Ligand‐Controlled Chemoselective and Enantioselective Cyclization of Enynes With Aroyl Chlorides

Z Zhen‐Yu Wang (Shanghai Frontiers Science Center for Drug Target Identification and Delivery National Key Laboratory of Innovative Immunotherapy, and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai China) L Ling‐Xia Zhang (School of Chinese Materia Medica Nanjing University of Chinese Medicine Nanjing Jiangsu China) Y Yuqing Jiang Y Yun‐Qian Zhang (CAS Key Laboratory of Receptor Research State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China) T Tian‐Qi Gao (School of Chinese Materia Medica Nanjing University of Chinese Medicine Nanjing Jiangsu China) G Genping Huang (Department of Chemistry, School of Science) H Hui Xu H Hui‐Xiong Dai (Shanghai Frontiers Science Center for Drug Target Identification and Delivery National Key Laboratory of Innovative Immunotherapy, and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai China)

Abstract

ABSTRACT Herein, we report a palladium‐catalyzed, ligand‐controlled approach for the switchable construction of cyclopropane‐fused heterocycles and seven‐membered N‐heterocyclic compounds via the chemoselective cyclization of enynes with aroyl chlorides. Furthermore, enantioselective synthesis of cyclopropane‐fused heterocycles was achieved using a chiral ligand. To highlight the synthetic utility, late‐stage modifications of acid chlorides derived from natural products and pharmaceuticals were demonstrated. DFT calculations reveal that the ligands play an important role in the chemoselective cyclization process by favoring either β‐H or β‐C elimination of the alkyl‐Pd(II) intermediate.

Article Details

Volume / Issue Vol. 65, Issue 27
Published July 01, 2026
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (8)

Z

Zhen‐Yu Wang

Shanghai Frontiers Science Center for Drug Target Identification and Delivery National Key Laboratory of Innovative Immunotherapy, and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai China

L

Ling‐Xia Zhang

School of Chinese Materia Medica Nanjing University of Chinese Medicine Nanjing Jiangsu China

Y

Yuqing Jiang

Y

Yun‐Qian Zhang

CAS Key Laboratory of Receptor Research State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China

T

Tian‐Qi Gao

School of Chinese Materia Medica Nanjing University of Chinese Medicine Nanjing Jiangsu China

G

Genping Huang

Department of Chemistry, School of Science

H

Hui Xu

H

Hui‐Xiong Dai

Shanghai Frontiers Science Center for Drug Target Identification and Delivery National Key Laboratory of Innovative Immunotherapy, and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai China