Introduction to Carboxylic Acid Derivatives

Under these conditions, the aldehyde cannot be isolated. Instead, it is further attacked by LAH to form an alkoxide, which is then protonated when H30 is added to the reaction flask. 

An alternative method for reducing carboxylic acids involves the use of borane (BH3). 

Reduction with borane is often preferred over reduction with LAH, because borane reacts selectively with a carboxyhc acid moiety in the presence of another carbonyl group. As an example, if the following reaction were performed with LAH instead of borane, both carbonyl groups would be reduced. 

11 Identify the reagents you would use to achieve each of the following transformations  

In the previous section, we learned about the reaction between a carboxyhc acid and LAH. This reaction is a reduction, because the carbon atom of the carboxylic acid moiety is reduced in the process  

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S. Carbonel, C. Fayet, and J. Gelas, Introduction of a carboxyl group through an acetal as a new route to carboxylic acid derivatives of sugars, Carbohydr. Res., 319 (1999) 63-73. 

Carboxylic acid derivative (Chapter 21 introduction) A compound in which an acyl group is bonded to an electronegative atom or substituent Y that can act as a leaving group in a substitution reaction, RCOY. 

The development of diversification linkers allows introduction of an additional element of diversity. Upon completion of the synthesis sequence, the linker is activated facilitating nucleophilic release of the library members from support In the ideal case, as implemented with the acylsulfonamide linker (Scheme 4a), the activated linker is sufficiently reactive that limiting amounts of nucleophile may be added to provide pure product after resin filtration.181 Diversification linkers have been developed for the preparation of carboxylic acid derivatives (Scheme 4a), amines (Scheme 4b),191 aromatic (Scheme 4c) and even heteroaromatic compounds (Scheme 4d).1101... 

Alternatively a dialkylacetonitrile with two different alkyl groups is readily obtained by two successive monoalkylations. The usual mild conditions are employed to introduce two primary alkyl groups introduction of more hindered alkyl groups requires reflux in THF for extended periods of time. In practice it is not necessary to isolate the intermediate monoalkyl derivative. Since dialkyl-acetonitriles are readily hydrolyzed to carboxylic acids, this new procedure provides an alternative to the classical malonic ester synthesis.9... 

In the chemistry of (3-lactam antibiotics, isolations of carboxylic acid derivatives are successfully achieved by formation of amidinium salts [56]. Lewis acid catalysed reaction of 4-substituted 1-trimethylsilyloxyfurans with 4-acetoxyazetidinone chiron leads to highly enantioselective construction of tricyclic carbapenam and penems, in which DBU (1) and Eshenmoser amidine (4) were used for the introduction of the exo double bond on the (3-lactam skeleton by demesylation (A route) and the isolation of carboxylic acids as... 

The metallocarbene intermediates are most often formed from thermal, photolytic, or metal-catalyzed deconposition of diazocarbonyl compounds, with concomitant loss of dinitrogen. Under transition metal catalysis, the initially formed species is a metallocarbene rather than a free carbene, and this is usually desirable due to the moderated reactivity (and, hence, fewer undesired side reactions) of the metal-complexed carbene. The two most common methods for introduction of the diazo group are acylation of diazoalkanes with suitably activated carboxylic acid derivatives and diazo transfer reactions in the case of more acidic active methylene substrates fScheme 16.12T... 

The introduction of a diphosphine ligand to the active site serine of a lipase via a phosphonate inhibitor was reported by Reetz et al. However, the linkage was found to be hydrolytically unstable [72]. Kamer and coworkers reported the covalent anchoring of phosphine ligands using another route. They modified the native Cys of photoactive yellow protein (PYP) using 1,1 -carbonyldiiniidazole (CDI)-activated carboxylic acid derivatives of mono- and diphosphanes (19 and 20 in Figure 10.13) [73,74]. Addition of [Pd(allyl)Cl]2 afforded metalloenzymes with allylic amination activity. Several Rh(I)... 

Another FGI that gives carboxylic acid products is the hydrolysis of carboxylic acid derivatives, such as esters and nitriles. Such hydrolysis reactions can either be acid catalyzed (H3O+) or base promoted (1. NaOH, H2O 2. H3O ) and involve an acyl substitution mechanism (addition-elimination) that replaces any acyl leaving group with a hydroxyl group. The synthesis of carboxylic acids via nitriles is especially noteworthy since the introduction of the cyano group via Sn2 with CN involves the formation of a new C-C bond (adds one new carbon to the alkyl halide carbon chain). 

Among all carboxylic acid derivatives, the amides, RCNR2, are the least susceptible to nucleophilic attack. After a brief introduction to amide naming, this section describes then-reactions. 

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