ASYMMETRIC SYNTHESIS--STRUCTURE, STEREOCHEMISTRY AND NMR

在开发制备手性醇的方法和制造

In developing methodologies to prepare chiral alcohols and to make tentative assignments of their absolute stereochemistry (based on their method of preparation), we have continued to examine the enantioselective hydrolysis of esters. These hydrolyses are catalyzed by enzymes in the mold Rhizopus nigricans, and the configuration of the alcohol formed can be predicted from considerations of the effective sizes of substituents on the carbinol carbon. While data on the absolute stereochemistry of the more rapidly hydrolyzed enantiomer of the ester were consistent with the rule, a quantitative analysis was carried out to determine the relative contributions that electronic, steric and polarizability factors make both to the formation of the enzyme-substrate complex and to the relative rates of hydrolysis of the enantiomers. Data on the optical purities of the alcohols formed and the percent hydrolysis were employed to calculate an "E" value which describes the relative rates of hydrolysis of the two acetate enantiomers. The data show the relative importance of steric, electronic and polarizability factors and demonstrate that it is possible to predict the optical purity of an alcohol formed using standard values of the size, electronegativity and polarizability of substituents. To complement the methodology developed for the preparation of chiral allylic alcohols described, we carried out a preliminary study to demonstrate that the ketal Claisen rearrangement (a rearrangement of vinyl ethers of allylic alcohols), a reaction that had not previously received much attention, can be used for the synthesis of several sesquiterpenes, cuparene, laurene, bazzanene and trichodiene. Each of these natural products contain a quaternary carbon atom. We propose to employ the established chirality of an allylic alcohol to control the absolute stereochemistry of a quaternary carbon atom formed in the rearrangement.