Aromatic enols

In the field of hydroxyindolizines the situation is more complicated. No ring carbonyl absorption occurs in the IR spectra of (21) and (22) (76AHC(S1)245), while an aromatic enol tautomer of (23) was excluded completely on the basis of IR and NMR arguments (80JOC5100). This may be due to peri interaction, since an equilibrium between (24) and (25) in DMSO has been deduced from NMR evidence. It was pointed out in Section 3.08.1 that indolizines show pyrroloid as well as pyridinoid properties. This dual character may be used to explain the relative stabilities of some hydroxyindolizines, for example (26) and (27), which have been shown to be the predominantly existing tautomers. 

Aromatic enols, that is, phenols, are generally more stable than their ketone tautomers. The pH-rate profile for the enolization reaction of 2,4-cyclohexadienone to parent phenol is shown in Fig. V.44 The rate constant kK of the reverse reaction was determined at pH = 1 by measuring the rate of isotopic exchange and correcting for isotope effects to determine the enolization constant Kb = = 5.4 x 1012, pA E = -12.73. The dashed line in... 

Aldol reactions using a quaternary chinchona alkaloid-based ammonium salt as orga-nocatalyst Several quaternary ammonium salts derived from cinchona alkaloids have proven to be excellent organocatalysts for asymmetric nucleophilic substitutions, Michael reactions and other syntheses. As described in more detail in, e.g., Chapters 3 and 4, those salts act as chiral phase-transfer catalysts. It is, therefore, not surprising that catalysts of type 31 have been also applied in the asymmetric aldol reaction [65, 66], The aldol reactions were performed with the aromatic enolate 30a and benzaldehyde in the presence of ammonium fluoride salts derived from cinchonidine and cinchonine, respectively, as a phase-transfer catalyst (10 mol%). For example, in the presence of the cinchonine-derived catalyst 31 the desired product (S)-32a was formed in 65% yield (Scheme 6.16). The enantioselectivity, however, was low (39% ee) [65],... 

Monodentate phosphoramidites, in particular (9) and its octahydro analogue, are found to be excellent ligands for the rhodium-catalysed asymmetric hydrogenation of aromatic enol acetates, enol carbamates, and 2-dienol carbamates with up to 98%... 

Arjona and Plumet recently contributed to the study of the use of non-aromatic enol and thioenol ethers as dienophiles with inverse electronic demand [140]. Cydoadditions using 76a also proved to be endo-selective and regiospecific (Figure 25). The regioisomers obtained were those having the heteroatom of the dienophile component adjacent (ortho) and anti to the carbonyl function, rather than ortho and anti to the dimethyl ketal function, as in the... 

The rate of enolate-carbonyl equilibration " is dependent on the forward and backward rates of proton exchange. Proton exchange from a carbon-based acid is known to be slower than that of a more electronegative atom donor (in particular, O and N atoms) . For a series of closely related molecules usually the more acidic a given molecule is, the faster the rate of proton transfer (high kreu note that thermodynamic and kinetic parameters are not related). For example, benzocyclobutanone (10) is less acidic and the rate of deprotonation is substantially slower (10 times) than the related benzocyclopentanone (12) due to its enolate (11) having unfavourable anti-aromatic character. Deprotonation of the simplest cyclobutanone (13) clearly does not lead to an unfavourable anti-aromatic enolate (14) . By assuming the internal strain of 14 is similar to that of 11, cyclobutanone (13) is evidently 10 " times more acidic than benzocyclopentanone (12). By the same vain, the more acidic propanone (15) has a faster rate of deprotonation (10 times) than the less acidic ethyl acetate (16) . ... 

MoOPH is less effective than the boron method for oxidation of aromatic enolates too. In a similar comparison the pyridine 269 was lithiated and treated with oxygen, MoOPH, or the boro-nate sequence to give the hydroxypyridine 271. The results are very clear.45... 

Even simple enols have substantial lifetimes, provided that bases or acids are completely excluded173. Thus, an aromatic enol 4 is prepared in situ by Norrish-type fragmentation of 2. If (-)-ephedrine is present in the reaction mixture, the enol reverts enantioselectively to (/ )-2-rnethy 1 -1 -indanone (3). With as little as 0.01 mol % catalyst, 45% ee is obtained176. The crucial enol 4 has also been generated from either the benzyl enol ester 5 by palladium on charcoal and hydrogen or from the allyl ester 6 by palladium acetate, triphenylphosphine and ammonium formate. In the presence of a chiral 1.2-hydroxyamine, e.g., ephedrine, substantial stereogenic induction in 2-methylindanone 3 was observed175. 

The first report of the preparation of a derivative of the system is due to Benary,68 who prepared 40 by the reaction sequence shown. It would be interesting to discover whether the product has any spectroscopic characteristics of the fully aromatic enolic form (41). 

In the search for new ligands for asymmetric catalysis Ben L. Feringa and coworkers developed the synthesis of chiral monodentate phosphoramidites (PipPhos) (Figure 3.20) which were excellent ligands for asymmetric hydrogenation of aromatic enol acetates, and enol carbamates with high ee values up to 98%. 

Structure of molecules ch4 Phenols as aromatic enols Nucleophilic aromatic substitution ch22... 

The signal that remains is the 2H signal for the protons in the 3 and 5 positions of the aromatic ring, so the product must be the one shown in the margin. We can explain why by using the same mechanism we used with the ketone on the previous page. Phenol is deuterated in the same way as other enols, except that the final product remains in the very stable, aromatic, enol form rather than reverting to the keto form. The first step (after initial replacement of the OH with OD) is addition of D3O+ to the enol. 

The ultimate stabilized enol is phenol. It is estimated that the equilibrium constant for formation of the aromatic enol form from the nonaromatic ketone is greater than IQi (Fig. 19.23). 

Phenols are aromatic enols, undergoing reactions typical of the hydroxy group and the aromatic ring. 

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