Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 25, 2011
Douglass F. Taber
University of Delaware

C-N Ring Construction: The Zakarian Synthesis of (-)-Rhazinilam

William D. Wulff of Michigan State University developed (J. Am. Chem. Soc. 2010, 132, 13100, DOI: 10.1021/ja1038648; Org. Lett. 2010, 12, 4908, DOI: 10.1021/ol102064b) a general enantio- and diastereocontrolled route from an imine 1 to the aziridine 3. Craig W. Lindsley of Vanderbilt University established (Org. Lett. 2010, 12, 3276. DOI: 10.1021/ol101276x) a complementary approach, not illustrated. Joseph P. Konopelski of the University of California, Santa Cruz designed (J. Am. Chem. Soc. 2010, 132, 11379. DOI: 10.1021/ja1050023) a practical and inexpensive flow apparatus for the cyclization of 4 to the β-lactam 5.

Manas K. Ghorai of the Indian Institute of Technology, Kanpur showed (J. Org. Chem. 2010, 75, 6173. DOI: 10.1021/jo101004x) that an aziridine 6 could be opened with malonate to give the γ-lactam 8. John P. Wolfe of the University of Michigan devised (J. Am. Chem. Soc. 2010, 132, 12157. DOI: 10.1021/ja106989h) a Pd catalyst for the enantioselective cyclization of 9 to 11. Sherry R. Chemler of the State University of New York at Buffalo observed (Angew. Chem. Int. Ed. 2010, 49, 6365. DOI: 10.1002/anie.201003499) that the cyclization of 12 to 14 proceeded with high diastereoselectivity. Glenn M. Sammis of the University of British Columbia devised (Synlett 2010, 3035. DOI: 10.1055/s-0030-1259062) conditions for the radical cyclization of 15 to 16.

Jeffrey S. Johnson of the University of North Carolina observed (J. Am. Chem. Soc. 2010, 132, 9688. DOI: 10.1021/ja1032277) that the opening of racemic 17 with 18 could be effected with high ee. The residual 17 was highly enriched in the non-reactive enantiomer. Kevin D. Moeller of Washington University found (Org. Lett. 2010, 12, 5174. DOI: 10.1021/ol102193x) that the n-BuLi catalyzed cyclization of 20 set the quaternary center of 21 with high relative control.

Yujiro Hayashi of the Tokyo University of Science, using the diphenyl prolinol TMS ether that he developed as an organocatalyst, designed (Org. Lett. 2010, 12, 4588. DOI: 10.1021/ol1018932) the sequential four-component coupling of 22, 23, benzaldehyde imine and allyl silane to give 24 with high relative and absolute stereocontrol. Derrick L. J. Clive of the University of Alberta showed (J. Org. Chem. 2010, 75, 5223. DOI: 10.1021/jo101010c) that 25, prepared in enantiomerically-pure form from serine, participated smoothly in the Claisen rearrangement, to deliver 27.

James L. Leighton of Columbia University extended (J. Am. Chem. Soc. 2010, 132, 10248. DOI: 10.1021/ja104480g) the utility of the inexpensive chiral auxiliary 30, using it to effect the combination of 28 and 29 to give 31. Keiji Maruoka of Kyoto University observed (Chem. Sci. 2010, 1, 499. DOI: 10.1039/C0SC00250J) that the enamine from the alkylation of 33 with 32 could be hydrogenated with high diastereocontrol to give 34.

Armen Zakarian of the University of California, Santa Barbara was able (Org. Lett. 2010, 12, 4224. DOI: 10.1021/ol101523z) to separate the two enantiomers of 35 by HPLC on a chiral stationary phase. Transannular Heck cyclization followed by hydrogenation then converted 35 to (-)-Rhazinilam (36).

D. F. Taber, Org. Chem. Highlights 2011, April 25.