Theoretical prediction and assignment of vicinal ¹H–¹H coupling constants of diastereomeric 3‐alkoxy‐6,7‐epoxy‐2‐oxabicyclo[3.3.0]octanes

Abstract

Spin-spin coupling constants between nuclei in NMR spectroscopy reflect their spatial arrangement. A number of calculation methods, applying different levels of theory, have been developed to support the stereochemical assignment of novel compounds. Nevertheless, revisions of the assignment of structures in the literature are not rare. In the present work, the reliability of the calculation methods amenable for a theoretical prediction of spin-spin coupling constants of vicinal protons to support correct stereochemical assignment of substitution at five-membered rings of 3-alkoxy-6,7-epoxy-2-oxabicyclo[3.3.0]octanes was studied. Experimental (3)J(H,H) coupling constants were compared with the coupling constants calculated for all possible diastereomers. The fully quantum chemical approach provided theoretical (3)J(H,H) coupling constants with an absolute deviation of no more than 1.1 Hz for 91% of the experimentally studied coupled spins, whereas the methods without quantum chemical geometry optimization resulted in completely unreliable predictions. Consequently, for a reliable stereochemical assignment of small and medium size molecules, the protocol for calculating the coupling constants based on the results of the quantum chemical geometry optimization is recommended.

Shortfall of B3LYP in Reproducing NMR JCH Couplings in Some Isomeric Epoxy Structures with Strong Stereoelectronic Effects: A Benchmark Study on DFT Functionals

“…First, we performed ac onformational analysiso fa ll of the flexible tricyclic systems 1-6. [16] The present benchmarking study secures the reliability of results with an exhaustive conformational search. Three forms A-C of 1-3 and four forms A-D of 4-6 were found within the energy window of DE tot = 16.4 kJ mol À1 (see Computational Details and Supporting Information).…”

“…First, we performed a conformational analysis of all of the flexible tricyclic systems 1 – 6 . The present benchmarking study secures the reliability of results with an exhaustive conformational search.…”

“…Herein, we supplement the above‐mentioned lack of benchmarking analyses by reporting a study on J CH in six isomeric (1 S ,5 S )‐3‐alkoxy‐6,7‐epoxy‐2‐oxabicyclo[3.3.0]octanes 1 – 6 (Figure ). These J values were measured in CDCl 3 solution at 800 MHz 1 H NMR spectrometer frequency and calculated by means of a variety of DF methods.…”

“…These J values were measured in CDCl 3 solution at 800 MHz 1 H NMR spectrometer frequency and calculated by means of a variety of DF methods. Stereorelations between the three constituent rings were previously established by analysis of experimental 3 J HH values, supported by their DFT‐B3LYP prediction . Diastereomeric epoxides 1 – 6 afforded 225 unique J couplings (67 1 J CH , 70 2 J CH , and 88 3 J CH ).…”

“…Stereorelations between the three constituent rings were previously established by analysiso fe xperimental 3 J HH values, supported by their DFT-B3LYP prediction. [16] Diastereomeric epoxides 1-6 afforded 225 unique J couplings (67 1 J CH ,7 0 2 J CH ,a nd 88 3 J CH ). All these J values were considered as components of the two attached J CH datasets( see Supporting Information): 2,3JCH_EPOXY (À7 < J obsd < 9Hz) and 1JCH_EPOXY( 126 < J obsd < 185 Hz).…”