Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 10, 2019
Douglass F. Taber
University of Delaware

Functional Group Protection: The Chen Synthesis of Oxycodone

Barry M. Trost of Stanford University devised a chemoselective protocol for removing a 2,2,2-trichloroethoxycarbonyl (Troc) group, converting 1 to 2 (Org. Lett. 2018, 20, 8043. DOI: 10.1021/acs.orglett.8b03642). Florence J. Williams of the University of Alberta showed that a 1:1 mixture of BBr3 with BCl3 was particularly effective for deprotecting the allyl ether 3 to 4 (Org. Lett. 2018, 20, 6332. DOI: 10.1021/acs.orglett.8b02356). Qian Wan of the Huazhong University of Science and Technology used 1,4-dithiothreitol to convert 5 to 6 (Org. Chem. Front. 2018, 5, 2427. DOI: 10.1039/C8QO00247A). Richard R. Schmidt of the University of Konstanz and Peng Peng of Shandong University selectively benzoylated 7, leading to 8 (Org. Lett. 2018, 20, 3862. DOI: 10.1021/acs.orglett.8b01446).

Arun Kumar Gupta of the Biocon Bristol Myers Squibb Research Centre developed conditions for removing the Boc protecting group from 9 to give 10, leaving the sensitive cyanomethyl ester intact (Tetrahedron Lett. 2018, 59, 4267. DOI: 10.1016/j.tetlet.2018.10.041). Masato Oikawa of Yokohama City University used UV light to convert 11 to 12 (Tetrahedron Lett. 2018, 59, 4259. DOI: 10.1016/j.tetlet.2018.10.045). Shiyue Fang of the Michigan Technological University developed the dM-Dmoc group of 13, readily removable under mild oxidizing conditions to give 14 (Beilstein J. Org. Chem. 2018, 14, 1750. DOI: 10.3762/bjoc.14.149). The N-Ts group has a reputation for being difficult to remove. Eietsu Hasegawa of Niigata University used the reagent 16, activated by irradiation with white light, to convert 15 to 17 (J. Org. Chem. 2018, 83, 10813. DOI: 10.1021/acs.joc.8b01536).

Hee-Kwon Kim of Chonbuk National University used the reagent 19 to convert the acid 18 to the t-butyl ester 20 (Tetrahedron 2018, 74, 3748. DOI: 10.1016/j.tet.2018.05.050). Pengfei Wang of the University of Alabama at Birmingham used UV light to deprotect 21 to 22. Alcohols could also be deprotected under similar conditions (J. Org. Chem. 2018, 83, 7459, 10736. DOI: 10.1021/acs.joc.8b00550). Michal Szostak of Rutgers University, Newark showed that the imide 23 underwent smooth esterification with phenol 24, leading to the phenyl ester 25 (Org. Lett. 2018, 20, 5622. DOI: 10.1021/acs.orglett.8b02323). Ashraf Brik of Technion-Israel Institute of Technology found that 26, prepared by native chemical ligation, could be deprotected to 27 by a Pd catalyst in the presence of glutathione (Org. Biomol. Chem. 2018, 16, 4061. DOI: 10.1039/C8OB00890F).

In the course of a synthesis of oxycodone (30), David Y.-K. Chen of Seoul National University prepared the prochiral hydroperoxide 28. Exposure to 2-methyl propionaldehyde in the presence of an enantiomerically-pure phosphoric acid converted it to 29, effecting enantioselective protection of one of the two alkenes (Chem. Commun. 2018, 54, 13018. DOI: 10.1039/C8CC07667G).

D. F. Taber, Org. Chem. Highlights 2019, June 10.