Added-metal-free catalytic nucleophilic addition of Grignard reagents to ketones |
| |
Authors: | Zong Hua Huang Huayin Liu Junfeng Bian Guangling Song Ling |
| |
Institution: | The State Key Lab of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China. |
| |
Abstract: | On the basis of the investigation of the combinational effect of quaternary ammonium salts and organic bases, an added-metal-free catalytic system for nucleophilic addition reactions of a variety of Grignard reagents to diverse ketones in THF solvent has been developed to produce tertiary alcohols in good to excellent yields. By using tetrabutylammonium chloride (NBu(4)Cl) as a catalyst and diglyme (DGDE) as an additive, this system strongly enhances the efficiency of addition at the expense of enolization and reduction. NBu(4)Cl should help to shift the Schlenk equilibrium of Grignard reagents to the side of dimeric Grignard reagents to favor the additions of Grignard reagents to ketones via a favored six-membered transition state to form the desired tertiary alcohols, and DGDE should increase the nucleophilic reactivities of Grignard reagents by coordination. This catalytic system has been applied in the efficient synthesis of Citalopram, an effective U.S. FDA-approved antidepressant, and a recyclable version of this catalytic synthesis has also been devised. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|