Mechanistic Studies of Wacker-Type Intramolecular Aerobic Oxidative Amination of Alkenes Catalyzed by Pd(OAc)2/Pyridine

• Published in: Journal of organic chemistry Vol. 76; no. 4; pp. 1031 - 1044
• Main Authors: Ye, Xuan, Liu, Guosheng, Popp, Brian V, Stahl, Shannon S
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 18.02.2011
• Subjects: Alkenes - chemistry; Amination; Catalysis; Catalysts: preparations and properties; Chemistry; Exact sciences and technology; General and physical chemistry; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Kinetics and mechanisms; Ligands; Molecular Structure; Organic chemistry; Organometallic Compounds - chemistry; Oxidation-Reduction; Palladium - chemistry; Preparations and properties; Pyridines - chemistry; Reactivity and mechanisms; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Bond length; Nitrogen heterocycle; Ligand; Hydrides; Pyrrolidine derivatives; Chemical reduction; Alkene; Amination; Wacker Oxidation; Reaction mechanism; Palladium II Acetate; Intramolecular reaction; Catalytic reaction; Theoretical study; Stepwise mechanism; Aerobe; Acetic acid derivative; Experimental study; Steady state; Pyridine; Cyclization; Transition state; Density functional method; Chelates; Catalyst; Ethylenic compound; Nucleophile
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/jo102338a

Wacker-type oxidative cyclization reactions have been the subject of extensive research for several decades, but few systematic mechanistic studies of these reactions have been reported. The present study features experimental and DFT computational studies of Pd(OAc)2/pyridine-catalyzed intramolecular aerobic oxidative amination of alkenes. The data support a stepwise catalytic mechanism that consists of (1) steady-state formation of a PdII-amidate−alkene chelate with release of 1 equiv of pyridine and AcOH from the catalyst center, (2) alkene insertion into a Pd−N bond, (3) reversible β-hydride elimination, (4) irreversible reductive elimination of AcOH, and (5) aerobic oxidation of palladium(0) to regenerate the active trans-Pd(OAc)2(py)2 catalyst. Evidence is obtained for two energetically viable pathways for the key C−N bond-forming step, featuring a pyridine-ligated and a pyridine-dissociated PdII species. Analysis of natural charges and bond lengths of the alkene-insertion transition state suggest that this reaction is best described as an intramolecular nucleophilic attack of the amidate ligand on the coordinated alkene.