Synthesis 2016; 48(12): 1910-1919
DOI: 10.1055/s-0035-1561621
special topic
© Georg Thieme Verlag Stuttgart · New York

Aluminum(III)-Catalyzed, Formal Homo-Nazarov-Type Ring-Opening Cyclizations toward the Synthesis of Functionalized Tetrahydroindolizines

Marchello A. Cavitt
a  School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA
,
Stefan France*
a  School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA
b  Petit Institute for Bioenginering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA   Email: Stefan.france@chemistry.gatech.edu
› Author Affiliations
Further Information

Publication History

Received: 15 February 2016

Accepted after revision: 21 March 2016

Publication Date:
28 April 2016 (online)

Abstract

A general approach to functionalized 5,6,7,8-tetrahydroindolizines (THIs) is disclosed. The THIs are directly formed from Al(OTf)3-catalyzed, formal homo-Nazarov-type ring-opening cyclizations of N-pyrrolyl cyclopropyl malonamides. The THI products were stable to silica gel chromatography and isolated in up to 97% yield with diastereomeric ratios up to 4.0:1. The cyclization demonstrates good substrate scope as aryl, heteroaryl, gem-dialkyl, heteroatomic, and silylmethyl donor groups on the cyclopropane are tolerated. Moreover, the protocol is both pharmaceutically relevant and environmentally friendly as a cheap, earth-abundant metal catalyst is used along with acetonitrile as a greener solvent.

Supporting Information

 
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