Nickel-catalyzed cross-coupling of photoredox-generated radicals: uncovering a general manifold for stereoconvergence in nickel-catalyzed cross-couplings

Abstract

The cross-coupling of sp(3)-hybridized organoboron reagents via photoredox/nickel dual catalysis represents a new paradigm of reactivity for engaging alkylmetallic reagents in transition-metal-catalyzed processes. Reported here is an investigation into the mechanistic details of this important transformation using density functional theory. Calculations bring to light a new reaction pathway involving an alkylnickel(I) complex generated by addition of an alkyl radical to Ni(0) that is likely to operate simultaneously with the previously proposed mechanism. Analysis of the enantioselective variant of the transformation reveals an unexpected manifold for stereoinduction involving dynamic kinetic resolution (DKR) of a Ni(III) intermediate wherein the stereodetermining step is reductive elimination. Furthermore, calculations suggest that the DKR-based stereoinduction manifold may be responsible for stereoselectivity observed in numerous other stereoconvergent Ni-catalyzed cross-couplings and reductive couplings.

Figure 1

Initially proposed catalytic cycles (blue) and possible alternative indicated by computation (red) for photoredox/nickel dual catalytic CCR of potassium benzyltrifluoroborate and aryl bromides. Ir = Ir[dFCF₃ppy]₂(bpy)PF₆.

Figure 2

Reaction coordinate for the competing pathways using 2,2′-bipyridine. Relative Gibbs free energy values calculated with SMD-water-(U)M06/6-311+G(d,p)//UB3LYP/6-31G(d) and SMD-water-(U)M06/6-311+G(d,p)//UB3LYP/LANL2DZ (in parentheses).

Figure 3

Competing diastereomeric transition states in the reductive elimination. Relative free energies (kcal/mol) are computed using SMD-water-(U)M06/6-311+G(d,p)//UB3LYP/6-31G(d).

Figure 4

Predicted and experimental reaction enantioselectivities.

Figure 5

Energy barriers for the competing unstabilized alkyl radical dissociation and reductive elimination transition states with chiral diamine ligand L2. Relative free energies (kcal/mol) are computed using SMD-water-(U)M06/6-311+G(d,p)//B3LYP/6-31G(d) in SMD (water) level of theory.