Application of [5+2] cycloaddition toward the functionalized bicyclo[4.3.1]decane ring system: synthetic study of phomoidride B (CP-263,114)

摘要

A synthetic study of a 1-arylnaphthalene lignan having a heteroaryl group, such as the pyridyl group, at the C(1)nposition was conducted in detail. The Diels–Alder reaction of 1-pyridylisobenzofuran precursor 1 with dimethylnmaleate or dimethyl fumarate gave desired 1,4-epoxides 2–5 in good yields as mixtures of exo and endondiastereoisomers. Intensive investigation of the following acid-promoted aromatisation using a Lewis acid or anBrønsted acid as a reaction promoter revealed that BF3u0001Et2O was the most suitable acid for this step. Examination ofnthe reaction rates in aromatisation of 1,4-epoxides 2–5 provided information for the elaboration of reactionnmechanisms in these reactions. Both the neighbouring-group effect of the 2-methoxycarbonyl substituent stabilisingnthe benzyl cation intermediate and the longer length of the C(1)–O bond in 1,4-epoxide in 2-endo form 3 (or 5) thannthat of the C(4)–O bond presumably contribute to enhancing the reaction rate, and aromatisation of the 2-endo formnwould be greatly favoured over that of the 2-exo form.