Professor of Chemistry Bill Malachowski and Alums Co-Author Article, June 2023

Ni-Catalyzed Enantioselective Intramolecular Mizoroki–Heck Reaction for the Synthesis of Phenanthridinone Derivatives

Authors: Diana Rachii, M.A. '21, Dana J. Caldwell '22, Yui Kosukegawa '23, Mary Sexton, M.A. '17, Ph.D. '21, Paul R. Rablen, and William P. Malachowski

Source: Journal of Organic Chemistry, Volume: 88, Issue: 13, Pages: 8203-8226, DOI: 10.1021/acs.joc.3c00202, June 2023

Publication Type: Article in a Periodical

Abstract: A Ni-catalyzed enantioselective intramolecular Mizoroki–Heck reaction has been developed to transform symmetrical 1,4-cyclohexadienes with attached aryl halides into phenanthridinone analogues containing quaternary stereocenters. Herein, we report important advances in reaction optimization enabling control of unwanted proto-dehalogenation and alkene reduction side products. Moreover, this approach provides direct access to six-membered ring heterocyclic systems bearing all-carbon quaternary stereocenters, which have been much more challenging to form enantioselectively with nickel-catalyzed Heck reactions. A wide range of substrates were demonstrated to work in good to excellent yields. Good enantioselectivity was demonstrated using a new synthesized chiral iQuinox-type bidentate ligand (L27). The sustainability, low price of nickel catalysts, and significantly faster reaction rate (1 h) versus that of a recently reported palladium-catalyzed reaction (20 h) make this process an attractive alternative.