Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 16, 2010
Douglass F. Taber
University of Delaware

Organocatalytic Carbocyclic Construction: The Christmann Synthesis of (+)-Rotundial

Karl Anker Jørgensen of Aarhus University found (Angew. Chem. Int. Ed. 2009, 48, 6650. DOI: 10.1002/ange.200903253) that an organocatalyst could mediate the fragmentation of the prochiral cyclopropane 1 with high ee to the easily-epimerized product 2. Guofu Zhong of Nanyang Technological University devised (Angew. Chem. Int. Ed. 2009, 48, 6089. DOI: 10.1002/ange.200901249) a dipolar cycloaddition strategy for the organocatalyzed combination of 3 and 4 with PhNHOH to give the highly-substituted cyclopentane 5.

Professor Jørgensen also established (Angew. Chem. Int. Ed. 2009, 48, 7338. DOI: 10.1002/anie.200903790) that conjugate addition of 7 to the prochiral cyclohexenone 6 proceeded with high ee. The initial adduct could be converted into the alkene 8, the alkyne, or the ketone. Wen-Jing Xiao of Central China Normal University, following up on the work of Gong and Cheng, developed (Tetrahedron 2009, 65, 9238. DOI: 10.1016/j.tet.2009.09.005) a simple organocatalyst for the desymmetrizing Michael addition of 9 to 10 to give 11 with high de and ee.

Control of sidechain chirality is an important aspect of carbocyclic construction. Samuel H. Gellman of the University of Wisconsin demonstrated (J. Am. Chem. Soc. 2009, 131, 16018. DOI: 10.1021/ja907233q) that the organocatalyzed addition of 13 to 12 proceeded with high facial selectivity and excellent diastereocontrol. In a complementary approach, Alexander J. A. Cobb of the University of Reading optimized (J. Am. Chem. Soc. 2009, 131, 16016. DOI: 10.1021/ja9070915) an organocatalyst for the cyclization of 15 to 16, again with high facial selectivity and excellent diastereocontrol.

Ying-Chun Chen of the West China School of Pharmacy established (Org. Lett. 2009, 11, 4660. DOI: 10.1021/ol901939b) conditions for the organocatalyzed combination of 17 with 18 to give 19. In a related approach, Bor-Cherng Hong of the National Chung Cheng University showed (Org. Lett. 2009, 11, 5246. DOI: 10.1021/ol9021832) that 20, 21 and 22 could be combined, under organocatalysis, to give 23 in high ee with excellent diastereocontrol. Both of these approaches, and several others that have been published recently, were carried out with aryl substituents. It remains to be seen whether alkyl substituents, that would be more useful in a target-directed synthesis, would be compatible with these methods for ring construction.

Synthetic strategies for the construction of polycarbocycles are also important. Gilles Dujardin of the Université de Maine found (Org. Lett. 2009, 11, 3060. DOI: 10.1021/ol901065e) that the activated Michael acceptor 25 condensed efficiently with the enamine derived from the combination of cyclohexanone 24 with an organocatalyst. One initial adduct (R = [MeO]3Ph) was carried on to the octalone 26. In this case, a full equivalent of the organocatalyst was employed, but it could be recovered and reused.

Hisashi Yamamoto of the University of Chicago devised (Chem. Commun. 2009, 5412. DOI: 10.1039/B912325C) an organocatalyst for the enantioselective intramolecular Michael addition of the prochiral keto aldehyde 27. Intramolecular aldol condensation of the initial adduct completed the preparation of the tricyclic enone 28.

The β-substituted aldehyde of 29 is reluctant to participate in Michael addition. Mathias Christmann of the TU Dortmund took advantage (Org. Lett. 2009, 11, 4116. DOI: 10.1021/ol901614t) of this in devising the organocatalyzed cyclization of 29 directly to the Vitex rotundifolia iridoid (+)-Rotundial (30).

D. F. Taber, Org. Chem. Highlights 2010, August 16.