A-Acylimidazolides

Protection of an alcohol function by esterification sometimes offers advantages over use of acetal or ether groups. Generally, ester groups are stable under acidic conditions. Esters are especially useful in protection during oxidations. Acetates and benzoates are the most commonly used ester derivatives. They can be conveniently prepared by reaction of unhindered alcohols with acetic anhydride or benzoyl chloride, respectively, in the presence of pyridine or other tertiary amines. 4-Dimethylaminopyridine (DMAP) is often used as a catalyst. The use of A-acylimidazolides (see Section 3.4.1) allows the... 

A-Acylimidazolides. A,iV -Thionylimidazole reacts with carboxylic acids to form A-acylimidazolides (eq 1) that readily acylate amines, amino acids, or alcohols. The products are readily purified since the byproducts, imidazole and SO2, are easily removed. N,N -Carbonyldiimidazole (GDI) is another useful reagent for formation of A-acylimidazolides. TDI is used less frequently for formation of A-acylimidazolides because of its high reactivity also, GDI is commercially available and easier to handle. Most reported transformations from A-acylimidazolides involve GDI however, TDI should give similar results. 

Ester Formation. A-acylimidazolides react with alcohols very fast in the presence of catalytic amounts of the alkoxide (eq 3). With this method the methyl ester of vitamin A has been obtained in 91% yield. ... 

Carbonyldiimidazole does certainly stand out as one of the most remarkable reagents for peptide coupling. Carboxylic acids react readily with this reagent to yield acyl imidazoles which in turn couple with the amino group of a peptide to produce a new acyl-nitrogen linkage with very little racemization. Reaction of the acylimidazolide with other nucleophiles can lead to a variety of carbonyl derivatives (62AG(E)35l). 

A convenient synthesis of a-acylamino aldehydes (541) has, for example, been developed which is based on the transformation of the a-acylamino acid (540) into its acylimidazolide with carbonyldiimidazole (79CC79). Diisobutylaluminum hydride reduction of the imi-dazolide then affords the aldehyde, generally in high optical purity (equation 6). 

In the second method, ethyl oxalyl chloride is converted first into ethyl a-oxo-1 //-imidazole-1 -acetate, which is then treated with a Grignard reagent.192 The precedent for this reaction is that acylimidazolides are highly reactive towards Grignard reagents to yield ketones without further significant reaction with the carbonyl function to give tertiary alcohols.193... 

Keto esters.—Acylimidazolides react readily with Grignard reagents to provide a general method for the synthesis of a-keto-esters yields are variable over a series of 11 examples. /3-hydroxy-esters and ketones, obtained by the aldol condensation, have been oxidized to /3-keto-esters and ketones most efficiently by the Swern procedure using dimethyl sulphoxide and oxalyl chloride. Sulphide contraction of thiopyrrolidines has been shown to be an effective synthesis of /3-keto-esters and nitriles (Scheme 42). ... 

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