Mechanistic elucidation of the uncatalyzed allylation of carbonyl compounds: a combined DFT and nudged elastic band study.

The uncatalyzed allylation of carbonyl compounds is a significant challenge in synthetic organic chemistry because of the high activation barriers often associated with non-activated substrates. This study examines the allylation of carbonyl compounds mediated by allylboronic acid to elucidate the distinct reactivity patterns observed in aldehydes and ketones. Model substrates such as methanal, propanone, and p-nitrobenzaldehyde were used to explore the full reaction pathways and related transition states. All reactions were exergonic, with activation barriers decreasing in the order propanone (35.5 kcal·mol-1) > methanal (23.9 kcal·mol-1) > p-nitrobenzaldehyde (20.8 kcal·mol-1), confirming that aldehydes are more reactive than ketones. NEB profiles indicate concerted but asynchronous pathways involving C-C bond formation, C-B cleavage, and proton transfer. ETS-NOCV/EDA-NOCV analysis revealed distinct electronic profiles at the transition state: methanal follows a concerted addition pathway primarily driven by σ-bond covalency, propanone proceeds via a dissociative-associative mechanism dominated by electrostatic interactions and Pauli repulsion, and p-nitrobenzaldehyde exhibits a cooperative multi-channel mechanism involving simultaneous C-C bond formation, proton transfer, and accompanying electron density redistribution within the conjugated framework. These findings clarify the electronic factors underlying the differing reactivity patterns of aldehydes and ketones in uncatalyzed allylation. All calculations were carried out using the ORCA 6.1.0 software package. The reaction pathways and transition states were studied with density functional theory (DFT) and the climbing-image nudged elastic band (CI-NEB) method. Geometry optimizations, frequency analyses, electronic structure evaluations, and NEB calculations were carried out at the ωB97X-V/def2-TZVP level of theory. Bulk solvent effects were accounted for using the SMD implicit-solvent model with water as the solvent. Single-point energy refinements were performed at the DLPNO-CCSD(T)-F12/cc-pVTZ-F12-CABS level. The chemical nature of the transition states was further analyzed using the ETS-NOCV/EDA-NOCV scheme to decompose the total interaction energy into electrostatic, Pauli repulsion, orbital, and dispersion components.