A Modular Access to 1,2-and 1,3-Disubstituted Cyclobutylboronic Esters by Consecutive Radical Additions

A modular approach to substituted cyclobutylboronic esters is described. It proceeds by successive intermolecular radical additions of xanthates to pinacolato 1-cyclobutenylboronate and to pinacolato bicyclo[1.1.0]but-1-ylboronate. Success hinges on tuning the stability of the alpha-boryl radical by exploiting the stabilizing influence of the trivalent boronic ester and the slightly destabilizing cyclobutane, which increases the sigma-character of the radical. Reductive removal of the xanthate group finally provides a range of 1,2- and 1,3-disubstituted cyclobutylboronic esters. The contrast with cyclopropylboronic esters is striking, since the strong destabilization by the highly strained cyclopropane ring allows the first radical addition to take place but not the second. Furthermore, the first adducts are geminal xanthyl boronic esters that can be converted into cyclobutanones. This chemistry furnishes cyclobutylboronic esters that would be quite difficult to obtain otherwise and thus complements existing methods.

Automated summary

This modular approach to substituted cyclobutylboronic esters involves successive intermolecular radical additions and reductive removal of xanthates to provide a range of 1,2- and 1,3-disubstituted cyclobutylboronic esters. The stability of the alpha-boryl radical is crucial for the success of the reaction, leveraging the stabilizing influence of the trivalent boronic ester and the slightly destabilizing cyclobutane. The chemistry described here complements existing methods by providing cyclobutylboronic esters that would be quite difficult to obtain otherwise.