Organic Chemistry Portal
Organic Chemistry Highlights

Monday, May 27, 2024
Douglass F. Taber
University of Delaware

Reactions of Alkenes: The Shenvi Synthesis of Eugenial C

Polyssena Renzi of the University of Turin demonstrated that purple LEDs promoted the thiol-ene addition of thiophenol to the alkene 1, leading to the sulfide 2 (Adv. Synth. Catal. 2023, 365, 4623. DOI: 10.1002/adsc.202300990). Wonjoo Lee, Younghoon Kim and Hyun Gil Cha of the Korea Research Institute of Chemical Technology showed that easily scaled ultrasound-produced DMDO converted the isosorbide-derived diene 3 to the bis-epoxide 4 (Chem. Asian J. 2023, 18, e202300744. DOI: 10.1002/asia.202300744). Dirk E. De Vos of KU Leuven employed electrolysis to oxidize the alkene 5 to the bis-acetate 6 (Angew. Chem. Int. Ed. 2023, 62, e202311539. DOI: 10.1002/anie.202311539). Sukbok Chang of the Korea Advanced Institute of Science and Technology used alkene migration to couple the enol ether 7 with the dioxazolone 8, leading to the amide 9 (J. Am. Chem. Soc. 2023, 145, 24940. DOI: 10.1021/jacs.3c09679). Tomislav Rovis of Columbia University reported a parallel investigation (ACS Catal. 2023, 13, 16337. DOI: 10.1021/acscatal.3c05075).

Tobias Ritter of the Max-Planck-Institute für Kohlenforschung assembled the enone 12 by acylating the alkene 11 with the acid chloride 10 (Angew. Chem. Int. Ed. 2023, 62, e202309498. DOI: 10.1002/anie.202309498). Ilhyong Ryu of the National Yang Ming Chiao Tung University added the bis sulfone 14 to the alkene 13, leading to the cyclohexanol 15 (Angew. Chem. Int. Ed. 2023, 62, e202311807. DOI: 10.1002/anie.202311807). Nuno Maulide of the University of Vienna added the aminal 17 to the more nucleophilic alkene of 16 to give the lactone 18 with high diastereocontrol (Chem. Sci. 2023, 14, 10806. DOI: 10.1039/D3SC04073A). Masilamani Jeganmohan of the Indian Institute of Technology Madras prepared the diene 21 by coupling the methacrylamide 20 with the alkene 19 (Org. Lett. 2023, 25, 6284. DOI: 10.1021/acs.orglett.3c02095).

Xiao-Feng Wu of the Dalian Institute of Chemical Physics assembled the amino amide 24 by the carbonylative coupling of the alkene 22 with dimethylacetamide 23 and aniline (Nature Commun. 2023, 14, 7439. DOI: 10.1038/s41467-023-43306-y). Similarly, Hanmin Huang of the University of Science and Technology of China effected the triply-convergent coupling of the alkene 25 with the methoxymethyl amine 26 and methyl bromoacetate 27, leading to the amino ester 28 (Nature Catal. 2023, 6, 847. DOI: 10.1038/s41929-023-01015-1). Yuqiang Li of the Shanghai AI Laboratory and Guoyin Yin of Wuhan University constructed the diester 30 by adding dimethyl fumarate 29 and phenylboronic acid to the alkene 19 (Nature Catal. 2023, 6, 1030. DOI: 10.1038/s41929-023-01032-0). It is also possible to include fluorine, as with the coupling of the quinoxalin-2(1H)-one 32 and the bromofluoromalonate 33 with the alkene 31 to give the fluorinated diester 34, as described by Yingsheng Zhao of Soochow University (Eur. J. Org. Chem. 2023, 26, e202300596. DOI: 10.1002/ejoc.202300596).

Eugenial C (38), isolated from the fruit of the Brazilian myrtle Eugenia umbelliflora, shows marked anti-bacterial activity. Ryan A. Shenvi of Scripps Research of La Jolla, CA assembled 38 via the convergent coupling of the alkene 35 with the benzylic bromide 36, leading to 37. It is a tribute to true natural product chemistry that when pandemic supply chain issues precluded the purchase of aromadendrene or globuol, precursors to 35, these investigators isolated their own from locally-gathered Eucalyptus fruit (J. Am. Chem. Soc. 2023, 145, 15714. DOI: 10.1021/jacs.3c05428).

D. F. Taber, Org. Chem. Highlights 2024, May 27.