Hydrogen-Bond-Assisted Organocatalytic Acetalization of Secondary Alcohols: Experimental and Theoretical Studies

An efficient method was developed
for the acetalization of secondary
alcohols in the presence of simple protic pyridinium salts. Direct
correlations between the structure and activity of the synthesized
catalysts were described. Stabilization via hydrogen bonding of the
hemiacetal intermediate by the pyridine derivatives, along with an
appropriate increase in the reaction rate, was revealed. The nature
of the observed experimental acceleration of the examined reactions
catalyzed by pyridinium salts comprising electron-withdrawing groups
at certain positions of the pyridinium ring was studied. In this vein,
the interpretation of the hydrogen-bonded pretransition-state complexes
and transition-state complexes with strong catalysts was also discussed
in terms of partial proton transfer. It was concluded that optimized
pretransition-state complexes of the catalyst and reactant are useful
for the prediction of catalyst efficiency prior to the experiment.