title: Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams.
abstract: The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures.
authors.affiliation: The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering and The Caltech Center for Catalysis and Chemical Synthesis, California Institute of Technology, Pasadena, California                 91125, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Behenna
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Liu
authors.forename: Taiga
authors.initials: T
authors.lastname: Yurino
authors.forename: Jimin
authors.initials: J
authors.lastname: Kim
authors.forename: David E
authors.initials: DE
authors.lastname: White
authors.forename: Scott C
authors.initials: SC
authors.lastname: Virgil
authors.forename: Brian M
authors.initials: BM
authors.lastname: Stoltz
mesh_terms: D000478:Alkylation; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D002264:Carboxylic Acids; D006571:Heterocyclic Compounds; D007769:Lactams; D010165:Palladium