Pd/GF-Phos-Catalyzed Asymmetric Three-Component Coupling Reaction to Access Chiral Diarylmethyl Alkynes
Guofeng Zhao, Yi Wu, Hai-Hong Wu, Junfeng Yang* and Junliang Zhang*
*Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, People’s Republic of China,
Email: yangjf
fudan.edu.cn, junliangzhangfudan.edu.cn
G. Zhao, Y. Wu, H.-H. Wu, J. Yang, J. Zhang, J. Am. Chem. Soc., 2021, 143, 17983-17988.
DOI: 10.1021/jacs.1c09742
see article for more reactions
Abstract
A chiral sulfinamide phosphine ligand enables a Pd-catalyzed enantioselective three-component coupling of N-tosylhydrazones, aryl halides, and terminal alkynes under mild conditions utilizing (GF-Phos) to provide chiral diarylmethyl alkynes. This reaction features readily available starting materials, general substrate scope, high enantioselectivity, and ease of scale-up.
see article for more examples
General Procedure
To a sealed tube was added [Pd(dmba)acac] (5 mol%), ligand (10 mol%), and 0.5 mL cyclohexane. The flask was evacuated and refilled with argon. After the catalyst/ligand solution was stirred for 1 h at 25°C, the solvent was evaporated. The flask was transfered to a glove box, CuBr2 (5 mol%), sodium hydroxide pearls (2.5 equiv) were added. Next cyclohexane 3.5 mL, aryl bromide (1.7 equiv), terminal alkynes (1.7 equiv) and N-tosylhydrazone (1.0 equiv) were added under argon atmosphere. The reaction mixture was kept stirring at 55°C for 9 h. After the reaction was completed, which was determined by TLC, the mixture was concentrated in vacuum and the mixture was directly purified by flash chromatography on silica gel to afford the desired product.
Key Words
propargylation of arenes, benzylation of arenes. multicomponent reactions
ID: J48-Y2021
