6 Electro-organic Chemistry By M. SAINSBURY School of Chemistry University of Bath Claverton Down Bath BA2 7AY 1 Introduction The subject of electro-organic chemistry continues to grow and more papers than ever have appeared during the last year.* Despite this increase however there is still a general reluctance on the part of organic chemists to incorporate the technique in multistage syntheses. Fortunately a very useful and detailed review of anodic and cathodic carbon-carbon bond-forming reactions has appeared,' which may help to redress this situation Of similar interest are surveys of the utility of electrochemical methods in the steroid field' and of the electrochemistry of the sulphonium group the latter being published as a chapter in a book in the Patai ~eries.~ From a commercial standpoint a review on electrosynthetic reactions used in the fine chemicals industry is also very timely.4 2 General and Mechanistic Aspects In a series of papers Savkant and his associatesSa-' have considered the complex relationships that exist between the distribution of products and the characteristic rates of reactions or rate ratios and the magnitudes of the various operational factors which are commonly encountered in preparative scale electrolyses.For example electrochemically induced aromatic nucleophilic substitution reactions compete with hydrogen abstraction from the solvent and also with electron transfer at the electrode and in the bulk solution. This four-way system has been studied by voltammetric analysis and by product isolation and it appears that in most cases the experimental conditions can be adjusted so that the competition only involves nucleophilic attack heterogeneous electron transfer and hydrogen-atom abstrac- tion.One consequence of the existence of these competing pathways is that there is a requirement for high reactivity of the nucleophile towards the aryl radicals in * Based on Chemical Absrracrs during the period November 1981 to November 1982. ' H. J. Schafer Angew. Chem. Int. Ed. Engf. 1981 20 911. K. Ponsold and H.Kasch 2.Chem. 1982,22 157. J. Grimshaw in 'The Chemistry of the Sulphonium Group,' ed. C. J. M. Stirling and S. Patai J. Wiley and Sons Ltd. 1981,Chapter 7,pp. 145-154. 'D. Pletcher Chem. Ind. 1982 358. (a)C.Amatore and J. M. Saveant J. Electroanal. Chem. Interfacial Electrochem. 1981 123 189. (6) C. Amatore and J. M. Saveant ibid. p. 203. (c) C. Amatore. F. M. Halla and J. M. Saveant ibid. p. 219.(d) C.Amatore J. Pinson and J. M. Saveant ibid. p. 231.(e)C. Amatore and J. M. Saveant ibid. 1981 125 1. (f) C. Amatore and J. M. SavCant ibid. p. 23.(g) C. Amatore and J. M. Saveant ibid.,1981 126,1. Ih 1 C. Amatore. J. Pinson and J. M.Saveant ibid. 1982.137.143.(i)J. Pinson J. M. Savtant and A. Thitbault J. Am. Chem. SOC.,1982,104,817 108 M. Sainsbury order that good yields of substituted products result. It is established that SRN1 type mechanisms operate in such reactions rather than the alternative SRN2 pro-cesses. Similarly Parker's have analysed the effects which the steric and electronic properties of the substrates have upon the entropies of formation of ion radicals These workers6e have also returned to the thorny question of the mechan- isms of aryl-aryl coupling reactions.In the case of 1,2-bis(3,4-dimethoxypheny1)ethane the intramolecular cyclization reaction follows the rate law (i) Rate = k,pp[ArCH2CH2Art]2 (9 This is consistent with either disproportionation (ii) followed by cyclization (iii); or with cyclization (iv) followed by rate-determining electron transfer (v). It is concluded that the second alternative is the more likely with electron transfer (v) being the rate-determining step (Scheme 1). 2Ar Art- Art Art + Ar- Ar (ii) Art Art + Ar+-Ar+ (iii) Ar Art Ar+-Ar'- - (iv) Ar+-Ar' + Ar Art + Ar+-Ar+ + Ar- Ar (v) Ar+-Ar' -+products (vi> Scheme 1 Aromatic chloro- and fluoro-compounds when oxidized undergo apparent nucleophilic substitution reactions with surprising ease.It seems that the initial radical cation undergoes ips0 attack by the nucleophile and that this is followed by loss of the substituent as a species at the same oxidation level as the nucleophile giving the radical cation of the product to be formed. A chain-transfer step involving this ion and a second substrate molecule then completes the reaction sequence which is summarized below (i-iv Scheme 2).' ArX 5[ArX]" (9 [ArX]? + Nu-B Ar'(Nu)X (ii) Ar'(Nu)X + [ArNu]+ + X-(iii) [ArNaIt + ArX -P ArNu + [ArX]? (iv) Scheme 2 Little is known about the nature of 1,3-radical cations derived from alkanes so that the anodic oxidation of the cyclopropane (1)is of some interest.However the first observable product is the cation (2),and from cyclic voltammetric studies there is no evidence for two one-electron transfer steps even at sweep rates as high as 2OVs-'. In the absence of base the cation cyclizes to 1,1,3-triphenylindenes (3) although if base is added further deprotonation to tetraphenylallene (4) occurs '(a)M. Svaan and V. D. Parker Acra Chem. Scand. Ser. B,1981 35 559; (b) ibid.. 1982 36 351. (c) ibid. p. 357. (d) ibid. p. 365. (e) B. Aalstad A. Ronlan and V. D. Parker ibid. p. 171. (f) B. Aalstad and A. RonlBn ibid. p. 317. (g) 0.Hammerich and V. D. Parker ibid. p. 519. ' L. Eberson L. Jonsson and L.G.-Wistrand Tetrahedron 1982,38,1087. Electro-organic Chemistry (Scheme 3). When substituted phenyl rings are attached to the cyclopropane unit the initially formed radical cation may be stabilized since now the voltammograms show two closely spaced equally intense waves.8 -"+I Ph,C =C =CPh2 (4) Scheme 3 The fate of the intermediate radical cations formed during the anodic oxidation of epoxides is changed dramatically when the solvent is free of efficient n~cleophiles.~ Thus if acetonitrile containing water is the solvent ketones are formed e.g. (5)+(6) + (7),but in super-dry acetonitrile or in methylene chloride the amount of current consumed is low (ca. 0.1 Fmol-') and the main product is the rearranged ketone (8)-a result which is comparable to ring opening of the epoxide in strongly acidic media.This electrocatalytic process is based upon the assumption that the standard oxidation potential of the ketone is larger than that of the corresponding epoxide thus ensuring that chain propagation is allowed (see Scheme 4). f 1 (8) Scheme 4 The factors that favour cyanomethylation rather than reductive saturation or hydrodimerization of a,@-unsaturated nitriles in acetonitrile have been ascer- tained.lo High dilution tends to effect reduction whereas an increase in temperature D. D. M. Wayner and D. R. Arnold I. Chem. SOC.,Chem. Commun. 1982,1087. J. Delauney A. Lebouc A. Tallec and J. Simonet J. Chern. SOC.,Chem. Commun. 1982 387. lo A. J. Bellamy J. B. Kerr C. J.McGregor and I. S. MacKirdy I. Chem. SOC.,Perkin Truns. 2,1982 161. 110 M. Sainsbury promotes cyanomethylation over hydrodimerization. The addition of water to the electrolyte medium suppresses cyanomethylation and also reduces the overall product yield but leaves the proportion of the hydrodimer in the mixture largely unchanged. An interesting comparison has been drawn between the electroreductive and the hydride-initiated cyclizations of w-bromoalkylidenemalonates." On cathodic reduction these substrates yield ring structures (9) with one atom less in the carbocycle than the products obtained by treatment with L-selectride (Scheme 5). During the electrochemical reactions the electrode potential is more positive than that needed for the reduction of an alkyl bromide so that initial carbon-bromine bond cleavage is unlikely.Overall however two electrons are transferred and so it is probable that one-electron addition and ring-closure occur in concert. Scheme 5 The electroreduction of carbon dioxide in the presence of buta-l,3-diene leads to a mixture of the anions of pent-3-enoic acid (ll),hex-3-enedioic acid (12) deca-3,7-dienedioic acid (13) and other isomeric decadienedioic acids.'* The first two products arise through the interaction of the radical anion of carbon dioxide with one or both termini of the diene whereas the Clo-acids result from the dimerization of the intermediate radical anion" (see Scheme 6). +e. +H' MeCH=CHCH2CO; (11) O;CCH2CH=CHCH2CO; (12) (-CH2CH=CHCH2CO; )2 (13) Scheme 6 All the chlorinated nitrobenzenes except the pentachloro-compound exhibit reversible one-electron waves at the potential of the first reduction peak during cyclic voltammetry in dimethylsulphoxide s~lution.'~ For these structures a pXo correlation of the peak potentials shows that the u constants are non-additive.Additivity is obtained however by applying an empirically determined correction factor for adjacent chlorine pairs. In a continuation of earlier work designed to examine the effect of the addition of electrochemically generated cyanomethyl anion to various electrophiles the '' S.T. Nugent M. M. Baker and R. D. Little Tetrahedron Lett. 1982 23 1339. j2 W. J. M. van Tilborg and C. J. Smit Rec. Trau. Chirn. Pays-Bas.1981 100 437. l3 R.D. Geer and H. J. Byker J. Org. Chern. 1982,47 1662. Electro-organic Chemistry relative acidities of a number of substituted acetonitriles [XCH2CN where X = Ph3P+ Ph3As+ (me~ityl)~P+ or PhS02] versus acetic acid have been determined. l4 Ph3PCH2CN is a stronger acid than acetic acid the others are weaker but (me~ityl)~P+CH~CN I- and PhS02CH2CN prove to be useful precursors of the cyanomethyl anion. Interestingly PhS02CH2CN undergoes one-electron rather than two-electron reduction at the potential of the first polarographic wave. It appears that half the molecules of PhS02CH2CN reaching the electrode surface accept two electrons while the other half are rendered inactive by deprotonation of the liberated cyanomethyl anions.In acetic acid however the latter process is inhibited and a two-electron wave is now observed since the anion formed is rapidly protonated by the acid present. A similar process arises during the electrochemical reduction of N -haloamides (RiCONClR2) in acetonitrile solution. This involves two consecutive one-electron transfer reactions ultimately generating the amide anion. In the case of N-haloamides where R2= H the anion formed may deprotonate incoming substrate so that the true nature of the electrode process is masked. From a synthetic point of view the reduction of N-haloamides can be used to prepare heterocyclic com- pounds for example the anion of the amide (14) undergoes an internal displacement reaction to yield the isoindolinone (15) (Scheme 7).15 +2e --c1-N CI’ ‘Me (14) Scheme 7 When 1,2-dibromobenzene is reduced in the presence of furan 1-naphthol is produced and it has been proposed that the reaction proceeds through the gener- ation of benzyne either via an ionic stepwise or a concerted mechanism.New work16 suggests that the first alternative is the more likely for when 1,2-dichloroben- zene is reduced in the presence of carbon dioxide the products are benzene and 2-chlorobenzoic acid. Added furan does not now afford 1-naphthol. The electrochemical reduction of N-bromosuccinimide in acetonitrile at a platinum cathode affords the succinimidyl radical in an overall one-electron transfer process. An intermediate in this reaction is the succinimide anion and its interaction l4 A.J. Bellamy and I. S. MacKirdy J. Chem. SOC.,Perkin Trans. 2 1981 1093. D. Berube and J. Lessard Can. J. Chem. 1982,60 1127. l6 F. Barba A. Guirado and A. Zapata Electrochim. Actu 1982 27 1335. 112 M. Sainsbury with a molecule of the substrate forms two equivalents of the radical. Thus three steps are involved the second of which is a relatively fast reduction of initially generated succinimidyl radical" (Scheme 8). Scheme 8 Cyclovoltammetric studies show that aromatic amines in aqueous or non-acidic media give rise to mono-cation radicals at the anode which in the absence of water then dimerize by tail-to-tail head-to-tail and even head-to-head coupling. '* Since the products are more readily oxidized than the parent amines further reactions occur at the same potential.Aniline for example yields 4-aminodiphenylamine benzidine hydrazobenzene and other related structures. Tetraphenylcyclobutane and pyridyl(pheny1)cyclobutanesundergo rapid [u2s + ,2,] cycloreversion on electrochemical reduction after one-electron transfer; on the other hand the tetra-cation (17) accepts two electrons and undergoes ring-opening to give the butane (18).19 3 Anodic Processes Various allenic hydrocarbons have been electrolysed in acetonitrile or methanol solution at a platinum anode maintained at ca. 2V.'' All undergo the loss of two electrons which is followed by nucleophilic attack of the solvent and/or water to afford products containing at least two of the functional groups C=C C=O NHCOMe and OH.2-Methylpenta-2,3-diene (19) is typical and gives the three amides (20) (21) and (22) in 14.4 5.3 and 3.9% yields respectively. The product composition is changed by variation in the concentration of the substrate and J. E. Barry M. Finkelstein W. M. Moore S. D. Ross L. Eberson and L. Jonsson J. Org. Chem. 1982,47,1292. '* L. R.Sharma A. K. Manchandra G. Singh and R.S. Verma. Electrochim. Acta 1982,27 223. l9 M. Horner and S. Hunig Justus Liebigs Ann. Chem. 1982 1409. *' J. Y.Becker and B. Zinger J. Chem. SOC. Perkin Trans. 2 1982,395;Tetrahedron 1982,38 1677. Electro-organic Chemistry electrolyte (usually lithium perchlorate) the electrode potential the temperature and the anode material. In some cases cyclized structures which include arenes pyrimidines and s-triazines are isolated.Heterocumulenes have also been studied.*l NHCOMe Me NHCOMe -Pr-LiCIO,/MeCN \/ Me>C=CHMe (MehC,/ + CCOCH Me 1.85 V // COCOMe ‘Me (19) NHCOMe + (Me)2C\/ CO CH (0H )Me (22) Stable triarylamine radical cations (23) have found use as electron-transfer ‘catalysts’ in the oxidative cleavage of benzyl esters. The parent amines are added either in stoicheiometric quantities to the esters and then electrolysed or the radical cations are generated and regenerated indirectly using an external divided cell (see Scheme 9).22 -e Scheme 9 Esters can be synthesized through the electrochemical oxidation of hydroquinone carboxylates in the presence of alcohols. High yields are reported for this transacyla- tion process which occurs either in acidic or basic media.23 Amines may replace alcohols in this procedure in which case the products are amide~~~ (see Scheme 10).(X = 0 or NH) Scheme 10 *’ J. Y. Becker and B. Zinger J. Am. Chem. SOC.,1982,104,2327. 22 S.Dapperheld and E. Steckhan Angew. Chem. Int. Ed. Engl. 1982,21 780. 23 R.W.Johnson M. D. Bednardki B. F. O’Leary and E. R. Grover Tetrahedron Lett. 1981,22,3715. 24 R. W.Johnson E. R. Grover and L. J. MacPherson Tetrahedron Lett. 1981,22 3719. 114 M. Sainsbury Further examples of indirect electro-oxidations (ex-cell methods) have been described. In one such report 4-methoxytoluene has been converted into anisal- dehyde by chemical oxidation with ammonium hexanitratocerate(Iv) followed by electrochemical re-oxidation of the spent reagent at carbon or platinum electrodes in methanol as Some aryl-aryl coupled product (25) is formed in aqueous methanol together with the aryl methyl ether (24) which is considered to be an intermediate in the oxidation (see Scheme 11).OMe0 OMe Me0 QMe Me I Me IMeI OMe u’ (24) Scheme 11 CHO 5-Cyclopentyl-5-hydroxypentanoicand 4-(2-hydroxycyclohexyl)butanoic acid lactones are obtained by the anodic oxidation of 1-decalone. The two products are assumed to arise through ring-closures of the cations (26) and (27) respectively and in this process the cation (26) is formed first and interconverted into the isomeric species (27) by a 1,2-sigmatropic rearrangement (see Scheme 12).26 A new means of protecting amino-acids uia their coupling with 2,6-di-t-butyl-4- phenylphenol (28 R = Ph) has been used in the synthesis of the hydrophobic segment of human lymphoblastoid interferon.Anodic oxidation of amino-acid esters in dichloromethane in the presence of the phenol leads to N-(3,5-di-t-butyl-4-oxo-l-phenyl-2,5-cyclohexadienyl)amino-acid esters (29) that are stable towards bases but which may be cleaved by hydrogenolysis or treatment with acids. ’’ S. Torii H. Tanaka T. Inokuchi S. Nakane M. Akada N. Saitoh and T. Sirakawa J. Org. Chem. 1982,41 1647. ’‘ F. Barba A. Guirado I. Barba and M. Lopez Tetrahedron Lett. 1982,23,463. Electro-organic Chemistry 115 aO+dH Scheme 12 Furthermore the amino-acids couple without racemization and the products crys- tallize readil~.~' The same phenol and a series of its analogues when oxidized in acetonitrile solution trap a molecule of solvent to yield benzo-1,3-oxazoles (30).28 Both processes proceed through the intermediacy of cations (see Scheme 13).R' R3 -B II BU1fjBUi -2e BUi$BUi HN-:40,R4 U i ~ B U t + -H+ .-(R= Ph) I I R3 \ I R R Ph N-C-C02R4 RI' I (28) R2 (29) lMeCN Me I R (R= alkyl aryl acyl halogen or nitro) Scheme 13 '' M. H. Khalifa. G. Jung,and A. Rieker Justus Liebigs Ann. Chem.. 1982. 1068. '* E.-L. Dreher J. Bracht M. El-Mobayed P. Hutter W. Winter and A. Rieker Chem. Ber. 1982 115 288. 116 M. Sainsbury In a continuation of studies reported last year Shono and his have shown that the a-methoxylated derivative of N,N-dimethylaniline prepared by the anodic oxidation of the parent amine in methanol solution may be treated with Lewis acids in the presence of electron-rich alkenes to afford tetrahydroquinolines (31).It is suggested that iminium species are intermediates in the final reactions (Scheme 14). Me Scheme 14 Although a number of methods are available for the selenation of double bonds few are known for triple bonds however an efficient route to a-arylseleno-a,& unsaturated aldehydes is provided by the electrochemical oxidation of 3-hydroxyalkynes in the presence of diaryldiselenides at a platinum foil anode.30 The electrolyte is aqueous acetonitrile containing tetraethylammonium perchlorate and the reaction is considered to involve the initial formation of a cationic species (32) which is attacked by water prior to final dehydration (see Scheme 15).L 1 SeAr Scheme 15 29 T. Shono Y.Matsumurz K. Inoue H.Ohmizu and S.Kashimura J. Am. Chem. Soc. 1982,104,5753. 30 K.Uneyama K. Takano and S.Torii Tetrahedron Lett. 1982.23 1161. Electro-organ ic Chemistry 117 Selective chlorination of the methyl group of the 3-methylbut-3-enoate unit of certain penicillin derivatives (e.g. 33 -+ 34) can be achieved through electrolysis in an undivided cell containing a mixture of dichloromethane sodium chloride and sulphuric acid using platinum foil electr~de.~~ Variations in sodium chloride con- centration can lead to both allylic and benzylic chlorination.Related studies leading from 4-arenesulphonylt hioazetidin-2 -ones (3 5)to 3 -chloromethyl-A3 -cephems (3 6) have also been reported by the same Me C0,Me C0,Me (33) (34) R~CONH R *CON PAC1 C0,R2 (35) Whereas the anodic oxidation of arylhydrazones simply regenerates the parent ketone and thus provides a mild method for the 'hydrolysis' of hydrazones the cyclic hydrazone (37) in the presence of one molar equivalent of pyridine gives 3,3-dimethylbutan-2-one (38).33A Favorskii-like rearrangement is presumed to be involved (Scheme 16). H' (37) 1 Scheme 16 Morphinandienones (41) of the flavinantine type are obtained in high yield via the anodic coupling of N-trifluoroacetyl-l-benzyl-l,2,3,4-tetrahydroisoquinolines (39) in acetonitrile-methanol solution but when the methanol is omitted neos- 31 S.Torii H. Tanaku N. Saitoh T. Siroi M. Sasaoka and J. Nokami TerruhedronLert, 1981,22 3193. 32 S.Torii H. Tanaku N. Saitoh T. Siroi M. Sasaoka and J. Nokami Tetrahedron Lett. 1982,23 2187; see also Chem. Lett. 1982 1829. 33 E.-C. Lin and M. R. Van de Mark J. Chem. SOC.,Chem. Commun. 1982. 1176. 118 M.Sainsbury pirodienones(42) are formed It seems likely that the effect of the methanol is to facilitate 0-demethylation of the initial reaction product (40) before rearrangement may occur (see Scheme 17). OMe ::$ocF3+MeoT& NCOCF,+ ' Me0 Me0 OMe (39) ?Me (40)IMeOH OMe I QMe OMe OMe (42) Scheme 17 Should 0-methylflavinantine (43) itself be oxidized in acidic solution the 10a- hydroxy derivative (44) is obtained together with the pentacycle (45).The formation of these two products is considered to be interrelated as indicated in Scheme 4 Cathodic Processes Although the electroreductive conversion of 1,3-dihalides into cyclopropanes is a published procedure the reduction of 1,3-dimethanesulphonatesappears to be a superior method.36 The starting materials can be readily made and in great variety from 1,3-dicarbonyl compounds by C-alkylation followed by reduction and treat- ment with methanesulphonyl chloride and base (see Scheme 19). Details of the mechanism of the ring-closure reaction have not been established. '' H. Klunenberg C. Schaffer and H.J. Schiifer Terrahedron Left. 1982,23,4581. 35 L. Christensen and L. L. Miller J. Org. Chem. 1981,46,4877. 36 T. Shono Y. Matsumura K. Tsubata and Y. Sugihara J. Org. Chem. 1982,41,3090. Electro-organic Chemistry OMe MeO$ --H' -e -e d Me NMe NMe Me 0 MeO MeO Me0% 0 0 (43) Meof$ -e H e--e CHO +---2H' NMe NMe \iMe H 1 MeO' Me0 ).I Meo II 0 0 0 (44) Me0 Me0 goEdMeo$:H Me0 NMe + Meo$, NMe Me0 NMe 0 0 0 (45) Scheme 18 Scheme 19 120 M. Sainsbury Hydroxy-ketones (47) have a number of practical uses but as yet a general synthetic route to them has been lacking. Polish workers have recently shown that such compounds are available through the electrochemical reduction of hydroper- oxides formed by ozonolysis of a-alkylcycloalkenes (46) at a lead ~athode.~' In the examples quoted product yields ranged from 45-70%.Me Pbcathode Me(=) 0,AcOt-OOH -MeCO(CH,),CH,OH (CH,) HOAc AcOH-NaOAc (CH )n CHO (47) (46 n 3 3) Scheme 20 Ammonium graphite lamellar compounds formed by the reduction of tetra- alkylammonium salts in the presence of graphite can act as efficient reductants for organic halides and ~ulphones.~~ The reactions are usually carried out in dipolar solvents such as N,N-dimethylformamide and the results compare favourably with similar reductions which use tetra-alkylammonium amalgams as reductants. Cathodic reduction of the bromo-ester (48) at a vitreous carbon electrode gives the corresponding DL-and rneso-succinates (49) and a triester tentatively con- sidered to have structure (50).The two types of products are thought to arise by a single mechanistic sequence rather than through the operation of alternative pathways.39 C0,Me PhC(Me)(Br)COZMe+ PhC(Me)COZMe + Me0,C -C(Me) e+-~(Me)CO,Me I I PhC(Me)COzMe Ph Me Ph (48) (49) (50) An optical yield of 45% is reported for the asymmetric reduction of the dibromocyclopropane (51 R = Br) to its monobromo-analogue (51 R = H) at a mercury pool cathode made chiral by adsorbed emetine cations. This result is assumed to reflect preferential presentation of one stereotopic face of the substrate to the electrode surface. Overall two electrons are transferred and the anion of the cyclopropane is protonated through interaction with the adsorbed alkal~id.~' Further work has shown that the reductive cyclization of i-(2-halophenyl)-j-phenyl compounds is a general process and offers an effective synthetic approach to a wide range of structures providing that the two aryl units are held close together in the substrate.The chlorophenylpyridine (52) for example affords the dibenzo[f h]isoquinoline (53)in 95% yield.41 37 J. Gora K. Smigielski and J. Kula Synthesis 1982 310. J. Berthelot M. Jubault and J. Simonet J. Chem. SOC.,Chem. Commun. 1982 759. 39 C. de Luca A Inesi and L. Rampazzo J. Chem. SOC.,Perkin Trans. 2 1982 1403. 40 R. Hazard S. Jaouannet and A. Tallec Tetrahedron 1982,38 93. 41 J. Grimshaw R. Hamilton and J. Trocha-Grimshaw J. Chem. SOC.,Perkin Trans.1 1982,229. Elec tro-organ ic Chemistry Reduction of aroylchlorides at a mercury pool cathode yields first a,& diketones and then 1,2-diaroylethene-l,2-diolates.The latter products are acylated by two molecules of the aroyl chlorides to give the corresponding E-and Z-ester~.~' The whole sequence is outlined in Scheme 21. 2ArCOCI 5 2ArCO' + 2C1-2ArCO' + ArCOCOAr 0-0-0-ArCO Ar ArCozIAr I 4ArCOCI 2ArCOCOAr 2Ar-(!=C-Ar + ArC=CAr x-I -4CI'-0-ArCO Ar Ar C0,Ar Scheme 21 When diary1 ketones or their N-phenylimines are reduced electrochemically in the presence of 4-bromo (or chloro) butanoyl chlorides cyclopropylcarbonyl deriva- tives are formed. The reduction of the anil (54) is illustrative (see Scheme 22),43 where B is a strong base which may be the radical anion of the amine or hydroxide ion.The solvent has a considerable effect upon the product distribution and in some cases dehydrodimers are formed as well as heterocyclic structures. +H,O Ph2C=NPh + CI(CH2)3COCI-PhzC(OH)N(Ph)CO(CH2)3Cl -HCI (54) (55) B PhZCO + PhNCO(CH2)3CI -BH' Ph2CHOCOq PhNHCOq Scheme 22 A model for the in vim electrochemical release of neurotransmitters such as dopamine (56)from presynaptic termini has been described.44 The dopamine unit in the form of its amide with isonicotinic acid is bound to a polystyrene polymer 42 A. Guirado F. Barba C. Manzanera and M. D. Velasco J. Org.Chem.,1982 47 142. 43 G. Belot C. Degrand and P.-L. Compagnon J. Org. Chem. 1982 47 325. 44 L.L. Miller A. N. K. Lau and E. K. Miller J. Am. Chem. SOC.,1982,104 5242. 122 M. Sainsbury as the unit (57) and this is then coated onto the surface of a glassy carbon electrode. Cleavage of the amide function is achieved and dopamine is released when the electrode is maintained at -1.2 V in a divided -CCH2CH-);;-I -H2NCH2CH2 O -O H O\CH2 -k>CONHCH2CH2 G O H \ OH 'OH (56) (57) 'Doubly dimeric' structures result from the cathodic reduction of 4-pyrones an acetonitrile-water solution. In these reactions a certain degree of selectivity is observed thus the pyrone (58 R' = R2 = Me) affords the dimer (59 R' = R2 = Me) in 45% yield and only minor amounts of the isomers (60) and (61).However when the pyrone (58; R' = Me R2 = Ph) is reduced structure (61; R' = Me R2 = Ph) is the only 0 R' 0 Rlfj-: R' R' R2 R'QlR2 0 0 R2 Hoe R2 OH R' (61) A dimeric compound (62) is also formed when phthalic anhydride is reduced in the presence of trimethylsilyl chloride.N-Phenylphthalimide similarly affords an isoindole (63) which may be trapped by the addition of dienophiles such as maleimide.46 45 G. Mason G. Le Guillanton and J. Simonet J. Chem. SOC.,Chem. Commun. 1982 571. 46 T. Troll and G. W. Ollmann Tetrahedron Lett. 1981 22 3497. Electro-organic Chemistry When 3-(2-furyl)propenenitriles (64) are reduced at a mercury pool cathode dehydrodimers (65) are the initial products. However these products may cyclize either spontaneously or in step-wise fashion depending upon the relative stereochemistries of the intermediates to enamines (66) (Scheme 23).47 R2 / R'0 'CH=C \ CN Scheme 23 J.Delaunay A. Lebouc G. Le Guiltanton L. M. Gomes and J. Simonet Electrochim. Actu 1982 27 287.