Direct Catalytic Asymmetric Aldol Additions of Methyl Ynones. Spontaneous Reversal in the Sense of Enantioinduction

摘要

The direct catalytic asymmetric aldol addition reaction has emerged as a powerful tool for the rapid assembly of enantiomerically enriched β-hydroxy carbonyl compounds. However, most of the examples reported to date are limited to rather simple nucleophiles, and hence development of processes which allow for the use of functionalized substrates is highly desirable. Although the synthetic value of ynones has long been appreciated, their ability to act as powerful Michael acceptors and the tendency of ynone-derived β-hydroxy ketones to undergo retro-aldol reactions has precluded the development of aldol addition methods with these substrates. Thus, the use of ynones in aldol additions is virtually unknown. The lack of methods for enantioselective aldol reactions of ynones provided a fitting challenge for the further development of our dinuclear zinc catalyst (Scheme 1). Herein, we report unusual effects in the asymmetric aldol addition of methyl ynones to pyruvaldehyde ketals, the products of which are well suited for structural elaboration.