A two-step Kinugasa/Conia-ene-type sequential reaction for the asymmetric synthesis of 8-methylene-2,6-diazaspiro[3.4]octane-1,5-diones

Abstract

2,6-Diazaspiro[3.4]octane-1,3-dione, integrating β-lactam and γ-lactam into one structure, is an important skeleton found in many bioactive molecules. This article describes a simple and practical synthesis of 8-methylene-2,6-diazaspiro[3.4]octane-1,5-diones from N-(prop-2-yn-1-yl)propiolamides and nitrones. The method proceeds via a two-step sequential process: a Kinugasa reaction, followed by a Conia-ene-type cyclization. The transformation afforded 8-methylene-2,6-diazaspiro[3.4]octane-1,5-diones in satisfactory yields and high diastereo- and enantioselectivity.