Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides

Minami Nakajima, Yukiko Oda, Takamasa Wada, Ryo Minamikawa, Kenji Shirokane, Takaaki Satou, Noritaka Chida

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

As the complexity of targeted molecules increases in modern organic synthesis, chemoselectivity is recognized as an important factor in the development of new methodologies. Chemoselective nucleophilic addition to amide carbonyl centers is a challenge because classical methods require harsh reaction conditions to overcome the poor electrophilicity of the amide carbonyl group. We have successfully developed a reductive nucleophilic addition of mild nucleophiles to tertiary amides, secondary amides, and N-methoxyamides that uses the Schwartz reagent [Cp2 ZrHCl]. The reaction took place in a highly chemoselective fashion in the presence of a variety of sensitive functional groups, such as methyl esters, which conventionally require protection prior to nucleophilic addition. The reaction will be applicable to the concise synthesis of complex natural alkaloids from readily available amide groups.

Original languageEnglish
Pages (from-to)17565-17571
Number of pages7
JournalChemistry (Weinheim an der Bergstrasse, Germany)
Volume20
Issue number52
DOIs
Publication statusPublished - 2014 Dec 22

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Amides
Synthetic Chemistry Techniques
Alkaloids
Nucleophiles
Functional groups
Esters
Molecules

Keywords

  • amides
  • chemoselectivity
  • nitrogen
  • nucleophilic addition
  • sequential reactions

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides. / Nakajima, Minami; Oda, Yukiko; Wada, Takamasa; Minamikawa, Ryo; Shirokane, Kenji; Satou, Takaaki; Chida, Noritaka.

In: Chemistry (Weinheim an der Bergstrasse, Germany), Vol. 20, No. 52, 22.12.2014, p. 17565-17571.

Research output: Contribution to journalArticle

Nakajima, Minami ; Oda, Yukiko ; Wada, Takamasa ; Minamikawa, Ryo ; Shirokane, Kenji ; Satou, Takaaki ; Chida, Noritaka. / Chemoselective reductive nucleophilic addition to tertiary amides, secondary amides, and N-methoxyamides. In: Chemistry (Weinheim an der Bergstrasse, Germany). 2014 ; Vol. 20, No. 52. pp. 17565-17571.
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AU - Satou, Takaaki

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