Macrocyclic Dienone Products

Diene 265, substituted by a bulky silyl ether to prevent cycloaddition before the metathesis process, produced in the presence of catalyst C the undesired furanophane 266 with a (Z) double bond as the sole reaction product in high yield. The same compound was obtained with Schrock s molybdenum catalyst B, while first-generation catalyst A led even under very high dilution only to an isomeric mixture of dimerized products. The (Z)-configured furanophane 266 after desilylation did not, in accordance with earlier observations, produce any TADA product. On the other hand, dienone 267 furnished the desired macrocycle (E)-268, though as minor component in a 2 1 isomeric mixture with (Z)-268. Alcohol 269 derived from E-268 then underwent the projected TADA reaction selectively to produce cycloadduct 270 (70% conversion) in a reversible process after 3 days. The final Lewis acid-mediated conversion to 272 however did not occur, delivering anhydrochatancin 271 instead. 

Figure 6.1 Representative structures of products accessible using the strategies outlined below include bis-arylidinealkenones (3), 2,6-dibenzylphenols (4), dienone (5 and 7) and Horning-crown (6 and 8) macrocycles, rods (9) and flexible phenol/formaldehyde oligomers (10).

The disconnections shown for (+)-brefeldin A suggest the use of an intramolecular cyclization to close the macrocycle. In fact, the cyclopentene was formed via an intermolecular PKR/retro-Diels-Alder sequence (82 goes to 83) to take advantage of the high reactivity of norbomadiene in the PKR. Furthermore, a new cyclopentenone is revealed by the retro-Diels-Alder reaction so that PKR product 84 is a synthetic equivalent for cyclopenta-dienone 85. 

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