Direct Catalytic Chemoselective α-Amination of Acylpyrazoles: A Concise Route to Unnatural α-Amino Acid Derivatives

Keisuke Tokumasu, Ryo Yazaki, Takashi Ohshima

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

A direct copper-catalyzed highly chemoselective α-amination is described. Acylpyrazole proved to be a highly efficient enolate precursor of a carboxylic acid oxidation state substrate, while preactivation by a stoichiometric amount of strong base has been used in catalytic α-aminations. The simultaneous activation of both coupling partners, enolization and metal nitrenoid formation, was crucial for obtaining the product, and wide functional group compatibility highlighted the mildness of the present catalysis. The bidentate coordination mode was amenable to highly chemoselective activation over ketone and much more acidic nitroalkyl functionality. Deuterium exchange experiments clearly demonstrated that exclusive enolization of acylpyrazole was achieved without the formation of a nitronate. The present catalysis was applied to late-stage α-amination, allowing for concise access to highly versatile α-amino acid derivatives. The product could be transformed into variety of useful building blocks.

Original languageEnglish
Pages (from-to)2664-2669
Number of pages6
JournalJournal of the American Chemical Society
Volume138
Issue number8
DOIs
Publication statusPublished - Mar 2 2016

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Amination
Amino acids
Derivatives
Catalysis
Amino Acids
Chemical activation
Deuterium
Carboxylic Acids
Ketones
Carboxylic acids
Functional groups
Copper
Metals
Oxidation
Substrates
Experiments

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

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abstract = "A direct copper-catalyzed highly chemoselective α-amination is described. Acylpyrazole proved to be a highly efficient enolate precursor of a carboxylic acid oxidation state substrate, while preactivation by a stoichiometric amount of strong base has been used in catalytic α-aminations. The simultaneous activation of both coupling partners, enolization and metal nitrenoid formation, was crucial for obtaining the product, and wide functional group compatibility highlighted the mildness of the present catalysis. The bidentate coordination mode was amenable to highly chemoselective activation over ketone and much more acidic nitroalkyl functionality. Deuterium exchange experiments clearly demonstrated that exclusive enolization of acylpyrazole was achieved without the formation of a nitronate. The present catalysis was applied to late-stage α-amination, allowing for concise access to highly versatile α-amino acid derivatives. The product could be transformed into variety of useful building blocks.",
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