title: Quaternary Stereogenic Centers through Enantioselective Heck Arylation of Acyclic Olefins with Aryldiazonium Salts: Application in a Concise Synthesis of (R)-Verapamil.
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.
authors.affiliation: Institute of Chemistry, State University of Campinas, Josué de Castro, 10384-612, São Paulo (Brazil).|Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel (Switzerland).
authors.forename: Caio C
authors.initials: CC
authors.lastname: Oliveira
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel (Switzerland). andreas.pfaltz@unibas.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfaltz
authors.affiliation: Institute of Chemistry, State University of Campinas, Josué de Castro, 10384-612, São Paulo (Brazil). roque@iqm.unicamp.br.
authors.forename: Carlos Roque Duarte
authors.initials: CR
authors.lastname: Correia
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003979:Diazonium Compounds / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D012492:Salts / Q000737:chemistry; D013237:Stereoisomerism; D014700:Verapamil / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000475:Alkenes; D003979:Diazonium Compounds; D012492:Salts; D014700:Verapamil
keywords: N,N ligands; enantioselective Heck; palladium; quaternary stereocenters; verapamil