Nucleophilic Trapping of Cationic Intermediates

Under these conditions, silver-assisted electrocyclic ring opening provided the haloallyl cation, which was subsequently trapped by isocyanate anion. Interception of the cationic species with isocyanate was successful since bromide was removed from the reaction mixture as a precipitate (AgBr). Finally, treatment of intermediate 9 with methanol furnished the desired carbamate in 96% yield. This example demonstrates the usefulness of the silver(I)-mediated process. Removal of free halide from the reaction mixture affords a long-lived cationic species that can be captured by a different nucleophile, such as solvent, the silver(I) counteranion, or an intramolecular nucleophile. This reactivity has been exploited in many different ways throughout the years and is examined in greater detail later in this chapter. 

The construction of complex intermediates from simple and readily available starting materials has been accomplished using the electrocyclic ring-opening reaction of halocyclopropanes. This is typically achieved through interception of the cationic haloallyl intermediate by solvent, the silver(I) counteranion, or some alternate tethered heteroatom or carbon-based nucleophile. Examples of these processes are described below. 

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A similar distinction between a system with pre-electrolysis with only one electrode (in this case anodic) process, and a system with simultaneous anodic and cathodic processes (in which anode and cathode are on opposite walls of a microchannel so that each liquid is only in contact with the desired electrode potential, analogous to the fuel cell configurations discussed above) was made by Horii et al. (2008) in their work on the in situ generation of carbocations for nucleophilic reactions. The carbocation is formed at the anode, and the reaction with the nucleophile is either downstream (in the pre-electrolysis case) or after diffusion across the liquid-liquid interface (in the case with both electrodes present at opposite walls). The concept was used for the anodic substitution of cyclic carbamates with allyltrimethylsilane, with moderate to good conversion yields without the need for low-temperature conditions. The advantages of the approach as claimed by the authors are efficient nucleophilic reactions in a single-pass operation, selective oxidation of substrates without oxidation of nucleophile, stabilization of cationic intermediates at ambient temperatures, by the use of ionic liquids as reaction media, and effective trapping of unstable cationic intermediates with a nucleophile. 

The silver(I)-mediated ring opening of halocyclopropanes has been used to construct complex frameworks through the inter- and intramolecular trapping of cationic intermediates with heteronucleophiles. An obvious extension of this work is the involvement of carbon-based nucleophiles to form new carbon-carbon bonds. In 1996, Kostikov and coworkers reported the participation of aromatic solvents in the capture of halocyclopropane-derived allyl cations even in the absence of silver(I).30 However, this early example of intermolecular attack by a carbon nucleophile is one of very few such reports. In the same year, Gassman et al. reported cationic cyclizations of gem-dibromocyclopropanes tethered to remote diene moieties (Scheme 4.16).31... 

Nucleophilic Trapping of Radical Cations. To investigate some of the properties of Mh radical cations these intermediates have been generated in two one-electron oxidant systems. The first contains iodine as oxidant and pyridine as nucleophile and solvent (8-10), while the second contains Mn(0Ac) in acetic acid (10,11). Studies with a number of PAH indicate that the formation of pyridinium-PAH or acetoxy-PAH by one-electron oxidation with Mn(0Ac)3 or iodine, respectively, is related to the ionization potential (IP) of the PAH. For PAH with relatively high IP, such as phenanthrene, chrysene, 5-methyl chrysene and dibenz[a,h]anthracene, no reaction occurs with these two oxidant systems. Another important factor influencing the specific reactivity of PAH radical cations with nucleophiles is localization of the positive charge at one or a few carbon atoms in the radical cation. 

Nitrogen-based nucleophiles have been thoroughly examined in the context of trapping the cationic intermediate generated from silver(I)-mediated halocyclopro-... 

The formation of vinyl cations has also been observed [61]. The acyclic vinyl iodide (24) was irradiated at 254 nm in CH3OH. This afforded reduction, nucleophilic-trapping, and allene intermediate products (Scheme 18). In the presence of CH3OD the allylic ether had 72% incorporation of deuterium at the vinylic position. On irradiation in CH2C12 or pentane, reduction and 1,3-diene product were observed. 

Concerning the mechanism of the Favorskii reaction, it is suggested that loss of the nucleofuge oecurs, resulting in a 2-oxyallyl cation, but that disrotatory ring closure is facile and the only products observed result from nucleophilic trapping of the cyclopropanone intermediate to provide cyclopropanols in fair to good yield. 

Other nucleophilic species can be present in the reaction medium to trap the cationic intermediate . The rate of acylation of an alkyne is indicated by reaction in the presence of an aromatic compound, leading to arylated products (equation 24). ° This reaction can take place at low temperatures where the... 

Under similar conditions a-phenylthio esters 9 afford fluorides 10 (Scheme 3.5) [25]. The mechanism of this Pummerer-type reaction involves initial nucleophilic addition of the sulfur atom to the electrophilic iodine center to form the iodosulfonium salt 11. The liberated fluoride anion acts as a base with resultant formation of the classical Pummerer intermediate 12. Subsequent trapping of cation 12 with fluoride anion yields the final product 10 (Scheme 3.5) [25]. 

The initial studies centered on the 1-norbomyl halides 8. On irradiation in CH3OH, they afford a mixture of the reduction product norbornane (9) and the ether 10, with the former predominating from bromide 8b and the latter from iodide 8a. The reduction product 9 arises via abstraction of a hydrogen atom by 1-norbornyl radical from the medium and ether 10 via nucleophilic trapping of the 1 -norbornyl cation. Irradiation of either hahde in CH3OD afforded ether 10 with no detectable incorporation of deuterium, indicating that it does not arise via acid-catalyzed addition of the alcohol to an initially formed unsaturated intermediate such as the bridgehead alkene 12 or the propeUane 13. 

Some general rules can be used to predict the outcome of irradiation of alkenyl haHdes. Thus, the photolysis of a-arylvinylhalides leads to stable a-arylvinyl cations, and the vinyl cation route is followed predominantly. A nucleophilic reagent can capture such intermediates. Conversely, in the cases that produce unstable vinyl cations, vinyl radicals are formed preferentially, or else the formation of radical and cation intermediates competes. Clearly, the nature of the substituent is important in predicting the reactions of the vinyl cations. Results indicate that the nucleophilic trapping of the vinyl cations follows the order d H << alkyl << Ph < p-MeC( H4 < p-MeOC( H4. The halogen employed is also important, with chlorides and bromides better than iodides at undergoing hssion. Fluorides, as mentioned previously, are inactive in photolysis. In aliphatic alkenyl halides, conversely, iodides afford ionic intermediates more preferentially than do bromides or chlorides. However, capture by nucleophiles is restricted to the nucleophilic solvent employed. 

The dependence of relative rates in radical addition reactions on the nucleophilicity of the attacking radical has also been demonstrated by Minisci and coworkers (Table 7)17. The evaluation of relative rate constants was in this case based on the product analysis in reactions, in which substituted alkyl radicals were first generated by oxidative decomposition of diacyl peroxides, then added to a mixture of two alkenes, one of them the diene. The final products were obtained by oxidation of the intermediate allyl radicals to cations which were trapped with methanol. The data for the acrylonitrile-butadiene... 

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