Tautomerization of enols

Example 2.7. Strong acids and bases as intermediates in the tautomerization of enols in water (neutral conditions). 

The research group of Muzart and Henin studied extensively the palladium-catalyzed EDP of allyl- or benzyl-carboxylated compounds. Mainly two types of substrates, prochiral enol carbonates A and racemic (3-keto esters B, were used to afford enols C as transient species [25]. In the presence of a chiral proton source, asymmetric protonation/tautomerization of enols led to enantioenriched ketones D... 

E and enol radical cations, E. After this occurs, however, it is not clear whether K forms simply through tautomerization of E, or by combination of radical ions of the keto form which may arise from tautomerization of enol radical ions, of which many pathways can be supposed. The detailed mechanism of the observed EGIPT luminescence remains to be established. 

The Scheidt group reported a highly diastereo- and enantioselective NHC-catalyzed reaction of a,p-unsaturated aldehydes with nitrones to afford y-amino esters. It is postulated that a rare six-membered heterocycle is generated as the initial product of the reaction, which gives the final y-amino ester product upon the addition of an alcohol. The mechanism for this reaction involves the addition of the homoenolate equivalent to the nitrone as the stereochemical-determining step, and catalyst turnover is promoted by an intramolecular acylation after the tautomerization of enol to acyl azolium (Scheme 7.60). 

In the 1,5-diene system, a hydroxyl substituent at C-3 gives the enol product. Subsequent tautomerization of enol providing the carbonyl compound is the driving force for the reaction. The process is termed as the Oxy-Cope rearrangement (Scheme 3.17). 

The tautomerization of enol, decarboxylative pro-cesses, ° as well as the biosynthetic methods are not covered in this chapter. Indeed, despite the fundamental discoveries delivered during the development of these important processes, their application in the course of natural product or drug synthesis remains sporadic and limited. Furthermore, because of the presence of several recent authoritative reviews,the mechanistic and fundamentals aspects are explained briefly. This chapter covers only the most relevant methodologies and the most recent reports, which have not been reviewed to date. 

Tautomerization of the enol form to 2 methylpropanoic acid completes the V process ... 

Hydroxyquinolines (Quinolinols). A number of methods have been employed for their preparation. A modified Chichibabia reaction of quinoline ia fused KOH—NaOH at 240°C produces 70% of 2-hydroxyquiQoline [59-31-4] (121). Alternative names based on the facile keto—enol tautomerism of two of these compounds are 2(1H) and 4(lJd)-quiQolinone none of the other quinolinols show this property. The treatment of... 

The keto-enol tautomerism of 1,2-benzisoxazoles has been examined and the existence of either form can be postulated on the basis of reactivity. IR analysis on the solid indicates the exclusive existence of the enol form, while in CHCI3 solution both appear to be present (71DIS(B)4483). 

Figure 1.11. NMR analysis of the keto-enol tautomerism of 2,4-pentanedione [CDCIa, 50% v/v, 25 °C, 60 MHz for H, 20 MHz for C]. (a) H NMR spectrum with integrais [resuit keto enoi = 13 87] (b) H broadband de-coupied C NMR spectrum (c) C NMR spectrum obtained by inverse gated H decoupiing with integrals [result keto enol = 15 85 ( 1)]...

Hydroxythiophenes 56 have two possible keto tautomers (57 and 58) [for review see (86HC1)]. As has been pointed out earlier (76AHCS1, p. 229), the tautomerism of 5-substituted eompounds was extensively studied by Lawesson and eoworkers (63T1867) and by Hornfeldt (63MI1 68MI1). For 5-alkyl eompounds, only the keto forms were present, whereas with R = phenyl, thienyl and ethoxyearbonyl substantial amounts of the enol forms were deteeted. Computations for the parent system (R = H) showed that the 4 -thiobutenolide of type 57 is most stable (Table VII). 

The 0,N-dideuterated enol was formed by hydrolysis of the O-trimethylsilyl ether 123 (R = TMS) (in 80% [D6]DMSO/20% D2O with 5. lO " M DCl). N-Methylindoxyl (formed by hydrolysis of its acetate) exists in the solid state as a mixture of the enol and the keto tautomers (34% enol/66% keto). The NMR spectrum of freshly prepared solution in DMSO demonstrated signals of both enol and keto forms. However, at equilibrium (reached in 18 h at RT) the ratio of enol to ketone depends strongly on the polarity of the solvent used thus, in [Dg]DMSO the tautomeric mixture contains 92% enol, while in CDCI3 the keto form predominates (97%). A solution with 100% enol could be generated by hydrolysis of its O-trimethylsilyl ether [conditions 80% [Dfi]DMSO/20% D2O with 5 10" M DCl at 32°C (86TL3275 87PAC1577 88TL250)]. 

Phenylmercury derivatives of 3-aminomethylene-l-methyloxindols have also been investigated (79KGS65). For studies of the effect of substituents on the electronic structure of silver and potassium salts of 3-(aryl)imi-nooxindole see 76MI2. The keto-enol and imino-enamine tautomerism of compounds of type 127 (with 128 and 129) has been investigated (85KGS921). 

This formulation is supported by the proton resonance spectrum of the trifluoromethyl compound 101 which shows that it exists in the CH form shownd However, strong electron-withdrawing groups in the 4-position apparently lead to enolization, and compound 102, for example, gives an intense color with ferric chloride, - Other 4-acylated oxazol-5-ones are often formulated as 103 (see, e.g, reference 113). Tautomerism of the type illustrated by the equilibrium 104 103 has been discussed (see reference 115 for further references). 

Base catalyzed nitrile hydrolysis involves nucleophilic addition of hydroxide ion to the polar C N bond to give an imine anion in a process similar to nucleophilic addition to a polar C=0 bond to give an alkoxide anion. Protonation then gives a hydroxy imine, which tautomerizes (Section 8.4) to an amide in a step similar to the tautomerization of an enol to a ketone. The mechanism is shown in Figure 20.4. 

Tautomerization of the hydroxyimine yields an amide in a reaction analgous to the tautomerization of an enol to give a ketone. 

Keto-enol tautomerism of carbon) ] compounds is catalyzed by both acids and bases. Acid catalysis occurs by protonation of the carbonyl oxygen atom to give an intermediate cation that Joses H+ from its a carbon to yield a neutral enol (Figure 22.1). This proton loss from the cation intermediate is similar to what occurs during an El reaction when a carbocation loses H+ to form an alkene (Section 11.10). 

Carbonyl compounds are in a rapid equilibrium with called keto-enol tautomerism. Although enol tautomers to only a small extent at equilibrium and can t usually be they nevertheless contain a highly nucleophilic double electrophiles. For example, aldehydes and ketones are at the a position by reaction with Cl2, Br2, or I2 in Alpha bromination of carboxylic acids can be similarly... 

Following hydrolysis, keto-enol tautomerization of the carbonyl group from C2 to Cl gives glucose 6-phosphate. The isomerization is the reverse of step 2 in glycolysis. 

H NMR spectroscopy frequently has been used in kinetic studies, for example, in the isomerization of 2,4,6-triphenyl-4//-thiopyran 56 (R= Ph) to its 2//-isomer 60 (R = H, 81JHC1517). l25Te NMR spectra were also measured for 4//-teluropyran 77 and related compounds (88MI1). Oxo-enol tautomerism of 4-hydroxy-2//-thiopyrans llOa-c in the solid state as well as in CDC13 solution was successfully studied by l3C NMR [86JCS(P2) 1887]. 

After succeeding in the asymmetric reductive acylation of ketones, we ventured to see if enol acetates can be used as acyl donors and precursors of ketones at the same time through deacylation and keto-enol tautomerization (Scheme 8). The overall reaction thus corresponds to the asymmetric reduction of enol acetate. For example, 1-phenylvinyl acetate was transformed to (f )-l-phenylethyl acetate by CALB and diruthenium complex 1 in the presence of 2,6-dimethyl-4-heptanol with 89% yield and 98% ee. Molecular hydrogen (1 atm) was almost equally effective for the transformation. A broad range of enol acetates were prepared from ketones and were successfully transformed into their corresponding (7 )-acetates under 1 atm H2 (Table 19). From unsymmetrical aliphatic ketones, enol acetates were obtained as the mixtures of regio- and geometrical isomers. Notably, however, the efficiency of the process was little affected by the isomeric composition of the enol acetates. 

The ZnO was a very effective reagent as it caused dehydrobromination, simultaneous deacetylation, and tautomerization of the resulting enol intermediate.69... 

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