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

Overview

Journal J Org Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2023 Jun 15

PMID 37321182

Authors

Diana Rachii

Dana J Caldwell

Yui Kosukegawa

Mary Sexton

Paul R Rablen

William P Malachowski

Affiliations

Soon will be listed here.

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 Quinox-type bidentate ligand (). 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.

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