Synthesis of trans/cis 4-substituted 3-furyl-2-phenethyltetrahydroisoquinolin-1-ones: conformation of the trans-4-(pyrrolidinylcarbonyl) derivative

The title compounds were synthesized starting from homophthalic anhydride and an imine. The amides obtained showed unexpected values for 3J3,4 that cannot be used to deduce their configuration and conformation. This problem was resolved for one representative compound (the 4-(pyrrolidinylcarbonyl) derivative) by means of detailed NMR studies, X-ray diffraction and theoretical calculations. The compound has the trans configuration. In the solid state, its conformation is with dipseudoaxial (aa) oriented substituents at positions 3 and 4. In different solvents and in the gas-phase, the majority of the data reveal that the observed value of 3J3,4 results from an equilibrium of the ee and aa conformers.