Enolate ions conversion

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

Both the malonic ester synthesis and the acetoacetic ester synthesis are easy to cany out because they involve unusually acidic dicarbonyi compounds. As a result, relatively mild bases such as sodium ethoxide in ethanol as solvent can be used to prepare the necessary enolate ions. Alternatively, however, it s also possible in many cases to directly alkylate the a position of monocarbonyl compounds. A strong, stericaliy hindered base such as LDA is needed so that complete conversion to the enolate ion takes place rather than a nucleophilic addition, and a nonprotic solvent must be used. 

The enol acetates, in turn, can be prepared by treatment of the parent ketone with an appropriate reagent. Such treatment generally gives a mixture of the two enol acetates in which one or the other predominates, depending on the reagent. The mixtures are easily separable. An alternate procedure involves conversion of a silyl enol ether (see 12-22) or a dialkylboron enol ether (an enol borinate, see p. 560) to the corresponding enolate ion. If the less hindered enolate ion is desired (e.g., 126), it can be prepared directly from the ketone by treatment with lithium diisopropylamide in THE or 1,2-dimethoxyethane at —78°C. ... 

Although the conversion of an aldehyde or a ketone to its enol tautomer is not generally a preparative procedure, the reactions do have their preparative aspects. If a full mole of base per mole of ketone is used, the enolate ion (10) is formed and can be isolated (see, e.g., 10-105). When enol ethers or esters are hydrolyzed, the enols initially formed immediately tautomerize to the aldehydes or ketones. In addition, the overall processes (forward plus reverse reactions) are often used for equilibration purposes. When an optically active compound in which the chirality is due to an asymmetric carbon a to a carbonyl group (as in 11) is treated with acid or base, racemization results. If there is another asymmetric center in the molecule. 

A number of other methods exist for the a halogenation of carboxylic acids or their derivatives. Acyl halides can be a brominated or chlorinated by use of NBS or NCS and HBr or HCl. The latter is an ionic, not a free-radical halogenation (see 14-2). Direct iodination of carboxylic acids has been achieved with I2—Cu acetate in HOAc. " ° Acyl chlorides can be a iodinated with I2 and a trace of HI. Carboxylic esters can be a halogenated by conversion to their enolate ions with lithium A-isopropylcyclohexylamide in THF and treatment of this solution at -78°C with... 

The second type of reaction which is commonly associated with carbonyl compounds involves the generation of a nucleophilic enol or enolate ion. Although the conversion of a ketone to the tautomeric enol does not necessarily involve any other species, the generation of an enolate requires a base (Fig. 3-4). In this latter reaction, the putative nucleophile may act as a general base. 

The increased amounts of rrans-fused product obtained in basic solutions was suggested to arise from hydrogenation of the relatively flat enolate ion which adsorbs irreversibly onto the catalyst surface. Hydrogenation proceeds by hydride ion transfer from the metal catalyst, followed by protonation. Conversely, in an acidic medium protonation occurs initially, followed by irreversible adsorption on the catalyst, and then transfer of a hydride ion. The stereochemistry of reduction is also related to catalyst activity, catalyst concentration, pressure and stirring rate, as they all affect hydrogen availability at the catalyst... 

The most general method of preparation for a amino acids is the amido-malonate synthesis, a straightforward extension of the malonic ester synthesis (Section 22.8). The reaction begins with conversion of diethyl acetamidomalonate into an enolate ion by treatment with base, followed by Sf 2 alkylation with a primary alkyl halide. Hydrolysis of both the amidel protecting group and the esters occurs when the alkylated product is warmed 1 with aqueous acid, and decarboxylation then takes place to yield an a-amiaOj acid. For example, aspartic acid can be prepared from ethyl bromoacetate ... 

Figure 34 illustrates the lowest energy rearrangement path for the CO-loss process of ionized phenol. It involves, in a first step, the enol-keto conversion 21-22. Starting from 22, a ring opening leads to structure 34 which, in turn, by ring closure produces ion 41. A direct and concerted isomerization 22 41 was not found. The CO loss from 41... 

While we must use polarity inversion to add the a-carbonyl cation synthon (1) to an enolate ion, no such tricks are needed to add synthon (3) allyl halides are easily made (Chapter 24) and are reactive in 8 2 reactions. The conversion of... 

Another general method of enol triflate synthesis is by conversion of a ketone into its enolate ion followed by trapping. For example, the enolate ion prepared by deprotonation of 4-tm-butylcyclohexanone with lithium diisopropylamide (LDA) was trapped by N-phenyltriflimide, but not by triflic anhydride, to give the corresponding enol triflate in 82% yield8,77 (equation 51). 

---