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

Abstract

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 /pyridinecatalyzed intramolecular aerobic oxidative amination of alkenes. The data support a stepwise catalytic mechanism that consists of (1) steady-state formation of a Pd II -amidate-alkene chelate with release of one equivalent 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 bondforming step, featuring a pyridine-ligated and a pyridine-dissociated Pd II 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.

Detection of Palladium(I) in Aerobic Oxidation Catalysis

“…Gas uptake kinetics were performed in the same manner as previously reported. [25] [(Z)-4-hexenyltosylamide] = 0.1 M, [DAF/Pd(OAc) 2 ] varied accordingly, 3 mL toluene, p (O 2 ) = 730 Torr. UV-visible experiments were performed in a 1 mm cuvette using a Cary 60 spectrometer.…”

Diazafluorenone-Promoted Oxidation Catalysis: Insights into the Role of Bidentate Ligands in Pd-Catalyzed Aerobic Aza-Wacker Reactions

“…10 Upon finding that a similar catalyst system, Pd(OAc) 2 /py (1:2 ratio), mediates efficient intramolecular oxidative amination of alkenes (eq 2; aza-Wacker reactions), 11 we undertook mechanistic studies of these reactions to gain insight into the ligand effects. 5e,12 In the alcohol oxidation reaction, Pd(OAc) 2 shows no catalytic turnover in the absence of pyridine. The initial catalytic rate maximizes at 1:1 Pd(OAc) 2 /py; however, catalyst decomposition into Pd black limits the total turnover numbers.…”

“…10b Related pyridine effects were observed for the aza-Wacker reaction, with the optimal balance observed with a 1:2 Pd(OAc) 2 /py catalyst system. 12c,13 …”

Synthesis of Vicinal Aminoalcohols by Stereoselective Aza‐Wacker Cyclizations: Access to (−)‐Acosamine by Redox Relay

“…A propyl-substituted alkene produced the oxazolidine 6 e with negligible alkene isomerization. [13] Finally, reaction with a trisubstituted alkene affords a tertiary CÀN bond (6 f); conditions B was more effective than condition A in this reaction.…”