title: N-Arylazetidines: Preparation through Anionic Ring Closure.
abstract: 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.
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180. Université de Versailles St-Quentin-en-Yvelines, Université Paris Saclay , 45, Avenue des Etats-Unis, Versailles 78035 Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Quinodoz
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180. Université de Versailles St-Quentin-en-Yvelines, Université Paris Saclay , 45, Avenue des Etats-Unis, Versailles 78035 Cedex, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Drouillat
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180. Université de Versailles St-Quentin-en-Yvelines, Université Paris Saclay , 45, Avenue des Etats-Unis, Versailles 78035 Cedex, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Wright
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180. Université de Versailles St-Quentin-en-Yvelines, Université Paris Saclay , 45, Avenue des Etats-Unis, Versailles 78035 Cedex, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Marrot
authors.affiliation: Institut Lavoisier de Versailles, UMR 8180. Université de Versailles St-Quentin-en-Yvelines, Université Paris Saclay , 45, Avenue des Etats-Unis, Versailles 78035 Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Couty