Carboxylic acid derivatives lactones

The formation of these carboxylic acid derivatives, lactone and betaine, and the presence of the methyl ketone group confirmed the structure of XLI as 2-acetyl-l-pyrrolidine acetic acid. This established the 1,2-position of the retronecine double bond unequivocally. 

The conversion of carboxylic acid derivatives (halides, esters and lactones, tertiary amides and lactams, nitriles) into aldehydes can be achieved with bulky aluminum hydrides (e.g. DIBAL = diisobutylaluminum hydride, lithium trialkoxyalanates). Simple addition of three equivalents of an alcohol to LiAlH, in THF solution produces those deactivated and selective reagents, e.g. lithium triisopropoxyalanate, LiAlH(OPr )j (J. Malek, 1972). 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

Esters undergo the same kinds of reactions that we ve seen for other carboxylic acid derivatives, but they are less reactive toward nucleophiles than either acid chlorides or anhydrides. All their reactions are equally applicable to both acyclic and cyclic esters, called lactones. 

A common procedure in C-C-bond formation is the aldol addition of enolates derived from carboxylic acid derivatives with aldehydes to provide the anion of the [5-hydroxy carboxylic acid derivative. If one starts with an activated acid derivative, the formation of a [Mac lone can follow. This procedure has been used by the group of Taylor [137] for the first synthesis of the l-oxo-2-oxa-5-azaspiro[3.4]octane framework. Schick and coworkers have utilized the method for their assembly of key intermediates for the preparation of enzyme inhibitors of the tetrahydrolipstatin and tetrahydroesterastin type [138]. Romo and coworkers used a Mukaiyama aldol/lac-tonization sequence as a concise and direct route to 3-lactones of type 2-253, starting from different aldehydes 2-251 and readily available thiopyridylsilylketenes 2-252 (Scheme 2.60) [139]. 

Like unsaturated ketones, a,0-unsaturated carboxylic acid derivatives, e.g. lactones and anhydrides, undergo cycloadditions to alkenes. As for the preparative conditions (direct irradiation or sensitized experiments) these compounds are situated somewhere in between enones on the one side and olefins on the other. 

A second route (route B in Fig. 1) relies on an initiation process with an (meth)acryl hydroxyl compound and is adopted from the chemical ROP of lactones. The controlled character of these polymerizations ensures a virtually quantitative initiation and thus incorporation of hydroxy-functional initiator (e.g., acrylate) into the polymer chain. However, this is not automatically the case for lipase-catalyzed ROP due to the different mechanism. The latter follows an activated monomer mechanism in which the lipase activates any carbonyl group of a carboxylic acid derivative present in the system. It has recently been shown that acrylation using hydroxy-functional acrylate initiators like hydroxy ethyl(meth)acrylate (HEMA or... 

An interesting variant of electrophilic cleavage is intramolecular attack at the linking carboxylic acid derivative by a substrate-bound electrophile (Figure 3.23). This cleavage strategy generally produces lactones. 

Treatment of products derived from the mandelic acid-based boron enolates with aqueous HF followed by NalOq releases a carboxylic acid. For example, the aldol product formed in Equation B5.7 is converted into a carboxylic acid (which lactonizes under the reaction conditions) as shown in Equation B5.9. 

A related Friedel-Crafts reaction of a carboxylic acid derived from lactone 38 to yield an anthrone 39 was employed by Uemura et al. [48,49]. However, a... 

Oxetanones ( -lactones) are useful synthetic intermediates which have been most often prepared by cyclization of p-halo or p-hydroxy acid derivatives or by addition of ketenes " to carbonyl compounds. They are starting materials for useful polymers and copolymers and have been used for the synthesis of alkenes and carboxylic acid derivatives. P-Lactones possessing antimicrobial activity have recently been found in bacterial cultures. ... 

In this section sequences are described in the course of which 7-hydroxy carboxylic acid derivatives are formed and immediately cyclized to 7-lactones. For instance, 7-keto ester (195) is reduced with super hydride to give the dkoxide ester (196) with 7 1 selectivity (equation 73) (1 >6) cannot be isolated, due to the rapid formation of lactone (197). Similarly, cuprates add to 7-aldehydo esters with high selectivity to form tra s-4,5-disubstituted 7-lactones after acidification (equation 74). ... 

Meyers approach to a-chiral lactones may be expanded to the 8-lactone series with ee values comparable to those achieved for lactones (equation 118). Mercuri- and similarly halo-lactonizations of 8,8-unsaturated carboxylic acid derivatives are an efficient way to achieve stereocontrolled heteroatom-carbon ring closure, e.g. of (333) to (334 equation 1IQ). ... 

Although carboxylic acids and their derivatives are somewhat weaker carbon acids than aldehydes and ketones, it is generally possible to quantitatively convert them to the corresponding metal enolates with dialkylamide bases, the most popular of which is LDA. - - Thus, monoanions of saturated esters, lactones, nitriles, /VA -dialkylamides and V-alkyllactams and dianions of carboxylic acids and V-unsub-stituted amides and lactams are easily prepared in aprotic solvents such as THF and C-alkylated with a variety of simple and functionalized SN2-reactive alkylating agents at room temperature or below. When more-hindered systems are involved, the basicity of the metal dialkylamide and the reactivity of the metal enolate can be enhanced by the addition of HMPA. Of course, many of the indirect methods used for the generation of aldehyde and ketone enolates are also applicable to the preparation of enolates of carboxylic acid derivatives (Section 1.1.2.1). O-Alkylations or dialkylations at carbon generally are of minimal importance with metal enolates of carboxylic acid derivatives. 

Phosgene is reported to combine with a wide range of oxygenated materials, including alcohols, ethers, ketones, carboxylic acids, anhydrides, lactones, esters, carbonic acid derivatives, etc. Only the reactions of COCIF with alcohols, phenols and cyclic ethers have been reported, resulting usually in the generation of fluoroformates. Such materials can often be usefully converted into the corresponding fluoro compound by means of decarboxylation in the presence of BF3, EtjO, pyridine, or other materials. 

The o-chloranil-derived lactones can be readily converted to chiral a-oxygenerated carboxylic acid derivatives through methanolysis followed by CAN oxidation. In each case, the optical activity could be fully preserved (Scheme 10.3). 

Intramolecular cyclization is a useful method for the preparation of lactones and cyclic ethers [34], The most common examples are iodolactonization and iodoetherification, the former using a carboxylic acid derivative as the nucleophile and the latter relying on a hydroxy group. Thus, butyrolactones are available from Y, -unsaturated carboxylic acid derivatives [1,35,36], while unsaturated alcohols lead to cyclic ethers [37-40], Lactones are also available from a wide variety of nucleophiles such as carbonates [41], orthoesters [42], or carbamates [43,44], which can all be used in place of a carboxylate anion [44,45],... 

Youssef M. S. K. Precision separation of enantiomers by liquid chromatography of diastereomeric derivatives. 5. Precision preparative separation of enantiomeric carboxylic acids and lactones by liquid chromatography and neighboring group assisted hydrolysis of diastereomeric amides, Angew. Chem., 1979, 91,... 

Other reactions of phosphorus pentachloiide (81) with carboxylic acid derivatives include those with acrylonitrile (92), as outlined, and with the lactone (93). ... 

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