Understanding the Origins of Site Selectivity in Hydrogen Atom Transfer Reactions from Carbohydrates to the Quinuclidinium Radical Cation: A Computational Study
Julia A. Turner, Timur Adrianov, Mark S. Taylor
Abstract
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 study, density functional theory calculations (M06-2X/def2-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···O hydrogen bonds in stabilizing transition states for HAT to the quinuclidinium radical cation.