Synlett 2003(10): 1568-1569
DOI: 10.1055/s-2003-40867
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

4-Dimethylamino-pyridine (DMAP)

Christoph Grondal*
Institute of Biotechnology 2, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany
e-Mail: c.grondal@fz-juelich.de;
Further Information

Publication History

Publication Date:
24 July 2003 (online)

Introduction

In 1969 Steglich and Höfle reported 4-(dimethylamino)-pyridine (DMAP) (1) as a very effective acylation catalyst. [1] Independently, the Russian group of Litvinenko and Kirichenko discovered that pyridine replaced by DMAP accelerates the reaction rate by ca. 10 [4] for the benzoylation of m-chloroaniline. [2] As a result of many investigations based on the fundamental work by Steglich et al., DMAP has been used in a large range of applications as a catalyst for acylation of alcohols, amines, phenols and enolates, [3-5] in particular for the acylation of sterically hindered secondary or tertiary alcohols. For example, 1-methyl-1-cyclohexanol is not acylated under basic conditions (pyridine, Ac2O), whereas in the presence of 4.1 mol% of DMAP a yield of 86% is achieved after 14 hours at room temperature. [1] It should be mentioned that DMAP shows good catalytic activity under certain conditions. Non-polar solvents like pyridine and Ac2O (rather than acid chlorides) are suitable.

The catalytic efficiency is probably due to the stabilization of an acylpyridinium ion, which plays an important role in the catalytic cycle (Scheme 1). Steric effects, the donor ability of the amine substituent, and the good nucleophilic properties of DMAP additionally affect the reactivity of DMAP. Hassner et al. pointed out that 2-dialkylamino-pyridines have no catalytic activity for steric reasons. [6]

Scheme 1

It is well known that DMAP does not only serve as a catalyst for acylation reactions and (trans-) esterifications [7] but also for various organic transformations like the Baylis-Hillman reaction, [8] the Dakin-West reaction, [9] the protection of amines, [10] C-acylations, [11] silylations, [5] applications in natural products chemistry, [12] and many others. [5]

    References

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