title: Overcoming product inhibition in catalysis of the intramolecular Schmidt reaction.
abstract: A method for carrying out the intramolecular Schmidt reaction of alkyl azides and ketones using a substoichiometric amount of catalyst is reported. Following extensive screening, the use of the strong hydrogen-bond-donating solvent hexafluoro-2-propanol was found to be consistent with low catalyst loadings, which ranged from 2.5 mol % for favorable substrates to 25 mol % for more difficult cases. Reaction optimization, broad substrate scope, and preliminary mechanistic studies of this improved version of the reaction are described.
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, Delbert M. Shankel Structural Biology Center, 2034 Becker Drive, West Campus, Lawrence, Kansas 66047, USA.
authors.forename: Hashim F
authors.initials: HF
authors.lastname: Motiwala
authors.forename: Charlie
authors.initials: C
authors.lastname: Fehl
authors.forename: Sze-Wan
authors.initials: SW
authors.lastname: Li
authors.forename: Erin
authors.initials: E
authors.lastname: Hirt
authors.forename: Patrick
authors.initials: P
authors.lastname: Porubsky
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D006860:Hydrogen Bonding; D007659:Ketones / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D000473:Alkanes; D001386:Azides; D007659:Ketones; D012997:Solvents