Metal-Free Directed Site-Selective Csp(3)-H Borylation of Saturated Cyclic Amines

The borylation of Csp(3)-H bonds is a challenging transformation that is typically restricted to transition metal catalysis. Herein, we report the site-selective metal-free Csp(3)-H borylation of saturated cyclic amines. It is possible to selectively borylate piperidine derivatives at the & alpha; or & beta; positions according to the reaction conditions. The mechanism was supported by NMR spectroscopy, calorimetry experiments and density functional theory (DFT) computations. It suggests that the piperidine is dehydrogenated by complexation with BBr3 to produce an enamine intermediate, which is in turn borylated at either the & alpha; or & beta; position according to the reaction conditions.

Automated summary

We report a metal-free, selective Csp(3)-H borylation of saturated cyclic amines. Piperidine derivatives can be selectively borylated at either the α or β positions depending on the reaction conditions. Mechanistic studies using NMR spectroscopy, calorimetry experiments, and density functional theory computations suggest that piperidine undergoes dehydrogenation through complexation with BBr3 to generate an enamine intermediate, which is then borylated at the α or β position based on the reaction conditions.