Ligand-Substrate Dispersion Facilitates the Copper-Catalyzed Hydroamination of Unactivated Olefins

Abstract

The current understanding of ligand effects in transition metal catalysis is mostly based on the analysis of catalyst-substrate through-bond and through-space interactions, with the latter commonly considered to be repulsive in nature. The dispersion interaction between the ligand and the substrate, a ubiquitous type of attractive noncovalent interaction, is seldom accounted for in the context of transition-metal-catalyzed transformations. Herein we report a computational model to quantitatively analyze the effects of different types of catalyst-substrate interactions on reactivity. Using this model, we show that in the copper(I) hydride (CuH)-catalyzed hydroamination of unactivated olefins, the substantially enhanced reactivity of copper catalysts based on bulky bidentate phosphine ligands originates from the attractive ligand-substrate dispersion interaction. These computational findings are validated by kinetic studies across a range of hydroamination reactions using structurally diverse phosphine ligands, revealing the critical role of bulky P-aryl groups in facilitating this process.

Figure 1

Concept of analyzing catalyst-substrate interactions in transition metal catalysis. a, Through-space and through-bond interactions in transition metal catalysis. b, Ligand effects on reactivity of CuH-catalyzed hydroamination of unactivated olefins.

Figure 2

Ligand effects in CuH-catalyzed hydroamination of olefins. a, The previously reported experimental results for the CuH-catalyzed olefin hydroamination using the copper catalyst based on SEGPHOS (L1) or DTBM-SEGPHOS (L2). b, The computed activation free energy (Δ G^‡) of the hydrocupration step with respect to the separated LCuH and olefin. Energies were calculated at the M06/SDD–6-311+G(d,p)/SMD(THF) level of theory with geometries optimized at the B3LYP/SDD–6-31G(d) level.

Figure 3

Relationships between the through-space ligand-substrate interaction and the activation energy. a, Dissection of the activation energy into through-space and through-bond interactions in the hydrocupration transition state using SEGPHOS (L1) as an example. The bidentate phosphine ligand is highlighted in yellow, and the olefin substrate is in blue. b, Linear correlations between the activation energy (ΔE^‡) and the through-space ligand-substrate interaction (ΔE_int-space).

Figure 4

Effects of ligand-substrate dispersion interactions on reactivity. a, Energy decomposition analysis of the ligand-substrate interaction energy in the transition states of hydrocupration of trans-4-octene using SEGPHOS and DTBM-SEGPHOS based catalysts. b, Dispersion interactions between the Pr substituents in the olefin substrate and the t-Bu groups on the DTBM-SEGPHOS ligand.

Figure 5

a, Linear correlation between ligand-substrate dispersion (ΔE_disp) and total ligand-substrate through-space interaction (ΔE_int-space) in the hydrocupration of terminal olefins CH₂=CHR and internal olefins trans-CHR=CHR (R = Me, Et, Pr, i-Pr, t-Bu, Cy, Bn, CHEt₂, Ph). b, Linear correlations between ligand-substrate dispersion (ΔE_disp) and activation energy (ΔE^‡).

Figure 6

Effects of dispersion on the reactivity of catalysts with different ligands. a, Computed activation free energies of hydrocupration of propene. b, Linear correlation between the computed relative rates (log(k/k₀)_theory) and the experimentally observed relative initial rates (log(k/k₀)_experiment). The catalyst based on SEGPHOS (L1) was used as the reference to calculate the relative rates. Ligands with 3,5-di-tert-butyl substituted P-aryl groups are highlighted in green.