Mechanistic Investigations of the Pd(0)-Catalyzed Enantioselective 1,1-Diarylation of Benzyl Acrylates

A mechanistic study of the Pd-catalyzed
enantioselective 1,1-diarylation
of benzyl acrylates that is facilitated by a chiral anion phase transfer
(CAPT) process is presented. Kinetic analysis, labeling, competition,
and nonlinear effect experiments confirm the hypothesized general
mechanism and reveal the role of the phosphate counterion in the CAPT
catalysis. The phosphate was found to be involved in the phase transfer
step and in the stereoinduction process, as expected, but also in
the unproductive reaction that provides the traditional Heck byproduct.
Multivariate correlations revealed the CAPT catalyst’s structural
features, affecting the production of this undesired byproduct, as
well as weak interactions responsible for enantioselectivity. Such
putative interactions include π-stacking and a CH···O
electrostatic attraction between the substrate benzyl moiety and the
phosphate. Analysis of the computed density functional theory transition
structures for the stereodetermining step of the reaction supports
the multivariate model obtained. The presented work provides the first
comprehensive study of the combined use of CAPT and transition metal
catalysis, setting the foundation for future applications.