Stereochemical assignment of four diastereoisomers of a maculalactone derivative by computational NMR calculations

• Published in: Journal of molecular structure Vol. 1178; pp. 467 - 478
• Main Authors: Previdi, Daniel, Nardini, Viviani, Rosa, Mayla Eduarda, Palaretti, Vinicius, da Silva, Gil Valdo José, Donate, Paulo Marcos
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-02-2019
• Subjects: Assignment; CP3; Maculalactone; NMR; γ-Butyrolactone; Assignment; NMR; γ-Butyrolactone; Maculalactone; CP3
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2018.10.064

Naturally occurring γ-butyrolactones and their synthetic analogues display a wide range of bioactivities. Here, the multicomponent reaction of dimethyl 2-benzyl-3-methylenesuccinate with bromobenzene and benzaldehyde catalyzed by cobalt (II) bromide afforded a maculalactone derivative with three stereogenic centers. This reaction presented moderate diastereoselectivity and yielded different proportions of all the four possible diastereoisomers. The anti:anti (majority), anti:syn, syn:anti, and syn:syn diastereoisomers were isolated and characterized by 1D and 2D NMR experiments. Because the stereochemical assignment of all the diastereoisomers by Nuclear Overhauser Effect Difference (NOEDiff) experiments was not definitive, the 1H and 13C NMR chemical shifts were predicted by theoretical calculations with the density functional theory at the B3LYP/6-31G(d) level. The relative configurations of all the four diastereoisomers were assigned by using the CP3 parameter to compare the experimental and the calculated data and by determining the CP3 probability, which provided high level of confidence.
[Display omitted]
•NMR chemical shifts calculation and the relative configurations of lactones.•Stereochemical assignment of diastereoisomers of a tri-benzylated γ-butyrolactone.•Determination of the relative configurations of a maculalactone derivative.•CP3 parameter applied to distinguish four diastereoisomers.•Assignment of the relative configurations corroborated a proposed reaction mechanism.