Enols typical reactivity

Their stability at low temperature means that lithium enolates are usually preferred, but sodium and potassium enolates can also be formed by abstraction of a proton by strong bases. The increased separation of the metal cation from the enolate anion with the larger alkali metals leads to more reactive but less stable enolates. Typical very strong Na and K bases include the hydrides (NaH, KH) or amide anions derived from ammonia (NaNH2, KNH2) or... 

Gorman, A. A., Gould, I. R., Hamblett, I., Time resolved Study of the Solvent and Temperature Dependence of Singlet Oxygen ( Ag) Reactivity toward Enol Ethers Reactivity Parameters Typical of Rapid Reversible Exciplex Formation, J. Am. Chem. Soc. 1982, 104, 7098 7104. 

Scheme 2.12 shows some representative Mannich reactions. Entries 1 and 2 show the preparation of typical Mannich bases from a ketone, formaldehyde, and a dialkylamine following the classical procedure. Alternatively, formaldehyde equivalents may be used, such as l>is-(di methyl ami no)methane in Entry 3. On treatment with trifluoroacetic acid, this aminal generates the iminium trifluoroacetate as a reactive electrophile. lV,A-(Dimethyl)methylene ammonium iodide is commercially available and is known as Eschenmoser s salt.192 This compound is sufficiently electrophilic to react directly with silyl enol ethers in neutral solution.183 The reagent can be added to a solution of an enolate or enolate precursor, which permits the reaction to be carried out under nonacidic conditions. Entries 4 and 5 illustrate the preparation of Mannich bases using Eschenmoser s salt in reactions with preformed enolates. 

Methyl transferases are responsible for methylation of a nucleophile, typically using SAM as the carbon donor. They are known to accept a wide range of nucleophiles such as halides (eq. 1 in Figure 13.22) [64], amines (eq. 2 in Figure 13.22) [65], hydroxyls, and enolates. As expected, the reactivity of methyl transfer to halides follows the order of iodide, bromide, and chloride, with chloride being the poorest acceptor. Methylation of amines in nucleotides and proteins plays important roles in biological activities. 

A perhaps more exotic substrate for the Heck reaction is 1,2-cyclohexanedione [25], The reactivity of this molecule under Heck coupling conditions can probably be attributed to its resonance enol form. This reaction is attractive, because the literature contains relatively few examples of the preparation of 3-aryl-l,2-cyclohexane-diones. Yields varied from good to modest when classic heating and electron-rich aryl bromides were used, and reaction times typically ranged from 16 to 48 h. Similar yields were obtained under continuous microwave irradiation with a single-mode microwave reactor for 10 min at 40-50 W (Eq. 11.10) [25],... 

The concept of a group is especially important in organic chemistry. A functional group represents a set of atoms that is closely linked with chemical reactivity and defined classes of substances. For instance, the functional group hydroxyl, -OH, is characteristic of the classes alcohol, phenol and enol. Alcohols are often represented by the general formula R-OH, in which R- represents a hydrocarbon group typical of aliphatic and alicyclic substances. 

In contrast to the ester enolates, the a.O-carboxylic dianions are intrinsically more reactive and their use in conjugate reactions is thus limited. Typically, a-substituted-a.O-carboxylic dianions add exclusively to a,(3-unsaturated esters155a and nitroalkenes,155b while additions to ot,(3-enones are sensitive to the substitution pattern of the enones.155c>d Notable is the conjugate addition of dihydrobenzoic acid dianions (207), from Birch reduction of benzoic acids, to oi,3-unsaturated esters (Scheme 77).155e... 

As long as nucleophilic addition of the preformed enolate to the second carbonyl component is rapid and the carbonyl electrophile is added after the enolate is formed, the product is predictable and is not a mixture. The rule of thumb to ensure success is that the carbonyl electrophile should be more reactive than the carbonyl compound from which the enolate is derived. If this condition is met, the carbonyl electrophile can have a protons and the structural possibilities are increased tremendously. Typical enolate-carbonyl pairs that have been condensed by this methodology include the following ... 

The conversion of enol ether 80 to cyclic ketal 83 in water in 12% yield exemplifies the chemoselectivity possible with 14D9.79 Although 83 is the normal product of the acid-catalyzed hydrolysis of 80 in organic solvents, it is never observed in water because the highly reactive oxocarbenium intermediate is rapidly trapped by the solvent to give ketone 82 (via hemiacetal 81) as the sole product. The ability of the antibody to protect the reactive oxonium ion intermediate from hydrolysis and partition it toward a product that is not typically observed under these conditions (i.e., 83) mimics the capabilities of rather sophisticated enzymes. Extension to other reactions involving reactive, water-incompatible intermediates can be easily imagined. 

When / -dicarbonyl enolates are allowed to react with alkynyliodonium salts, typically in ter/-butyl alcohol or THF, alkynyl- and/or cyclopentenyl- -dicarbonyl compounds are obtained. The product compositions are largely regulated by the migratory aptitude of R in the alkynyl moiety and the availability of alkyl side chains for the MC-insertion (MCI) pathway (equation 45). These divergent modes of reactivity are nicely illustrated by the reactions of the 2-phenyl-1,3-indandionate ion with ethynylfphenyl)- and 4-methyl-1-hexynyl(phenyl)iodonium tetrafluoroborates (equation 1 15)27 2. 

Phenol complexes of [Os] display pronounced reactivity toward Michael acceptors under very mild conditions. The reactivity is due, in part, to the acidity of the hydroxyl proton, which can be easily removed to generate an extended enolate. Reactions of [Os]-phenol complexes are therefore typically catalyzed using amine bases rather than Lewis acids. The regio-chemistry of addition to C4-substituted phenol complexes is dependent upon the reaction conditions. Reactions that proceed under kinetic control typically lead to addition of the electrophile at C4. In reactions that are under thermodynamic control, the electrophile is added at C2. These C2-selective reactions have, in some cases, allowed the isolation of o-quinone methide complexes. As with other [Os] systems, electrophilic additions to phenol complexes occur anti to the face involved in metal coordination. 

Michael addition of tin enolates to a,/3-unsaturated esters is accomplished in the presence of catalytic amount of Bu4NBr. Other typical system using lithium enolates or silyl enolates with catalysts (Lewis acid or Bu4NF) fails to give the Michael products. An ab initio calculation reveals that higher reactivity is caused by high coordination of the tin enolate and the keto enol tautomerization for Michael adducts contributes to thermodynamical stabilization (Equation (77)).231 232... 

Figure 4-7 shows a typical hetero Diels-Alder reaction of a nitrosoalkene. Upon in situ generation of the heterodiene 4-34 from the oxime 4-33, cycloaddition occurred in the presence of the silyl enol ether 4-35 to give the 5,6-dihydro-4H- 1,2-oxazine 4-36 in excellent yield [366]. Such conversions are very suitable for achieving kinetic resolutions of -/Z-isomeric silyl enol ethers since the Z-isomers are distinctly less reactive towards 4-34 [367]. 

Here follows a list of carbonyl substituents that prevent enolization. They are arranged roughly in order of reactivity with the most reactive towards nucleophilic attack by an enolate at the top. You do, of course, need two substituents to block enolization so typical compounds also appear in the list. 

Propen-2-ol (acetone enol) and ethenol (acetaldehyde enol) were some of the first reactive molecules that were generated and characterized by NRMS [65]. Neutral enols are typically less stable than their oxo tautomers and undergo facile isomerization by acid or base catalyzed proton transfer in solution [66] or... 

Under typical Birch reduction conditions a,P-unsaturated aldehydes, ketones and carboxylic esters are reduced to enolates, which can be trapped regiospecifically by reactive alkylating agents or other electrophiles ... 

Since the Lewis acid-promoted reactions of the oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide a versatile method for selective C-H activation and C-C bond formation at the a-position of amides [138]. Typically, TiCl4-promoted reaction of a-t-butyldioxypyrrolidine 66, which can be obtained by the ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with f-BuOOH, with a silyl enol ether gave keto amide 67 (81%), while the similar reaction with less reactive 1,3-diene gave a-substituted amide 68 (Eq. 3.80). 

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