Stereoselective Synthesis of Highly Substituted Piperidines

Abstract

Enantiopure piperidines 4 may be accessed in very good unsaturated imide. The stereoselectivity is controlled by A(1.2) strain between the imine N-alkyl group and the overall yields and high stereoselectivity from the bifunctional products 2 of the silyloxy Cope rearrangement of chiral aldol conjugate double bond. In an alternate approach, polyalkylsubstituted piperidines were prepared by the addition of products 1 by sequential nucleophilic addition of primary amines and subsequent hydrogenation. The reaction is organozinc reagents to cyanopiperidines readily obtained from the Cope products in the presence of a silver salt. proposed to proceed by initial imine formation followed by an intramolecular aza-conjugate addition to the α,β-Eur.

The Bruylants and related reactions

“…Allyl and propargyl zinc halides are quite good nucleophiles and appear as fair substitutes in the Bruylants reaction. [73][74][75] Bernardi et al performed the Bruylants reaction under Barbier and Reformatsky conditions and thus generated the organometallic species in situ. 76 In this work, -aminonitriles were prepared by the Suginome's procedure, from aldehydes and bis(dialkylamino)cyanoboranes.…”

Grob Fragmentation of 2-Azabicyclo[2.2.2]oct-7-ene: Tool for the Stereoselective Synthesis of Polysubstituted Piperidines

“…The piperidine ring can be formed either through aza-Diels−Alder reactions, 5 intramolecular reductive aminations, 6 intramolecular allene hydroaminations, 7 or intramolecular aza-Michael additions. 8 All of these methods are multistep syntheses and often lack generality.…”

“…In particular, only a few examples of stereoselective synthesis of 2,3,4-trisubstituted piperidines have been published. The piperidine ring can be formed either through aza-Diels–Alder reactions, intramolecular reductive aminations, intramolecular allene hydroaminations, or intramolecular aza-Michael additions . All of these methods are multistep syntheses and often lack generality.…”