Enamines anodic oxidation

Guertler et al. (1996) described a wide range of cycloaddition reaction between 2-vinyl indoles acting as heterodienes and cyclic or acyclic enamines bearing acceptor groups in (3 positions. The reaction was induced by the formation of 2-vinylindole cation-radicals through anodic oxidation. The synthesis of 4a-carbomethoxy-6-cyano-5,7-dimethylindolo[l,2-a]-l,2,3,4,4a,12a-hexahydro-1,8-naphthyridine can serve as an example (Scheme 7.24). 

Anodic oxidation of enamine ketones or esters in CH30H-NaC104 at a graphite anode gives substituted pyrroles in 15-45% yield.101 Formation of the symmetrically substituted pyrroles 47 indicated radical dimerization of radical-cations formed as primary products from 46. This process leads to dications from which the pyrroles can be formed by cyclization and elimination of an amine [Eq. (44)]. 

The anodic oxidation of methyl N,/V-dialkylcarbamate in methanol, containing Et4NOTs, yielded three types of products a-methoxylated compounds, enamine-type products, and dealkylated carbamates.197 Methyl N-pyrrolidinylcarbamate (137), for example, gave on constant current oxidation... 

In the electrooxidation, one electron is transferred from the enamine to the anode to form a cation radical intermediate which is very unstable, its lifetime being less than 0.2 ms. When the anodic oxidation is carried out in a nucleophilic solvent such as methanol, the intermediate reacts rapidly with the solvent2. The anodic oxidation of morpholinoenamines (la,b) in methanol, for instance, yields two types of enamine,... 

An enamine (4) prepared from aniline and an aromatic ketone yields indole-type compounds (5 and 6) upon anodic oxidation (equation 3)4. 

Although the reactivity of enaminones is not always the same as that of typical enamines due to the additional conjugative interaction with the carbonyl group, the anodic oxidation of enaminones seems useful in organic synthesis since they yield dimerized or cyclized products upon anodic oxidation. In anodic oxidation of the enaminones or enaminoesters in methanol containing sodium perchlorate, for instance, derivatives of pyrrole are formed via initial dimerization (equation 4)5. 

Tetrahydroquinoline derivatives can be obtained by cycloaddition of aromatic imines or immonium salts with enamines having an a-hydrogen186,187. Anodic oxidation of A,A-dimethylaniline 323 in methanol to a-methoxylated compound 324 and subsequent... 

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... 

Generally, enamines, enamino esters and ketones, enamides and enecarbamates can give the following products after anodic oxidation (Scheme 7) ... 

Anodic oxidation of an A-benzoylated enamine in acetonitrile/methanol/Na2C03 leads not only to the formation of the dimethoxylated starting material but also to a methoxy-substituted oxazoline through intramolecular nucleophilic attack of the benzoyl oxygen [157]. In another case, an electron-rich aromatic system can act as a nucleophile in an intramolecular cyclization with the enamine radical cation or dication [Eq. (29)] [157]. 

In the case of the enaminonitrile XVIIa, coupling through the phenyl ring is observed [127a]. Enamines related to the key intermediate in thiamine diphosphate-dependent enzymatic pathways lead to dimers in a one-electron oxidation via a thiazolium cation radical as intermediate [127b]. Anodic oxidation of enaminones, prepared from / -substituted acetophenones and A,A-dimethylformamide dimethylacetal, afford dimers and substituted furans in fair yield [127c]. 

Cycloadditions between 2-vinylindoles as heterodienes and acceptor substituted enamines can be induced by formation of 2-vinylindole radical cations either via anodic oxidation or photoelectron transfer. In this way pyridoindoles and indolo-naphthyridines are formed in one step under complete regio- and stereochemical control [Eq. (24b)] [248b]. 

Anodic oxidation of enamines in NaCN-MeOH with iodide ion as mediator provides ring-fused cyclopropane aminonitriles with the nitrile group exclusively in exo position [Eq. (29)] [256]. This reaction is possibly an electrocyclic ring closure of an intermediate allyl cation LXXIII. 

Alkoxylation may be achieved by anodic oxidation in an alcohol, often methanol (MeOH), containing a suitable electrolyte, such as KOH, NaOMe, NaCN, NaBp4, or NH4NO3 [9-12,31,32]. Substrates that have been alkoxylated in this manner include aromatic compounds (both nuclear and side-chain alkoxylation has been observed), alkenes, ethers including vinyl ethers, enamines, N, AA-dialkylamines, AA-alkylsubstituted amides, and A-alkylsubstituted carbamates. In many cases alkoxylation by substitution is a side reaction only to concurrent alkoxylation by addition [7,9,11,33]. 

An elegant work is reported concerning the oxidation of 2-alkyl and 2-benzylthia-zolium salts, in the presence of a base, with the scope of finding a structural relationship for the thiamine-bound intermediate which intervene in the oxidative decarboxylation of a-ketoacids catalysed by thiamin diphosphate-dependent enzymes. 2-Alkyl and 2-benzylthiazolium salts, which are not electroactive, can be transformed into electroactive species by treatment with the base (trimethylsilyl)amide. Subsequent anodic oxidation affords the corresponding symmetrical dimers, by an EC mechanism (Scheme 72). As expected, the stabilizing effect of the substituents R, R at the a-carbon on the radical cation follows the order H < Me < OMe. When R is aryl, electron-donating p-substituents again enhance the enamine oxidation. 

Anodic oxidation (C/LiClOVMeOH) of the aspidofractinine-type alkaloid, kopsamine (577) yielded a dimerization product 579, characterized by the presenee of a central tetrahydrofuran ring and a C2 axis of symmetry (363). Photochemically induced coupling of deacetylaspidospermine (578) gave the dimer 580, charaeterized by a 10, 10 -bond (364). Oxidation of vindoline by horseradish peroxidase gave the 14,3 -linked enamine dimer 581, while similar oxidation of 16-O-acetylvindoline led to the stable conjugated iminium salt, without formation of any dimerization product (365). 

Jang and co-workers explored the asymmetric a-alkylation of aldehydes with xanthene by merging electro-oxidation and organocatalysis to synthesize the corresponding xanthene-derived benzylic products 65a in up to 68% yield and 68% ee (Scheme 2.22). This study showed that anodic oxidation, in addition to stoichiometric amounts of chemical oxidation, was applicable to the benzylic C—H bond functionalization for coupling with enamine. 

Anodic regioselective acetamidosulfeny-lation of alkenes is similarly achieved by oxidation of diphenyldisulfide in acetonitrile [81]. Cyclic enamines, which are intermediates in the oxidation of cyclic N-methoxycarbonyl amines, react in aqueous acetonitrile that contains chloride ions to a-hydroxy- 8-chloro compounds via intermediate chloronium ions [82]. Enolethers undergo a regioselective azidomethoxyla-tion to yield acetals of a-azido carbonyl compounds upon electrolysis in methanol containing sodium azide [83]. The reaction proceeds possibly via addition of an anodicaUy generated azide radical. 

An analogous process has been developed for unbranched aldehydes which can be transformed into a-amino ketones when oxidized in the presence of an secondary amine and iodine, as the mediator, in aqueous terf-butanol. The actual reactive species is probably the enamine which is attacked by iodine cations and subsequently by water. Carbonyl transposition reaction releases iodine anions which can be anodically reoxidized [197]. 

---