Organic Chemistry Portal
Organic Chemistry Highlights

Monday, January 28, 2019
Douglass F. Taber
University of Delaware

Functional Group Protection: The Hodgson Synthesis of (-)-6,7-Dideoxysqualestatin H5

Petr KlŠn of Masaryk University deprotected the alkyne 1 by irradiation with 525 nm LEDs, followed by decarboxylation of the resulting free acid to give 2 (Chem. Commun. 2018, 54, 5558. DOI: 10.1039/C8CC03341B). Kengo Akagawa of the University of Tokyo developed a strategy for iterative polyketide synthesis based on the cyclization of 3 to 4 (J. Org. Chem. 2018, 83, 4279. DOI: 10.1021/acs.joc.8b00497).

Chi Wi Ong of the National Sun Yat Sen University selectively deprotected 5, leading to 6 (Tetrahedron Lett. 2018, 59, 365. DOI: 10.1016/j.tetlet.2017.12.060). Mattan Hurevich of the Hebrew University of Jerusalem used 350 nm LEDs to prepare 8 by deprotecting 7 (Synlett 2018, 29, 880. DOI: 10.1055/s-0036-1591915). Selective acylation of carbohydrates has usually involved a lengthy scheme of protection and deprotection. Zaher M. A. Judeh of Nanyang Technological University showed that using the appropriate organocatalyst, 9 could be selectively acylated with 10 to give 11 (Synlett 2018, 29, 1079. DOI: 10.1055/s-0036-1591753). Hideaki Fujii of Kitasato University found that 12 could be desilylated to 13 by exposure to SO3H silica gel (Tetrahedron 2017, 73, 5425. DOI: 10.1016/j.tet.2017.07.047).

Sophie A. L. Rousseaux of the University of Toronto demonstrated that the adduct between CO2 and 14 could be activated, then combined with benzyl alcohol to give the urethane 15 (J. Org. Chem. 2018, 83, 913. DOI: 10.1021/acs.joc.7b02905). Unsymmetrical ureas could also be prepared using this strategy. Kirsten Zeitler of the Universitšt Leipzig showed that such CO2 adducts could be alkylated with 17, to give the Pac-protected 18, that could be converted back to 16 photocatalytically on irradiation with visible light (J. Org. Chem. 2018, 83, 3738. DOI: 10.1021/acs.joc.8b00096). Zhiguo Zhang and Guisheng Zhang of Henan Normal University oxidatively deprotected 19 to give 20 (J. Org. Chem. 2018, 83, 1369. DOI: 10.1021/acs.joc.7b02880). Craig S. Harris of Nestlť Skin Health devised conditions for the selective deacylation of 21 to 22 (Eur. J. Org. Chem. 2018, 2995. DOI: 10.1002/ejoc.201800304).

Shiyue Fang of Michigan Technological University developed the dithianylmethyl (dM-Dim) group 23. Mild oxidation followed by exposure to base liberated the carboxylic acid 24 (Tetrahedron Lett. 2018, 59, 1763. DOI: 10.1016/j.tetlet.2018.03.076). Oscar Verho of Stockholm University established that acylation of the 8-aminoquinoline amide 25 gave an intermediate that in turn acylated 26, leading to 27 (J. Org. Chem. 2018, 83, 4464. DOI: 10.1021/acs.joc.8b00174).

David M. Hodgson of the University of Oxford observed that the trisubstituted alkene of 6,7-dideoxysqualestatin H5 (25) was not stable to TFA. As an alternative, the bromoalkene 23 was brought through the cyclization to 24. Methylation followed by saponification then completed the synthesis (Chem. Commun. 2018, 54, 5354. DOI: 10.1039/C8CC02690D).

D. F. Taber, Org. Chem. Highlights 2019, January 28.