Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 11, 2018
Douglass F. Taber
University of Delaware

Functional Group Protecting: The Rawal Synthesis of (-)-N-Methylwelwitindolinone B Isothiocyanate

Hiroshi Nagase of the University of Tsukuba selectively (Tetrahedron 2017, 73, 5751. DOI: 10.1016/j.tet.2017.08.014) ketalized 1 with ethylene glycol 2, leaving the aldehyde of 3 still exposed. Floris P. J. T. Rutjes of Radboud University directly (J. Org. Chem. 2017, 82, 6671. DOI: 10.1021/acs.joc.7b00632) oxidized the methyl ether 4 to the ketone 5.

Yasunori Toda and Hiroyuki Suga of Shinshu University devised (ACS Catal. 2017, 7, 6150. DOI: 10.1021/acscatal.7b02281) an organocatalyst that directed the selective primary acylation of 6 with 7, leading to 8. Christopher D. Maycock of the Universidade de Lisboa developed (Tetrahedron 2017, 73, 1165. DOI: 10.1016/j.tet.2017.01.020) the nonvolatile reagent 10, that alkylated the alkoxide derived from 9 to give 11. Mark S. Taylor of the University of Toronto showed (J. Am. Chem. Soc. 2017, 139, 15515. DOI: 10.1021/jacs.7b09420) that the areneboronic acid 13 played a dual role in the selective preparation of 14 from 12.

Benzyl ethers are ubiquitous protecting groups. Huan Cong of the Technical Institute of Physics and Chemistry, Beijing devised (ACS Catal. 2017, 7, 8134. DOI: 10.1021/acscatal.7b03029) a protocol for the selective oxidation of the benzyl ether 15 to the benzoate 16.

Chenhui Sun of the Beijing Institute of Technology used (Synlett 2017, 28, 2675. DOI: 10.1055/s-0036-1588533) cyanogen bromide to convert the allyl amine 17 to the cyanamide 18. C. Oliver Kappe of the University of Graz designed (Angew. Chem. Int. Ed. 2017, 56, 13786. DOI: 10.1002/anie.201708533 ) a flow system for the in situ generation and use of the very reactive cyanogen bromide. Michel R. Gagné of the University of North Carolina employed (Synlett 2017, 28, 2429. DOI: 10.1055/s-0036-1590967) sonication to promote the deprotection of 19, leading to 20. Edvinas Orentas of Vilnius University investigated (J. Org. Chem. 2017, 82, 13423. DOI: 10.1021/acs.joc.7b02507) the acid-mediated deprotection of a range of sulfonamides (not illustrated).

Hélène Lebel of the Université de Montréal employed (Org. Lett. 2017, 19, 4407. DOI: 10.1021/acs.orglett.7b02231) 23 in flow to oxidize a primary or secondary amine, or methylamine 22, to the diazonium intermediate and couple it directly with an acid 21, leading to the ester 24. In the course of a synthesis of leucinostatin A (Chem. Eur. J.2017, 23, 11792. DOI: 10.1002/chem.201703239), Takumi Watanabe and Masakatsu Shibasaki of the Institute of Microbial Chemistry were able to saponify the ester 25 to the acid 26, without competing β-elimination of the silyloxy ketone. Jin-Quan Yu of Scripps-La Jolla used (Org. Lett. 2017, 19, 5860. DOI: 10.1021/acs.orglett.7b02841) the epoxide 28 to mediate the alcoholysis of the amide 27 to the ester 29. Pengfei Wang of the University of Alabama at Birmingham found (J. Org. Chem. 2017, 82, 7309. DOI: 10.1021/acs.joc.7b00927) that the o-dimethylaminobenzyl ester 30 was readily cleaved under irradiation, to give 31.

A particular challenge in the synthesis of N-methylwelwitindolinone B isothocyanate (35) was the installation of the delicate homoallylic secondary chloride. Viresh H. Rawal of the University of Chicago solved (Angew. Chem. Int. Ed. 2017, 56, 9962. DOI: 10.1002/anie.201705322) this problem by Pt-catalyzed addition of 33 to the vinyl group of 32 to give 34.

D. F. Taber, Org. Chem. Highlights 2018, June 11.