1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 A Copper (II) Acetate Mediated Oxidative-Coupling of Styrenes and Ethers Through an Unactivated C(sp 3 ) À H Bond Functionalization Zhan Yan, a, b Nai-Xing Wang, a, * Xue-Wang Gao, a Jian-Li Li, b, * Yue-Hua Wu, a Tong Zhang, a Shi-Lu Chen, c, * and Yalan Xing d, * a Technical Institute of Physics and Chemistry & University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China Fax: + 86-10-62554670 E-mail: nxwang@mail.ipc.ac.cn b Chemistry and Material Science College, Northwest University, Xian, 710127, Peoples Republic of China Fax: + 86-29-88308396 E-mail: lijianli@nwu.edu.cn c School of Chemistry, Beijing Institute of Technology, Beijing, 100081, Peoples Republic of China Fax: + 86-10-68913154 E-mail: shlchen@bit.edu.cn d Department of Chemistry, William Paterson University of New Jersey, 300 Pompton Road, Wayne, New Jersey 07470, United States Fax: 0-973-720-3462 E-mail: xingy@wpunj.edu Manuscript received: September 18, 2018; Revised manuscript received: December 4, 2018; Version of record online: January 23, 2019 Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.201801243 Abstract: A Copper (II) Acetate Mediated Oxida- tive Coupling of Styrenes and Ethers Through an Unactivated C(sp 3 ) À H Bond Functionalization A functionalization of unactivated C(sp 3 )-H bond of ethers with styrenes was described. This C À C bond formation has been developed using t-butyl hydroperoxide (TBHP) as a radical initiator and DBU as an additive agent. Typical ethers under- went a free-radical addition of styrenes to give direct difunctionalization products with excellent regioselectivity and efficiency. This reaction fea- tures good yields and functional group compatibil- ity with simple operation and mild conditions. A plausible reaction mechanism has been proposed. DFT simulation and theory calculation also pro- vided important evidence for the proposed free- radical mechanism. Keywords: copper acetate; C(sp 3 ) À H functionaliza- tion; ether; oxidative cross-coupling; radical; styrene Transition metal catalyzed C À H functionalization has received tremendous attention due to its step conven- ience, atom economy, and environmental benignness. [1] Especially in recent years, functionalization of unac- tivated C(sp 3 ) À H bond has been considered as one of the most effective strategies in organic synthesis. [2] With broad applications in chemical industry, pharmaceutical, agriculture and its acquiring sources, alkenes and its derivatives perform various kinds of reactions with substrates bearing diverse functional groups, [3] such as ethers, [3a] amines, [3b] etc. Thus, difunctionalization reactions of alkene, such as diami- nation, [4] dihydroxylation, [5] hydroxyacetoxylation, [6] aminoacetoxylation [7] and several others [8] have been intensively investigated because these methods allow the rapid increase of molecular complexity in a highly efficient manner. To take advantages of the difunctionalization of styrenes, our group developed a series of new reac- tions through an oxidative free radical cross-cou- pling. [9] Our methods were achieved by metal catalysts and simple operations which make the reaction easy to control. Several typical substrates namely alco- hol, [9a] ketone [9b] and nitrile [9c] were reported. Herein, we would like to report a Cu(OAc) 2 catalyzed direct oxidative coupling of styrenes with ethers via C(sp 3 ) À H bond functionalization (Scheme 1). To the best of our knowledge, this is the first report of the COMMUNICATIONS DOI: 10.1002/adsc.201801243 Adv. Synth. Catal. 2019, 361, 1007 – 1011 1007  2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim