Highly Enantioselective Catalytic Alkynylation of Quinolones: Substrate Scope, Mechanistic Studies, and Applications in the Syntheses of Chiral N-Heterocyclic Alkaloids and Diamines

Yong Guan; Tadas A Buivydas; Remy F Lalisse; Kalen B Laybourn; Charlotte Stern; Margaret Richins; Sean M Burns; Arielle Shelby; Christopher M Hadad; Anita E Mattson

doi:10.1021/acscatal.3c01536

Highly Enantioselective Catalytic Alkynylation of Quinolones: Substrate Scope, Mechanistic Studies, and Applications in the Syntheses of Chiral N-Heterocyclic Alkaloids and Diamines

ACS Catal. 2023 May 23;13(11):7661-7668. doi: 10.1021/acscatal.3c01536. eCollection 2023 Jun 2.

Affiliations

¹ Department of Chemistry and Biochemistry, Worcester Polytechnic Institute, 60 Prescott Street, Worcester, Massachusetts 01609, United States.
² Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.
³ Integrated Molecular Structure Education and Research Center, Northwestern University, Evanston, Illinois 60208, United States.
⁴ Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.

Abstract

The alkynylation of 4-siloxyquinolinium triflates has been achieved under the influence of copper bis(oxazoline) catalysis. The identification of the optimal bis(oxazoline) ligand was informed through a computational approach that enabled the dihydroquinoline products to be produced with up to 96% enantiomeric excess. The conversions of the dihydroquinoline products to biologically relevant and diverse targets are reported.