Organic Chemistry Portal
Organic Chemistry Highlights

Monday, January 30, 2017
Douglass F. Taber
University of Delaware

Organic Functional Group Interchange: The Wang/Tian/Li Synthesis of Ubiquitin

Leila Khazdooz and Amin Zarei of the Islamic Azad University developed (Tetrahedron Lett. 2016, 57, 168. DOI: 10.1016/j.tetlet.2015.11.078) a convenient protocol for the conversion of an alcohol 1 to the iodide 2. Bromides could also be prepared. James M. Takacs of the University of Nebraska observed (ACS Catal. 2016, 6, 2205. DOI: 10.1021/acscatal.6b00175) substantial selectivity in the borrowed hydrogen amination of 3 to 4. Charles E. Jakobsche of Clark University uncovered (Tetrahedron Lett. 2016, 57, 502. DOI: 10.1016/j.tetlet.2015.12.070) an oxidative procedure for the conversion of the amide 5 to the ester 6. Gregory C. Fu of Caltech established (J. Am. Chem. Soc. 2016, 138, 6404. DOI: 10.1021/jacs.6b03465) that the silylation of 7 to 8 proceeded via a radical intermediate, so the two diastereomers of 7 gave the same exo/endo ratio in the product.

Hongbin Sun of China Pharmaceutical University and Ang Li of the Shanghai Institute of Organic Chemistry established (Org. Biomol. Chem. 2016, 14, 5591. DOI: 10.1039/C6OB00345A) conditions for the conversion of an enol triflate 9 to the alkyne 10. Terminal alkynes could also be prepared this way. Yoshiya Fukumoto of Osaka University improved (J. Org. Chem. 2016, 81, 3161. DOI: 10.1021/acs.joc.6b00116) the Ru-catalyzed conversion of an alkyne 11 to the nitrile 12. Sobi Asako and Kazuhiko Takai of Okayama University silylated (ACS Catal. 2016, 6, 3387. DOI: 10.1021/acscatal.6b00627) the allene 13, readily prepared from the terminal alkyne, to give the Z-allyl silane 14. Sanjay Batra of the Central Drug Research Institute oxidatively cleaved (Adv. Synth. Catal. 2016, 358, 500. DOI: 10.1002/adsc.201500906) the alkyne 15 to the primary amide 16.

Trond Ulven of the University of Southern Denmark developed (Org. Biomol. Chem. 2016, 14, 430. DOI: 10.1039/C5OB02129D) a protocol with the reagent 19 to promote amide bond formation both with hindered substrates and with electron deficient amines, as illustrated by the preparation of 20 by the coupling of 17 with 18. Alina Ghinet of the Université de Lille found (Tetrahedron Lett. 2016, 57, 1165. DOI: 10.1016/j.tetlet.2016.02.004) that ZrCl4 was an effective catalyst for the acylation of 22 with the ester 21 to give 23.

Craig S. Harris of Galderma R&D demonstrated (Tetrahedron Lett. 2016, 57, 2165. DOI: 10.1016/j.tetlet.2016.04.003) that even a very hindered hydroxamic acid 25 could be prepared from the ester 24 by exposure to aqueous hydroxylamine in the presence of DBU. Bradley L. Pentelute of MIT showed (Org. Lett. 2016, 18, 1222. DOI: 10.1021/acs.orglett.5b03625) that the hydrazide 26 of even a fully unprotected peptide could be oxidized and coupled in situ with a nucleophile, in this case methoxyamine to give 27.

Native chemical ligation has become the workhorse for long-chain peptide assembly, in particular as it has been coupled with subsequent desulfurization to convert cysteine to alanine residues. Feng Wang of Tsinghua University, Chang-Lin Tian of the University of Science and Technology and Yi-Ming Li of the Hefei University of Technology found (Chem. Eur. J. 2016, 22, 7623. DOI: 10.1002/chem.201600101) that with methylthioglycolate as the thiol component, the three fragments 28, 29 and 30 could be coupled and the product then desulfurized in a one-pot procedure, leading to natural L-ubiquitin (31).

D. F. Taber, Org. Chem. Highlights 2017, January 30.