Application of Lewis acid catalyzed tropone [6+4] cycloadditions to the synthesis of the core of CP-225,917.
The carbocyclic core of CP-225,917 and CP-263,114 is accessible through the [6+4] cycloaddition of a tropone with a 2-substituted cyclopentadiene. Examination of this reaction has revealed for the first time that this cycloaddition process is catalyzed by Lewis acids, including lanthanide triflates. Cycloadditions of several mono-, di-, and trisubstituted tropones with 2-silyloxycyclopentadienes using ZnCl(2) catalysis are found to proceed in good yield and, in many cases, with excellent diastereoselectivity. Subsequent transformation to the core of the CP-molecules involves a site-selective Baeyer-Villiger oxidation of a tricyclic diketone, followed by a syn-elimination process. [reaction: see text]
Isakovic
L
L
Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec, Canada, H3A 2K6.
Ashenhurst
J A
JA
Gleason
J L
JL
D000143:Acids / Q000737:chemistry*; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors; D008299:Maleic Anhydrides / Q000138:chemical synthesis* / Q000737:chemistry; D014334:Tropolone / Q000031:analogs & derivatives* / Q000737:chemistry*
D000143:Acids; C104959:CP 225917; D004791:Enzyme Inhibitors; D008299:Maleic Anhydrides; D014334:Tropolone; C003730:tropone; D013186:Farnesyl-Diphosphate Farnesyltransferase