Enolization of acetone

The graphic that opened this chapter IS an electrostatic potential map of the enol of acetone... 

Examine the enolate of acetone on Learn mg By Modeling How IS the negative charge distributed between oxygen and the a carbon" ... 

Learning By Model mg contains molecu lar models of the enolates of acetone and 2 4 pentanedione Compare the two with respect to the dis tribution of negative charge... 

Anions of (3-keto esters are said to be synthetically equivalent to the enolates of ketones. The anion of ethyl acetoacetate is synthetically equivalent to the enolate of acetone, for example. The use of synthetically equivalent groups is a common tactic in synthetic organic chemistry. One of the skills that characterize the most creative practitioners of organic synthesis is an ability to recognize situations in which otherwise difficult transfonnations can be achieved through the use of synthetically equivalent reagents. 

Coward and Bruice, 1969. The reference intramolecular reaction is the enolization of acetone catalysed by trimethylamine... 

The excellent agreement with the experimental and calculated isotope effect (calculated for formaldehyde, 3.22, and for acetaldehyde, 3.3 experimental value 2.9) supports the computational approach. This suggests that the computed transition structure for hydride transfer in the reaction of the lithium enolate of acetone with acetaldehyde (Figure 30) is realistic. 

TABLE 6. Computed reaction and activation energies and corresponding isotope effects for the sequence of reactions between lithium vinyloxide (LiEn) and formaldehyde and between the hthium enolate of acetone (AcCH2Li) and acetaldehyde. Reproduced with permission from Reference 29. Copyright 1998 American Chemical Society... 

Aryl radical additions to anions are generally very fast, with many reactions occurring at or near the diffusion limit. For example, competition studies involving mixtures of nucleophiles competing for the phenyl radical showed that the relative reactivities were within a factor of 10, suggesting encounter control,and absolute rate constants for additions of cyanophenyl and 1-naphthyl radicals to thiophenox-ide, diethyl phosphite anion, and the enolate of acetone are within an order of magnitude of the diffusional rate constant. ... 

A comparison of the suitability of solvents for use in Srn 1 reactions was made in benzenoid systems46 and in heteroaromatic systems.47 The marked dependence of solvent effect on the nature of the aromatic substrate, the nucleophile, its counterion and the temperature at which the reaction is carried out, however, often make comparisons difficult. Bunnett and coworkers46 chose to study the reaction of iodoben-zene with potassium diethyl phosphite, sodium benzenethiolate, the potassium enolate of acetone, and lithium r-butylamide. From extensive data based on the reactions with K+ (EtO)2PO (an extremely reactive nucleophile in Srn 1 reactions and a relatively weak base) the solvents of choice (based on yields of diethyl phenylphosphonate, given in parentheses) were found to be liquid ammonia (96%), acetonitrile (94%), r-butyl alcohol (74%), DMSO (68%), DMF (63%), DME (56%) and DMA (53%). The powerful dipolar aprotic solvents HMPA (4%), sulfolane (20%) and NMP (10%) were found not to be suitable. A similar but more discriminating trend was found in reactions of iodobenzene with the other nucleophilic salts listed above.46 Nearly comparable suitability of liquid ammonia and DMSO have been found with other substrate/nucleophile combinations. For example, the reaction of p-iodotoluene with Ph2P (equation (14) gives 89% and 78% isolated yields (of the corresponding phosphine oxide) in liquid ammonia and DMSO respectively.4 ... 

AUylic alkylation. In the presence of this Pd(0) complex and hls(tl iphcnylphosphine)ethane, allylic acetates can be alkylated by lithium enolates of cyclohexanone, 3-pentanone, acetophenone, and mesityl oxide in 40-80% yield. The i I m I ion was shown to occur with overall retention of configuration in the case of the lithium enolate of acetone (equation I). 

Laroff GP, Fischer H (1973) The enol of acetone during photochemical reaction of 3-hydroxy-4-methyl-2-butanone and of acetone. Helv Chim Acta 56 2011 -2020 Lehni M, Fischer H (1983) Effects of diffusion on the self-termination kinetics of isopropylol radicals in solution. Int J Chem Kinet 15 733-757... 

Using a transition state model for enolate formation and a database search, a thiourea with a pendant amine has been designed as a catalyst, and its ability to hydrogen bond the enolate of acetone explored.287 Both in-plane and out-of-plane hydrogen bonds, to a lone a pair and the carbonyl 7r-bond, respectively, were considered. 

The useful synthetic intermediate 30, from which methyl cyclopropyl ketone can be made, comes from the 4-hydroxyketone 31, disconnected to the enolate of acetone 32 and ethylene oxide. 

Though we could use the lithium enolate of acetone, there is an advantage in using ethyl acetoacetate 24. The intermediate 34 cyclises under the reaction conditions and the stable lactone 35 is isolated. Treatment with HBr opens the lactone and decarboxylation gives4 30. This two-step sequence requires only mild conditions. 

The disconnection looks tricky but it is all right if you simply reverse the rearrangement, by drawing the mechanism for the imaginary reverse reaction. There may well be two possible starting materials. Thus cyclopentene 40, needed for a photochemical experiment, could be disconnected as 40a or 40b. There is no obvious way to continue from 41 but 42 has an enone that could be made from aldehyde 43 and some reagent for the enolate of acetone 44. 

S,.S)-Bissetone (28), when traced back to building block 27, only lacks the 3-carbon branch, i. e. acetone. Indeed, the lithium enolate of acetone proved to be a suitable three-carbon synthon attacking the carbonyl function with a 4 1 preference from the proaxial side (27 -> 30). The benzoyl group shift directly following the attack elaborates the desired 2-oxopropyl-branehed tetrahydro-pyranone 31, the dibenzoate of bissetone in fact, from which the parent compound is generated simply by de-O-benzoylation (48) ... 

Figure 12.13 shows that the iso-A enols of the /3-diketones A react with an a,/3-unsaturated carboxonium ion C that acts as a C electrophile. This oxocarbenium ion is formed by reversible protonation of the oc,/3-unsaturated methyl vinyl ketone in acetic acid. However, the oxocarbenium ion C in this figure does not react with the iso-A enols at its carbonyl carbon atom—as the protonated acetone in Figure 12.12 does with the enol of acetone—but at the center C-/3 of the conjugated C=C double bond. Accordingly, an addition reaction takes place whose regioselectivity resembles that of a 1,4-addition of an organometallic compound to an 0C,/3-unsaturated carbonyl compound (see Section 10.6). 1,4-additions of enols (like in this case) or enolates (as in Section 13.6) to a,/3-unsaturated carbonyl and carboxyl compounds are referred to as Michael additions. 

Enolization of Acetone. Hydrogen from water is transferred to the CH of the acetone... 

Having read Chapter 27, you should be able to suggest why the enolate of acetone Iteelf would net be a good choice in this reaction,... 

Koltholf and Johnson (1951) have investigated the effects of cationic and anionic micelles on the acid catalyzed iodination, and hence the enolization, of acetone (equation 44). The rate constant for this reaction... 

Thiophene halides have been coupled with in situ generated tributyltin enolate of acetone in the presence of a palladium catalyst (Pd2(dba)3) along with 2-dimethylamino-2 -diphenylphosphino-l,r-biphenyl as the phosphine ligand) to give the corresponding arylacetone 125-126 in good yields <03TL8869>. 

An example of the second kind is the acid catalyzed enolization of acetone [16, 17], viz. 

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