title: Temperature dependence of turnover in a Sc(OTf)3-catalyzed intramolecular Schmidt reaction.
abstract: The intramolecular Schmidt reaction of ketones and tethered azides is an efficient method for the generation of amides and lactams. This reaction is catalyzed by Lewis acids, which tightly bind the strongly basic amide product and result in product inhibition. We report herein conditions to achieve a catalytic Schmidt reaction using substoichiometric amounts of the heat-stable Lewis acid Sc(OTf)3. This species was shown to effectively release products of the Schmidt reaction in a temperature-dependent fashion. Thus, heat was able to promote catalyst turnover. A brief substrate scope was conducted using these conditions.
authors.affiliation: University of Kansas, Department of Medicinal Chemistry, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, United States.
authors.forename: Charlie
authors.initials: C
authors.lastname: Fehl
authors.affiliation: University of Kansas, Department of Medicinal Chemistry, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, United States.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Hirt
authors.affiliation: University of Kansas, Department of Medicinal Chemistry, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, United States.
authors.forename: Sze-Wan
authors.initials: SW
authors.lastname: Li
authors.affiliation: University of Kansas, Department of Medicinal Chemistry, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
keywords: Intramolecular Schmidt reaction; Polycyclic lactams; Ring expansion; Scandium triflate catalysis; Turnover