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

Rory C Mykura, Pradip Songara, Eugenia Luc, Jack Rogers, Ellie Stammers, Varinder K Aggarwal*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

1 Citation (Scopus)
27 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)11436-11441
Number of pages6
JournalAngewandte Chemie - International Edition
Volume60
Issue number20
Early online date12 Apr 2021
DOIs
Publication statusPublished - 3 May 2021

Bibliographical note

Funding Information:
R.C.M., P.S. E.S., and J.R. thank the Bristol Chemical Synthesis Centre for Doctoral Training, funded by the EPSRC (EP/L015366/1, EP/G036764/1), and AstraZeneca. We thank University of Bristol for financial support. We thank Dr. Tom Hayhow (AZ) for useful discussions.

Publisher Copyright:
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH

Structured keywords

  • BCS and TECS CDTs

Keywords

  • Boronic Esters
  • C-C coupling
  • lithiated carbamates
  • carbocycles
  • cyclobutane

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