Organic Chemistry Portal
Organic Chemistry Highlights

Monday, January 29, 2024
Douglass F. Taber
University of Delaware

Oxidation: The Frantz Route to Artemisinin

Imre Pápai and Tibor Soós of the Institute of Organic Chemistry, Budapest prepared the oxetane 3 by the relay ring-closing methathesis of the alkene 1 with the diene 2 (Angew. Chem. Int. Ed. 2023, 62, e202216879. DOI: 10.1002/anie.202216879). Ohyun Kwon of UCLA ozonized the alkene 4 to an intermediate that under Cu catalysis could be coupled with phthalimide, leading to the protected amino alcohol 5 (Science 2023, 381, 877. DOI: 10.1126/science.adi4758). Kensuke Kiyokawa and Satoshi Minakata of Osaka University assembled the α-amino amide 8 by coupling the amide 6 with the hypervalent iodine reagent 7 (Chem. Eur. J. 2023, 29, e202203722. DOI: 10.1002/chem.202203722). Hui Chen and Shelley D. Minteer of the University of Utah devised the three-stage oxidation of heptane (9) followed by coupling with 10, leading to the α-amino aldehyde 11 (ACS Catal. 2023, 13, 563. DOI: 10.1021/acscatal.2c04003).

Jieping Zhu of the Ecole Polytechnique Fédéral de Lausanne effected the oxidative ring expansion of the alkene 12 to the cycloheptanone 13 (Science 2023, 379, 1363. DOI: 10.1126/science.adg3182). Mu-Hyun Baik of KAIST, Djamaladdin G. Musaev of Emory University and Richmond Sarpong of the University of California, Berkeley prepared the aldehyde 15 by the oxidative cleavage of the amide 14 (J. Am. Chem. Soc. 2023, 145, 11245. DOI: 10.1021/jacs.3c01318). E. J. Corey of Harvard University reported the use of nitrosyl triflate to selectively convert caryophyllene (16) to the keto aldehyde 17 (Org. Lett. 2023, 25, 1872. DOI: 10.1021/acs.orglett.3c00353). Liangzhen Hu and Yan Xiong of Chongqing University prepared the α-acetoxy ketone 19 by the oxidation of the propiolic acid 18 (Org. Biomol. Chem. 2023, 21, 1457. DOI: 10.1039/D2OB02281H).

Hui Qian of Fudan University and Shengming Ma of the Shanghai Institute of Organic Chemistry achieved the selective oxidation of the acetonide 20 to the lactone 21 (Chem. Commun. 2023, 59, 5281. DOI: 10.1039/D3CC00963G). Xiao-song Xue and Yiyun Chen, also of the Shanghai Institute of Organic Chemistry, used the dimethyl benziodoxole 23 to activate both the cyclobutanol 22 and phthalimide, leading to the protected amine 24 (ACS Catal. 2023, 13, 3749. DOI: 10.1021/acscatal.3c00230). In an interesting alternative to Baeyer-Villiger oxidation, Jens Christoffers of the Carl von Ossietzky Universität Oldenburg α-hydroxylated the β-keto ester 25, then used cyanide to rearrange the resulting alcohol to the lactone 26 (Eur. J. Org. Chem. 2023, 26, e202201391. DOI: 10.1002/ejoc.202201391). Hongya Li and Yu Yuan of the University of Central Florida oxidized the nitro alcohol 27 to the lactone 28 (Org. Lett. 2023, 25, 31. DOI: 10.1021/acs.orglett.2c03727).

Artemisinic acid (30) is the key precursor to the important anti-malarial artemisinin (31). Using an optimized version of tetramethylpiperidide stoichiometric deprotonation, Doug E. Frantz of the University of Texas at San Antonio effected the direct oxidation of the readily-prepared amorphadiene (29) to the crystalline 30 (Org. Lett. 2023, 25, 277. DOI: 10.1021/acs.orglett.2c04145).

D. F. Taber, Org. Chem. Highlights 2024, January 29.