Enolates by deprotonation

Section 21 10 It is possible to generate ester enolates by deprotonation provided that the base used is very strong Lithium diisopropylamide (LDA) is often used for this purpose It also converts ketones quantitatively to their enolates... 

Scheme 1.5 gives some examples of alkylation of ketone enolates. Entries 1 and 2 involve formation of the enolates by deprotonation with LDA. In Entry 2, equilibration... 

This /3-keto ester cannot form a stable enolate by deprotonation. It is present in only small amounts at equilibrium. The major product is formed by way of the other enolate. 

These reactions consist of two steps. The first is the formation of a stabilized anion—usually (but not always) an enolate—by deprotonation with base. The second is a substitution reaction attack of the nucleophilic anion on an electrophilic alkyl halide. All the factors controlling SnI and Sn2 reactions, which we discussed at length in Chapter 17, are applicable here, step l formation of enolate anion step 2 alkylation (SN2 reaction with alkyl halide)... 

Racemic chiral enones are versatile substrates for DKR . Reduction of rac-80 with (5 )-[p-TolCuCl(BINAP)], polymethylhydrosiloxane and f-BuONa/f-BuOH in toluene, followed by TBAF, yields diastereoselectively (/f,R)-81 (equation 12). The chiral copper mediator preferentially reduces the (/f)-enantiomer of enone 80, whereas the unreacted (5)-80 efficiently racemizes via an enolate by deprotonation-reprotonation under the basic conditions of the reaction. 

DKR of the mixed anhydride rac-82 has been achieved on addition to a solution of the covalent nucleophilic mediator (DHQD)2AQN (83) in EtOH-EtaO (equation 13) , to yield the ethyl ester (R)-84. The remaining (5 )-enantiomer of 82 is efficiently racemized through enolization by deprotonation-reprotonation, under basic conditions by 83. 

After formation of the enolate by deprotonation with LiHMDS, the ester moiety is introduced by reaction with methyl cyanoformate to give P-ketoester 20 in 70 % yield over three steps. Structure 20 represents a 1,3-dicarbonyl compound that preferentially exists in the enol form. 

As will be described below, self-reproduction of chirality can be accomplished through alkylations of endocyclic as well as exocyclic enolates. It generally entails (i) production of a ring containing a temporary, auxiliary chiral center by derivatization of an optically active a-hydroxy or a-amino ester (ii) formation of an enolate by deprotonation at the original asymmetric a-carbon atom (iii) use of intramolecular chirality transfer to control the stereochemistry of alkylation of the enolate and (iv) generation of the chiral a-alkylated ester by hydrolysis. 

Nozaki and coworkers reported that diethylaluminum 2,2,6,6-tetramethylpiperidine (DATMP) is capable of producing diethylaluminum enolates by deprotonation of ketones or esters at -23°C in THF (Scheme 6.23) [43]. Unlike the instabih-ty of the corresponding lithium enolate, the aldol reaction of the aluminum enolate of t-butyl acetate prevails over the alkoxy ehmination that produces the ketene species, even at -23 °C. 

Alkali Metal Enolates by Deprotonation of Carbonyl Compounds... 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

No protons on ff-carbon atom cannot form stabilized enolate by deprotonation... 

The alkylations in this chapter will each consist of two steps. The first is the formation of a stabilized anion— usually (but not always) an enolate—by deprotonation with base. 

Starting from 3,4-dimethylcyclohex-2-enone, a methyl group and the ester function are introduced in a single step. Prior to the reduction of the ester with aluminium hydride, the keto-function is protected as an enolate by deprotonation with sodium hydride. The aluminate thus produced is protonated diastereose-... 

A more common variation of the aldol addition is to generate the enolate by deprotonation. In special cases, the initially formed alkoxide undergoes further acylation under recych2ation (Scheme 3.66). 

Alkali Metal Enolates by Deprotonation of Carbonyl Compounds 1.422 Alkali Metal Enolates by Addition to a,fi-Unsaturated Carbonyl Compounds... 

Among alkali metal enolates, those derived from ketones are the most robust one they are stable in etheric solutions at 0 C. The formation of aldehyde enolates by deprotonation is difficult because of the very fast occurring aldol addition. Whereas LDA has been reported to be definitely unsuitable for the generation preformed aldehyde enolates [15], potassium amide in Hquid ammonia, potassium hydride in THE, and super active lithium hydride seem to be appropriate bases forthe metallation of aldehydes [16]. In general, preformed alkali metal enolates of aldehydes did not find wide application in stereoselective synthesis. Ester enolates are very frequently used, although they are more capricious than ketone enolates. They have to be formed fast and quantitatively, because otherwise a Claisen condensation readily occurs between enolate and ester. A complication with ester enolates originates from their inherent tendency to form ketene under elimination... 

Among the ingredients of the various recipes for the generation of lithium enolates by deprotonation, lithium salts, in particular lithium chloride, enjoyed very frequent applications [1,68]. It seems that the selectivity-enhancing effect of lithium chloride in enolate-forming reactions was detected by serendipity during the in situ quench of lithium enolates by chlorotrimethylsUane present in the... 

---