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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.,
Pfaltz Andreas,
Correia Carlos Roque Duarte
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201507927
Subject(s) - stereocenter , enantioselective synthesis , chemistry , oxazoline , enantiomer , stereochemistry , combinatorial chemistry , catalysis , organic chemistry
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.