Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 26, 2018
Douglass F. Taber
University of Delaware

C-H Functionalization: The Renata Synthesis of Manzacidin C

Timothy NoŽl of the Eindhoven University of Technology established flow conditions for the oxidation of the diester 1 to the ketone 2 (Angew. Chem. Int. Ed. 2018, 57, 4078. DOI: 10.1002/anie.201800818). Vladimir Gevorgyan of the University of Illinois at Chicago oxidized the sulfonamide 3 to the alkene 4 (J. Am. Chem. Soc. 2018, 140, 2465. DOI: 10.1021/jacs.8b00488). Yoshiharu Iwabuchi of Tohoku University showed that the hydroperoxide from the singlet oxygenation of 5 could readily be dehydrated to the enone 6 (Chem. Commun. 2018, 54, 798. DOI: 10.1039/C7CC08957K). David A. Nagib of Ohio State University devised conditions for the β-diodination of 7, leading, after hydrolysis and elimination, to the iodo alkene 8 (Chem. Sci. 2018, 9, 4500. DOI: 10.1039/C8SC01214H).

Zheng Huang of the Shangahi Institute of Organic Chemistry found that the transfer dehydrogenation of the alkane 9 with 10 and subsequent alkene migration and carbonylation could be carried out in a single pot, leading to the aldehyde 11 (J. Am. Chem. Soc. 2018, 140, 4157. DOI: 10.1021/jacs.8b01526). Djamaladdin G. Musaev and Huw M. L. Davies of Emory University and Matthew S. Sigman of the University of Utah developed a Rh catalysis that mediated the regioselective, diastereoselective and enantioselective insertion of 13 into 12, leading to 14 (ACS Catal. 2018, 8, 678, DOI: 10.1021/acscatal.7b03421; Nature Chem. 2018, 10, 1048, DOI: 10.1038/s41557-018-0087-7). Bing-Feng Shi of Zhejiang University coupled 15 with 16 to give 17 (Angew. Chem. Int. Ed. 2018, 57, 5858. DOI: 10.1002/anie.201801445). In another example of photoredox catalysis, Kounosuke Oisaki and Motomu Kanai of the University of Tokyo inserted 19 into 18, leading to 20 (Chem. Commun. 2018, 54, 3215. DOI: 10.1039/C7CC09457D).

Sukbok Chang of KAIST observed high diastereoselectivity in the cyclization of 21 to 22 (Science 2018, 359, 1016. DOI: 10.1126/science.aap7503). Mark J. Coster of Griffith University also achieved high diastereocontrol in the Rh-mediated cyclization of 23 to the spiroacetal 24 (Tetrahedron 2018, 74, 1313. DOI: 10.1016/j.tet.2018.01.043).

Professor Gevorgyan uncovered conditions for the atom transfer cyclization of 25 to 26 (Angew. Chem. Int. Ed. 2018, 57, 2712. DOI: 10.1002/anie.201712775). Shinya Harusawa of the Osaka University of Pharmaceutical Sciences cyclized the cyanophosphate 27, by way of the intermediate alkylidene carbene, to the cyclopentene 28 (Tetrahedron 2018, 74, 2143. DOI: 10.1016/j.tet.2018.03.020).

Manzacidin C (31), isolated from the sponge Hymeniacidon sp., blocks the α-adrenoceptor. The preparative enzymatic hydroxylation of 29 to 30 was a key step in the synthesis of 31 developed by Hans Renata of Scripps/La Jolla (J. Am. Chem. Soc. 2018, 140, 1165. DOI: 10.1021/jacs.7b12918).

D. F. Taber, Org. Chem. Highlights 2018, November 26.