Radical cations chemoselectivity

Chemoselective oxidation of 3-arylsul-fenylmethyl-A -cephem affords 3-meth-oxymethyl-A -cephem in an anodic substitution. From the two thioethers, the arylthio group is more easily oxididized to a radical cation, that then undergoes cleavage to a thiyl radical and a carbocation (Fig. 31) [152]. 

Demuth et al. recently developed an efficient radical cationic cyclization of functionalized polyalkenes using 1,4-dicyano-tetramethylben-zene (DCTMB) as an acceptor and biphenyl (BP) as co-sensitizer [43]. The transformation is in general highly stereo- and chemoselective and the substitution pattern of the polyalkene allows the construction of either five-or six-membered rings (Sch. 21). So far, this methodology has been applied for the synthesis of several natural products such as stypoldione, hydroxyspongianone and abietanes, respectively [43]. 

As shown in Table 4.1, formation of the mixed adduct is favored over homodimerization of 8a with the simple styrene 13a, but this selectivity is inverted for the case of the more bulky dienophile tra 5-[3-methylstyrene 13b, presumably due to steric effects. Although the overall reaction is highly exothermic on the radical cation surface, the reaction is not insensitive to steric effects. Chemoselectivity in the radical cation cycloaddition is largely a consequence of a substrate s ability to stabilize the radical cation of the oxidized species through the formation of a weakly bound ion-molecule complex. Such complexes have been known for a long time in gas-phase... 

In addition to the steric issues in chemoselectivity, which are intrinsic to the reaction of a given set of substrates, solvent and sensitizer effects are of importance for a direct control on selectivity because they can be controlled. The reaction of 8a and 13c catalyzed by sensitizer 6 shows an overall increase in cross-product formation with increasing solvent polarity. Entries 4 and 5 in Table 4.1 demonstrate that use of 3a reduces the formation of cross-products in polar solvents. This difference can be rationalized by the fact that after ET by 6, a strongly complexed ion pair is formed, whereas in the case of 3a, the sensitizer is neutral and can dissociate more easily from the radical cation formed. 

Results shown in Scheme 4.5 and Table 4.2 demonstrate a preferred formation of cross-adducts at lower concentrations. Lower concentrations allow radical cations to equilibrate between 18 + /18 and 18+/19. Due to the unfavorable steric bulk discussed earlier between 18 + /18, a predominant population of 18 + /19 is present in solution leading to a higher chemoselectivity. 

In the cases discussed so far, the charged species has been the diene radical cation due to its generally lower oxidation potential. Consequently, chemoselectivity has a greater dependence on the substituents of the diene rather than the dienophUe. Results summarized in Scheme 4.6 and Table 4.3 for the electron-rich dienophile, show an approximately 1 1 selectivity when using 8a. Placing substituents at the 1-position as in 8b,c completely inhibits the formation of cross-adducts, while substitution at the 2-position of the dienes leads to preferential formation of the cross-adduct. 

A surprising steric sensitivity is frequently observed for these radical cation reactions. As was shown previously during the discussion of chemoselectivity, the variable positioning of bulky substituents has effects on periselectivity as well. DFT calculations on the influence of diene substitutions for the neutral reaction have demonstrated a behavior similar to that of the radical cation reaction. Although... 

The most important class of photocatalytic transformations is the oxidation of a range of organic substrates. This reactivity follows from either trapping of an electron-hole pair to produce a photogenerated surface-adsorbed radical cation or from radicals produced by activated oxygen radicals (surface oxides or adsorbed hydroxyl, hydroperoxyl, or peroxyl radicals) [165]. Thus, photoelectrochemistry is an excellent means for intitiating chemoselective oxidation. 

Recently, substituted amides and lactams, such as dimethylformamide (DMF) or 2-pyrrolidones, were used as electron donors in the photoalkylation of 1,2,4,5-tetracyanobenzene (TCB) [45], The success of the reaction was ascribed to the high reduction potential of TCB in the excited state that made the initial step-that is, the oxidation of amides [Ei/2 DMF = 2.29 V versus standard calomel electrode (SCE)]-possible. It should be noted here that the ensuing deprotonation step was found to be chemoselective when using N-methylpyrrolidone (NMP), as illustrated in Scheme 14.8b. Accordingly, deprotonation of the lactam radical cation intermediate occurred exclusively at the methylene, and not from the methyl group. Tricyano benzene 12 was thus isolated in 41% yield. 

The direct photolysis of alkyl or aryl halides in solution to form carbon-centered radicals is rarely used in organic synthesis." Alkyl iodides usually afford mixtures of radical and ionic products, while alkyl bromides can produce radical-derived products but in low yield. A notable exception is the photocycliza-tion of haloarenes, which has been shown to produce carbon-centered radicals that can add to aromatic rings. A similar reaction has recently been observed on irradiation of iodoheterocycles, with substituted benzenes or electron-poor alkenes, to form arylated or alkylated heterocycles in good yield. Related reactions have also been reported on irradiation of 4-chloroanilines in the presence of (electron-rich) alkenes, although in this case, the alkylations appear to involve the formation of a phenyl cation. An alternative approach to form carbon-centered radicals is to irradiate the alkyl iodide or bromide in the presence of triethylamine this is proposed to form an amine-haHde exciplex, which cleanly breaks down to give a carbon-centered radical and a halide anion. Cossy and co-workers have shown this to be a fast, convenient, and chemoselective method of radical generation, which has recently been used to prepare the bicyclic core of ( )-bisabolangelone (Scheme 1). ... 

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