Controlling selectivity in N-heterocycle directed borylation of indoles. Issue 13 (16th March 2021)

• Record Type: Journal Article
• Authors: Iqbal, S. A.; Yuan, K.; Cid, J.; Pahl, J.; Ingleson, M. J.
• Is Part Of: Organic & biomolecular chemistry. Volume 19:Issue 13(2021)
• Page Start: 2949
• Page End: 2958
• Publication Date: 2021-03-16
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d1ob00018g
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : N-Heterocycle directing groups lead to selective borylation of indole at C2 or C7 controlled by heterocycle ring size. With five membered heterocycle directing groups, C2 borylation is disfavoured due to an increased degree of distortion. 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.