FR2638162A1 - Optically active chiral orthoborates and peroxyboranes and their use - Google Patents

Abstract

The present invention relates to new optically active chiral orthoborates and peroxyboranes obtained from alkyl orthoborate and from an alkyl hydroperoxide. It also relates to their use for the preparation of optically active chiral epoxides.

Description

ORTHOBORATES AND OPTICALLY ACTIVE CHIRAL PEROXYBORANES
AND THEIR USE
The present invention relates to novel boron derivatives.

More particularly, it relates to optically active chiral derivatives of orthoborates and peroxyboranes. It also relates to their use for the enantioselective synthesis of chiral epoxides from prochiral ethylenic derivatives
It is known, for example, according to French patents
FR 1 445 653, FR 1 458 153 and FR 1 447 267 to prepare organoperoxyboranes and to use them for the synthesis of epoxides.

Patent FR 1 458 153 describes the synthesis of tris (alkylperoxy) boranes B (O-Or) 2 from the alkyl ofthoborates B (ORt @ 3 by action on them of the alkyl hydroperoxides ROOH. alkylpercoxy) boranes of the aforementioned patent, are used according to patent FR 1 447 267 for the synthesis of epoxide compounds from the corresponding olefins.

 The general reaction for the preparation of trialkylperoxidic boron derivatives from borates and hydroperoxide and their uses in the synthesis of epoxide compounds are well known to date.

 On the other hand, nothing makes it possible, on reading these patents, to provide a reagent making it possible to obtain enantiomerically pure epoxides from an ethylenic derivative called prochiral. The term prochiral ethylenic derivative is understood to mean any derivative which, after saturation of the double bond, gives rise to a chiral saturated compound.

 Among the documents describing asymmetric epoxidation, mention may be made of the SHARPLESS article (JACS, 1980, 102, 59761 using a titanium metal catalyst in the oxidation state TV, a hydroperoxide and a tartaric acid ester. This asymmetric epoxidation method gives satisfactory results only for the epoxidation of allylic alcohols.The alcohol function of the allylic alcohols would allow the complexation of the olefinic substrate on the metal center, which would lead to an organization of a transition state or a reaction intermediate and thus to enantioselective epoxidation.

 This epoxidation is chemo selective. Allyl alcohols having another double bond further removed from the alcohol function are not affected on this second unsaturation.

 This reaction described by SHARPLESS is particularly specific for unsaturations located in zazou in ss of an alcohol function.

Some organic compounds with particularly complicated structures have been used as asymmetric epoxidation reagents such as
sulfonyloxaziridines (DAVIS, HARAKAL, AWAD, JACS 1983, 105,313)
- cyanohelicenes (BENHAS5INE, GORSANE, PECHER, MARTIN,
Bull. Soc. Chem. Belg. 1986, 95, 557),
the porphyrinic complexes of iron (III) chiral (GROVES,
MYERS, JACS, 1983, 105, 5791).

 All of these organic compounds allow a good selectivity in epoxidized derivatives but their complexity requires a long and delicate preparation which makes the epoxidation process economically unthinkable, at the industrial level.

 The present invention has made it possible to achieve an economically industrializable process for the enantioselective preparation of chiral epoxides. This process involves optically active chiral boron derivatives which are novel products.

 The invention thus relates to novel optically active borates and chiral peroxyboranes and their use in the enantioselective synthesis of chiral epoxides.

dans laquelle
- R3 représente un groupe alkyle, un groupe aryle ou
aralkyle, ayant de préférence 1 à 20 atomes de carbone
- R1 etXou R représente chacun indépendamment un groupe
chiral optiquement actif choisi parmi les radicaux
alkyle, alkényle, cetoalkyle, aryle, aralkyle,
éventuellement substitué par un groupe alkyle,
halogéno, halogénoalkyle alcoxy, halogènoalcoxy ou
- R1 et R2 réprésentent ensemble un sei groupe chiral
optiquenent actif choisi parmi les radicaux alkylidène,
alkenylene, cetoalkylidéne, arylidéne, éventuellement
substitué par un ou plusieurs groupes alkyle,
halogénoalkyle, hényle, alkyloxycarbonyle, alcoxy, halogénoalcoxy
- n est égal à 1 ou 2
Cn préfère parmi les composés de formule générale (I} les composés pour lesquels n est égal a 1 et R représente un groupe alkyle contenant 1 å 4 atomes de carbone et tout particulièrement ceux pour lesquels R3 représente un groupe méthyle.The novel chiral orthoborates and optically active chiral peroxyboranes have the following general formula (I)

in which
R3 represents an alkyl group, an aryl group or
aralkyl, preferably having 1 to 20 carbon atoms
- R1 and X or R represent each independently a group
optically active chiral selected from the radicals
alkyl, alkenyl, cetoalkyl, aryl, aralkyl,
optionally substituted by an alkyl group,
halo, haloalkyl alkoxy, haloalkoxy or
- R1 and R2 together represent a sei chiral group
active ingredient selected from alkylidene radicals,
alkenylene, cetoalkylidene, arylidene, optionally
substituted with one or more alkyl groups,
haloalkyl, henyl, alkyloxycarbonyl, alkoxy, haloalkoxy
n is 1 or 2
Preferred among the compounds of the general formula (I) are the compounds for which n is 1 and R is an alkyl group containing 1 to 4 carbon atoms, and especially those for which R 3 is methyl.

dans laquelle
- R a la méme signification que précédemment
- R4 représente une liaison covaiente ou un motif alkylidene
ayant 1 à 2 atomes de carbone
- Rs et R réprésentent des groupes identiques ou différents
choisis parmi les radicaux alkyloxycarbonyle, alkyle,
alkylidène, aryle, arylidéne. Parmi ces groupes
arylidène, on préfère les groupes naphtylidène.Parmi
les groupes alkylidéne, on préfère le pinène,
On préfère dans l'ensemble des composés de formule (II) ou n est égal d 2 ceux pour lesquels :
- R, représente une liaison covalente,
- R3 représente un groupe tertiobutyle,
- RU et P représente chacun un groupe alkyloxycarbonyle.Compounds for which R and R form a single optically active chiral group chosen from compounds belonging to formula (II) are also preferred among the compounds of general formula (I):

in which
- R has the same meaning as before
R4 represents a covalent bond or an alkylidene unit
having 1 to 2 carbon atoms
- Rs and R represent identical or different groups
chosen from alkyloxycarbonyl and alkyl radicals,
alkylidene, aryl, arylidene. Of these groups
arylidene, the naphthylidene groups are preferred.
alkylene groups, pinene is preferred,
In general, compounds of formula (II) are preferred or n is equal to those for which:
- R, represents a covalent bond,
R3 represents a tert-butyl group,
- RU and P each represents an alkyloxycarbonyl group.

Among all the chiral orthoborates, there may be mentioned in particular the compounds of the following formula and their optical antipodes.

Among the preceding compounds, it is preferred to use the compounds of formula (A), (B) or (C),
These chiral orthoborates are prepared in a manner known per se by condensation of an alkyl orthoborate, preferably methyl orthoborate (B (OCHa)), with one of the two enantiomers of a chiral diol or diketone.

 Among the chiral diols, there may be mentioned tartrates of methyl, ethyl, isopropyl; pinanediol; binaphthol; 1,1-bisphenyl, 1,2-propanediol.

The chiral-optically active peroxyboranes are prepared from optically active chiral orthoborates by hydroperoxide exchange. The hydroperoxides are chosen in particular from
tert-butyl hydroperoxide,
cyclohexyl hydroperoxide,
- cumyl hydroperoxide,
triphenylmethyl hydroperoxide,
- Tetralin hydroperoxide.

 The optically active chiral peroxyboranes corresponding to formula (I), with n = 2, will then be tert-butyl, cyclohexyl, aryl, triphenylmethyl and tetralin peroxyboranes.

 The optically active chiral peroxyboranes obtained are used to enantioselectively prepare, from ethylenic derivatives, chiral epoxides.

 The optically active chiral epoxides are prepared by contacting any, but prochiral, ethylenic derivative with chiral peroxides of the formula (I) wherein n is 2.

 Among the ethylenic derivatives, mention may be made of all the linear or branched, cyclic aliphatic mono or polyolefins, as well as the more complicated aryl organic compounds.

This method can be used to synthesize in particular
pheromones
- Balfourodine,
3-dimethoxy arancyamycinone,
the epoxide of transtilbene,
the epoxide of the octene,
phenyl-zyclohexene epoxide,
- the angelicalactone.

 According to a first method for preparing optically active chiral epoxides, the optically active chiral peroxyborane of formula (I) where n = 2 and the ethylenic derivative in the olefin itself which can be used as a solvent or in a inert solvent under the operating conditions such as, for example, cyclohexane.

 The contacting is preferably carried out at a temperature of between 90 and 1200 ° C. for a few hours.

 According to a second method for preparing optically active chiral epoxides, the optically active chiral orthoborate of formula (I) or (II) or n = 1 is brought into the presence of a hydroperoxide and the ethylenic derivative has a temperature of preferably about This second method of implementation avoids the extemporaneous preparation of the peroxyborane.

 Most of the chiral epoxide derivatives are used as synthesis intermediates in the pharmaceutical industry, in the electronic and optoelectronic components industry.

 The present invention will be more fully described with the aid of the following examples which should not be considered as limiting the invention.

EXAMPLE I - SYNTHESIS OF COMPLEX B (I)

Experimental part
In a 500 ml two-neck flask equipped with a thermometer and a Dean-Stark apparatus surmounted by a calcium chloride guard, place 17.8 g (100 mmol) of dried methyl tartrate leaving it for 24 hours under the vacuum of a ramp (0.5 torr), 40 ml (350 mmol) of B (OMe) 3 and 250 ml of dry cyclohexane.

 Working under slow heating conditions (5 hours with distillation of the methanol formed), chemical yields of 95 to 98% are obtained in recovered product after evaporation of the solvent under the empty ramp (P = 0.5 torr).

The product obtained is characterized by different physical methods - elementary analysis
% determined% calculated
C 38.2 38.57
H, 5.09
B 4.7 4.96
The results of the elemental analysis and the NMRtH and 11B spectra correspond to the proposed structure.

We measured the specific rotational powers of the product at different wavelengths (c = 37.7, CH2Cl2)

<tb><SEP> (nm)
<tb> 589 <SEP> - 34.5 <SEP>
<tb> 578 <SEP> -36.2
<tb> 546 <SEP> -41.7
<tb> 436 <SEP> -77.5
<tb> 365 <SEP> -138.3
<Tb>
EXAMPLE 2 - SYNTHESIS OF COMPLEX B (II)

 The synthesis is carried out exactly under the same conditions as the synthesis of B (I) 11.7 g (50 mml) of isopropyl tartrate (DIPT), 20 ml (175 mmol ', B (OMe) 3 in 100 ml cyclohexane.

 13.67 g of a viscous colorless oil (yield = 98% / DIPT) are obtained.

 The NMR spectrum confirms the proposed structure.

Elemental analysis
% determined% calculated
C 46.2 43.2
H 6.9 7; 0
B 3.1 3.95
Specific rotational powers of B (II) at different lengths
waves (c = 27.9; CH2Cl2

<tb> (nm) <SEP>
<tb> 589 <SEP> -32.6
<tb> 578 <SEP> -33.2
<tb> 546 <SEP> -39.4
<tb> 436 <SEP> -72.7
<tb> 365 <SEP> -128.9 <SEP>
<Tb>
EXAMPLE 3 - SYNTHESIS OF COMPOUND B (III)

 The synthesis is carried out under conditions similar to the synthesis of B (I) 10.3 g (50 mmol) of diethyl tartrate (DET), 25 ml (220 mmol) of B (OMe) 3, 100 ml of cyclohexane. 11.95 g of a viscous red oil are obtained (yield = 96% / DET).

 The NMRH spectrum confirms the structure.

- Elementary analysis
% determined% calculated
C 44.1 43.94
H 6.0 6.15
B 3.9 4.39
Rotatory power of B (III) (C = 29.6, CH2Cl2)

<tb><SEP> (nm) <xJ0 <SEP>
<tb> 589 <SEP> -27.6
<tb> 578 <SEP> -28.3
<tb> 546 <SEP> -10.2
<tb> 436 <SEP> -12.5
<tb> 365 <SEP> -12.8
<Tb>
EXAMPLE 4 - SYNTHESIS OF B (IV)

 Working under the conditions described for the synthesis of B (t) 0.89 g t5 mmol) methyl tartrate, 5.8 ml (10 mmol) of a 1.7 M solution of B (I) in CH2Cl21 50 ml of cyclohexane.

 After reaction and evaporation of the solvent, 2.69 g of a slightly brown colored oil (yield = 98 t) are recovered.

 The various physical analyzes confirm the proposed structure.

- Elementary analysis
% calculated%% determined
C 39.3 37.7
H 4.4 5.0
B 3.9 3.75
EXAMPLE 5 - SYNTHESIS OF B (V)

a) Synthesis of pinanediol (Tetrahedron letters, 1980, 449)
In a three-necked 100 ml flask equipped with an addition funnel, a thermometer and a water cooler, 25 mmol (3.4 g) of alpha-pinene, 3.75 g ( 34 mmol) of trimethylamine N-oxide dihydrate
Me3NO.2H2O, 2 ml of pyridine, 15 ml of water and 50 ml of tert-butanol.

The dropping funnel is filled with a solution of 20 mg (0.08 mmol) of osmium tetroxide in 1 ml of tert-butanol. The entire assembly is placed under a nitrogen atmosphere. The solution contained in the dropping funnel is added dropwise. Then the violet solution is refluxed for 24 hours. The cooled mixture at ambient temperature is treated with 20 ml of a 20% aqueous solution of sodium chloride and then concentrated under vacuum with a rotary evaporator to remove tert-butanol, the concentrated mixture is saturated with sodium chloride and then extracted. twice with 20 ml of ether.

The organic solution is then dried over MgSO 4. After evaporation of the ether, a white solid is recovered which is distilled under vacuum (bp 101-102 / 1 mmHg) and that it dries for 24 hours under a vacuum of a ramp (1 mmHg). After drying, 2.1 g of solid (12.3 mmol, yield = 50%) are recovered.

b) Synthesis of B (V)

 In a schlenk surmounted by a Dean-stark itself surmounted by a refrigerant protected by a CaCl2 guard, place 1.43 g (8.4 mmol), pinanediol 6 ml (52.8 mmol) of B (OMe) 3.50 ml dry cyclohexane. The mixture is heated slowly until the reflux temperature (initially 380 ° C.) stabilizes at 800 ° C. (5 hours of reflux). 1.54 g of a white solid are recovered after evaporation of the solvent.

 We carried out the NMRH and 11B spectra of the product as well as the elemental analysis.

- Elementary analysis
t determined% calculated
C 62.9 62.89
H 9.0 9.11
EXAMPLE 6 TO 11 - SYNTHESIS OF EPOXYDES
Standard condition of epoxidation.

 All epoxidations were conducted in a schlenk surmounted by a Dean-stark apparatus.

 The assembly is placed under a nitrogen atmosphere.

 The oxidation is conducted by hovering the schlenk in an oil bath thermostated at 1800 C.

EXAMPLE 6 - OCTENE-1 EPOXIDATION
In a 50 ml Schlenk, 15 ml (95 mmol) of octene-1, 3.5 ml (9.5 mmol) of a 2.7 M solution of tertiary butyl hydroperoxide (TBHP) are placed in the isooctane. 4.2 ml (9.5 mmol) of a solution of B (I) in dichloromethane.

 The schlenk is placed in a bath of thermostatic oil at 1000 C.

After 17 hours, 5 ml of liquid was collected in the
Dean-Stark.

 The amount of hydroperoxide is determined by iodometry: the consumption is total.

 1.2 g (9.5 mmol) of epoxide (100% yield relative to the hydroperoxide) are obtained, dose by gas chromatography.

 The solution is hydrolysed with an aqueous alkaline solution (30 g of NaOH, 10 g of NaCl in 80 ml of water) for 3 hours.

The reaction crude (n = 3.4 g) is added to a solution containing 4 g (154 mmol) of sodium methoxide dissolved in 100 ml of methanol. The whole is brought to reflux (680 C) during 4 hours in an assembly isolated from the atmospheric moisture by a guard
CaCl2.

 The cooled mixture is then hydrolysed with a saturated aqueous solution of Nazi.

 The organic solution is collected dried over Na 2 SO 4 and concentrated to remove methanol and octene-1. To better entrain octene-1, it is often necessary to add to the concentrated solution very viscous n-octane boiling point close to that of octene-1.

 Finally, 0.7 g (4.9 mmol) of crude alcohol is obtained, which corresponds to a recovery yield of approximately 50%.

 The crude alcohol ether is purified by flash chromatography on silica eluting with a pentane / AcOEt (80:20) mixture. The pure alcohol ether is obtained.

The enantometric excess of the product is determined by 1 H-NMR in the presence of a chiral chemical shift agent Eu (hfc) 3.

EXAMPLE 7 - OXIDATION OF TRANS-STILBENE
In a 50 ml Schlenk, 9 g (50 mmol) of transstilbene, 2.1 ml (9.5 mmol) of a solution of B (I) in CH 2 Cl 2, 1.8 ml (9.5 mmol) are placed. of a 2.7 M solution of TBHP. The schlenk is immersed in an oil bath at 1000 C for 18 hours. At the end of the reaction, the solution took an ocher color.

 The amount of TBHP remaining is measured by iodometry. The amount of epoxide obtained is determined by GPC with an internal standard (C20H42).

 After cooling, the solution is hydrolysed with an aqueous solution containing 5% NaOH for 3 hours at room temperature. The light yellow organic phase is washed with a saturated aqueous solution of NaCl to neutral pH, and then dried over MgSO4. After evaporation of the solvent, 8.8 g of a pale yellow solid are recovered.

 A 600 mg sample is purified by flash chromatography (on SiO 2 with pentane and then ethyl acetate as eluent). 110 mg of a yellow solid are then obtained. This solid is then preparative plate chromatography. 60 mg of a very pure epoxide (gas phase chromatographic analysis and nuclear magnetic resonance) are recovered.

Determination of enantiometric excess (ee)
A solution containing 14.6 ± 0.1 g of trans-stilbene epoxide in 2 ml of benzene (concentration 0.73 ± 0.005 g, 100 ml) is placed in the vessel of a Perkin-Elmer 241 polarimeter.

l'époxyde majoritaire étant (-)-S,S-trans-stilbéne-époxyde. The measured angle (&alpha;) for the sodium D line (2 = 589 nm) is
&alpha; = 0.965 0.0O2
The specific rotational power of the (+) - transstibene epoxide is known (J.Org.chem., 30, 4094 (1965): [&alpha;] D20-357 + 1 (C = 0.59, benzene), the enantiomeric excess of the reaction mixture is therefore

the major epoxide being (-) - S, S-trans-stilbene-epoxide.

 We will describe tex 8 to 11) experiments carried out, with various hydroperoxides and various complexes, the same procedure having been used.

TABLE 1

Examples <SEP> Substrate <SEP> Complex <SEP> Hydroperoxide <SEP> Solvent <SEP> Hydroperoxide <SEP> Yield / <SEP> es
<Tb>

<SEP> (Number <SEP> of <SEP> moles) <SEP> (Number <SEP> of <SEP> moles) <SEP> (Number <SEP> of <SEP> moles) <SEP> (Vol. <SEP > in <SEP> ml) <SEP> consumed <SEP> Hyd
<tb> Comparative <SEP> 5-Stilbene (16.7) <SEP> - <SEP> TBHP (3) <SEP> Toluene (5) <SEP> 70 <SEP>% <SEP> 90 <SEP>% <SEP> 0 <SEP>%
<tb><SEP> 6 <SEP> Octene- (95) <SEP> B (I) <SEP> (9.5) <SEP> TBHP (9.5) <SEP> - <SEP> 100 <SEP> % <SEP> 100 <SEP>% <SEP> 14 <SEP>%
<tb><SEP> 7 <SEP> t-Stilbene (50) <SEP> B (II) <SEP> (9.5) <SEP> TBHP (9.5) <SEP> Toluene (15) <SEP> 100 <SEP>% <SEP> 80 <SEP>% <SEP> 38 <SEP>%
<tb><SEP> 8 <SEP> t-Stilbene (50) <SEP> B (IV) <SEP> (9.5) <SEP> TBHP (9.5) <SEP> Toluene (15) <SEP> 100 <SEP>% <SEP> 16 <SEP>% <SEP> 4 <SEP>%
<tb><SEP> 9 <SEP> t-Stilbene (50) <SEP> B (I) <SEP> (9.5) <SEP> TBHP (9.5) <SEP> Toluene (25) <SEP> 100 <SEP>% <SEP> 80 <SEP>% <SEP> 37 <SEP>%
<tb><SEP> 10 <SEP> t-Stilbene (50) <SEP> B (I) <SEP> (9.5) <SEP> Hydroperoxide <SEP> from <SEP> Toluene (15) <SEP> 90 <SEP>% <SEP> 40 <SEP>% <SEP> 20 <SEP>%
<tb><SEP> cyclohexyl <SEP> (9.5)
<tb><SEP> 11 <SEP> Styrene (95) <SEP> B (I) <SEP> (9.5) <SEP> TBHP (9.5) <SEP> - <SEP> 100 <SEP>% <SEP> 14 <SEP>% <SEP> 25 <SEP>%
<tb> TBHP = Tert-Butyl Hydroperoxide

Claims (9)

 active ingredients according to general formula (I):  1. New orthoborates and optically chiral peroxyboranes  preferably pinene.  aryl, arylidene, preferably naphthylidene, alkylidene,  chosen from alkyloxycarbonyl, alkyl,  - Rs and R6 represent identical or different groups  having 1 & 2 carbon atoms,  R4 represents a covalent bond or an alkylidene unit  R3 has the same meaning as before,  in which

 next  active agents according to claim 1 having the formula (II)  n is 1 or 2 2.New orthoborates and optically chiral peroxyboranes  phenyl, alkyloxycarbonyl, alkoxy, halogenoalkoxy  by one or more alkyl, haloalkyl,  cetoalkylidene, arylidene, possibly substituted  chosen from alkylidene and alkenylene radicals,  - R1 and R together represent a single chiral group  alkoxy, haloalkoxy or  by an alkyl group. halo, haloalkyl,  cetoalkyl, aryl, aralkyl, optionally substituted  chiral selected from alkyl, alkenyl,  - R1 and / or R: each represents independently a group  carbon  arylalkyl preferably having 1 to 20 carbon atoms  Ra represents an alkyl group, an aryl group,  in which 3. New chiral orthoborates according to claims 1 or 2  characterized in that n is 1 and R3 is a group  alkyl having 1 to 4 carbon atoms. 4. New chiral peroxyboranes according to claims 1 or 2  characterized in that n is 2 and R is one  alkyl group having 4 to 20 carbon atoms. 5. New chiral peroxyboranes according to claim 4  characterized in that in the compound of formula (II)  R represents a covalent bond,  R represents tert-butyl,  - R and R6 represent an alkyloxycarbonyl group. 6. Process for the enantioselective preparation of chiral epoxides  characterized in that a derivative is brought into  ethylene and a peroxyborane of formula (I) in which  is equal to 2. 7. Method according to claim 6 characterized in that the  Ethylenic derivatives are olefins. 8. Process for the preparation of optically active chiral epoxides  characterized in that a derivative is brought into  ethylene, and an orthoborate of formula (I) or (II) in  which n is equal to 1 with an alkyl hydroperoxyl,  cycloalkyl or aryl. 9. Process for the preparation of optically active chiral epoxides  characterized in that one puts in the presence  in a first step an alkyl orthoborate with a  the two enantiomers of a diol or a chiral dicetone,  in a second step, add a hydroperoxide  alkyl, cycloalkyl or arylalkyl and a derivative  Prochiral ethylenic.