Enolates from hydroxyl acids

Hydroxyl Loss from the Ionized Enol of Acetic Acid... 

Some enantiomerically pure substituted 2-oxazolidinones are excellent as chiral auxiliaries. From the pioneering studies 2 conducted in the early 1980 s of the uses of such auxiliaries has emerged what is perhaps the most widely used method today for the preparation of enantiomerically highly enriched a-alkylalkanoic acids, alcohols and aldehydes, that is, the alkylation of enolates from chiral 3-acylated 2-oxazolidinones followed by auxiliary removal2 59. The early work has been reviewed60-62. These enantiomerically pure cyclic imide auxiliaries have been used not only for alkylations but also in a plethora of a-functionalization reactions, such as diastereoselective aldol, a-hydroxylation, a-amination and Diels-Alder reactions and these are discussed elsewhere in this volume. 

Notice that the hydroxyl group on the ketone does not interfere with the reaction, No doubt the first molecule of base removes the OH proton and the second molecule forms the enolate (the only possible enolate in either molecule). Fast condensation with highly electrophilic diethyl oxalate follows, The drug itself results from simple acid treatment of this product. 

Oxaziridines. Davis has developed the use of chiral 2-sulfonyloxaziridines derived from camphorsulfonic acid as chiral auxiliaries in the asymmetric oxidation reactions. Although other oxaziridines may be preferable, the camphor-derived oxaziridines can be used for the oxidation of sulfides and disulfides to sulfoxides and thiosulfinates as well as for the epoxidation of alkenes. On the other hand, the camphoryloxaziridines are the preferred reagents for hydroxylation of lithium enolates of esters, amides, and ketones, as utilized in the synthesis of kjellmanianone (eq 17). ... 

The procedure can be extended to achieve selective a-bromination and iodination of carboxylic acids and the general mechanism of the a-halogenation is outlined in Chapter 5, p 170. The autocatalytic effects in the selective a-chlorination of propionic acid to the 2-chloro and 2,2-dichloro acids have been studied in a semibatch reaction at 90-130 °C. The reaction was performed in the presence of chlorosulfonic acid and dichloroacetic acid as catalysts and oxygen as the radical scavenger. Kinetic experiments indicated autocatalytic formation of both products and that the selectivity was independent of the chlorine concentration in the liquid phase. The results confirmed the validity of the proposed reaction scheme which involved formation of the reaction intermediate, propanoyl chloride from propionic acid and chlorosulfonic acid, the acid-catalysed enolization of the acid, and a hydroxyl-chlorine exchange reaction. The acid-catalysed enolization was the rate-determining step in the reaction sequence. ... 

The selective a-chlorination of propanoic acid to 2-chloro- and 2,2-dichloropro-panoic acid at 80-130 °C in the presence of chlorosulfonic and dichloroethanoic acid as catalysts and oxygen as the radical scavenger was examined. The results confirmed previous studies (Chapter 5, Section 5.6), indicating that the intermediate was propanoyl chloride formed from propanoic acid and chlorosulfonic acid by acid-catalysed enolization and substitution of the hydroxyl group by chlorine. 

Symmetrical labile ethers such as cycloalkenyl ethers (15) or mixed acetals (16) can also be prepared from the 3-hydroxyl group by acid-catalyzed exchange etherification or by acid-catalyzed addition to cyclohexanone methyl enol ether. 

---