Mechanistic Insights into Carbonyl-Directed Rhodium-Catalyzed Hydroboration: ab Initio Study of a Cyclic γ,δ-Unsaturated Amide

[Image: see text] A two-point binding mechanism for the cationic rhodium(I)-catalyzed carbonyl-directed catalytic asymmetric hydroboration of a cyclic γ,δ-unsaturated amide is investigated using density functional theory. Geometry optimizations and harmonic frequency calculations for the model reaction are carried out using the basis set 6-31+G** for C, O, P, B, N, and H and LANL2DZ for Rh atoms. The Gibbs free energy of each species in THF solvent is obtained based on the single-point energy computed using the PCM model at the ECP28MWB/6-311+G(d,p) level plus the thermal correction to Gibbs free energy by deducting translational entropy contribution. The Rh-catalyzed reaction cycle involves the following sequence of events: (1) chelation of the cyclic γ,δ-unsaturated amide via alkene and carbonyl complexation in a model active catalytic species, [Rh(L2)(2)S(2)](+), (2) oxidative addition of pinacol borane (pinBH), (3) migratory insertion of the alkene double bond into Rh–H (preferred pathway) or Rh–B bond, (4) isomerization of the resulting intermediate, and finally, (5) reductive elimination to form the B–C or H–C bond with regeneration of the catalyst. Free energy profiles for potential pathways leading to the major γ-borylated product are computed and discussed in detail. The potential pathways considered include (1) pathways proceeding via migratory insertion into the Rh–H bond (pathways I, I-1, and I-2), (2) a potential pathway proceeding via migratory insertion into the Rh–B bond (pathway II), and two potential competing routes to a β-borylated byproduct (pathway III). The results find that the Rh–H migratory insertion pathway I-2, followed in sequence by an unanticipated isomerization via amide rotation and reductive elimination, is the most favorable reaction pathway. A secondary consequence of amide rotation is access to a competing β-hydride elimination pathway. The pathways computed in this study are supported by and help explain related experimental results.