Enolates salts

Enolate Initiators. In principle, ester enolate anions should represent the ideal initiators for anionic polymeri2ation of alkyl methacrylates. Although general procedures have been developed for the preparation of a variety of alkaU metal enolate salts, many of these compounds are unstable except at low temperatures (67,102,103). Usehil initiating systems for acrylate polymeri2ation have been prepared from complexes of ester enolates with alkak metal alkoxides (104,105). 

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Reduction of a conjugated enone to a saturated ketone requires the addition of two electrons and two protons. As in the case of the Birch reduction of aromatic compounds, the exact order of these additions has been the subject of study and speculation. Barton proposed that two electrons add initially giving a dicarbanion of the structure (49) which then is protonated rapidly at the / -position by ammonia, forming the enolate salt (50) of the saturated ketone. Stork later suggested that the radical-anion (51), a one electron... 

The unconjugated ketone can be isolated if the enolate salt (59) is quenched with ammonium chloride 6-dehydrotestosterone affords androst-5-en-I7-ol-3-one in 74% yield under such conditions. If the intermediate enolate salt is quenched with water, the hydroxide ion so formed may isomerize the 5-en-3-one to the corresponding 4-en-3-one before the product can be isolated. 

Reductions of unsaturated ketones and a-acetoxy ketones usually are effected with an excess of reducing agent. For optimum yields of saturated ketones, the intermediate enolate salt obviously must not become protonated while... 

A more fundamental issue than that of adventitious proton donors is the intrinsic stability of ketone enolate salts in liquid ammonia. Even... 

Lithium-ammonia reduction of l7a-ethyl-19-nortestosterone (68) using Procedure 8a (section V) affords the 4,5a-dihydro compound (69) in 85% yield after a reaction time of 12 minutes after a reaction time of 80 minutes, the yield of (69) is 76%. Lfsing sodium in the same reduction, the yields of compound (69) are 79 and 77 % after reaction times of 8 and 80 minutes respectively. Both the lithium and sodium enolates appear to be reasonably stable in liquid ammonia in the presence of alkali metal. Since the enolate salts are poorly soluble in ammonia, their resistance to protonation by it may be due in part to this factor. 

As first demonstrated by Stork,the metal enolate formed by metal-ammoni reduction of a conjugated enone or a ketol acetate can be alkylated in liquic ammonia. The reductive alkylation reaction is synthetically useful since ii permits alkylation of a ketone at the a-position other than the one at whicf thermodynamically controlled enolate salt formation occurs. Direct methyl-ation of 5a-androstan-17-ol-3-one occurs at C-2 whereas reductive methyl-... 

Common reagents such as lithium diisopropylamide (LDA see Chapter 11, Problem 5) react with carbonyl compounds to yield lithium enolate salts and diisopropylamine, e.g., for reaction with cyclohexanone. 

Enolate chemistry is often the chemistry of the enolate salts. 

Two isomeric structures can be obtained for these products ( -113 and/or Z-113). The stereochemistry was conveniently elucidated on the basis of NMR data which showed coupling constant values 7(H,CO) consistent with the -isomers only. The formation of 113 was explained to occur via the enolate salts (86JHC199). Catalytic... 

The product of simple addition across the double bond is only weakly acidic whereas the final product has a hydrogen activated by two carbethoxy groups and is removed from the equilibrium by conversion to the enolate salt. The stability of the final salt serves to drag the reaction over the barrier that the cyclobutane intermediate must represent. 

The Reformatsky reaction has been applied to the synthesis of fused pyranones and provides an example of selective isomer formation by careful choice of substrate. Hydroxy-methylenecyclohexanone (315) and methyl bromoacetate give 5,6,7,8-tetrahydro-l-benzopyran-2-one (316) through alkylation at the hydroxymethylene carbon atom (54JA6388). However, the benzoyl derivative (317) is unable to form an enolate salt and alkylation occurs at the carbonyl carbon atom, leading to 5,6,7,8-tetrahydro-2-benzopyran-3-one (318) (45HCA771). 

Furthermore, if the carbonyl compound has a hydrogen located on the carbon next to the carbonyl group, the Grignarji reagent can behave as a base and remove this hydrogen as a proton. The result is that the compound becomes an enolate salt and RMgX becomes RH. 

With 2,4-pentanedione, polyvalent metal cations often form very stable and only slightly polar enolate salts, better known as metal chelates. Cupric ion forms a particularly stable dark-blue chelate ... 

Exercise 18-31 Arguing from the factors that appear to regulate the ratio of C- to O-alkylation of enolate anions (Section 17-4), show how you could decide whether the reaction of the sodium enolate salt of ethyl 3-oxobutanoate with a strong acid would give, as the initial product, mostly the enol form, mostly the keto form, or the equilibrium mixture. 

Obviously, the condensation product must be recovered from the enol salt and isolated under conditions that avoid reversion to starting materials. The best procedure is to quench the reaction mixture by pouring it into an excess of cold dilute acid. 

Enolate anions of esters, such as ethyl 3-oxobutanoate or diethyl propanedioate, react with aeyl halides or anhydrides to give acylation products. These reactions are carried out best using sodium hydride instead of sodium ethoxide for production of the enol salt, because then no alcohol is liberated to react with the acyl halide or anhydride ... 

Salts of alkanamines also are useful for generating enolate salts of carbonyl compounds (Sections 17-4A and 18-8C). 

Similar changes take place in the acidification of the enol salt of a carbonyl compound, the principal difference being the much longer life of the acf-nitro compound compared to that of an enol of a simple ketone (see Section 17-IB), Primary and secondary nitro compounds undergo aldol additions and Michael additions with suitable carbonyl compounds and basic catalysts ... 

The Kolbe-Schmitt reaction is related to enzymatic carboxylations as of D-ribulose 1,5-diphosphate with carbon dioxide, a key step in photosynthesis (Section 20-9). The overall result is C—C bond formation by addition of C02 to an enolate salt or its enamine equivalent. 

The mechanism of the chemical reduction of enones with metal (Li, Na, etc.) in liquid ammonia can be described by the following equation in which the substrate 212 receives two electrons from the metal to give the dianion intermediate 213. This intermediate is then successively transformed into the enolate salt 214 and the ketone 2T5 with an appropriate proton donor source. It can readily be seen that the stereochemical outcome of this reaction depends on the stereochemistry of the protonation step 213 - 214. An excellent review on this topic has been recently written by Caine (60). This subject will be only briefly discussed here. 

Baldwin and Kruse (57) have found that the enolate salts 196A-B (M=Li or K) give the enol-ether 197 and no cyclopentanone 198. In contrast to this result, the enolates 199A-B (M=Li or K) under the same conditions gave only the cyclohexanone 201. In this case, the enol-ether 200 was not formed. 

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