Silyl enol ether radical cations

Reactions of Silyl Enol Ether Radical Cations. 213... 

Similar to the deprotonation of enol radical cations, silyl enol ether radical cations can undergo loss of trialkylsilyl cations (most likely not as ionic silicenium ions [190]). Based on photoinduced electron transfer (PET), Gass-man devised a strategy for the selective deprotection of trimethylsilyl enol ethers in the presence of trimethylsilyl ethers [191]. Using 1-cyanonapthalene (1-CN) ( = 1.84 V) in acetonitrile/methanol or acetonitrile/water trimethylsilyl enol ether 93 ( j = 1.29 V) readily afforded cyclohexanone 64 in 60%. Mechanistically it was proposed that the silyl enol ether radical cation 93 undergoes O-Si bond cleavage, most likely induced by added methanol [192-194], and that radical 66 abstracts a hydrogen from methanol. Alternatively, back electron transfer from 1-CN - to 66 would yield the enolate of cyclohexanone which should be readily protonated by the solvent. 

Oxidative coupling of silyl enol ethers as a useful synthetic method for carbon-carbon bond formation has been known for a long time. Several oxidants have been successfully applied to synthesize 1,4-diketones from silyl enol ethers, e.g. AgjO [201], Cu(OTf)2 [202], Pb(OAc)4 [203] and iodosobenzene/BFj EtjO [204]. Although some of these reagents above are known to react as one-electron oxidants, the potential involvement of silyl enol ether radical cations in the above reactions has not been studied. Some recent papers, however, have now established the presence of silyl enol ether radical cations in similar C-C bond formation reactions under well-defined one-electron oxidative conditions. For example, C-C bond formation was reported in the photoinduced electron transfer reaction of 2,3-dichIoro-1,4-naphthoquinone (98) with various silyl enol ethers 99 [205], From similar reactions with methoxy alkenes [206,207] it was assumed that, after photoexcitation, an ion radical pair is formed. 

Although several intermediates are possible in the cyclization reaction, strong evidence was presented for the mechanistic proposal, that cyclization takes place at the stage of the silyl enol ether radical cation. 

In summary, the literature survey provides clear evidence for a-carbonyl radical intermediates but no convincing proof for further oxidation to a-carbonyl cation in the vast majority of silyl enol ether radical cation reactions. This suggests that for most cases, silyl enol ethers are more readily oxidized than the corresponding a-carbonyl radicals. Only in oxidations of -aryl substituted silyl enol ethers, a-carbonyl cation intermediates have been invoked. For example, one-electron oxidation of 87d with TTA" " in acetonitrile/MeOH afforded 76 in analogy to the a-Umpolung of ketones via enol radical cations (Scheme 4), and oxidation of 124 with FePHEN provided benzofuran 19 [171]. 

The two reaction channels described represent the most important steps following the generation of the initial radical cation and can be directly incorporated into synthetic applications involving silyl enol ether radical cations. Deprotonation of the radical cation is a way to conduct a ketone-enone transformation via the silyl enol ether. Other synthetic applications utilizing the radical cation or the a-carbonyl radical are coupling reactions of silyl enol ethers, intramolecular addition to double bonds, or introduction of substituents other than carbon at the a-carbonyl position, respectively. Examples for these synthetic transformations will be presented in the following sections. 

Kochi and co-workers presented a synthesis of a-nitroketones involving silyl enol ether radical cations as key intermediates. Remarkably, the reaction of silyl enol ethers with tetranitromethane yielded a-nitroketones under both thermal and photochemical conditions. 

SCHEME 8 Stabilizing effects in tetralone based silyl enol ether radical cations. 

The same authors also observed an interesting difference in the behavior of the a- and (3-tetralone silyl enol ethers 3 and 4, providing a further indication for the presence of radical ions as reactive intermediates in this reaction. The a-tetralone silyl enol ether radical cation 36 reacted with nitrogen dioxide to form cation 37, whereas the (3-tetralone based radical cation 38 reacted much more slowly and gave a mixture of products (Scheme 8). Due to the mesomeric stabilization of the radical cation 38, its lifetime increased dramatically as observed by time resolved spectroscopy. This favors a cage escape of the radical cation and opens the possibility for further reactions. 

Ramsden et al. have obtained similar results for tetralone silyl enol ether radical cations. They investigated the reaction of various silyl enol ethers with xenon difluoride in acetonitrile and found a new method for the selective preparation of a-fluoroketones (Scheme 9). 

The general mechanistic scenario of the silyl enol ether coupling (44—>53) can be described as formation of a silyl enol ether radical cation 45 and its corresponding a-carbonyl radical 50, addition of this electrophile to a second silyl enol ether double bond, a second one electron oxidation of the intermediate radical 51, and a final desilylation to 53 (Scheme 11). Ceric (IV) ammonium nitrate (CAN),2wo dichloro-... 

Coupling reactions of silyl enol ether radical cations with double bonds other than silyl enol ethers have been investigated as well. Reactions with butadiene, ethyl vinyl ether, and allylic silanes have been reported. 

We also observed similar phenomena in the reaction of silyl enol ethers with cation radicals derived from allylic sulfides. For example, oxidation of allyl phenyl sulfide (3) with ammonium hexanitratocerate (CAN) in the presence of silyl enol ether 4 gave a-phenylthio-Y,5-un-saturated ketone 5. In this reaction, silyl enol ether 4 reacts with cation radical of allyl phenyl sulfide CR3 to give sulfonium intermediate C3, and successive deprotonation and [2,3]-Wittig rearrangement affords a-phenylthio-Y,6-unsaturated ketone 5 (Scheme 2). Direct carbon-carbon bond formation is so difficult that nucleophiles attack the heteroatom of the cation radicals. 

This vanadium method enables the cross-coupling only in combinations of silyl enol ethers having a large difference in reactivity toward radicals and in their reducing ability. To accomplish the crosscoupling reaction of two carbonyl compounds, we tried the reaction of silyl enol ethers and a-stannyl esters based on the following consideration. a-Stannyl esters (keto form) are known to be in equilibrium with the enol form such as stannyl enol ethers, but the equilibrium is mostly shifted toward the keto form. When a mixture of an a-stannyl ester such as 45 and a silyl enol ether is oxidized, it is very likely that the stannyl enol ether will be oxidized preferentially to the silyl enol ether. The cation radical of 45 apparently cleaves immediately giving an a-keto radical, which reacts with the silyl enol ether selectively because of the low concentration of the stannyl enol... 

Since Scheme 4 implies formation of a-carbonyl radicals after deprotonation of enol radical cations, the same oxidation chemistry should potentially be accessible from various enol derivatives as enolates, silyl enol ethers and enol esters (Scheme 5). On the other hand, enol ether radical cations do not fit in this systematization since they are attacked by nucleophiles at the double bond faster than providing a-carbonyl radical intermediates through O-C bond cleavage (Sect. 4.3). 

Cyclic and acyclic silyl enol ethers can be nitrated with tetranitromethane to give a-nitro ketones in 64-96% yield (Eqs. 2.42 and 2.43).84 The mechanism involves the electron transfer from the silyl enol ether to tetranitromethane. A fast homolytic coupling of the resultant cation radical of silyl enol ether with N02 leads to a-nitro ketones. Tetranitromethane is a neutral reagent it is commercially available or readily prepared.85... 

Addition of alkyllithium to cyclobutanones and transmetallation with VO(OEt)Cl2 is considered to give a similar alkoxide intermediates, which are converted to either the y-chloroketones 239 or the olefinic ketone 240 depending on the substituent of cyclobutanones. Deprotonation of the cationic species, formed by further oxidation of the radical intermediate, leads to 240. The oxovanadium compound also induces tandem nucleophilic addition of silyl enol ethers and oxidative ring-opening transformation to produce 6-chloro-l,3-diketones and 2-tetrahydrofurylidene ketones. (Scheme 95)... 

Schafer reported that the electrochemical oxidation of silyl enol ethers results in the homo-coupling products. 1,4-diketones (Scheme 25) [59], A mechanism involving the dimerization of initially formed cation radical species seems to be reasonable. Another possible mechanism involves the decomposition of the cation radical by Si-O bond cleavage to give the radical species which dimerizes to form the 1,4-diketone. In the case of the anodic oxidation of allylsilanes and benzylsilanes, the radical intermediate is immediately oxidized to give the cationic species, because oxidation potentials of allyl radicals and benzyl radicals are relatively low. But in the case of a-oxoalkyl radicals, the oxidation to the cationic species seems to be retarded. Presumably, the oxidation potential of such radicals becomes more positive because of the electron-withdrawing effect of the carbonyl group. Therefore, the dimerization seems to take place preferentially. 

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

In addition to the former example, Pandey et al. achieved efficient a-aryla-tion of ketones by the reaction of silyl enol ethers with arene radical cations generated by photoinduced electron transfer from 1,4-dicyanonaphthalene. Using this strategy various five-, six-, seven-, and eight-membered benzannulated compounds are accessible in yields in the range 60-70% [39],... 

Since silyl enol ethers have a silyl group ji to the jr-system, anodic oxidation of silyl enol ethers takes place easily. In fact, anodic oxidation of silyl enol ethers proceeds smoothly to provide the homo-coupling products, 1,4-diketones (equations 37 and 38)42. This dimerization of the initially generated cation radical intermediate is more likely than the reaction of acyl cations formed by two electron oxidation of unreacted silyl enol ethers in these anodic reactions. 

Hirano et al. reported on the stereoselective cyclization to give tetralin derivatives using the phenanthrene-p-dicyanobenzene sensitizer system. Pandey independently reported the intramolecular photocyclization of methoxybenzene derivatives bearing silyl enol ether chromophore via their heterodimer radical cations in the presence of 1,4-dicyanonaphthalene gave benzo-annulated cyclic ketones in 70% yields [490] (Scheme 133). 

Pandey, G., Karthikeyan, M., and Mumgan, A. (1998) New intramolecular a-arylation strategy of ketones by the reaction of silyl enol ethers to photosensitized electron transfer generated arene radical cations construction of benzannulated and benzospiroannulated compounds. Journal of Organic Chemistry, 63, 2867-2872. 

Substrates containing an electron-rich double bond, such as enol ethers and enol acetates, are easily oxidized by means of PET to electron-deficient aromatic compounds, such as dicyanoanthracene (DCA) or dicyanonaphthalene (DCN), which act as photosensitizers. Cyclization reactions of the initially formed silyloxy radical cation in cyclic silyl enol ethers tethered to an olefinic or an electron-rich aromatic ring, can produce bicyclic and tricyclic ketones with definite stereochemistry (Scheme 9.14) [20, 21]. 

A versatile strategy for efficient intramolecular oc-arylation of ketones was achieved by the reaction of silyle enol ethers with PET-generated arene radical cations. This strategy involved one-electron transfer from the excited methoxy-substituted arenes to ground-state DCN [42]. Pandey et al. reported the construction of five- to eight-membered benzannulated as well as benzospiroannulated compounds using this approach (Sch. 20) [42a]. The course of the reaction can be controlled via the silyl enol ether obtained... 

The reaction proceeds as follows a cation radical CR16 initially formed by one-electron oxidation fragments into 2-dithianyl cation C16 and a stannyl radical, and the cation C16 reacts with the silyl enol ether (Scheme 11). Formation of the stannyl radical was confirmed by trapping the stannyl radical with carbon tetrabromide to give tributyl-stannyl bromide. 

In the electrochemical oxidation, similar reaction was observed (Scheme 12). Cation radical CR26 generated by electrochemical oxidation of a-stannyl sulfides cleaves to give carbocation C26, which react with allyltrimethylsilane or the silyl enol ether of cyclohexanone to give the usual addition products. In this electrochemical reaction, stannyl derivatives also afforded the desired product 27 or 28 in better yield compared with the corresponding silyl derivatives. 

Cyclobutadiene iron tricarbonyl complexes also stabilized carbocations on an adjacent carbon. The cation reacts with silyl enol ethers to afford alkylated complexes such as (127) (Scheme 187). A samarimn diiodide -mediated intermolecular radical cychzation of iron tricarbonyl complex (128) is depicted in Scheme 188. An excellent stereocontrol at three contiguous centers is observed. 

Although the authors do not provide oxidation potentials, it is presumed from oxidation potential considerations that the 1,2-disubstituted silyl enol ethers 102 are oxidized to the radical cation intermediates which after O-Si... 

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