Asymmetric synthesis and applications of β-amino Weinreb amides: asymmetric synthesis of (S)-coniine

Organic & Biomolecular Chemistry Pub Date: 2004-04-05 DOI: 10.1039/B402531H

Abstract

Conjugate addition of lithium (S)-N-benzyl-N-α-methylbenzylamide to a range of α,β-unsaturated Weinreb amides proceeds with high levels of diastereoselectivity (>95% de). The β-amino Weinreb amide products may be transformed into β-amino ketones via reactions with Grignard reagents, while treatment with DIBAL-H furnishes β-amino aldehydes. Trapping of the aldehyde via Wadsworth–Emmons reaction and subsequent manipulation offers an efficient route to homochiral δ-amino acid derivatives and 2-substituted piperidines. The application of this methodology for the synthesis of (S)-coniine is demonstrated.

Graphical abstract: Asymmetric synthesis and applications of β-amino Weinreb amides: asymmetric synthesis of (S)-coniine
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