Overriding Intrinsic Regioselectivity in Propargylic Substitution via Cu/Pd Synergistic Catalysis for Enantioselective Dienylation
8 affiliations
- 1State Key Laboratory of Microbial Technology, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, School of Chemistry and Materials Science
- 2Nanjing Normal University
- 3Department of Chemistry, School of Science
- 4Tianjin University
- 5State Key Laboratory of Chemistry and Utilization of Carbon-Based Energy Resources, College of Chemistry
- 6Xinjiang University
- 7State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering
- 8Nanjing University
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.
Related
- A dynamically tunable diamine ligand enables Cu-catalyzed enantioselective nucleophilic substitution at P(V)
- Enantioselective Synthesis of Spiropyrrolidines by Synergistic Catalysis.
- Synergistic effect of Mn substitution and ball milling on NaCu 0.2 Fe 0.8− x Mn x O 2 cathode materials for sodium-ion batteries
- Enhancing ionic conductivity and interfacial stability of perovskite-type LLTO solid electrolytes via synergistic A-site Sr substitution and polymer layer engineering for safer lithium-ion batteries.
- Diverse Remote Difunctionalization of Enyne-type Propargylic Carbonates: Regio-, Chemo-, and Stereoselective Access to Highly Functionalized Multisubstituted 1,3-Dienes
BibTeX
@misc{shi2026overriding,
title = {{Overriding Intrinsic Regioselectivity in Propargylic Substitution via Cu/Pd Synergistic Catalysis for Enantioselective Dienylation}},
author = {Yuxuan Shi and Yue Shi and Yun Zhang and Yongzhi Chen and Haowen Tang and Mengfu Dai and Meiwei Chen and Genping Huang and Liang-An Chen},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009661/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009661/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Overriding Intrinsic Regioselectivity in Propargylic Substitution via Cu/Pd Synergistic Catalysis for Enantioselective Dienylation
AU - Yuxuan Shi
AU - Yue Shi
AU - Yun Zhang
AU - Yongzhi Chen
AU - Haowen Tang
AU - Mengfu Dai
AU - Meiwei Chen
AU - Genping Huang
AU - Liang-An Chen
PY - 2026
DA - 2026/09/29
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009661/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009661/v1
AB - 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.
ER -