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Monday, October 8, 2018
Douglass F. Taber
University of Delaware

Benzene Derivatives: The Schmidt Synthesis of (+)-Duocarmycin SA

Belén Martín-Matute of Stockholm University developed the Ir-catalyzed ortho iodination of 1 to 2 (ACS Catal. 2018, 8, 920. ). Robert J. Phipps of the University of Cambridge also used an Ir catalyst to effect the meta borylation of 3 to give 4 (ACS Catal. 2018, 8, 3764. )

Krishna Nand Singh of Banaras Hindu University effected net acylation of 6 with 5, leading to the benzophenone 7 (Org. Lett. 2018, 20, 744. ). Koichi Tanaka of Kansai University achieved high enantioselectivity in the addition of 8 to 9 to give 10 (Chem. Commun. 2018, 54, 6328. ). Hua-Li Qin of the Wuhan University of Technology devised a protocol for the conversion of a phenol 11 to the nitrile 12 (Org. Chem. Front. 2018, 5, 1835. ). Timothy F. Jamison of MIT and Yuan-Qing Fang and Matthew M. Bio of Snapdragon Chemistry established an electrochemical flow method for preparing 15 by the coupling of 13 with 14 (Org. Lett. 2018, 20, 1338. ). At the same time, Klavs F. Jensen of MIT and Richard I. Robinson of Novartis described a photochemical flow procedure for a closely-related coupling (Org. Process Res. Dev. 2018, 22, 542, not illustrated. ).

Lukas J. Goossen of Ruhr-Universität Bochum assembled 18 by coupling 16 with 17 (Chem. Sci. 2018, 9, 5289, ; Chem. Eur. J. 2018, 24, 4537, ). This, and the conversion of 1 to 2, are particularly significant because the carboxylate can be directly converted to, inter alia, alkyl and acyl (J. Am. Chem. Soc. 2018, 140, 3724. ), bromo (Chem. Sci. 2018, 9, 3860. , and stannyl (Org. Lett. 2018, 20, 385. ). The development of the Catellani strategy continues, with Yanghui Zhang of Tongji University (ACS Catal. 2018, 8, 3775. ) and Qianghui Zhou of Wuhan University (Angew. Chem. Int. Ed. 2018, 57, 7161. ) devising the borono-Catellani, illustrated by the preparation of 22 by the coupling of 19, 20 and 21. For the epoxide version, reported by Professor Zhou (Angew. Chem. Int. Ed. 2018, 57, 3444. ) and earlier by Guangbin Dong of the University of Chicago (Angew. Chem. Int. Ed. 2018, 57, 1697. ), the assembly of 26 by the addition of 23 to 24 was best supported by a modified norbornene such as 25.

The diene 27 is readily prepared by the reductive alkylation of benzoic acid. Chih-Ming Chou of the National University of Kaohsiung (Org. Lett. 2018, 20, 1328. ) and Armido Studer of the University of Münster (ACS Catal. 2018, 8, 1213. ) showed that 27 could be oxidatively coupled with 28, leading to 29. Jing Liu, now at TP Therapeutics, identified an unexpected inhibitor of Suzuki coupling, a key reaction for preparing substituted aromatics (Org. Process Res. Dev. 2018, 22, 111, not illustrated. ).

Yin Wei and Min Shi of the Shanghai Institute of Organic Chemistry assembled the alkyne 32 by the addition of 31 to 30 (Adv. Synth. Catal. 2018, 360, 808. ). Xinying Zhang and Xuesen Fang of Henan Normal University combined 33, 34, and 35 to give 36 (J. Org. Chem. 2018, 83, 5313. ).

In conjunction with the development of antibody/drug conjugate-based therapeutics, Michael A. Schmidt of Bristol-Myers Squibb developed a practical synthesis of the potent antitumor antibiotic duocarmycin SA (40) (J. Org. Chem. 2018, 83, 3928. ). A key step in the synthesis was the vicarious nucleophilic substitution addition of the sulfone 38 to 37 to give 39.

D. F. Taber, Org. Chem. Highlights 2018, October 8.
URL: https://www.organic-chemistry.org/Highlights/2018/08October.shtm