Direct N-Cyclopropylation of Cyclic Amides and Azoles Employing a Cyclopropylbismuth Reagent

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• 作者：Alexandre Gagnon ; Miguel St-Onge ; Kelly Little ; Martin Duplessis ; Francis Barabé
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：January 10, 2007
• 年：2007
• 卷：129
• 期：1
• 页码：44 - 45
• 全文大小：51K
• 年卷期：v.129,no.1(January 10, 2007)
• ISSN：1520-5126

文摘

Cyclopropanes are commonly found in medicinal chemistry since they provide unique spatial and electronic features, combined with high metabolic stability in liver microsomes. Although many methods are found in the chemist's arsenal to connect a cyclopropyl group to a carbon atom, none exist that perform the direct transfer of this useful fragment onto the nitrogen of a heterocycle or an amide. Considering the importance of nitrogenated compounds in the pharmaceutical industry, we sought to develop an expedient method to N-cyclopropylate azoles and amides. We report herein the direct cyclopropyl transfer reaction onto cyclic amides, isatins, oxindoles, imides, and carbamates employing a nonpyrophoric cyclopropylbismuth reagent. The reaction is catalyzed by copper acetate and proceeds smoothly in dichloromethane at 50 C in the presence of pyridine. The N-cyclopropylation reaction can also be applied to the preparation of N-cyclopropyl indoles, benzimidazoles, pyrroles, and pyrazoles.