Copper‐Catalyzed Asymmetric Coupling of Allenyl Radicals with Terminal Alkynes to Access Tetrasubstituted Allenes

• Published in: Angewandte Chemie International Edition Vol. 60; no. 4; pp. 2160 - 2164
• Main Authors: Dong, Xiao‐Yang, Zhan, Tian‐Ya, Jiang, Sheng‐Peng, Liu, Xiao‐Dong, Ye, Liu, Li, Zhong‐Liang, Gu, Qiang‐Shuai, Liu, Xin‐Yuan
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 25-01-2021
• Edition: International ed. in English
• Subjects: 1,4-enynes; alkyl bromides; Alkynes; allenes; Aromatic compounds; asymmetric radical reactions; Asymmetry; Chirality; Copper; Coupling; Forging; Functional groups; Radicals; Substrates; allenes; copper; alkyl bromides; 1,4-enynes; asymmetric radical reactions
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202013022

In contrast to the wealth of asymmetric transformations for generating central chirality from alkyl radicals, the enantiocontrol over the allenyl radicals for forging axial chirality represents an uncharted domain. The challenge arises from the unique elongated linear configuration of the allenyl radicals that necessitates the stereo‐differentiation of remote motifs away from the radical reaction site. We herein describe a copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes via the coupling of allenyl radicals with terminal alkynes, providing diverse synthetically challenging tetrasubstituted chiral allenes. A chiral N,N,P‐ligand is crucial for both the reaction initiation and the enantiocontrol over the highly reactive allenyl radicals. The reaction features a broad substrate scope, covering a variety of (hetero)aryl and alkyl alkynes and 1,3‐enynes as well as radical precursors with excellent functional group tolerance.
A copper‐catalyzed asymmetric radical 1,4‐carboalkynylation of 1,3‐enynes is realized, providing diverse tetrasubstituted chiral allenes. The utilization of the copper/chiral N,N,P‐ligand is crucial for the enantiocontrol over the allenyl radicals, which is difficult due to their elongated linear configuration that necessitates the stereo‐differentiation of remote motifs away from the reaction site.