Origin of Stereodivergence in Cooperative Asymmetric Catalysis with Simultaneous Involvement of Two Chiral Catalysts

Accomplishing high diastereo- and enantioselectivities simultaneously is a persistent challenge in asymmetric catalysis. The use of two chiral catalysts in one-pot conditions might offer new avenues to this end. Chirality transfer from a catalyst to product gets increasingly complex due to potential chiral match-mismatch issues. The origin of high enantio- and diastereoselectivities in the reaction between a racemic aldehyde and an allyl alcohol, catalyzed by using axially chiral iridium phosphoramidites PR/S–Ir and cinchona amine is established through transition-state modeling. The multipoint contact analysis of the stereocontrolling transition state revealed how the stereodivergence could be achieved by inverting the configuration of the chiral catalysts that are involved in the activation of the reacting partners. While the enantiocontrol is identified as being decided in the generation of PR/S–Ir−π-allyl intermediate from the allyl alcohol, the diastereocontrol arises due to the differential stabilizations in the C–C bond formation transition states. The analysis of the weak interactions in the transition states responsible for chiral induction revealed that the geometric disposition of the quinoline ring at the C8 chiral carbon of cinchona–enamine plays an anchoring role. The quinolone ring is noted as participating in a π-stacking interaction with the phenyl ring of the Ir−π-allyl moiety in the case of PR with the (8R,9R)-cinchona catalyst combination, whereas a series of C–H···π interactions is identified as vital to the relative stabilization of the stereocontrolling transition states when PR is used with (8S,9S)-cinchona.