Catalytic Enantioselective Synthesis of N-C Axially Chiral Mebroqualone and Its Derivatives through Reductive Asymmetric Desymmetrization

Motohiro Hirai; Shumpei Terada; Hiroaki Yoshida; Kenki Ebine; Tomoaki Hirata; Osamu Kitagawa

doi:10.1021/acs.orglett.6b02865

Catalytic Enantioselective Synthesis of N-C Axially Chiral Mebroqualone and Its Derivatives through Reductive Asymmetric Desymmetrization

Org Lett. 2016 Nov 4;18(21):5700-5703. doi: 10.1021/acs.orglett.6b02865. Epub 2016 Oct 26.

Authors

Motohiro Hirai¹, Shumpei Terada¹, Hiroaki Yoshida¹, Kenki Ebine¹, Tomoaki Hirata¹, Osamu Kitagawa¹

Affiliation

¹ Department of Applied Chemistry, Shibaura Institute of Technology , 3-7-5 Toyosu, Kohto-ku, Tokyo 135-8548, Japan.

PMID: 27783530
DOI: 10.1021/acs.orglett.6b02865

Abstract

In the presence of (R)-DTBM-SEGPHOS-Pd(OAc)₂ catalyst, treatment of various 3-(2,6-dibromophenyl)quinazolin-4-ones with NaBH₄ gave optically active N-C axially chiral quinazolinone (mebroqualone) derivatives through reductive asymmetric desymmetrization (enantioselective monohydrodebromination) followed by kinetic resolution of the resulting monobromophenyl products (up to 99% ee). The enantioselectivity strongly depended on the substituent (R²) at the C4'position, amount of NaBH₄, and reaction temperature.

Publication types

Research Support, Non-U.S. Gov't