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Studies on the Lithiation, Borylation, and 1,2‐Metalate Rearrangement of O ‐Cycloalkyl 2,4,6‐Triisopropylbenzoates
Author(s) -
Mykura Rory C.,
Songara Pradip,
Luc Eugenia,
Rogers Jack,
Stammers Ellie,
Aggarwal Varinder K.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202101374
Subject(s) - borylation , deprotonation , chemistry , medicinal chemistry , stereochemistry , organic chemistry , aryl , ion , alkyl
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. Although 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.