Efficient and flexible synthesis of highly functionalised 4-aminooxazoles by a gold-catalysed intermolecular formal [3+2]-dipolar cycloaddition

Research output: Contribution to journalArticle

Authors

Colleges, School and Institutes

Abstract

Oxazoles are important motifs within bioactive and functional materials. Complex, fully substituted and functionalised 4-amino oxazoles are accessed by an efficient intermolecular reaction between an ynamide and N-acyl pyridinium N-aminide in the presence of a gold catalyst. The formal [3+2]-dipolar cycloaddition employs a nucleophilic nitrenoid approach to access 1,3-N,O-dipole character in a controllable fashion. The selectivity for a cycloaddition
pathway provides stark contrast against the indiscriminate reactivity of electrophilic acyl nitrenes. Protocols for the formation of acyl-functionalised aminides are reported from accessible precursors including carboxylic esters and acids. The function of these aminides in the oxazole-forming reaction has been explored and it is shown that substantial elaboration is accommodated despite proximity to the reactive centre. As a result functional oxazole-based motifs
such as chiral oxazoles with biologically pertinent substitution are readily accessible. The use of ynamide types that are unexplored or little used
in gold catalysis have been evaluated. Unusual all heteroatom substitution patterns around the oxazole are shown to be accessible using thioynamides. The study shows that a close stoichiometry of reactants is suitable alongside relatively low loadings of the bench-stable precatalysts in practically straightforward multi-mmol scale reactions. The efficiency and flexibility of this
regioselective intermolecular preparation is demonstrated in the ready synthesis of oxazoles with substantial structural and functional group variation.

Details

Original languageEnglish
Pages (from-to)226-239
JournalAdvanced Synthesis & Catalysis
Volume358
Issue number2
Early online date5 Jan 2016
Publication statusPublished - 21 Jan 2016

Keywords

  • cycloaddition, dipoles, gold, oxazoles, ynamides