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

Marchello A. Cavitt; Stefan France

doi:10.1055/s-0035-1561621

Synthesis, Inhaltsverzeichnis

Synthesis 2016; 48(12): 1910-1919
DOI: 10.1055/s-0035-1561621

special topic

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

Marchello A. Cavitt

^aSchool of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA

,

Stefan France*

^aSchool of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332, USA

^bPetit Institute for Bioenginering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA eMail: Stefan.france@chemistry.gatech.edu

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Abstract

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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.

Key words

heterocycles - fused-ring systems - ring-opening cyclizations - tetrahydroindolizines - formal homo-Nazarov cyclization - donor-acceptor cyclopropanes

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Referenzen

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Zusatzmaterial

Supporting Information