Catalytic C-F Bond Activation at Room Temperature: Enolate Cross-Couplings Enabled by [Pd(1-MeNAP)TFA]2 and LiHMDS
Nele Krüger1, Jie Shen1, Sourav Manna1
1Department of Organic Chemistry I, Fakultät für Chemie und Biochemie, Ruhr-Universität Bochum, Bochum, Germany.
None:
Due to their exceptional stability, only few transition metal catalysts are capable of activating C─F bonds for C-C-coupling reactions, usually under harsh conditions or with highly reactive nucleophiles. We herein report that a methyl naphthyl (MeNAP) palladium trifluoroacetate/tBuBrettPhos catalyst with lithium bis(trimethylsilyl)amide (LiHMDS) as the base enables α-arylations of in situ generated enolates with non-activated aryl fluorides. The reaction proceeds under mild conditions at room temperature and extends to ketone, ester, nitrile, and even amide enolates. DFT calculations reveal that the coordination of lithium salts to the fluorine atom decisively facilitates the insertion of Pd into the C─F bond, explaining why this so far elusive reaction is now possible at such exceptionally mild conditions.
Related Concept Videos
Cycloaddition Reactions: MO Requirements for Thermal Activation
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Thermal Electrocyclic Reactions: Stereochemistry
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Cycloaddition Reactions: Overview
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
![Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-(phosphinetriyl)tripiperidine]}palladium Under Mild Reaction Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F51444.jpg&w=3840&q=50)

