title: Remodeling and Enhancing Schmidt Reaction Pathways in Hexafluoroisopropanol.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry and ‡X-ray Crystallography Laboratory, University of Kansas , Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, Kansas 66047, United States.
authors.forename: Hashim F
authors.initials: HF
authors.lastname: Motiwala
authors.affiliation: Department of Medicinal Chemistry and ‡X-ray Crystallography Laboratory, University of Kansas , Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, Kansas 66047, United States.
authors.forename: Manwika
authors.initials: M
authors.lastname: Charaschanya
authors.affiliation: Department of Medicinal Chemistry and ‡X-ray Crystallography Laboratory, University of Kansas , Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, Kansas 66047, United States.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Day
authors.affiliation: Department of Medicinal Chemistry and ‡X-ray Crystallography Laboratory, University of Kansas , Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, Kansas 66047, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé