Formation of Eight-membered Carbocycles by RCM

In order to increase conformational flexibihty in the cychzation precursor, Paquette et al. considered the relocation of the double bond from the A to the site to project axially the two Cl and C5 substituents. As shown by MM3 calculations on model systems, the closer proximity of these two substituents in the isomer could allow a more RCM. Diene 352 was then prepared and 

RCM strategy that was thwarted by conformational constraints imposing a cyclic carbonate protecting group of the C1-C2 diol motif. 

7 Synthesis of Natural Products Containing Medium-size Carbocycles 

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