Citlalitrione synthesis

Carbene cyclization 36 Carvone (starting material) 33 Citlalitrione synthesis 24 C-H Activation 122 C-H to alcohol 157... 

Leo Paquette of Ohio State recently reported (J. Am. Chem. Soc. 125 1567, 2003) the total synthesis of jatrophatrione 1 and citlalitrione 2. These diterpenes, which share a central highly-subsituted 5-9-5 core, show remarkable tumor-inhibitory activity. 

A transannular ene-reaction was featured in the reaction cascade that was used by Paquette and co-workers in their synthesis of the [5.9.5] tricyclic diterpenes jatrophatrione and citlalitrione. This reaction cascade involved initiating the stereoselective anionic oxy-Cope reaction of 43 by treatment with KOf-Bu and 18-crown-6 followed by trapping the enolate 44 with methyl iodide to give intermediate 45 (Scheme 20.13). This was followed by the spontaneous transannular ene-reaction to give 46 in 70% overall yield. It was converted to jatrophatrione and citMitrione after additional transformations. 

SCHEME 20.13. The transannular ene-reaction in the synthesis of jatrophatrione and citlalitrione. 

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