Reversal of diastereoselectivity in the benzylation of the lithium enolates of phosphonopropanoamides by changing the base equivalents

Phosphonopropanoamides bearing (S)-α-methylbenzylamine were easily obtained, and the benzylation of their enolates examined. Surprisingly, a reversal of the π-facial diastereoselectivity was observed by changing the number of equivalents of the lithium base. Reaction of the lithium enolate obtained using 2.0 equiv of LDA, LiHMDS or LTMP with benzyl bromide afforded the (R,S)-diastereoisomer, whereas the use of ⩾2.5 equiv of lithium base gave the (S,S)-diastereoisomer. In contrast, a reversal of diastereoselectivity was not observed with sodium or potassium bases. This reversal is attributed to the formation of aggregates of the enolates. The results presented here provide valuable guidelines to tune the selective preparation of enantiopure compounds from the same source of chirality.

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