Metal‐Free Catalytic Functionalization of Second −C_sp²−H Bond of 1‐Methyl Pyrrole Using Bishomocubane‐Derived Aminoborane Frustrated Lewis Pairs: A Computational Study

Abstract

Bishomocubane, as a molecular scaffold, has been designed to functionalize the −Csp2−H bond of 1‐methyl pyrrole. The newly designed molecular scaffold showed noteworthy improvements in the reaction energetics than the phenylene scaffold. The DFT (ωB97XD/6‐31+G(d,p)) calculations revealed that the dimethyl amine (A) and piperidine (B) analogues of bishomocubane frustrated Lewis pairs (FLP) can catalyze the first −Csp2−H functionalization much more easily than that of the phenylene FLP. The previous results showed that the second −Csp2−H functionalization was found to be energetically difficult. The DFT calculations suggest that the piperidine analogue of bishomocubane, 1‐Pip‐2‐BH2‐C10H10 (B), can lead the second −Csp2−H functionalization facile than the reported FLPs. The rate‐determining step of the second −Csp2−H functionalization is significantly lower with the catalyst (B) by ∼9.0 kcal/mol compared to the phenylene catalyst (II). The improved reactivity of bishomocubane FLPs has been examined with molecular electrostatic potential (MESP) analysis and the conceptual density functional theory (CDFT) calculations. The hyperconjugative stabilization interaction (n→σ*) and the strain relief between the Lewis pairs play a crucial role in the stability of rate‐determining transition states. This study reveals that saturated hydrocarbon scaffolds are promising candidates as FLP catalysts in such reactions.