A Synthetic Route to Highly Substituted 1-Aminonaphthalenes from Readily Available Benzaldehydes

J Org Chem. 2024 Jan 19;89(2):1310-1314. doi: 10.1021/acs.joc.3c02324. Epub 2024 Jan 3.

Abstract

We report an efficient route for the synthesis of highly substituted 1-aminonaphthalenes from benzaldehydes. The method employs a stereoselective Still-Gennari modification of the Horner-Wadsworth-Emmons olefination to afford (E)-benzylidenesuccinonitrile precursors, which undergo Bronsted acid mediated benzannulation to afford 1-aminonaphthalene derivatives in 35-95% yield. The abundance of commercially available benzaldehydes, coupled with the simplicity of our method, enables many previously unexplored naphthalene substitution patterns to become readily accessible.