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Published November 21, 2012 | Supplemental Material + Accepted Version
Journal Article Open

The Reaction Mechanism of the Enantioselective Tsuji Allylation: Inner-Sphere and Outer-Sphere Pathways, Internal Rearrangements, and Asymmetric C–C Bond Formation


We use first principles quantum mechanics (density functional theory) to report a detailed reaction mechanism of the asymmetric Tsuji allylation involving prochiral nucleophiles and nonprochiral allyl fragments, which is consistent with experimental findings. The observed enantioselectivity is best explained with an inner-sphere mechanism involving the formation of a 5-coordinate Pd species that undergoes a ligand rearrangement, which is selective with regard to the prochiral faces of the intermediate enolate. Subsequent reductive elimination generates the product and a Pd^0 complex. The reductive elimination occurs via an unconventional seven-centered transition state that contrasts dramatically with the standard three-centered C–C reductive elimination mechanism. Although limitations in the present theory prevent the conclusive identification of the enantioselective step, we note that three different computational schemes using different levels of theory all find that inner-sphere pathways are lower in energy than outer-sphere pathways. This result qualitatively contrasts with established allylation reaction mechanisms involving prochiral nucleophiles and prochiral allyl fragments. Energetic profiles of all reaction pathways are presented in detail.

Additional Information

© 2012 American Chemical Society. Received: July 19, 2012; published: October 28, 2012. We thank K. Tani, A. Harned, and J. Enquist for experimental collaboration and discussion, and M. Day and L. Henling for crystallography assistance. J.A.K. thanks A. Tkatchenko for discussions and calculations with dispersion-corrected DFT. This research was partly funded by Chevron-Texaco, and the facilities used were funded by grants from ARO−DURIP, ONR-DURIP, IBM-SUR, Fannie and John Hertz Foundation (D.C.B.), and Eli Lilly (J.T.M.) with additional support from NSF (CTS-0608889 and CHE-1214158, W.A.G.) and NIHNIGMS (R01GM080269-01, B.M.S.).

Attached Files

Accepted Version - nihms420064.pdf

Supplemental Material - ja306860n_si_001.pdf

Supplemental Material - ja306860n_si_002.cif


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August 19, 2023
October 20, 2023