Nucleophilic Dearomatization of Pyridines under Enamine Catalysis: Regio-, Diastereo-, and Enantioselective Addition of Aldehydes to Activated N-Alkylpyridinium Salts

Org Lett. 2017 Feb 17;19(4):834-837. doi: 10.1021/acs.orglett.6b03824. Epub 2017 Jan 27.

Abstract

Catalytic addition of chiral enamines to azinium salts is a powerful tool for the synthesis of enantioenriched heterocycles. An unprecedented asymmetric dearomative addition of aldehydes to activated N-alkylpyridinium salts is presented. The process exhibits complete C-4 regioselectivity along with high levels of diastereo- and enantiocontrol, achieving a high-yielding synthesis of a broad range of optically active 1,4-dihydropyridines. Moreover, the presented methodology enables the synthesis of functionalized octahydropyrrolo[2,3-c]pyridines, the core structure of anticancer peptidomimetics.

Publication types

  • Research Support, Non-U.S. Gov't