Kinetic resolution, of vinyl epoxides

In the course of our earlier studies on terpenylboranes we developed a simple transformation of a- into 3-pinene," and a stereoselective synthesis of allylic alcohols by the reduction of vinylic epoxides.12 An extension of these studies to contrathermo-dynamic isomerization of a-thujene, 2- and 3-carene,13 and kinetic resolution of vinylic epoxides by the reduction with terpenylboranes,14 is described. 

SYNTHESIS OF (+)-3(10>CARENE, (+)-SABINENE, AND KINETIC RESOLUTION OF VINYLIC EPOXIDES... 

Kinetic resolution of vinylic epoxides by the reduction with terpenyl dialkylboranes of high optical purity is a simple and direct method for the preparation of enantiomerically enriched epoxides. It allows for convenient configurational assignment of epoxides if the configuration of the corresponding allylic alcohol is known. Both enantiomers can be prepared using readily available enantiomeric diisopinocampheylboranes. 

Various catalytic or stoichiometric asymmetric syntheses and resolutions offer excellent approaches to the chiral co-side chain. Among these methods, kinetic resolution by Sharpless epoxidation,14 amino alcohol-catalyzed organozinc alkylation of a vinylic aldehyde,15 lithium acetylide addition to an alkanal,16 reduction of the corresponding prochiral ketones,17 and BINAL-H reduction18 are all worth mentioning. 

The use of vinyl epoxides as substrates in enantioselective copper-catalyzed reactions, on the other hand, has met with more success. An interesting chiral ligand effect on Cu(OTf)2-catalyzed reactions between cyclic vinyloxiranes and dialkylzinc reagents was noted by Feringa et al. [51]. The 2,2 -binaphthyl phosphorus amidite ligands 32 and 43 (Fig. 8.5), which have been successfully used in copper-catalyzed enantioselective conjugate additions to enones [37], allowed kinetic resolution of racemic cyclic vinyloxiranes (Scheme 8.26). 

Efficient kinetic resolution of chiral unsaturated secondary alcohols by irreversible enzyme-mediated acylation (with vinyl acetate as acylating agent, a crude preparation of Pseudomonas AK, and hexane as solvent) is possible, provided one relatively large and one small substituent are attached to the carbinol carbon. However, the method can be used to resolve substrates that are not amenable to asymmetric epoxidation (see examples 23, 25, 27, 29, where the double bond is either deactivated by an electron-withdrawing substituent, or is of the propargyl alcohol type). Acylation of the / -enantiomer consistently proceeds faster than that of the 5-enantiomer. An example of an allenic alcohol was also reported248. 

Three different principles of selectivity are required to achieve this result. First, the difference in rate of epoxidation by the catalyst of a disubstituted versus a monosubstituted olefin must be such that the propenyl group is epoxidized in complete preference to the vinyl group. The effect of this selectivity is to reduce the choice of olefinic faces to four of the two propenyl groups. Second, the inherent enantiofacial selectivity of the catalyst as represented in Figure 6A.1 will narrow the choice of propenyl faces from four to two. Finally, the steric factor responsible for kinetic resolution of 1-substituted allylic alcohols (Fig. 6A.2) will determine the final choice between the propenyl groups in the enantiomers of 80. The net result is the formation of epoxy alcohol 81 and enrichment of the unreacted allylic alcohol in the (35)-enantiomer. 

Kinetic resolution of chiral aUylic alcohols.7 Partial (at least 60% conversion) asymmetric epoxidation can be used for kinetic resolution of chiral allylic alcohols, particularly of secondary allylic alcohols in which chirality resides at the carbinol carbon such as 1, drawn in accordance with the usual enantioface selection rule (Scheme I). (S)-l undergoes asymmetric epoxidation with L-diisopropyl tartrate (DIPT) 104 times faster than (R)-l. The optical purity of the recovered allylic alcohol after kinetic resolution carried to 60% conversion is often > 90%. In theory, any degree of enantiomeric purity is attainable by use of higher conversions. Secondary allylic alcohols generally conform to the reactivity pattern of 1 the (Z)-allylic alcohols are less satisfactory substrates, particularly those substituted at the /1-vinyl position by a bulky substituent. 

Chiral to side-chain units can also be obtained by various catalytic and stoichiometric asymmetric synthesis as well as by resolution (30). Scheme 14 shows the preparation of these side-chain units using kinetic resolution by the Sharpless epoxidation (31), amino alcohol-catalyzed organozinc alkylation of a vinylic aldehyde (32), lithium acetylide ad-... 

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