Diboron(4)-Catalyzed Remote [3+2] Cycloaddition of Cyclopropanes via Dearomative/Rearomative Radical Transmission through Pyridine

Ring structures such as pyridine, cyclopentane or their combinations are important motifs in bioactive molecules. In contrast to previous cycloaddition reactions that necessitated a directly bonded initiating functional group, this work demonstrated a novel through-(hetero)arene radical transmission concept for selective activation of a remote bond. An efficient, metal-free and atom-economical [3+2] cycloaddition between 4-pyridinyl cyclopropanes and alkenes or alkynes has been developed for modular synthesis of pyridine-substituted cyclopentanes, cyclopentenes and bicyclo[2.1.1]hexanes that are difficult to access using known methods. This complexity-building reaction was catalyzed by a very simple and inexpensive diboron(4) compound and took place via dearomative/rearomative processes. The substrate scope was broad and more than 100 new compounds were prepared in generally high yields. Mechanistic experiments and density function theory (DFT) investigation supported a radical relay catalytic cycle involving alkylidene dihydropyridine radical intermediates and boronyl radical transfer.

Automated summary

This study developed a novel method for selective activation of a remote bond using a through-(hetero)arene radical transmission concept. By a metal-free [3+2] cycloaddition reaction, pyridine-substituted cyclopentanes, cyclopentenes, and bicyclo[2.1.1]hexanes that are difficult to access using known methods were synthesized. The reaction was catalyzed by a simple and inexpensive diboron(4) compound and proceeded via dearomative/rearomative processes.