Mechanistic study of the Ni‐catalyzed hydroalkylation of 1,3‐dienes: The origins of regio‐ and enantioselectivities and a further rational design

Abstract

The development of the catalytic regio‐ and enantioselective hydrofunctionalization of 1,3‐dienes remains a challenge and requires deep insight into the reaction mechanisms. We herein thoroughly studied the reaction mechanism of the Ni‐catalyzed hydroalkylation of 1,3‐dienes with ketones by density functional theory (DFT) calculations. It reveals that the reaction is initiated by stepwise oxidative addition of EtO‐H followed by 1,3‐diene migratory insertion to generate the alkylnickel(II) intermediate, rather than the experimentally proposed ligand‐to‐ligand hydrogen transfer (LLHT) mechanism. In addition, we rationalized the role of tBuOK in the subsequent addition of enolate of ketone and transmetalation process. Based on the whole catalysis, the CC reductive elimination step, turns out to be the rate‐ and enantioselectivity‐determining step. Furthermore, we disclosed the origins of the regio‐ and enantioselectivity of the product, and found that the 1,2‐selectivity lies in the combination effects of the ligand‐substrate electrostatic interactions, orbital interactions and Pauli repulsions, while the enantioselectivity mainly arises from substrate‐ligand steric repulsions. Based on mechanistic study, new biaryl bisphosphine ligands affording higher enantioselectivity were designed, which will help to improve current catalytic systems and develop new transition‐metal‐catalyzed hydroalkylations.

A computational mechanistic study on the Ni-catalyzed asymmetric alkynyl propyl hydroxyaminations: origin of enantioselectivity and further rational design

“…27 Previous studies also calibrated the good performance of the BP86 functional for the Ni-catalyzed reactions. 28–32 The solvation effects of the experimentally used solvent ( i.e. , 1,4-dioxane) were taken into consideration by using the IEFPCM 33,34 solvation model.…”