Mechanistic insights into neosilyllithium-catalyzed hydroboration of nitriles, aldehydes, and esters: a DLPNO-CCSD(T) study.

Over the past few years, alkali and alkaline earth metals have emerged as alternative catalysts to transition metal organometallics to catalyze the hydroboration of unsaturated compounds. A highly selective and cost-effective lithium-catalyzed method for the synthesis of an organoborane has been established based on the addition of a B-H bond to an unsaturated bond (polarized or unpolarized) using pinacolborane (HBPin). In the present work, the neosilyllithium-catalyzed hydroboration of nitriles, aldehydes, and esters has been investigated using high-level DLPNO-CCSD(T) calculations to unravel the mechanistic pathways and substrate-dependent reactivity. Using non-covalent interaction (NCI) analysis, intrinsic bond orbital (IBO) analysis, and activation strain analysis (ASA), we thoroughly analyzed the nature of key intermediates and transition states. The DLPNO-CCSD(T) study reveals that the initial interaction between neosilyllithium and pinacolborane forms a stable zwitterionic intermediate, which polarizes the B-H bond and enables efficient hydride transfer. Specifically, the hydroboration of nitriles involves two sequential hydride transfers, where the first reduction of nitrile to imine occurs via a six-membered transition state, with a huge free energy barrier of ∼15 kcal mol^-1, while the second step with imine-to-amine reduction proceeds with a tiny barrier of ∼3.1 kcal mol^-1. ASA analysis of the transition state suggests that the linear geometry of the nitrile group incurs a significant distortion penalty compared to the pre-bent imine geometry, making the second hydride transfer much facile in nature. The hydroboration aldehydes require a moderate free energy barrier for the hydride transfer (∼8.3 kcal mol^-1), and the desired products are thermodynamically stable. On the other hand, for esters, the computed Gibbs free energy profile displays a notably higher activation barrier (∼17.5 kcal mol^-1), compared to aldehydes, which agrees with experimental observations that the hydroboration of esters is more challenging. A significant steric hindrance surrounding the ester functional group has been demonstrated to markedly augment the strain energy during the hydride transfer step, engendering a higher activation energy barrier for esters compared to aldehydes. Our findings suggest an interplay of steric and electronic factors in dictating substrate reactivity and the dual role of HBPin as both a hydride donor and a functional group acceptor in the neosilyllithium-catalysed hydroboration reaction.