Reductive conjugate addition nitro-Mannich route for the stereoselective synthesis of 1,2,3,4-tetrahydroquinoxalines?

Organic & Biomolecular Chemistry Pub Date: 2016-08-10 DOI: 10.1039/C6OB01530A

Abstract

A concise, high yielding and structurally divergent synthesis of complex 1,2,3,4-tetrahydroquinoxalines with excellent diastereoselectivity is described. A wide array of nitroalkenes and imines derived from commercially available aromatic aldehydes and 2-chloroanalines were subjected to a key reductive conjugate addition nitro-Mannich reaction to give diastereomerically pure β-nitro amines. Sequential reduction of the nitro function followed by Pd-catalyzed intramolecular N-arylation of the resultant primary amine onto the 2-chloroanailine gives highly substituted 1,2,3,4-tetrahydroquinoxalines. Non basic imines were found to participate better in the nitro-Mannich reaction if the stronger acid methanesulfonic acid was used to promote the reaction. The 3 step reaction sequence should be useful for the array synthesis of drug like scaffolds.

Graphical abstract: Reductive conjugate addition nitro-Mannich route for the stereoselective synthesis of 1,2,3,4-tetrahydroquinoxalines
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