Organic Chemistry Portal
Organic Chemistry Highlights

Monday, January 18, 2010
Douglass F. Taber
University of Delaware

Alkene and Alkyne Metathesis: Navenone B (Cossy), (+)-Asperpentyn (Daesung Lee), (-)-Amphidinolide K (Eun Lee), Norhalichondrin B (Phillips)

A variety of antibiotics and immune-suppressive agents contain extended arrays of all-(E)-polyenes. Samir Bouzbouz of CNS Rouen and Janine Cossy of ESPCI Paris devised (Synlett 2009, 803. DOI: 10.1055/s-0028-1087953) a simple iterative route to polyacetates such as 1, and demonstrated that after cross-metathesis, elimination, in this case to give Navenone B (3), was facile. Both ketones and esters can promote the elimination.

Daesung Lee of the University of Illinois at Chicago designed (Org. Lett. 2009, 11, 571. DOI: 10.1021/ol802675j) a clever chain-walking ring-closing enyne metathesis, cyclizing 4 to 5. Deprotection led to (+)-Asperpentyn 6. This should be a general entry to such polyoxygenated cyclohexenes. (For the structures of H2 and G2: The Grubbs Reaction in Organic Synthesis: Part One of Three 2004, September 13).

One of the challenges in the synthesis of (-)-Amphidinoloide K (10) is the assembly of the complex conjugated diene. Eun Lee of Seoul National University found (Angew. Chem. Int. Ed. 2009, 48, 2364. DOI: 10.1002/anie.200805266) a solution to this problem in the Ru-catalyzed cross metathesis between the alkyne 7 and the alkene 8. Note that the cross metathesis proceeded with high regioselectivity, and with substantial (7.5:1) control of the product alkene geometry.

For the construction of complex natural products such as Norhalichondrin B (14), it is important to employ a convergent synthetic strategy. For this to be successful, efficient methods for convergent coupling are required. In the course of a synthesis of 14, Andrew J. Phillips of the University of Colorado showed (Angew. Chem. Int. Ed. 2009, 48, 2346. DOI: 10.1002/anie.200806111) that Ru-mediated cross metathesis could be used to couple the enone 11 with the alkene 12. A less congested version of H2, designed by Robert H. Grubbs of Caltech, was used for the coupling. The electron-deficient alkene of 11 and the more electron-rich alkene of 12 made a matched set, promoting the cross coupling.

Note again, in this context, the desirability of leaving the allylic alcohol of 12 unprotected to facilitate Ru-catalyzed alkene cross metathesis.

D. F. Taber, Org. Chem. Highlights 2010, January 18.