Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)-Verapamil

Author(s)

Oliveira, Caio C. ^{[1, 2]} ; Pfaltz, Andreas ^[1] ; Duarte Correia, Carlos Roque ^[2]

Affiliation

^[1] Univ Basel, Dept Chem, CH-4056 Basel - Switzerland

^[2] Univ Estadual Campinas, Inst Chem, BR-10384612 Sao Paulo - Brazil

• Document type: Journal article
• Source: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION; v. 54, n. 47, p. 14036-14039, NOV 16 2015.
• Web of Science Citations: 39

Abstract

We describe herein a highly regio- and enantioselective Pd-catalyzed Heck arylation of unactivated trisubstituted acyclic olefins to provide all-carbon quaternary stereogenic centers. Chiral N,N ligands of the pyrimidine-and pyrazino-oxazoline class were developed for that purpose, providing the desired products in good to high yields with enantiomeric ratios up to > 99:1. Both linear and branched substituents on the olefins were well-tolerated. The potential of this new method is demonstrated by the straightforward synthesis of several O-methyl lactols and lactones containing quaternary stereocenters, together with a concise enantioselective total synthesis of the calcium channel blocker verapamil. (AU)

• FAPESP's process: 14/00588-0 - Regio and enantioselective Heck-Matsuda reaction with allylic alcohols using non symmetrical ligands
• Grantee: Caio Costa Oliveira
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC