0, C2; 125.4, C2"'and C6'''; 129, 7, C3"'and C5'''; 136.7, C4'" ; 146. 9, Cl"'. Mass spectrum : m/z 900 (M+, 1%), 885 (0.4), 855 (1), 417 (4), 205 (4), 149   (20),   107 (30),   81   (47), 69   (100),     55   (50). 



  *(d) Protection during dichromate oxidation 

 <Desc/Clms Page number 44> 

 
 EMI44.1 
 Pyridinium dichromate (0. 550 g, 1. 46   nunol)   was added to a solution of 5,   5-   bis (3, 3,   4, 4,   5,5,   6,     6,   7,7,   8,   $, 8-tridecafluorooctyl)-2- [4-(1-hydroxyethyl)phenyl]-1,3- dioxane 38 (0.   440   g, 0.49 mmol) in CH2Cl2 (25 mL). The mixture was stirred at   r. t. for   20   h,   then filtered, and the solid residue was washed with Et2O (3 x   ZO   mL).

   The   titrate   and washings were combined and evaporated under vacuum to give a brown solid   (0,     424     g) that was   passed through a short-pad of silica gel with 15 : 85   Et2O   : light petroleum to give 5, 5-bis(3,3,4,4,5,5,6,6, 7, 7,8,8,8-tridecafluoroctyl)-2-(4- ethanoylphenyl)-1,3-dioxane 39 as a white solid (0. 411 g, 94%). 
 EMI44.2 
 



  (e) Protection during hydrazone formation t13 > eF13 ol 
8 4 
CHsS H ", Ve 
HN fA, N02 
W 40 
2 4[5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxan-2-yl]benzaldehyde   2,   4-dinitrophenylhydrazone 40 (Found : C,   37.   34; H, 1.63 ; N, 5. 32. C28H20F26O3 requires: C, 37. 23; H, 2.09; N, 5. 26%). 



  Applications in sequential chemical transformations (a) Tagging through aldehyde protection, aldol condensation,   dihydropyridine   formation 

 <Desc/Clms Page number 45> 

 
 EMI45.1 
 
C6FI3 sFl3 
4, ir,, 
NU CH2CH3 CH3 
A F 33 e 2 < H b CH3e) leq g e¯ CHasH r, xW CH3sw EN > OCH 
CHO. CH3 CH ? CH3 HNOCi-izCil3 terephthalaldehyde O (5 H3 0 
41 42 43 (i) Piperidine   (0.   016 g, 0.20 mmol) and glacial acetic acid (0.   012     g,     0. 20 mmol)   were added sequentially to a stirred mixture of   4- [5, 5-bis (3, 3, 4, 4, 5,   5, 6,   6,   7,7,   8, 8, 8-   tridecafluorootl) 3-dioxane]benzaldehyde 33 (0.150 g, 0.17 mmol) and ethyl   acetoacetate   (3 mL, 0.15 mmol) at room temperature.

   After 5 h, the mixture was loaded on to a   FRP-SPE cartridge.   The cartridge was flushed with 70 : 30 MeOH : H2O then Et2O. The fraction from Et2O was evaporated under vacuum to afford ethyl 2{4-[5,5-   bis (3,   3,   8     4,   5,   5,   6,6, 7, 7,   &commat;,   8, 8-tridecafluorooctyl)-1,3-dioxan-2-yl]phenylmethylidene}-3- oxopentanoate 41 as a yellow oil (0. 138 g, 82%). The product was a mixture of E and Z isomers. 



   E isomer (Found: C, 39.85 ; H,   2.   44. C33H26F26O5 requires: C, 39.77; H, 2.63%). vmax 2722, 1719,   1699,   1624,   1260,   1204, 1145, 1065, 1016, 708. 1H NMR (300 MHz,    CDCl3): #1.33, t, J 7.2 Hz, COOCH2CH3; 1.44, m, (H1')2; 2.05, m, (H2')2; 2.09, m,     (Hl")     2   ; 2.16, m,   (H2")     2 ;   2.32, s,   COCHg ;   3.73,   d,   J 11.3 H, Hax4 and Hax6 ; 3. 97,   d,     J   
11.3   Hz,     W     and H. q6   ; 4. 29, q, J 7. 2   Hz,   COOCH2CH3; 5.44, s, H2 ; 7.41,   d,     J   8.3   ha   H2''' and H6''' or H3''' and H5''';

   7.47, d, J 8. 3   Hz,   H3''' and H5''' or H2''' and H6'''; 7.66,   s,     H1iv 13C NMR (75.6 MHz): #14.1, COOCH2CH3    ; 21.5, C1''; 22.7, C1'; 24.3, t,   J     22.   5   Ha,   C2'; 25. 5, t, J 22.9 Hz, C2''; 31.1, COCH3; 33.5, C5 ;   61.     6,   COOCH2CH3; 74.   2,     C4   and   C6   ; 101.4,   C2 ; 126.   6, C2"'and C6''' or C3''' and C5'''; 129.6, C3''' and C5''' or C2''' and C6'''; 133. 7, C1''' or C4''' or C2iv; 134.6, C4''' or C2iv or C1'''; 139.4, C2iv or C1''' or C4'''; 139.6, C1iv; 164.2, COOCH2CH3; 203. 2, COCH3. 



     Z isomer) 1H NMR (300 MHz, CDCl3): #1.27,    t, J 7.2 Hz, COOCH2CH3; 1.44, m,   btx     3   ; 2.   05,   m, (H2')2; 2.09, m, (H1'') 2; 2.16, m, (H2'')2; 2. 42, s, COCH3; 3.73, d, J 11.3 H, Hax4 and Hax6; 3.   97,   d,   J     11.     3   Hz, Heq4 and Heq6 ; 4. 31, q, J 7.2 Hz, COOCH2CH3 ; 5.44, s, H2 ; 7.   48,   s, H2''', H3'", H5''' and H6'''; 7.55, s, H1iv.13C NMR (75.6 MHz);   #13.   7, COOCH2C ; ; 21.5, C1''; 22.7, C1'; 24. 2, t, J 22.6 Hz, C2'; 25.5, t, J 22.2 Hz,   C2" ;   26.5, COCH3 ; 33.   5,   C5; 61. 7, COOCH2CH3 ; 74.2, C4 and C6; 101.4, C2; 126.6, C2''' and   C6"'or   C3''' and C5'''; 129. 6, C3''' and C5''' or C2''' and C6''';

   133. 7,   Cl"'or   C4''' or C2iv; 135. 0, C4'"or   or   or C1'''; 139. 7, C2iv or C1''' or C4'''; 140.4, C1iv; 167.6, COOCH2CH3; 194.5, COCH3. 

 <Desc/Clms Page number 46> 

 



  (ii) Glacial acetic acid   (0.   024   g,   0.40 mmol) was added to a stirred mixture of keto ester   41   (0.   195   g, 0.20 mmol) and methyl   3-aminocrotonate     (0.   220,   1.     91   mmol) at room temperature. After 20   h,   the mixture was loaded on to a   FRP-SPE   cartridge. The cartridge was flushed with   70@    30   MeOSzO   then Et2O. The   fraction from Et2O   afforded 2,6-dimethyl-3,5-bis(ethoxycarbonyl)-4-{4-[5,5-bis (3, 3,4,4,5,5,6,6, 7, 7,8,8,8- tridecafluorooctyl)-1,3-dioxan-2-yl]phenyl}-1,4-dihydropyridine 42 as a yellow oil (0.198 g, 92%). 



  Removal of polyfluorinated acetal tags (i) 2,2-Diphenyl-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 10 (0.216 g, 0.37 mmol) and   2   M HCI (1 mL) were refluxed together in acetone (10   mL)   for 24 h. 



  The mixture was diluted with   H20   (30   mL)   and extracted with   Et20   (3 x 20   mL).   The extracts were combined, dried over anhydrous Na2SO4 and evaporated to dryness to give a pale solid (0, 213 g) that was   chrornatographed   on silica gel (12   g).   Elution with 5 : 95 Et2O/light petroleum gave benzophenone 43 as a white solid (0.060   g,   99%). 



  Elution with   100%   Et2O afforded 2-(3,3,4,4,5,5,6, 6,7, 7,   8, 8, 8-tridecafluorooetyl)-1, 3-   propanediol 1 (0.   172   g, 87%) as a white solid. 

 <Desc/Clms Page number 47> 

 
 EMI47.1 
 



  Compound library synthesis using fluorous tagging strategies 
F13 its 6F 13 SF, 3 'r''i'i'i' 
4 4 . 4 
CL. O 00 00  -'
4 4 4 4 h4 h ! h4 h4 ) 2"T (t j (j /Ct A r
0 0 
44 45 46 47 
 EMI47.2 
 (a) Alkoxybenzaldehyde synthesis General method for phenolic ether formation: A sample of the phenol 12 or 15 (1 mol.   equiv.),   powdered   KOR   (20 mol. equiv.) and alkyl halide (20 mol. equiv. ) were warmed together in   anhydrous   DMF   (10   L per mol) in a bath at 70 C. The mixture was heated for 20   h   then cooled and 10% volume of H2O was added. The resulting mixture was transferred on to a   FRP-SPE   cartridge   (5   g).

   The   cartridge was eluted sequentially   with 70:30 MeOH/H2O (3 x 4 mL), H2O (3 x 4   mL)   and Et2O (3 x 4 mL). The Et2O eluants were combined and evaporated under vacuum to dryness. The crude product was examined by NMR spectroscopy and   LC-MS   analysis to determine the conversion of the reaction and the purity of the crude product. 



  The general method was used to prepare :   (i)   (2-(3-Butoxyphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane
44 

 <Desc/Clms Page number 48> 

 
 EMI48.1 
 
44   2- (3-Hydroxyphenyt)-5- (3, 3, 4, 4, 5, 5,   6,   6,   7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 12 (0. 107   g, 0. 20 mmol)   and n-butyl bromide (0.44   nE,   4. 01 mmol) gave a   73   : 27 mixture of trans-and cis- 2-(3-butoxyphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)- 1, 3-dioxane 44 as white needles (0.099 g, 84%, 98. 7% GC-MS purity) m. p.   64-65"C   (light petroleum) (Found : C, 45.40 ;   H,     4.   00.

   C22H23F13O3 requires: C, 45. 37; H, 3. 98%) vmax 2721, 2670, 1604, 1591, 1322, 1240, 1209, 1141, 1121, 1073, 781, 707,    697 cm-1. 1H NMR (300 MHz); # 0.96, t, J 7.3 Hz, (H4"')3-, 1.44, m, (H1')2; 1.47, m, (H3"')2; 1.75, m, (H2")', 2.05, m, H5; 2.15, m, (H2')2; 3.58, dd, J 11.7, 11.3 Hz, H@x4   and Hax6; 3.97, t, J 6.6 Hz, (H1")2; 4.26, dd, J 11.7, 4.5 Hz, Heq4 and Heq6; 5.40, s, H2; 6. 87, ddd,   J     8.     3,   2.3, 0.8 Hz, H4"; 7. 03, dd, J 7.9, 3.0 Hz, H6"; 7.04, m, H2"'; 7. 26, dd,   J   8. 3, 7. 9 Hz, H5". 13C NMR (75. 6 MHz)   ; # 13.7, C4""; 18.8, t, J 4.0 Hz, C1';    19. 1,   C3'" ;   28.0, t, J 22.5 Hz, C2'; 31. 2, C2"' ; 33. 5, CS ;   67.   5, C1"'; 71. 7, C4 and C6; 101.4, C2;   ni.   6, C2"; 115. 5, C4";

   118.   1,     C6" ;   129. 3, C5" ; 139. 3, C1"; 159.2, C3". Mass spectrum; m/z 582 (M+, 10%), 525 (6), 509 (7), 433 (6), 387 (4), 178 (32), 150 (10), 138 (17), 121 (100), 94 (50). 



  (ii) 2-(3-Isopropoxyphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-diaxane   45   
 EMI48.2 
 

 <Desc/Clms Page number 49> 

 2-(3-Hydroxyphenyl)-5-(3,3,4, 4,   5,   5,   6,     6,   7, 7,8,8,8-tridecafluorooctyl)-1,3-dioxane 12   (0.     015 g, 0.   03 mmol) and   2-bromopropane   (0.05 mL, 0.58 mmol) gave 2-(3- isopropoxyphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 45 as   a   white solid   (0.     013   g 88%, 95% GC-MS purity).

   The solid comprised trans and cis   diastereomenc   components in a ratio of 76 : 24, evidenced in the 1H NMR spectrum through the appearance of the   (H2)     signals at D 5.   39 and 5.47, respectively, The solid was recrystallized from light petroleum to give 2-(3-isopropoxyphenyl)-5- (3, 3, 4, 5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 45 as white flakes m. p.   43-   44 C (Found; C, 44.49; H, 3. 46.

   C21H21F13O3   requires : C, 44. 38   ; H, 3.72%). 1H NMR   (300     1Hz): #1.32,   d, J 6.0 Hz, 2xCH3; 1. 43, m,   (Hl ;   2. 05, m, H5 ; 2. 15, m, (H2')2; 3.   57,   dd, J 11.7, 11.3 Hz, Hax4 and Hax6 ; 4. 26, dd,   J 11.   7,4. 5 Hz, Heq4 and Heq6 ; 4. 56, sept,   J 6.0 Hz, 3"-OCH(CH#)2; 5.38,    s, H2 ; 6.88, ddd, J 8. 3, 2.6, 6 1 Hz, H4' ';   7.   02,   m,   H6" ; 7. 03, m, H2"   7. 26, d J8.   3, 7. 9 Hz, H5". 13C NMR (75. 6 MHz) :   #    18.   S,   t, J 4.0 Hz,   CI' ; 20. 0, 2xCH3 ;   28.0, t, J 22.   5   Hz,   C2' ;   33.5, C5; 69. 8, 3"'-OCH (CH3)   2   ; 71. 7, C4 and C6 ; 101.4, C2;

   113.   4,   C2"; 116. 6,   C4" ; 118. 1, C6" ; 129.   3, C5"; 139.4, C1"; 157.9, C3". Mass spectrum : m/z 568 (M+, 1%), 525 (3), 509 (1), 433 (1), 387 (1),   138   (6),   122   (100), 94 (30). 



  (iii) 2-(3-Allyloxyphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane   46   
 EMI49.1 
   46   2-(3-Hydroxyphenyl)-5-(3, 3,4, 4,5, 5, 6, 6, 7,7,   8,     8,   8-tridecafluorooctyl)-1, 3-dioxane 12 (0. 108 g, 0.21 mmol) and allyl bromide (0.35   mL,   4. 05 mmol) gave   2- (3-   allyloxyphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 46   &commat; 095   g,   821/a,   95% GC-MS purity m.p. 69.5-70 C (Found: C, 44.23; H, 3.31.

   C21H19F13O3 requires : C, 44.54 ;   R   3.   38%). 1H NMR (300 MHz): #1.44,    m, (H1')2; 2.10, m, (H2')2;   2.   16, m, H5 ; 3.58, dd, J 11. 7, 11.3 Hz, Hax4 and Hax6; 4. 25, dd, J 11.7, 4.5 Hz, Heq4 and Heq6 ; 4.   54,   dt, J 5. 3,1. 5 Hz, (H1"')2; 5.27, ddt,   J     10. 6, 1. 5,   1.5   Hz)   Hz3"' ; 5.   40,     s,   H2; 5. 41, ddt, J 17. 3,1. 5,   1.     5 Hz, H@3"';    6. 05, ddt, J 17. 3,10. 6, 5.3 Hz, H2"'; 6.90, ddd, 

 <Desc/Clms Page number 50> 

   J     8.   3,2.   6,   1.1 Hz, H4";

   7.   05,   m,   H6" ;   7.06, m,   H2" ;   7. 26, dd, J 8.3, 7.9 Hz, H5"¯13C NMR (75. 6 MHz) :   #      18.   0,   t,   J 4. 0 Hz, C1'; 28.1, t, J 22.5 Hz, C2'; 33.   5,     C5   ; 68.   7,   C1"'; 71.   7,   C4 and C6; 101.3, C2; 112. 0,   C2"   ; 115.7, C4"; 117. 4, C3"'; 118 5, C6"; 129. 3,   C5" ; 133,   2, C2"'; 139.4, C1"; 158. 6,   C3".   Mass spectrum; m/z 566 (M+, 1%0, 550 (1), 509 (0.5), 433 (1), 387 (1), 161 (31), 133   (27),     121     (45),     105     (25),   65   (39), 55 (53),   41 (100). 



  (iv) 2-(3-Benzyloxyphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 47 
 EMI50.1 
 
47   2-   (3-Hydroxyphenyl)-5-(3, 3,4, 4,   5, 5, 6, 6,   7,7,   8,   8,8-tridecafluorooctyl)-1,3-dioxane 12 ( 0.251 g, 0. 48 mmol) and benzyl bromide (1. 0 mL, 8. 41 mmol) gave   Zu   benzyloxyphenyl)-5-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 47 as a   white   solid (0 015 g, 88%, 96% GC-MS purity). The solid comprised trans and cis diastereomeric components in a ratio of   65   ;   35,   evidenced in the'H NMR spectrum through the appearance of the   (H2)   signals at   D 5.   41 and 5.   50,   respectively.

   The solid was   recrystallized   from light petroleum to give 2-(3-benzyloxyphenyl)-5- (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 47 as white flakes   m.   p. 105-   106 C   (Found : C, 48. 63 ; R 3.06. C25H21F13O3 requires: C, 48.71 ;   H,   3. 43%). 1H NMR (300   MHz): #1.43, m, (H1')2; 2.18, m, H5   ; 2.   08,   m, (H2')2 ;   3.   58, dd, J 11.7, 11.3 Hz,   Bol4     and Ha@6   ;   4.     26,   dd, J 11. 7, 4.5 Hz, Heq4 and Heq6; 5. 07,   s,   OCH2Ph; 5. 41, s, H2;   6.   95, ddd, J 8. 3,   2.     6,   0.   8   Hz, H4"; 7. 07, d, J 7.5 Hz, H6"; 7.14,   m,   H2";

   7. 28, dd, J 8. 3, 7.9 Hz,   H5".   7.29-7.   45,   m,   H2"', H3"', H4"', H5"', H6"'. 13C NMR (75.6 MHz): # 18.    8,   t   J 3.6 Hz, C1'; 28.1, t, J 22.9 Hz, C2'; 33. 5, C5; 69.9, OCH2Ph ; 71.7, C4 and C6;   101.   3, C2 ; 112. 2, C2"; 115.7, C4" ; 118. 6, C6" ; 127.4, C2"' and C6'" ; 127. 8, C3"'and C5"'; 128, 4, C4"'; 129.3,   C5" ; 136.   9, C1"'; 139.5, C1"; 158. 8,   C3".   Mass spectrum : m/z   616   (M+, 4%), 525 (2),   433     (1),   120   (10), 91 (100), 73 (5),   65 (14), 55   (15).   

 <Desc/Clms Page number 51> 

 



    (v)   2-(3-Butyloxyphenyl)-5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3dioxane   48   
 EMI51.1 
    48     2- 3-Hydroxyphenyl)-5, 5-bis (3, 3,   4, 4, 5,5, 6, 6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane   15     (0.   060 g,   0.     07   mmol) and n-butyl bromide   (0.   13   mL,   1.25 mmol) gave 2-(3butoxyphenyl)-5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 48 as a colourless oil b. p. 225 C/1.   0 mnil-t   (0.059 g,   92%, 97% GC-MS purity) (Found :   C, 38.42; H, 2.50. C30H26F26O3 requires: C, 38.81 ; H, 2.82%). 



  (vi) 2-(3-Isopropoxyphenyl)-5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3dioxane 49 
 EMI51.2 
   2-     (3-Hydroxyphenyl)-S,     5-bis     (3,     3,     4,     4,   5,   5,     6,     6,   7, 7,8,8,8-tridecafluorooctyl)-1,3-dioxane 15   (0.   100   g,     0.     12   mmol) and   2-bromopropane   (0.   22 mL,   2.29 mmol) gave an off-white solid   (0.     104   g,   87%   conversion, 83% GC-MS purity) which by   GC-MS   comprised 87% ether 49 and 13% unreacted phenol 15.

   The crude product was passed through   a   short pad of silica   gel with 5@95 Et2O/light petroleum to give    a white solid that was recrystallized from light petroleum to give 2-(3-isopropoxyphenyl)-5,5- bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 49 as white needles   (0.   082   dz     78%)   m. p.   49-50 C   (Found : C, 38.17 ; H, 2, 45.

   C29H24F26O3 requires : C, 38. 09 ; H, 2. 65%).   1H NMR (300 MHz): #1.32, d, J 6.   0 Hz,   2xCH)   ; 1.45,   m, (Hl') 2 ; 2. 00,    (H2')2; 2. 08, m, (H1")2; 2.24, m,   (H2")   2; 3.72, d, J 11,7 Hz, Hax4 and Hax6; 3.95, d,   J   11.7 Hz, Heq4 and Heq6 ;   4.   56, sept, J 6.0 Hz, 3"'-OCH(CH3)2 ; 5. 39,   s, H2   ; 6. 88, ddd,   J   

 <Desc/Clms Page number 52> 

   8.   3,   2.   3,0. 8 Hz, H4"'; 7.00, m, H2"' and H6"'; 7.27, dd, J 8.3, 7.9 Hz, H5"'. 13C NMR (75. 6   MHz): #21.   7, C1"; 21.9, 2xCH3; 22.8, C1'; 24.3, t, J 22.9 Hz, C2'; 25.6, t, J 22.5 Hz, C2"; 33.4, C5; 69.8, 3"'-OCH(CH3)2; 74.1, C4 and C6; 102.1, C2 ; 113. 3, C2"'; 116. 7, C4"'; 118. 1,   C6'" ;

   129.   5,   Cl"';   138.   8,   C1"'; 157.9, C3'". Mass spectrum: m/z 915 (M+1, 1%), 871   (1), 855   (1),   779   (1), 401   (3),     165     (26),     121   (100), 94   (43), 77 (23), 65   (28). NMR   confirmed   by COSY and HMQC. 



    (vii)   2-(3-Allyloxyphenyl)-5,5-bis(3,3,4,4,5,5,6,6, 7, 7,   $,     8,   8-tridecafluorooctyl)-1,3- 
 EMI52.1 
 ojceSO dioxane 50 } 6F13 > 
1'I", o çJ 1" 4 '-y 
01, ' (,.",. 2" so 1W Q   2-(3-Hydroxyphenyl)-5} 5-tis   (3,3, 4,4, 5, 5,6,6, 7,7, 8,8,8-tridecafluorooctyl)-1,3-dioxane   15 (0. 026 $,   0.03 mmol) and allyl bromide (0. 04 mL, 0. 47 mmol) gave 2-(3- allyloxyphenyl)-5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 50 as a colourless oil   (0.   026 g, 96%, 98% GC-MS purity) b.p. 250 C/1.0 mmHg (Found: C, 37.99; H, 2.13.

   C29H22F26O3 requires C, 38. 17; H, 2.43%). 1H NMR (300 MHz,   CoCO   :   6     1.   45, m, (H1')2; 1.98, m, (H2')2; 2.07, m, (H1'')2 ; 2.20, m, (H2'')2 ; 3. 72, d, J 11.7 Hz,   H   and Hax6; 3.96, d, J 11.7   Hz,   Heq4 and Heq6 ; 4.54, dt, J 5. 3, 1.5 Hz, (H1iv)2; 5.27, ddt, J 10.6, 1.   5,   1.5 Hz, HZ3iv; 5.41, s, H2 ; 5. 41, ddt, J 17.3, 1. 5,1. 5   Hz,   HE3iv; 6.05, ddt, J 17.3, 10.6, 5.3 Hz, H2iv; 6.93, ddd, J 8. 3,   2.   6,0. 8 Hz,   H4iv ;   7.03, m, H2''' and H6'''; 7.   29,   dd, J 8. 3,7. 9 Hz, H5'''. 



  (viii) 2-(3-Benzyloxyphenyl)-5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3- dioxane 51 

 <Desc/Clms Page number 53> 

 
 EMI53.1 
 2- (3-Hydroxyphenyl)-5, 5-bis (3,3, 4,4, 5,5,   6,     6,   7, 7,8,8,8-tridecafluorooctyl)-1,3-dioxane 15   (0.     031   g, 0.04 mmol) and benzyl bromide (0.1   mL,   0. 82 mmol) gave   2- (3-   benzyloxyphenyl)-5,5-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 51 (0.034 g, 99%, 98% GC-MS purity) m.p. 82-82.5 C (Found: C, 41. 16; H, 2.46. 



  C33H24F26O3 requires: C, 41. 18   ; H, 2.51%). 1H NMR (300 MHz): #1.   45,   m, (Hl') 2 ;     2.   00, M, (H2')2; 2.09, m, (H1")2; 2.22, M, (H2")2; 3.73, d, J 11. 3   Hz,     H,,,   and Hax6; 3.96,   d,     T   11.3 Hz, Heq4 and Heq6; 5.07, s, 3"'-OCH2Ph; 5.41, s, H2; 6.98, d, J 7.9 Hz, H4"'; 7.06, d, J 7. 5   Hz,   H6"'; 7.11,   s,   H2"' ; 7. 30, m, H5"'; 7.32-7.42, m, H2iv, H3iv, H4iv,   H5iv and H6iv;. 13C NMR (75.6 MHz); #21.6, C1"; 22.8, C1';    24.5, C2'; 25. 6 C2"; 33.4, C5; 69.9, 3"'-OCH2Ph ; 74.1, C4 and   C6 ; 102.   0,   CZ 2, C2"'; 115. 8, C4"', 118   C6"' ; 127.4, C2iv and C6iv; 127.9, C4iv; 128.5, C3iv and C5iv; 129.5, C5"';

   136. 7,   C     ;   138.9, C1"'; 158.8, C3"'. Mass spectrum; m/z 963 (M+1, 1%), 872 (1), 779 (1), 401 (32),   373 (11), 327 (9), 213   (78),   197 (25), 155   (17), 135 (28), 122   (100).   



    Polyfluorinated   reagents for   tagging through acetalation of alcohols, 1,   2-diols, 1, 3-diols and 1, 4-diols 
 EMI53.2 
 (a) Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) ketone 52 white needles m. p. 62-   63 C   dit. m.   o.   62-63 C) (b) Synthesis of 1, 1-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,1-dimethoxy- 
 EMI53.3 
 methane 53 
CHsQPCHa 
C613 6F13 
10 

 <Desc/Clms Page number 54> 

 
Bis   (3, 3, 4,   4,   5,   5, 6,   6,   7,7, 8,   8,   8-tridecafluorooctyl) ketone 52 (2. 96 g,   4.   11 mmol) was dissolved in warm   anhydrous   MeOH (178 mL) under argon.

   Trimethyl orthoformate   (2-61   g, 24.67 mmol) and 18M sulfuric acid (18 drops) were added and the mixture heated under gentle reflux for   48     h.   The mixture was cooled and concentrated under reduced pressure, and then diluted with ethyl acetate (100   mL)   and water (50 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2 x 
50 mL). The combined organic extracts were washed with   5%   aq. sodium bicarbonate   (50   mL) and brine (50   mL), and   the solution dried (Na2SO4) and evaporated to give 
1, 1-bis(3,3,4,4,5,5,6,6, 7,7, 8, 8, 8-tridecafluorooctyl)-1,1-dimethoxymethane 53 as a colourless oil (3. 01 g, 95%) (Found: C, 29.74 ; H, 1.89.

   C19H14F26O2 requires C, 29.   70 ;     e H,   1.   84%). 1H NMR (CDcl3, 300 MHz): # 1.85-2.00, 4H,m, RFCH2,CH2   ;   2.   00-2. 20,   4H,     m,     RFCH2CH2; 3.19, 6H, s, 2 x OCH3. 13C NMR (CDCl3, 75.6 MHz): #    23.   2,   
RFCH2, CH2 ; 25. 8, t, J 22.5 Hz,   RpCHiCH   ; 47. 9, 2 x OCH3;   101.   0, (RFCH2CH2)2C(OCH3)2. EI-MS : mlz 768   (&commat;,    61%), 421   (100),     375     (12),   169   (10),   
131   (15), 119 (27),   101   (48),   69 (88). 



   (c) Synthesis of 2,2-bis(3,3,4,4,5,5,6,6,7,7,8, 8, 8-tridecafluorooctyl)ethanal 54 
Pyridinium dichromate (0. 786 g, 2.09 mmol) was added to   a   solution of alcohol   49     (1.   384   g,   1. 87 mmol) in   CHzCl2   (30 mL). The mixture was stirred at r. t. for   20     h,   then filtered, and the solid residue was washed with   Et20   (3 x 20   mL).   The filtrate and washings were combined and evaporated under vacuum to give a brown solid   (1.   281 g) that was chromatographed on silica gel (30 g).

   Elution with   4 96 Etz ht   petroleum gave initially bis   (3,   3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl) ketone 52 as a white solid   (0.   361 g,   27 / .   Further elution with the same solvent gave a second product that was recrystallized from light petroleum to give 2,   2-   bis(3,3,4,4,5,5,6,6, 7, 7,8,8,8-tridecafluorooctyl)ethanal 54 as a white powder (0. 520 g,   38oxo)   m. p.   48-49 C   (Found : C, 29, 25 ; H,   1,   33. C18H10F26O requires: C, 29.37; H,   1.37%). 1H NMR (300 MHz): #1.81, m, Ha1' and H1a"; 2.05, m, Hb1' and Hb1";    2.   15,     m, (H2) 2   and (H2")2; 2. 49,   m,     H2; 9.67, s, H1. 13C NMR (75.6 MHz): # 19.1.

   C1' and   
C1"; 28.1, t, J 22.5 Hz, C2' and C2"; 49.4, C2 ; 201.6, C1. Mass spectrum: m/z 737 (M+, 
2%), 736 (M+, trace), 717 (6), 687 (6), 667 (7), 467   (15),   390 (100), 373   (18),   327   (23),   
169   (13),     119     (35)   77 (83), 57 (92). 



    Applications of acetalation of diols using polyfluorinated reagents   53 and 54   (a)   1,   3-Dioxane forrxation   (b) Selective formation of acetals 

 <Desc/Clms Page number 55> 

 Acetal protection   of diols using polyfluorinated reagents   53 and   54   
 EMI55.1 
 (a) 2-[1,   5-Bis (3, 3, 4, 4, 5, 5, 6,   6,   7,   7,   8,   8, 8-tridecafluorooctyl)pent-3-yl]-5,5-dimethyl-1,3dioxane   55   2, 2-Bis (3, 3, 4,4,   5, 5, 6, 6,   7,7, 8, 8, 8-tridecafluorooctyl)ethanal 54 (0.

     175 g, 0.   24 mmol) and 2, 2-dimethyl-1, 3-propanediol   (0 029   g,   0.   27 mmol) were treated by Method 3 with Amberlyst 15   (0.   030 g) as catalyst to give a colourless oil   (0.     189   g) which was distilled to give 2, 2-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)methyl-5,5-dimethyl-1, 3dioxane 55 as a colourless oil (0.179 g, 92%) b. p.   125 C   (oven)/0.2 mmHg (Found; C,   33. 47   ; H, 2.   24.   C24H22F26O2 requires: C, 33.59;

   H, 2.45%). 1H NMR (300 MHz):   00-72,   s, (CH3)ax; 1.16, s, (CH3)eq; 1.   65,   m, Ha1' and Ha1" ; 1. 72,   m,   H1"'; 1.85, m, Hb1' and Hb1"; 2. 20,   m,   (H2')2 and (H2")Z; 3.39, d, J 10.9 Hz, Hax4 and Hax6; 3.62, d, J 10.   9   Hz, Heq4 and Heq6 ;   4.     38,   d, J 3.4 Hz, H2. 13C NMR (75.6 MHz,   CDCl3): # 19.   7,   t   J 4. 0 Hz, C1' and C1"; 21.6, (CH3)ax; 22. 7, (CH3)eq ;   28.   7, t, J 21.8 Hz, C2' and C2"; 30. 0,   CS,   40. 9,   Cl"' ; 77. 2, C4 and C6 ;   103.1, C2. Mass spectrum : m/z 822 (M+, absent), 375   (6%), 327 (3), 119 (5),   115 (100), 87 (23), 77 (11), 69 (78), 56 (79). 



  (b) 2,2-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 56 1,1-Bis(3,3, 4,4, 5,   5,   6, 6, 7, 7,   8,   8, 8-tridecafluorooctyl)-1,1-dimethoxy-methane 53 (100   mg,     0.   13 mmol) was dissolved in toluene (5-mL).   Propane-1,   3-diol   (20   mg, 0. 26 mmol)   andp-toluenesulfanic acid   (10 mg,   0.   525 mmol) were added and the mixture refluxed under a Dean-Stark apparatus for 18 h. The toluene was removed under reduced pressure and the residue taken up in diethyl ether   (50   mL) and the solution washed with   0. 5M KOH   (25 mL). The organic extract was washed with water (25   mL)   and dried (K2CO3).

   Evaporation of the solvent gave a colourless oil (97   mg),   which was flash chromatographed on silica get using a gradient of diethyl ether in light   petroleum. 2, 2-   

 <Desc/Clms Page number 56> 

 Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane 56 was obtained as a colourless oil   (86     mg,   85%) (Found; C, 31.14; H, 1.85. C20H14F26O2 requires C,   30.   79;   H,     1.81%). 1H NMR (CDCl3, 300 MHz): # 1.64-1.75, 2H, m, -OCH2CH2CH2O-;    1.92- 2. 05, 4H, m, RFCH2, CH2 ; 2. 06-2. 35, 4H, m, RFCH2CH2; 3.89, 4H, t, J 5.3 Hz, -    OCH2CH2CH2- 13C NMR (CDCl3, 75.5 MHz): # 25.1, -OCH2CH2CH2O-; 25.2,   RFCH2,CH2; 29.6, RFCH2CH2; 59.5, -OCH2CH2CH2O-; 97.7, C2.

   EI-MS: m/z 703 (28), 433 (100), 375 (88), 327   (8),     277   (10),   131   (25),   112     (50)   and 69 (70). 



    (cL2,     2-bis   (3,3, 4,4, 5, 5,   6, 6,   7, 7,8,8,8-tridecafluorooctyl)-5-methyl-1,3-dioxolane 57   l, I-Bis (3, 3, 4,   4,   5,     5,   6,6,7,7,8,8,8-tridecafluorooctyl)-1,1-dimethoxymethane 53 (100   mg,   0. 13 mmol) was dissolved in benzene   (5   mL) and to this propylene glycol (20 mg, 0. 26 mmol) and p-toluenesulfonic acid   (10   mg, 0.052   mmole)   were added and the mixture refluxed under a Dean-Stark apparatus for 48 h. The solvent was removed under reduced pressure, and the residue taken up in diethyl ether (100   mL).

   The   solution was washed with 0.5   M   KOH (50 mL) and then H20 (50 mL), dried   (Na2S04),   and evaporated to give 2,2-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)- 5-methyl- 1, 3-dioxolane 57 as a colourless oil   (103   mg, 98%) (Found : C, 30. 83; H, 1.88. 



  C20H14F26O2 requires C, 30. 79;   R   1. 81%). 1H NMR (CDCl3, 300 MHz) :   8 1. 3O, 3R d     Y6. 0 Hz, 4-CH3   ; 1.   80-2.     00,     4H   m,   RFC,-H2, CH2   ; 2. 10-2. 30,   41-L     m,   RFCH2CH2; 3.42, 1H,   tn     I   7. 9 Hz, Ha5; 4.12, 1H, t, J 6.03   Hz,   Hb5; 4.20-4.30,1H, m, H4. 13C NMR   (CDC13,   75.   6 MHz): # 18.1, 4-CH3    ; 25. 5, RFCH2,CH2 ; 28.1, RFCH2CH2 ; 71. 5,   C5 ;   72.9, C4; 109.0, C2. EI-MS: m/z 433 (100%), 417   (25),   375 (95), 327 (8), 277 (8), 169 (10),   131 (18), 119 (20), 113 (32),   77 (35), 69 (55). 



   (-)-trans-4,5-bis(ethoxycarbonyl)-2, 2-bis (3,3, 4,   4, 5, 5, 6, 6, 7, 7, 8, 8, 8-   tridecafluorooctyl)-1, 3-dioxolane 58 A solution of (-)-diethyl tartrate (53.   6   mg, 0.26 mmol),   p-toluenesulfonic   acid (5 mg, 0.026   rnmol)   and 1,1-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,1-   dimethoxymethane   53   (437     mg,   0. 56 mmol) in toluene   (15     mL)   was refluxed under a Dean-Stark apparatus for 20 hours. The solution was cooled and diluted with diethyl ether   (50     mi)   and 0.5 M   aq.     KOH   (25 mL) were added. The organic layer was separated and the aqueous layer extracted   with diethyl ether (50 mL).

   The combined   organic extracts were washed with water (50 mL) and dried (Na2SO4). Removal of the solvent gave a colourless oil (300 mg) that was subjected to repeated flash chromatography using an increasing gradient of diethyl ether in light petroleum. The   fraction eluted with 20   : 80 diethyl   ether/light   petroleum gave (-)-trans-4, 5- bis (ethoxycarbonyl)-2, 2-bis (3,   3,   4,4,   5, 5, 6, 6,   7,7, 8,8,8-tridecafluorooctyl)-1,3-dioxolane 58 as a white solid (165 mg, 69 %) m.   p.     25-27'C     (Found : C,   33. 10; H, 2.27. 

 <Desc/Clms Page number 57> 

 



    C25H20F26O6 requires C, 32.98; H, 2.21%). 1H NMR (CDCl3, 300 MHz): # 1.31 (6H, t,     J   7.17   Hz,   2 x OCH2CH3),   1.   95-2. 10 (4H, m, RFCH2,CH2), 2. 15-2. 40   (4H,     m,   RFCH2CH2), 4. 20-4. 40 (4H, dq, J 7.14, 2. 64 Hz,-2   x   OCH2CH3-), 4. 73 (2H, s,   X   Hs). 



    1#C NMR (CDCl3, 75.6 MHz): # 13.8, 2 x OCH2CH3   ; 25. 1, RFCH2, CH2; 28.0, RFCH2CH2 ; 62.2, 2 x OCH2CH3 ;   78.     0,   C4 and C5; 114.   0,   C2; 168.6, CO2CH2CH3 EI- MS; m/z 910 (M+, absent), 563 (85%), 417 (25), 375   (52),   243   (12),   189 (15), 161 (22),   115 (100),   87 (58). 



    (axis   (3,3, 4,4,   5, 5, 6, 6,   7, 7,8,8,8-tridecafluorooctyl)-6-methyl-1,3-dioxane 58 
1, 1-Bis (3,   3,   4,4,   5,   5,   6,     6, 7, 7, 8,   8, 8-tridecafluorooctyl)-1,1-dimethoxymethane 53   (200     mg,     0.   26   mmol),   1,3-butanediol (46 mg, 0.

   52 mmol) and ptoluenesulfonic acid (10   mg,     0.   05 mmol) were heated together at reflux in toluene   (5   mL) under   a   Dean-Stark apparatus   for 20 h-The reaction mixture was concentrated   under reduced pressure, diluted   with Et2Q (50 mL3,   and the solution washed with   0.   5M KOH   (25   mL) and Hz0 (25 mL), and dried (Na2SO4).

   Evaporation of solvent and flash chromatography of the residue using a gradient of   Etz4   in light petroleum gave   2,     2-   bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-6-methyl-1,3-dioxane 58 as a colourless oil (85   mg,   41%) (Found: C, 31. 66; H,   2.     00.   C21H16F26O2 requires : C, 31. 75;

   H, 2.   03%). 1H NMR (300 MHZ, CDCl3); #    1. 16, 3H,   d,     J6.   0   Hx,   6-CH3 ;   1.   50,   2R     m,   H5 ; 1. 80, 2H, m, RFCH2CH2; 2 10, 2H, m, RFCH2CH2; 2.30, 2H, m, RFCH2CH2; 3.90, 2H,    m, H4; 3.95, 1H, m, H6. 13C NMR (CDCl3, 75.6 MHz): # 21.6, RFCH2CH2; 21.8, 6-   CH3; 24.3, t, J 21.8 Hz, RFCH2CH2; 26.0, t, J 22.6 Hz, RFCH2CH2; 29.5, RFCH2CH2;   32.   2, C5; 59.6, C4 ;   65.   0,   C6 ; 98.   1,   C2.   EI-MS: m/z (495, 12%), 447 (10), 401 (15), 375   (14), 105 (100).   



  Later fractions   yielded bis (3, 3, 4,   4,   5,     5, 6,   6,7, 7,8,8,8-tridecafluorooctyl) ketone 52 (85   mg,   45   %)   as a white solid. 



  Competitive reactions in the polyfluorinated   acetal protecuon   of alcohols (a) Reaction of 1, 2,4-butanetriol with 1,1-bis (3,   3,     4, 4,   5, 5,   6p6, 7,   7, 8, 8,8- tridecafluorooctyl)-1,1-dimethoxymethane 53 
 EMI57.1 
 A solution ofp-toluenesulfonic acid (10 mg,   0.   05 mmol), 1, 2, 4-butanetriol (112 mg, I mmol) and dimethyl acetal   53   (400 mg, 0. 5 mmol) in toluene   (10     mL)   was heated under reflux in a Dean-Stark apparatus   for 20 h. The   solution was diluted with   Et20   (50   m   and the solution washed with 0.5 M aq.

   KOH (25 mL) and then H2O (25 mL). 

 <Desc/Clms Page number 58> 

 Removal of the solvent under reduced pressure gave a colourless oil (384 mg) that was flash chromatographed using a gradient of Et20 and light petroleum, to yield in order, the fluorous ketone   52   (90 mg, 23%), 2,2-bis(3',3',4',4',5',5',6',6',7',7',8',8',8'tridecafluorooctyl)-4-hydroxyethyl)-1,3-dixoane 60 as a colourless oil   (144   mg, 34%) (Found : C, 31. 29; H, 1. 73.

   C21H16F26O3 requires C, 31. 13; H, 1.99 %). 1H NMR (300   Zu     CDCIs)     #    : 1.   43,     IR     d,     J   2. 4 Hz, Heq5; 1. 65, 1H, m, Hax5; 1.80,   2ici,     m,   RFCH2CH2; 2.10, 2H, m, RFCH2CH2; 2. 20, 2H, m, RFCH2CH2; 2.30, 2H, m,   RFCH2CH2; 3.60, 2H, m, CH2OH; 3.95, 2H, m, H@6; 4.00, 1H, m, Hb6. 13C NMR    (75. 5   MH2,     Cd13) : D   21. 6, RFCH2CH2 ; 24. 3,   RICHS   ;   25,   9, RFCH2CH2, C5 ;   29.   4, RFCH2CH2 ; 59.1, C6; 65.8, C1'; 69.7, C4; 98. 4, C2.

   EI-MS: m/z 810 (M+, absent),   779   (3%), 703 (2), 463 (15),   375   (12), 169 (5), 131 (10), 89 (30), 71   (100),   57   (40). R 3416     (br     O'H), 2962 (C-H),   2879 (C-H),   1455   (C-O), 1315 (C-O), 1233 (C-O), 1199, 1121, 1077,   955,   914   846,   812 and 702   cm'' ; and   2, 2-bis (3',3',4',4',5',5',6',6',7',7',8',8',8'tridecafluorooctyl)-4-(2"-hydroxyethyl)-1,3-dioxolane 61 as a colourless oil   (183   mg,   43%) (Found ;   C, 30. 89 ; H, 1.67.

   C21H16F26O3 requires C, 31.13, H, 1.99%). 1H NMR (300   MHb,     CDCl3); # 1.85, 2H, m, H1"; 1.   95,   4H,   m, 2 x RFCH2CH2; 2.15, 4H, m, 2 x RFCH2CH2; 3.60, 1H, t, J 8.3 Hz, H5 ; 3. 80, 2H, m, H2"; 4. 20, 1H, m, H5;   4.   30,   1H, m,   H4. 13C NMR (75.6   Nffiz,     CDCl3): #25.7, m, RFCH2CH2; 28.0, RFCH2CH2; 35.7, C1";   59. 8, C2"; 70.4, C5; 75.3, C4; 109. 0, C2. IR 3390 (O-H), 2969, 2885, 1455, 1324, 1251, 1040 cm-1, EI-MS; m/z 810 (M+, absent), 463 (25%), 417 0,   375 (20), 263 (3),   131 (15),   89     (4),   71   (100).   



  (b) Treatment of erythritol with 1,1-bis(3, 3,4, 4,   5,   5, 6,   6,   7, 7,8,8,8-tridecafluorooctyl)-1,1-   dimethoxymethane   53 
 EMI58.1 
 Dimethyl acetal 53 (100   mg,   0. 13 mmol), erythritol (meso-1,2, 3,   4-butanediol)     (32   mg, 0. 26 mmol)   andp-toluenesulfonic acid   (2. 5 mg, 0.013 mmol) in toluene (10   mL)   were heated together at reflux under a Dean-Stark apparatus for 20 h. The solution was concentrated under reduced pressure, the residue taken up in Et2O   (50   mL), and the solution washed with 0.   5   M aq. KOH (25 mL) and H2O (25 mL), and then dried    (NaZSO4).

   Removal of solvent gave a colourless oil, which was repeatedly flash   

 <Desc/Clms Page number 59> 

 chromatographed. The fraction eluted with 10 : 90 to 30 ; 70 Et2O : light petroleum initially gave a mixture of products. More careful chromatography   gave,.   in order of elution, fluorous ketone 52   (25   mg), a   37   : 63 mixture of fluorous ketone 52 and   1,   4- bis   (perfluorohexyl) butane,   and cis-2, 2-bis(3',3',4',4',5',5',6',6',7',7',8',8',8'-    tridecafluoroctyl). @furo[3,4-d]-1,3-dioxolane 63 as a colourless oil (6 mg, 60%) (Found :   C;   H, C21H16F26O3 requires C, ; H, %). #max 1319,    1240, 1205, 1145, 1068, 1031 cm-1. 



    1H NMR (300 MHz, CDCl3): # 1.    85, 2H, m, RFCH2CH2; 2.00, 2H, m, RFCH2CH2; 2.15, 2H, m, RFCH2CH2; 2.35, 2H, m, RFCH2CH2; 3. 40,   zip   d, J 10.5 Hz, CHaHb ; 4. 05, 2H, d, J 11.6 Hz, CHaHb ;   4.     79,   2H, s, 2   x   CH. 13 C NMR (75.6 MHz, CDCl3) :   0   24.   5,   t, @ J 21.1 Hza, RFCH2CH2; 26.2, t,   J 22.   6   Hz,   RFCH2CH2; 26.   8,   RFCH2CH2; 28.1, RFCH2CH2 ; 73.5, CH2O; 81.3, CH; 112.2, C2. EI-MS; m/z 807 (M-1, 1%), 461 (32), 375 (5), 149 (5), 87 (10), 69 (100). 



  The fraction eluted with   80 : 20 EtaO0Light petroleum, upon further chromatography gave   2, 2-bis(3',3',4',4',5',5',6',6',7',7',8',8',8'-tridecafluoroctyl-4S*-(1R*,2-dihyroxyethyl)-1,3- dioxolane 62 as a white solid (39   mg,   36   %)   m. p.   58-60 C   (Found: C, 30. 63 ; R 2. 06. 



    C2iHisF2604 requires   C, 30. 52; H,   1.     95%).     #max    3400,   1238,   1200 cm-1. 1H NMR (300 MHz, CDCl3) :   #      1.   79,   J4   t, J 4.9 Hz, OH; 1.95, 4H, m, 2x RFCH2CH2; 2. 16, 4H, m,   Z     x   RFCH2CH2 ; 2.33, 1H, d, J 4.9 Hz, OH; 3.64, 1H, m, H5; 3.76, 1H, m, H4; 3.80, 1H, m, H5; 3.96, 1H, t, J 6.4 Hz, CH2OH; 4.   10,     lit   q, J 6.4 Hz, CHOH; 4.15,   1H.   t, J 6. 4   zu   CH2OH. 13C NMR (75. 6   Mein,   CDCl3) :   CI   25.7, t, J 22.5 Hz, RFCH2CH2; 27. 8,   d,     J   20, 3 Hz, RFCH2CH2; 63. 4, C5 ; 67. 0, CH2OH; 72. 0, C4 ;

   77.3.   CHO ; 109.   3, C2. EI-MS: m/z 826 (M+, absent), 765 (4%), 479 (15), 375 (20), 105 (12), 87 (73), 69 (100); and meso-4,4'-bi[2,2-bis(3',3',4',4',5',5',6',6',7',7',8',8',8'-tridecafluoroctyl)-1,3-dioxolane 64 as a white   solid (23   mg, 11. 5 %) m.p. 63-64 C (Found: C, 29.74: H, 1.63. 



    C32Fs204   requires, C, 29.   82; H, 1.45). #max 1236, 1192, 1146 cm-1. 1H NMR   (300MHz,   CDCl3): # 1.93 (8H, m,    4 x RFCH2CH2), 2.15 (8H, m, 4 x RFCH2CH2), 3.83 (2H, m), 4.12 (2H, m), 4. 18 (2H,m) 13C NMR (75. 5   MHz, CDCl3): # 25.    73 (m, RFCH2CH2), 27.42 (m,   RFCH2CH2),   67.07 (CH2OH), 76.72 (CHO), 110.04 (C2). El- MS: m/z 1530 (M+, absent), 1184 (7%), 766 (22), 479 (10), 461   (15), 418 (60),   375   (90).   



  (c) Treatment of threitol with 1,1-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,1- dimethoxymethane 53 

 <Desc/Clms Page number 60> 

 
 EMI60.1 
 
Dimethyl acetal 53   (100   mg, 0.13 mmol) and   DL-threitol     (+/-1,   2,   3, 4-butanediol)   (32 mg, 0.26 mmol) were dissolved in toluene (10 mL),   p-toluenesulfonic   acid   (2. 5 mg,   
0.003 mmol) was added, and the mixture heated under a Dean-Stark apparatus for 20 h. 



   The solution was diluted with EtzO (50   mL)   and the solution washed with 0. 5 M   SOR   (25   rnL)   and H2O (25 mL), and then dried (Na2SO4). Removal of solvent gave a colourless oil   (132     mg)   that was flash chromatographed on silica gel, eluting with a gradient   of Et2Q and li$ht petroleum   to yield, in order : fluorous ketone 52 (31 mg), (+/- )-4,4'-bi[2,2-bis(3',3',4',4',5',5',6',6',7',7',8',8',8'-tridecafluorooctyl)-1,3-dioxolane 67 as a colourless oil (23 mg,   12%)   (Found : C, 29. 76 ;   H,     1.   44.

   C38H22F52O4 requires C, 
29.82, H, 1. 45%).   #max    1241, 1192 1120   cm-1. 1HNMR (300 MHz, CDCl3); # 1.96 (8H,   m, 4   x   RFCH2CH2), 2.20 (8H, m, 4   x   RFCH2CH2), 3.72   (2R   m,   CH2),   4.13 (4H, m, 
CH2, 2   x     CH)."C NMR   (75.5 MHz, CDCl3), 25.43   (m,   RFCH2CH2), 27.61 (RFCH2CH2), 66. 25 (CH2), 76. 01 (CH), 110.29 (C2). EI-MS : m/z 1530 (M+, absent), 
1184 (5%), 765 (15), 461 (18), 418 (45), 375 (100); trans-4,5-bis(hydroxymethyl)-2,2- bis(3',3',4',4',5',5',6',6',7',7',8',8',8'-tridecafluorooctyl)-1,3-dioxolane 66 (12 mg, 11%) (Found: C, 30. 38;   R   1.95 : C21H16F26O4 requires C, 30. 52; H, 1.95%).

   IR 3376, 1322    
1238, 1148, 1030 cm-1. 1H NMR (300 MHz, CDCl3): # 1.97 (6H, m, RFCH2CH2, OH),   
2.23 (4H, m, RFCH2CH2), 3.75 (2H, d, J 12 Hz, CH2OH), 3.85 (2H, d, J 12 Hz, 
CH2OH), 4. 04   zip     s   H4, H5). 13C NMR (75.6 MHz,   CDC 5.   59 (t, J   23.   4   W   
RFCH2CH2), 28.64 (RFCH2CH2), 61.71 (2   x     CHsOH),   78. 76 (C4, C5), 109.26   (C2).   EI- MS: m/z 826 (M+, absent), 795 (2 %), 479 (40), 375 (20), 87 (75); and 2,2- bis (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl-4S*-(1S*,2-dihydroxyethyl)-1,3- idoxolane 65 (35 mg, 33 %) (Found: C, 30.43; H, 2.03.

   C21H16F26O4 requires C,   30.   52;   H,   1. 95%).   #max 3414, 1249 1238, 1192, 1030 cm-1. 1H NMR (300 MHz, CDCl3)    :   #   
2.00, 5H, m, 2 x RFCH2CH2, OH; 2.20, 4H, m, 2 x RFCH2CH2; 2. 40-2. 50, 1H, bs, OH;   3.   70, 3H, m, H4, H5; 3. 90,   1H,   t, J 7.5   a   CH2OH; 4.10, 1H, m, CH2OH; 4.20, 1H, m, CHOH. 13C NMR (75.6 MHz, CDCl3) : 26.0, RFCH2CH2 ; 28.4, RFCH2CH2 ; 64.4,   C5 ;   66.9, C2" ; 71. 9, C4 ; 78.2, C1"; 110. 2, C2. EI-MS: m/z 826 (M+, absent), 795 (1 %), 765 (5), 479 (20), 375 (18), 105 (20), 87   (100).   

 <Desc/Clms Page number 61> 

 



  Reactions of polyfluorinated acetal protected substances (a) Oxidative cleavage of diol 65 A solution of NaIO4 (41 mg 0. 14 mmol) in   HO (1 mL)   was added to a solution of diol 65   (38   mg, 0. 048 mmol) in   1,   4-dioxane (2   mL)   and the mixture was stirred for 3 d. The solution was filtered through Biter aid with the aid of CHCl3 (20 mL).

   The filtrate was evaporated to dryness under reduced pressure, and the residue extracted with CHC13 (2 x 50   mL).   Removal of solvent gave a colourless oil (61 mg), which was flash   chromatographed, elutrng with   50: 50 Et2O/light petroleum, to yield   zu   bis (3, 3, 4, 4,5, 5, 6,   6,   7,   7,     8,   8,8-tridecafluorooctyl)-1,3-dioxolan-4-yl]carboxaldehyde 68 as a colourless oil (22 mg, 40%) 
 EMI61.1 
 (Found :

   C, 30. 39 ; 1,   1.     31.   C20H12F26O3 requires C, 30.24, H, 1.   52%).     #max 3453,    1740, 
1455,   1321,   1238   cm-1. 1H NMR (300 MHz, CDCl3): #    1. 95,   4R   m,   2   x RFCH2CH2;   2.   10, 4H,   m,   2 x RFCH2CH2; 4.10, 1H, m, H5 ; 4.25, 1H,   t,   J 9.0 Hz, H5 ; 4. 49, 1   dt, J   
6.   0     X   1.   5     a7     H4; 9.71, 1H, d, J 1.5 Hz, 4-CHO. 13C NMR (75.6 MHz, CDCl3): #   25.7, t, J 22.6 Hz, RFCH2CH2; 27.3, RFCH2CH2; 65.5, C5; 79.8, C4; 111.4, C2; 198.7, 
CHO.   EI-MS   :

     iZ     794   (M+, absent), 765 (10%), 447 (38), 375 (8), 169 (32), 119 (88),    169 (100).   



  (b) Mild oxidation of 2,2-bis (3, 3, 4, 4,   5,     5,   6, 6,7,7,8,8,8-tridecafluorooctyl-4S*-(1S*,2-   dihydroxyethyl)-1,   3-dioxolane 65 using pyridinium dichromate Pyridinium dichromate   (81     mg,   0.21 mol) was added portionwise to a solution of 2, 2- bis   (3, 3,   4, 4, 5,5, 6,   6,     7,   7, 8,8,8-tridecafluorooctyl-4S*-(1S*,2-dihydroxyethyl)-1,3- dioxolane 65   (35 mg,   0.04 mmol) in dry   CHsCIa   (2 mL). The mixture was stirred at r. t. for   20   h.

   The solution was filtered through filter aid and the pad washed several times with CH2Cl2   (50     The     The organic titrate was evaporated to dryness under reduced   pressure to give a brown oil (33 mg) that was flash chromatography using an   Et7,   in light petroleum gradient to give 2-[2,2-bis(3',3',4',4',5',5',6',6',7',7',8',8',8'- tridecafluorooctyl)-1,3-dioxolan-4-yl]ethanal 69 as   a colourless oil (t 48   
 EMI61.2 
 

 <Desc/Clms Page number 62> 

 (Found: C, 31.08; H, 1.71.

   C21H14F26O3 requires C, 31.   21; H, 1.75%). #max    2963, 2880,   1730   (C=O), 1455, 1322, 1240, 1196, 1145, 1121, 1088 1025 cm-1. 1H NMR (300   MHz, CDCl3): # 1.90, 4H,    m, 2 x RFCH2CH2; 2.20, 4H, m, 2 x RFCH2CH2; 2.65, 1H,   dd,   J   17.   7,6. 7 Hz, CH2CHO; 3.00, 1H, ddd, J 17.7, 6, 1.1 Hz, CH2CHO; 3.55, 1H, t, J   8.   3 Hz, H5; 4.30, 1H, m, H5 ; 4. 55, 1H, m, H4 ; 9.   79,   s, CHO. 13C NMR (75.6 MHz,   CDCIs)   :   # 25.67 (RFCH2CH2),    27.76   (Rr-CH2¯CI-12),   47.40 (CH2CHO), 69.   92 (Cs),   71.   29   (C4), 109.24 (C2), 198. 52 (CHO).

   EI-MS : m/z 808 (M+, absent), 765 (M+-CH2CHO, 1),   461   (M+-CH2CH2C6F13, 2), 417 (5), 375   (8),   87   (15),   69   (100).   



    Unreacted   alcohol 65 (10   mg, 29%) was   obtained from 70 : 30   Et20   : light petroleum. 



    (c)   Vigorous oxidation of2, 2-bis (3,3, 4,4, 5, 5,6, 6,7, 7,   8,   8,   8-tridecafluorooetyl-4S*-   (1S*,2-dihydroxyethyl)-1,3-dioxolane 65 using pyridinium dichromate Pyridinium dichromate (267   rng, 0. 7 mmol)   was added slowly to a solution of alcohol 65 (115 mg, 0.14 mmol) in dry CH2Cl2. The mixture was stirred at r. t. for 3 d, then filtered through filter aid with the aid of CH2Cl2 (50 mL).

   Evaporation of the solvent and flash   chrornatography   of the residue on silica gel gave aldehyde   69   (17 mg,   17%),   followed in the 95:5 Et2O/light petroleum fraction, 2-[2,2- bis(3',3',4',4',5',5',6',6',7',7',8',8',8'-tridecafluorooctyl)-1,3-dioxolan-4-yl]ethanoic acid 70 as a white solid (124 mg, 24%) m.p. 58-60 C (light petroleum) 
 EMI62.1 
   (Found :   C, 30. 58; H, 1.44. C21H14F26O4 requires C, 30.60; H, 1.71%).   Vx   3400-3000   (0-H),     2960,   2927, 1720 (C=O),   1455,     1322,   1240, 1202, 1145, 1121, 1088, 1024 cm-1. 



  1H NMR   (300MHz, CDCl3): #    1. 90,   4R   m,   2   x RFCH2CH2 ; 2. 20,   4H,     %   2 x   RCHzCHz   ; 2.60,   1R,     dd,     #    17   Hz,     7   Hz, CH2COOH ; 2. 80, 1H, dd,   J   17, 7   Hz,   CH2COOH; 3. 70,   zu     t,   J 3 Hz, H5; 4.30, 1H, m, H5 ; 4, 50, 1H, m, H4.'3C NMR (75.6 MHz, CDCl3) 25.7, RFCH2CH2; 27.6, RFCH2CH2; 38.0, C2; 69. 6, C5'; 72.4, C4';   109.     5,   C2'; 175.5, C1. EI-MS: m/z 824 (M+, absent), 765 (1%), 477 (12), 417   (6), 375     (5),     131   (6), 119 (10), 103 (12), 85 (100). 



  (d)   Hydnde   de reduction of (-)-trans-4,5-bis(ethoxycarbonyl)-2,2- bis   (3,   3, 4, 4,5,5,6,6, 7,   7,     8,   8, 8-tridecafluorooctyl)-1, 3-dioxolane (-)-58 Diester (-)58 (60 mg, 0.   06   mol) in dry Et2O   (2     mL)   was added dropwise to a suspension of   LiAJBLt   (12. 5   mg,   0. 32 mmol) in dry Et2O (1 mL). The mixture was 

 <Desc/Clms Page number 63> 

 stirred at ambient temperature for 20   h,   then quenched with 10% aq. KOH, and filtered through filter   aid. The titrate   was separated and the aqueous layer extracted exhaustively with Et2O (25 mL).

   The combined organic extracts were dried (Na2SO4), evaporated to dryness, and the resulting colourless oil   (3 7 mg) flash cbromatographod,   eluting with   75 :   25   Et20   ; light petroleum to yield (-)-trans-4,5-bis(hydroxymethyl)- 2,2-bis (3,   3,   4,   4, 5, 5, 6,   6,7, 7,   8,     8, 8-iridecafluorooctyl)-1, 3-dioxolane (-)-66 as   a colourless oil (36 mg, 67 %), which had identical spectroscopic properties to those observed for the racemic sample. 



  References 1. Pereira, S.M., Savage, G.   P.,   Simpson, G.   W.,     bo.   Commun., 1995, 25, 1023-    
1026. 



  2. a. Hov th, I.T., Rabai, J. Science, 1994, 266, 72-75; b. Horvatb, I. T. , Ac  Chem. 



   Res. 1998, 31, 41-650 ; c. Gladysz, J. A. , Scietice, 1994, 266, 55-56 ; d. Curran,     D.   P., Angew. Chem., Int.Ed.Engl., 1998, 37, 1174. 



  3. Curran, D.P., Chemtracts-Organic Chemistry, 1996, 75-87. 



  4. Studer, A., Hadida, S. , Ferritto, R, Kim, S.-Y., Jeger,   P.,     Wipi.     P.,   Curran, D. P., 
Science, 1997,   275,   823-826.    



  S. Bhattacharyya, P., Gudmunsen, D., Hope, E. G. , Kemmitt, R. D. W. , Paige, D. R.,   
Stuart, A.M., J. Chem. Soc., Perkin Trans. 1, 1997, 3609-3612 and references therein. 



  6.   a.     Currant,     DP, Hadida,   S. , J. Am. Chem. Soc., 1996, 118, 2531; b. Larhed, M.,   Hoshmo,   M., Hadida, S., Curran, D.P., Hallberg, A., J. Org. Chem., 1997,   62,   
5583-5587; c. Curran, D.P., Hadida, S., He, M., J. Org. Chem., 1997, 62, 6714- 
6715; d. Curran, D.P., Luo, Z., Degenkolb, P., Bioorg. Med. Chem. Lett., 1998, 8, 
2403-2408. 



    7.     Studer,     A.,   Curran, D. P., Tetrahedron, 1997,   53,   6681-6696. 



    S.   Studer, A., Jeger, P.   Wipf,   P. , Curran,   D.   P., J. Org. Chem., 1997, 62, 2917-2924. 



  9. Kainz, S., Koch, D., Baumann, W., Leitner, W., Angew. Chem., Int. Ed. Engl.,    1997, 36, 1628.   



  10.   Ogawa,   A.,   CUITS,   D.P., J. Org. Chem., 1997, 62, 450-451. 



  11.   FC-72   is   a   commercial solvent, b.p. 56 C, that is sold by 3M and is a mixture of perfluorohexanes,   C6F14.   



  12. Kainz, S. , Luo, Z., Curran, D. P., Leitner, W., Synthesis, 1998, 1425-1427. 



  13."Fishing-out", see Walters, M. A., Chemtracts-Organic Chemistry, 1998, 11, 1013-
1024. 

 <Desc/Clms Page number 64> 

 



    14.     T. W Greene and P. G.   M.   Wuts,"Protective   Groups in Organic Synthesis", 2nd Ed. 



   (Wiley : New York 1991). 



  15.   P. JKocienski,"Protecting Groups", (Thieme : Stuttgart 1994 ¯   16. Alexakis, A., Mangeney, P., tetrahedron Asymm., 1990, 1, 477-511. 



    17. Seebach, D. , Ae7gew. Chem., Int. Edn. Engl., 1979, 18, 239-258.   



  18.   Schmeltz,     K.   C. , Fluorinated alcohols, US Patent 3478116, 1969, 9pp 19. Schmeltz, K.   C.,     Fluorinated   polyesters, US Patent 3504016, 1970, Spp 20. Schmeltz, K. C., Fluorinated   polyurethanes for oil-and waterproofing textiles, US   
Patent 3547894,1970, 5pp 21. Schmeltz, K.C., Fluorinated acids and esters, US Patent 3578701, 1971, 9pp (Chem.

   Abstr., 1971, 72,   33199m)   
Throughout this specification the   word"comprise",   or variations such as   "comprises"or"compnsing", wxll be understood   to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step,   or group of elements,   integers or steps. 



   Moreover, any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed in Australia before the priority date of each claim   of this application.   



   Furthermore, it win be appreciated by persons skilled in the art that numerous variations   and/or   modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

CLAIMS ; 1. A method for producing a compound of Formula III as shown in reaction Scheme 1 : EMI65.1 Scheme 1' wherein each X is independently selected from 0 or S ; n=0-2; R1 to R8, which may be the same or different, are independently selected from the group consisting of H, optionally substituted straight or branehed alkyl, CF3, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkylene, optionally substituted straight or branched alkene, optionally substituted, bridged or non-bridged 3-to S-membered saturated or unsaturated carbocylic or heterocyclic ring and -(CH2)mZR11, in which m = 0-3, Z is O, S or is absent,

or R7 and R8 together form a substituted or unsubstituted 3-to 8-membered ring ; R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one substituent R'to Ra is the group R9 is selected from a single covalent bond between X groups (when X = S), R SiR. or C(O)R10, wherein R10 is optionally substituted alkyl ; and Y is O or (OR10)2.

2. A method according to claim 1, wherein compound H is an aldehyde.

3. A method according to claim 1, wherein compound II is a ketone.

4. A method according to claim 1, wherein compound II is an acetal.

5. A method according to claim 1 carried out in the presence of an acid catalyst.

6. A method according to any one of the preceding claims, wherein the reaction is carried out in the presence of a catalyst selected from ISO4, CH3SO3H, <Desc/Clms Page number 66> CF3SO3H, CH3C6H4SO3H, pyridinium p-toluenesulfonate, Me3SiCl, Me3SiO3SGF3, SnCl4, TiCl3, HgCl2, and lanthanide alkylsulfonate salts.

7. A method according to any one of the preceding claims wherein the reaction is carried out in the presence of a non-hydroxylic solvent.

8. A method according to claim 7, wherein the solvent is selected from toluene, cyclohexane, BTP and mixtures of two or more thereof 9. A method according to claims 1 to 6 carried our in the absence of solvent at elevated temperature with continuous removal of volatiles.

10. A method according to any one of the preceding claims, wherein R11 is C6F13.

11. A method according to claim 1, wherein n=0.

12. A method according to claim 1, wherein n=1.

13. A method according to daim 1, wherein n==2.

14. A method according to any one of the preceding claims, wherein at least one of R7 and R8 is a substituted or unsnbstituted phenyl group.

I S. A method according to claim 1, wherein compound III is an acetal.

16. A method according to claim 1, wherein compound III is a ketal.

17. A method according to claim 1, wherein the compound of formula I is selected ftom the group consisting of A compound according to claim 9 selected from the group consisting of2- (3, 3, 4, 4, 5, 5, 6,6, 7,7, 8, 8, 8-Tridecafluorooctyl)-1,3- propanediol, 2,2-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3- propanediol, 1,1-Bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2,2-dimethyl- 1, 3-propanediol, 1-(3, 3, 4,4,5,5,6,6, 7,7, 8, 8, $-tridecafluorooctyl)-l, 2-ethanediol, bis 1-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,2-ethanediol, and 1,1- bis (3,3, 4,4, 5, 5, 6, 6,7,7,8,8,8-tridecafluorooctyl)-1,4-butanediol.

<Desc/Clms Page number 67>

18. A compound of formula T : EMI67.1 wherein each X is independently selected from 0 or S, n=0-2 ; R'to R6, wbich may be the same or different, are independently selected from the group H, optionally substituted straight or branched alkyl, CF3 or a group- (C.

H2)mZR11 in which m=0-3, Z is 0, S or is absent, a ; ad Ri1 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one of Rl to 1 is the group- (CH2)mZR11; and SEe is selected from a single covalent bond between X groups (when X is S), H, SIR103 or C(O)R10 wherein R10 is substituted or unsubstituted alkyl, provided that when each X is O, n = 1, one or both of R3 and R4 are - (CH2)mR11 in which m = 0-3 and R"is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, and at least one of R1, R2, R5, R6 or R9 is other that H.

19. A compound according to claim 1S, wherein 20. A compound according to claim to claim 18 or claim 19, wherein Rll is C6F13.

21. A compound according to any one of claims 18 to 20, wherein each R is H.

22. A compound according to anyone of claims IS to 21, wherein at least two of R1 to R4 are the group- (CH2)mZR11.

23. A compound selected from the group consisting of 2-(3,3,4,4,5,5, 6, 6, 7, 7,8, 8, 8- Tridecafluorooctyl)-1,3-propanediol, 2, 2-Bis (3, 3, 4,4, 5, 5, 6, 6,7,7,8,8,8- tridecafluorooctyl)-1,3-propanediol, 1,1-Bis (3, 3, 4, 4, 5, 5,6, 6, 7,7,8,8,8- tridecafluorooctyl)-2, 2-dimethyl-1, 3-propanediol, 1- (3, 3, 4, 4,5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-1, 2-ethanediol, 1,1-Bis(3,3,4,4,5,5,6, 6, 7, 7, 8, 8, 8- tridecafluorooctyl)-1,2-ethanediol, and 1,1-bis(3,3, 4, 4, 5, 5, 6, 6, 7, 7, 8,8,8- triecafluorootr 4-butanediol. <Desc/Clms Page number 68>

24. A compound according to claim 18, wherein n=0.

25, A compound according to claim 18, wherein R9 is SiR103.

26. 1, 1-Bis (3,3, 4,4, 5, 5, 6, 6,7, 7, 8,8,8-tridecafluorooctyl)-1,3-bis(trimethylsilyloxy)- 2,2-dimethylpropane.

27. 2- (3, 3, 4,4, 5, 5, 6, 6,7, 7, 8,8-tridecafluorooctyl)propane-1,3-diol dimesylate.

28. 2- (3, 3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl)propane-1,3-dithiol diacetate.

29. A compound according to claim 18, wherein each X is S.

30. A compound of formula III : EMI68.1 wherein each X is selected independently from 0, S or CH2; n=0-2; R1 to R8, which may be the same or different, are independently selected from the group consisting of H, optionally substituted branched or straight chained alkyl optionally interrupted by one or more heteroatom (s), optionally substituted straight or branched alkene optionally interrupted by heteroatoms, CF3, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkylene,, optionally substituted 3-to 8-membered saturated or unsaturated carbocyclic ring, optionally substituted 3-to 8-xnembered saturated or unsaturated heterocyclic ring,

optionally substituted 3-to 8-membered, heteroaromatic ring and -(CH2)mZR11, in which m = 0-3, Z is 0, S or is absent, or when n is 1 or,'., at least one of the pairs and R2, R3 and R4, Its and Razor R7 and R8 optionally form a substituted or unsubstitutcd 3-to 7-membered ring <Desc/Clms Page number 69> optionally containing one or more heteroatom (s) or an oxo (=0) group or, when n=O, at least one of the pairs R1 and R2, R2 and R or R7 and f optiaily form a substituted or unsubstituted 3-to 7-membered ring optionally containing one or more heteroatom (s)

or an oxo (==0) group ; and R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one substituent Rlto R8 is the group- (CH2)mZR11.

31. A compound according to claim 30, wherein each X is O.

32. A compound according to claim 30 which is an acetal.

33. A compound according to claim 30 which is a ketal.

34. A compound selected from the group consisting of 5- (3, 3, 4,4, 5, 5, 6, 6, 7,7, 8, 8, 8- tridecafluorooctyl)-1, 3-dioxane-2-spirocyclopentane, 2-phenyl-5- (3,3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 8-tridecafluorooctyl)-1,3-dioxane, 2-methyl-2-phenyl-5- (3,3, 4,4, 5, 5, 6, 6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane, 2, 2-diphenyl-5- (3, 3,4, 4,5, 5, 6, 6, 7,7, 8, 8, 8-tridecafluorooctyl)-1, 3-dioxane, 2, 2-diethyl-5- (3, 3, 4, 4, 5, 5, 6, 6, 7,7, S, 8,

8-tridecafluorooctyl)-1, 3-dioxane, 2- (3-hydroxylphenyl)-5- (3,3, 4,4,5,5,6,6, 7,7, 8, 8,8-tridecafluorooctyl)-1,3-dioxane, 5,5- Bis (3, 3, 4,4, 5, 5, 6, 6,7, 7,8,8,8-tridecafluorooctyl)-2-ethyl-1,3-dioxane, 5,5- Bis (3, 3, 4, 4, 5, 5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-phenyl-1,3-dioxane, 5,5- Bis (3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctyl)-2-(3-hydroxyphenyl)-1,3-dioxane, 4, 4-Bis (3, 3, 4, 4, 5, 5, 6, 6, 7, 7,8, 8, 8-tridecafluorooctyl)-5,5-dimethyl-2-ethyl-1, 3- dioxane, 4, 4-Bis (3, 3, 4, 4,5,5,6,6, 7, 7, 8,8,8-tridecafluorooctyl)-5,5-dimethyl-2- phenyl-1,3-dioxane, 4,4-Bis(3,3,4, 4, 5, 5, 6,6,7,7,8,8,8-tridecafluorooctyl)-2-phenyl- 2,5, 5-trimethyl-1,

3-dioxane, 4,4-Bis (3,3, 4, 4, 5, 5, 6, 6,7,7,8,8,8-tridecafluorooctyl)- 5, 5-dimethyl-2- (3-hydroxyphenyl)-1, 3-dioxane, 4, 4-Bis (3, 3, 4, 4, 5, 5, 6, 6, 7,7, 8, 8, s- tridecafluorooctyl)-2-phenyl-1,3-dioxolane, 4, 4-Bis (3, 3, 4, 4,5, 5, 6, 6, 7, 7, 8, 8, 8- tridecafluorooctyl)-2-methyl-Z-phenyl-1, 3-dioxolane, 4,4- Bis (3, 3, 4, 4, 5,5 6, 6, 7, 7, 8,8-tridecafluorooctyl)-2-(3-hydroxyphenyl)-1,3- dioxolane, 4,4-bis(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-2-phenyl-1, 3- dioxepane. Synthesis of 5- (3, 3,4,

4, 5, 5, 6, 6, 7,7, 8, 8, 8-tridecafluorooctyl)-1,3-dithiane, 4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,2-dithiacyclopentane, 2-(3- Hydroxyphenyl)-5- (3, 3,4, 4,5,5,6,6, 7,7, 8, 8, 8-tridecafluorooctyl)-1, 3-dioxane, 1S- <Desc/Clms Page number 70> (endo,endo)-2-(5,5-bis(3, 3,4, 4, 5, 5, 6, 6, 7,7,8,8,8-tridecafluorooctyl)-1,3-dioxan-2- yl)-3- (2-methyl-5, 5-bis (3,3, 4, 4,5, 5, 6, 6, 7,7, 8,8,8-tridecafluorooctyl)-1,3-dioxan-2- yl) bicyclo[2.2.1]hept-5-ene, 1S-(endo,endo)-3-acetyl-2-(5,5- bis (3,3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8,8-tridecafluorooctyl)-1,

3-dioxan-2-yl)bicyclo [2. 2.1]hept- 5-ene, 5, 5-bis (3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 8-tridecafluorooctyl)-2- (4-ethanoylphenyl)- 1, 3-dioxane, 5, 5-Bis (3,3, 4,4, 5, 5, 6, 6,7,7,8,8,8-tridecafluorooctyl)-2-(2-phenyl-(E)- ethenyl)-1, 3-dioxane, 4-[5,5-bis (3, 3, 4,4, 5,5,6,6, 7,7, 8, 8, 8-tridecafluorooctyl)-1, 3- dioxane]benzaldehyde, 1, 4-bis [5, 5-bis (3,3, 4, 4, 5, 5, 6,6, 7,7,8,8,8-tridecafluorooctyl)- 1, 3-dioxane] benzene, 4, 4-bis (3, 3, 4,4, 5, 5, 6, 6, 7,7, 8, 8, $-tidecafluorooctyl)-5,

5- dimethyl-2-(2-phenyl-(E)-ethenyl)-1,3-dioxane, 4, 4-bis (3,3, 4,4, 5,5,6, 6, 7,7,8,8,8- tridecafluorooctyl)-5, 5-dimethyl-2- (2-phenylethyl)-1, 3-dioxane, 4,4- bis (3, 3, 4,4,5, 5, 6, 6,7, 7, 8,8,8-tridecafluorooctyl)-5,5-dimethyl-2-(2-phenyloxiranyl)- 1, 3-dioxane, 5, 5-bis (3,3, 4,4, 5, 5, 6, 6, 7, 7,8,8,8-tridecafluorooctyl)-2-[4-(1- hydroxyethyl)phenyl]-1,3-dioxane, 5, 5-biS (3,3,4,4,5,5,6,6,7, 7, 8, 8, 8- tridecafluorooctyl)-2- [4- (l"hydroxyethyl) phenyl]-1, 3-dioxane, 4 [5, 5- bis (3,3, 4, 4, 5, 5, 6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxan-2-yl]benzaldehyde, 4- [5,

5-bis (3, 3, 4, 4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane]benzaldehyde 3, ethyl 2-{4-[5,5-bis (3,3, 4,4, 5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxan-2- yl]phenylmethylidene}-3-oxopentanoate, 2, 6-dimethylS 5-bis (ethoxycarbonyl)'4- {4-[5,5-bis(3,3,4, 4,5, 5, 6, 6, 7, 7, 8, 8, 8-tridecafluorooctyl)-1, 3-dioxan-2-yl] phenyl}- 1,4-dihydropyridine, 2-(3-Butoxyphenyl)-5-(3,3,4,4,5, 5, 6, 6, 7,7, 8, 8, 8- tridecafluorooctyl)-1,3-dioxane, 2-(3-Hydroxyphenyl)-5-(3, 3, 4, 4, 5, 5, 6, 6, 7, 7, 8, 8, 8- tndecafluorooctyl) 3-dioxane, 2-(3-butoxyphenyl)-5-(3, 3,4, 4,5, 5,6, 6, 7,7, 8,8,8- tridecafluorooctyl)-1,

3-dioxane, 2-(3-isopropoxyphenyl)-5- (3, 3, 4, 4, 5, 5, 6,6, 7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane, 2-(3-Allyloxyphenyl)-5- (3,3, 4,4, 5, 5,6, 6, 7,7, 8, 8, 8-tridecafluorooctyl)-1,3-dioxane, 2-(3-Benzyloxyphenyl)- 5- (3, 3,4, 4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1,3-dioxane, 2-(3-butyloxphenyl)- 5, 5-bis (3,3, 4,4, 5,5, 6, 6, 7,7, 8, 8, 8-tridecafluorooctyl)-1,3-dioxane, 2-(3- Isopropoxyphenyl)-5, 5-bis (3,3, 4,4, 5, 5, 6, 6, 7, 7, 8, 8,8-tridecafluorooctyl)-1,3-dioxane, 2- (3-Allyloxyphenyl)-5, 5-bis (3,3, 4,4,5, 5, 6, 6,7, 7,

8, 8, 8-tridecafluorooctyl)-1,3- dioxane, 2-(3-Benzyloxyphenyl)-5, 5-bis (3, 3, 4, 4, 5,5,6,6,7,7,8,8,8- tridecafluorooctyl)-1,3-dioxane, 2-[1,5-Bis (3,3, 4,4, 5, 5, 6, 6,7, 7,8, 8, 8- tridecafluorooctyl) pent-3-yl]-5, 5-dimethyl-1, 3-dioxane, 2, 2- Bis(3,3,4, 4, 5, 5, 6, 6, 7,7, 8, 8,8-tridecafluorooctyl)-1,3-dioxane, 1,1- Bis (3, 3, 4, 4, 5, 5,6, 6,7, 7, 8, 8,8-tridecafluorooctyl)-1,1-dimethoxymethane, 2,2- bis (3, 3, 4,4, 5, 5, 6, 6, 7, 7, 8, 8, 8-tridecafluorooctyl)-5-methyl-1,3-dioxolane, (-)

-trans- <Desc/Clms Page number 71> 4, 5-bis (ethoxycarbonyl)-2, 2-bis (3,3, 4,4, 5,5,6, 6, 7, 7, 8, 8, 8-tndecafluoroocty !)-l, 3- dioxolane, 2, is (3', 3', 4', 4', 5', 5', 6', 6', 7', 7', 8', 8'8'-tridecafluorooctyl)-4- hydroxyethyl)-1,3-dioxane, 2,2-bis (3', 3', 4', 4', 5', 5', 6', 6', 7', 7', 8', 8', 8'- tridecafluorooctyl)-4- (2"-hydroxyethyl)-1, 3-dioxolane, 2,2- bis (3', 3', 4', 4', 5', 5', 6', 6',7',7',8',8',

8'-tridecafluoroctyl)furo [3, 4-d]-1, 3-dioxolane, 2,2- bis (3, 3,4, 4, 5, 5, 6, 6, 7, 7, 8, 8,8-tridecafluoroctyl-4S*-(1R*,2-dihydroxyethyl)-1,3- dioxolane, 4, 4'-bi[2,2-bis(3',3',4',4',5', 5', 6', 6', 7', 7',8',8',8'-tridecafluoroctyl)-1,3- dioxolane, 4, 4'-bi[2,2-bis(3',3',4',4', 5', 5', 6', 6', 7',7',8',8',8'-tridecafluorooctyl)-1,3- dioxolane, 4,5-bis (hydroxymethyl)-2, 2-bis (3', 3',4',4',5',5',6',6',7',7',8',8',8'- trideGafluorooctyl)-1, 3-dioxolane, bis (3, 3, 4, 4, 5,5, 6, 6, 7,7, 8, 8, 8-tridecafluorooctyl)- 1, 3-dioxolan-4-yl]carboxaldehyde, 2-[2,

2-bis(3',3',4',4',5',5',6',6',7',7',8',8',8'- tridecafluorooctyl)-1, 3-dioxolan-4-yl] ethanal, 2- [2, 2- bis (3', 3', 4', 4',5',5',6',6',7',7',8',8',8'-tridecafluorooctyl)-1,3-dioxolan-4-yl]ethanoic acid, 4, 5-bis (hydroxymethyl)-2, 2-bis (3,3, 4,4, 5,5,6, 6, 7, 7, 8, 8, 8-tridecailuorOoctl)- dioxolane.

35. A solvent consisting or a compound according to any one of claims 30 to 34 or comprising said compound and least one other solvent.

36. Use of a compound according to any one of claims 30 to 35 as a solvent optionally with at least one other solvent.

37, Use of at least one compound according to any one of claims 30 to 36 in a sequential chemical transformation.

38. Use according to claim 37 including the step of forming a compound of any one of claims 30 to 36 by a method according to any one of claims 1 to 17.

39. Use according to claim 37 or 38, wherein the at least one compound is used in the formation of a compound library through parallel or mixed synthesis.

40. Use of a compound of any one of claims 30 to 36 in a separation strategy involving liquid-liquid extraction, fluorous reverse phase solid phase extraction, chromatography or precipitation. <Desc/Clms Page number 72>

41. Use according to claim 40 including the step of forming the compound of any one of claims 30 to 36 by a method in accordance with any one of claims 1 to 17.

42. A method for producing a chemical product, the method comprising the steps ; (a) performing the method of any one of claims 1 to 17 to produce a tagged acetal or ketal of formula IJI ; (b) chemically transforming the tagged acetal or ketal of step (a) into a modified tagged acetal or ketal of formula ni ; (c) chemically transforming the modified tagged acetal or ketal of step (b) to form a product.

43. A method according to claim 42, wherein step (b) is repeated 2 or more times.

44. A method according to claim 43, wherein each repeated step (b) is the same chemical transformation.

45 A method according to claim 43, wherein repeated step (b) involves at least one different chemical transformation.

46. A method according to any one of claims 42 to 45, wherein the product of step (c) is in accordance with formula Irai.

47. A method according to any one of claims 42 to 45, wherein the product retains the tag.

48. A method according to any one of claims 42 to 45, wherein the tag is absent from the product.

49. A method according to any one of claims 42 to 48, wherein the product is a library of compounds.

50. A compound of formula 1 <Desc/Clms Page number 73> EMI73.1 wherein the R1R2(R9X)C group taken together and the R1R2(R9X)C group taken together are individually or separately a nitrile (-CN), an ester (-CO2R12), a thionoester (-C (S) OR'2), a thiolester (-C(O)SR12), an amide (-CONR12R13) or a thioacide (-CSNR12R13) and n=1-2; R3 to R4, which may be the same or different, are independently selected from the group H, CH3, CF3 or a group -(CH2)mZR11 in which m = 0-3, Z=O, S or is absent, and R11 is a fully fluonnated straight or'branched alkyl chain of 4 to 12 carbons in length, provided that at least one of R3 or R4 is the group - (CH2)mZR11.

51. A compound of formula I EMI73.2 1 wherein the R1R2(R9X)C group taken together is a nitrite (-CN), an ester (- CO2R12), a thionoester (-C (S)OR12), a thiolester (-C (O) SR12), an amide (-CONR12R13) or a thioamide (-CSNR12R13) and taken individually, X = 0 or S; n =0-2 ; R1 to R6, which may be the same or different, are independently selected from the group H CH3, CF3 or a group 4CH, mZR11 in which m=0-3, Z=O, S or is absent, and R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one of R1 to R6 is the group -(CH2)mZR11;

and R ? is selected from a single covalent bond between X groups (when X = S), H, SiR103 or C (O)R10 wherein R10 is alkyl, provided that when X = 0, n = 1, one or both of R3 and R4 are- (CH2)mR11 in which m = 0-3 and R"is a fully fluonnated straight or branched alkyl chain of 4 to 12 carbons in length, at least one of R1, R2, R5, R6 or R9 is other that H. <Desc/Clms Page number 74>

52. A compound of formula I EMI74.1 wherein the R1R2(R9X)C group taken together is a branched or straight chain alkyl, aryl, alkaryl, polyether or polyamine group that is hydrophobia hydrophilic or fluorophilic ; and taken individually, X=O or S; n=0-2; R3 to R6, which may be the same or different, are independently selected from the group H, CEI3, CF3 or a group- (CH2)mZR11 in which m = 0-3, Z = 0, S or is absent, and R11 is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length, provided that at least one of R1 to R6 is the group- (CH2)mZR11 ; ;

and R9 is selected from a single covalent bond between X groups (when X = S), H, SiR103 or C (O) R10 wherein R10 is alkyl, provided that when X = O, n = 1, one or both of R3 and R4 are - (CH2)1 nR11 in which m = 0-3 and R"is a fully fluorinated straight or branched alkyl chain of 4 to 12 carbons in length.

53. A compound of formula M EMI74.2 wherein X = O or S; n=0-2 ; R'-R6, which may be the same or different, are individually selected fron, the group consisting of H, CH3, CF3 or a group- (CH2)mZR 11 in which m = 0-3, Z = 0, S or is absent, and R11 is a fully fluorinated straight or branched alkyl <Desc/Clms Page number 75> chain of 4 to 12 carbons in length, provided that at least one of the substituents R1-R6 is the group -(CH2)mZR11 ;

and the R7R8C group when taken together is a carbonyl (C=O), thiocarbonyl (C=S), iminyl (C=NR11), borane (BR15), or borate (BOR15), in which R15 is H or CH3, or a branched or straight chain alkyl, aryl, aralkyl, polyether or polyamine group of 2-12 atoms in length that is hydrophobic, hydrophilic or fluorophilic.

54. A compound of formula HI EMI75.1 wherein one X = 0 or S ; the second X=CH2, CR16R17, or a carbonyl group, n=0-2; R1-R8, R17, R18 which may be the same or different, are individually selected from the group consisting of H, CH3, CF3 or a group- (CH2) mZR" in which m = 0-3, Z = 0, S or is absent, and R11 is a fully fluorinated straight or branched alkyl chain of 4 to} 2 carbons in length, provided that at least one of the substituents R1-R8 is the group -(CH2)mZR11.