The Chelate Effect Rationalizes Observed Rate Acceleration and Enantioselectivity in BINOL-Catalyzed Petasis Reactions

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Density Functional Theory calculations afforded insight into the origin of the reaction rate acceleration (≥500 fold) and enantioselectivity (≥99% ee) of BINOL-catalyzed three-component Petasis reactions observed experimentally. BINOL accelerates the rate determining step by forming a B(IV) chelate, which involves the loss of water from the hemiaminal moiety to generate an iminium cation. Subsequent vinyl group transfer from B(IV) to the iminium carbon affords the enantiomerically enriched product and a cyclic trigonal B(III)BINOL complex, which rapidly releases the BINOL allowing it to re-enter the catalytic cycle. In the transition state of the vinyl transfer step, C-H---O hydrogen bonding between the iminium C-H and O of (R)-BINOL directs the vinyl group addition to the Re-face of the iminium carbon. This mechanism explains both the rate acceleration and high enantioselectivity of the stereo determining step.

Keywords: BINOL; Chelate effect; DFT; Petasis reaction; enantioselectivity.