Organic Chemistry Portal
Organic Chemistry Highlights

Monday, January 25, 2010
Douglass F. Taber
University of Delaware

Enantioselective Preparation of Alcohols and Amines: The Suh Synthesis of (-)-Macrosphelide J

Keiji Maruoka of Kyoto University (J. Am. Chem. Soc. 2009, 131, 3450. DOI: 10.1021/ja809963s) and Yujiro Hayashi of the Tokyo University of Science (Chem. Commun. 2009, 3083. DOI: 10.1039/b902287b) independently developed organocatalysts for the enantioselective α-benzoylation of aliphatic aldehydes such as 1. The product 3 can be readily carried on to, inter alia, either enantiomer of the epoxide. Chengjian Zhu of Nanjing University designed (Adv. Synth. Catal. 2009, 351, 920. DOI: 10.1002/adsc.200800767) a chiral salen complex that mediated the enantioselective opening of both cyclohexene oxide (4) and cyclopentene oxide. This reagent combination might also engage just one of the two enantiomers of a racemic cycloalkene epoxide.

Lin Pu of the University of Virginia established (Org. Lett. 2009, 11, 2441. DOI: 10.1021/ol900667g) a BINOL catalyst for the addition of ethyl propiolate 7 to an aliphatic aldehyde 6 to give the propargylic alcohol 8 in high ee. In a complementary approach, Do Hyun Ryu of Sungkyunkwan University found (Angew. Chem. Int. Ed. 2009, 48, 4398. DOI: 10.1002/anie.200900351) that an oxazaborolidinium salt catalyzed the addition of 7 to 9 to give 10 with high ee and high geometric control.

Jianliang Xiao of the University of Liverpool devised (J. Am. Chem. Soc. 2009, 131, 6967. DOI: 10.1021/ja9021683) an Ir catalyst for the enantioselective reductive amination of a ketone 11 to the amine 13. Karl B. Hansen, Yi Hsiao and Feng Xu, then all at Merck Rahway, showed (J. Am. Chem. Soc. 2009, 131, 8798. DOI: 10.1021/ja902462q) that it was possible to hydrogenate a vinylogous primary amide 14 to the amine 15 with high enantiocontrol.

Takashi Ooi of Nagoya University designed (J. Am. Chem. Soc. 2009, 131, 7242. DOI: 10.1021/ja903271t) a chiral P-spiro tetraaminophosphonium catalyst that mediated the enantioselective addition of anilines to nitroalkenes such as 16. The product 18 could be carried on to the 1,2-diamine, or to the α-amino acid.

Masahiro Terada of Tohoku University devised (Angew. Chem. Int. Ed. 2009, 48, 2553. DOI: 10.1002/anie.200805385) a BINOL-derived phosphonic acid to catalyze the enantioselective 1,2-addition of the enamide 20 to the imine derived from 19. Yixin Lu of the National University of Singapore found (Org. Lett. 2009, 11, 1721. DOI: 10.1021/ol9003349) that a cinchona alkaloid-derived thiourea effectively catalyzed the enantioselective conjugate addition of nitroalkanes such as 22 to the acceptor 23. Wing Yiu Yu and Albert S. C. Chan of The Hong Kong Polytechnic University prepared (Adv. Synth. Catal. 2009, 351, 1250. DOI: 10.1002/adsc.200900084) α,α-dimethyl β-amino acid esters by the 1,2-addition of alkynes to the imine 25.

(-)-Macrosphelide J (34) is a trimeric ester containing a sensitive β-alkoxy ketone. Young-Ger Suh of Seoul National University set (Chem. Commun. 2009, 2463. DOI: 10.1039/b817693k) the absolute configuration of the key secondary alcohol of 34 by the highly diastereoselective cycloaddition of the nitrile oxide derived from 29 to the Oppolzer sultam 28. The challenging reduction of the isoxazoline 33 was accomplished with the Kulinkovich reagent.

D. F. Taber, Org. Chem. Highlights 2010, January 25.