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

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@article{41fee01010a14970b88c25aceba34d2c,
title = "Efficient and flexible synthesis of highly functionalised 4-aminooxazoles by a gold-catalysed intermolecular formal [3+2]-dipolar cycloaddition",
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 cycloadditionpathway 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 motifssuch as chiral oxazoles with biologically pertinent substitution are readily accessible. The use of ynamide types that are unexplored or little usedin 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 thisregioselective intermolecular preparation is demonstrated in the ready synthesis of oxazoles with substantial structural and functional group variation.",
keywords = "cycloaddition, dipoles, gold, oxazoles, ynamides",
author = "Paul Davies and Andrew Gillie and Raju Jannapureddy",
year = "2016",
month = jan,
day = "21",
doi = "10.1002/adsc.201500905",
language = "English",
volume = "358",
pages = "226--239",
journal = "Advanced Synthesis & Catalysis",
issn = "1615-4169",
publisher = "Wiley-VCH Verlag",
number = "2",

}

RIS

TY - JOUR

T1 - Efficient and flexible synthesis of highly functionalised 4-aminooxazoles by a gold-catalysed intermolecular formal [3+2]-dipolar cycloaddition

AU - Davies, Paul

AU - Gillie, Andrew

AU - Jannapureddy, Raju

PY - 2016/1/21

Y1 - 2016/1/21

N2 - 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 cycloadditionpathway 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 motifssuch as chiral oxazoles with biologically pertinent substitution are readily accessible. The use of ynamide types that are unexplored or little usedin 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 thisregioselective intermolecular preparation is demonstrated in the ready synthesis of oxazoles with substantial structural and functional group variation.

AB - 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 cycloadditionpathway 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 motifssuch as chiral oxazoles with biologically pertinent substitution are readily accessible. The use of ynamide types that are unexplored or little usedin 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 thisregioselective intermolecular preparation is demonstrated in the ready synthesis of oxazoles with substantial structural and functional group variation.

KW - cycloaddition

KW - dipoles

KW - gold

KW - oxazoles

KW - ynamides

U2 - 10.1002/adsc.201500905

DO - 10.1002/adsc.201500905

M3 - Article

VL - 358

SP - 226

EP - 239

JO - Advanced Synthesis & Catalysis

JF - Advanced Synthesis & Catalysis

SN - 1615-4169

IS - 2

ER -