MXPA99011790A - Alkene borates and a process for covalently coupling organic compounds - Google Patents

Abstract

This invention describes a process for covalently coupling organic compounds which comprises reacting an olefinic compound having a halogen or halogen-like substituent at a coupling position with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base. The invention also describes a process for preparing alkene borate intermediates comprising reacting an olefinic compound having a halogen or halogen-like substituent with a diboron derivative in the presence of a Group VIII metal catalyst and a suitable base.

Description

ALKENE BORATES AND A PROCESS TO COUPLED ORGANIC COMPOUNDS COVALENTLY FIELD OF THE INVENTION This invention relates to a process for covalently coupling organic compounds, in particular to a process for covalently linking an olefinic portion via an organoboron intermediate to other organic compounds. The invention also relates to a process for the preparation of organoboron intermediates.

BACKGROUND OF THE INVENTION The process for forming covalent bonds between olefinic compounds and organic compounds, both inter and intra-molecular, is of particular importance to synthetic organic chemistry. Many of these reactions are known, each requiring its own special reaction conditions, catalysts, activation groups, and so on. Some types of coupling reactions comprising olefinic portions include the Michael reaction and the reactions described in the following references: Transition Metals in the Synthesis of Complex Organic Molecules (L.S. Hegedus, University Science Books, 1994, ISBN 0-0935702-28-8); Handbook of Palladiun Catalysed P1754 / 99MX Organic Reactions (J: Malleron, J. Fiaud and J. Legros, Academic Press, 1997, ISBN 0-12-466615-9); Palladiu Reagents and Catalysts (Innovations in Organic Synthesis by J. Tsuji, John Wiley &Sons, 1995, ISBN, 0-471-95483-7) and N. Miyuara and A. Suzuki, Chem Rev. 1995, 95, 2457- 2483 The palladium catalysts, their complexes and their salts are well recognized for the activation of the C-H bond towards the coupling reactions. In this regard, Heck's reaction of an alkene with an aryl or vinyl halide in the presence of palladium derivatives has been the subject of an intensive study. However, the commercial development of Heck's reaction has not progressed as quickly as one might have expected. Other catalysts of group VIII metals, such as platinum, have also been used to activate these carbon bonds. The success of the Heck reaction depends to a large extent on the substrates and the reaction conditions. When two β-hydrogens are present in the alkene, the reaction leads in general to the formation of the (E) -alkenes which are frequently contaminated with the corresponding (Z) -alkenes. Although alkene (alkenyl borate) borates can be reacted with a variety of organic molecules to give coupled products via P1754 / 99MX the formation of new carbon-carbon bonds (see for example, the above references) the process for the preparation of the alkenyl borates by the commonly used hydroboration reaction of the alkynes is limited due to the difficulties encountered through the lack of regiochemistry and / or chemoselectivity (such as the reduction of a number of different functional groups (see, N. Miyuara and A. Suzuki, Chem Rev. 1995, 95, 2457-2483). Improved methodologies for the synthesis of alkene borates It has now been found that alkene borates can be synthesized from haloalkenes or pseudo-haloalkenes under mild conditions and in the presence of a range of substituents. at least mitigates, one or more of the limitations found in the use of the hydroboration methodology and is fundamentally different since the starting material is an alkene and not an alkyne. The coupling of the alkenyl borates with an organic compound can be achieved in the presence of a group VIII metal catalyst and a suitable base.

SUMMARY OF THE INVENTION Accordingly, the invention provides a process for covalently coupling organic compounds, which comprises reacting a P1754 / 99MX olefinic compound containing a halogen-type substituent or a halogen, in a position of vinyl coupling with a diboro derivative in the presence of a group VIII metal catalyst and a suitable base. In a modality, this process can be used to prepare a symmetric product. In this mode, the coupling proceeds in two steps. In the first step, the diboro derivative reacts with an olefinic compound in the presence of the group VIII metal catalyst and a suitable base to form an intermediate compound of the alkene borate, this intermediate compound reacts in the presence of the base with the remaining olefinic compound. According to this embodiment, the covalent coupling comprises a covalent bond between the coupling positions of the two molecules of the olefinic compound. Preferably, the suitable base used to catalyze the reaction with the diboro derivative is also capable of catalyzing the coupling of the intermediate compound of the alkene borate compound to the remaining olefinic compound. However, if necessary, a stronger base can be made or the reaction mixture can be heated after the formation of the intermediate compound of the alkene borate compound, to catalyze or promote the coupling reaction.

P1754./99MX The process according to the invention also allows the preparation of non-symmetrical products. Accordingly, in another embodiment of the invention, a process for covalently coupling organic compounds is provided, which comprises: reacting an olefinic compound having a halogen or halogen-type substituent in a vinyl coupling position with a diboron derivative in the the presence of a group VIII catalyst and a suitable base to form an intermediate compound of alkene borate, and reacting the intermediate compound of alkene borate with an organic compound having a halogen or halogen-type substituent in a coupling position in the presence of a group VIII metal catalyst and a suitable base, whereby the olefinic compound is coupled to the organic compound via a direct link between the respective coupling positions. The process according to this embodiment allows the preparation of non-symmetrical compounds when the organic compound is different from the olefinic compound, although symmetrical products will be obtained if the organic compound is the same as the olefinic compound. It is especially convenient to carry out the process in an individual pot without isolation P1754 / 99MX of the alkene borate intermediate, however, it has been found that the presence of the unreacted diboro derivative can interfere with the coupling step, resulting in the formation of undesired by-products. Accordingly, in another embodiment of the present invention there is provided a process for covalently coupling organic processes, which comprises: reacting an olefinic compound having a halogen or halogen-type substituent in a vinyl coupling position with a diboron derivative in the the presence of a group VIII metal catalyst and a suitable base to form an intermediate compound of alkene borate, adding water or water and a suitable base for decomposing the excess diborium derivative, reacting the intermediate compound of alkene borate with an organic compound having a halogen or halogen-type substituent in a coupling position in the presence of a group VIII metal catalyst and a suitable base, whereby the olefinic compound is coupled to the organic compound of a direct bond between the respective coupling positions. Preferably, the reaction was carried out in an individual kettle although it is possible to isolate the intermediate compound of alkene borate P1754 / 99MX before the final coupling step. If the reaction is carried out in an individual kettle, it is preferred that the base added to decompose the diboro derivative is suitable to catalyze the coupling reaction. In this case, there is no need to add the additional base with the organic compound in the coupling reaction. In another embodiment, after the formation of borate of the intermediate compound of alkene borate, the coupling of the intermediate compound of alkene borate with the organic compound is achieved by increasing the temperature of the reaction mixture at a temperature sufficient for the occurrence of the coupling reaction. In this embodiment, it may not be necessary to add a stronger base to catalyze the coupling reaction. In cases where there is a need to remove the derivative in excess of diborum, but the use of water or water and the base is harmful due to the sensitivity of the substituents, etc., or other factors, the excess diborium derivative can be decompose by the addition of mild oxidizing agents after the formation of the intermediate compound of alkene borate. Accordingly, in a further embodiment, a process for covalently coupling organic compounds is provided, which comprises: P1754 / 99MX reacting an olefinic compound having a halogen or a halogen-type substituent in a vinyl coupling position with a diboro derivative in the presence of a group VIII metal catalyst and a suitable base to form an intermediate borate compound of alkene; adding a mild oxidizing agent to decompose the excess diborium derivative; reacting the intermediate compound of alkene borate with an organic compound having a halogen or halogen-type substituent in a coupling position in the presence of a metal catalyst of group VIII and a suitable base by which the olefinic compound is coupled to the organic compound via a direct link between the respective coupling positions. The mild oxidizing agent can be any compound that will break the B-B bond of the diboro derivative that is not strong enough to break the boron-carbon bonds of the intermediate compound of alkene borate. Suitable mild oxidizing agents are: N-chlorosuccinamide, dioxygen gas, chloramine-T, chloramine-B, 1-chlorotriazole, 1,3-dichloro-5,5-dimethylhydantoin, trichloroisocyanuric acid and potassium salt of dichloroisocyanuric acid. Oxidants such as. hydrogen peroxide, ozone, bromine, t-butyl hydroperoxide, P1754 / 99MX potassium persulfate, sodium hypochlorite and peracids, are too strong for use in this process; the use of strong oxidants is not part of this invention. The terms "olefinic" and "olefinic compound" as used herein refer to any organic compound having at least one carbon-to-carbon double bond that is not part of a pseudo-aromatic or aromatic system. The olefinic compounds may be selected from branched or straight-chain, optionally substituted cyclic alkenes, and monomer molecules and macromolecules such as polymers and dendrimers, which include at least one carbon-to-carbon double bond. Examples of olefinic compounds include, but are not limited to, ethylene, propylene, but-1-ene, but-2-ene, pent-1-ene, pent-2-ene, cyclopentene, 1-methylpent-2. eno, hex-1-ene, hex-2-ene, hex-3-ene, cyclohexene, hept-1-ene, hept-2-ene, hept-3-ene, oct-1-ene, oct-2- ene, cyclohexene, non-1-ene, non-4-ene, dec-1-ene, dec-3-ene, buta-1,3-diene, penta-1,4-diene, cycloopenta-1, 4- diene, hex-1, diene, cyclohexa-1,3-diene, cyclohexa-1,4-diene, cyclohepta-1,3,6-triene and cycloocta-1,3,5,7-tetraene, each of which may be optionally substituted. Preferably, the branched or cyclic, straight-chain alkene contains between 2 and 20 carbon atoms.

P1754 / 99MX In one embodiment, the olefinic compound is a compound of the formula I Rl R1 I wherein R1, R2 and R3 are each independently selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, acyl, arylalkyl and heteroarylalguilo (each of which may be optionally substituted) cyano, isocyano, formyl, carboxyl, nitro , halo, alkoxy, alkenoxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitroalkyl, nitroalkenyl, nitroalkynyl, arylamino, diarylamino, dibenzylamino, alkynylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy, alkylsulfonyloxy, arylsulfenyloxy, heterocycloxy, arylsophenyl, carboalkoxy , carbaryloxy, alkylthio, benzylthio, acylthio, sulfonamide, sulfanyl, sulfo, carboxy (including carboxylate), carbamoyl, carboximidyl, sulfinyl, sulfinimidyl, sulfinohydroximyl, sulfonimidyl, sulfondiimil, sulfonohydroximyl, sulfanyl, phosphorus-containing groups (including phosphinyl, phosphinimidyl, phosphonyl) , dihydroxyphosphane, hydroxyphosphate, phosphone (including phosphorus) born) and hydrohydroxyphosphoryl), guanidinyl, duanidino, ureido and ureylene, and X is a halogen or a P1754 / 99MX halogen type substituent. As used herein, "organic compound having a halogen or halogen-type substituent in a housing position" refers to an organic compound having a carbon to halogen bond or carbon to halogen-type substituent in a position where desired the coupling to the olefinic compound. The organic compound can be aliphatic, olefinic, allylic, acetylenic, aromatic, polymeric or dendritic. The compound may be an olefinic compound as defined above or a part thereof an olefinic compound. The organic compound may have one or more, preferably between 1 and 6, halogen or halogen-type substituents in housing substitutions. The terms "aromatic" and "aromatic compound (s)" as used herein refers to any compound or portion that includes or consists of one or more aromatic or pseudoaromatic rings. The rings may be carbocyclic or heterocyclic, and may be mono- or polycyclic ring systems. Examples of suitable rings include, but are not limited to, benzene, biphenyl, terphenyl, quaternphenyl, naphthalene, tetrahydronaphthalene, 1-benzylnaphthalene, anthracene, dihydroanthracene, benzatracene, dibenzatracene, phenanthracene, pyrylene, pyridine, 4-phenylpyridine, 3- P1754 / 99MX phenylpyridine, thiophene, benzothiophene, naphthothiophene, thianthrene, furan, pyrene, isobenzofuran, chromene, xanthene, phenoxathine, pyrrole, imidazole, pyrazole, pyrazine, pyrimidine, pyridazine, indole, indolizine, isoindol, purine, quinoline, isoquinoline, phthalazine, quinoxaline, quinazoline, pteridine, carbazole, carboline, phenanthridine, acridine , phenanthroline, phenazine, isothiazole, isooxaxol, phenoxazine and the like, each of which may be optionally substituted. The terms "aromatic" and "aromatic compound (s)" include molecules and macromolecules such as polymers and macropolymers and dendrimers that include or consist of one or more aromatic or pseudoaromatic rings. The term "pseudoaromatic" refers to a ring system that is not strictly aromatic but that is stable by means of the dislocation of p-electrons and behaves in a manner similar to aromatic rings. Examples of pseudoaromatic rings include, but are not limited to: furan, thiophene, pyrrole and the like. The term "coupling position" as used herein refers to a position in an organic compound in which coupling to another organic compound is desired. A coupling position on a carbon atom that is part of an olefinic carbon to carbon bond is also referred to as "a vinyl coupling position".

P1754 / 99MX Each olefinic compound or organic compound can have one or more, preferably between 1 and 6, coupling positions. In this "optionally substituted" specification it means that a group may or may not be further substituted with one or more groups selected from alkyl, alkenyl, alkynyl, aryl, halo, haloalkyl, haloalkenyl, haloalkynyl, haloaryl, hydroxy, alkoxy, alkenyloxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, isocyano, cyano, formyl, carboxyl, nitro, nitroalkyl, nitroalkenyl, nitroalkynyl, nitroaryl, nitroheterocyclyl, amino, alkylamino, dialkylamino, alkenylamino, alkynylamino, arylamino, diarylamino, benzylamino, imino, alkylimine, alkenylimine, alkylinimino, arylimino, benzylimino, dibenzylamino acyl, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy, alkylsulfonyloxy, arylsphenyloxy, heterocyclyl, heterocycloxy, heterocyclic, haloheterocyclyl, alkylsulfenyl, arylsulfenyl, carboalkoxy, carbonyloxy, mercapto, alkylthio, benzylthio, acylthio , sulfonamido, sulfanil, sulfo and groups that conti They include phosphorus, alkoxysilyl, silyl, alkylsilyl, alkylalkoxysilyl, phenoxysilyl, alkylphenoxyl, alkoxyphenoxy silyl and arylphenoxy silyl. Olefinic compounds must include P1754 / 99MX minus a halogen or halogen-type substituent in a vinyl coupling position to allow reaction with the diboro derivative. Similarly, the organic compound should have a halogen or halogen-type substituent in a housing position to allow reaction with the intermediate compound of alkene borate. Preferred halogen substituents include I, Br and Cl. The reactivity of the aromatic ring compounds, substituted with -chloro can be increased by the selection of appropriate ligands in the metal catalyst of group VIII. The terms "halogen-type substituents" and "pseudo-halide" refer to any substituent, if present, may undergo substitution with a diboron derivative in the presence of a group VIII metal catalyst and a base to give an intermediate of an alkene borate, or if present in an organic compound, can undergo substitution with an intermediate compound of alkene borate to give a coupled product. Examples of the halogen substituents include triflates and mesylates, diazonium salts, phosphates and those described in Palladiun Reagents & Catalysts (Innovations in Organic Synthesis by J. Tsuji, John Wiley &Sons, 1995, ISBN- 0471-95483-7). The process according to the present invention is especially suitable for coupling P1754 / 99MX olefinic compounds containing substituents that are reactive with organometallic compounds, such as Grignard reagents or alkyl lithium, therefore unsuitable for reaction using standard Grignard methodology unless these substituents are first protected. One class of reactive substituents are substituents containing active hydrogen. The term "active hydrogen-containing substituent" as used herein refers to a substituent that contains a reactive hydrogen atom. Examples of these substituents include, but are not limited to, hydroxy, amino, imino, acetylene, carboxy (including carboxylate), carbamoyl, carboximidyl, sulfo, sulfinyl, sulfinimidyl, sulfinohydroximyl, sulfonimidyl, sulfondiimidyl, sulfonohydroximyl, sultamyl, fosfinyl, phosphinimidyl, phosphonyl, dihydroxyphosfanyl, hydroxyphosphane, phosphono (including phosphonate) hydrohydroxyphosphoryl, alofañyl, guanidino, hydantoyl, ureido, and ureylene. Of the substituents, it is particularly surprising that the reaction can be carried out with hydroxy and amino substituents in view of their high reactivity. Carboxyl, sulfo and the like substituents (ie, acids) may require an additional base. Other reactive substituents include trimethylsilyl. In the above definitions, the term P1754.99MX "alkyl", used either alone or in compound words such as "alkenyloxyalkyl", "alkylthio", "alkylamino" and "dialkylamino" denotes branched or cyclic alkyl, straight chain, preferably alkyl of 1-20 carbon atoms. carbon or cycloalkyl. Examples of branched or straight-chain algae include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, amyl, isoamyl, sec-amyl, 1,2-dimethylpropyl, 1,1-dimethyl-propyl. , hexyl, 4-methylpentyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 1, 1-dimethylbutyl, 2,2-dimethylbutyl, 3, 3-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 1 , 2,2, -trimethylpropyl, 1, 1, 2, trimethylpropyl, heptyl, 5-methoxyhexyl, 1-methylhexyl, 2,2-dimethylpentyl, 3, 3-dimethylpentyl, 4,4-dimethylpentyl, 1,2-dimethylpentyl, 1,3-dimethylpentyl, 1,4-dimethyl-pentyl, 1,2,3-trimethylbutyl, 1,1-trimethylbutyl, 1,1,3-trimethylbutyl, octyl, 6-methylheptyl, 1-methylheptyl, 1, 1, 3, 3-tetramethylbutyl, nonyl, l-, 2-, 3-, 4-, 5-, 6- or 7-methyl-octyl, l-, 2-, 3-, 4- or 5-ethylheptyl, l-, 2-or 3-propylhexyl, decyl, l-, 2-, 3-, 4-, 5-, 6-, 7- and 8 -methylnonyl, 1-, 2-, 3-, 4-, 5- , or 6-ethylctyl, l-, 2-, 3- or 4-propylheptyl, undecyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-methyldecyl, 1-, 2-, 3 -, 4-, 5-, 6- or 7-ethylnonyl, 1-, 2-, 3-, 4- or 5-propyloctyl, 1-, 2- or 3-butylheptyl, 1-pentylhexyl, dodecyl, l-, 2- P1754 / 99MX, 3-, 4-, 5-, 6-, 7-, 8-, 9- or 10-methylundecyl, l-, 2-, 3-, 4-, 5-, 6-, 7-o 8-ethyldecyl, 1-, 2-, 3-, 4-, 5- or 6-propylnonyl, l-, 2-, 3- or 4-butyloctyl,, 1-2-pentylheptyl and the like. Examples of cyclic alkyl include mono- or polycyclic alkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, and the like. The term "alkoxy" denotes straight or branched chain alkoxy, preferably alkoxy of 1-20 carbon atoms. Examples of carbon include methoxy, ethoxy, n-propoxy, isopropoxy and different butoxy isomers. The term "alkenyl" denotes groups formed from branched, straight chain cyclics that include ethylenically mono-, di- or polyunsaturated alkyl or cycloalkyl groups, as previously defined, preferably alkenyl of 2 to 20 carbon atoms. Examples of alkenyl include vinyl, allyl, 1-methylvinyl, butenyl, iso-butenyl, 3-methyl-2-butenyl, 1-pentenyl, cyclopentenyl, 1-methyl-cyclopentenyl, 1-hexenyl, 3-hexenyl, cyclohexenyl, -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- P1754 / 99MX cyclohexadienyl, 1,3-cycloheptadienyl, 1,3,5-cycloheptatrienyl and 1,3,5,7-cyclooctatetraenyl. The term "alkynyl" denotes groups formed from straight chain cyclic branched alkyne including those structurally similar to alkyl and cycloalkyl groups as previously defined, preferably alkynyl of 2 to 20 carbon atoms. Examples of alkynyl include ethynyl, 2-propynyl and 2-or 3-butynyl. The term "acyl" either alone or in compound words such as "acyloxy", "acylthio", "acylamino" or "diacylamino" denotes carbamoyl, aliphatic acyl group and acyl group containing an aromatic ring, which is referred to as a ring Aromatic or heterocyclic acyl which is referred to as the heterocyclic acyl preferably acyl of 1 to 20 carbon atoms. Examples of acyl include carbamoyl; branched straight chain alkanoyl such as formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoyl, decanoyl, indecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl , octadecanoyl, nonadecanoyl, and icosanoyl; alkoxycarbonyl, such as methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, t-pentyloxycarbonyl and heptyloxycarbonyl; cycloalkylcarbonyl such as cyclopropylcarbonyl, P1754 / 99HX cyclobutylcarbonyl, cyclopentylcarbonyl and cyclohexylcarbonyl, alkylsulfonyl such as methylsulfonyl and ethylsulfonyl; alkoxysulfonyl such as methoxysulfonyl and ethoxysulfonyl, aroyl such as benzoyl, toluoyl and naphthoyl; aralkanoyl such as phenylalkanoyl (e.g. phenylacetyl, phenylpropanoyl, phenylbutanoyl, phenylisobutyl, phenylpentanoyl and phenylhexanoyl) and naphthylalkanoyl (e.g. naphthylacetyl, naphthylpropanoyl and naphthylbutanoyl; aralquenoilo as phenylalkenoyl (e.g. phenylpropenoyl, phenylbutenoyl, fenilmetacriloilo, phenylpentenoyl and phenylhexenoyl and naphthylalkenoyl ( for example, naphthylpropenoyl, naphthylbutenoyl and naf tilpentenoilo); I aralkoxycarbonyl such as phenylalkoxycarbonyl) (e.g. benzyloxycarbonyl); aryloxycarbonyl such as phenoxycarbonyl and naphthyloxycarbonyl, I aryloxyalkanoyl such as phenoxyacetyl and phenoxypropionyl; I arylcarbamoyl such as phenylcarbamoyl; I arylthiocarbamoyl such as phenylthiocarbamoyl; I arylglyoxyloyl such as phenylglyoxyloyl and naphthylglyoxyloyl, arylsulfonyl such as phenylsulfonyl and naphthylsulfonyl, heterocycliccarbonyl, heterocycliccaleneyl such as thienylacetyl, thienylpropanoyl, thienylbutanoyl, thienylpentanoyl, thienylhexanoyl, thiazolylacetyl, thiadiazolylacetyl and tetrazolylacetyl, P1754 / 99MX heterocyclicketoyl such as heterocyclicpropenoyl, heterocyclicbutenoyl, hetericiclicpentenoyl and heterocyclichexenoyl; and heterocyclyglycyloxy such as thiazolylglyoxyloyl and thienylglyoxyloyl. The terms "heterocyclic", "heterocyclyl" and "heterocyclyl" as used herein on their property or as part of a term "heterocyclickenoyl", "heterocycloy" or "haloheterocyclic" refers to aromatic, pseudo-aromatic and non-aromatic rings, or ring systems containing one or more heteroatoms selected from N, S, 0 and P and which may be optionally substituted. Preferably, the rings or ring systems have from 3 to 20 carbon atoms. The rings or ring systems may be selected from those described above with respect to the definition of "aromatic compound (s)". The term "aryl" as used herein, on its property or as part of a group such as "haloaryl" and "aryloxycarbonyl" refers to aromatic and pseudoaromatic rings, or ring systems composed of carbon atoms, optionally together with one or more atoms. Preferably, the rings or ring systems have between 3 and 20 carbon atoms. Ring or ring systems may optionally be P1754 / 99MX are substituted and may be selected from those described above with respect to the definition of "aromatic compound (s)". The diboro derivative may be an ester or other stable derivative of diboric acid. Examples of suitable esters include those of the formula (RO) 2B-B (RO) 2 wherein R is optionally substituted alkyl or optionally substituted aryl or -B (OR) 2 represents a cyclic group of the formula - B R * wherein R 'is optionally substituted alkylene, arylene or other divalent group comprising linked aliphatic or aromatic moieties. The preferred diboro derivative includes bis (pinacolato) diboro (the pinacol ester of diboric acid), bis (ethanediolate) diboro, bis (n-propanediolate) diboro and bis (neopentanediolate) dibor.

Diboro derivatives will be more easily treatable to subsequent hydrolysis than others and may allow the use of milder reaction conditions. In addition, the judicious choice of the used diboro derivative can facilitate control over the normal reaction products. The diborium ester derivatives can be made following the P1754 / 99HX method by Brotherton et al. [R.J. Brotherton, A.L. McCloskey, L.L. Peterson and H. Steinberg, J. Amer. Che. Soc. 82, 6242 (196); R.J. Brotherton, A.L. McCloskey, J.L. Boone and H.M. Manasevit, J. AMER. Che. Soc. 82 6245 (1960)]. In this process, B (NMe2) 3, obtained by the reaction of BC13 with NHMe2, is converted to BrB (NMe2) 2 by the reaction with a stoichiometric amount of BBr3. The reduction in reflux of toluene with a sodium metal gives the diboro compound [B (NMe2) 2] 2 which, after purification by distillation, can be reacted with the alcohol (e.g., pinacol), in the presence of a stoichiometric amount of HCl to give the desired ester product. Bis (neopentanediolate) diboro is described by Nguyen et al [Nguyen, P., Lesley, G., Taylor, NJ, Marder, TB, Pickett, N / L /, Clegg, W., Elsegood, MRJ, and Norman, NC, Inorgani c Chem, 1994, 33, 4623-24]. Other methods for the preparation of diboro derivatives are known to those skilled in the art. The term "group VIII metal catalyst" as used herein, refers to a catalyst comprising a metal from group 8 of the periodic table described in Chemical and Engineering News, 63 (5), 27, 1985. Examples of these metals include Ni Pt and Pd. Preferably, the catalyst is a palladium catalyst as P1754 / 99MX describes later, although other analogous catalysts of group VIII metals can also be used. Examples of suitable Ni catalysts include black nickel, Raney nickel, carbon nickel and nickel agglomerates or a nickel complex. Examples of suitable Pt catalysts include black platinum, platinum on carbon and platinum agglomerates or a platinum complex. The metal catalyst of group VIII may additionally include other metals. The palladium catalyst may be a palladium complex. Examples of suitable palladium catalysts include but are not limited to, PdCl2, Pd (0Ac) 2, PdCl2 (dppf) CH2C12, Pd (PPh3) 4 and related catalysts which are complexes of phosphine ligands (such as (Ph2P ( CH2) pPPh2) where n is 2 to 4, P (o-tolyl) 3, P (i-Pr) 3 P (cyclohexyl) 3, P (o-MeOPh) 3, P (p-MeOPh) 3 / dppp , dppb, TDMPP, TTMPP, TMPP, TMSPP and related water-soluble phosphines), related ligands (such as triarylarsine, triaryl antimony, triaryl bismuth), phosphite ligands (such as P (OEt) 3, P (Op-tolyl) 3, P (Oo-tolyl) 3 and P (0-iPr) 3 and other suitable ligands including those containing P and / or N atoms to coordinate the palladium atoms (such as for example pyridine, substituted with alkyl and aryl) , 2, 2'-bipyridyl, 2, 2'-bipyridyl substituted with alkyl and secondary and tertiary amines P1754 / 99MX voluminous) and other simple palladium salts either in the presence or absence of ligands. The palladium catalyst includes palladium and palladium complexes supported or bound in solid supports, such as palladium in carbon, as well as palladium black, palladium agglomerates, palladium agglomerates containing other metals and palladium in porous glass as described in J . Li, A. W-H. Mau and C.R. Strauss, Chemical Communications, 1997, p. 1275). The same different palladium catalyst can be used to catalyze different steps in the process. The palladium catalyst can also be selected from those described in U.S. Patent No. 5,686,608. In certain reactions, there are advantages in using ligands with altered basicity and / or steric volume. The process can be carried out in any suitable solvent or solvent mixture. Examples of these solvents include lower alcohols, and their esters with lower aliphatic carboxylic acids, cyclic and lower secondary and tertiary amines, lower aliphatic carboxylic acid amides and lower aliphatic secondary amines, DMSO, aromatic hydrocarbons, nitromethane, acetonitrile, benzonitrile , ethers, polyethers, cyclic ethers, lower aromatic ethers and mixtures thereof, including mixtures with other solvents.

P1754 / 99MX Preferred solvents include methanol, ethanol, isopropanol, DMSO, DMF, dioxane, DME, diethyl ether, THF or mixture thereof with other solvents. The exclusion of water from solvents in general is not essential and in some cases the presence of water is preferred. The addition of the additional diborum derivative can be useful when the solvents are not anhydrous. The temperature at which each step of the process according to the invention is carried out will depend on a number of factors including the desired reaction rate, solubility and reactivity of the reagents in the selected solvent, boiling point of the solvent, etc. The temperature of the reaction will generally be in the range of -100 to 2502 C. In a preferred embodiment, the process is carried out at a temperature between 0 and 12 O2 C, more preferably between 0 and 802 C, and in a more preferred between 15 and 40s C. The term "suitable base" as used herein, refers to a basic compound which, when present in the reaction mixture, is capable of catalyzing, promoting or assisting the reaction between the reagents. The base may be suitable to catalyze an individual step or more than one step depending on the desired result of the reaction. For example, you can choose a base that catalyzes the P1754 / 99MX reaction between the olefinic compound and the diborum derivative, but which is not sufficiently strong under the conditions used in the reaction to further catalyze the reaction of the intermediate compound of alkene borate with the additional olefinic compound or other organic compound. In this case, water, or water and a strong base can be added to decompose excess diborum derivative and that can also catalyze the reaction of the middle compound of alkene borate with the organic compound. It is also preferred that a base that is soluble in the solvent to which it is added be chosen. Examples of bases that are suitable for catalyzing the reaction of the olefinic compound with the diboron derivative include alkyl carboxylate (eg potassium acetate), fluorides, hydroxides and carbonates of Li, Na, K, Rb, Cs, ammonium , alkylammonium, Mg, Ca, and Ba; phosphates and aryl phosphates of Li, Na, K, Rb and Cs; phosphate esters (for example C6H5OP (0) (ONa) 2) of Li, Na, K, Rb, Cs, ammonium and alkylammonium; phenoxides of Li, Na, K. Rb and Cs, alkoxides of Li, Na, K, Rb and Cs; and thallium hydroxide. Some of these bases can be used in conjunction with a base transfer reagent, such as for example tetraalkylammonium salts or the crown ethers. Suitable base examples to catalyze reaction of the olefinic compounds with P1754 / 99MX the diboro derivative without generally catalyzing further reaction of the intermediate compound of alkene borate include alkyl and aryl carboxylates, fluorides, Li, Na, K, Rb, Cs, ammonium and alkylammonium phosphates. Depending on the reaction temperature, stronger bases such as carbonates may be used. Examples of suitable bases for decomposing the excess diborium derivative and / or catalyzing the reaction of the intermediate compound of alkene borate are the organic compound which includes the stronger bases listed above which include cesium carbonate, potassium carbonate, phosphate of potassium and alkali metal hydroxides. As used herein, the term "alkene borate intermediate" refers to the product of the reaction catalyzed by a group VIII metal base of an olefinic compound containing a halogen or a halogen-type substituent at a position of Vinyl coupling and a diboro derivative, the product includes a carbon to boron bond in the coupling position. In another aspect of the invention, there is provided a process for preparing an intermediate compound of alkene borate comprising reacting a diboron derivative with a compound Olefinic P1754 / 99MX having a halogen or halogen-type substituent and a substituent containing active hydrogen in the presence of a Group VIII metal catalyst and a suitable base. In a further aspect of the invention, there is provided a process for preparing an intermediate compound of alkene borate, which comprises reacting a boron derivative with an olefinic compound containing a halogen or halogen-type substituent in a protic solvent in the presence of a metal catalyst of group VIII and a suitable base. A first step in the purification of the intermediate compound of alkene borate formed in this way, can be the decomposition of any excess diborium derivative by the use of water, water and a suitable base, or by the use of a mild oxidizing agent. . In a further aspect of the invention, a process for the preparation of an olefinic boric acid is provided, by hydrolyzing the alkene borate intermediate as hereinafter described using established procedures. The ease of hydrolysis is a function of the diboro ester used. Some intermediate compounds of alkene borate are more prone to hydrolysis than those derived from bis (pinacolato) diboro. This method only refers to P1754 / 99MX intermediate alkene borate compounds that are boric esters. Some of the intermediate compounds of alkene borate and olefinic boric acids are new and represent a further aspect of the present invention. Examples of these intermediate alkene borate compounds that can be prepared according to the present invention are listed in the table. 2, while some known intermediate compounds of alkene borate prepared according to the present invention are listed in Table 1.

P1754 / 99MX Table 1. New alkene borates prepared by the diboro methodology. 54 / 99MX Table 2. New alkene borates prepared by the diboro methodology. 54 / 99MX P1754 / 99MX COMPOSITE NAME 5. 2- (1,2-Dimethylprop-l-enyl) -4,4,5,5-tetramethyl-1,3, 2-dioxaborolane. 2- (1,2-Dimethylprop-l-enyl) -5,5-dimethyl-1,3, 2-dioxaborin. 5, 5-Dimethyl-2- (1,2, 2-trifeniIvinyl) -1,3, 2-dioxaborin. 8. 4,4,5, 5-Tetramethyl-2- (1,2,2-trifeniIvinyl) -1,3,2-dioxaborolane. Ethyl (Z) -2 (4,4,5, 5-tetramethyl-l, 3,2-dioxaborlane-2-yl) ethenyl ether.

P1754 / 99MX 10 4, 4 -Dimeti 1-2- (4,4,5, 5- tetramethyl-1,3,2-dioxaborlane-2-yl) cyclohex-2-en-l-one. 11. (E) -2 -Metí 1-3- (4,4,5, 5- tetramethyl- 1,3, 2-dioxaborlano-2-yl) prop-2-enenitrile. 12. (Z) -3- (4,4,5, 5-tetramethyl-l, 3,2-dioxaborlane-2-yl) prop-2-enoate of ethyl 13 2-Bicyclo [3.2.1] oct-2 -in-3yl-4, 4,5,5-tetramethyl-1,2, dioxaborolane. 14 Acid 1,2,2, -Triphenylvinylboronic acid.

The term "linking group" as used herein refers to any chain of atoms that links one aryl group to another. Examples of the linking group include polymer chains, optionally substituted alkylene group, and any other suitable divalent group. The process according to the present invention is applicable to the chemistry in the solid polymer support or resin bead in the same way that conventional chemistry is used in the combination chemistry and in the preparation of chemical libraries. In this manner, a suitable organic compound having a halogen or halogen-type substituent in a coupling position that chemically bonds to a polymer surface is P1754 / 99MX can react with an intermediate compound of alkene borate in the presence of a group VIII metal catalyst and a suitable base to form a coupled product bound to the surface of the polymer. Then reagents and by-products can be washed in excess from the surface, leaving only the reaction product on the surface. The coupled product can then be isolated by proper cleavage of the chemical bond from the surface of the polymer. The process is also possible using alternative strategy to react an halogen-containing olefinic compound or halogen-type substituent bonded to a polymeric surface with a diboron derivative in the presence of a group VIII metal catalyst and a suitable base to form a compound alkene intermediate chemically bound to the polymeric surface. This intermediate compound can then be reacted in an organic compound having a halogen or halogen-type substituent in a coupling position in the presence of a group VIII metal catalyst and a suitable base for preparing the coupled product chemically bonded to the polymer. Excess reagents and products can be removed by proper washing and the coupled product can be isolated by chemical cleavage of the polymer link. It is also possible to prepare polymers by P1754 / 99MX reaction of olefinic compounds having more than one halogen or halogen-type substituent in a vinyl coupling position. These olefinic compounds can be reacted with a diboro derivative in the presence of a metal catalyst of group VIII of a suitable base to form an intermediate compound of alkene borate having more than one boron functionality. These intermediates can be reacted with organic compounds having more than one halogen or halogen-type substituent to form a polymer. If the olefinic compound has three or more halogen or halogen-type substituents that react with the diboron derivative then it is possible to prepare the dendritic molecules with the process of the present invention. The olefinic compound and the organic compound may be separate molecules, or they may be linked together such that the intermediate alkene borate compound formed after the reaction with the diboro derivative is capable of reacting in a coupling position located elsewhere in the molecule, to provide an intramolecular reaction, such as a ring closure reaction. Similarly, the process according to the invention allows the intramolecular bond to be present between double bonds located in different parts of a molecule, with the proviso P1754 / 99MX that each double bond has a vinyl halogen or halogen-type substituent. A process according to the invention is also useful for the preparation of reactive intermediates which, after coupling, take part in additional or arrangement reactions. An example of this intermediate compound is one formed by the reaction of an ether containing vinyl halide with one of R1, R2 or R3 (formula I) which is -OR with a diboro derivative. The subsequent coupling of the resulting intermediate alkene borate compound with an organic compound gives an acetone in the hydrolysis of the enol ether. The process according to the present invention provides an alternative method for coupling olefinic portions to organic compounds. The process allows the use of mild conditions and avoids the use of expensive, difficult to handle and / or toxic reagents and solvents. In this regard, boron and boron compounds are generally non-toxic. The reactions can also be carried out in relatively inexpensive solvents such as methanol and ethanol and in view of the measured control over the reaction steps, it is contemplated that it will be possible to carry out the reactions on an industrial scale. In view of the mild reaction conditions, it is also possible to perform the coupling without the need to protect most substituents P1754 / 99MX reagents. The following examples are provided to illustrate the preferred embodiments of the invention. However, it should be understood that the following description will not replace the generality of the invention described previously.

EXAMPLES Example 1. (a) They were stirred in ethanol (5 ml) at 80 ° C. for 17 hours Bis (pinacolato) diboro (0.283 g, 1.11 mmol), bromotriphenylethylene (0.337 g, 1.0 mmol), PdCl2 (dppf) .CH2C12 (26.4 mg), and (C6H5) P (O) (ONa) 2H20 (0.712 g, 3.01 mmol). Gas chromatography of the reaction solution in ether, after washing with water, had a main peak (more than 70% of the total integral) identified as the desired alkene borate by the retention time-GC / spectroscopy. In addition the other peaks in 1 CG were identified as the starting materials and P1754 / 99MX triphenylethylene. The reaction conditions (time / temperature) were not optimized. (b) The product can also be processed under the above reaction conditions with the phosphate base being replaced by CsF or K2C03. With potassium acetate or Cs2C03 as a base, the reaction (80aC in alcohol) gives large amounts of triphenylethylene. DMSO will be produced as the reaction solvent and at 802C / 16.5 h gives the desired product together with triphenylethylene. (c) The above reaction can be carried out successfully at lower temperatures with a strong base such as potassium carbonate. For example, the reaction of Bis (pinacolato) diboro (0.142 g, 0.56 mmol), bromotriphenylethylene (0.168 g, 0.5 mmol), 12.8 mg PdCl2 (dppf) .CH2C12 and K2C03 (0.211 g, 1.53 mmol) in ethanol ( 5 ml) at 302C gave, after 18 hours of reaction time, the triphenylenylboronic acid ester together with a little triphenylethylene. The only different peak was due to a trace (less than 2% of the integrated area) of unreacted bis (pinacolato) diboro. Example 2 P1754 / 99MX Diboro (0.281 g, 1.11 mmol), K2C03 (0.409 g, 2.96 mmol) and 50 mg of palladium (10%) in carbon were placed in a reaction tube under nitrogen. After the addition of 2-bromo-3-methyl-2-butene (0.152 g, 1.02 mmol) and dry ethanol (5 ml), the reaction was stirred 302C for 19.5 h. The GC of the reaction solution after washing an aliquot dissolved in ether demonstrated the presence of the desired alkene borate.

Use 3 Diboro (0.281 g, 1.11 mmol), K2CO3 (0.404 g, 2.93 mmol) and 27 mg of bis (benzonitrile) dichloropalladium were placed in a reaction tube under nitrogen. After the addition of 2-bromo-3-methyl-2-butene (0.146 g, 0.98 mmol) and dry ethanol (5 ml), the reaction was stirred at 30 ° C for 19.5 h. The GC of the reaction solution, after washing an aliquot dissolved with water, demonstrated the presence of the desired alkene borate. This was confirmed by GC / MS. The formation of this ester was also catalyzed in ethanol by NiCl 2 (dppf). CH2C12, and nickel acetate tetrahydrate at 302C using K2C03 as the base. It was also found that cis-Dichlorobis (diphenylphosphine) platinum and tetrakis (triphenyl-phosphine) platinum catalyze the P1754 / 99HX formation of pinacol alkenyl borate from 2-bromo-3-methyl-2-butene and bis (pinacolato) diboro at 302C in methanol in the presence of K2CO3. The dichloropalladium complex with 1,4-bis (diphenylphosphino) butane in ethanol at 30 ° C, catalyzed the formation of the pinacol ester of triphenylethylboronic acid from bromotriphenylethylene and bis (pinacolato) diboro in the presence of K 2 CO 3 as a base. Example 4 Nitrogen bis (pinacolato) diboro (0.282 g, 1.11 mmol), 25 mg PdCl2 (dppf) were placed in a reaction tube. CH2C12 and potassium acetate (0.300 g, 3 mmol). After the addition of β-bromostyrene (0.189 g, 1.03 mmol) and dry ethanol (5 ml), the reaction solution was stirred at 30 ° C. for 16 h. The GC of the reaction solution, after washing in an aliquot dissolved in ether with water, had a peak identified by GC / MS as the pinacol ester product of styrylboronic acid.

P1754 / 99MX In a Schlenk tube under nitrogen a mixture of bis (pinacolato) diboro (0.253 mg, 0.996 mmol), 2-bromo-3-methyl-2-butene (136 mg, 0.913 mmol) was sealed and stirred at 30 ° C. for 18 h, PdCl2 (dppf) .CH2C12 (22 mg, 0.027 mmol) and potassium carbonate (380 mg, 2.75 mmol) in dry isopropyl alcohol (6 ml). Gaseous chromatographic analysis of the reaction mixture showed a major peak identified as the desired alkene borate by GC / MS as well as some unreacted diboro compound, and the alkene halide starting material.

Example 6 In a Schlenk tube under nitrogen, a mixture of bis (pinacolato) diborium was sealed and stirred at 30 ° C.

P1754 / 99MX (327 mg, 1.29 mmol), 2-bromo-3-methyl-2-butene (171 mg, 1.15 mmol), PdCl2 (dppf). CH2C12 (61 mg, 0.075 mmol) and potassium carbonate (475 g, 3.44 mmol) in dry dioxane (5.5 mL). After 3 days, the GC analysis of the reaction mixture showed three major peaks, identified as the desired alkene borate, and the unreacted starting materials by GC / MS. Example 7 In a Schlenk tube under nitrogen, a mixture of bis (neopentanediiolate) diboron (247 mg, 1.09 mmol), 2-bromo-3-methyl-2-butene (148 mg, 0.993 mmol), PdCl 2 (34 mg) was sealed and stirred at 30 ° C. dppf) .CH2C12 (26 mg, 0.032 mmol) and potassium carbonate (426 mg, 3.08 mmol) in dry isopropyl alcohol (6 ml). After 16.5 h of GC analysis of the reaction mixture, it showed two major peaks, identified as the desired alkene borate and the unreacted alkene halide by GC / MS. Only traces of the diboro compound and the dimer were detected.

P1754 / 99MX Example 8 In a Schlenk tube under nitrogen, a mixture of bis (pinacolato) diboro (412 mg, 1.62 mmol), 2-bromo-2-methylpropene (197 mg, 1.46 mmol), PdCl2 (dppf) was sealed and stirred at 30 ° C. CH2C12 (40 g, 0.049 mmol) and potassium acetate (440 mg, 4.48 mmol) in dry DMSO (8 mL). After 17 h of GC analysis of the reaction mixture showed two main peaks identified as the desired alkene borate and the unreacted diboro compound by GC / MS.

Example 9 P1754 / 99MX In a Schlenk tube under nitrogen, a mixture of bis (neopentanediolate) diboro (185 g, 0.819 mmol), bromotriphenylethylene (253 mg, 0.755 mmol), PdCl2 (dppf) .CH2C12 (21 mg, 0.026 mmol) and acetate of potassium (237 mg, 2.41 mmol) in dry DMSO (5 ml) was sealed and stirred at 802C. After 17 h the GC analysis of the reaction mixture showed a major peak, identified as the alkene borate by GC / MS.

Example 10 In a Schlenk tube under nitrogen, a mixture of bis (neopentanediolate) diborium (189 mg, 0.837 mmol), bromotriphenylethylene (255 mg, 0.761 mmol), PdCl2 (dppf) .CH2C12 (24 mg, 0.029 mmol) was sealed and stirred and stirred at 80 ° C. ) and potassium acetate (251 mg, 2.56 mmol) in dry ethanol (5.5 ml). After 18 h, the GC analysis of the reaction mixture showed three major peaks, identified as the desired alkene borate, alkene halide and dehalogenated alkene by GC / MS.

P1754 / 99MX Example 11 In a Schlenk tube under nitrogen, a mixture of bis (neopentanediolate) diboron (187 mg, 0.828 mmol), bro-trifarylethylene (251 mg, 0.749 mmol), PdCl2 (dppf), CH2C12 (20 mg, 0.024 mmol) and potassium carbonate ( 325 mg, 2.35 mmol) in dry ethanol (5.5 ml) was sealed and stirred at 80 ° C. After 18 h, the GC analysis of the reaction mixture showed two main peaks, identified as the desired alkene borate and the alkene deoalogenated by GC / MS.

Example 12 P1754 / 99MX In a Schlenk tube under nitrogen, a mixture of bis (pinacolato) diboro (255 mg, 1.00 mmol), bromotriphenylethylene (298 mg, 0.889 mmol), PdCl2 (dppf), CH2C12 (26 mg) was sealed and stirred at 30 ° C. 0.032 mmol) and potassium carbonate (376 mg, 2.72 mmol) in dry isopropyl alcohol (5 ml). After 18 h, GC analysis of the reaction mixture showed a major peak, identified as the desired alkene borate by GC / MS.

Example 13 In a Schlenk tube under nitrogen, a mixture of bis (neopentanediolate) diboron (277 mg, 1.23 mmol), β-bromostyrene (202 mg, 1.10 mmol), PdCl 2 (dppf), CH 2 C 12 (29 mg; 0.036 mmol) and potassium acetate (329 mg, 3.35 mmol) in dry DMSO (5 mL). After 18 h, the GC and GC / MS analyzes detected alkene borate, dimer and the diborium compound.

P1754 / 99MX Example 14 In a Schlenk tube under nitrogen, a mixture of bis (pinacolato) diboro (284 mg, 1.12 mmol), cis-l-bromo-2-ethoxyethylene (152 mg, 1.01 rrvmol), PdCl2 (dppf) .CH2C12 (53 mg; 0.065 mmol) and potassium carbonate (414 mg, 3.02 mmol) in dry methanol (5 mL) was sealed and stirred at 302C. After 16 h, GC and GC / MS analyzes detected alkene halide, composed of diborus, alkene borate and dimer.

Example 15 In a Schlenk tube under nitrogen, a mixture of bis (pinacolato) diboro (251 mg, 0.988 mmol), P1754 / 99MX 2-bromoalyltrimethylsilane, (172 mg, 0.890 mmol), PdCl2 (dppf) .CH2C12 (45 mg, 0.055 mmol) and potassium carbonate (383 mg, 2.77 mmol) in dry methanol (5.5 mL) was sealed and stirred at 302C for 16.5 h. The GC of the reaction solutions showed a major peak identified as the alkene borate by GC / MS.

In a Schlenk tube under nitrogen, a mixture of bis (pinacolato) diboro (249 mg, 0.981 mmol), 4,4-dimethyl-2-iodo-2-cyclohexanone (220 mg, 0.880) was sealed and stirred at 30 ° C. for 25.5 h. mmol), PdCl2 (dppf) .CH2C12 (44 mg, 0.054 mmol) and potassium carbonate (386 mg, 2.79 mmol) in dry methanol (5 ml). The GC of the reaction solution showed three main peaks identified as alkene borate alkene halide and starting materials of the diborium compound by GC / MS.

P1754 / 99MX Example 17 Nitrogen bis (pinacolato) diboro (0.280 g, 1.10 mmol), 26 mg PdCl2 (dppf) was placed in a reaction tube. CH2C12 and 0.419 g (3 mmol) K2C03. After the addition of 0.140 g (0.98 mmol) of 3-chlorobicyclo [3.2.1] oct-2-ene and 5 ml of dry ethanol, the reaction solution was stirred at 302C for 24. The GC of the reaction solution , after washing in the aliquot dissolved in ether with water, had a peak identified by GC / MS (m / z = 235; M ++ l) as the desired alkene borate. The product was also formed under the same reaction conditions using CsF (0.61 g, 4 mmol) as the base in place of K2C03.

P1754 / 99HX Diboro bis (pinacolato) (0.284 g, 1.12 mmol), 24 mg PdCl2 (dppf) were placed in a reaction tube under nitrogen. CH2C12 and 0.413 g (3 mmol) K2C03. After the addition of 0.232 g (1.03 mmol) of ethyl cis-iodoacrylate 5 ml of dry ethanol the reaction solution was stirred at 252C. The GC of the reaction solution after washing an aliquot dissolved in ether with water had a peak identified by GC / MS [m / z = 227 (M ++ l), m / z = 255 (M + + 29) , m / z = 267 (M + + 41)] as the desired alkene borate. The product is also formed under the same reaction conditions using CsF (0.61 g, 4 mmol) as the base instead of K2C03.

Example 19 Nitrogen bis (pinacolato) diboro (0.284 g, 1.12 mmol) was placed in a reaction tube, 50 mg PdCl2 (dppf) .CH2C12 and 0.61 g (4 mmol) CsF. After the addition of 0.143 g (0.98 mmol) of 2-bromo-2-methylacrylonitrile and 4 ml of dry dioxane and 1 ml of P1754 / 99MX pyridine, the reaction solution was stirred at 502C for 19 h. The GC / MS of the reaction solution, after washing in an aliquot dissolved in ether with water, indicated that the alkene borate had formed [m / z = 193 (M ++ l), m / z = 222 (M ++ 29), m / z = 234 (M + -41)].

Example 20 Nitrogen bis (pinacolato) diboro (0.283 g, 1.11 mmol), 24.1 mg PdCl2 (dppf) were placed in a reaction tube. CH2C12 and 0.416 g (3 mmol) K2C03. After the addition of 0.152 g (1.02 mmol) of 2-bromo-3-methyl-2-butene and 5 ml of dry DMF, the reaction solution was stirred at 30 ° C. The GC of the reaction solution, after washing in an aliquot dissolved in ether with water, had a main peak (more than 85% in the integrated area of the ge peaks) identified as the product of the boric acid ester by GC / MS. Something (less than 10% of the integrated peak area) the pinacol ester of diboric acid remained unreacted. Dimer formation was minimal (less than 2% in total peak areas).

P1754 / 99MX Example 21 Nitrogen bis (pinacol) diboro (0.283 g, 1.11 mmol), 25 mg PdCl2 (dppf) .CH2C12 and 0.250 g (3 mmol) NaHC03 were placed in a reaction tube under nitrogen. After the addition of 0.146 g (0.98 mmol) of 2-bromo-3-methyl-2-butene and 5 ml of dry ethanol, the reaction solution was stirred at 30 ° C. The GC of the reaction solution, after washing an aliquot dissolved in ether with water, indicated that the product of the boric acid ester had formed and this was confirmed by GC / MS. No dimer was observed.

Example 22 A methanolic solution of 5,5-dimethyl-2- (1,2, 2-trifeni Ivinyl) -1,3,2-dioxaborin was analyzed.

Pure P1754 / 99MX by GC using HPLC (Waters 600E), using a Zorbax column (ODS) under the following conditions:? = 230 nm, 2 ml / min, 80% CH3CN: 20% H20. Two peaks were detected, at 1.9 min. (due to partial hydrolysis) and 7.9 min. (due to alkene borate). The area ratio of the start / product material = 5.2.

Some water was added to this sample and the solution was allowed to stand at room temperature. After 20 minutes, the HPLC analysis showed an individual peak at 1.9 minutes. Analysis of the sample hydrolyzed by GC and GC / MS indicated [M-B (0H) 2] +. Triphenylethylene HPLC under the same conditions produced an individual peak at 8.6 minutes.

The above results indicate rapid hydrolysis of 5,5-dimethyl-2- (1,2,2-triphenylvinyl) -1,3,2-dioxaborinone to 1,2,2-triphenylvinylboronic acid on exposure to water.

Example 23 2,3,4, 5-tetramethyl-2,4-hexadiene This example describes the formation of an alkenylboronic acid ester using a strong base and the subsequent coupling of boric acid ester with more alkenyl bromide by increasing the P1754 / 99MX reaction temperature to produce the symmetrical diene. This reaction proceeds via the intermediate compound of alkene borate. This intermediate compound is reacted with: 2-bromo-3-methyl-2-butene in a kettle to give Bis (pinacolato) diboro (0.282 g, 1.11 mmol), 26.4 mg PdCl2 (dppf) were placed. CH2C1 and K2CO3 (0.0424 g, 3.07 mmol), in a reaction tube under nitrogen. After the addition of 2-bromo-3-methyl-2-butene (0.286 g, 1.92 mmol) and 5 ml of dry ethanol, the reaction solution was stirred at 302C for 18 h. The GC of the reaction solution, after washing an aliquot dissolved in ether with water, showed two main peaks identified as the desired alkene borate and the 2-bromo-3-methyl-2-butene in excess by GC / MS . A bit of bis (pinacolato) diboro (less than 2% of the integrated peak area) remained unreacted. No dimer was observed. The reaction temperature was increased to 60 aC for 23 h and the GC indicated that the alkenylboronic acid ester had reacted completely and 2, 3, 4, 5-tetramethyl-2,4-hexadiene was the only major product observed in GC . This is P1754 / 99MX confirmed by GC / MS. The formation of the pinacol ester of alkenylboronic acid from 2-bromo-3-methyl-2-butene using (PdCl2 (dppf), CH2C1 as a catalyst and K2C03 as the base was carried out at lower temperatures, in DMSO this reaction is more slower than in ethanol and this is also the case when potassium acetate is used instead of K2CO3 as the base.High yields of alkeneboronate are formed with K3PO4 as a base and a reaction temperature of 202 C. Alkeneboronate is also formed in dioxane as solvent with little dimer formation when CsF is used as a base and a reaction temperature of 602C.

Example 24 A synthesis in kettle in this compound proceeds by the initial synthesis of the ester of alkenylboric acid at 30SC in the presence of K2C03 and bis (pinacolato) diboro in excess followed by the destruction of the diborium species in excess by P1754 / 99MX basic hydrolysis and then the addition of 4-bromo-l, 2- (methylenedioxy) benzene and increasing the reaction temperature to 602C. They were placed in a reaction tube under nitrogen bis (pinacolato) (0.384 g, 1.51 mmol), 24.7 mg PdCl2 (dppf) .CH2C12 and 0.564 g (4.1 mmol) K2C03. After the addition of 0.150 g (1.0 mmol) of 2-bromo-3-methyl-2-butene and 5 ml of dry ethanol, the reaction solution was stirred at 302C for 21 h. After the addition of 0.5 ml of water, the reaction was heated to 302C for an additional 3 h. The GC of the reaction solution, after washing in an aliquot dissolved in ether with water, indicated that the diborium compound was almost completely hydrolyzed by the aqueous base. Then 4-bromo-l, 2- (methylenedioxy) benzene (0.195 g, 0.97 mmol) was added and the reaction solution was heated at 60 ° C for 6 h. All alkeneborate had reacted and the main product, identified by GC / MS, were the alkenylaryl species coupled. Some biaryl compound was observed in this reaction, but this can be further reduced by extending the basic hydrolysis time to ensure complete removal of the diboric acid ester.

P1754 / 99MX Example 25 Nitrogen bis (pinacolato) (0.281 g, 1.10 mol), 21.1 mg of palatal acetate and K2CO3 (0.417 g, 3 mmol) were placed in a reaction tube under nitrogen. After the addition of 2-bromo-3-methyl-2-butene (0.149 g, 1.0 mmol ") and dry Stanol (5 ml), the reaction solution was stirred at 30 aC for 19.5 h. The reaction had only one major peak (80% of the integrated area) identified by the reaction time as the desired alkene borate.No 2-bromo-3-methyl-2-b, utene or bis (pinacolato) diboro was observed in the reaction solution The pinacol ester of the alkenylboronic acid formed was coupled with β-bromostyrene in the presence of palladium acetate by heating the reaction solution at 60 ° C. without the addition of the base plus The coupled product was identified by GC / MS ..

P1754 / 99MX Example 26 The pinacol ester of diboric acid (320 mg, 1.2 mmol), 2-bromo-3-methyl-2-butene (149 mg, 1 mmol), PdCl2 (dppf) .CH2C1 (40 mg) and KOAc (300 mg, 3 mmol) were stirred in methanol (6 ml) at 60 ° C until all the bromide had reacted (GC analysis of a small sample, new peak at 4.9 min, diboric ester at 8.1 min). The excess diboro compound was decomposed with H20 (0.5 ml) and Cs2C? 3 (960 mg, 3 mmol) for stirring at room temperature for about 3 h. P-Iodotoluene (218 mg, 1 mmol) was added and the reaction mixture was heated to 60 ° C until all the alkenyl borate had reacted (new peak at 5.4 min in the GC trace).

Example 27 In a Schlenk tube it was sealed and stirred at 302C P1754 / 99MX for 18 h a mixture of bis (pinacolato) dibora (271 mg, 1.07 mmol), 3-bromo-3-butene-1-ol (146 mg, 0.967 mmol), PdCl2 (dppf) .CH2C1 (26 mg 0.032 mmol) and potassium carbonate (415 mg, 3.00 mmol) in dry MeOH (5 ml). A sample of the reaction mixture was brought into dichloromethane, washed with dilute HCl (aqueous) and dried (MgSO). Analysis of the reaction mixture by GC / MS showed the presence of the dimer (m / z = 143; M ++ l).

Example 28 In a Schlenk tube under nitrogen, a mixture of bis (pinacolato) diboro (250 mg, 0.984 mmol), 3-bromo-2-methylacrylonitrile (131 mg, 0.897 mmol), PdCl2 was sealed and stirred at 30 ° C for 22 h. (dppf) .CH2C1 (46 mg, 0.056 mmol) and cesium fluoride (408 mg, 2.69 mmol) in dry dioxane (5.5 ml). The GC of the reaction solution showed two main peaks identified as the alkene dimer and the diboro compound selected by GC / MS. A small amount of borate was also detected P1754 / 99MX alkene. Other compounds can be prepared in a similar manner. Throughout this specification and the claims that follow, unless the context requires otherwise, the word "comprises", or variations such as "comprise" or "comprising", shall be understood to imply the inclusion of a designated whole number or group of integers, but not the exclusion of any other whole number or group of integers. Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications different from those specifically described. It is to be understood that the invention includes all these variations and modifications. The invention also includes all steps, features, compositions and compounds required to or indicated in this specification, individually or collectively, and all combinations of any two or more of the steps or features.

P1754 / 99MX

Claims (57)

1. NOVELTY OF THE INVENTION Having described the present invention, it is considered as a novelty and, therefore, what is claimed as property is contained in the following CLAIMS 1. A process for covalently coupling organic compounds comprising reacting an olefinic compound having a halogen or halogen-type substituent in a vinyl coupling position with a diboro derivative in the presence of a Group VIII metal catalyst and a suitable base.
2. 2. A process according to claim 1, wherein the diboro derivative is reacted with the olefinic compound to form a covalently coupled, symmetric product, the reaction proceeds via an intermediate alkene borate intermediate, this intermediate reacts with the compound remaining olefinic to form the coupled product, the covalent coupling comprises a covalent bond between the vinyl coupling positions of the two molecules of the olefinic compound.
3. 3. A process according to claim 2, wherein the suitable base catalyzes both the formation of the intermediate compound of alkene borate and the subsequent reaction with the remaining olefinic compound. P1754 / 99MX
4. 4. A process according to claim 2, wherein the suitable base only catalyzes the formation of the intermediate compound of the alkene borate under the reaction conditions, a strong base is added and / or the temperature is increased after the formation of the intermediate compound to catalyze the reaction of the intermediate compound with the remaining olefinic compound.
5. 5. A process for covalently coupling organic compounds according to claim 1, comprising: (i) reacting an olefinic compound having a halogen or halogen-type substituent, in a vinyl coupling position, with a diboron derivative in the presence of a metal catalyst of group VIII and a suitable base to form an intermediate compound of alkene borate, and (ii) reacting the intermediate compound of alkene borate with an organic compound having a halogen or halogen-type substituent in a composition of coupling in the presence of a group VIII metal catalyst and a suitable base, whereby the olefinic compound is coupled to the organic compound via the direct link between the respective coupling positions.
6. 6. A process according to claim 5, wherein the organic compound is different from the P1754 / 99MX olefinic compound.
7. 7. A process according to claim 5, wherein the water or water and a suitable base are added after the formation of the intermediate compound of alkene borate to decompose the unreacted diboron derivative.
8. 8. A process according to claim 5 or claim 7, carried out in an individual kettle.
9. 9. A process according to claim 5, wherein the intermediate compound of alkene borate is isolated before the reaction with the organic compound.
10. 10. A process according to any of claims 5 to 8 wherein, the organic compound is an aromatic or pseudoaromatic ring compound having a halogen or halogen-type substituent.
11. 11. A process according to any of claims 5 to 8, wherein the organic compound is an olefinic compound with a halogen or halogen-type substituent in a vinyl coupling position.
12. 12. A process according to any of claims 5 to 8, wherein the organic compound is an aliphatic compound having a halogen or halogen-type substituent.
13. 13. A process according to any of claims 5 to 8, wherein the compound Organic P1754 / 99MX is an allylic compound that has a halogen or halogen-type substituent.
14. 14. A process according to any of claims 5 to 8, wherein the organic compound is an acetylenic compound having a halogen or halogen-type substituent.
15. 15. A process according to claim 2 or claim 5, wherein the organic compound has more than one halogen or halogen-type substituent at the vinyl coupling positions.
16. 16. A process according to claim 5, wherein the olefinic compound has a substituent that is reactive with the organometallic compounds.
17. 17. A process according to claim 5, wherein the olefinic compound has a substituent containing active hydrogen.
18. 18. A process according to claim 5, wherein at least one of the olefinic compound and the organic compound has more than one halogen or halogen-type substituent.
19. 19. A process according to any of claims 1 to 8, wherein the Group VIII metal catalyst comprises palladium, nickel or platinum.
20. 20. A process according to claim 19, wherein the Group VIII metal catalyst is a palladium catalyst.
21. 21. A process according to claim 20, P1754 / 99MX wherein the palladium catalyst is a palladium complex.
22. 22. A process according to claim 19, wherein the catalyst is a nickel complex.
23. 23. A process according to claim 21, wherein the palladium complex is selected from PdCl2, Pd (OAc) 2, PdCl2 (dppf) CH2C12. Pd (PPh3) 4, or one containing trianisylphosphine, tritolylphosphine, Ph2P (CH2) nPPh2 where n is 2, 3 or 4, tricyclohexylphosphine or benzonitrile.
24. 24. A process according to claim 21 or claim 23, wherein the palladium complex is attached to a solid support.
25. 25. A process according to claim 20, wherein the catalyst is selected from a group consisting of palladium black, palladium on carbon, palladium agglomerates and palladium on porous glass.
26. 26. A process according to claim 22, wherein the catalyst is selected from a group consisting of nickel black, Raney nickel, nickel in carbon and nickel agglomerates or a nickel complex attached to a solid support.
27. 27. A process according to claim 19, wherein the Group VIII metal catalyst is a platinum catalyst.
28. 28. A process according to claim 27, wherein the platinum catalyst is selected from P1754 / 99MX from platinum black, platinum in carbon and platinum agglomerates or a platinum complex or a platinum complex bound to a solid support.
29. 29. A process according to claim 1 or claim 5, wherein the olefinic compound is a compound of the formula I. R * / «C - R3 X wherein R1, R2 and R3 are each independently selected from alkyl, alkenyl, alkynyl, aryl, heteroaryl, acyl, arylalkyl and heteroarylalkyl (each of which may be optionally substituted); cyano, isocyano, formyl, carboxyl, nitro, halo, alkoxy, alkenoxy, aryloxy, benzyloxy, haloalkoxy, haloalkenyloxy, haloaryloxy, nitroalkyl, nitroalkenyl, nitroalkynyl, arylamino, diarylamino, dibenzylamino, alkenylacyl, alkynylacyl, arylacyl, acylamino, diacylamino, acyloxy, alkylsulfonyloxy, arylsulfenyloxy, heterocycloxy, arylsulfenyl, carboalkoxy, carbonyloxy, alkyloxy, benzylthio, acylthio, sulfonamide, sulfanyl, sulfo, carboxy, carbamoyl, carboximidyl, sulfinyl, sulfinimidyl, sulfinohydroximyl, sulfonimidyl, sulfonitridyl, sulfonohydroximyl, sulfamyl, groups containing P1754 / 99MX phosphorus, guanidinyl, duanidyl, ureido and ureylene, and X is a halogen or halogen-type substituent.
30. 30. A process according to any of claims 1 to 29, wherein the diboro derivative is an ester or other stable derivative of diboric acid.
31. 31. A process according to claim 30, wherein the diboro derivative is a compound of the formula (RO) 2B-B (RO) 2 where R is optionally substituted alkyl or aryl or -B (0R) 2 represents a cyclic group of the formula where R 'is optionally substituted alkenyl, arylene or other equivalent group comprising linked aromatic and aliphatic portions.
32. 32. A process according to claim 31, wherein the diboro derivative is selected from the group consisting of bis (pinacolato) diboro, bis (ethanediolate) diboro, bis (n-propanediolate) diboro and bis (neopentyldiolate) diboro. P1754 / 99MX
33. 33. A process according to any of claims 1 to 32, carried out in the presence of a solvent.
34. 34. A process according to claim 33, wherein the solvent is a protic solvent.
35. 35. A process according to claim 34, wherein the protic solvent is water or an alcohol.
36. 36. A process according to claim 34, wherein the solvent is water, methanol, ethanol, isopropanol or a mixture thereof.
37. 37. A process according to claim 33, wherein the solvent is DMSO, DMF, dioxane, DME, diethyl ether, THF or a mixture thereof.
38. 38. A process according to any of claims 1 to 36, carried out at a temperature between 02C and 1202C.
39. 39. A process according to claim 38, wherein the temperature is in the range of 15 to 40 aC.
40. 40. A process according to claim 5, wherein the suitable base of step (i) is capable of catalyzing the reaction of the olefinic compound with a diboron derivative, but is not sufficiently strong under the conditions used in the reaction to catalyze the reaction of the intermediate compound of alkene borate with the organic compound.
41. 41. A process according to claim 40, P1754 / 99MX wherein the suitable base is selected from a group consisting of aryl carboxylates and alkyl, carbonates, fluorides and phosphates of Li, Na, K, Rb, Cs, ammonium and alkylammonium.
42. 42. A process according to claim 1 or claim 5, wherein the suitable base is selected from a group consisting of aryl carboxylates and alkyl, fluorides, hydroxides and carbonates of Li, Na, K, Rb, Cs, ammonium, alkylammonium, Mg, Ca and Ba; phosphates, and aryl phosphates of Li, Na, K, Rb and Cs; Phosphate esters of Li, Na, K, Rb, and Cs; phenoxides of Li, Na, K, Rb, and Cs; alkoxides of Li, Na, K, Rb, and Cs; and thallium hydroxides.
43. 43. A process according to claim 5, wherein the suitable base of step (ii) is selected from cesium carbonate, potassium carbonate, potassium phosphate and alkali metal hydroxides.
44. 44. A process according to claim 5, wherein one of the olefinic compound and the organic compound is a polymer.
45. 45. A functionalized polymeric solid when prepared according to the process of claim 44.
46. 46. A process according to claim 5, wherein either the olefinic compound or the organic compound is chemically bonded to a solid polymer support. P1754 / 99MX
47. 47. A process for preparing intermediate compounds of alkene borate comprising reacting the olefinic compound having a halogen or halogen-type substituent and a substituent containing active hydrogen with a diboron derivative in the presence of a metal catalyst. in a Group VIII and an adequate base.
48. 48. A process for preparing intermediate compounds of alkene borate comprising selecting an olefin compound having a halogen-type halogen substituent with a diboro derivative in a protic solvent, DMSO, DMF, dioxane, DME, diethyl ether, THF or a mixture of them in the presence of a Group VIII metal catalyst of a suitable base.
49. 49. A process according to claim 47 or claim 48, wherein water, water and a suitable base, or a mild oxidizing agent are added to decompose the unreacted diboron derivative.
50. 50. An intermediate compound of alkene borate prepared according to the process of any of claims 47 to 49.
51. 51. A process for preparing an alkene-boronic acid by hydrolyzing an intermediate compound of alkene borate of claim 50.
52. 52. A polymer prepared according to the process of claim 1, wherein the compound Olefin P1754 / 99MX has more than one halogen or halogen-type substituent.
53. 53. A dendrimer prepared according to the process of claim 1, wherein the olefinic compound has more than two halogens or halogen-type substituents.
54. 54. A process according to claim 5, wherein the olefinic compound and the organic compound bond together such that the intermediate compound of alkene borate formed after the reaction of the olefinic compound with the diboro derivative reacts with an organic compound to provide an intramolecular ring closure.
55. 55. New alkene borates selected from a group consisting of: 2- (1,2-dimethylprop-1-enyl) -4,4,5,5-tetramethyl-1,2,2-dioxaborlane, 2- (1,2-dimethylprop-l-enyl) -5,5-dimethyl-1-1, 3,2-dioxaborin, 5,5-dimethyl-2- (1,2, 2-triphenylvinyl) -1,3, 2-dioxaborin, 4,4,5, 5-tetramethyl-2- (1,2, 2-trifeniIvinyl) -1,3,2-dioxaborlane, ethyl (Z) -2 (4,4,5,5-tetramethyl) -1, 3, 2-dioxaborlane-2-yl) ethenyl ether, 4, 4-dimeti1-2- (4,4,5,5, tetramethyl-1, 3,2-dioxaborlane-2-yl) cyclohex -2-en-l-one, (E) -2 -methyl- 3- (4,4,5, 5- tetramethyl-1, 3,2- P1754 / 99MX dioxaborlane-2-yl) prop-2-enonitrile, ethyl (Z) -3- (4,4,5, 5- tetramethyl-1,3, 2-dioxaborlane-2-yl) prop-2-enoate , 2-bicyclo [3.2.1] oct-2-en-3-yl-4, 4,5, 5-tetramethyl-1,3, 2-dioxaborolane, and 1,2, 2-triphenylvinylboronic acid.
56. 56. A process for covalently coupling organic compounds, comprising: reacting an olefinic compound having a halogen or a halogen-type substituent in a vinyl coupling position with diboron derivative in the presence of a Group VIII metal catalyst and a suitable base to form an intermediate compound of alkene borate; add a mild oxidizing agent to decompose excess diborum derivative; and reacting the alkene intermediate in an organic compound having a halogen or halogen-type substituent in a coupling position in the presence of a Group VIII metal catalyst and a suitable base, whereby the olefinic compound is coupled to the organic compound via direct bond between the respective coupling positions.
57. 57. A process according to claim 56, wherein the mild oxidizing agent is selected from N-chlorosuccinimide, dioxygen gas, chloramine-T, chloramine-B, 1-chlorotriazole, 1,3- P1754 / 99MX dichloro-5, 5-dimethylhydantoin, trichloroisocyanuric acid and potassium salt of dichloroisocyanuric acid. P1754 / 99MX