Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)‐Verapamil. Issue 47 (25th September 2015)

• Record Type: Journal Article
• Authors: Oliveira, Caio C.; Pfaltz, Andreas; Correia, Carlos Roque Duarte
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 47(2015)
• Page Start: 14036
• Page End: 14039
• Publication Date: 2015-09-25
• Subjects: enantioselective Heck -- N, N ligands -- palladium -- quaternary stereocenters -- verapamil; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201507927
• Languages: English
• ISSNs: 1433-7851

Abstract

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. Abstract : The combination of designed chiral N, N‐based ligands and aryldiazonium salts allowed the enantioselective construction of all‐carbon quaternary stereocenters through a Heck reaction with acyclic olefins. The molecular complexity provided by this new method enabled a concise total synthesis of ( R )‐verapamil.