Enamines radical cation

Bach and coworkers investigated the photocycloaddition of 7V-acyl, 7V-alkyl enamines 125 with benzaldehyde [125]. The 3-amido oxetanes 126 were formed with excellent regioselectivity (analogous to reactions with enolethers—vide supra) and good diastereoselectivity (Sch. 41). Enamines, not deactivated by acylation at the nitrogen atom are poor substrates for Paterno-Buchi reactions due to preferred electron transfer reactivity (formation of the corresponding enamine radical cation and subsequent reactions). 

Enamines are usually unstable compounds, especially primary ones. By contrast, enamine radical cations as produced by electron ionization (El) in the source of a mass spectrometer have been found to be very stable by recent ab initio calculations1. Among isomeric nitrogen-containing hydrocarbon radical cations with one degree of unsaturation, [C H2w+iN] +, ionized enamines and cycloalkylamines are the most stable these isomers lie usually in deep wells on the potential energy surface, and may also... 

The second type of the reaction involves the initial formation of an enamine radical cation by reaction with an oxidant (equation 2), which then leads to products by processes such as dimerization, etc. 

Formation of an enamine radical cation 45 was proposed as the chain initiation step in the autooxidation of enamines and SchifFs bases of a,/ -unsaturated ketones to give unsaturated 1,4-diones37. Pyrrolidine enamine of 10-methyl-A1(9)-octal-2-one (44) reacts with oxygen at room temperature to produce, after acid hydrolysis, 10-methyl-A1 (9)-octalin-2,8-dione (47) in 20% yield. Addition of a catalytic amount of FeCl3, Cu(OAc)2 or CuCl2 causes a pronounced enhancement in the oxidation rate and increases the yield to 80-85% after 1 h. 

A head-to-head cyclodimerization of A-vinyl carbazole by means of ferric or cer-ium(IV) salts takes place in the presence of 2,2 -bipyridyl in methanol, through the corresponding enamine radical-cation intermediate85 (Scheme 62). 

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]. 

Enaminoesters, -ketones, and -nitriles have also successfully been applied in electro-chemically induced radical cation cycloaddition reactions, especially with 2-vinylindoles or 2-vinylpyrroles. Some examples are given in Eq. (31). Depending on the structures, the reaction starts with the formation of either the vinylindole or vinylpyrrole radical cation or the radical cation of the enamidoester, -ketone, or -nitrile. In Eq. (32), a representative reaction pathway for the cycloaddition between a 2-vinylpyrrole and an acceptor-substituted enamine is formulated via the enamine radical cation [159]. 

The observations that these reactions are inhibited by nitrobenzene (a free radical inhibitor), no hydrogenated by-products are formed and that CF BrCl gives only a-CFjCl carbonyl compounds, led the authors to propose a radical chain mechanism for these reactions (Scheme 1). The chain initiation step is the formation of XFiC radical and enamine radical cation by electron transfer from the enamine to BrCFjX. The addition of this perhaloalkyl radical to the enamine generates a RjNC R R" type radical which is known to have an unusually low oxidation potential with 1/2 in the range of — 1 V (sce). An electron transfer from this radical to another molecule of perhaloalkane then takes place to form the iminium salt and another perhaloalkyl radical which continues the chain. A similar mechanism operates in the case of Rp. ... 

The ability of enamines to form in situ generated radicals gives rise to an entirely new principle of activation and thus to a series of very usefijl and highly selective previously unknown C-C bond formation processes. Thus, enamine catalysis changed into SOMOsingly occupied molecular orbital) (Figure 4.2) [24]. For direct experimental evidence of an enamine radical cation in SOMO catalysis see Reference [25]. These types of transformations were extensively elaborated by the MacMillan group. The first steps in this new concept were accomplished by the formation of radicals of enamines of imidazoHdin-4-ones. 

Enamine Radical Cation The Concept of SOMO Activation... 

Electron-transfer/organocatalytic reactions were postulated in oxamination reactions [9] later it was demonstrated [10] that the reaction follows preferentially a polar enamine activation manifold when FeCls was used in DME as oxidizing agent the metal coordinates rapidly to the nitroxyl radical of TEMPO (2,2,6,6-tetramethylpiperidine-l-oxyl) (Scheme 39.2) [llj. SOMO conditions were find by replacing the metal salt by a non-coordinating oxidizer such as tris(p-bromophenyl) aminium hexachloroantimonate [12]. Under these conditions the ET reaction arguably afforded the enamine radical cation, which was trapped by TEMPO, or by styrene as a purported SOMOphile partner. 

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