Radicals, anti-Markovnikov nucleophilic

Electron transfer sensitization allows either the radical cation or the radical anion of an aromatic alkene to form as desired, which finally results in nucleophile addition with Markovnikov and anti-Markovnikov regiochemistry. In an apolar solvent, the tight radical ion pair undergoes a stereoselective reaction when the electron-accepting sensitizer is chiral (Figure 3.10). ... 

Substituted cyclopropane systems also undergo nucleophilic addition of suitable solvents (MeOH). For example, the photoinduced ET reaction of 1,2-dimethyl-3-phenylcyclopropane (112, R = Me) with p-dicyanobenzene formed a ring-opened ether by anti-Markovnikov addition. The reaction occurs with essentially complete inversion of configuration at carbon, suggesting a nucleophilic cleavage of a one-electron cyclopropane bond, generating 113. The retention of chirality confirms that the stereochemistry of the parent molecule is unperturbed in the radical cation 112 " ". 

Dimer formation can be quenched by conducting the experiment in a nucleophilic solvent, and the product obtained is characteristic of radical cation trapping. The anti-Markovnikov addition of acetone across the C-C single bond of the methylated analogue, eq. 41 (116,117),... 

After proton transfer and radical coupling, the observed product is obtained. In the presence of nucleophilic solvents, the radical cation can be intercepted before coupling, leading to anti-Markovnikov addition across the olefinic double bonds, eq. 65 (198) ... 

When electron transfer reactions of olefins are carried out in nucleophilic solvents (alcohols) or in the presence of an ionic nucleophile (KCN/acetonitrile/2,2,2-trifluoroethanol), the major products formed are derived by anti-Markovnikov addition of the nucleophile to the olefin. In several cases, nucleophilic capture completely suppresses dimer formation [122, 143]. It is important to realize that the observed mode of addition reflects the formation of the more stable (allylic) intermediate and cannot be interpreted as evidence for the charge density distribution in the radical cation. 

There is a considerable current interest in synthetic applications of radical cation chemistry. Alkene radical cations have been studied extensively, notable examples include the anti Markovnikov addition of nucleophiles [209], and the photo-NO-CAS reaction [210]. The synthetic utility of radical cation mediated chemistry, and... 

Formation of cycloadducts can be completely quenched by conducting the experiment in a nucleophilic solvent. This intercepts radical cations so rapidly that they cannot react with the olefins to yield adducts. In Scheme 54 the regiochemistry of solvent addition to I-phenylcyclohexene is seen to depend on the oxidizability or reducibiiity of the electron-transfer sensitizer. With ]-cyanonaphthalene the radical cation of the olefin is generated, and nucleophilic capture then occurs at position 2 to afford the more stable radical. Electron transfer from excited 1,4-dimethoxynaphthalene, however, generates a radical anion. Its protonation in position 2 gives a radical that is oxidized by back electron transfer to the sensitizer radical before being attacked by the nucleophilic solvent in position 1. Thus, by judicious choice of the electron-transfer sensitizer, it is possible to direct the photochemical addition in either a Markovnikov (157) or anti-Markovnikov (158) fashion (Maroulis and Arnold, 1979). 

The photoinduced anti-Markovnikov addition of methanol to 1,1-diphenylethene reported by Arnold and co-workers in 1973 provides the first example of the addition of a nucleophile to an arylalkene radical cation. There are now a number of studies that demonstrate the generality of nucleophilic addition of alcohols, amines, and anions such as cyanide to aryl- and diaryl-alkene radical cations. Product studies and mechanistic work have established that addition occurs at the 3-position of I-aryl or 1,1 -diarylalkene radical cations to give arylmethyl or diaryl-methyl radical-derived products as shown in Scheme I for the addition of methanol to 1,1-diphenylethene. For neutral nucleophiles, such as alcohols and amines, radical formation requires prior deprotonation of the 1,3-distonic radical cation formed in the initial addition reaction. The final product usually results from reduction of the radical by the sensitizer radical anion to give an anion that is then protonated, although other radical... 

Synthesize the compound shown below from methylcyclopentane and 2-methylpropane using those compounds as the source of the carbon atoms and any other reagents necessary. Synthetic tools you might need include Markovnikov or anti-Markovnikov hydration, Markovnikov or anti-Markovnikov hydrobromination, radical halogenation, elimination, and nucleophilic substitution reactions. 

In 1992 Ogawa, Sonoda et al. carried out the first catalytic addition of aromatic thiols [143] and selenols [144] to alkynes with Pd(OAc)2. Although the Markovnikov isomer was the major product of the reactions, the yields were not very high [145]. The catalytic reaction was accompanied with non-catalytic addition, leading to the anti-Markovnikov isomers (free radical or nucleophilic reactions) as well as double bond isomerization in the case of thiols (TH F, 67 °C) and selenols (benzene, 80 °C) [143, 144]. The isomerization reaction was especially pronounced with Pd(PhCN)2Cl2 catalyst [146]. It is interesting to note that the intermediate metal complex taking part in the catalytic reaction was denoted as Pd(SPh)2L [146]. 

Retrosynthetic analysis of nitrile 164 disconnects the C-CN bond because it is clear that the six carbons of the methylcyclopentene starting material are more or less intact in the remainder of the molecule. This disconnection requires a C-C bond-forming reaction involving cyanide. Because cyanide is associated with a carbon nucleophile, assign Cj to the cyanide and to the cyclopentene carbon. The synthetic equivalent for Cg is an alkyl halide, and 2-bromo-l-methylcyclopentane (168) is the disconnect product. Bromide 168 is obtained directly from the alkene starting material, but it requires the use of a radical process to generate the anti-Markovnikov product (see Chapter 10, Section 10.8.2). 

Another three components synthesis is involved in the extensively investigated NOCAS process (nucleophile olefin combination aromatic substitution, path h) [89,90], In this case, a nucleophile adds to an alkene radical cation and again the interaction between the resulting radical and the radical anion of the aromatic nitrile may follow two paths. The first is electron transfer, which results in sensitized anti-Markovnikov addition onto the alkene, and is favored with stabilized, reducible radicals such as the benzyl radicals obtained from aryl olefins. The latter one is... 

As was discussed in detail in Sections 4.4.1 through 4.4.4, here are two mechanisms by which acids add to alkenes, the AdE2 and AdgS processes. The reaction is carried out in the dark to minimize free radical side reactions (Chapter 11). In the Ad 2, the proton adds by pathway Ag to produce the more stable carbocation intermediate (Markovnikov s rule) in a second step the cation is trapped by a nucleophile, path An-The Adg2 often gives a mixture of syn and anti addition since the nucleophile can approach the carbocation from either top or bottom face. Adg2 example ... 

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