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

• Published in: Journal of molecular structure 2015-12, Vol.1101, p.212-218
• Main Authors: Resende, G.C., Alvarenga, E.S., Willoughby, P.H.
• Format: Article
• Language: English
• Subjects: DFT-GIAO; Diels–Alder; Gaussian; Phthalides; α,β-unsaturated γ-lactone
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2015.08.028

Naturally occurring phthalides and their synthetic analogs, feature a wide range of bioactivities. In our work, the Diels–Alder reaction between 5-isopropoxyfuran-2(5H)-one and cyclopentadiene was chosen as the key step to obtain tetrahydroisobenzofuran-1(3H)-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 (13C and 1H) is the most efficient method for assignment of the correct diastereoisomers. [Display omitted] •Anti-endo, anti-exo and syn-endo adducts were structurally elucidated.•Key NMR coupling constants, and NOE interactions have been measured for all isomers.•The MAEs determined for hydrogen chemical shifts were smaller than for carbon.•The best isomer selections have been obtained by DP4 analyses using 13C and 1H data.