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Direct Synthesis of α-Aryl-α-Trifluoromethyl Alcohols via Nickel Catalyzed Cross-Electrophile Coupling.

ABSTRACT: A nickel-catalyzed reductive cross-electrophile coupling between the redox-active N-trifluoroethoxyphthalimide and iodoarenes is documented. The protocol reproduces a formal arylation of trifluoroacetaldehyde under mild conditions in high yields (up to 88 %) and with large functional group tolerance (30 examples). A combined computational and experimental investigation revealed a pivotal solvent assisted 1,2-Hydrogen Atom Transfer (HAT) process to generate a nucleophilic α-hydroxy-α-trifluoromethyl C-centered radical for the Csp² -Csp³ bond forming process.

SUBMITTER: Lombardi L

PROVIDER: S-EPMC9828748 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Direct Synthesis of α-Aryl-α-Trifluoromethyl Alcohols via Nickel Catalyzed Cross-Electrophile Coupling.

Lombardi Lorenzo L Cerveri Alessandro A Giovanelli Riccardo R Castiñeira Reis Marta M Silva López Carlos C Bertuzzi Giulio G Bandini Marco M

Angewandte Chemie (International ed. in English) 20221018 47

A nickel-catalyzed reductive cross-electrophile coupling between the redox-active N-trifluoroethoxyphthalimide and iodoarenes is documented. The protocol reproduces a formal arylation of trifluoroacetaldehyde under mild conditions in high yields (up to 88 %) and with large functional group tolerance (30 examples). A combined computational and experimental investigation revealed a pivotal solvent assisted 1,2-Hydrogen Atom Transfer (HAT) process to generate a nucleophilic α-hydroxy-α-trifluoromet ...[more]

PMID: 36161744

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