title: Asymmetric fluorination of α-branched cyclohexanones enabled by a combination of chiral anion phase-transfer catalysis and enamine catalysis using protected amino acids.
abstract: We report a study involving the successful merger of two separate chiral catalytic cycles: a chiral anion phase-transfer catalysis cycle to activate Selectfluor and an enamine activation cycle, using a protected amino acid as organocatalyst. We have demonstrated the viability of this approach with the direct asymmetric fluorination of α-substituted cyclohexanones to generate quaternary fluorine-containing stereocenters. With these two chiral catalytic cycles operating together in a matched sense, high enantioselectivites can be achieved, and we envisage that this dual catalysis method has the potential to be more broadly applicable, given the breadth of enamine catalysis. It also represents a rare example of chiral enamine catalysis operating successfully on α-branched ketones, substrates commonly inert to this activation mode.
authors.affiliation: Department of Chemistry, University of California , Berkeley, California 94720, United States .
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Phipps
authors.forename: F Dean
authors.initials: FD
authors.lastname: Toste
mesh_terms: D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D000838:Anions / Q000737:chemistry; D002384:Catalysis; D003512:Cyclohexanones / Q000737:chemistry*; D054879:Halogenation; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D044367:Phase Transition
chemical_list: D000588:Amines; D000596:Amino Acids; D000838:Anions; D003512:Cyclohexanones; D006845:Hydrocarbons, Fluorinated