Organic Chemistry Portal
Organic Chemistry Highlights

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. DOI: 10.1021/acscatal.7b02987). 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. DOI: 10.1021/acscatal.8b00423)

Krishna Nand Singh of Banaras Hindu University effected net acylation of 6 with 5, leading to the benzophenone 7 (Org. Lett. 2018, 20, 744. DOI: 10.1021/acs.orglett.7b03882). Koichi Tanaka of Kansai University achieved high enantioselectivity in the addition of 8 to 9 to give 10 (Chem. Commun. 2018, 54, 6328. DOI: 10.1039/C8CC03447H). 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. DOI: 10.1039/C8QO00295A). 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. DOI: 10.1021/acs.orglett.8b00070). 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. DOI: 10.1021/acs.oprd.8b00018).

Lukas J. Goossen of Ruhr-Universität Bochum assembled 18 by allylating 16 with 17 (Chem. Sci. 2018, 9, 5289, DOI: 10.1039/C8SC01741G; Chem. Eur. J. 2018, 24, 4537, DOI: 10.1002/chem.201800757). 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. DOI: 10.1021/jacs.7b12865), bromo (Chem. Sci. 2018, 9, 3860. DOI: 10.1039/C8SC01016A, and stannyl (Org. Lett. 2018, 20, 385. DOI: 10.1021/acs.orglett.7b03669). The development of the Catellani strategy continues, with Yanghui Zhang of Tongji University (ACS Catal. 2018, 8, 3775. DOI: 10.1021/acscatal.8b00637) and Qianghui Zhou of Wuhan University (Angew. Chem. Int. Ed. 2018, 57, 7161. DOI: 10.1002/anie.201803865) 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. DOI: 10.1002/anie.201800573) and earlier by Guangbin Dong of the University of Chicago (Angew. Chem. Int. Ed. 2018, 57, 1697. DOI: 10.1002/anie.201712393), 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. DOI: 10.1021/acs.orglett.8b00064) and Armido Studer of the University of Münster (ACS Catal. 2018, 8, 1213. DOI: 10.1021/acscatal.8b00083) 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. DOI: 10.1021/acs.oprd.7b00342).

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. DOI: 10.1002/adsc.201701329). Xinying Zhang and Xuesen Fang of Henan Normal University combined 33, 34, and 35 to give 36 (J. Org. Chem. 2018, 83, 5313. DOI: 10.1021/acs.joc.8b00473).

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. DOI: 10.1021/acs.joc.8b00285). 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.