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

作者：Cavitt Marchello A; France Stefan^*

来源：Synthesis (Germany), 2016, 48(12): 1910-1919.

DOI：10.1055/s-0035-1561621

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

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.

• 出版日期2016-6