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

• Record Type: Journal Article
• Authors: Oliveira, Caio C.; Pfaltz, Andreas; Correia, Carlos Roque Duarte
• Is Part Of: Angewandte Chemie. Volume 127:Number 47(2015)
• Page Start: 14242
• Page End: 14245
• Publication Date: 2015-09-25
• Subjects: Heck‐Reaktion -- N, N‐Liganden -- Palladium -- Quartäre Stereozentren -- Verapamil; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201507927
• Languages: English
• ISSNs: 0044-8249

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 : Maßgeschneiderte chirale N, N‐Liganden und Aryldiazoniumsalze ermöglichen die enantioselektive Einführung ausschließlich kohlenstoffsubstituierter quartärer Stereozentren durch eine Heck‐Reacktion mit acyclischen Olefinen. Die Methode führt zu komplexen Molekülgerüsten, was eine kurze Totalsynthese von ( R )‐Verapamil belegt.