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 language | English |
|---|---|
| Pages (from-to) | 12688-12695 |
| Number of pages | 8 |
| Journal | Journal of the American Chemical Society |
| Volume | 139 |
| Issue number | 36 |
| DOIs | |
| Publication status | Published - Sep 13 2017 |
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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 journal › Article
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TY - JOUR
T1 - Mechanistic Investigations of the Pd(0)-Catalyzed Enantioselective 1,1-Diarylation of Benzyl Acrylates
AU - Orlandi, Manuel
AU - Hilton, Margaret J.
AU - Yamamoto, Eiji
AU - Toste, F. Dean
AU - Sigman, Matthew S.
PY - 2017/9/13
Y1 - 2017/9/13
N2 - 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.
AB - 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.
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U2 - 10.1021/jacs.7b06917
DO - 10.1021/jacs.7b06917
M3 - Article
VL - 139
SP - 12688
EP - 12695
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 36
ER -