Organic Chemistry Portal
Organic Chemistry Highlights

Monday, July 11, 2016
Douglass F. Taber
University of Delaware

Enantioselective Preparation of Alcohols and Amines: The Kunz Synthesis of Tetraponerine-8

Kuiling Ding of the Shanghai Institute of Organic Chemistry developed (Chem. Eur. J. 2015, 21, 16387. DOI: 10.1002/chem.201503229) conditions for the enantioselective preparation of the β-aryloxy acid 2 by the hydrogenation of 1. Kazutaka Shibatomi of the Toyohashi University of Technology showed (Chem. Eur. J. 2015, 21, 14095. DOI: 10.1002/chem.201502042) that 4 could be prepared by the enantioselective chlorination of 3 followed by displacement.

Xin-Yuan Liu and Bin Tan of the South China University of Science and Technology used (J. Am. Chem. Soc. 2015, 137, 14039. DOI: 10.1021/jacs.5b09117) an enantioselective Passerini reaction to convert 5 to 7. Michael J. Krische of the University of Texas devised (J. Am. Chem. Soc. 2015, 137, 16024. DOI: 10.1021/jacs.5b12131) a protocol for the preparation of 10 by the coupling of the alcohol 8 with 9. Peng Jiao of Beijing Normal University assembled (Org. Lett. 2015, 17, 3194. DOI: 10.1021/acs.orglett.5b00826) 13 by adding the nitronate 12 to the readily-prepared α-methylene aldehyde 11. James L. Leighton of Columbia University opened (Org. Lett. 2015, 17, 5858. DOI: 10.1021/acs.orglett.5b03034) the epoxide 14 with the alkyne 15 to give 16.

Xiang-Ping Hu of the Dalian Institute of Chemical Physics showed (ACS Catal. 2015, 5, 5026. DOI: 10.1021/acscatal.5b01283) that 18 could be prepared in high ee by the addition of phenylhydrazine to the racemic propargylic acetate 17. Stephen L. Buchwald of MIT achieved (Science 2015, 349, 62, DOI: 10.1126/science.aab3753; J. Am. Chem. Soc. 2015, 137, 9716, DOI: 10.1021/jacs.5b05446) high ee and high regioselectivity in the amination of 19, leading to 20.

Li Deng of Brandeis University assembled (Nature 2015, 523, 445. DOI: 10.1038/nature14617) 23 in high ee by the conjugate addition to 22 of the anion derived from 21. Zheng Wang and Professor Ding achieved (J. Am. Chem. Soc. 2015, 137, 15346. DOI: 10.1021/jacs.5b07764) high ee in the conversion of 24 to 25. Takanori Shibata of Waseda University effected (Chem. Commun. 2015, 51, 16660. DOI: 10.1039/C5CC07102J) enantioselective conjugate addition of 26 to 27 to give 28. The N-pyridyl group was readily removed. Till Opatz of the Johannes Gutenberg-University prepared (J. Org. Chem. 2015, 80, 6864. DOI: 10.1021/acs.joc.5b00868) the α-quaternary amine 30 by the diastereoselective alkylation of 29.

Tetraponerine-8 (34), isolated from the toxin of the Papua New Guinean ant Tetraponera punctulata, is an efficient inhibitor of nicotinic acetylcholine receptors. En route to 34, Horst Kunz, also of Johannes Gutenberg-University, established (Synthesis 2015, 47, 2299. DOI: 10.1055/s-0034-1380215) the second secondary amine of 33 by the D-arabinopyranosyl-directed hetero Diels-Alder addition of 31 to the Danishefsky diene 32.

D. F. Taber, Org. Chem. Highlights 2016, July 11.