Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 29, 2010
Douglass F. Taber
University of Delaware

Stereocontrolled Construction of C-O Rings: The Seeberger/Hilvert Synthesis of KDN

Simple thought it appears, there has not been a good protocol for opening an epoxide 1 with a stabilized enolate. Ferdinando Pizzo of the Universitŗ di Perugia developed (Tetrahedron Lett. 2010, 51, 1566. DOI: 10.1016/j.tetlet.2010.01.055) a solution to this problem. Masahiro Terada of Tohoku University found (Angew. Chem. Int. Ed. 2010, 49, 1858. DOI: 10.1002/anie.200906647) that under organocatalysis, the prochiral 4 condensed with aromatic aldehydes with high relative and absolute stereocontrol. Jon T. Njardarson, now at the University of Arizona, showed (Angew. Chem. Int. Ed. 2010, 49, 1648. DOI: 10.1002/anie.200906830) that the geometry of the epoxide 7 dictated the relative configuration of the product dihydrofuran 8.

John P. Wolfe of the University of Michigan devised (Org. Lett. 2010, 12, 1268. DOI: 10.1021/ol1001472) conditions for the diastereocontrolled cyclization of 9 to 10. Robert Britton of Simon Fraser University observed (Org. Lett. 2010, 12, 1716. DOI: 10.1021/ol100260z) that the microwave-induced closure of 12 proceeded with clean inversion. Christian B. W. Stark of the Universitšt Leipzig established (Angew. Chem. Int. Ed. 2010, 49, 1587. DOI: 10.1002/anie.200903090) that the Ru-mediated oxidative cyclization of 14 to 15 was also highly diastereocontrolled.

Two all-trans diastereomers could emerge from the cascade aldol condensation of 16 with an aldehyde. Takashi Yamazaki of the Tokyo University of Agriculture and Technology devised (Org. Lett. 2010, 12, 268. DOI: 10.1021/ol902592t) conditions for the selective preparation of either diastereomer. Xuegong She of Lanzhou University uncovered (J. Am. Chem. Soc. 2010, 132, 1788. DOI: 10.1021/ja910346m) conditions for the Pt-mediated cyclization of the simple substrate 18 to the tetrahydropyran 19.

Michael J. Zacuto of Merck Process established (Org. Lett. 2010, 12, 684. DOI: 10.1021/ol9026667) the Ru-catalyzed cyclization of 20 to 21. When an OH was not available, NH insertion was also efficient. Fabien Gagosz of the Ecole Polytechnique Palaiseau devised (J. Am. Chem. Soc. 2010, 132, 3543. DOI: 10.1021/ja9100134) the mechanistically-distinct Au-mediated cyclization of 22 to 23.

Glenn C. Micalizio of Scripps/Florida used (J. Am. Chem. Soc. 2010, 132, 7602. DOI: 10.1021/ja102888f) the protocol he had developed to couple 24 and 25 to give a intermediate trisubstituted alkene. Oxidative cleavage of the alkene delivered the ketone, that under acidic conditions cyclized to the spiroketal 26. Kaori Ando of Gifu University extended (Org. Lett. 2010, 11, 1460. DOI: 10.1021/ol100071d) the Z-selective Horner-Emmons condensation to macrolide construction, cyclizing 27 to 28.

Peter H. Seeberger, now at the Max-Planck-Institute Potsdam, and Donald Hilvert of ETH Zurich deployed (Nat. Chem. 2010, 2, 102. DOI: 10.1038/nchem.504) the promiscuous aldolase macrophomate synthase to add 30 to 29, to give, after deprotection, the valuable higher sugar KDN (31). Over a wide range of α-chiral aldehydes, the addition of 30 was efficient, and proceeded to give the same absolute configuration of the newly-established stereogenic center.

D. F. Taber, Org. Chem. Highlights 2010, November 29.