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Monday, April 16, 2012
Douglass F. Taber
University of Delaware

C-O Natural Products: (-)-Hybridalactone (Fürstner), (+)- Anthecotulide (Hodgson), (-)-Kumausallene (Tang), (±)-Communiol E (Kobayashi), (-)-Exiguolide (Scheidt), Cyanolide A (Rychnovsky)

Control of the absolute configuration of adjacent alkylated stereogenic centers is a classic challenge in organic synthesis. In the course of the synthesis of (-)-Hybridalactone (4), Alois Fürstner of the Max-Planck-Institut Mülheim effected (J. Am. Chem. Soc. 2011, 133, 13471. DOI: 10.1021/ja204027a) catalytic enantioselective conjugate addition to the simple acceptor 1. The initial adduct, formed in 80% ee, could readily be recrystallized to high ee.

In an alternative approach to high ee 2,3-dialkyl γ-lactones, David M. Hodgson of the University of Oxford cyclized (Org. Lett. 2011, 13, 5751. DOI: 10.1021/ol202425e) the alkyne 5 to an aldehyde, that was condensed with 6 to give 7. Coupling with 8 then delivered (+)-Anthecotulide (9).

The enantiomerically-pure diol 10 is readily available from acetylacetone. Weiping Tang of the University of Wisconsin dissolved (Org. Lett. 2011, 13, 3664. DOI: 10.1021/ol201477u) the symmetry of 10 by Pd-mediated cyclocarbonylation. The conversion of the lactone 11 to (-)-Kumausallene 12 was enabled by an elegant intramolecular bromoetherification.

Shoji Kobayshi of the Osaka Institute of Technology developed (J. Org. Chem. 2011, 76, 7096. DOI: 10.1021/jo201064h) a powerful oxy-Favorskii rearrangement, that enabled the preparation of both four- and five-membered rings with good diastereocontrol, as exemplified by the conversion of 13 to 14. With the electron-withdrawing ether oxygen adjacent to the ester carbonyl, Dibal reduction of 14 proceeded cleanly to the aldehyde. Addition of ethyl lithium followed by deprotection completed the synthesis of (±)-Communiol E.

En route to (-)-Exiguolide (18), Karl A. Scheidt of Northwestern University showed (Angew. Chem. Int. Ed. 2011, 50, 9112. DOI: 10.1002/anie.201102790) that 16 could be cyclized efficiently to 17. The cyclization may be assisted by a scaffolding effect from the dioxinone ring.

Dimeric macrolides such as Cyanolide A (21) are usually prepared by lactonization of the corresponding hydroxy acid. Scott D. Rychnovsky of UC Irvine devised (J. Am. Chem. Soc. 2011, 133, 9727. DOI: 10.1021/ja204228q) a complementary strategy, the double Sakurai dimerization of the silyl acetal 19 to 20.

D. F. Taber, Org. Chem. Highlights 2012, April 16.