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

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)2S2]+, (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.