Issue 43, 2023

Borylation directed borylation of N-alkyl anilines using iodine activated pyrazaboles

Abstract

Doubly electrophilic pyrazabole derivatives (pyrazabole = [H2B(μ-C3N2H3)]2) combined with one equiv. of base effect the ortho-borylation of N-alkyl anilines. Initial studies found that the bis(trifluoromethane)sulfonimide ([NTf2]) pyrazabole derivative, [H(NTf2)B(μ-C3N2H3)]2, is highly effective for ortho-borylation, with this process proceeding through N–H borylation and then ortho C–H borylation. The activation of pyrazabole by I2 was developed as a cheaper and simpler alternative to using HNTf2 as the activator. The addition of I2 forms mono or ditopic pyrazabole electrophiles dependent on stoichiometry. The ditopic electrophile [H(I)B(μ-C3N2H3)]2 was also effective for the ortho-borylation of N-alkyl-anilines, with the primary C–H borylation products readily transformed into pinacol boronate esters (BPin) derivatives. Comparison of borylation reactions using the di-NTf2-and the diiodo-pyrazabole congeners revealed that more forcing conditions are required with the latter. Furthermore, the presence of iodide leads to competitive formation of side products, including [HB(μ-C3N2H3)3BH]+, which are not active for C–H borylation. Using [H(I)B(μ-C3N2H3)]2 and 0.2 equiv. of [Et3NH][NTf2] combines the higher yields of the NTf2 system with the ease of handling and lower cost of the iodide system generating an attractive process applicable to a range of N-alkyl-anilines. This methodology represents a metal free and transiently directed C–H borylation approach to form N-alkyl-2-BPin-aniline derivatives.

Graphical abstract: Borylation directed borylation of N-alkyl anilines using iodine activated pyrazaboles

Supplementary files

Article information

Article type
Edge Article
Submitted
15 Aug. 2023
Accepted
02 Okt. 2023
First published
17 Okt. 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2023,14, 12041-12048

Borylation directed borylation of N-alkyl anilines using iodine activated pyrazaboles

C. R. P. Millet, E. Noone, A. V. Schellbach, J. Pahl, J. Łosiewicz, G. S. Nichol and M. J. Ingleson, Chem. Sci., 2023, 14, 12041 DOI: 10.1039/D3SC04269C

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