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Three-component coupling approach for the synthesis of diverse heterocycles utilizing reactive nitrilium trapping.

ABSTRACT: The formation of an unexpected heterocyclic scaffold, a benzoxazole, in a three-component reaction between a ketone, isocyanide, and 2-aminophenol was encountered. This reaction involved a benzo[b][1,4]oxazine intermediate resulting from intramolecular attack of the aminophenol hydroxyl group on the nitrilium ion. Unlike previous literature examples, the trapped nitrilium benzo[b][1,4]oxazine could readily be subjected to ring opening with bis-nucleophiles. The reaction scope includes simple linear as well as complex cyclic ketones and substituted 2-aminophenols. A representative benzoxazole product could be further diversified to yield drug-like compounds.

SUBMITTER: Varadi A

PROVIDER: S-EPMC3969103 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Three-component coupling approach for the synthesis of diverse heterocycles utilizing reactive nitrilium trapping.

Váradi András A Palmer Travis C TC Notis Paula R PR Redel-Traub Gabriel N GN Afonin Daniel D Subrath Joan J JJ Pasternak Gavril W GW Hu Chunhua C Sharma Indrajeet I Majumdar Susruta S

Organic letters 20140228 6

The formation of an unexpected heterocyclic scaffold, a benzoxazole, in a three-component reaction between a ketone, isocyanide, and 2-aminophenol was encountered. This reaction involved a benzo[b][1,4]oxazine intermediate resulting from intramolecular attack of the aminophenol hydroxyl group on the nitrilium ion. Unlike previous literature examples, the trapped nitrilium benzo[b][1,4]oxazine could readily be subjected to ring opening with bis-nucleophiles. The reaction scope includes simple lin ...[more]

PMID: 24580074

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