Imino-anhydride intermediate

Addition of a carboxylic acid thus afforded the imide via the rearrangement of an imino anhydride intermediate. Deprotection of the acetyl group to access the A-glycosylamino acid can be easily obtained by reaction with piperidine in DMF. 

One of the Ugi-4CR variants with high synthetic potential is the split-Ugi reaction, which was reported in 2006 by the group of Tron aud Giovenzana (Scheme 7.18) [51]. In this reaction, after the formation of the imino-anhydride intermediate 43, the Mumm rearraugement took place by the nucleophilic attack of the other amine present in the diamine reagent. In this manner, the backbone obtained in the general Ugi-4CR was split, and from the point of view of the diamine reagent, a desynunetrization process has occurred as one of... 

A new split-Ugi reaction is the subject of a short review (37 references). The classical four-component reaction of aldehyde, primary amine, carboxylic acid and isocyanide has been modified using a secondary amine instead. This allows the Mumm-like rearrangement step to be avoided, freezing the reaction at the imino-anhydride intermediate, which is susceptible to alternative nucleophilic trapping. 

With fused-ring oxazoles of the type 211 imino anhydrides may be isolated in good yields in methanol. However, oxygenation in inert solvents such as methylene chloride takes an entirely different course and results in the formation of u-cyano acids or esters. Photooxidation of fused-ring oxazoles unsubstituted in the 2-position, such as 213, appears to proceed through the intermediate transannular peroxide 214, which then undergoes intramolecular rearrangement178 to form the cyano anhydride (215). Loss of CO from this mixed anhydride of formic acid leads to w-cyano acid (216), the observed product, in 80-90% yields.126... 

The protonation by the carboxylic acid moiety to give an imi-nium ion followed by a nucleophilic attack of the isonitrile leads to the formation of a nitrilium ion intermediate, which is subsequently intercepted by the corresponding carboxylate anion. The resulting imino anhydride typically undergoes an irreversible transacylation (Mumm rearrangement) to give a final Ugi product (Fig. Ic). For the construction of a 2D library array, only two of the four possible components involved in the Ugi reaction are varied. 

Nitroimidazoles substituted by an aromatic ring at the 2-position are also active as antitrichomonal agents. Reaction of p-fluorobenzonitrile (83) with saturated ethanolic hydrogen chloride affords imino-ether 84. Condensation of that intermediate with the dimethyl acetal from 2-aminoacetaldehyde gives the imidazole 85. Nitration of that heterocycle with nitric acid in acetic anhydride gives 86. Alkylation with ethylene chlorohydrin, presumably under neutral conditions, completes the synthesis of the anti-... 

Polymer-bound isonitrile (423), obtained from TentaGel-NH2 through treatment of the resin with formic acid and acetic anhydride, followed by dehydration of the resulting formamide with tosyl chloride and pyridine, has been employed in the preparation of N-substituted amino add ester [349]. Thus, Ugi MCR, performed in the presence of an alcohol instead of the carboxylic component, gave rise to an imino-ether spedes (426). Several Lewis acids were tested in searching for optimal reaction conditions. Boron trifluoride etherate displayed the better yields in term of desired product of the Ugi-type reaction. Amino acid methyl esters (427) were thus obtained when using methanol as the alcohol component, after deavage from the resin of the intermediate imino-ethers by an acetone/water mixture (Scheme 87). 

More recently, the same group reported that acetic anhydride can also act as an electrophile to trap the zwitterionic intermediate 109 and developed a three-component synthesis of 2,5-dihydro-5-imino-2-methylfuran-3,4-dicarboxylates [74]. More significantly, they developed an elegant four-component synthesis of 3,4-dihydro-coumarin derivatives by reaction of salicylaldehyde, Meldrum s acid, isocyanide, and... 

In this way, pyridine V-sulfonyl- and V-acylimines can be nitrated at the imino group in acetic acid-acetic anhydride.17 Intermediates of type... 

In the classical process a phenylethylamine reacts with a carboxylic acid chloride or anhydride to form an amide, which can be cyclised, with loss of water, to a 3,4-dihydroisoquinoline, then readily dehydrogenated to the isoquinoline using palladium, sulfur, or diphenyl disulfide. Common cyclisation agents are phosphorus pentoxide (P Ojq), phosphorus oxychloride and phosphorus pen-tachloride. The electrophilic intermediate is very probably an imino chloride, or phosphate the former have been isolated and treated with Lewis acids when they are converted into isonitrilium salts, which cyclise efficiently to 3,4-dihy-droisoquinolines. ... 

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