A Theoretical Study on the Borane-Catalyzed Reductive Amination of Aniline and Benzaldehyde with Dihydrogen: The Origins of Chemoselectivity.

Density functional theory calculations are used in this study to investigate the product selectivity and mechanism of borane-catalyzed reductive aldehyde amination by a H 2 reducing agent. Knowing that different boranes yield different products, two typical boranes, (B(2,6-Cl 2 C 6 H 3 )( p -HC 6 F 4 ) 2 and B(C 6 F 5 ) 3 ), are studied. Of the seven possible pathways of B(2,6-Cl 2 C 6 H 3 )( p -HC 6 F 4 ) 2 -catalyzed aldehyde amination analyzed herein, four are favorable. Three of the four favorable pathways involve imine intermediates, and the fourth is a Lewis acid-base synergistic pathway that involves amine-alcohol condensation. As for the B(C 6 F 5 ) 3 catalyst, it forms a highly stable Lewis adduct with aniline, which impedes the hydrogenation of imine. Therefore, the product of B(C 6 F 5 ) 3 -catalyzed reductive amination of benzaldehyde and aniline is an imine. The linear relationship between the charge on the boron atom in the Lewis acid and the relative energies of the Lewis adduct and H 2 splitting transition state indicates that this parameter determines product selectivity. Indeed, when the natural charge on boron is larger than 1, an amine is produced, whereas when the charge is less than 1, an imine is produced. Hence, the selectivity of products can be controlled by adjusting the natural charge of the boron atom in the Lewis acid catalyst.