Carboxylation of cyclic ethers

Cyclic ethers are substrates of great interest as sources of cyclic monomeric carbonates or even as co-monomers for the production of polymers through ringopening carboxylative polymerization. Their reactivity is driven by different parameters, such as  

The ring size and the ring stress energy three-, four-, five-, and six-membered ethers have a quite different reactivity (see Table 6.2) 

The substituents on the ring groups which may produce a different charge localization on O or ethereal Cs have an influence on the rate of opening of the ring 

Name Number of atoms in the ring Ring-strain energy (kJ mol ) Basicity (pXb) Backbone 

Values in italics indicate a lack of confidence. Adapted with permission from [118]. Copyright (2013) Elsevier 

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Polyelkers. Antibiotics within this family contain a number of cyclic ether and ketal units and have a carboxylic acid group. They form complexes with mono- and divalent cations that arc soluble in nonpolar organic solvents. They interact with bacterial cell membranes and allow cations to pass through the membranes causing cell death. Because of this property they have been classified as ionophores. Monensin, lasalocid, and maduramicin are examples of polyethers that are used commercially as anticoccidial agents in poultry and as growth promotants in ruminants. 

Trimethylsilyldiethylamine as Halosilane Equivalent. Tri-methylsilyldiethylamine has recently found applications in preparation (in situ) of difficult-to-handle and highly moisture-sensitive iodosilanes and bromosilanes. This method has been used for a variety of synthetic transformations, including cleavage of cyclic ethers, cyclic acetals, and oxazolidines. The conversion of esters to carboxylic acids may also be accomplished with trimethylsi-lyldiethylamine as shown in the following examples. It may be suggested that other reactions of iodosilane and bromosilane can be carried out by means of trimethylsilyldiethylamine. 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

To verify the generality of the cyclization of iodopyrazolecarboxylic acids, copper p-phenylbenzoylacetylide was used in the reaction with 3-iodo-l-methylpyra-zole-4-carboxylic acid. The assumed intermediate, alkynylpyrazolylcarboxylic acid, has a distribution of the electron density which is the most favorable for closure of the five-membered cyclic ether. However, the reaction leads only to the 5-lactone (Scheme 120). 

Ethers in which at least one group is primary alkyl can be oxidized to the corresponding carboxylic esters in high yields with ruthenium tetroxide. Molecular oxygen with a binuclear copper (II) complex " or PdCVCuCVCO " also converts ethers to esters. Cyclic ethers give lactones. " The reaction, a special case of 19-14,... 

Ni(cyclam)]2+ was shown to be an efficient electrocatalyst for the intramolecular cyclization-carboxylation of allyl or propargyl-2-haloaryl ethers,200 and for the synthesis of cyclic carbonates from epoxides and carbon dioxide.201... 

Scheme 13 Cyclic ethers and lactones by allyloxylation-cyclization of unsaturated alcohols and carboxylic acids.

Epoxides readily undergo anionic copolymerization with lactones and cyclic anhydrides because the propagating centers are similar—alkoxide and carboxylate [Aida et al., 1985 Cherdron and Ohse, 1966 Inoue and Aida, 1989 Luston and Vass, 1984]. Most of the polymerizations show alternating behavior, with the formation of polyester, but the mechanism for alternation is unclear. There are few reports of cationic copolymerizations of lactones and cyclic ethers other than the copolymerizations of [5-propiolactone with tetrahydrofuran and... 

The reagent most commonly used for oxidation of ethers is RuO. The subject is well summarized in an early review by Gore [75], Primary methyl ethers RCHjOCHj are oxidised to esters RCOOCH, and secondary methyl ethers R R CjHjOCHj to ketones R COR while with benzyl ethers PhCH OR the esters PhCOOR are formed. For cyclic ethers, the carbon atoms adjacent to the O atom are oxidised, and if there are two secondary carbon atoms the main products are lactones, sometimes with partial hydrolysis to carboxylic acids [75], There is a short review on oxidation of ethers by RuO, principally on the mechanisms involved [76],... 

The products of the electrochemical perfluorination of aliphatic or cyclic ethers are the corresponding perfluorinated ethers. Byproducts are perfluorinated ethers with shorter carbon chains, perfluoroalkanes, perfluorocarboxylic acid fluorides and oxygen difluoride. Cyclic perfluorinated ethers can be produced by electrochemical fluorination of alcohols,32 aliphatic carboxylic acids33 or of their acid halides34 containing not less than four carbon atoms in the chain. 

Saturated alkane-1,2-carboxylic acids and alkane-1,3-carboxylic acids give, in general, three types of products bis(trifluoromethyl)alkancs, cyclic a,a,a, a -tetrafluoro ethers and linear bis(pentafluoroalkyl) ethers. The 1,2-dicarboxylic acids, succinic and halosuccinic acids, give as the main products the cyclic ethers 6, derivatives of tetrahydrofuran, in ca. 30-50% yield, but from 1,3-dicarboxylic acids the yields of the corresponding six-membered ethers 9 are 16%.118... 

Particularly high yields of cyclic tetrafluoro ethers are obtained from acids in which the carboxylic groups are fixed in cis positions relative to one another. Thus, reaction of d.v-cyclo-hexanc-l,2-dicarboxylic acid gives the cyclic ether 12 in 70% yield with very limited formation of 1,2-bis(trifluoromethyl)cyclohexane.118... 

A significant portion of the neutral ethyl ether extract from the salts of carboxylated methyl linoleate consists of ,/3-unsaturated cyclic ketones. This material is produced in small but significant amounts (4-10%) (Table I) from the carboxylation of polyunsaturates but not from the corresponding monounsaturated fatty acids and esters (19). These ,/ -unsaturated cyclic ketones were identified spectroscopically (IR, UV, and NMR) as 4. This structural assignment was firmly established by mass spectral analyses before and after hydrogenation of the carbon-carbon double bond. 

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