We present a mechanistic survey on the LCu-catalyzed (L = chiral 2,2′-bipyridine ligand) enantioselective boron conjugate addition reaction, carried out using density functional theory (DFT) and artificial force induced reaction (AFIR) methods. The computed catalytic cycle for Cu(I)- and Cu(II)-based catalysts consists of three steps: (a) boron-boron bond cleavage of B2(pin)2, (b) boron conjugate addition on the β carbon of chalcone, and (c) protonation. The enantioselectivity of the reaction with LCuI or LCuII catalysts is solely governed at the boron conjugate addition step. The multicomponent (MC)-AFIR search and the subsequent DFT calculations for the LCuI catalyst determined transition states (TSs), which lead to CuI-O-enolate and CuI-C-enolate, and both equally contribute to the C-B bond formation with no enantioselectivity. On the other hand, a MC-AFIR search and the subsequent DFT calculations for the analogous LCuII catalyst showed that only the transition state (TS) leading to CuII-O-enolate contributes to the reaction. Furthermore, the TSs leading to the R and S forms of CuII-O-enolates are energetically well separated, with the R form being of lower energy, which is consistent with experimental observations. Our study provides important mechanistic insights for designing transition-metal catalysts for Cu-catalyzed enantioselective boron conjugate addition reactions.
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