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 ParisTech devised ( Synlett 2009, 803) 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 (Organic Lett. 2009, 11 , 571) a clever chain-walking ring-closing ene-yne 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, see Organic Highlights, September 13, 2004. 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) 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) 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.