Solid Phase Diels−Alder Reactions of Amino Acid Derived Trienes

Abstract

The known diethyl phosphonoacetyl-Wang resin 1 was treated with an Fmoc-protected amino aldehyde in the presence of Et3N and LiBr. The Fmoc group was then removed with piperidine to give primary amines 3. With or without N-benzylation, 3 was transformed to resin-bound trienes by either reductive alkylation with dienals or by acylation with activated dienocarboxylic acids. Trienes 5 cyclized at room temperature to give the predominant trans-fused bicyclic products 6. Trienes 10 containing a furan moiety were constructed similarly, and their cycloadditions also proceeded at room temperature to produce epoxyisohydroindolines 11, which were derived from an endo transition state pathway. Compounds 12 and 14 containing vinylfuran moieties reacted to form tricyclic products 13 and 15. These examples demonstrated that furan rings can be used in solid-phase Diels−Alder reactions to generate libraries of functionalized polycyclic compounds.