A Practical Route to 2,3-Di-/1,2,3-Trisubstituted Indolizines from α-EWG Ketene S,S-Acetals and Their Application in Bis(1-indolizinyl)methane Synthesis

Shaoguang Sun; Mang Wang; Hongxia Deng; Qun Liu

doi:10.1055/s-2008-1032144

PAPER

A Practical Route to 2,3-Di-/1,2,3-Trisubstituted Indolizines from α-EWG Ketene S,S-Acetals and Their Application in Bis(1-indolizinyl)methane Synthesis

Shaoguang Sun, Mang Wang*, Hongxia Deng, Qun Liu*
Department of Chemistry, Northeast Normal University, Changchun 130024, P. R. of China
Fax: +86(431)85099759; e-Mail: wangm452@nenu.edu.cn;

Abstract

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Abstract

An easy synthesis of 2,3-di-/1,2,3-trisubstituted indolizines has been developed via a formal [3+2] annulation of α-EWG ketene S,S-acetals with 2-pyridine-/2-quinolinecarbaldehyde. The disubstituted products are formed via an intramolecular aza-Michael addition and subsequent elimination of acetic acid, followed by desulfenylation assisted by acetic acid, whereas the trisubstituted products are obtained via a similar conjugate addition followed by elimination of alkanethiol. This strategy has been applied to the synthesis of bis(1-indolizinyl)methanes by the condensation of a 2,3-disubstituted indolizine with aldehydes/ketones in the presence of a catalytic amount of BF₃·OEt₂.

Key words

indolizines - α-EWG ketene S,S-acetals - bis(1-indolizinyl)methanes - annulation - condensation

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Crystal data for 7d: C₂₉H₂₃ClN₄S₂, yellowish, M = 527.08, monoclinic, space group P2 (1)/n, a = 15.109 (3) Å, b = 11.0197 (18) Å, c = 16.741 (3) Å, V = 2630.8 (7) Å³, α = 90.00, β = 109.287 (2), γ = 90.00, Z = 4, T = 293 K, F ₀₀₀ = 1096, R1 = 0.0610, wR2 = 0.1646. The supplementary crystallographic data for this structure (CCDC 657119) can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/products/csd/request.

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