Understanding non-covalent interactions in Ni-catalyzed reactions: Mechanistic insights into stereoselective tetrasubstituted allene synthesis

Abstract

We report a nickel-catalyzed approach for the efficient synthesis of tetrasubstituted allenes from tertiary propargylic substrates, which remains a significant challenge due to competing substitution reactions and regioselectivity issues. Leveraging an optimized Ni-PˆN catalytic system, the notable non-covalent interactions (NCIs) overcome inherent stability issues and achieve regio- and stereoselectivity. Through a combination of experimental and computational analyses, we elucidate the stabilization mechanisms of the critical β-[Ni]-alkenyl intermediate from the reactions of arylated propargyl substrates. Our findings demonstrate that NCIs, in particular hydrogen bonding interactions between a unique free amino-type PˆN ligand and the substrate, are key to achieving precise control over the process. The efficiency of the process is greatly influenced by subtle differences in the ligand system through control of the bite angle and coordination length in the key nickel complex intermediates. © 2024 Elsevier Inc.