Catalytic enantioselective reductive domino alkylarylation of acrylates via nickel/photoredoxcatalysis

Pengcheng Qian^1,5, Haixing Guan^1,2,5, Yan-En Wang³, Qianqian Lu¹, Fan Zhang¹, Dan Xiong¹,Patrick J. Walsh^4*,Jianyou Mao^1*

1Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, 30 South Puzhu Road,Nanjing 211816, P.R. China

2Experimental Center, Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University ofTraditional Chinese Medicine, Jinan, PR China

3College of Science, Hebei Agricultural University, Baoding, PR China

4Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia,Pennsylvania 19104-6323, United States

5These authors contributed equally: Pengcheng Qian, Haixing Guan

Abstract:Nonsteroidal anti-inflammatory drug derivatives (NSAIDs) are an important class of medications.Here we show a visible-light-promoted photoredox/nickel catalyzed approach toconstruct enantioenriched NSAIDs via a three-component alkyl arylation of acrylates. Thisreductive cross-electrophile coupling avoids preformed organometallic reagents and replacesstoichiometric metal reductants by an organic reductant (Hantzsch ester). A broad range offunctional groups are well-tolerated under mild conditions with high enantioselectivities (upto 93% ee) and good yields (up to 90%). A study of the reaction mechanism, as well asliterature precedence, enabled a working reaction mechanism to be presented. Key stepsinclude a reduction of the alkyl bromide to the radical, Giese addition of the alkyl radical tothe acrylate and capture of the α-carbonyl radical by the enantioenriched nickel catalyst.Reductive elimination from the proposed Ni(III) intermediate generates the product andforms Ni(I).

Nat.Commun.2021,12, 6613(2021年影响因子:14.919).

论文链接：https://www.nature.com/articles/s41467-021-26794-8?utm_source=xmol&utm_medium=affiliate&utm_content=meta&utm_campaign=DDCN_1_GL01_metadata#citeas