Overriding Intrinsic Regioselectivity in Propargylic Substitution via Cu/Pd Synergistic Catalysis for Enantioselective Dienylation
Year: 2026
Type: preprint
Abstract: Propargylic substitution is a fundamental strategy in asymmetric catalysis for constructing enantioenriched unsaturated molecules, yet the dienylation pathway via nucleophilic attack at the central carbon of propargyl/allenyl-metal intermediates has remained elusive. Here we report that Cu/Pd synergistic catalysis enables the first catalytic asymmetric dienylation with broad carbon nucleophiles, delivering enantioenriched 1,3‑dienes with exceptional levels of regioselectivity (>20:1), enantioselectivity (up to 99% ee), and E/Z selectivity (>20:1). Mechanistic and DFT studies establish distinct roles for the two metals: palladium governs regiocontrol, while the chiral copper complex is responsible for enantioselectivity, enabling complementary dienylation with high regio- and enantioselectivity. Stronger palladium–terminal-carbon interactions make terminal attack energetically costly and direct the regioselective reaction to the central carbon of the π-propargyl-Pd complex, thereby overriding the inherent preference for propargylation and allenylation. The synthetic utility is demonstrated by diverse transformations of the enantioenriched diene products, thereby enabling the rapid assembly of complex molecular architectures. Beyond providing a general strategy for reprogramming the innate regioselectivity of π‑propargyl chemistry, this work highlights the potential of bimetallic synergistic catalysis as a practical platform for tackling long‑standing selectivity challenges in asymmetric synthesis.
Source: ChemRxiv
Authors: Yuxuan Shi, Yue Shi, Yun Zhang, Yongzhi Chen, Haowen Tang, Mengfu Dai, Meiwei Chen, Genping Huang, Liang-An Chen
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7214805529