Chirality Matching Induces Molecularity Change and Diastereodivergence in Iridium-Catalyzed Allylation of Propargylic C−H Bonds

We report a combined experimental and computational investigation into the mechanisms of the iridium-catalyzed stereoselective propargylic C−H allylation reaction. In situ NMR, kinetic isotope effects, kinetics studies, stoichiometric experiments, and computational studies shed light on the catalytically active iridium species and the origins of the unusual diastereodivergence observed upon switching from enantiopure to racemic ligand. Specifically, the reaction conducted using enantiopure phosphoramidite ligand proceeds via a monometallic mechanism involving oxidative addition, rate-determining deprotonation of an Ir(III)-π-alkyne intermediate, and stereoselectivity-determining C−C bond formation through a seven-membered, cyclic transition state. By contrast, the use of racemic ligand favors a distinct bimetallic pathway involving the reaction between a nucleophilic iridium-stabilized η2-propargylic anion and an electrophilic iridium π-allyl intermediate. Examples of reactions where a single-catalyst precursor partitions to give distinct catalytic species that react bimolecularly are rare, and the ability to switch between a monometallic and a bimetallic mechanism through a simple change in ligand optical purity remains unknown, to the best of our knowledge. Because the inner-sphere monometallic and outer-sphere bimetallic pathways lead to opposite sense of diastereocontrol, this reaction offers an elegant strategy to achieve diastereodivergent catalysis via tuning of the optical purity of the chiral ligand. These results provide valuable insights into the further design and development of transition metal-catalyzed C−H functionalization reactions as well as stereoselective transformations in general.