Metal‐Free Directed Site‐Selective Csp³‐H Borylation of Saturated Cyclic Amines

Abstract

The borylation of Csp3‐H bonds is a challenging transformation that is typically restricted to transition metal catalysis. Herein, we report the site‐selective metal‐free Csp3–H borylation of saturated cyclic amines. It is possible to selectively borylate piperidine derivatives at the α or β 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 α or β position according to the reaction conditions.

BX3-mediated borylation for the synthesis of organoboron compounds

“…Very recently, Fontaine's group first disclosed an elegant strategy for the metal-free Csp 3 –H borylation of 2-dialkylaminopyridines using BBr 3 (Scheme 23). 69 Mechanism studies found that an enamine is formed in the borylation followed by subsequent Csp 3 –H insertion or electrophilic borylation.…”

Regioselective ortho halogenation of N-aryl amides and ureas via oxidative halodeboronation: harnessing boron reactivity for efficient C–halogen bond installation

“…1B ). 7 More recently, we showed that the chemistry is not limited to only hydroxyl and Bpin, but it can also be used for installing halogens to phenyl pyridines and aryl aldehydes ( Fig. 1B ).…”