Organic Chemistry Portal
Organic Chemistry Highlights

Monday, February 16, 2015
Douglass F. Taber
University of Delaware

Alkylated Stereogenic Centers: The Jia Synthesis of (-)-Goniomitine

John W. Wong of Pfizer and Kurt Faber of the University of Graz used (Adv. Synth. Catal. 2014, 356, 1878. DOI: 10.1002/adsc.201301055) a wild-type enzyme to reduce the nitrile 1 to 2 in high ee. Takafumi Yamagami of Mitsubishi Tanabe Pharma described (Org. Process Res. Dev. 2014, 18, 437. DOI: 10.1021/op400354g) the practical diastereoselective coupling of the racemic acid 3 with the inexpensive pantolactone 4 to give, via the ketene, the ester 5 in high de.

Takeshi Ohkuma of Hokkaido University devised (Org. Lett. 2014, 16, 808. DOI: 10.1021/ol403545b) a Ru/Li catalyst for the enantioselective addition of in situ generated HCN to an N-acyl pyrrole 6 to give 7 in high ee. Yujiro Hayashi of Tohoku University found (Chem. Lett. 2014, 43, 556. DOI: 10.1246/cl.131199) that an aldehyde 8 could be added to formalin, leading in high ee to the masked aldehyde 9. Stephen P. Fletcher of the University of Oxford prepared (Org. Lett. 2014, 16, 3288. DOI: 10.1021/ol501292x) the lactone 12 in high ee by adding an alkyl zirconocene, prepared from the alkene 11, to the unsaturated lactone 10.

In a remarkable display of catalyst control, Masakatsu Shibasaki of the Institute of Microbial Chemistry and Shigeki Matsunaga of the University of Tokyo opened (J. Am. Chem. Soc. 2014, 136, 9190. DOI: 10.1021/ja5039165) the racemic aziridine 13 with malonate 14 using a bimetallic catalyst. One enantiomer of the aziridine was converted specifically to the branched product 15 in high ee. The other enantiomer of the aziridine was converted to the regioisomeric opening product.

Kimberly S. Peterson of the University of North Carolina at Greensboro used (J. Org. Chem. 2014, 79, 2303. DOI: 10.1021/jo402853v) an enantiomerically-pure organophosphate to selectively deprotect the bis tert-butyl ester 16, leading to 17. Chunling Fu of Zhejiang University and Shengming Ma of the Shanghai Institute of Organic Chemistry showed (Chem. Commun. 2014, 50, 4445. DOI: 10.1039/C4CC00767K) that an organocatalyst could mediate the brominative oxidation of 18 to 19. The ee of the product was easily improved via selective crystallization of the derived dinitrophenylhydrazone.

James P. Morken of Boston College developed (Org. Lett. 2014, 16, 2096. DOI: 10.1021/ol500456s) conditions for the allylation of an allylic acetate such as 20, to deliver the coupled product 21 with high maintenance of ee. Hirohisa Ohmiya and Masaya Sawamura, also of Hokkaido University, described (Angew. Chem. Int. Ed. 2014, 53, 4954. DOI: 10.1002/anie.201402386) the direct enantioselective coupling of 24, prepared in situ from the corresponding alkene, with the allylic chloride 23 to give 25. Amir H. Hoveyda, also of Boston College, assembled (Angew. Chem. Int. Ed. 2014, 53, 1910. DOI: 10.1002/anie.201309456) 28 by adding 27, prepared in situ from the alkyne, to the enone 26. Matthew S. Sigman of the University of Utah constructed (Nature 2014, 508, 340. DOI: 10.1038/nature13231) the quaternary center of 30 by the Pd-mediated addition of phenyl boronic acid to the alkene 29.

The alkaloid (-)-Goniomitine (34), isolated from Gonioma malagasy, shows nanomolar antiproliferative activity against several human tumor cell lines. Yanxing Jia of Peking University prepared (Org. Lett. 2014, 16, 3416. DOI: 10.1021/ol501341b) the quaternary center of 34 by diastereoselective alkylation of the β-hydroxy ester 31.

D. F. Taber, Org. Chem. Highlights 2015, February 16.