文献类型：期刊文献

英文题名：Catalytic Asymmetric Barbier Reaction of Ketones with Unactivated Alkyl Electrophiles

作者：Xia, Hanyu[1];Jiang, Xingni[1];Lin, Di[1];Zhang, Shaoping[1];Yu, Zhiying[1];Wu, Xianqing[1];Qu, Jingping[1];Chen, Yifeng[1,2,3]

机构：[1]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Sci Ctr Materiobiol & Dynam Chem, Key Lab Adv Mat & Joint Int Res Lab Precis Chem &, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Organometall Chem, Shanghai 200032, Peoples R China;[3]Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Peoples R China

年份：2024

卷号：146

期号：41

起止页码：28468

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20244117169029);WOS:【SCI-EXPANDED(收录号:WOS:001328584400001)，CCR-EXPANDED(收录号:WOS:001328584400001)】；

基金：This work was supported by National Natural Science Foundation of China (22171079, 22371071, 92356301), Natural Science Foundation of Shanghai Municipality (21ZR1480400), Shanghai Municipal Science and Technology Major Project (Grant No. 2018SHZDZX03), Sinopec Seeding Program (C0607-0876), the Program of Introducing Talents of Discipline to Universities (B16017), Scientific Committee of Shanghai (21JC1401700), Shanghai Sailing Program (23YF1408800) and the Fundamental Research Funds for the Central Universities. The authors thank the Analysis and Testing Center of East China University of Science and Technology for help with NMR and HRMS analysis.

语种：英文

外文关键词：Addition reactions - Aldehydes - Carboxylation - Catalysis - Enantioselectivity - Redox reactions

摘要：The Barbier reaction is a reductive-type addition of an aldehyde or ketone with an organic electrophile in the presence of a terminal metal reductant, providing a straightforward and efficient method for carbon-carbon bond formation. This reaction possesses the advantage of circumventing the preparation of moisture- and air-sensitive organometallic reagents. However, the catalytic Barbier reaction of ketones to construct tetrasubstituted stereogenic centers is largely underdeveloped, despite its great potential for accessing synthetically challenging chiral tertiary alcohol. Particularly, the leveraging of unactivated alkyl electrophiles as coupling components is still rarely exploited. Herein, we disclose a photoredox-assisted cobalt-catalyzed asymmetric alkylative Barbier-type addition reaction of ketones to address the aforementioned challenges, thereby allowing for the construction of highly congested tetrasubstituted carbon centers. The alkyl addition fragments could be either readily accessible unactivated alkyl halides or redox-active esters generated through a decarboxylative pathway. Both types of alkyl electrophiles include primary, secondary, and tertiary ones, thus affording diverse enantioenriched tertiary alcohols with a broad substrate scope. This enantioselective protocol is applied for the expedient synthesis of core structure of Sofdra, a very recent FDA-approved drug in 2024. The newly developed bisoxazolinephosphine (NPN) ligand enables high enantioselectivity in this asymmetric reductive addition process.