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

• Published in: Angewandte Chemie International Edition 2023-09, Vol.62 (39), p.e202309295-n/a
• Main Authors: Kumar Someswara Ashwathappa, Puneeth, Higashi, Takuya, Desrosiers, Vincent, Omaña, Alvaro A., Fontaine, Frédéric‐Georges
• Format: Article
• Language: English
• Subjects: Amines; Borylation; Calorimetry; Catalysis; Dehydrogenation; Density functional theory; Directing Group; Enamine; Magnetic resonance spectroscopy; Metal-Free; NMR spectroscopy; Piperidine; Transition metals
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202309295

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. Cyclic amines can undergo Csp3−H borylation using BBr3. At high temperature in a microwave reactor, the α‐borylation is preferred, whereas the presence of a Lewis base at lower temperature will lead to the β‐borylation selectively. Mechanistic studies support the presence of an enamine intermediate for both processes.