文献类型：期刊文献

英文题名：Synthesis of Chiral 3-Substituted Phthalides by a Sequential Organocatalytic Enantioselective Aldol-Lactonization Reaction. Three-Step Synthesis of (S)-(-)-3-Butylphthalide

作者：Zhang, Haoyi[1];Zhang, Shilei[1,3];Liu, Lu[1];Luo, Guangshun[1];Duan, Wenhu[1,2];Wang, Wei[1,2,3]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut Sci, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;[3]Univ New Mexico, Dept Chem & Biol Chem, Albuquerque, NM 87131 USA

年份：2010

卷号：75

期号：2

起止页码：368

外文期刊名：JOURNAL OF ORGANIC CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000273400300011)，CCR-EXPANDED(收录号:WOS:000273400300011)】；

基金：Financial support of this research is supported by the School of Pharmacy, East China University of Science and Technology and the China 111 Project (Grant No. B07023).

语种：英文

摘要：The development of efficient methods for the facile construction of important molecular frameworks is an important goal in organic synthesis. Chiral 3-substituted phthalides are widely distributed in it large collection of natural products with broad, potent, and potentially path-pointing biological activities. In this investigation, we have uncovered all unprecedented organocatalytic asymmetric aldol-lactonization reaction of 2-formylbenzoic esters with ketones/aldehydes for convenient construction of the enantioenriched "privileged" scaffold. As a result of the sensitive nature Of Substrate structures of an organocatalytic enantioselective aldol reaction, after extensive optimization of reaction conditions, catalyst L-prolinamide alcohol IV is identified as the best promoter. Interestingly, it is found that in this reaction, addition of an acid additive PhCO2H can significantly enhance reaction efficiency with use of only as low as 2.5 mol % IV for the process. Moreover, due to the sensitivity of reaction conditions toward it sequential aldol-lactonization process without affecting enantioselectivity and racemization, it is essential to remove the catalyst for the subsequent facile lactonization reaction in the presence of K2CO3. The aldol-lactonization processes serve as it powerful approach to the preparation of synthetically and biologically important 3-substitued phthalides with a high level of enantioselectivities. A 3-step catalytic asymmetric synthesis of the natural product of 3-butylphthalide is reported.