Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 27, 2015
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Weinreb Synthesis of Myrioneurinol

Terminal epoxides such as 1 are readily available in high enantiomeric excess. Christopher D. Bray of Queen Mary University of London observed (Tetrahedron Lett. 2014, 55, 5890. DOI: 10.1016/j.tetlet.2014.08.009) clean inversion in the conversion of 1 to the aziridine 3 with the reagent 2. Yong-Chun Luo and Peng-Fei Xu of Lanzhou University opened (Org. Lett. 2014, 16, 4896. DOI: 10.1021/ol5024079) the activated cyclopropane 4 with benzyl azide, then heated the adduct to expel N2, leading to the azetidine 5.

Zhenming Du of Roche Shanghai and Michelangelo Scalone of Roche Basel developed (Org. Process Res. Dev. 2014, 18, 1702. DOI: 10.1021/op500250b) practical conditions for the asymmetric hydrogenation of 6 to the pyrrolidine 7. Young Ho Rhee of the Pohang University of Science and Technology showed (Chem. Eur. J. 2014, 20, 16391. DOI: 10.1002/chem.201404659) that depending on the diol protecting group, addition of allyl silane to 8 could lead to either the cis product 9, or the trans diastereomer (not illustrated). Ohyun Kwon of UCLA used (J. Am. Chem. Soc. 2014, 136, 11890. DOI: 10.1021/ja505592h) an organocatalyst to convert the racemic allene 10 into 12 in high ee. Tom Livinghouse of Montana State University cyclized (Angew. Chem. Int. Ed. 2014, 53, 14352. DOI: 10.1002/anie.201407768) the hydrazine 13 into an intermediate organozinc species that was then coupled with allyl bromide to give 14.

Yonggang Chen of Merck Process and Xumu Zhang of Rutgers University devised (Angew. Chem. Int. Ed. 2014, 53, 12761. DOI: 10.1002/anie.201406762) practical conditions for the reduction of 15 to the piperidine 16. Teck-Peng Loh of the Nanyang Technological University and the University of Science and Technology of China effected (Chem. Commun. 2014, 50, 8324. DOI: 10.1039/C4CC02645D) asymmetric phenylation of biomass-derived 17 to give an intermediate that was oxidatively rearranged, then reduced to 18. Robert R. Knowles of Princeton University showed (J. Am. Chem. Soc. 2014, 136, 12217. DOI: 10.1021/ja5056774) that the cyclization of 19 to 20 proceeded with high diastereoselectivity. Maria J. Alves of the Universidade do Minho osmylated (Synlett 2014, 25, 1751. DOI: 10.1055/s-0034-1378227) the adduct from the Diels-Alder cycloaddition of 22 to 21 to give 23 in high ee.

Sebastian Stecko and Bartlomiej Furman of the Polish Academy of Sciences reduced (J. Org. Chem. 2014, 79, 10487. DOI: 10.1021/jo502146z) the lactam 24 with the Schwartz reagent to give an intermediate that added to the Danishefsky diene 25 to give the bicyclic enamide 26. Xing-Wen Sun and Guo-Qiang Lin of Fudan University used (Chem. Commun. 2014, 50, 15913. DOI: 10.1039/C4CC07703B) an organocatalyst to add 27 to the nitroalkene 28, then condensed the product with the endocyclic ketimine 29 to give the bicyclic 30 in high ee.

Myrioneurinol 33, isolated from the Vietnamese tree Myrioneuron nutans, was shown to have significant anti-malarial activity. A key step in the total synthesis of 33 reported (Angew. Chem. Int. Ed. 2014, 53, 14162. DOI: 10.1002/anie.201407810) by Steven M. Weinreb of Pennsylvania State University was the diastereoselective cyclization of 31 to 32.

D. F. Taber, Org. Chem. Highlights 2015, April 27.