Expanding Stereoelectronic Limits of <i>endo</i>-<i>tet</i> Cyclizations: Synthesis of Benz[<i>b</i>]azepines from Donor–Acceptor Cyclopropanes

Abstract

The importance of intramolecular constraints in cyclic transition-state geometries is especially pronounced in <i>n</i>-<i>endo</i>-<i>tet</i> cyclizations, where the usual backside approach of a nucleophile to the breaking bond is impossible for the rings containing less than eight atoms. Herein, we expand the limits of <i>endo</i>-<i>tet</i> cyclizations and show that donor-acceptor cyclopropanes can provide a seven-membered ring via a genuine 6-<i>endo</i>-<i>tet</i> process. Substrates containing a <i>N</i>-alkyl-<i>N</i>-arylcarbamoyl moiety as an acceptor group undergo Lewis acid-induced cyclization to form tetrahydrobenz[<i>b</i>]azepin-2-ones in high yields. The reaction proceeds with the inversion of the configuration at the electrophilic carbon. In this process, a formally six-membered transition state yields a seven-membered ring as the pre-existing cycle is merged into the forming ring. The stereochemistry of the products can be controlled by the reaction time and by the nature of Lewis acid, opening access to both diastereomers by tuning of the reaction conditions.