N-Arylazetidines: Preparation through Anionic Ring Closure

详细信息    查看全文

• 作者：Pierre Quinodoz ; Bruno Drouillat ; Karen Wright ; Jérôme Marrot ; François Couty
• 刊名：Journal of Organic Chemistry
• 出版年：2016
• 出版时间：April 1, 2016
• 年：2016
• 卷：81
• 期：7
• 页码：2899-2910
• 全文大小：541K
• ISSN：1520-6904

文摘

We report herein an efficient synthesis of diversely substituted N-aryl-2-cyanoazetidines based on an anionic ring-closure reaction. These compounds can be prepared from β-amino alcohols in enantiomerically pure form through a three-step sequence involving (i) copper-catalyzed N-arylation, (ii) N-cyanomethylation of the secondary aniline, and (iii) one-pot mesylation followed by ring closure induced by a base. This high-yielding sequence gives access to azetidines with a predictable and adjustable substitution pattern and also with predictable diastereoselectivity. These compounds are susceptible to multiple further derivatizations through Suzuki coupling or nitrile transformation, thus appearing as valuable new scaffolds for medicinal chemistry. Their rigid shape, featuring an almost planar N-arylamine and a planar four-membered ring, was revealed by both AM1 calculations and X-ray crystallography.