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

Manuel Orlandi, Margaret J. Hilton, Eiji Yamamoto, F. Dean Toste, Matthew S. Sigman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)12688-12695
Number of pages8
JournalJournal of the American Chemical Society
Volume139
Issue number36
DOIs
Publication statusPublished - Sep 13 2017

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Acrylates
Anions
Negative ions
Phosphates
Catalysis
Byproducts
Enantioselectivity
Phase Transition
Static Electricity
Labeling
Transition metals
Density functional theory
Electrostatics
Metals
Catalysts
Kinetics
Substrates
Experiments

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Mechanistic Investigations of the Pd(0)-Catalyzed Enantioselective 1,1-Diarylation of Benzyl Acrylates. / Orlandi, Manuel; Hilton, Margaret J.; Yamamoto, Eiji; Toste, F. Dean; Sigman, Matthew S.

In: Journal of the American Chemical Society, Vol. 139, No. 36, 13.09.2017, p. 12688-12695.

Research output: Contribution to journalArticle

Orlandi, Manuel ; Hilton, Margaret J. ; Yamamoto, Eiji ; Toste, F. Dean ; Sigman, Matthew S. / Mechanistic Investigations of the Pd(0)-Catalyzed Enantioselective 1,1-Diarylation of Benzyl Acrylates. In: Journal of the American Chemical Society. 2017 ; Vol. 139, No. 36. pp. 12688-12695.
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