Organic Chemistry Portal
Organic Chemistry Highlights

Monday, May 30, 2022
Douglass F. Taber
University of Delaware

Carbon-Carbon Bond Formation: The Houk/Cai Synthesis of Artemisinin

Following the Wenkert approach, Jun Huang and Zhen Yang of Peking University prepared the alkylated aldehyde 2 by conversion of the aldehyde 1 to the silyl enol ether, followed by cyclopropanation and hydrolysis (J. Am. Chem. Soc. 2021, 143, 18287. DOI: 10.1021/jacs.1c08880). Mary P. Watson of the University of Delaware showed that the pyridinium salt prepared by coupling the amine 3 with the commercial pyrilium salt 4 could be coupled with Zn(CN)2 to give the nitrile 5 (Org. Lett. 2021, 23, 6242. DOI: 10.1021/acs.orglett.1c01959). Paolo Melchiorre of ICIQ used photoactivation to add the amino acid-derived acyloxyphthalimide 6 in a conjugate sense to acrylonitrile 7, leading to the nitrile 8 (J. Am. Chem. Soc. 2021, 143, 12304. DOI: 10.1021/jacs.1c05607). Chao-Jun Li of McGill University assembled the ester 11 by Cu-mediated conjugate addition of the hydrazone of the aldehyde 9 to ethyl acrylate 10 (J. Org. Chem. 2021, 86, 13111. DOI: 10.1021/acs.joc.1c01380).

Wangqing Kong of Wuhan University observed high regio- and stereoselectivity in the preparation of the allylic alcohol 13 by the addition of methanol to the propargyl ether 12 (Chem. Sci. 2021, 12, 9372. DOI: 10.1039/D1SC02625A). Yinlong Guo and Zheng Huang of the Shanghai Institute of Organic Chemistry also achieved high geometric control in the isomerization of the alkenyl borate 12 to the trisubstituted alkene 13 (ACS Catal. 2021, 11, 10138. DOI: 10.1021/acscatal.1c02432). Gui-Juan Cheng of the Chinese University of Hong Kong and Xianjie Fang of Shanghai Jiao Tong University coupled the allylic alcohol 16 with acetone cyanohydrin 17 to give the α-branched nitrile 18 (ACS Catal. 2021, 11, 13880. DOI: 10.1021/acscatal.1c03729). Xia Zhang and Dawen Niu of Sichuan University found that coupling of the geometric mixture of enol ethers 19 with the organozinc 20 led to the enol ether 21 with high geometric control (Chem. Commun. 2012, 57, 12273. DOI: 10.1039/D1CC05347G).

Xingjie Zhang and Guisheng Zhang of Henan Normal University prepared the alkyne 24 by coupling the pyridinium salt derived from the amine 22 with the alkyne 23 (Nature Commun. 2021, 12, 4904. DOI: 10.1038/s41467-021-25222-1). Yin Wei and Min Shi, also of the Shanghai Institute of Organic Chemistry, assembled the alkyne 27 by adding the acyloxyphthalimide 25 to the enone 26 (Chem. Sci. 2021, 12, 9088. DOI: 10.1039/D1SC01889B).

Zhenyang Lin of the Hong Kong University of Science and Technology and Guosheng Liu of the Shanghai Institute of Organic Chemistry prepared the trisubstituted allene 29 in high ee by adding trimethylsilyl cyanide to the alkyne 28 (J. Am. Chem. Soc. 2021, 143, 14451. DOI: 10.1021/jacs.1c07190). Rubén Sánchez-Obregón of the Universidad Nacional Autónoma de México assembled the tetrasubstituted allene 32 by adding the alkyne 30 to ethyl cinnamate 31 (Tetrahedron Lett. 2021, 153425. DOI: 10.1016/j.tetlet.2021.153425).

Artemisinin (35) is the key active component of current anti-malarials. In the course of a synthesis of 35, K. N. Houk of UCLA and Quan Cai of Fudan University used the Barluenga protocol to convert the acid 33 into the allylic alcohol 34 (Nature Catal. 2021, 4, 892. DOI: 10.1038/s41929-021-00687-x).

D. F. Taber, Org. Chem. Highlights 2022, May 30.