Asymmetric synthesis using chiral acetals. Studies on the nucleophilic addition of organometallics to chiral .ALPHA.-keto acetals in open-chain systems.

Abstract

Nucleophilic addition of organometallic reagents (Grignard reagents and organolithium reagents) to three chiral α-keto acetals (1a-c) in open-chain systems was studied. The reactions of the chiral a-keto acetals (1a, 1b) having a chiral auxiliary as a ketone equivalent with Grignard reagents proceeded in a highly diastereoselective manner (> 94% diastereomeric excess (de)). As an application of the reaction, the syntheses of the key intermediates (6, 8) for (R) -and (S) -mevalolactone were achieved from the product obtained by the reaction of 1a and vinylmagnesium bromide. On the other hand, in the reactions of the chiral α-keto acetal (1c) having a chiral auxiliary as an aldehyde equivalent, lower stereoselectivity was observed even when Grignard reagents were used as addends. The difference of stereoselectivity among the three chiral α-keto acetals (1a-c) is discussed.