Direct Acyl Substitution of Carboxylic Acids: A Chemoselective O- to N-Acyl Migration in the Traceless Staudinger Ligation

Authors

  • Andrew D. Kosal,

    1. Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556 (USA), Fax: (+1) 574-631-6652
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  • Erin E. Wilson,

    1. Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556 (USA), Fax: (+1) 574-631-6652
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  • Prof. Dr. Brandon L. Ashfeld

    Corresponding author
    1. Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556 (USA), Fax: (+1) 574-631-6652
    • Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland Science Hall, Notre Dame, IN 46556 (USA), Fax: (+1) 574-631-6652===

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Abstract

A chlorophosphite-modified, Staudinger-like acylation of azides involving a highly chemoselective, direct nucleophilic acyl substitution of carboxylic acids is described. The reaction provides the corresponding amides with analytical purity in 32–97 % yield after a simple aqueous workup without the need for a pre-activation step. The use of chlorophosphites as dual carboxylic acid–azide activating agents enables the formation of acyl C[BOND]N bonds in the presence of a wide range of nucleophilic and electrophilic functional groups, including amines, alcohols, amides, aldehydes, and ketones. The coupling of carboxylic acids and azides for the formation of alkyl amides, sulfonyl amides, lactams, and dipeptides is described.

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