Syntheses of Civetone

After the development of the modern metathesis catalysts, [185] the synthesis of civetone was one of the first applications of ring-closing metathesis. [186] A Claisen condensation followed by metathesis can be used to prepare civetone, but even under extreme dilution (10 -10 molar), the maximum yield is only 24 %, because of considerable polymer formation. 

Recently Y. Tanabe published a one-pot synthesis starting from methyl dec-9-enoate. [187,188] Key steps are a Lewis acid-catalysed Claisen condensation and a ring-closing metathesis. It is noteworthy that the metathesis proceeds in presence of a titanium enolate complex. Decarboxylation follows spontaneously and gives the product in 48 % yield. 

When the synthesis is carried out in a stepwise manner, civetone is obtained with a yield of even 74 %. 

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Cp2TiMe2 and WOCI4 or WCle is an effective catalytic system for the metathesis of olefins. Importantly, the system tolerates carboxylic esters, and this enabled it to be used to effect the key steps in syntheses of civetone and other macrolides. Unsaturated ketones or acetals are not suitable substrates. 

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