The Inner-Sphere Process in the Enantioselective Tsuji Allylation Reaction with (S)-t-Bu-phosphinooxazoline Ligands
John A. Keith, Douglas C. Behenna, Justin T. Mohr, Sandy Ma, Smaranda C. Marinescu, Jonas Oxgaard, Brian M. Stoltz, William A. Goddard III
Abstract
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 Pd^0 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.
Group Members
Keith, J. A., Behenna, D. C., Mohr, J. T., Ma, S., Marinescu, S. C., Oxgaard, J., Stoltz, B. M., & III, W. A. G. (2007). The Inner-Sphere Process in the Enantioselective Tsuji Allylation Reaction with (S)-t-Bu-phosphinooxazoline Ligands. *J. Am. Chem. Soc.*, *129*(39), 11876-11877. https://doi.org/10.1021/ja070516j