Tandem benzannulation-ring closing metathesis strategy for the synthesis of benzo-fused nitrogen heterocycles ;

Abstract

A tandem benzannulation-ring closing metathesis strategy for the efficient synthesis of benzo-fused nitrogen heterocycles such as dihydroquinolines, benzazepines, and benzazocines has been developed. This strategy is based on the benzannulation reaction of ynamides with cyclobutenones or [alpha]-diazo ketones to generate highly-substituted aniline derivatives, which then participate in ring-closing metathesis reactions to form nitrogen heterocycles. The synthetic utility of this strategy has been demonstrated by its successful application in a formal synthesis of the natural product (+)-FR900482. In addition, an environmentally-friendly approach to the synthesis of amides and lactams has been developed using supercritical carbon dioxide as a 'green' replacement solvent. The amide products are generated from the addition of amines to ketenes, which are formed in situ from the retro-ene reaction of alkynyl ethers.