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Issue 5, 2013
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N-Heterocyclic carbene (NHC) catalyzed chemoselective acylation of alcohols in the presence of amines with various acylating reagents

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Abstract

This edge article reports the synthesis and full characterization including X-ray analysis of three different acylazolium ions. The reactivity of these acylazolium ions as acylating reagents of amines and alcohols is discussed. Whereas benzylamine slowly reacts with the acylazolium ions, benzyl alcohol acylation does not occur. However, upon activation of the alcohol with an N-heterocyclic carbene (NHC) as catalyst, efficient esterification is achieved. Importantly, benzylester formation is obtained in the presence of benzylamine upon selective alcohol activation by the NHC. High level DFT calculations reveal that alcohol activation occurs by strong H-bond formation between the NHC and the alcohol thereby increasing the nucleophilicity of the alcohol. For oxidatively generated acylazolium ions under NHC catalysis, the carbene has a dual role (cooperative catalysis): (a) the NHC is used for generation of the acylazolium ion and (b) the NHC is used for activation of the alcohol in the subsequent acylation step. NHC-catalyzed selective acylation of benzyl alcohol in the presence of benzylamine can also be achieved with trifluoroethyl and hexafluoroisopropylesters as acylation reagents. Moreover, an enol acetate also shows high O-selectivity as a chemoselective acetylation reagent. Kinetic and mechanistic studies are provided and some examples of the chemoselective acylation of amino alcohols are presented.

Graphical abstract: N-Heterocyclic carbene (NHC) catalyzed chemoselective acylation of alcohols in the presence of amines with various acylating reagents

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Publication details

The article was received on 11 Jan 2013, accepted on 04 Mar 2013 and first published on 05 Mar 2013


Article type: Edge Article
DOI: 10.1039/C3SC00099K
Citation: Chem. Sci., 2013,4, 2177-2184
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    N-Heterocyclic carbene (NHC) catalyzed chemoselective acylation of alcohols in the presence of amines with various acylating reagents

    R. C. Samanta, S. De Sarkar, R. Fröhlich, S. Grimme and A. Studer, Chem. Sci., 2013, 4, 2177
    DOI: 10.1039/C3SC00099K

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