title: Reductive conjugate addition nitro-Mannich route for the stereoselective synthesis of 1,2,3,4-tetrahydroquinoxalines.
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.
authors.affiliation: Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK. j.c.anderson@ucl.ac.uk.
authors.forename: James C
authors.initials: JC
authors.lastname: Anderson
authors.forename: Ian B
authors.initials: IB
authors.lastname: Campbell
authors.forename: Sebastien
authors.initials: S
authors.lastname: Campos
authors.forename: Iain H
authors.initials: IH
authors.lastname: Reid
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Rundell
authors.forename: Jonathan
authors.initials: J
authors.lastname: Shannon
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Tizzard