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; M J Ingleson

doi:10.1039/d3sc04269c

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

Chem Sci. 2023 Oct 17;14(43):12041-12048. doi: 10.1039/d3sc04269c. eCollection 2023 Nov 8.

Authors

C R P Millet¹, E Noone¹, A V Schellbach¹, J Pahl¹, J Łosiewicz¹, G S Nichol¹, M J Ingleson¹

Affiliation

¹ EaStCHEM School of Chemistry, University of Edinburgh Edinburgh EH9 3FJ UK michael.ingleson@edinburgh.ac.uk.

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.