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

利用碘活化吡唑硼烷对N-烷基苯胺进行硼化导向硼化反应

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Abstract

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.

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