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

Abstract

Unprecedented scatter plots of calculated versus measured NMR J coupling constants in six densely oxygen functionalized epoxides are found with some B3LYP protocols, an effect attributed to stereoelectronic effects. Hence, 26 other exchange-correlation density functionals (xc DFs) are benchmarked in this work. Very good results are achieved with mPW1PW91 and PBE0 in conjunction with the pcJ-1 basis set (BS) of moderate size. A thorough statistical analysis of 53 relationships between the predicted and observed J datasets is presented. The effects of some xc DFs, including their x and c parts, and BSs on the calculation results are discussed, also in the context of DFT modeling of electron-density distributions. Moreover, related J datasets predicted with 11 different DF methods are considered and compared with the experimental data. Finally, some proposals for further improvement of existing DFs based on the available J (n=1-3) values are briefly outlined, in line with recent results on the DFT electron densities.

Observation of untoward 3Jcc correlations in 1,1‐ADEQUATE spectra of pyrimidine analogs: Avoiding potential interpretation pitfalls

“…DFT was then used to determine if the large 3 J CC coupling constants could be accurately predicted. Several different model chemistries were evaluated that have been previously shown to produce high‐quality coupling constant predictions . Most frequently, the B3LYP functional combined with moderately sized basis sets (e.g., triple‐zeta) has been utilized for n J HH and n J CH coupling constant predictions, but there are fewer reports on n J CC calculations .…”

“…found B3LYP/EPR‐III predicted 27 1 J CC values for three bicyclic terpene natural products with a maximum deviation of 3.4 Hz (5%) . In a comprehensive benchmark study of 27 density functionals, Adamson and coworkers observed the highest accuracy (mean absolute deviation of 0.20 Hz) for the mPW1PW91 functional paired with the pcJ‐1 basis set for prediction of n J CH values for several epoxy compounds . Lastly, we also considered the B3PW91/6‐311++G(d,p) model chemistry employed by Bugaj et al .…”

“…Several different model chemistries were evaluated that have been previously shown to produce high-quality coupling constant predictions. [21][22][23][24] Most frequently, the B3LYP functional combined with moderately sized basis sets (e.g., triple-zeta) has been utilized for n J HH and n J CH coupling constant predictions, [21][22][23][24][25][26][27][28] but there are fewer reports on n J CC calculations. [21,22,24,25,29] The NMR = "mixed" keyword, which uncontracts the basis set and adds tight s and d polarization functions to the core electrons for evaluation of the Fermi contact term, was recommended by the developers of the Gaussian software as a method to more rapidly approach the basis set limit for coupling constant calculations.…”

“…[22] In a comprehensive benchmark study of 27 density functionals, Adamson and coworkers observed the highest accuracy (mean absolute deviation of 0.20 Hz) for the mPW1PW91 functional paired with the pcJ-1 basis set for prediction of n J CH values for several epoxy compounds. [23] Lastly, we also considered the B3PW91/6-TABLE 1 Summary of 3 J CC coupling constants for pyrimidine analogs with electronegative substitutions at the 5-position. The coupling constants were measured using J-modulated-ADEQUATE [10] and calculated by density functional theory (DFT) [21] : B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) using NMR = "mixed" keyword.…”

“…b Method 2 [22] : B3LYP/EPR-III//B3LYP/D95** [note: 6-31G(d) basis set was used for Cl, Br, and S atoms]. c Method 3 [23] : mPW1PW91/pcJ-1//B3LYP/6-311+G(d,p) with implicit solvent model. d Method 4 [24] : B3PW91/6-311++G(d, p)//B3PW91/6-311++G(d,p).…”