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

Abstract

Density functional theory calculations are used in this study to investigate the product selectivity and mechanism of borane-catalyzed reductive aldehyde amination by a H2 reducing agent. Knowing that different boranes yield different products, two typical boranes, (B­(2,6-Cl2C6H3)­(p-HC6F4)2 and B­(C6F5)3), are studied. Of the seven possible pathways of B­(2,6-Cl2C6H3)­(p-HC6F4)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(C6F5)3 catalyst, it forms a highly stable Lewis adduct with aniline, which impedes the hydrogenation of imine. Therefore, the product of B­(C6F5)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 H2 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.

Metal-Free Phosphination and Continued Functionalization of Pyridine: A Theoretical Study

“…The 3D-optimized structures were visualized using the CYLview program [ 47 ], and the calculated frequency values were used to correct the free energy at 298.15 K and 1 atm. Based on the “the theory of free volume” [ 48 , 49 , 50 , 51 , 52 , 53 ], a correction factor of −2.55 (or 2.55) kcal mol −1 was added to the free energy values to account for the effect of the ideal gas phase model in overestimating the contribution of entropy. Meanwhile, the Gibbs energies were corrected to standard state 1 M [ 54 ].…”

Theoretical study of reductive CO2 functionalization with amines and phenylsilanes: what kind of solvents can be used as catalysts?

“…The calculations were performed using the software Gaussian16. 40 The geometries of all minima and transition states were optimized and characterized at the M06-2X/6-311G** level of theory, [41][42][43][44] and the calculations were conducted in solvent, according to the SMD 45 method. To obtain accurate energy values, single-point energy calculations of the minimum energy conformers were conducted at the M06-2X/def2TZVP level of theory.…”

Density Functional Theory Study on the Selective Reductive Amination of Aldehydes and Ketones over Their Reductions to Alcohols Using Sodium Triacetoxyborohydride

“…However, few studies have computationally probed systems that do not contain transition metal catalysts, with even fewer studies analyzing boron complexes. In the study of Zhao et al ., 18 DFT was used to examine the reaction mechanisms of borane-catalyzed reductive amination between benzaldehyde and aniline, with molecular hydrogen as the reducing agent and tetrahydrofuran (THF) as the solvent. Their results showed that the product of this reaction varied depending on the nature of the Lewis acid catalyst (borane complexes) and could in fact be controlled by adjusting the natural charge on the boron atom.…”