Latent carboxylic acid

The furan ring served as a latent carboxylic acid... 

The mechanism of the Strecker reaction has received considerable attention over its lifespan.4 The conversion of a carbonyl compound into an a-amino acid, by this method, requires a two-step process. The first step consists of the three-component condensation of cyanide and ammonia with the carbonyl compound 1 to produce an intermediate, a-aminonitrile 3. The second step involves the hydrolysis of the nitrile functional group to reveal the latent carboxylic acid 4. Whereas the second step is fairly straightforward and can be done under basic or acid conditions, the first step is more involved than one may expect. The widely accepted sequence for the first step is the nucleophilic addition of ammonia to the carbonyl carbon to produce the corresponding imine derivative 2. Once formed, this initial species is captured by the cyanide anion to generate the requisite a-aminonitrile 3. 

Synthetically useful ozonolyses of heteroaromatic systems include the preparation of pyridine derivatives from quinolines (eq 22), the preparation of versatile A-acyl amides by the ozono-lysis of imidazoles (eq 23), and the unmasking of a latent carboxylic acid function by theozonolysisof a furan system (eq 24). ... 

However, certain additives can decrease the rate of thermal decomposition [28]. These additives include cyclic sulfates, sulfones, sultones, aliphatic and aromatic anhydrides, and polymers with pendant carboxylic acid functional groups. Most of these materials are latent acids, which decompose on heating in the presence of moisture to form a strong acid, as shown for cyclic sulfate, 9, in Eq. 5. 

The Ugi reaction is the four-component condensation of an amine, aldehyde or ketone, carboxylic acid and isocyanide to give an o -acylamino amide [22-24], Although this process has the potential to introduce considerable diversity, the products themselves are not heterocycles but through appropriate choice of substrates, latent functionality in one of the precursors can intercept either an intermediate or further derivatize the acylamino amide Ugi product through post-modification. Thus variants of the Ugi reaction have been investigated under microwave-assisted conditions for the synthesis of diverse heterocyclic libraries [16,19-24],... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

A more generally satisfactory method is the hydrolysis of cyanohydrins. Here a mixture of the carbonyl compound and aqueous sodium cyanide is gradually acidified at room temperature resulting in the sequential formation of the cyanohydrin and its subsequent hydrolysis to the acid (the cyano group is of course a latent carboxyl group). 

A new type of latent-active glycosyl donors, 2 -carboxybenxyl glycosides and their benzyl esters, have been recently introduced [62-64]. The active carboxylic acids are readily available from the latent benzyl esters by catalytic hydrogenation in the presence of ammonium acetate. In an example [62] shown in Scheme 5.24 the latent mannoside (136) was glycosylated with the active donor (135) to provide exclusively the p-linked disaccharide (137) in excellent yield. The latent... 

Synthetic use of the a-aminonitrile intermediates from the Strecker reaction have also been investigated.46 In this manner, it was possible to assemble the core scaffold of the indolizidine alkaloids 112. Treating 110, which contained the amine component and a dimethoxyacetal as a latent carbonyl component, with cyanide under acidic conditions initiated an intramolecular cyclization to afford the Strecker reaction intermediate a-aminonitrile 111. While one could hydrolyze the nitrile functionality to unmask a carboxylic acid, in this case, the nitrile was used to introduce the requisite sidechains needed in the construction of the indolizidine alkaloids 112. 

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