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

Abstract

Karl Anker Jørgensen of Aarhus University found (Angew. Chem. Int. Ed. 2009, 48, 6650) 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) 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) 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) 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) 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) 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 (Organic Lett. 2009, 11, 4660) 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 (Organic Lett. 2009, 11, 5246) 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, which would be more useful in a target-directed synthesis, would be compatible with these methods for ring construction.