Enantioselective a-Functionalization of Carbonyl Compounds

The enantioselective oxygenation procedures, epoxidation and dihydroxylation, developed by Barry Sharpless have dominated single-enantiomer organic synthesis. Recently, several additional methods for enantioselective oxidation have been developed, based on the a-functionalization of carbonyl compounds. 

With cyclic enones. Professor Yamamoto has developed (7. Am. Chem. Soc. 2004, 126, 5962) an enantioselective double functionalization. The organocatalyst 8 mediates conjugate addition of N and a -oxygenation, to give 9. 

Enantioselective halogenation is a powerful transformation, directly installing an efficient leaving group. Thomas Leckta of Johns Hopkins University has shown J. Am. Chem. Soc. 2004,126,4245) that benzoylquinine 11 catalyzes the a-chlorination of ketenes derived from acid chlorides such as 10, to give 12 in high ee. 

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The use of enamine catalysis in the enantioselective a-functionalization of carbonyl compounds has been reviewed, including aldol, Mannich, and alkylation processes," and a short review has examined enantioselective a-alkylation of aldehydes Benzodithiolylium tetrafluoroborate (133) is a water-stable salt and can be added enantioselectively to aldehydes at the a-position in the presence of simple chiral organocatalysts, giving the corresponding alcohol. The sulfurs can be readily cleaved with H2/Raney Ni, rendering the process a formal tf-methylation of aldehydes." a ,/3-Unsaturated aldehydes undergo enantioselective a- and y-alkylation via dien-amine activation, using a diarylprolinol TMS ether as catalyst." ... 

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