Theoretical Investigation on the ClBcat‐Promoted Synthesis of Heterocyclic Boronic Esters

Abstract

AbstractA metal‐free oxyboration reaction, in which no acidic proton is involved and no intermediates bearing B−O σ‐bond were observed, was recently reported by the Blum group. Since it showed potential as a general strategy to synthesize heterocyclic boronic esters, understanding the mechanistic details is very important. Two possible pathways of this oxyboration reaction were examined. Moreover, three key processes were highlighted in the pathway, including borylative cyclization, chloride shift, and demethylation. According to the calculations, the early demethylation (which leads to a formal O−B bond) was found to be slightly exergonic, but to have an inaccessible barrier, whereas demethylation after the cyclization step was feasible. The rate‐determining step (RDS) was identified as the intramolecular cyclization for the oxyboration. Further theoretical investigation on the model reaction, in which an indole boronic ester is the product, revealed some interesting differences of reactivity between oxygen and nitrogen. Based on our calculation results, the N−C bond, which is usually treated as inert, can be cleaved in this case. Moreover, the there is a strong tendency for the RDS to shift from cyclization (as observed in the former oxyboration) to demethylation. Experiments were also conducted to confirm the calculations.