DMAP catalysis, anhydride

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 Glaxo synthesis of zanamivir (2) started with the esterification of commercially available A-acetyl-neuraminic acid (88) with methanolic HCl to give the methyl ester as shown in Scheme 7.14 (Chandler and Weir, 1993 Chandler et ah, 1995 Patel, 1994 Weir et al., 1994). Global acetylation of all the hydroxyl groups with acetic anhydride in pyridine with catalysis by 4-(dimethylamino)pyridine (DMAP) led to the penta-acetoxy compound 89. Treatment of 89 with trimethylsilyl triflate in ethyl acetate at 52°C introduced the oxazoline as well as the 2,3-double bond to provide 86. Addition of trimethysilyl azide to the activated allylic oxazoline group led to the stereoselective introduction of azide at the C-4 position to afford 83 as in Scheme 7.13. 

Butenolides. The fmnal steps in a synthesis of jolkinolide E (4) involve formation of the butenolide ring by reaction of the a-hydroxy ketone 1 with the mixed anhydride of trichloroacetic acid amd a-(diethylphosphono)propionic acid (2) with catalysis by DMAP. The ester 3 undergoes an intramolecular Wittig-Horner reaction in the presence of NaH to give 4. ... 

The combination of carboxyl activation by a carbodiimide and catalysis by DMAP provides a useful method for in situ activation of carboxylic acids for reaction with alcohols.10 The reaction proceeds at room temperature. Carbodiimides are widely applied in the synthesis of polypeptides from amino acids. The proposed mechanism for this esterification reaction involves activation of the acid via isourea 28 followed by reaction with another acid molecule to form anhydride... 

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). 

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... 

Inverse phase-transfer catalysis (IPTC) can be applied to synthesize symmetric and antisymmetric acid anhydride in organic synthesis." - "- - - - " > Pyridine 1-oxide (PNO), 4-dimethylaminopyridine (DMAP), 4-pyrrolidinopyridine (PPY) and l-methyl-2(lH)-pyridothione are usually used as the inverse phase-transfer eatalysts... 

Shiina accomplished the total synthesis of pseudo 7b by a key cyclization reaction to form the nine-membered ring, which was efHciendy achieved by their original mixed-anhydride method promoted by MNBA under basic catalysis (Scheme 5.37) [89]. Lactonization of the seco-acid 100 was carried out in the presence of MNBA and DMAP, and the desired monomeric lactone 101 was obtained in 71% yield along with the dimeric lactide 102 (7%) [36, 37]. 

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