Fluorine is the most electronegative element in the periodic table, and the introduction of one or more fluorine atoms into a molecule can result in greatly perturbed properties. Methods to introduce fluorine into small organic molecules have been actively investigated for many years by specialists in the field of fluorine chemistry. The earliest advances in catalytic asymmetric fluorination were made by exploiting transition metal enolates, capable of a bidentate mode of coordination to a metal. In 2002, Sodeoka and coworkers reported the enantioselective fluorination of β-ketoesters catalyzed by a chiral palladium complex. In 2005, Shibata and co-workers reported enantioselective chlorination and fluorination of carbonyl compounds capable of two-point binding. In 2011, Gade and co-workers described the synthesis of a new class of chiral tridentate N-donor pincer ligands, bis(oxazolinyl-methyldiene)isoindolines.

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.

We report a catalytic enantioselective electrophilic fluorination of alkenes to form tertiary and quaternary C(sp3)-F bonds and generate β-amino- and β-aryl-allylic fluorides. The reaction takes advantage of the ability of chiral phosphate anions to serve as solid-liquid phase transfer catalysts and hydrogen bond with directing groups on the substrate. A variety of heterocyclic, carbocyclic, and acyclic alkenes react with good to excellent yields and high enantioselectivities. Further, we demonstrate a one-pot, tandem dihalogenation-cyclization reaction, using the same catalytic system twice in series, with an analogous electrophilic brominating reagent in the second step.

We report a catalytic enantioselective electrophilic fluorination of alkenes to form tertiary and quaternary C(sp3)-F bonds and generate β-amino- and β-aryl-allylic fluorides. The reaction takes advantage of the ability of chiral phosphate anions to serve as solid-liquid phase transfer catalysts and hydrogen bond with directing groups on the substrate. A variety of heterocyclic, carbocyclic, and acyclic alkenes react with good to excellent yields and high enantioselectivities. Further, we demonstrate a one-pot, tandem dihalogenation-cyclization reaction, using the same catalytic system twice in series, with an analogous electrophilic brominating reagent in the second step.