Intramolecular Diels–Alder reactions of the furan diene (IMDAF); rapid construction of highly functionalised isoquinoline skeletons

Abstract

Intramolecular Diels–Alder reaction of substituted furans has been investigated as a prelude to focused application to the synthesis of isoquinoline alkaloids. Several conditions have been investigated for the model compound 6 containing both unactivated dienophile and diene. The best conversion to cycloadduct 8(84%) was achieved with β-cyclodextrin catalysis. The thermal cyclisation of methoxyfuran precursor 11 gave 55% yield of the cycloadduct 13 and 40% yield of anisole derivative 14. Finally, the phenyl-substituted precursor 23 was cyclised in a yield of 13% at the expense of undesired elimination of 2-phenylbutadiene. These studies provide preliminary evidence that highly functionalised isoquinolines are accessible by the intramolecular Diels–Alder reaction of furans.