Enantioselective Cycloalkenone Synthesis

An asymmetric alkylation of a chiral enaminone has been established, and addition of Grignard reagents has been shown to produce the cycloalkenone. These reactions may provide an efficient means of preparing optically pure, substituted cycloalkenones (Scheme 1).

Scheme 1

The effort currently required to prepare optically enriched (84% ee) 3a (8 steps; 13-21% yield from cyclohexane-1,3-dione) illustrates the need for more efficient means for the synthesis of optically pure cycloalkenones. Application of our reaction sequence would reduce the number of steps from eight to three (Scheme 2).

Scheme 2

Efforts to date have centered on the use of (S)-2-(methoxymethyl)pyrrolidine as a chiral auxiliary. Despite the distance of the pre-existing center of asymmetry, stereoselectivity in the alkylation of the kinetic enolate of 1a is significant (Scheme 3), and the diastereomeric products are isolated by flash chromatography.

Scheme 3

Additional Information

Thomas T. Shawe
Associate Professor
Department of Chemistry,
Bucknell University

e-mail: shawe@bucknell.edu
phone: 570-577-1750
fax: 570-577-1739