Macrocycle Syntheses by Ring Closing Metathesis RCM

This assumption, however, has been totally revised in recent years surprisingly enough, RCM turned out to be among the best entries into macrocycles even with con-formationally flexible diene substrates, provided that a few basic parameters are properly assessed [32]. These key features indicate that a subtle template effect is responsible for the effectiveness and scope of RCM-based ring closure reactions. 

Although the experimental data summarized above provide convincing evidence that a subtle and transient template effect resulting from a finely tuned Lewis-acid/Lewis-base interaction is operative in productive RCM-based macrocyclizations, it should be emphasized that a detailed spectroscopic characterization of the key intermediates involved has not yet been achieved. Therefore structure A represents just a mnemotic device indicating that polarity, distance, and affinity are key issues in such transformations but does not imply any structural information [32]. 

A more detailed assessment of this retrosynthetic scheme, however, reveals a potential difficulty, if the relay model outlined above is valid. Assuming that the cataly.st attacks the 4-pentenoate entity of the envisaged cyclization precursor 34, a fairly stable six-membered chelate structure may be obtained which can intercept the catalyst in an unproductive form. 

Although the precise mode of action of the binary RCM catalyst (i.e., (PCy3)2Cl2Ru=CHPh+H(OiPr)4) remains to be elucidated, its key role within the gloeosporone synthesis gives further credence to the notion that a transient and kinetically labile chelate complex acts as a crucial template which shapes the diene precursor and thereby provides internal bias for ring closure. 

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