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Stereoselective Synthesis of Highly Substituted Piperidines
Author(s) -
Schneider Christoph,
Börner Christoph,
Schuffenhauer Ansgar
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199912)1999:12<3353::aid-ejoc3353>3.0.co;2-q
Subject(s) - chemistry , stereoselectivity , stereochemistry , combinatorial chemistry , organic chemistry , catalysis
Enantiopure piperidines 4 may be accessed in very good overall yields and high stereoselectivity from the bifunctional products 2 of the silyloxy Cope rearrangement of chiral aldol products 1 by sequential nucleophilic addition of primary amines and subsequent hydrogenation. The reaction is proposed to proceed by initial imine formation followed by an intramolecular aza‐conjugate addition to the α,β‐unsaturated imide. The stereoselectivity is controlled by A(1.2) strain between the imine N ‐alkyl group and the conjugate double bond. In an alternate approach, polyalkyl‐substituted piperidines were prepared by the addition of organozinc reagents to cyanopiperidines readily obtained from the Cope products in the presence of a silver salt.