Enantioselective synthesis of 1,2,5,6-tetrahydropyridines (THPs) via proline-catalyzed direct Mannich-cyclization/domino oxidation–reduction sequence: application for medicinally important N-heterocycles?

RSC Advances Pub Date: 2016-06-16 DOI: 10.1039/C6RA12965J

Abstract

An enantioselective multi-component synthesis of 1,2,5,6-tetrahydropyridines (THPs) has been developed through a one-pot domino-process. This transformation proceeds through proline-catalyzed direct Mannich reaction-cyclization of glutaraldehyde with in situ generated imines, followed by site-selective oxidation–reduction sequence under mild conditions. Chiral 1,2,5,6-THPs are obtained in good to high yields (up to 80%) and with the excellent enantioselectivity (up to 98?:?2 er). The usefulness of this operationally simple method is also shown to synthesize other medicinally important nitrogen-heterocycles.

Graphical abstract: Enantioselective synthesis of 1,2,5,6-tetrahydropyridines (THPs) via proline-catalyzed direct Mannich-cyclization/domino oxidation–reduction sequence: application for medicinally important N-heterocycles
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