The Inner-Sphere Process in the Enantioselective Tsuji Allylation Reaction with (<i>S</i>)-<i>t</i>-Bu-phosphinooxazoline Ligands

We propose an inner-sphere mechanism explaining the unique performance of the Tsuji asymmetrical allylation reaction using hard prochiral enolate nucleophiles and non-prochiral allyl groups. Using first principles quantum mechanics (B3LYP density functional theory), we find that the pathway for this reaction involves nucleophilic attack followed by interconversion from a five-coordinate Pd complex to a four-coordinate complex. This intermediate is trapped in a potential well and escapes via reductive elimination that proceeds through a seven-membered transition state to generate the product and a Pd0 complex. This seven-membered transition state contrasts dramatically from the usual three-centered C−C reductive elimination paradigm generally associated with C−C coupling reactions. This inner-sphere asymmetric allylation pathway involving hard enolates is energetically more favorable than outer-sphere nucleophilic attack, a process understood to occur in asymmetric allylic alkylations with soft enolates.