Asymmetric synthesis and applications of beta-amino Weinreb amides: asymmetric synthesis of (S)-coniine.
Conjugate addition of lithium (S)-N-benzyl-N-alpha-methylbenzylamide to a range of alpha, beta-unsaturated Weinreb amides proceeds with high levels of diastereoselectivity (>95% de). The beta-amino Weinreb amide products may be transformed into beta-amino ketones via reactions with Grignard reagents, while treatment with DIBAL-H furnishes beta-amino aldehydes. Trapping of the aldehyde via Wadsworth-Emmons reaction and subsequent manipulation offers an efficient route to homochiral delta-amino acid derivatives and 2-substituted piperidines. The application of this methodology for the synthesis of (S)-coniine is demonstrated.
Burke
Anthony J
AJ
Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, UK OX1 3TA.
Davies
Stephen G
SG
Garner
A Christopher
AC
McCarthy
Tom D
TD
Roberts
Paul M
PM
Smith
Andrew D
AD
Rodriguez-Solla
Humberto
H
Vickers
Richard J
RJ
D000447:Aldehydes / Q000138:chemical synthesis; D000470:Alkaloids / Q000138:chemical synthesis*; D000577:Amides / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis; D018020:Lithium Compounds / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis*
D000447:Aldehydes; D000470:Alkaloids; D000577:Amides; D007659:Ketones; D018020:Lithium Compounds; D010880:Piperidines; C007112:coniine