Isobutyrophenone enolate

In the aldol-Tishchenko reaction, a lithium enolate reacts with 2 mol of aldehyde, ultimately giving, via an intramolecular hydride transfer, a hydroxy ester (51) with up to three chiral centres (R, derived from rYhIO). The kinetics of the reaction of the lithium enolate of p-(phenylsulfonyl)isobutyrophenone with benzaldehyde have been measured in THF. ° A kinetic isotope effect of fee/ o = 2.0 was found, using benzaldehyde-fil. The results and proposed mechanism, with hydride transfer rate limiting, are supported by ab initio MO calculations. 

The mechanism of the aldol-Tishchenko reaction has been probed by determination of kinetics and isotope effects for formation of diol-monoester on reaction between the lithium enolate of p-(phenylsulfonyl)isobutyrophenone (LiSIBP) and two molecules of benzaldehyde. ". The results are consistent with the formation of an initial lithium aldolate (25) followed by reaction with a second aldehyde to form an acetal (26), and finally a rate-limiting intramolecular hydride transfer (Tishchenko... 

In 1998, Hasanayn and Streitwieser reported the kinetics and isotope effects of the Aldol-Tishchenko reaction . They studied the reaction between lithium enolates of isobu-tyrophenone and two molecule of beuzaldehyde, which results iu the formation of a 1,3-diol monoester after protonation (Figure 28). They analyzed several aspects of this mechanism experimentally. Ab initio molecular orbital calculatious ou models are used to study the equilibrium and transition state structures. The spectroscopic properties of the lithium enolate of p-(phenylsulfonyl) isobutyrophenone (LiSIBP) have allowed kinetic study of the reaction. The computed equilibrium and transition state structures for the compounds in the sequence of reactions in Figure 28 are given along with the computed reaction barriers and energy in Figure 29 and Table 6. 

Streitwieser and coworkers recently reported that the lithium enolate of p-(phenylsul-fonyl)isobutyrophenone exists as a monomer-dimer mixture iu THE, with the equilibrium constant = (5.0 0.1) x 10 M . The rate of the reaction of the enolate with p-tert-butylbenzyl bromide was measured spectrophotometricaUy at the enolate concentration range of 7 x 10 to 5 x 10 M, where the percentage of the monomer was 4.5 to 11%. The logarithmic plot of the rate vs the enolate concentration was linear with a slope of 0.50 0.04, indicating that the reacting species is the monomer that exists as a minor component in the equilibrium with the dimer. 

Several examples of Bi(OTf)3-catalyzed Mannich-type reactions with various silyl enol ethers are summarized in Table 12. Silyl enol ethers derived from aromatic and aliphatic ketones were reacted with an equimolar mixture of aldehyde and aniline (Scheme 10). The corresponding (3-amino ketones 27 were obtained in good yields (Table 12, entries 1M-) from aromatic-derived silyl enol ethers, except for the more hindered isobutyrophenone derivative. Silyl enol ethers derived from cyclopentanone or cyclohexanone afforded the (3-amino ketones in good yields (Table 12, entries 5 and 6). 

Rates of acid-catalysed enolization of isobutyrophenone and its ot-d analogue have been measured in H2O and D2O, by bromine scavenging.1403 Results include a solvent isotope effect, ku /kDi, of 0.56, and a substrate isotope effect, h/ d, of 6.2 (both for the enolization reaction). Combination of the data with that for ketonization in D2O140b gives the first isotope effect for the keto-enol equilibrium of a simple ketone e(H20)/ e(D20) = 0.92. The results are discussed in terms of the isotopic fiuctionation factors and the medium effect. 

A study of acid-catalysed enolization and carbon-acid ionization of isobutyrophenone has combined the solvent isotope effect k /kv = 0.56 and substrate isotope effect kH/kD = 6.2 determined for the enolization in H2O and D2O with literature information in order to estimate the solvent isotope effect on the enolization equilibrium, A e(H20)/A e(D20) = 0.92, and on the CH ionization of butyrophenone, kf (R20)/kK(D20) = 5.4.130 This is the first report of an isotope effect on AY forketo-enol equilibrium of a simple aldehyde or ketone. 

By comparison, the lithium enolate of p-(phenylsulfonyl)isobutyrophenone (SIBP) was found mainly dimeric in THF, in equilibrium with its very reactive monomer (K, = 5 x 104 M-1)254. In the presence of lithium bromide, this dimer gave birth to a well-characterized 1 1 LiSIBP-LiBr mixed aggregate255. Similarly, a 1 1 LiSIBP-LiHMDS was demonstrated upon addition of lithium hexamethyldisilazide (Scheme 63)256. 

The mixed Tishchenko reaction involves the reaction of the aldol prodnct 113 from one aldehyde with another aldehyde having no a-hydrogens to yield an ester The products were proposed to be formed through an aldol step (equation 33), followed by addition of another aldehyde (equation 34) and an intramolecular hydride transfer (equation 35). However, several aspects of this mechanism need to be clarified. As part of the continuing mechanistic studies carried out by Streitwieser and coworkers on reactions of alkali enolates ", it was found that the aldol-Tishchenko reaction between certain lithium eno-lates and benzaldehyde proceeded cleanly in thf at room temperature". Reaction of the lithium enolate of isobutyrophenone (Liibp) with 1 equiv of benzaldehyde in thf at — 65 °C affords a convenient route to the normal aldol product 113 (R = R" = Ph, R = Me). At room temperature, however, the only product observed after acid workup was the diol-monoester 116, apparently derived from the corresponding lithium ester alcoholate (115, R = R" = Ph, R = Me), which was quantitatively transformed into 116 after quenching. As found in other systems", only the anti diol-monoester diastereomer was formed. 

A study of acid-catalysed enolization and carbon-acid ionization of isobutyrophenone has combined the solvent isotope effect — 0.56 and substrate isotope effect... 

The alkylation reactions of enolate anions of both ketones and esters have been extensively utilized in synthesis. Both stable enolates, such as those derived from 6-ketoesters, 6-diketones, and malonate esters, as well as less stable enolates of monofunctional ketones, esters, nitriles, etc., are reactive. Many aspects of the relationships among reactivity, stereochemistry, and mechanism have been clarified. The starting point for the discussion of these reactions is the structure of the enolates. Studies of ketone enolates in solution indicate that both tetrameric and dimeric clusters can exist. THF, a solvent in which many synthetic reactions are performed, favors tetrameric structures for the lithium enolate of isobutyrophenone, for example. ... 

It is a useful base for effecting formation of potassium enolates. It was used for methylation of isobutyrophenone to give pivalophenone in 767 yield. ... 

Studies of ketone enolates in solution indicate both tetrameric and dimeric clusters can exist. Tetrahydrofuran, a solvent in which many synthetic reactions are performed, favors tetrameric structures for the lithium enolate of isobutyrophenone, for example. ... 

More basic enolates exhibit generally similar behavior. The sodium enolate of isobutyrophenone reacts with ethyl bromide in dimethoxyethane to give five times as much C-alkylation as O-alkylation. ... 

But also simple ketone enolates without a chelating a-substituent were found to exist under the form of the O-bound tautomers. This is clearly evidenced by crystal structures of bis(amidoamine)-complexed zinc enolates 49 and 50 derived of diisopropyl ketone and acetophenone, respectively. They feature carbon-carbon double bonds, and their core unit is formed by a square or parallelogramshaped Zu202 skeleton. NMR studies revealed related structures for zinc enolates of isobutyrophenone, cyclohexanone, and 2,2-dimethylcyclopentanone (Scheme 3.16) [83]. The mononuclear enolate 51 of methyl mesityl ketone wherein zinc is chelated by TMEDA has the O-bound structure [84a] as well as mixed alkali zinc enolates derived of the same ketone [84]. 

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