Stereocontrolled alkylation of chiral pyridinium salt toward a short enantioselective access to 2-alkyl- and 2,6-dialkyl-1,2,5,6-tetrahydropyridines.
Nenhuma Miniatura disponível
Data
2000
Título da Revista
ISSN da Revista
Título de Volume
Editor
Resumo
Treatment of salts 1a–b with Grignard reagents gives, after
reduction of the resulting unstable dihydropyridines 7, the
tetrahydropyridines 8a–c, with modest selectivities but in
very few steps and under practical conditions. Higher stereoand
regioselectivities are obtained with salt 1c which gives
the tetrahydropyridines 15a–e. In addition, the dihydropyrid-
Introduction
The enantioselective synthesis of six-membered nitrogen
heterocycles has been the subject of a large number of studies
during the past few years due to the interest of these
intermediates in natural alkaloid and medicinal chemistry.
As a consequence, efficient methods are now available for
preparing chiral 2- and 2,6-substituted piperidines.[1] However,
few methods are available concerning the corresponding
enantiopure substituted tetrahydropyridines.[2] Therefore,
we now present a strategy which is briefly summarized
in Scheme 1. The main features of this approach are: (a)
selective alkylation with Grignard reagents[3–5] of pyridinium
salts 1 (Scheme 1), now readily available from chiral
primary amines;[6] (b) protonation of the resulting dihydropyridines
2 to give dihydropyridinium salt equivalents
3;[7] (c) additional treatment with a Grignard reagent affording
the 2,6-disubstituted tetrahydropyridines 4.
Scheme 1. General strategy for the enantioselective construction of
substituted tetrahydropyridines
The interest of this approach is illustrated by the short
synthesis from salt 1c (Scheme 2) of (2)-lupetidin, (1)-
solenopsin A and indolizidines (2)-5 and (2)-6, this last
synthesis being designed as an example of further ring elaboration
of the tetrahydropyridines 4.
[a] Institut de Chimie des Substances Naturelles, C.N.R.S.
Avenue de la Terrasse, 91198 Gif-Sur-Yvette CEDEX, France
Fax: (internat.) 1 33-1/69077247
E-mail: marazano@icsn.cnrs-gif.fr
[b] Departamento de Quimica, ICEB, Universidad Federal de
Ouro Preto,
Campus Morro de Cruzeiro, 35400.00, Ouro Preto, MG, Brazil
Eur. J. Org. Chem. 2000, 139121399 Ó WILEY-VCH VerlagGmbH, D-69451Weinheim, 2000 14342193X/00/040821391 $ 17.501.50/0 1391
ine intermediates 11b cyclize to give the new oxazolidine derivatives
12a–e, which turn out to be good precursors of the
2,6-trans-disubstituted tetrahydropyridines 21a–e. Selective
syntheses of (–)-lupetidin, (+)-solenopsin, and indolizidines
(–)-5 and (–)-6 are presented as representative examples of
applications.
Descrição
Palavras-chave
Alkaloids, Alkylations, Asymmetric synthesis, Grignard reactions
Citação
BERTIN, B. G. et al. Stereocontrolled alkylation of chiral pyridinium salt toward a short enantioselective access to 2-alkyl- and 2,6-dialkyl-1,2,5,6-tetrahydropyridines. European Journal of Organic Chemistry, Alemanha, v. 1, p. 1391-1399, 2000. Disponível em: <http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1099-0690(200004)2000:8%3C1391::AID-EJOC1391%3E3.0.CO;2-D/abstract>. Acesso em: 20 mai. 2017.