Enol radical cations

Fig-1 Influence of the pH value on the ratio of the electron transfer, forming enol ether 8, and the water trapping, yielding products 9+10, of the enol radical cation 7 in a DNA double strand... 

Schmittel, M. Umpolung of Ketones via Enol Radical Cations. 169, 183-230 (1994). 

Schmittel, M. Umpolung of Ketones via Enol Radical Cations. 169, 183-230 (1994). Schroder, A., Mekelburger, H.-B., and Vogtle, F. Belt-, Ball-, and Tube-shaped Molecules. 172, 179-201 (1994). 

The one-electron chemistry of enols has been intensively studied by Schmit-tel [108]. He has shown that the thermodynamic stability order of the ketone tautomer and the enol tautomer in the solution phase is inverted upon one-electron oxidation [109, 110]. Therefore enols are much more easily oxidized than the corresponding ketone tautomer. Supposing that the enolization is faster than the electron transfer, it ought to be possible to oxidize the enol present in small amounts beside the ketone in the equilibrium mixture. The following cyclization reactions are as useful approach to the chemistry of enol radical cations and can be considered as the a-umpolung of ketones. 

Two possible mechanisms are proposed. Primarily the enol radical cation is formed. It either undergoes deprotonation because of its intrinsic acidity, producing an a-carbonyl radical, which is oxidized in a further one-electron oxidation step to an a-carbonyl cation. Cyclization leads to an intermediate cyclo-hexadienyl cation. On the other hand, cyclization of the enol radical cation can be faster than deprotonation, producing a distonic radical cation, which, after proton loss and second one-electron oxidation, leads to the same cyclo-hexadienyl cation intermediate as in the first reaction pathway. After a 1,2-methyl shift and further deprotonation, the benzofuran is obtained. Since the oxidation potentials of the enols are about 0.3-0.5 V higher than those of the corresponding a-carbonyl radicals, the author prefers the first reaction pathway via a-carbonyl cations [112]. Under the same reaction conditions, the oxidation of 2-mesityl-2-phenylethenol 74 does not lead to benzofuran but to oxazole 75 in yields of up to 85 %. The oxazole 75 is generated by nucleophilic attack of acetonitrile on the a-carbonyl cation or the proceeding enol radical cation. 

The greater stability of simple ketones relative to their enol tautomers is reversed on formation of the corresponding radical cations (88a) (88b). In appropriate cases, ionization of the ketone to its cation is followed by spontaneous hydrogen transfer to give the enol radical cation. 1,5-Hydrogen transfer via a six-membered-ring transition state is a common route. Characterization of such mechanisms has been reviewed for a variety of such reactions in cryogenic matrices, where many of the processes that compete in solution are suppressed. ... 

Schmidtke H-H (1994) Vibrational Progressions in Electronic Spectra of Complex Compounds Indicating Stron Vibronic Coupling. 171 69-112 Schmittel M (1994) Umpolung of Ketones via Enol Radical Cations. 169 183-230 Schonherr T (1997) Angular Overtap Model Applied to Transition Metal Complexes and dN-Ions in Oxide Host Lattices. 191 87-152... 

Osterheld, T. H. Brauman, J. 1. Infrared mnltiple-photon dissociation of the acetone enol radical cation. Dependence of nonstatistical dissociation on internal energy, J. Am. Chem. Soc. 1993,115,10311-10316. 

For several tautomeric systems ketones/enols, imines/enamin and others) a distinct reversal of the stability order is observed when going from the neutral compounds to the radical cations, the first use of which in a new preparative a-Umpolung reaction has been documented for keto/enol systems. The present review provides a critical evaluation of the chemistry of enol radical cations in solution with a special emphasis on the Umpolung reaction and the intermediates thereof. Other enol type of radical cations are discussed with respect to their potential to provide a-carbonyl radical and a-carbonyl cation intermediates. Hence, this article does not constitute a comprehensive summary on all enol type of radical cation reactions. All potentials in this review are referenced versus SCE, unless noted otherwise. Potentials measured against the ferrocene/ferrocenium couple were converted to SCE by adding 0.334 V. 

Similarly, the reversal of the thermochemical stability order upon one-electron oxidation has been demonstrated theoretically and experimentally for several heteroatom substituted carbonyl/enol pairs, e.g. esters [52,53] and acids [54,55]. A recent detailed evaluation of the substituent effect by Heinrich, Frenking and Schwarz using ab initio molecular orbital calculations [56] is summarized in Table 3. Both a- and 7t-donors X stabilize the two cationic tautomeric forms, but with Ji-donating groups (X F, OH, NHj) the enol radical cations are much more stable than the corresponding keto ions. On the other hand, with c-donor/rt-withdrawing substituents this thermochemical preference is less pronounced and in the case X BeH the order of relative stabilities of ionic keto/enol pairs is even reverted. 

Despite the importance of keto/enol tautomers [57] only a small amount of work has been devoted to the study of enol radical cations in condensed phase. This is directly related to the fact that simple enols as the thermodynamically less stable tautomers [58] are usually not isolable, sinre the kinetic barrier for ketonization is rather low [59,60]. Much more is known about the chemistry of enol and keto radical cations in the gas-phase [61]. For details the reader is referred to recent comprehensive reviews [62]. The only available data on the thermodynamics of enol/keto radical cations in solution stem from a recent study [63]. Using stable dimesityl substituted enols the relative stabilities were determined by a thermochemical cycle approach. 

Table 4. Thermochemistry of keto and enol radical cations in CHjCN [63]...

Since the resulting radical cations proved to be highly reactive with lifetimes much below 10 s in acetonitrile (results from fast scan cyclic voltammetry [64]), only irreversible oxidation potentials of the enols and ketones were obtained. Therefore, the data can only be viewed as a good estimate (Table 4). Nevertheless, in agreement with gas-phase results, it is evident that, in solution as well, enol radical cations are more stable than the corresponding ketone ions. Unfortunately, no solution data are so far available for simple aliphatic systems. 

How can one use this thermochemical effect for a preparative route to enol radical cation intermediates in solution Since one usually has to start with the ketone tautomer, two possibilities are conceivable at first from Fig. 2 (1) direct oxidation of the ketone to the ketone radical cation followed by a 1,3-hydrogen migration to provide the enol radical cation, or (2) selective one-electron oxidation of the enol that is present in the equilibrium situation under fast enolization conditions. 

From several early calculations [65,66], it soon became evident that the rearrangement of ketone to enol radical cations is a slow process with activation... 

All together, route 2 (Fig. 2) seems to be much more promising for offering access to enol radical cations in solution. As a consequence of the inversion of the stability order in keto/enol systems upon one-electron oxidation, the... 

Whereas little is known about ketone and enol radical cations in solution, the related one-electron oxidation of phenols has been extensively studied [72]. Nowadays, anodic oxidation of phenols constitutes a valuable synthetic access to phenoxenium ions [73] which are important intermediates for carbon-carbon bond formation processes [74-76] and to various natural products [77]. In light of the biological relevance of phenol oxidation [78,79] redox potentials of phenols [72,80] and phenolates [80-85] as well as pK values of phenol radical cations [80,86,87] are documented in various solvents. Some of the data will be quoted later in comparison with enol systems. 

Fortunately, the low enol content in simple ketone systems does not necessarily impose an obstacle to generating the corresponding enol radical cations in solution. As outlined in Sect. 2 the selective oxidation of the enol tautomer even in the presence of a vast excess of the ketone opens up an indirect, but quantitative access to enol radical cation intermediates for all systems, if an appropriate oxidant has been chosen. The first, albeit indirect evidence for this selective oxidation step stems from kinetic studies by Henry [109] and Littler [110-112] and will be discussed in more detail in Sect. 3.3. Direct evidence for a specific oxidation of enols was provided by Orliac-Le Moing and Simonet [108]. Using voltammetry at a rotating disc electrode they were able to establish a linear correlation between the anodic current and the enol content for various a-cyano ketones 11. In electrolysis experiments the corresponding 1,4-diketones 13 were obtained in high current yield (ca. 90%). 

A scheme was presented to explain formation of the diketones. Accordingly, two reactions of enol radical cations are plausible (1) deprotonation and (2) reaction with a nucleophile. The role of water as base or nucleophile in the proposed ECC process was tested, but no decisive mechanistic results were obtained to rigorously differentiate between the alternative pathways (Scheme 1). The potential involvement of a-carbonyl cations (path 3) was not considered. 

That deprotonation of enol radical cations is a plausible reaction can be deduced from Yoshida s work [107,113] on the electrooxidative addition of 1,3-dicarbonyl compounds 14 in acetonitrile to substituted olefins yielding dihydro-furans 18 as [3 + 2] cycloaddition products in good to excellent yields. Al-... 

As a general problem, early studies were always obscured in terms of interpretation by the simultaneous presence of both enol and keto tautomers. Only recently, a direct study of the chemistry of enol radical cations was undertaken using stable simple enols of the Fuson type [63,64]. Extensive work originally by Fuson [115-117] and later by Rappoport [118] showed for a series of sterically hindered, mesityl-substituted systems that both the kinetically stabilized enols and the corresponding ketones can be prepared in tautomeri-cally pure form. 

From a mechanistic point of view two possible hypotheses were discussed (Scheme 2). Since radical cations are intrinsically very acidic [29-32] one would expect enol radical cation 27 to deprotonate efficiently and rapidly thus providing an a-carbonyl radical (mechanism 1). In a further one-electron oxidation step the a-carbonyl cation is formed, that cyclizes to an intermediate cyclohexadienyl cation 28. After a 1,2-methyl shift and deprotonation the benzofuran 29 is obtained. The mechanistic proposal is in line with benzofuran formation from a-carbonyl cations as demonstrated by Okamoto [120]. Interestingly, the above mechanism was first proposed by Bailey to explain the formation of 3% of benzofuran 24 in the ozonization of enol 8 [121], Years later, however, the mechanistic hypothesis was proven to be untenable [122] under ozonization conditions. A priori, it cannot be excluded that intramolecular cyclization of the enol radical cation 27 " is faster than deprotonation (mechanism 2). The distonic radical cation formed is expected to lose a proton readily and after a second one-electron oxidation the same cyclohexadienyl cation intermediate as in mechanism 1 is formed. 

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