Structural elucidation of dioxa‐cage compounds from tetrahydroisobenzofuran‐1(3H)‐one: analysis of NMR data and GIAO chemical shifts calculations

Abstract

The polycyclic compounds, especially the dioxa-cages, have attracted considerable attention in recent years. In our work, a series of 9β-substituted 3-oxo-4,11-dioxatetracyclo[5.2.1.1 .0 ]undecane compounds were unexpectedly isolated during bromination, chlorination and epoxidation reactions of the 3-hydroxy-3a,4,7,7a-tetrahydro-4,7-methanoisobenzofuran-1(3H)-one. After careful analysis of the NMR data, the chemical shifts of the isolated and the expected products were predicted by theoretical calculations using density functional theory and gauge including atomic orbitals. The best correlation between calculated and experimental data was evaluated by comparing mean absolute errors and applying DP4 probability methodology. Results from both approaches indicated a correct structural elucidation. Copyright © 2016 John Wiley & Sons, Ltd.

Deciphering molecular structures: NMR spectroscopy and quantum mechanical insights of halogenated 4H‐Chromenediones

“…Worthy of mention in that regard are IGLO (an individual gauge for localized orbitals), LORG (localized orbital/local origin method), CSGT (continuous set of Gaussian transformations), and GIAO (gaugeincluding atomic orbital), the last being most frequently used. 29,[35][36][37][38] Other variables that are essential for obtaining accurate results are the level of theory and the basis sets that are used. Among the nearly infinite number of available combinations, DFT (Density Functional Theory) is widely used due to its accuracy and manageable computational resource requirements.…”

“…30,49 This approach was first described by Bifulco, 29 and has been successfully applied in several situations in our research group. 22,25,31,36,38,[50][51][52][53][54][55][56][57][58] 2 | RESULTS AND DISCUSSION 2.1 | Synthesis and mechanism α-santonin (1) is known for having a versatile photochemical reactivity that is highly dependent on reaction conditions, such as the polarity and acidity of the solvent employed, suitable wavelength irradiation, and temperature. 46,59,60 Photosantonic acids (2), the starting material used in the synthesis of halogenated 4H-chromenediones, were obtained by irradiation of the sesquiterpene lactone α-santonin (1) in the ultraviolet region using a mixture of H 2 O/acetic acid 1:1 as solvent (Scheme 1).…”

“…Distinctive approaches can be used to calculate shielding tensors. Worthy of mention in that regard are IGLO (an individual gauge for localized orbitals), LORG (localized orbital/local origin method), CSGT (continuous set of Gaussian transformations), and GIAO (gauge‐including atomic orbital), the last being most frequently used 29,35–38 …”

“…This force field is recognized for its generally good performance and accuracy in the conformational analysis and searching of small organic molecules, compared to other commonly used force fields 47,48 ; ii) optimization of the geometries of these conformers using the M062x/6–31 + G(d,p) level of theory and iefpcm (chloroform) solvation model; iii) calculation of shielding tensors for each structure using DFT‐GIAO and B3LYP/6‐311 + G(2d,p); iv) conversion of these tensors to the corresponding chemical shifts and weighting them according to their Boltzmann distribution across all conformers, and v) comparison with experimental data, employing corrected mean absolute error (CMAE), DP4, and DP4 + probabilities tools 30,49 . This approach was first described by Bifulco, 29 and has been successfully applied in several situations in our research group 22,25,31,36,38,50–58 …”