Synthetic approach to analogues of betulinic acid

2-Methylcyclohexane-1,3-dione 14 was converted via the Wieland-Miescher analogue 15 into the 6-silyloxy-2,5,5,8a-tetramethyldecalin-1-one 21 by an efficient process. Several routes were examined to transform this compound into the pentacyclic triterpene skeleton of betulinic acid and its structural analogues. For example, the iodide 39, easily prepared from 21, was converted via a Sonogashira-hydroboration-Suzuki process into the E-triene 45. Photolysis of 45 using a benzanthrone sensitizer afforded the Z-triene 43. However, all attempts at effecting the cyclization of this triene 43 to the cyclohexadiene 47 (electrocyclic via photochemical or thermal means, metal-catalyzed processes, oxidative and radical cyclizations) failed to produce the key pentacyclic material.