Lactonization of carboxylic acids

Enol lactones of carboxylic acids [X = —COR— (to C2) with exocyclic and X = —COR— (to C3) with endocyclic lactones Section VIII]. 

Isothioureas (148) and (149) have been developed as organocatalysts for asymmetric intramolecular Michael addition-lactonization of carboxylic acids R CH2C02H with... 

Lactones, which may be regarded as cyclic or inner esters, react similarly. Anhydrides of carboxylic acids also react with hydroxylamine to form hydroxamic acids ... 

Epoxides provide another useful a -synthon. Nucleophilic ring opening with dianions of carboxylic acids (P.L. Creger, 1972) leads to y-hydroxy carboxylic acids or y-lactones. Addition of imidoester anions to epoxides yields y-hydroxyaldehyde derivatives after reduction (H.W. Adickes, 1969). 

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). 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

The photolysis of carboxylic acids and derivatives as lactones, esters and anhydrides can yield decarboxylated products 253>. This reaction has been utilized in the synthesis of a-lactones from cyclic diacyl peroxides 254) (2.34) and in the synthesis of [2,2]paracyclophane by bis-decarboxylation of a lactone precursor (2.35) 255). This latter product was also obtained by photoinduced desulfurization of the analogous cyclic sulfide in the presence of triethyl phosphite 256). 

The chemistry of a-haloketones, a-haloaldehydes and a-haloimines Nitrones, nitronates and nitroxides Crown ethers and analogs Cyclopropane derived reactive intermediates Synthesis of carboxylic acids, esters and their derivatives The silicon-heteroatom bond Syntheses of lactones and lactams The syntheses of sulphones, sulphoxides and cyclic sulphides... 

Hydrocarboxylation of Alkynes Intramolecular addition of carboxylic acids (weak nucleophiles) to alkynes led to lactones, which were first reported by Schmidbaur et al. in the reaction of acetic add with 3-hexynes to obtain, in addition to enol ester, 3-hexanone. Traces of water were probably present in the solvent to enable the process to be carried out [99]. 

Carboxylic esters are produced by the addition of carboxylic acids to olefins, a reaction that is usually acid-catalyzed (by proton or Lewis acids182) and similar in mechanism to 5-4. Since Markovnikov s rule is followed, hard-to-get esters of tertiary alcohols can be prepared from olefins of the form R2C=CHR.183 When a carboxylic acid that contains a double bond in the chain is treated with a strong acid, the addition occurs internally and the product is a y- and/or a 8-lactone, regardless of the original position of the double bond in the chain, since strong acids catalyze double bond shifts (2-2).184 The double bond always migrates to a position favorable for the reaction, whether this has to be toward or away from the carboxyl group. Carboxylic esters have also been prepared by the acyloxymercuration-demercuration of olefins (similar to the procedures mentioned in 5-2 and 5-4).185... 

Carboxylic acid anhydrides generally react with sulfur tetrafluoride in the same manner as carboxylic acids to give acid fluorides, then trifluoromethyl derivatives. Various cyclic anhydrides, which are particularly stable under acidic conditions, react without cleavage to give, in a stepwise fashion, difluoro lactones and a,a,a, a -tetrafluoro ethers. Conversely, the corresponding diacids are readily dehydrated by sulfur tetrafluoride to give anhydrides in the first step of the reaction. Therefore, in this section reactions of carboxylic acids and carboxylic acid anhydrides are discussed together. 

Two types of esterification reaction that can be studied with water as solvent are lactone formation, in which the alcohol is part of the same molecule as the acid, and the lsO-exchange reaction of carboxylic acids, which makes it possible to examine A-2 reactions of carboxylic acids under the conditions used for ester hydrolysis. Work in both these fields confirms the similarities between ester hydrolysis and formation. The hydrolysis and formation of y-butyrolactone have already been discussed (p. 109). We deal here with the lsO-exchange reactions of carboxylic acids. 

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