Nitrile Hydroboration by Cooperative Iron Catalysis: An Experimental and Computational Study

Abstract

Reductive amination is a challenging reaction in catalysis that often gives poor yield and selectivity. We present an iron-catalyzed approach of synthesizing amines through reduction of nitriles through hydroboration with good yield under ambient conditions. Our detailed mechanistic study establishes the factors that influence the selectivity and turnover. The kinetics and mechanism of the iron-catalyzed hydroboration of benzonitrile to bis(boryl)benzylamine have been investigated by initial rates, temperature dependence, kinetic isotope effects, and computational studies. In contrast to other iron-catalyzed nitrile hydroboration, this study reveals that B─H bond activation is not rate-determining. Moreover, the rate-determining step was revealed to be C─H bond reductive elimination with an equilibrium isotope effect in operation. Through this combined approached, an Fe(0)/(II) catalytic manifold proceeding via metal-ligand cooperativity has been determined.

Keywords: DFT calculations; cooperative catalysis; hydroboration; iron catalysis; kinetic measurements.

Figure 1

Selected iron complexes effective for hydroboration of nitriles and N‐heteroarenes and the precatalyst, complex A used for this work.

Scheme 1

Substrate scope for the iron(0)‐ catalyzed hydroboration of aromatic and aliphatic nitriles.^{[a] [a]} Reactions were performed with substrate (0.205 mmol), HBpin (0.410 mmol, 2.0 equiv.), Complex A (1.0 mol%), in 0.6 mL of benzene‐[d]₆ for 1–6 hours at 50 °C. ^[b] 3.0 equivalents of HBpin were used. ^[c] 5 hours. ^[d] 4 hours. ^[e] 6 hours. ^[f] 9 hours.

Figure 2

a) synthesis of complex C, b) Solid‐state structure of complex C, c) utilizing complex C as a catalyst in hydroboration. ^[a] Ellipsoids are drawn at the 50% probability level, methyl groups and hydrogen atoms on isopropyl groups have been omitted for clarity. Selected distances of C (Å): Fe─P1 2.3121(6), Fe─P2 2.2792(6), Fe─N1 1.9376(19), Fe─B1 2.318(2), N1─C32 1.154(3) C32─C33 1.440(3).

Figure 3

a) van ’t Hoff plot for the reaction rate law order in [complex A]; b) van ’t Hoff plot for the reaction rate law order in [HBpin]; c) van ’t Hoff plot for the reaction rate law order in [nitrile]; d) Initial rates of hydroboration at different temperatures. e) Eyring plot f) Arrhenius plot.

Scheme 2

Potential mechanism for the equilibrium isotope effect (EIE).

Figure 4

UB3LYP‐GD3BJ/BS2//UB3LYP‐GD3BJ/BS1 calculated potential energy profile for the first hydroboration step of benzonitrile by HBpin on complex C in the triplet spin state. The spin state is identified with superscript. Enthalpies and free energies (in parenthesis) are reported in kcal mol⁻¹, obtained at 323 K, and contain zero‐point, solvent, entropic, and thermal corrections. Optimized geometries give bond lengths in Å, bond angles in degrees, and the imaginary frequency in cm⁻¹.

Scheme 3

On‐ versus Off‐Cycle Resting State Formation with Calculated Reaction Free Energy.

Figure 5

UB3LYP‐GD3BJ/BS2//UB3LYP‐GD3BJ/BS1 calculated potential energy profile for the second hydroboration step of benzonitrile by HBpin in the triplet spin state. The spin state is identified with superscript. Enthalpies and free energies (in parenthesis) are reported in kcal mol⁻¹, obtained at 323 K, and contain zero‐point, solvent, entropic, and thermal corrections. Optimized geometries give bond lengths in Å, bond angles in degrees, and the imaginary frequency in cm⁻¹.

Scheme 4

Proposed catalytic cycle based on the kinetic and computational data.