Cyclization–cycloaddition cascades for the construction of azapolycyclic ring systems

Abstract

Cyclic 2-amidofuranones were obtained from the Rh(II)-catalyzed reaction of alpha-diazoketo substituted pyrrolidine derivatives. These compounds are derived by a [1,4]-hydrogen transfer from an initially formed carbonyl ylide dipole. Acylation of the amido-substituted furanone with pivalyl chloride provided a fused amidofuran, which underwent bimolecular Diels-Alder cycloaddition with N-phenylmaleimide. The Rh(II)-catalyzed decomposition of ethyl 2-diazo-3-oxo-(2-oxo-1-pent-4-enoyl-pyrrolidine-3-yl)propionate was also examined. In this case, the alkenyl group tethered to the amido carbonyl underwent smooth intramolecular [4+2]-cycloaddition with the amidofuran obtained from the acylation reaction. An alternate route for the synthesis of cyclic amidofurans was developed using a Pummerer induced cyclization of the thiophenyl substituted acetal derived from the aldol reaction of methoxyphenylsulfanyl acetaldehyde with α-valerolactam. Treatment of the amido-substituted acetal with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) generated an oxonium ion, which readily cyclized onto the adjacent carbonyl group. The amidofuran that was formed underwent an intramolecular Diels-Alder reaction when heated at 110°C in toluene. Subsequent ring opening of the transient [4+2]-cycloadduct followed by elimination of methanol and tautomerization of the resulting cyclohexadienone gave rise to the observed phenolic lactam in good overall yield.Key words: intramolecular, cyclization, Diels-Alder, diazo-ketoamide, rhodium(II).