Carbon-oxygen bonds ester formation

The general acid-catalyzed hydrolysis of orthoesters involves proton transfer from the acid to an ester oxygen atom followed by ratedetermining cleavage of a carbon-oxygen bond and formation of... 

In contrast to phosphorus esters, sulfur esters are usually cleaved at the carbon-oxygen bond with carbon-fluorine bond formation Cleavage of esteri nf methanesulfonic acid, p-toluenesidfonic acid, and especially trifluoromethane-sulfonic acid (tnflic acid) by fluoride ion is the most widely used method for the conversion of hydroxy compounds to fluoro derivatives Potassium fluoride, triethylamine trihydrofluoride, and tetrabutylammonium fluoride are common sources of the fluoride ion For the cleavage of a variety of alkyl mesylates and tosylates with potassium fluoride, polyethylene glycol 400 is a solvent of choice, the yields are limited by solvolysis of the leaving group by the solvent, but this phenomenon is controlled by bulky substituents, either in the sulfonic acid part or in the alcohol part of the ester [42] (equation 29)... 

The acyl carbon atom is also sp2-hybridised, much more electrophilic than an aryl carbon atom, and highly stabilised by the structure where the negative charge is on the oxygen atom (Figure 12.18). The acyl oxygen atom may, as in acid catalysed alcoholysis of esters, be protonated, before or after the formation of the new carbon-oxygen bond. 

In the discussion of the general base catalyzed addition step above (p. 120) the objection was raised that it was difficult to believe that general base catalysis would be necessary for the addition of water to so reactive a species as a protonated ester. An answer to this objection is implicit in the discussion above of the mechanism of hydrolysis of orthoesters. It appears that the protonated orthoester, which would be the initial product of the simple addition of a molecule of water to a protonated ester, is too reactive a species to exist in aqueous solution, and that carbon-oxygen bond-cleavage is concerted with the transfer of the proton to the orthoester. The formation of a protortated orthoester by the addition of a molecule of water to the conjugate acid of an ester will be even less likely, and it seems entirely reasonable, therefore, that the formation of the neutral orthoester, by a general base catalyzed process, should be the favoured mechanism. 

Nitrone-Nitrile Oxide Cycloaddition. Unsaturated sugars have been used for the simultaneous formation of carbon-carbon and carbon-oxygen bonds in a cir-relation. One of the best ways to achieve this transformation is the cycloaddition of nitrone or nitrile oxides. The cycloaddition of nitrones with olefins has been reviewed [133]. The regioselec-tivity is almost complete when using activated double bonds, such as enone, enelactone (see compound 98, Scheme 35), or esters. 

The carbonylation of alcohols can proceed with formation of carboxylic acid by catalytic insertion of CO into the carbon-oxygen bond. An alternative reaction gives rise to oxalate or formate esters, when the CO is inserted into the oxygen-hydrogen bond. The members of the nickel triad carbonylate alcohols to give each of these products, and they will be discussed separately. 

Allylic esters undergo both uncatalyzed and acid-catalyzed heterolysis. There is an important difference between the two processes uncatalyzed alkyl carbon-oxygen bond fission produces a carbonium carboxylate ion pair, while acid-catalyzed alkyl carbon-oxygen fission results in formation of an allylic carbonium ion and an uncharged carboxylic acid molecule. 

Isotopes may be conveniently used to obtain additional information about reaction mechanisms. A particular example is the formation of an ester from benzoic acid and methyl alcohol. By labeling the methyl alcohol with it can be shown that the carbon-oxygen bond in the alcohol remains intact during the course of the reaction, implying that an OH group is lost from the acid [13]. 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

There are other mechanisms for ester formation, and some of them do not involve breaking a carbon—oxygen bond in the starting carboxylic acid. Sometimes the car-boxylate anion is nucleophilic enough to act as the displacing agent in an Sn2 reaction. The partner in the displacement reaction must be especially reactive. In practice, this means that a primary halide or even more reactive species such as a methyl halide must be used (Fig. 17.30). 

The initial step is an oxidative addition of RhCI(PPh3)3 to a C-0 bond of the ester moiety and produces rhodium-carbon and rhodium-oxygen bonds. Adjacent rhodium species can undergo further reaction with the formation of anhydride linkages. This anhydride formation may occur between adjacent pairs of reactants, between pairs in the same chain, or between pairs that are present in different chains. All of these reactions are observed, and in however the last reaction is the one of interest here since this leads to cross-linking and char formation. Rhodium is present in both the chary material and in the soluble fractions. From the reaction pathway in order for rhodium elimination to occur, two rhodium-inserted... 

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