C-N Ring Construction: The Song/Qin Synthesis of Mitragynine

Jennifer M. Schomaker of the University of Wisconsin employed a silver catalyst to cyclize the carbamimidate 1 to the aziridine 2 (Chem. Commun. 2024, 60, 224. DOI: 10.1039/D3CC05670H). James H. Frederich of Florida State University used the Tebbe reagent to convert the ketone 3 into the azetidine 4 (Adv. Synth. Catal. 2024, 366, 2214. DOI: 10.1002/adsc.202301527).

Phil S. Baran of Scripps/La Jolla used the Schweizer reagent, vinyl triphenyl phosphonium bromide (6) to cyclize the aldehyde derived from the amino alcohol 5 to the dihydropyrrole 7 (Angew. Chem. Int. Ed. 2024, 63, e202401107. DOI: 10.1002/anie.202401107). Weigang He of the Changsu Institute of Technology and Weiqing Xie of Northwest A&F University assembled the pyrrolidine 10 by combining the oxindole 8 with the alkynyl ketone 9 (Org. Chem. Front. 2024, 11, 703. DOI: 10.1039/D3QO01898A). Yang Yang of the Huazhong University of Science and Technology constructed the pyrrolidine 13 from the aziridine 11 and the silyl enol ether 12 (Org. Chem. Front. 2024, 11, 668. DOI: 10.1039/D3QO01835K). Hua Wu of Shanghai Jiao Tong University employed a BINOL-derived phosphoric acid to guide the coupling of the α-diketone 14 with the aldehyde 15, leading to the enone 16 (Angew. Chem. Int. Ed. 2024, 63, e202317182. DOI: 10.1002/anie.202317182).

Hanmin Huang of the University of Science and Technology of China added the aminal 18 to the N-allyl amine 17, leading to the piperidine 19 (Org. Lett. 2024, 26, 2467. DOI: 10.1021/acs.orglett.4c00641). Qin-Shi Zhao of the Kunming Institute of Botany effected the oxidative cyclization of the allyl silane 20 to the piperidine 21 (J. Am. Chem. Soc. 2024, 146, 7616. DOI: 10.1021/jacs.3c13869). Pei Tang of Sichuan University and Fen-Er Chen of Fudan University prepared the piperidine 23 by hydrogenating the pyridinium salt 22 (Org. Chem. Front. 2024, 11, 3225. DOI: 10.1039/D4QO00322E). Yanfeng Dang of Tianjin University and Xiu-Qin Dong and Chun-Jiang Wang of Wuhan University constructed the piperidine 26 by combining the alanine imine 24 with the allyl carbonate 25 (Nature Commun. 2024, 15, 127. DOI: 10.1038/s41467-023-44336-2).

Hans Renata of Rice University used a transaminase to cyclize the diketone 27 to the hexahydroazepine 28 (Nature Synth. 2024, 3, 662. DOI: 10.1038/s44160-024-00514-8). Łukasz Albrecht of the Lodz University of Technology used a Hayashi-Jørgensen amine to mediate the addition of the pyrrole 29 to the unsaturated aldehyde 30, leading to the indolizidine 31 (Org. Lett. 2024, 26, 814. DOI: 10.1021/acs.orglett.3c03911).

Mitragynine (34), isolated from the tropical evergreen tree Mitragyna speciosa, is a G-protein-biased agonist of the μ-opioid receptor. Hao Song and Yong Qin, also of Sichuan University, established the relative and absolute configuration of 34 by the enantioselective hydrogenation of the lactam 32 to 33 (Org. Chem. Front. 2024, 11, 1456. DOI: 10.1039/D3QO02034G).