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

Doubly electrophilic pyrazabole derivatives (pyrazabole = [H 2 B(μ-C 3 N 2 H 3 )] 2 ) combined with one equiv. of base effect the ortho -borylation of N -alkyl anilines. Initial studies found that the bis(trifluoromethane)sulfonimide ([NTf 2 ] - ) pyrazabole derivative, [H(NTf 2 )B(μ-C 3 N 2 H 3 )] 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 I 2 was developed as a cheaper and simpler alternative to using HNTf 2 as the activator. The addition of I 2 forms mono or ditopic pyrazabole electrophiles dependent on stoichiometry. The ditopic electrophile [H(I)B(μ-C 3 N 2 H 3 )] 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-NTf 2 -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-C 3 N 2 H 3 ) 3 BH] + , which are not active for C-H borylation. Using [H(I)B(μ-C 3 N 2 H 3 )] 2 and 0.2 equiv. of [Et 3 NH][NTf 2 ] combines the higher yields of the NTf 2 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.