Acid-Mediated Denitrogenation/Rearrangement/Coupling of -Benzyl Azides with Triazolyl-Substituted Cycloalkanones

Organic molecules containing alpha-triazolyl or beta-amino cyclic ketone fragments have been individually proven to show good bioactivities and to be useful in asymmetric and pharmaceutical syntheses. A triflic acid-promoted simple and efficient method for the synthesis of unsymmetrical alpha-triazolyl-alpha '-(aminomethyl)cycloalkanones from benzyl azides and alpha-triazolylcycloalkanones has been developed. A series of unsymmetrical alpha,alpha '-disubstituted cycloalkanones were obtained with high syn- and up to 82% yield. Examination of the reaction mechanism showed that the benzyl azides undergo protonation, nitrogen elimination, rearrangement, and electrophilic attack by the enol forms of the cyclic ketones.