STAAB Reagent

Dehydrative cyclization of A-(4-methoxyphcnyl) protected 7-aminoalcohols 157 by the Staab reagent (1,1 -carbonyldiimidazole, CDI) led to the formation of iV-(4-methoxyphenyl)azetidines 158 (Equation 37) <2004SL2751>. The reactions were carried out in a Kugelrohr apparatus. The imidazole formed in the reaction was separated by filtration through silica gel. 

STAAB Reagent 358 STAUOINGER Azide reduction 359 STAUDINGER PFENNINQER Thsrane dnxide synthesis 360... 

FIGURE 6.10 The side chain of histidine is readily acylated (A) by activated residues. The imidazolide produced is an activated species similar to the intermediate generated by reaction (B) of a carboxylic acid with coupling reagent carbonyldiimidazole. (Staab, 1956). Imida-zolides acylate amino and hydroxyl groups. Isomerization of histidyl during activation results from abstraction (C) of the a-proton by the 7t-nitrogen. 

Staab introduced azolides as versatile reagents in organic synthesis. The reaction of carbonyldiimid-azolide with carboxylic acids produces imidazolides under mild conditions which can be converted by the action of hydrogen halides to acid halides in high yield (equation 20). The method does not even require the isolation of the imidazolides, but can be carried out as a one-pot synthesis. The possibility of carrying out this reaction at low temperatures allows the preparation of temperature sensitive compounds. Formyl chloride, which decomposes at -40 °C, has been prepared in this way. 

The use of imidazolides in organic synthesis has been propagated by Staab and coworkers." " Acid anhydrides can also be prepared with carbonyldiimidazolide. The reaction of a carboxylic acid with this reagent leads to acid anhydride if the transacylation equilibrium (equation 35) can be shifted to the side of the anhydride. This is possible either if the acid is used in twofold excess and forms an insoluble salt with the liberated imidazole or if trifluoro- or trichloro-acetylimidazolide is taken as the reagent. Symmetrical acid anhydrides can be obtained in a number of cases in good yield according to equation (36). 20... 

Synthesis of carbonyl compounds. Staab developed interesting syntheses of ketones and of aldehydes using imidazole. An aliphatic or aromatic acid is convertible via the acid chloride into the imidazolide, the carbonyl group of which is susceptible to nucleophilic attack. Thus ketones are obtainable, often in good yield, by reaction of an imidazolide with a Grignard reagent. The imidazolide is reduced... 

A novel and efficient coupling reagent, carbonyldiimidazole (CDI) was discovered [45] by H.A. Staab in Heidelberg, in 1957. The reactive intermediates, acylimidazoles were known before as potent acylating agents [5,35]. In spite of... 

The success achieved with dicyclohexylcarbodiimide stimulated an unrelenting search for even better coupling reagents. Some really effective compounds could be found, for instance carbonyldiimidazole (Staab 1957) which mediates coupling in a novel manner, through reactive N-acyl intermediates ... 

The reagent reacts with carboxylic acids to form imidazolides which give esters with alcohols under basic catalysis H. A. Staab and A. Mannschreck, Chem. Ber., 95, 1284 (1962). 

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