2.

(A) Structures of reagents employed by Houk and co-workers for computational analysis of Denton’s catalytic Mitsunobu reaction. (B) Simplified scale diagram of the computational energy surface for the catalytic Mitsunobu reaction described by Houk and co-workers. Energies for all species and transition states are quoted in kcal mol^–1. Where no computational barrier is provided, the process is assumed to be very fast, and an arbitrary barrier of 0.1 kcal mol^–1 has been assumed for the forward process, and is indicated with an asterisk (*). (C) Reaction scheme showing the equilibria involved in the catalytic cycle, the uncatalyzed reaction, and the physical removal of water, that together describe the catalytic Mitsunobu reaction. The rate constants for the forward (k _n) and backward (k _–n) processes can be approximated from the calculated energy levels using the Eyring equation (see Supporting Information Section S2 for details).