Enol ethers anodic oxidation

Anodic oxidation reactions have been utilized to reverse the polarity of enol ethers and to initiate radical cation cyclizations. As shown below, the ketene acetal 97 is oxidized on a... 

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. 

Different nucleophiles such as methanol, allylsilanes, silyl enol ethers, trimethylsilyl-cyanide, and arenes can be used in this process [62]. When the sulfide itself contains an unsaturated or aromatic fragment and the process is carried out in the absence of a nucleophile, an intramolecular anodic sub-stitution/cyclization might occur [61-63]. Methyl esters of 2-benzothiazolyl-2-alkyl or aryl-acetic acid, oxidized in MeOH/Et4 NCIO4 or H2SO4 in the presence of CUCI2, form 2,2-dimethoxy products (Eq. 7) [64]. 

The utility of the electrode to promote bond formation between functional groups of the same polarity provides researchers with an opportunity to explore the chemistry of interesting intermediates, and synthetic strategies that are based on their intermediacy [1,2], Reduction at a cathode, or oxidation at an anode, renders electron-poor sites rich, and electron-rich sites, poor. For example, the reduction of an a, 8-unsaturated ketone leads to a radical anion in which the -carbon possesses nucleophilic, rather than electrophilic character. Similarly, oxidation of an enol ether affords a radical cation wherein the -carbon displays electrophilic, rather than its usual nucleophilic behavior [3]. 

The oxidation of enol ethers at a reticulated vitreous carbon anode [2, 3] (Scheme 1) in a mixture of methanol/THF containing tetraethylammonium tosylate as the electrolyte and 2,6-lutidine as the base leads to substituted tetrahydrofu-ran and tetrahydropyran rings in good yields (51-96%). The major product obtained had a trans-stereochemistry. The cyclization failed to make seven-membered ring products. In order to determine the... 

In all of the cyclization reactions, Moeller has found only a small difference between the use of alkyl and silyl enol ethers. Since both styrenes and enol ethers have similar oxidation potentials, even the styrene moiety could function as the initiator for oxidative cyclization reactions. The anodic oxidation of simple styrene type precursors leads to low yields of cyclized products so that enol ether moiety seems to be the more efficient initiator for intramolecular anodic coupling reactions [93]. 

Azide ions are oxidised at low positive potentials and generate azide radicals. Azide radicals will add to an alkene. Thus the anodic oxidation of enol ethers in... 

Radical cations of 2-alkylidene-l,3-dithianes can be generated electrochemically by anodic oxidation using a reticulated vitreous carbon (RVC) anode <2002TL7159>. These intermediates readily react with nucleophiles at C-1. Upon removal of the second electron, the sulfur-stabilized cations were trapped by nucleophilic solvents, such as MeOH, to furnish the final cycloaddition products. Hydroxy groups <20010L1729> and secondary amides <2005OL3553> were employed as O-nucleophiles and enol ethers as C-nucleophiles (Scheme 50) <2002JA10101>. 

The electrolytic oxidation of N- methoxycarbonylpiperidines provides an interesting and potentially valuable method for the functionalization of piperidine derivatives (81JA1172). Anodic oxidation of piperidine (101) gave (102) which reacted, presumably through the acyl imine, with enol ethers to form a carbon-carbon bond a to the nitrogen atom (Scheme 9). The regiochemical control in this reaction is illustrated by the exclusive oxidation at the less substituted carbon atom (55JA439). 

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. 

On the other hand, indirect anodic oxidation of cyclic silyl enol ethers in the presence of iodide ions gives a-iodocyclic ketones (equation 39)43. 

Intramolecular anodic oxidation of allylsilane moiety with enol ether moiety gives the corresponding cyclized product 110 (equation 84)152. 

Moeller has carried out an extensive series of studies of the electrochemical oxidation of electron-rich w-alkenes. One olefinic component is an enol ether, which is converted into an electrophilic center upon oxidation this center then attacks the other site intramolecu-larly. The anodic oxidation of the bis-enol ethers 21 in methanol25 exemplifies the course of such reactions (Scheme 4). The products are w-acetals (22), formed in 50-70% yield in many cases. The cyclization can be used to produce quaternary25 and angularly fused26 bicyclic and tricyclic structures (equation 11). In its original form, this work involved oxidation of a mono-enol ether bearing a nearby styrene-type double bond27. 

Annulation of furans via electrochemical oxidation at the anode has become an important process for the synthesis of complex polycycles, and was covered in a review <2000T9527>. Furans tethered at the 3-position to electron-rich alkenes, enol ethers, or vinyl sulfides were converted to [6,5] and [7,5]-fused ring systems <1996JOC1578, 2002OL3763, 2004JOG3726, 2005JA8034>, as illustrated in Scheme 20. Analysis of crude reaction mixtures and side... 

The addition of medioxy groups to an unsaturated carbon takes place by anodic oxidation of enol ethers in methanol containing sodium methoxide yields are generally satisfactory (equation 21). 

The anodic oxidation of enol ethers at a graphite anode in methanol containing 2,6-lutidine and sodium perchlorate results in the dimerization of the enol ethers to acetals of 1,4-dica nyl compounds (equation 22). The mechanism of dimerization is thought to involve a tail-tail coupling of the cation radicals generated by the one-electron oxidation of the enol ethers. 

The anodic oxidation of enamines in methanol containing sodium methoxide as the supporting electrolyte shows a reaction pattern different from that of enol ethers or enol acetates. The main products are mixtures of isomeric methoxylated enamines, (18) and (19), with yields in the range 74-76% (equation... 

The anodic oxidation of enol ethers in methanol yields a-methoxylated carbonyl conqKxinds, which are useful intermediates for the synthesis of carbonyl compounds utilizing the technique of oxidative cleavage of glycols (equation 4S). ... 

Under oxidative conditions (anode, aminium salts) in the presence of methanol/base most enol ethers are known to be dimethoxylated, with or without dimerization [235,251-255], thus opening up a way to formal a-Umpolung products 158. 

A more efficient and economic procedure for the preparation of / -acetamido nitro compounds from alkenes, conjugated dienes and silyl enol ethers is based on the electrochemical generation of nitronium tetrafluoroborate in acetonitrile solution by anodic oxidation of dinitrogen tetrox-ide, using a divided cell (Table 6, Method B)142-143. From 1,3-dienes, mixtures of regio- and diastereomers were obtained. 

The second modification is Umpolmg of the carbonyl group via conversion into the corresponding enol ethers or enols and subsequent oxidation to give the radical cations of enol ether and enol, respectively [192]. The oxidation potentials of these substrates are approximately 1 V (relative to the SCE) and thus oxidation is feasible even with moderately active oxidants or via anodic oxidation. Subsequent reactions of the enol radical cations and radical cations of enol ethers can result in a-substitution products (e.g. by running the reaction in the presence of nucleophiles) and re-formation of the carbonyl group (Scheme 47). Thus, the overall process corresponds to a-activation of carbonyl substrates via intermediate tautomeric enols (and sometimes also enolates) [193, 194]. 

If the anodic oxidation of N-alkylanilines is performed in the presence of nucleophiles like enol ethers, nucleophilic substitution in the of-position to nitrogen by the enol ether can be observed in low yields. The electrophilic intermediate is the N-aryl iminium ion or the N-aryl imine after loss of two electrons and one or two protons. These intermediates add to the enol ether to give acetals (up to 26%) as addition products, or the first addition step is followed by an electrophilic aromatic substitution to form tetrahydroqui-nolines (13-39%) [47]. It should be noted at this point that better results for the nucleophilic a-substitution to nitrogen can be obtained with N,N-dialkylanilines (see next subsection). Optimum results, however, are obtained with N-acylated compounds via the intermediate N-acyl iminium ions (see Ref. 8). 

Aliphatic amines are mainly converted to a-substituted products [99,100], whereby especially the a-methoxylation leads to valuable reagents for synthesis. The intermediate iminium salts can be directly trapped by silyl enol ethers to form Mannich bases [108]. If the a-position is blocked or steric conditions favor it, N,N coupling to hydrazo or azo compounds occurs (Table 5, numbers 17-19). 1,1-Disubstituted hydrazines are dimerized to tetrazenes in fair to excellent yields (Table 5, numbers 20-24). The intermediate diaze-nium ions can attack enolizable carbonyl compounds to form aza-Mannich bases [109]. Arylazonaphthols undergo anodic oxidation, producing radical cations. These couple to biphenylbisazo compounds (up to 34%) or can be trapped by anisidine to form azodiphe-nylamines (up to 74%) [110a]. 

The coupling of an allyl or acyl moiety onto carbon atoms is achieved by anodic oxidation of a-heteroatom substituted organostannanes or Oj -acetals in the presence of allylsilanes or silyl enol ethers. The reaction probably involves carbocations as intermediates that undergo electrophilic addition to the double bond [245c]. 

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