Isolation and stereochemical assignment of phthalides resulting from the Diels–Alder reaction between 5-isopropoxyfuran-2(5H)-one and cyclopentadiene

Naturally occurring phthalides and their synthetic analogs, feature a wide range of bioactivities. In our work, the Diels–Alder reaction between 5-isopropoxyfuran-2(5 H )-one and cyclopentadiene was chosen as the key step to obtain tetrahydroisobenzofuran-1(3 H )-one derivatives. The anti-endo (major), anti-exo and syn-endo adducts were isolated and structurally elucidated by nmr experiments. In order to rationalize the experimental finding, chemical shifts were predicted by theoretical calculations using density functional theory at B3LYP/6-31G(d,p) and B3LYP/6-311 + G(2d,p) levels. The goodness-of-fit between calculated and experimental data was evaluated by comparing mean absolute errors and applying DP4 probability methodology. Results demonstrated that DP4 probability of combined data ( 13 C and 1 H) is the most efficient method for assignment of the correct diastereoisomers.