Remodeling and Enhancing Schmidt Reaction Pathways in Hexafluoroisopropanol

The effect of carrying out two variations
of the Schmidt reaction
with ketone electrophiles in hexafluoroisopropanol (HFIP) solvent
has been studied. When TMSN3 is reacted with ketones in
the presence of triflic acid (TfOH) promoter, tetrazoles are obtained
as the major products. This observation is in contrast to established
methods, which usually lead to amides or lactams arising from formal
NH insertion as the major products. The full product profiles of several
examples of this reaction are also reported and found to include mechanistically
interesting products (e.g., double ring expansion). Application of
TfOH promoter in HFIP was also found to promote the reaction of a
hydroxyalkyl azide with a ketone, which affords lactams following
nucleophilic opening of initially formed iminium ether more efficiently
than previously reported methods.