Computationally Assisted Stereochemical Elucidation of Intermediates Encountered En Route to Pyrrole-Imidazole Natural Products: NMR Chemical Shift Calculations Utilizing CREST/DP4+ Applied to Oxidative Spirocyclizations of Tetrahydrobenzimidazoles
ORCID
Lovely: https://orcid.org/0000-0001-7012-2001
MSU Affiliation
College of Arts and Sciences; Department of Chemistry
Creation Date
2026-06-30
Abstract
Herein, we investigate the use of Boltzmann-weighted NMR chemical shift calculations as a tool for elucidating the stereochemical outcomes of oxidative rearrangement reactions not easily determined by standard NMR experiments. Included is a modular set of scripts for a streamlined workflow integrating xTB/CREST, Gaussian, and DP4+ probability analysis. The use of CREST for this application is assessed by generating conformer ensembles of varying quality through the adjustment of CREST’s main parameters. Results support Boltzmann-weighted NMR chemical shift calculations as a viable method for distinguishing diastereomeric spirocyclic compounds and validate CREST as a free alternative to other proprietary software for the generation of relevant conformation ensembles.
Publication Date
7-2-2025
Publication Title
The Journal of Organic Chemistry
Publisher
SAGE Publications [Commercial Publisher]
First Page
9355
Last Page
9364
Rights
© 2025 American Chemical Society
Recommended Citation
Fulton, B. B., & Lovely, C. J. (2025). Computationally Assisted Stereochemical Elucidation of Intermediates Encountered En Route to Pyrrole-Imidazole Natural Products: NMR Chemical Shift Calculations Utilizing CREST/DP4+ Applied to Oxidative Spirocyclizations of Tetrahydrobenzimidazoles. The Journal of Organic Chemistry, 90(27), 9355–9364. https://doi.org/10.1021/acs.joc.5c00600
