Organic Chemistry Portal
Organic Chemistry Highlights

Monday, February 8, 2010
Douglass F. Taber
University of Delaware

Enantioselective Construction of Alkylated Centers: The Maier Synthesis of Platencin

Jaesook Yun of Sungkyunkwan University devised (J. Org. Chem. 2009, 74, 4232. DOI: 10.1021/jo900530s) a method, based on conjugate addition to a cyano alkyne, for the preparation of nitriles such as 1 with high geometric control. Enantioselective conjugate reduction then delivered the doubly arylated stereogenic center of 2 in high ee. Pher G. Andersson of Uppsala University described (J. Am. Chem. Soc. 2009, 131, 8855. DOI: 10.1021/ja9013375) a similar approach to diarylated ternary stereogenic centers. Motomu Kanai and Masakatsu Shibasaki of the University of Tokyo developed (J. Am. Chem. Soc. 2009, 131, 3858. DOI: 10.1021/ja9005018) a complementary approach to dialkylated stereogenic centers, based on enantioselective conjugate cyanation of α-methylene N-acylpyrroles such as 3.

Cathleen M. Crudden of Queen’s University established (J. Am. Chem. Soc. 2009, 131, 5024. DOI: 10.1021/ja8094075) that a benzylic organoborane, prepared by enantioselective hydroboration of styrene, coupled with an aryl iodide such as 6 in good yield and with > 90% retention of ee. Kwunmin Chen of National Taiwan Normal University devised (Adv. Synth. Catal. 2009, 351, 1273. DOI: 10.1002/adsc.200800771) an organocatalyst for the enantioselective Michael addition of an α,α,-dialkyl aldehyde such as 9 to a nitroalkene. Wenhu Duan of the East China University of Science & Technology and Wei Wang of the University of New Mexico together developed (Org. Lett. 2009, 11, 2864. DOI: 10.1021/ol9010322) an organocatalyst for the enantioselective addition of nitromethane 12 to an unsaturated ketone such as 11. Xiaodong Shi of West Virginia University found (Angew. Chem. Int. Ed. 2009, 48, 1279. DOI: 10.1002/anie.200805558) that commercial diphenyl prolinol effectively promoted enantioselective conjugate addition of 15 to 14.

Enantioselective methods for the construction of alkylated quaternary centers have also been put forward. Kin-ichi Tadano of Keio University devised (Tetrahedron Lett. 2009, 50, 1139. DOI: 10.1016/j.tetlet.2008.12.091) a glucose-derived chiral auxiliary that effectively directed the absolute sense of the alkylation of 17. Li Deng of Brandeis University reported (Tetrahedron 2009, 65, 3139. DOI: 10.1016/j.tet.2008.11.054) further details of his elegant Cinchona-mediated conjugate addition of 19 to 20. Francesca Marini of the Università degli Studi di Perugia extended (Adv. Synth. Catal. 2009, 351, 103. DOI: 10.1002/adsc.200800592) this approach to selenones, effecting, over two steps, enantioselective vinylation. Professor Shibasaki and Shigeki Matsunaga of the University of Tokyo established (Angew. Chem. Int. Ed. 2009, 48, 2218. DOI: 10.1002/anie.200805967) an alternative protocol for enantioselective alkenylation, the Co*-mediated addition of 25 to 26, to give 27.

In the course of a synthesis of platencin, Martin E. Maier of the Universität Tübingen used (Angew. Chem. Int. Ed. 2009, 48, 3685. DOI: 10.1002/anie.200900447) the Trost procedure to set the absolute configuration of the alkyated quaternary center of 29. Mukaiyama conjugate addition converted 30 to 32 with high diastereocontrol. To effect rearrangement to the desired 33, he then generated the alkyl radical from the ketone using the protocol we had reported (Tetrahedron Lett. 1993, 34, 6209. DOI: 10.1016/S0040-4039(00)73711-7).

D. F. Taber, Org. Chem. Highlights 2010, February 8.