Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 0611 640

Supplement A3: The Chemistry of Double-Bonded Functional Groups. Edited by Saul Patai Copyright 1997 John Wiley & Sons, Ltd.

ISBN: 0-471-95956-1

CHAPTER 12

The electrochemistry of the C=C, C=O and C=N groups

I. INTRODUCTION

This review describes the electrochemical behavior of compounds containing the CDC, CDO and CDN functional group. The review covers both anodic oxidation and cathodic reduction of such compounds. The electrochemistry of these functionalities was reviewed

611

B. Anodic Oxidation

It is easier to oxidize an alkene electrochemically than to reduce it, because it is easier to reach powerfully oxidizing anode potentials12 (at which one can remove an electron from the HOMO of the alkene) without interference from the solvent or electrolyte than it is with reductions, where one can normally not achieve sufficiently negative cathode potentials to be able to add an electron to the LUMO. Even so, anodic oxidation of alkenes is relatively rarely observed; almost always the alkene is part of a conjugated system or it bears an electron-supplying substituent, which raises the HOMO energy.

Oxidation of hydrocarbons, even alkanes and arenes, generally proceeds by removal of an electron from the hydrocarbon by the anode to afford a radical cation. Depending on the experimental conditions, the radical cation can react with a nucleophilic component of the medium or lose a proton or alkyl group. Either type of reaction affords a neutral radical. The radical is in general easier to reduce than the starting hydrocarbon because in the case of the radical the electron is being removed from a nonbonding molecular orbital, whereas with the starting hydrocarbon the electron being removed is in a bonding orbital. The product of this second electron transfer is a carbocation, which can undergo reaction(s) typical of such species. The oxidation of ˛-pinene (3) in methanol13 is typical of such oxidations (equation 5). The initially formed radical cation can relieve ring strain by bond cleavage to afford an allylic radical cation (4). Further oxidation of 4 and nucleophilic attack by the solvent lead to the observed products (5), which are stereoisomeric derivatives of the corresponding diol, sobrerol. Interestingly, a cathodic equivalent to the conversion of 3 to 5 has been observed previously14.

Anodic oxidation of 6 represents a variant on this scheme. Ring opening by cleavage of the bridge bond as observed for the radical cation of 3 does not take place. Instead, the 1,2- shift characteristic of these bicyclo[2.2.1] ring systems takes place to afford, ultimately, 7 stereospecifically15 (equation 6). Oxidation of tropilidene (1) affords the tropylium ion

(8)16; when the reaction is carried out in NaOMe/MeOH the product is tropyl methyl ether, which can be treated with acid to regenerate 8 or heated to induce rearrangement to 917. The latter can be oxidized further, followed by acid catalyzed hydrolysis, to afford tropone in good yield (Scheme 1). This work has been extended to a synthesis of 4-substituted tropones18.

OS

Anodic oxidation of alkenes is more readily accomplished when the double bond bears an electron-supplying group. Enol ethers, acetates and even a few enols have been studied. Removal of an electron from an enol derivative (10) affords a radical cation in which the major resonance contributor is presumably structure 11b, in which the positive charge is localized on the atom bearing the oxygen atom. Loss of a proton or alkyl group from 11 or reaction with a nucleophilic component of the medium leads to a neutral radical, which generally suffers further oxidation to a carbocation. Anodic oxidation thus converts the normally nucleophilic enol derivative 10 to at least two highly electrophilic species, 11 and 12. (Scheme 2). Synthetic applications can be designed to take advantage of this umpolung of reactivity of the enol derivative. Oxidation of enol acetates in the presence of a source of fluoride affords ˛-fluoroketones (equation 7)19. Two processes must take place: nucleophilic attack by fluoride and deacetylation, which probably also involves nucleophilic attack by fluoride on the carbonyl group. Plausible mechanisms may be written in which these two steps can take place in either order. Similarly, oxidation of cyclic enol derivatives in the presence of triphenylphosphine affords ˛-triphenylphosphonioketones (13), which can readily be converted into ˛-alkylidene ketones (14) (equation 8)20. On the other hand, oxidation of the dimesitylvinyl acetates 15 in the absence of an added nucleophile results in formation of benzofurans. It was suggested that the radical cation of 15 decomposes to an acetyl radical and cation 16. Intramolecular electrophilic attack on the adjacent arene ring, followed by methyl rearrangement, would lead to the observed products (equation 9)21. Evidence for this mechanism is the concomitant formation of biacetyl

of the double bond in this process; the actual electroactive species is the methyl viologen dication (24) which is reduced at the cathode to the corresponding monocation, which then participates as an electrocatalyst in the enzymatic reduction process. This is representative of an increasing number of electroenzymatic processes which have been studied in recent years in an effort to combine the high degree of selectivity of enzymatic processes with the relatively low cost of electricity compared with that of redox coenzymes such as NADPH and NADH (see Section V.C).

EWG = electron-withdrawing group

Electrochemical reduction of imines (25; Schiff bases) in acidic media proceeds via the iminium species, i.e. the protonated imine (26) (Scheme 5)29. Since 26 bears a positive charge, it is very easily reduced, so much so that the resulting neutral radical (27) is formed at a potential positive of its reduction potential. The products are therefore derived from 27 rather than the corresponding carbanion (28). This stands in contrast with the electrochemical behavior of imines in neutral media, where 27 is immediately reduced to 2830. Thus, cathodic reduction of bis-imines of 1,2-diamines (29) in DMF containing methanesulfonic acid affords tetrahydropyrazines (equation 13)31. A similar reaction can

SCHEME 5

be used to prepare bis-azacrown ethers (30)32; the imine can be prepared in situ.

Reduction of N-alkyl iminium salts also ought to afford radical-derived products. Indeed, reduction of oxazolinium salts (31) results in isolation of the corresponding dimers, which can in turn be converted to the corresponding benzils by acid hydrolysis33 (equation 14). In a similar vein, electrochemical reduction of N-butenyl iminium salts (32) affords cyclopentane derivatives (equation 15)34.

(32)

It is known that electrochemical reduction of oximes in protic media occurs in two steps: the N O bond is first reduced to form an imine and the latter is then reduced to afford a primary amine1,29. Tallec has shown that the amine from oxime 33 can be trapped intramolecularly (equation 16)35. Interestingly, the SS diastereomer predominates; the chiral pyrrolidine ring derivative serves to control the stereochemistry of formation of the new benzylic chiral center. Electrochemical reductive cross-coupling of O-methyl oximes with carbonyl compounds in isopropanol at a tin cathode affords adducts (equation 17) which can be reduced further to 2-amino alcohols36. In this fashion, menthone could

be condensed with acetaldehyde O-methyl oxime to afford a chiral adduct which was effective as a promoter for the enantioselective addition of diethylzinc to aldehydes.

Finally, reduction of 1,1-dichloroimines leads to formation of isocyanides in good yield (equation 18)37.

Compounds containing the CDN functional group derivatives undergo anodic oxidation when the nitrogen atom bears an electron-rich heteroatom. Perhaps the simplest such species are aldoximes, which are anodically oxidized to nitrile oxides (34)38. The reaction was carried out in an undivided cell39, hence the species 34 underwent immediate reduction to a nitrile (equation 19). However, since nitrile oxides are 1,3-dipolar species, one could in principle carry out the oxidation in a divided cell in the presence of a good 1,3-dipolarophile40 to effect the synthesis of substituted heterocycles.

Oxidation of silyl tosylhydrazones (35) in an aprotic medium (dichloromethane) also results in the formation of nitriles, but in this case the conversion is apparently a true anodic process41 in which the key difference from the anodic behavior of oximes is the presence of the p-toluensulfonyl group, which facilitates cleavage of the N N single bond (equation 20).

NHTs

N

[O]