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

Anthony J. Burke; Stephen G. Davies; A. Christopher Garner; Tom D. McCarthy; Paul M. Roberts; Andrew D. Smith; Humberto Rodriguez-Solla; Richard J. Vickers

doi:10.1039/b402531h

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

Anthony J. Burke, Stephen G. Davies^*, A. Christopher Garner, Tom D. McCarthy, Paul M. Roberts, Andrew D. Smith, Humberto Rodriguez-Solla, Richard J. Vickers

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Conjugate addition of lithium (S)-N-benzyl-N-a-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.

Original language	English
Pages (from-to)	1387-1394
Number of pages	8
Journal	Organic and Biomolecular Chemistry
Volume	2
Issue number	9
DOIs	https://doi.org/10.1039/b402531h
Publication status	Published - 7 May 2004

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title = "Asymmetric synthesis and applications of β-amino Weinreb amides: Asymmetric synthesis of (S)-coniine",

abstract = "Conjugate addition of lithium (S)-N-benzyl-N-a-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.",

author = "Burke, {Anthony J.} and Davies, {Stephen G.} and Garner, {A. Christopher} and McCarthy, {Tom D.} and Roberts, {Paul M.} and Smith, {Andrew D.} and Humberto Rodriguez-Solla and Vickers, {Richard J.}",

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TY - JOUR

T1 - Asymmetric synthesis and applications of β-amino Weinreb amides

T2 - Asymmetric synthesis of (S)-coniine

AU - Burke, Anthony J.

AU - Davies, Stephen G.

AU - Garner, A. Christopher

AU - McCarthy, Tom D.

AU - Roberts, Paul M.

AU - Smith, Andrew D.

AU - Rodriguez-Solla, Humberto

AU - Vickers, Richard J.

PY - 2004/5/7

Y1 - 2004/5/7

N2 - Conjugate addition of lithium (S)-N-benzyl-N-a-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.

AB - Conjugate addition of lithium (S)-N-benzyl-N-a-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.

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U2 - 10.1039/b402531h

DO - 10.1039/b402531h

M3 - Article

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AN - SCOPUS:2542446198

SN - 1477-0520

VL - 2

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EP - 1394

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 9

ER -

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

Abstract

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