Optically active diols, synthesis

Optically active diols are useful building blocks for the synthesis of chiral diphosphite ligands. Chiral diphosphites based on commercially available optically active 1,2 and 1,4-diols, l,2 5,5-diisopropylidene-D-mannitol, L-a,a,a,a-tetramethyl-l,3-dioxalan-4,5-dimethanol and L-diethyl tartrate, were first used in the asymmetric hydroformylation of styrene [75],... 

Epoxide hydrolase has emerged as an important enzyme for the asymmetric synthesis of enantiopure epoxides and diols [24]. The hydrolase HXN-200 has been shown to catalyse the enantioselective hydrolysis of meso epoxides to give optically active diols (Scheme 4.14) [25]. A related group of enzymes is the haloalkane dehalogenases that display epoxide hydrolase activity with nucleophiles other than water (Scheme 4.15) [26]. 

One recently reported synthesis of diols has been discussed earlier (Scheme 9). In a publication already mentioned in this Report on asymmetric syntheses based on chiral diamines containing a pyrrolidine ring, a synthesis of optically active diols (Scheme 28) from two consecutive Grignard additions to... 

From those examples, it becomes apparent that enzymes that are involved in the synthesis of epoxides are particularly well suited to be used in conjunction with EHs for the generation of optically active diols or epoxides. As these compounds are highly attractive chiral synthons, one can expect that, in the future, more and more bi (or tri) enzymatic processes will be developed with EHs as the key components. 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

In general, yields of (/ )-acyloins and (2S,3/ )-diols, respectively, are low due to the formation of several byproducts (mainly reduction products of the substrate). Nevertheless, the optically active compounds thus obtained are extremely useful intermediates for the synthesis of many natural products51. 

T. Iida, N. Yamamoto, N. Matsunaga, H.-G. Woo, M. Shibasaki, Enantioselective Ring Opening of Epoxides with 4-Methoxyphenol Catalyzed by Gallium Hetero-bimetallic Complexes An Efficient Method for the Synthesis of Optically Active 1,2-Diol Monoethers, Angew. Chem Int. Ed. EngL 1998,32 2223-2226. 

As already hinted at above, chiral dioxetanes, obtained through the highly stereoselective [2 + 2] cycloaddition of singlet oxygen to the chiral enecarbamate, provide a convenient preparation of optically active 1,2 diols as building blocks for asymmetric synthesis (Scheme 5) . Reduction of the dioxetane 2c by L-methionine, followed by release of the oxazolidinone auxiliary by NaBH4/DBU reduction, affords the enantiomerically pure like-5 diol (for additional cases, see Table 4 in Reference 19e). 

A chiral recognition was observed in aminolysis of 3-acyl-4(R)-methoxycarbonyl-l,3-thiazolidine-2-thione, a derivative of (R)-cysteine, by racemic amines to give an optically active amide [(S)-excess] and amine [(R)-excess]264). In the reaction of cyclic meso-1,3-diols with chiral N-protected phenylalanyl chlorides, Yamada et al.26S) observed the preferential formation of one of the two possible diastereomeric monoesters, which has been used for the synthesis of optically active steroids 266) and prostaglandins 267). 

Another regioselective addition to an epoxide was used as one step in a synthesis of the r-butyldiphenylsilyl ether (7) of verrucarinic acid from 5.3 The diol was converted into the optically active epoxy alcohol by the Sharpless method (10, 64-65) and then oxidized to the epoxy acid 6 by the new ruthenium-catalyzed oxidation of Sharpless et al. (this volume). This epoxy acid undergoes almost exclusive / -addition with trimethylaluminum to give the desired product 7. 

L. G. Lee and G. M. Whitesides, Preparation of optically active 1,2-diols and a-hydroxy ketones using glycerol dehydrogenase as catalyst limits to enzyme-catalyzed synthesis due to noncompetitive and mixed inhibition by product, J. Org. Chem. 1986, 51, 25-36. 

Diols such as the optically active 1,1 -binaphthyl-2-2 -diol (BINOL) have been used as versatile templates and chiral auxiliaries in catalysts employed successfully in asymmetric synthesis. The application of enzymes in the enantioselective access to axially dissymmetric compounds was first reported by Fujimoto and coworkers.83 In aqueous media, the asymmetric hydrolysis of the racemic binaphthyl dibutyrate (the ester) using whole cells from bacteria species afforded the (A)-diol with 96%ee and the unreacted substrate (A)-ester with 94% ee at 50 % conversion. Recently, in non-aqueous media, lipases from Pseudomonas cepacia and Ps. fluorescens have been employed in the enantioselective resolution and desymmetrization of racemic 6,6 -disubstituted BINOL derivatives using vinyl acetate.84 The monoacetate (K)-73 (product) was obtained in 32-44 % chemical yields and 78-96% ee depending on the derivatives used. The unreacted BINOL (S)-72 was obtained in 30-52 % chemical yield and 55-80% ee. 

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