Construction of Fused BN-Heterocycles via Boron Atom Insertion: DFT Insights into the Lewis Acid-Base (BBr3/NEt3) Cooperative Mechanism and Selectivity

Abstract

The BBr3-mediated N-heterocycle editing reaction through boron atom insertion strategy reported by Song et al. (Angew. Chem., Int. Ed. 2024, 63, e202318613), has been systematically explored by density functional theory (DFT) calculations. The present results reveal that, in addition to BBr3 acting as a boron source and nucleophile, the Lewis base NEt3 also plays a crucial role. Specifically, the Lewis acid-base cooperative interaction between BBr3 and NEt3 facilitates the ring-opening of the substrate 1-(2-vinylphenyl) azetidine, the rate-determining step of the overall cascade reaction. Notably, the organic base NEt3 facilitates the formation of the real nucleophilic species BBr4⁻, thereby promoting the progression of the reaction. Furthermore, the formation of an exceptionally stable C4NB π-ring intermediate and the difference in distortion and exchange-repulsion energies, caused by substrate structural characteristics, are responsible for chemoselectivity and regioselectivity of substrates bearing typical structural motifs and functional groups, respectively. These computational findings not only provide profound mechanistic insights into the tandem reactions involved in the construction of fused BN‐heterocycles, but also elucidate the underlying factors governing substrate preference.