Striking AcOH Acceleration in Direct Intramolecular Allylic Amination Reactions

An experiment was conducted to demonstrate that a strong accelerating effect occurs in direct intramolecular allylic amination when the reaction is conducted in AcOH rather than in CHCl or THF. A round bottom flask under air was charged with N-tosylcarbamate 3a-j, Pd(OAc)2, bis-sulfoxide ligand LL, phenylbenzoquinone and AcOH. The reaction was allowed to stir at 45°C for 24 h. The reaction mixture was hydrolysed and extracted with AcOEt. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Cyclisation of 3a was repeated in CH2Cl 2 and in AcOH by using stoichiometric amounts of Pd(OAc) without benzoquinone. Stoichiometric tests and computational DFT analysis of the palladium reoxidation step provide an overview of the structural and energetic role of acetic acid in increasing the efficacy of the entire catalytic cycle.