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

Abstract

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 non-covalent 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.

autoDIAS: a python tool for an automated distortion/interaction activation strain analysis

“…This analysis can be applied to single geometries or multiple geometries along a scan or reaction coordinate, to provide information on the nature of interaction between the fragments and the potential energy surface. This method has been widely applied for a broad range of chemical systems such as cycloadditions, ene reactions, metal complexes and catalysis, organocatalysis, and addition and substitution reactions …”

Regio‐ and Enantioselective Formal Hydroamination of Enamines for the Synthesis of 1,2‐Diamines

“…[15] Through computational studies this effect was traced to attractive dispersion interactions between the bulky ligands,f or example,t he tBu moieties in DTBM-SEGPHOS (L6), and the substrate,lowering the energy of the transition state in the hydrocupration step. [17] Switching to the bulky bidentate phosphine ligands L2-L4 resulted in increased yields and excellent enantioselectivities (entries [2][3][4]. Encouraged by these results,t wo additional ligands were explored.…”

“…To our delight, the desired 1,2-diamine 3a was detected in the crude reaction mixture ( 1 HNMR spectroscopy), albeit in trace quantities (entry 1). [17] Switching to the bulky bidentate phosphine ligands L2-L4 resulted in increased yields and excellent enantioselectivities (entries [2][3][4]. [15] Through computational studies this effect was traced to attractive dispersion interactions between the bulky ligands,f or example,t he tBu moieties in DTBM-SEGPHOS (L6), and the substrate,lowering the energy of the transition state in the hydrocupration step.…”

Alkene Hydroamination via Earth‐Abundant Transition Metal (Iron, Cobalt, Copper and Zinc) Catalysis: A Mechanistic Overview

“…Electronic stabilization of copper species E by the neighboring aryl (or silyl) group and formation of a less sterically hindered alkylcopper intermediate rationalize the observation of a Markovnikov and anti ‐Markovnikov selectivity for arylalkenes (and vinylsilanes) and linear alkenes, respectively. Examination of the through‐bond and through‐space interactions between the Cu(I)–H catalyst ligated to diverse biphosphine and alkylalkenes by DFT calculations shows that the superior reactivity noted with the bulky ligand DTBM‐SEGPHOS emanates principally from a better stabilization of the hydrocupration transition state via superior dispersion interactions from the tert ‐butyl substituent of the phosphine and the alkyl substituent of the alkene . Indeed, for terminal and internal alkenes and in contrast to arylalkenes, the rate‐limiting step is the hydrocupration step .…”