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Ni-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination.

ABSTRACT: This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines, which are challenging to access by traditional reductive amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrated by a single-step synthesis of antimigraine drug flunarizine (Sibelium) and high yielding derivatization of paroxetine (Paxil) and metoprolol (Lopressor). Mechanistic investigations support a sequential oxidative addition mechanism rather than a pathway proceeding via ?-amino radical formation. Accordingly, application of catalytic conditions to an intramolecular reductive coupling is demonstrated for the synthesis of endo- and exocyclic benzhydryl amines.

SUBMITTER: Heinz C

PROVIDER: S-EPMC6698183 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Ni-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination.

Heinz Christoph C Lutz J Patrick JP Simmons Eric M EM Miller Michael M MM Ewing William R WR Doyle Abigail G AG

Journal of the American Chemical Society 20180201 6

This report describes a three-component, Ni-catalyzed reductive coupling that enables the convergent synthesis of tertiary benzhydryl amines, which are challenging to access by traditional reductive amination methodologies. The reaction makes use of iminium ions generated in situ from the condensation of secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo reaction with several distinct classes of organic electrophiles. The synthetic value of this process is demonstrat ...[more]

PMID: 29341599

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