Title: Brønsted Acid Catalyzed Dearomatization by Intramolecular Hydroalkoxylation/Claisen Rearrangement: Diastereo- and Enantioselective Synthesis of Spirolactams

Authors: Longwu Ye*, Peng-Fei Chen, Bo Zhou, Peng Wu, Binju Wang

Abstract: Described herein is a novel Brønsted acid-catalyzed intramolecular hydroalkoxylation/Claisen rearrangement, allowing practical and atom-economical synthesis of a range of valuable spiro lactams from readily available ynamides in generally good to excellent yields with excellent diastereoselectivities and broad substrate scope. Importantly, an unexpected dearomatization of nonactivated arenes and heteroaromatic compounds is involved in this tandem sequence. Moreover, the asymmetric version of this tandem cyclization is also achieved via efficient kinetic resolution by chiral phosphoric acid catalysis. In addition, [3,3]-rearrangement is proved to be kinetically preferred over the related [1,3]-rearrangement by theoretical calculations.

Full-Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202113464