Organic Chemistry Portal
Organic Chemistry Highlights

Monday, September 17, 2018
Douglass F. Taber
University of Delaware

C-C Bond Formation: The Hoveyda Synthesis of Prostaglandin E2

Kensuke Kiyokawa and Satoshi Minakata of Osaka University showed that the silyl enol ether 1 could be oxidized with 2 to give the keto nitrile 3 (Org. Lett. 2017, 19, 4672. DOI: 10.1021/acs.orglett.7b02313). Jen-Chieh Hsieh and Chien-Hong Cheng of Tamkang University devised a protocol for the reductive conjugate addition of 5 to 4, leading to the ester 6 (Chem. Commun. 2017, 53, 11584. DOI: 10.1039/C7CC06881F). Darren J. Dixon of the University of Oxford prepared the amine 9 by reducing the amide 7, then adding the Grignard reagent 8 (Chem. Sci. 2017, 8, 7492. DOI: 10.1039/C7SC03613B). Nuno Maulide of the University of Vienna constructed 14 by activating the amide 10 with 11 and 12, then adding the enolate of 13 (J. Am. Chem. Soc. 2017, 139, 16040. DOI: 10.1021/jacs.7b08813).

Xiao-Chen Wang of Nankai University used 16 to rearrange the cyclopropane 15 to the alkene 17 (Angew. Chem. Int. Ed. 2017, 56, 4028. DOI: 10.1002/anie.201700864). Hegui Gong of Shanghai University showed that even a tertiary halide such as 18 could participate in allylic coupling with 19, leading to 20 (Angew. Chem. Int. Ed. 2017, 56, 13103. DOI: 10.1002/anie.201705521). Organopalladium intermediates are usually subject to rapid β-hydride elimination. Rui Shang and Yao Fu of the University of Science and Technology of China found that under blue light irradiation, even the tertiary halide 22 could participate in Heck coupling with 21 to give 23 (J. Am. Chem. Soc. 2017, 139, 18307. DOI: 10.1021/jacs.7b10009). Loránd Kiss and Ferenc Fülöp of the University of Szeged demonstrated that the chelating ability of the amide of 24 enabled selective cross metathesis with 25, leading to 26 (Eur. J. Org. Chem. 2017, 1894. DOI: 10.1002/ejoc.201700064).

The protected cyanohydrin 27 was readily prepared from the corresponding ketone. Shinya Harusawa of the Osaka University of Pharmaceutical Sciences observed that treatment of 27 with NaN3 converted it to the alkyne 28 (J. Org. Chem. 2017, 82, 5538. DOI: 10.1021/acs.joc.7b00346). Sunliang Cui of Zhejiang University prepared the alkyne 31 by coupling 30 with 29 (Org. Lett. 2017, 19, 1744. DOI: 10.1021/acs.orglett.7b00499).

Shengming Ma, also of Zhejiang University, prepared the allene 34 by the Rh-mediated addition of 32 to the alcohol 33 (Org Chem. Front. 2017, 4, 2002. DOI: 10.1039/C7QO00588A). Mariola Tortosa of the Universidad Autónoma de Madrid achieved high diastereocontrol in the rearrangement of 35 to 36 (Chem. Eur. J. 2017, 23, 17478. DOI: 10.1002/chem.201705019).

Although many synthetic routes to prostaglandins have been developed, most suffer from the need to deprotect the final product. Amir H. Hoveyda of Boston College developed a Ru catalyst that, in conjuction with 2-butene as a capping agent, enabled the cross metathesis of the acid 38 with the unprotected diol 37, to give prostaglandin E2 (39) directly (J. Am. Chem. Soc. 2017, 139, 10919. DOI: 10.1021/jacs.7b06552).

D. F. Taber, Org. Chem. Highlights 2018, September 17.