Facile Synthesis of N-Substituted Amides from Alkenes and Amides by a Brønsted Acid Mediated Electrophilic Addition Reaction

Abstract

A facile and widely applicable method for the synthesis of N-substituted amides from alkenes and amides using Brønsted acids was developed. Treatment of various alkenes with amides and an alkali metal halide or methanesulfonic acid in trifluoroacetic acid afforded the corresponding N-substituted amides in good to high yield. The reaction proceeds via the direct electrophilic addition of the amides to the alkenes. Various functional groups such as ester, ether, imide, amide, and halogen were tolerated under the reaction conditions. High substrate-dependent cis stereoselectivity in the synthesis was also observed for methylenecyclohexane and methylcyclohexene derivatives possessing a substituent at the 4-position. Furthermore, a practical application of this reaction has been demonstrated by the synthesis of an intermediate of a bioactive compound on a large scale.

Key words

alkenes - amides - electrophilic addition - Brønsted acids­ - alkali metal halides

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