Studies on the lithiation, borylation, and 1,2‐metalate rearrangement of O‐cycloalkyl 2,4,6‐triisopropylbenzoates

A broad range of acyclic primary and secondary 2,4,6‐triisopropylbenzoate (TIB) esters have been used in lithiation‐borylation reactions, but cyclic TIB esters have not. We have studied the use of cyclic TIB esters in lithiation‐borylation reactions and looked at the effect of ring size (3 → 6‐membered rings) on the three key steps of the lithiation–borylation protocol: deprotonation, borylation and 1,2‐metalate rearrangement. While all rings sizes could be deprotonated, the cyclohexyl case was impractically slow, and the cyclopentyl example underwent α‐elimination faster than deprotonation at −78 °C and so could not be used. Both cyclobutyl and cyclopropyl cases underwent rapid borylation, but only the cyclobutyl substrate underwent 1,2‐metalate rearrangement. Thus, the cyclobutyl TIB ester occupies a “Goldilocks zone,” being small enough for deprotonation and large enough to enable 1,2‐migration. The generality of the reaction was explored with a broad range of boronic esters.