DMAP catalysis, anhydride acylation

In the preceding examples, the asymmetric catalyst is a Lewis acid and hence the catalytic processes reported so far involve electrophilic activation by a metal-centred chiral Lewis acid. There is another strategy, although less explored, which consists of designing chiral Lewis bases for nucleophilic catalysis. It is well known that Lewis bases such as nitrogen heterocycles and tertiary phosphines and amines catalyse a variety of important chemical processes. For instance 4-(dimethylamino)pyridine (DMAP) catalyses the acylation of alcohols by anhydrides the mechanism by which DMAP accelerates this process provides an instmctive illustration of how nucleophiles can... 

DMAP acts as an efficient acyl transfer agent, so that alcohols resistant to acetylation hy Acetic Anhydride-Pyridine usually react well in the presence of DMAP. Sterically hindered phenols can be converted into salicylaldehydes via a benzofurandione prepared by DMAP catalysis (eq 2). ... 

The mechanism of catalysis by DMAP is considered to involve an N-acylpyridinium ion. However, the identity of the anion also affects the reactivity so that a complete formulation requires that the ion pair characteristics of the acylpyridinium ion be taken into account. Interestingly, in the presence of DMAP, acetic anhydride is a more reactive acylating agent than acetyl chlorode. This reversal of the normal reactivity order can be explained if the acetate ion, a stronger base than chloride, is involved in deprotonating the alcohol ... 

The acylation of alcohols by anhydrides, catalyzed by 4-(dimethylamino)pyridine (DMAP), is one of the most frequently described in the literature examples of nucleophilic catalysis (Figure 5.6). 

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