Organic Chemistry Portal
Organic Chemistry Highlights

Monday, July 20, 2015
Douglass F. Taber
University of Delaware

Construction of Alkylated Stereogenic Centers: The Zhu Synthesis of (-)-Rhazinilam

Zheng Huang of the Shanghai Institute of Organic Chemistry (J. Am. Chem. Soc. 2014, 136, 15501. DOI: 10.1021/ja5093908) and Zhan Lu of Zhejiang University (Org. Lett. 2014, 16, 6452. DOI: 10.1021/ol503282r) effected enantioselective hydroboration of α-alkyl styrenes, as illustrated by the conversion of 1 to 2. Stephen L. Buchwald of MIT devised (J. Am. Chem. Soc. 2014, 136, 15913. DOI: 10.1021/ja509786v) a Cu catalyst for the anti-Markovnikov hydroamination of 3 to 5.

John F. Hartwig of the University of California, Berkeley developed (Angew. Chem. Int. Ed. 2014, 53, 8691, 12172. DOI: 10.1002/anie.201405575) an Ir catalyst for the enantioselective coupling of 6 with 7 to give 8. Hirohisa Ohmiya and Masaya Sawamura of Hokkaido University established (J. Am. Chem. Soc. 2014, 136, 13932. DOI: 10.1021/ja5084333) conditions for the preparation of 11 by the SN2' displacement of the allylic phosphate 9 with the alkyne 10. Ying-Chun Chen of Sichuan University added (Org. Lett. 2014, 16, 6000. DOI: 10.1021/ol503017h) the allyl ketone 12 to 13 to give 14. Huw M. L. Davies of Emory University showed (J. Am. Chem. Soc. 2014, 136, 9792. DOI: 10.1021/ja504797x) that the Rh carbene derived from 16 could insert into the C-H bond of 15 to give 17 in high ee.

K. N. Houk of UCLA and Wen-Hua Zheng of Nanjing University relied (J. Am. Chem. Soc. 2014, 136, 12249. DOI: 10.1021/ja507332x) on a Brřnsted acid to promote the enantioselective oxidation of the prochiral acetal 18 to the ester 19. Xinhao Zhang of Peking University Shenzhen Graduate School and Qian Cai of the Guangzhou Institutes of Biomedicine and Health cyclized (Angew. Chem. Int. Ed. 2014, 53, 9555. DOI: 10.1002/anie.201403844) the prochiral amine 20 to 21 using a Cu catalyst.

Sanzhong Luo of the Institute of Chemistry, Chinese Academy of Sciences employed (J. Am. Chem. Soc. 2014, 136, 14642. DOI: 10.1021/ja508605a) an organocatalyst to mediate the enantioselective alkylation of the acetoacetate 22 with the bromide 23 under photoredox conditions. Takanori Shibata of Waseda University added (Chem. Eur. J. 2014, 20, 8893. DOI: 10.1002/chem.201403446) Me3Al to 25 in a conjugate sense to give, after cyclization, the enol lactone 26. Xingzhong Zeng of Boehringer Ingelheim showed (Angew. Chem. Int. Ed. 2014, 53, 12153. DOI: 10.1002/anie.201406247) that conjugate addition of Me2Zn to 27 gave 28 in high ee. Alexandre Alexakis of the University of Geneva devised (Chem. Eur. J. 2014, 20, 16694. DOI: 10.1002/chem.201404668) a two-step protocol for the enantioselective construction of the α-quaternary alkyne 30 by the sequential coupling of two different Grignard reagents with the dichloride 29.

(-)-Rhazinilam 33, isolated from the evergreen dwarf shrub Rhazya stricta Decaisne, has been shown to interfere with tubulin polymerization and dynamics. Jieping Zhu of the Ecole Polytechnique Fédérale de Lausanne secured (Angew. Chem. Int. Ed. 2014, 53, 9926. DOI: 10.1002/anie.201405842) the absolute configuration of the quaternary center of the intermediate aldehyde 32 by the enantioselective opening of the prochiral bis-lactone 31.

We note with sorrow the passing of Professor Tsutomu Katsuki of Kyushu University, whose inciteful contributions to asymmetric catalysis have often been highlighted on these pages.

D. F. Taber, Org. Chem. Highlights 2015, July 20.