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Tandem insertion-cyclization reaction of isocyanides in the synthesis of 1,4-diaryl-1H-imidazoles: presence of N-arylformimidate intermediate.

Authors
  • Pooi, Benjamin
  • Lee, Jeongbin
  • Choi, Kyujin
  • Hirao, Hajime
  • Hong, Soon Hyeok
Type
Published Article
Journal
The Journal of Organic Chemistry
Publisher
American Chemical Society
Publication Date
Oct 03, 2014
Volume
79
Issue
19
Pages
9231–9245
Identifiers
DOI: 10.1021/jo501652w
PMID: 25188915
Source
Medline
License
Unknown

Abstract

A straightforward and high-yielding synthesis of 1,4-diaryl-1H-imidazoles is reported. 1,4-Diaryl-1H-imidazoles have been difficult to access in ambient conditions, but our method utilizes two different facets of isocyanide reactivity to achieve it. The reaction is believed to involve (1) NHC-copper-catalyzed isocyanide insertion into alcohol to form an N-arylformimidate intermediate and (2) subsequent base-promoted cycloaddition with benzyl isocyanide derivatives. There is cooperation between these two processes through the deprotonation of benzyl isocyanide by KOtBu. The deprotonation gives tert-butyl alcohol and the benzyl isocyanide anion, which are used for the first and second steps of the reaction, respectively. Various control and kinetic experiments were carried out to gain an in-depth understanding of the reaction mechanism and isocyanide reactivity. The reaction mechanism determined by density functional theory calculations was consistent with the experimental data and provided detailed explanations for the reactivity trends.

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