Eno late ions

A more general method for preparation ofa-amino acids is the amidotnalmatesynthesis, a straightforward extension of the malonic ester synthesis (Section 22.7). The reaction begins with conversion of diethyl acetamidomalonate into an eno-late ion by treatment with base, followed by S 2 alkylation with a primary alkyl halide. Hydrolysis of both the amide protecting group and the esters occurs when the alkylated product is warmed with aqueous acid, and decarboxylation then takes place to vield an a-amino acid. For example aspartic acid can be prepared from, ethyl bromoacetate, BrCh CCHEt ... 

The mechanism of the C02 transfer reaction with acetyl CoA to give mal-onyl CoA is thought to involve C02 as the reactive species. One proposal is that loss of C02 is favored by hydrogen-bond formation between the A -carboxy-biotin carbonyl group and a nearby acidic site in the enzyme. Simultaneous deprotonation of acetyl CoA by a basic site in the enzyme gives a thioester eno-late ion that can react with C02 as it is formed (Figure 29.6). 

This enzyme catalyzes the decarboxylation of acetoacetate to acetone and carbon dioxide. The nonenzymatic reaction involves the expulsion of a highly basic eno-late ion at neutral pH (equation 2.36), but the enzymatic reaction circumvents this by the prior formation of a Schiff base with a lysine residue. The protonated imine is then readily expelled. 

On the other hand we might want to carry nut a carbonyl cotidcoM tion reaction. Since wo need to generate only a small amount of the eno-late ion in the presence of unreacted carbonyl compound, the aldol reactiaa requires only a tmtaiytie amount of a weaker base, rather than a full uk-nt. Once ft condensatioa haa occurred, the basic calalynt le rcg<... 

Conjugate addition of the cuprate to the a,(3-unsaturated ketone leads to an eno-late ion, 143. It is possible to have this enolate anion reacts with an electrophilic species tandem vicinal difunctionalization), in some cases at the O and in other cases at the For example, if an alkyl halide R X is present (R = primary... 

Most alcohols are resistant to dehydration by dilute acid or base (Section 17.7), but aidol products are special because of the carbonyl group. Under basic conditions, an acidic a hydrogen is removed, yielding an eno-late ion that expels the "OH leaving group in an E2-like reaction. Under acidic conditions, an enol is formed, the -OH group is protonated, and water is eliminated. 

Addition to oxaloacetate. Acetyl CoA enters the citric acid cycle in stepj 1 by nucleophilic addition to the ketone carbonyl group of oxaloacetate to give citryl CoA (Section 26.15). The addition is an aldol reaction of an eno-late ion from acetyl CoA, and is catalyzed by the enzyme citrate synthase, as discussed in Section 26.15. Citryl CoA is then hydrolyzed to citrate. 

In addition to different bonding characteristics of the reaction intermediate on the different surfaces, at least two other interactions that differ on the different surfaces can be identified. The atomic arrangement of an ideal Zn-polar surface is such that a layer of Zn ions is more outwardly situated than the next layer of 0 ions. Because the exposed ions are Zn ions which are nonpolarizable, this surface is a hard acid (14) Conversely, an ideal 0-polar surface has a layer of 0 ions more outwardly situated than the next layer of Zn ions. These exposed 0 ions make the surface a soft base. The intermediate in 2-propanol decomposition is an eno late ion (13 ). Being a base, it should interact more strongly with a hard acid than a soft base. 

The actual synthetic sequence can be depicted as follows. Deprotonation of the malonate a-carbon followed by 8 2 displacement at the C-Br bond (better leaving group recall Section 6-7) of the substrate gives a 5-chloropentyl malonate derivative. Subsequent treatment with another equivalent of base removes the remaining a-hydrogen, and the resulting eno-late ion displaces chloride intramolecularly to form the ring. Hydrolysis and decarboxylation complete the synthesis ... 

Aromatic substrates with a CF3 group either ortho or para to the halogen, on reaction with the the eno-lates from acetone or pinacolone, undergo reactions in which HF is eliminated from the initially formed SrnI product.88 The normal substitution product is obtained, however, on treatment of /n-CF)-iodoben-zene with ketone enolates70 88 or on reaction of o-CF3-iodobenzene with (EtO PO- ion.88... 

Treatment with base (usually LDA) at low temperature produces an enolate, and you can clearly see that the auxiliary has been designed to favour attack by electrophiles on only one face of that enolate. Notice too that the bulky auxiliary means that only the Z-enolate forms alkylation of the E-eno-late on the top face would give the diaster eoisomeric product. Coordination of the lithium ion to the other carbonyl oxygen makes the whole structure rigid, fixing the isopropyl group where it can provide maximum hindrance to attack on the wrong5 face. 

Reagent 1 also undergoes asymmetric Michael additions with enolate ions. Michael additions with disubstituted lithium eno-lates proceed with almost complete tt-facial diastereoselectivity. Starting with these Michael additions, (—)-methyl jasmonate (eq 4) and (—)-estrone methyl ether (eq 5) can be obtained in high enantiomeric purities. 

Since they are negatively charged, enolate ions behave as nucleophile and undergo many of the reactions we ve already studied. For example, eno-lates react with primary alkyl halides in the Sn2 reaction. The nucleophili enolate ion displaces halide ion, and a new C-C bond forms ... 

Halogenation of aldehydes and ketones occurs under both basic and aci( conditions. As you might expect, the base-promoted reaction occurs throi an enoiate ion intermediate. Even relatively weak bases such as hydro ion are effective for halogenation because it s not necessary to convert, ketone completely into its enoiate ion. As soon as a small amount of eno-late is generated, it reacts immediately with the halogen. 

Enolization occurs on the side of the ketone away from the bromine atom and the eno-late cyclizes as before but the cyclopropanone intermediate is symmetrical so that the product is the same whichever C—C bond breaks after nucleophilic attack by the methoxide ion. 

The kinetics of reactions of substituted ethyl arylacetates with quinone methides and structurally related diethyl benzylidenemalonates and of reactions of pyridinium, iso-quinolinium, and quinolinium ylides with diarylcarbenium ions, quinone methides, and arylidene malonates have been studied using solvent DMSO. Pyridinium substitution is found to have a similar effect on the reactivity of carbanionic reaction centres as alkoxycarbonyl substitution. The structures and ambident reactivities of azolium eno-lates have been investigated. ... 

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