Acyl‐Directed ortho‐Borylation of Anilines and C7 Borylation of Indoles using just BBr3

Saqib A Iqbal,Richard J Procter,Jessica Cid,Marina Uzelac,Kang Yuan,Michael J Ingleson

doi:10.1002/ange.201909786

Saqib A Iqbal, Richard J Procter + Show 4 more

Open Access

https://doi.org/10.1002/ange.201909786

Copy DOI

Abstract

AbstractIndoles are privileged heterocycles found in many biologically active pharmaceuticals and natural products. However, the selective functionalization of the benzenoid moiety in indoles in preference to the more reactive pyrrolic unit is a significant challenge. Herein we report that N‐acyl directing groups enable the C7‐selective C−H borylation of indoles using just BBr3. This transformation shows some functional‐group tolerance and notably proceeds with C6 substituted indoles. The directing group can be readily removed in situ and the products isolated as the pinacol boronate esters. Acyl‐directed electrophilic borylation can be extended to carbazoles and anilines with excellent ortho selectivity. 4‐amino‐indoles are amenable to this process, with acyl group installation and directed electrophilic C−H borylation enabling selective formation of C5‐BPin‐indoles.

Highlights

Indoles are privileged heterocycles found in many biologically active pharmaceuticals and natural products
Transition metal catalysed C7-H indole functionalisation often uses bulky phosphinyl directing groups installed at N1 which are challenging to remove,5,6a,14 in limited cases N-acyl directing groups have been used[5, 15] and these are more readily removed
We demonstrate that N-acyl directing groups are compatible with BBr3 and lead to C7-H borylation of indoles generating useful C7-BPin products on work up (Scheme 1, bottom)

Summary

Edinburgh Research Explorer

Acyl Directed ortho-Borylation of Anilines and C7 Borylation of Indoles using just BBr3. Citation for published version: Iqbal, S, Cid, J, Procter, R, Uzelac, M, Yuan, K & Ingleson, M 2019, 'Acyl Directed ortho-Borylation of Anilines and C7 Borylation of Indoles using just BBr3', Angewandte Chemie International Edition, vol 58, no. Link: Link to publication record in Edinburgh Research Explorer Document Version: Peer reviewed version. Procter,b Marina Uzelac,a Kang Yuana and Michael J.

Range of

Conflict of interest

Table of Contents Entry