Synthetic studies towards the pinguisanes; synthesis of 4-epi-pinguisone

Abstract

Two procedures have been developed for the synthesis of the appropriate indene skeleton required for construction of pinguisone and 4-epi-pinguisone. Whereas 1-methoxy-3-(trimethylsiloxy)buta-1,3-diene (Danishefsky's diene) was completely unreactive towards 2,3,4-trimethyl-2-cyclopent-2-en-1-one, Diels–Alder cycloaddition was found to occur at very high pressure (13–15 kBar) with the more reactive dienophile methyl 2,3-dimethyl-5-oxocyclopent-1-ene-1-carboxylate giving, after hydrolysis, (3R*,3aS*,7aR*)-methyl 2,3,3a,7a-tetrahydro-3,3a-dimethyl-1,5(4H)-dioxoindene-7a-carboxylate in good yield. The structure of this compound was confirmed by X-ray diffraction. Reaction of the lithium enolate of the diene with the more reactive dienophile at low temperatures gave one Michael addition only; however, the resulting oxo ester was converted into the desired indene intermediate in a good overall yield. Model studies provided a route which, when applied to the indene intermediate, enabled an efficient conversion to (3R*,3aS*,7aS*)-2,3,3a,7a-tetrahydro-3,3a,7a-trimethylindene-1,5(4H)-dione. Conjugate addition with lithium dimethylcuprate gave the undesired epimer exclusively which on further elaboration gave 4-epi-pinguisone and 4-epi-pinguisanol.