Issue 13, 2021

Controlling selectivity in N-heterocycle directed borylation of indoles

Abstract

Electrophilic borylation of indoles with BX3 (X = Cl or Br) using directing groups installed at N1 can proceed at the C2 or the C7 position. The six membered heterocycle directing groups utilised herein, pyridines and pyrimidine, result in indole C2 borylation being the dominant outcome (in the absence of a C2-substituent). In contrast, C7 borylation was achieved using five membered heterocycle directing groups, such as thiazole and benzoxazole. Calculations on the borylation of indole substituted with a five (thiazole) and a six (pyrimidine) membered heterocycle directing group indicated that borylation proceeds via borenium cations with arenium cation formation having the highest barrier in both cases. The C7 borylated isomer was calculated to be the thermodynamically favoured product with both five and six membered heterocycle directing groups, but for pyrimidine directed indole borylation the C2 product was calculated to be the kinetic product. This is in contrast to thiazole directed indole borylation with BCl3 where the C7 borylated isomer is the kinetic product too. Thus, heterocycle ring size is a useful way to control C2 vs. C7 selectivity in N-heterocycle directed indole C–H borylation.

Graphical abstract: Controlling selectivity in N-heterocycle directed borylation of indoles

Supplementary files

Article information

Article type
Paper
Submitted
05 yan 2021
Accepted
10 mar 2021
First published
11 mar 2021
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2021,19, 2949-2958

Controlling selectivity in N-heterocycle directed borylation of indoles

S. A. Iqbal, K. Yuan, J. Cid, J. Pahl and M. J. Ingleson, Org. Biomol. Chem., 2021, 19, 2949 DOI: 10.1039/D1OB00018G

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