Understanding the Origins of Site Selectivity in Hydrogen Atom Transfer Reactions from Carbohydrates to the Quinuclidinium Radical Cation: A Computational Study

The use of quinuclidine as a hydrogen atom transfer (HAT) mediator, along with a light-absorbing photoredox catalyst, has proved to be a powerful and general approach for achieving site-selective radical formation from carbohydrate substrates. Despite numerous literature reports documenting the scope and limitations of such processes, a general rationale for the origins of site selectivity in the key HAT step has not been advanced. In this TZVP/PCM(acetonitrile)) were used to model transition states for HAT to the quinuclidinium radical cation from pyranosides and furanosides having various configurations and substitution patterns. The data set (>120 transition state geometries and energies) has allowed for a detailed examination of the factors that influence the relative rates, augmented by additional analysis using the atoms in molecules (AIM) and distortion/interaction-activation strain frameworks. The trends that have emerged regarding the effects of configuration, conformation, substitution, and noncovalent interactions are consistent with experimental observations and reveal a key role for C-H center dot center dot center dot O hydrogen bonds in stabilizing transition states for HAT to the quinuclidinium radical cation.

Automated summary

The use of quinuclidine and a light-absorbing photoredox catalyst allows for site-selective radical formation from carbohydrate substrates. However, the factors influencing the site selectivity in hydrogen atom transfer (HAT) step have not been fully understood. This study used computational modeling to investigate the relative rates of HAT to the quinuclidinium radical cation from pyranosides and furanosides with different configurations and substitution patterns, revealing the important role of C-H...O hydrogen bonds in stabilizing transition states.