Functional Group Oxidation: The Liu/Du Synthesis of Varioxiranol B

Electronically, C-H bonds adjacent to a cyclopropane should show increased nucleophilicity. This was born out by the selective oxidation of 1 to 3 using the dioxirane 2 reported by K. N. Houk of UCLA and Massimo Bietti of the Università "Tor Vergata" (J. Am. Chem. Soc. 2023, 145, 24021. DOI: 10.1021/jacs.3c07163). Xukai Zhou and Guangbin Dong of the University of Chicago used the hydrazonamide 5 to effect the oxidative cleavage of the ketone 4 to the bromide 6 (J. Am. Chem. Soc. 2023, 145, 21096. DOI: 10.1021/jacs.3c08176). Nuno Maulide of the University of Vienna established that t-butylsulfinamide 8 could effect the conversion of the amide 7 to the α-amino amide 9 (Angew. Chem. Int. Ed. 2023, 62, e202304990. DOI: 10.1002/anie.202304990). Jie-Sheng Tian of Northwestern Polytechnical University found that the enamine derived from the aldehyde 10 and dibenzylamine 11 could be directly oxidized to the α-amino ketone 12 (Org. Lett. 2023, 25, 8922. DOI: 10.1021/acs.orglett.3c03771).

Benjamin List of the Max-Planck-Institut für Kohlenforschung showed that the cyclohexanone 13 could be directly oxidized to the cyclohexenone 14 (Angew. Chem. Int. Ed. 2023, 62, e202307081. DOI: 10.1002/anie.202307081). Zhankui Sun of Shanghai Jiao Tong University devised a protocol for the oxidative decarboxylation of the acid 15 to the aldehyde 16 (Synlett 2023, 34, 2029. DOI: 10.1055/a-2102-7006). Shohei Hamada of Kyoto Pharmaceutical University observed that the allylic silyl ether of 17 could be selectively oxidized to the unsaturated aldehyde 18, leaving the aliphatic silyl ether intact (ACS Catal. 2023, 13, 8031. DOI: 10.1021/acscatal.3c01153). Shenlin Huang of Nanjing Forestry University and Lan-Gui Xie of Nanjing Normal University used DMTSM (20) to convert the alkyne 19 to the α-sulfenylated α,β-unsaturated aldehyde 21 (Org. Chem. Front. 2023, 10, 2416. DOI: 10.1039/D3QO00236E).

Shyam Sathyamoorthi of the University of Kansas used Selectfluor to oxidize the alcohol 22 to the acid 23 (J. Org. Chem. 2023, 88, 11240. DOI: 10.1021/acs.joc.3c01307). Adrián Gómez-Suárez of Bergische Universität Wuppertal effected the oxidative cleavage of the malononitrile 24 to the ester 25 (Chem. Commun. 2024, 60, 1456. DOI: 10.1039/D3CC06172H). Jin-Quan Yu of Scripps/La Jolla selectively dehydrogenated the acid 26 to the cyclopentene 27 (J. Am. Chem. Soc. 2023, 145, 20951. DOI: 10.1021/jacs.3c06423). Cristiano Bolchi of the Università degli Studi di Milano used oxone to cleave the ketone 28 to the amido acid 29 (J. Org. Chem. 2023, 88, 15461. DOI: 10.1021/acs.joc.3c01513).

Varioxiranol B (32) was isolated from the marine sponge associated fungus Emiricella variecolor. Less oxygenated variants isolated from the same source at 10 µM inhibited hepatic lipid accumulation without toxicity. Jun Liu and Yuguo Du of the Key Laboratory of Environmental Chemistry and Eco-toxicology, Beijing established a general route to this class of natural products, including 32, starting with the preparation of the aldehyde 31 by way of the previously-reported selective bromination of 2,3-dimethyl anisole 30 (Tetrahedron 2023, 145, 133621. DOI: 10.1016/j.tet.2023.133621).