Synthesis 2018; 50(24): 4837-4845
DOI: 10.1055/s-0037-1610133
paper
© Georg Thieme Verlag Stuttgart · New York

Sequential Pyridine Dearomatization–Mizoroki–Heck Cyclization for the Construction of Fused (Dihydropyrido)isoindolinone Ring Systems

Madhur S. Joshi
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA   Email: chris-pigge@uiowa.edu
,
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA   Email: chris-pigge@uiowa.edu
› Author Affiliations
Early portions of this work were supported by a grant from the U.S. National Science Foundation (CHE-1265488).
Further Information

Publication History

Received: 14 February 2018

Accepted after revision: 09 April 2018

Publication Date:
29 May 2018 (eFirst)

Abstract

Acylation of 4-alkylpyridines with 2-iodobenzoyl chlorides under basic conditions results in pyridine dearomatization via formation of 4-alkylidene dihydropyridines. These reasonably stable intermediates are further transformed through Pd-catalyzed Mizoroki–Heck cyclization to afford dihydropyrido-fused isoindolinone products in good yield. This study demonstrates successful harnessing of reactive dearomatized pyridine anhydrobases in metal-catalyzed C–C bond-forming reactions, and provides an efficient entry to isoindolinone ring systems structurally related to several indolizidine alkaloid frameworks.

Supporting Information

 
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