Organic Chemistry Portal
Organic Chemistry Highlights

Monday, March 23, 2020
Douglass F. Taber
University of Delaware

Functional Group Protecting: The Newhouse Synthesis of Principinol D

Munetaka Kunishima of Kanazawa University prepared 2, an efficient reagent for converting an alcohol 1 into the ether 3 (Org. Lett. 2019, 21, 3093. DOI: 10.1021/acs.orglett.9b00732). Hiromune Ando of Gifu University showed that 6, prepared by combining 4 with 5, was more soluble and easier to handle than the corresponding derivative without the t-butyl group (Org. Lett. 2019, 21, 4197. DOI: 10.1021/acs.orglett.9b01372). Walter Leitner of RWTH Aachen used hydrogenation to deprotect 7 to 8 (Synlett 2019, 30, 405. DOI: 10.1055/s-0037-1611678). Frederic Robert and Yannick Landais of the University of Bordeaux observed that under the silylation conditions they had developed, 9 was converted to the alkene 10 (Chem. Eur. J. 2019, 25, 728. DOI: 10.1002/chem.201803989).

C. Oliver Kappe of the University of Graz used a flow apparatus to generate benzyl bromide in situ, then couple it with 11 to give the benzylamine 12 (Org. Biomol. Chem. 2019, 17, 1384. DOI: 10.1039/C9OB00044E). Bryan Li and Ruizhi Li of Pfizer used flow thermolysis to convert the Boc-protected 13 to 14 (J. Org. Chem. 2019, 84, 4846. DOI: 10.1021/acs.joc.8b02909). Steven D. Bull of the Université Paris-Sud and David J. Aitken of the University of Bath selectively deprotected 15 to 16 (Org. Lett. 2019, 21, 100. DOI: 10.1021/acs.orglett.8b03533). Timothy M. Dore of New York University Abu Dhabi demonstrated that on irradiation, the quaternary ammonium salt 17 released the dialkyl aniline 18 (J. Org. Chem. 2019, 84, 7342. DOI: 10.1021/acs.joc.9b01031).

John D. Chisholm of Syracuse University showed that 20 was an efficient reagent for the conversion of the acid 19 to 21 (J. Org. Chem. 2019, 84, 7871. DOI: 10.1021/acs.joc.9b00745). Yukihiro Motoyama of Toyota Technological Institute deprotected the tert-butyl ester 22 to the acid 23 (Adv. Synth. Catal. 2019, 361, 673. DOI: 10.1002/adsc.201801279). Hexin Zie of the East China University of Science and Technology demonstrated that the ester 24 was readily deprotected to 25 (Tetrahedron Lett. 2019, 60, 1658. DOI: 10.1016/j.tetlet.2019.05.039). Lutai Pan of the Guiyang University of Chinese Medicine and Yonggui Robin Chi of Nanyang Technological University devised conditions for the enantioselective combination of 27 with an acid 26 to give the mixed acetal 28 in high ee (Nature Comm. 2019, 10, 1675. DOI: 10.1038/s41467-019-09445-x). One can imagine many applications for such enantiomerically-pure esters.

In the endgame of a synthesis of the rearranged kaurane diterpenoid principinol D (30), Timothy R. Newhouse faced the challenge of selectively converting one of the ketones to the exo methylene, while at the same time converting the other exo methylene to the tertiary alcohol. In this context, the Mukaiyama hydration proved to be particularly effective (J. Am. Chem. Soc. 2019, 141, 8088. DOI: 10.1021/jacs.9b03751).

D. F. Taber, Org. Chem. Highlights 2020, March 23.