Electrolytic radical cyclization

In practice, reduction of 35 (—2.43 V vs SCE) in the presence of 3,5-dimethylphenol as a proton donor, tetra- -butylammonium hexafluorophos-phate as the supporting electrolyte, and DMF as the solvent, led to the y-hydroxy ester 40 and lactone 41 [22]. No sign of any material resulting from cyclization onto the alkene was detected. It was concluded that radical cyclization does not occur in this instance, and that the homogeneous electron transfer rate exceeds that of a 5-exo-trig radical cyclization, thereby implying the operation of either a radical anion or carbanion cyclization pathway. 

Aminyl radicals also can be generated via electrochemical oxidation of amide bases or O-substituted hydroxylamines. Suginome has studied radical cyclizations involving oxidations of lithium alkenylamides as a route to ccs-l-methyl-2,5-disubstituted pyrrolidines (85TL6085). Electrolysis of lithium alkenylamide 17a, generated from the amine and butyllithium at - 78°C, led to the formation of 18a, exclusively cis, in 52% yield (Scheme 4). The reactions require 0.25 M UC104 in THF HMPA (30 1) as the supporting electrolyte. A variety of 2-substituted amines were studied. 

The pyrazole ring is resistant to oxidation and reduction. Only ozonolysis, electrolytic oxidations, or strong base can cause ring fission. On photolysis, pyrazoles undergo an unusual rearrangement to yield imidazoles via cleavage of the N —N2 bond, followed by cyclization of the radical iatermediate to azirine (27). 

With 6-alkenoic acids the intermediate radical partially cyclizes to a cyclopentyl-methyl radical in a 5-exo-trig cycHzation [139] (Eq. 6) [138 a, 140] (see also chap. 6). To prevent double bond migration with enoic acids the electrolyte has to be hindered to become alkaline by using a mercury cathode. Z-4-Enoic acids partially isomerize to -configurated products. Results from methyl and deuterium labelled carboxylic acids support an isomerization by way of a reversible ring closure to cyclopropyl-carbinyl radicals. The double bonds of Z-N-enoic acids with N > 5 fully retain their configuration [140]. 

Electrolysis of b-al Ionic ketone 61 at a controlled cathode potential of-2.43 V (versus Ag/AgI) in anhydrous DMF using tetraethylammonium p-toluenesulfonate as co-electrolyte provides the derived ketyl radical that undergoes a 5-exo-trig selective ring closure, presumably via transition structure 62 (Scheme 11.19). The cyclization product is further reduced and subsequently protonated to afford traus-configurcd cyclopentanol 63 as single diastereomer in a total yield of 55% [80]. 

A series of bicyclo[3.3.0]octanols are accessible by electroreductive tandem cyclization of linear allyl pentenyl ketones 189, as shown by Kariv-Miller et al. [189]. The electrolyses are carried out with an Hg-pool cathode and a Pt-flag anode. As electrolyte, tetrabutylammonium tetrafluororborate is used. The reaction is stereoselective, yielding only two isomers 192 and 193. In a competing reaction, a small amount of the monocyclic alcohol is formed. Since all the monocycles have the 1-allyl and the 2-methyl group in trans geometry it is assumed that this terminates the reaction. The formation of a bicyclic product requires that the first cyclization provides the cis radical anion which leads to cis-ring juncture [190] (Scheme 37). 

Tetraphenylethylene cyclizes anodically to 9,10-diphenylphenanthrene analogously to its photooxidative cyclization. The attempted anodic cyclization of cis- or frans-stilbene to phenanthrene however failed due to electrophilic reaction of the intermediate radical cation with the solvent 37S Primary aromatic amines are oxidized to radical cations which, depending on the pH of the electrolyte couple to aminodiphenylamines (C-N coupling (84) in Eq. (172) ), yield benzidines (85) at low pH (C-C coupling) or dimerize to hydrazobenzene (86) (N-N coupling) which is subsequently oxidized to azobenzene (Eq. (172) ) 2 5,376,377)... 

Reduction of alkylidene malonates (60) in MeOH in an undivided cell using alkali metal halides as supporting electrolytes results in the unusual formation of 3,4-disubsti-tuted 1,1,2,2-cyclobutanetetracarboxylates, 61 [141]. Cyclobutane formation requires 4-7 F and is not a radical anion-catalyzed cycloaddition. The process was explained by the mechanism in Scheme 11, where the cyclization takes place by chemical oxidation of the... 

The use of a nitrate salt results in better yields and cleaner reaction than is observed with NaOR. A mechanism involving initial discharge of N03 to form NO3 , which then abstracts a hydrogen atom from one of the TV-alkyl groups, is considered the most likely one in this case. When, for example, NaOMe is used as supporting electrolyte, the reaction most likely involves the substrate radical cation as the primary intermediate, followed by deprotonation and oxidation to the corresponding carbocation, which finally reacts with methanol. In this context it is of interest to notice that the intramolecular alkoxylation expected for the series of hydroxyamides shown in Eq. (27) did not take place in MeCN only polymeric material was formed [71]. When the reaction was instead carried out in MeOH, only the normal methoxylation products were formed, as in Eq. (28). These, however, could easily be converted to the cyclized products by addition of acid. 

Similarly, reduction of 6-heptene-2-one (XI) at Hg in DMF-0.1 M TBA" " yields the alcohol, whereas reduction in the presence of catalytic amounts of DMP yields cis- 2-dimethylcyclopentanol (95%) [90]. The cyclization is suggested to occur at the stage of the radical anion of XI, since in diglyme-0.5% H2O DMP promoted the formation of the pinacol of XI. The cyclization is similar to that described by Shono et al. [91], who reduced XI in MeOH-dioxane at a carbon cathode with 2 M TEA as electrolyte see Chapter 10. 

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