Electrochemical annulation

Two sequential electrochemical annulations of an electron-rich 3,4-disubstituted furan ring were employed to generate the fused tricyclic ring system of arteannuins. The second reaction, as depicted below, represented the formation of a quaternary carbon center by a formal 6-endo cyclization under these anodic oxidation conditions <07OL4599>. 

As illustrated in the following scheme, a two-step electrochemical annulation directed to polycyclic systems containing annulated furans has been extended to the formation of seven-membered ring fused furans <05JA8034>. Mechanistic insights were also provided. 

For the indole, methyl sustitution at the 2-position (i.e. 71) appears to sterically block C—C annulation vs C—N annulation (Scheme 46)126a. Note also that electrochemical methods are only useful for the substituted vinylindoles, as unsubstituted indoles passivate the working electrode. The results of cycloadditions of substituted enamines 66 and 69 to vinylindoles 65 and 71 are summarized in Tables 7 and 8. 

Several reports appear in the more recent literature of syntheses using electrochemical or PIET oxidation of compounds containing >C=N— bonds. These fall into three categories based upon a mechanism or presumed mechanism Cycloadditions, nucleophilic attack on >C=N— + cation radicals and radical annulations. The latter will not be reviewed here179 as none of the annulations appears to involve >C=N— + cation radicals. It should be pointed out that it is by no means certain that the electronic structure of >C=N— + is that of a 7r-cation radical rather than of an iminium cation radical (Figure 5). As will be seen below, reactivity appears sometimes in one guise and sometimes in the other. 

Cobaloxime can also be applied to annulation reactions of 3-bromo-2-propargyl-oxytetrahydropyrans 259 (X=0) using 50 mol% (py)(dmgH)Co(III)Cl 255 and electrochemical reduction at platinum electrodes to regenerate the catalyst. Bicyclic products 260 were obtained in 35-87% yield (entry 2) [309]. Much cheaper zinc electrodes can also be applied thus keeping the electrolysis conditions essentially neutral and affording the products in similar yields of 54—80% using only 5 mol% of 255 [310],... 

Inspired by Nature, hydroxocobalamine 247 (X=OH) itself or modified vitamin B12 derivatives (review [331]) were probed as catalysts for radical cyclizations. This methodology is mediated by light and electrochemical or chemical reduction to close the catalytic cycle. It was applied to total syntheses of forskolin 280 by Pattenden [325] (Fig. 67, entry 13) as well as of jasmonate 284 and prostaglandin precursors 287 by Scheffold (entry 14) [326, 327], Starting materials were bromoacetaldehyde cyclohexenyl or cyclopentenyl acetals 278, 281, or 285, which cyclized in the presence of 247 to annulated butyrolactols 279, 283, or 287. In the forskolin synthesis the cyclized radical was reduced directly, while a radical addition ensued in the presence of acetoxyacrylonitrile 282 or ynone 286 in... 

Bryce and co-workers reported that the crown-annulated TTF derivatives 98 and 99 were used for UV-Vis spectroscopic and electrochemical studies of metal complexation <1996J(P2)1587>. Solution electrochemical studies showed that metal complexation to the crown unit leads to a small anodic shift in the first oxidation potential of the TTF system. Langmuir-Blodgett films of amphiphilic 99 have been assembled on solid substrates by Y-type deposition. Compounds 100-104 were used to prepare self-assembled monolayers on gold and platinum surfaces <1998AM395, 2000JOC8269>. The self-assembled monolayers of 104 were the most stable in this series of TTF-crowns. Electrochemical data for the self-assembled monolayers of 100-104 in MeCN showed two reversible one-electron waves, typical of the TTF system. The self-assembled monolayers of 102-104 exhibited an electrochemical response in aqueous electrolyes, which was observed between 50 and 100 cycles. 

Annulation of furans via electrochemical oxidation at the anode has become an important process for the synthesis of complex polycycles, and was covered in a review <2000T9527>. Furans tethered at the 3-position to electron-rich alkenes, enol ethers, or vinyl sulfides were converted to [6,5] and [7,5]-fused ring systems <1996JOC1578, 2002OL3763, 2004JOG3726, 2005JA8034>, as illustrated in Scheme 20. Analysis of crude reaction mixtures and side... 

BusSnH-mediated intramolecular arylations of various heteroarenes such as substituted pyrroles, indoles, pyridones and imidazoles have also been reported [51]. In addition, aryl bromides, chlorides and iodides have been used as substrates in electrochemically induced radical biaryl synthesis [52]. Curran introduced [4-1-1] annulations incorporating aromatic substitution reactions with vinyl radicals for the synthesis of the core structure of various camptothecin derivatives [53]. The vinyl radicals have been generated from alkynes by radical addition reactions [53, 54]. For example, aryl radical 27, generated from the corresponding iodide or bromide, was allowed to react with phenyl isonitrile to afford imidoyl radical 28, which further reacts in a 5-exo-dig process to vinyl radical 29 (Scheme 8) [53a,b]. The vinyl radical 29 then reacts in a 1,6-cyclization followed by oxidation to the tetracycle 30. There is some evidence [55] that the homolytic aromatic substitution can also occur via initial ipso attack to afford spiro radical 31, followed by opening of this cyclo-... 

Pyrroles annulated with various kinds of polycyclic aromatic compounds such as the pyrrolo benzothiadiazole (578) have been claimed to be good precursors for polypyrroles. The polymers derived from (578) have a lowered band gap and interesting properties such as the high stability of the cation radicals formed by electrochemical oxidation. They also show ESR signals which are not affected after storage at room temperature for long periods of time in a laboratory atmosphere, <94CC1019>. 

Extreme hindrance of an electrochemical reaction is always endangered to be released by contaminants. Thus hydrogen evolution on the lead surface would enormously be increased by the precipitation of traces of other metals, like those shown in Fig. 1.20. Such a contamination shifts the Tafel line more to the right and annuls or at least aggravates the exceptional situation of lead. 

The porphyrin-TTF series was extended and the behavior of symmetric and asymmetric donor-acceptor systems evaluated. Novel symmetric porphyrin-te-trathiafulvalene-porphyrin triads annulated through quinoxaline linkers into planar and extended ji-conjugated molecules were synthesized and its behavior compared with porphyrin-tetrathiafulvalene dyads [231]. Cyclic voltammetry and spectro-electrochemical methods were utilized to elucidate the redox processes of both compounds. The first oxidation of the triad in the peripheral porphyrin sites was followed by the formation of TTF radicals, but this sequence was reversed in the corresponding dyad. Ab initio calculations were realized demonstrating that TTF-type and porphyrin-type HOMOs have similar energies thus explaining that behavior. 

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