Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 13, 2022
Douglass F. Taber
University of Delaware

Substituted Benzenes: The Yang/Zhang Synthesis of Cephanolide B

Duen-Ren Hou of the National Central University devised a simple protocol for the direct acetoxylation of the substituted benzene 1, leading to the aryl acetate 2 (Org. Lett. 2021, 23, 8127. DOI: 10.1021/acs.orglett.1c02183). Manuel van Gemmeren of Westfälische Wilhelms-Universität Münster demonstrated the facile conversion of the benzoate 3 to the ring-deuterated benzoate 4 (J. Am. Chem. Soc. 2021, 143, 16370. DOI: 10.1021/jacs.1c08233).

Bill Morandi of ETH Zürich used 1-iodobutane (6) to convert the benzoic acid 5 to the iodobenzene 7 (Angew. Chem. Int. Ed. 2021, 60, 17211. DOI: 10.1002/anie.202103269). Weiran Yang of Nanchang University described a parallel investigation with anthranilic acids (Org. Chem. Front. 2021, 8, 4479. DOI: 10.1039/D1QO00461A). Tobias Ritter of the Max-Planck-Institut für Kohlenforschung prepared the phenol 9 directly from the lithium benzoate 8 (Angew. Chem. Int. Ed. 2021, 60, 24012. DOI: 10.1002/anie.202108971).

Ferdinand H. Lutter and Matthieu Jouffroy of Janssen Pharmaceutica assembled the aryl alkyne 12 by coupling the benzoic acid 10 with TMS-acetylene 11 (Chem. Eur. J. 2021, 27, 14816. DOI: 10.1002/chem.202102130). Tao Wu, also of Nanchang University, prepared the α-aryl ketone 15 by coupling the ketone 14 with the nitrobenzene derivative 13 (Org. Lett. 2021, 23, 881. DOI: 10.1021/acs.orglett.0c04104). Antonio M. Echavarren of ICIQ used the bromoalkyne 17 to effect the ortho alkynylation of the nitroaromatic 16, leading to 18 (Chem. Sci. 2021, 12, 14731. DOI: 10.1021/acs.orglett.1c02764). Arkaitz Correa of the University of the Basque Country showed that pendant tyrosines on even complex polypeptides could be ring-acylated with primary alcohols, as exemplified by the preparation of 21 by the coupling of 19 with 1-butanol 20 (Org. Lett. 2021, 23, 7279. DOI: 10.1021/acs.orglett.1c02764). Dattatraya H. Dethe of the Indian Institute of Technology Kanpur used a Ru catalyst to mediate the assembly of the aryl succinimide 24 by the addition of the benzyl alcohol 22 to the N-benzyl maleimide 23 (Org. Lett. 2021, 23, 6267. DOI: 10.1021/acs.orglett.1c02040). Yuanyuan Liu of East China Normal University observed high preference for the para product 27 from the coupling of the α-diazo ester 26 with the phenol 25 (Org. Chem. Front. 2021, 8, 6252. DOI: 10.1039/D1QO01184G).

Nagatoshi Nishiwaki of the Kochi University of Technology devised a practical preparation of nitroacetonitrile, allowing ready preparation of the substituted acrylonitrile 28, that could be combined with the diene 29 to give, after elimination and oxidation, the benzonitrile 30 (J. Org. Chem. 2021, 86, 13177. DOI: 10.1021/acs.joc.1c01515). Tatsuya Morofuji and Naokazu Kano of Gakushin University used dinitrochlorobenzene 32 and pyrrolidine 33 to convert the pyridine 31 to the biphenyl 34 (Org. Lett. 2021, 23, 6126. DOI: 10.1021/acs.orglett.1c02225).

The cephanolide diterpenoids isolated from the coniferous shrub Cephalotaxus sinensis, exemplified by cephanolide B (37), show antineoplastic, antiviral and antitumor properties. Zhen Yang and Zichun Zhang of Peking University Shenzhen Graduate School envisioned that Pauson-Khand cyclization of the alkyne 35 would be followed by 6π-electrocyclization to give an intermediate that could be aromatized, leading to the ketone 36 (Org. Lett. 2021, 23, 9237. DOI: 10.1021/acs.orglett.1c03579).

D. F. Taber, Org. Chem. Highlights 2022, June 13.