文献类型：期刊文献

英文题名：Organocatalytic Enantioselective Direct Additions of Aldehydes to 4-Vinylpyridines and Electron-Deficient Vinylarenes and Their Synthetic Applications

作者：Wang, Sinan[1,2];Li, Xiangmin[1,2,3];Liu, Hongwei[1,2];Xu, Li[1,2];Zhuang, Jinchen[1,2];Li, Jian[1,2];Li, Hao[1,2];Wang, Wei[1,2,3]

机构：[1]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, State Key Lab Bioengn Reactor, Shanghai 200237, Peoples R China;[3]Univ New Mexico, Dept Chem & Chem Biol, Albuquerque, NM 87131 USA

年份：2015

卷号：137

期号：6

起止页码：2303

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20150900569118);WOS:【SCI-EXPANDED(收录号:WOS:000349807000031)，CCR-EXPANDED(收录号:WOS:000349807000031)】；

基金：Financial support of this research from the program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (201226 to H. Li), the National Natural Science Foundation of China (21372073 to W.W.), the Fundamental Research Funds for the Central Universities and East China University of Science and Technology (startup funds to H. Li and W.W.), the China 111 Project (Grant B07023 to H. Li and W.W.), the Chinese Scholarship Council (X.L.) and the National Science Foundation (CHE-1057569 to W.W.) is gratefully acknowledged.

语种：英文

外文关键词：Ethers - Synthesis (chemical) - Catalysis - Enantioselectivity - Chemical activation - Pyridine

摘要：We describe a synergistic catalysis strategy for the asymmetric direct addition of simple aldehydes to 4-vinylpyridines. By means of independent activation of weakly electrophilic 4-vinylpyridines by the Bronsted acid CF3SO3H (TfOH) and aldehydes by chiral diphenylprolinol tert-butyldimethylsilyl (TBDMS) ether-catalyzed formation of nucleophilic enamines in a cooperative manner, the previously unattainable highly enantioselective addition process has been realized for the first time. Notably, the power of the addition process is fueled by its high efficiency in the production of synthetically valued chiral pyridines. H-1 NMR studies of the process suggested that the nucleophilic enamine formed in situ from the chiral amine catalyst and the aldehyde is directly added to the trimeric 4-vinylpyridinium-derived species as a highly active electrophile generated from the 4-vinylpyridine in the presence of TfOH. Moreover, inspired by the similar electronic natures of pyridine and nitrobenzene, we have achieved an unprecedented chiral diphenylprolinol TBDMS ether-promoted, highly enantioselective direct addition of aldehydes to 2-nitrostyrenes without the use of TfOH as a cocatalyst. In this approach, introducing a strong electron-withdrawing group such as NO2, CF3, SO2Me, etc. on the 2-nitrostyrene creates a highly electrophilic vinyl moiety, which enables the direct addition of the in situ-formed enamine derived from the chiral amine promoter and the aldehyde. This method significantly expands the scope of the enantioselective addition process. While the electron-withdrawing nitro group is essential for activation of the vinyl group, we have demonstrated that it can be readily transformed to diverse functionalities. Furthermore, as shown, a chiral pyridine adduct serves as a key building block in the synthesis of the potent fibrinogen receptor antagonist L-734,217.