Nucleophilic and Electrophilic Radicals

The trifluoromethyl group is the most prominent fluorinated side chain. An excellent review on all aspects of the introduction of the trifluoromethyl group into organic compounds is available (92T6555). The trifluoromethyl group can be introduced as radical, nucleophilic and electrophilic species as well as by functional group transformations. 

Reactions of chloramine include radical, nucleophilic, and electrophilic substitution of chlorine, electrophilic substitution of hydrogen, and oxidative additions, for example ... 

Within an aromatic substitution transform the terms RLENERGY, NLENERGY, and ELENERGY refer to the radical, nucleophilic, and electrophilic localization energies respectively. Several types of statements use these terms, e.g. ... 

Finally, much of the wealth of information for radical, nucleophilic, and electrophilic substitution results from the exploration of a second (or further) substitution reaction of the aromatic ring. For example, as shown in Equation 6.92, the reaction of some electrophile, ET, with benzene (CefT), where aU six positions are equivalent, can, at some rate under some specified reaction conditions of solvent and temperature, produce a substitution compound, where Ei has replaced (been substituted for) a proton (Ft+). ... 

Electronic effects in conjugated systems may be computed with the Hiickel HMO method. Electron densities are used to predict aromatic substitution reactions, and it is possible to refer to radical, nucleophilic, and electrophilic localization energies.For the latter, the term ELENERGY is used in a transform, for example IF ELENERGY ON ATOM 1 BETTER THAN ATOM 2 THEN ADD 20. 

In so far as the composition of the electrical effect is considered, the values of p given in Table XVll show that for both nucleophilic and electrophilic radicals, the resonance effect seems to predominate, probably in the case of the former and almost certainly in the case of the latter. 

Analogously, 5-tributylstannylimidazole 29 was easily obtained from the regioselective deprotonation of 1,2-disubstituted imidazole 28 at C(5) followed by treatment with tributyltin chloride [24]. In the presence of 2.6 equivalents of LiCl, the Stille reaction of 29 with aryl triflate 30 afforded the desired 1,2,5-trisubstituted imidazole 31 with 2,6-di-tert-butyl-4-methylphenol (BHT) as a radical scavenger. Reversal of the nucleophile and electrophile of the Stille reaction also provided satisfactory results. For example, the coupling reaction of 5-bromoimidazole 33, derived from imidazole 32 via a regioselective bromination at C(5), and vinylstannane 34 produced adduct 35 [24],... 

This section will cover aspects of monohydride terminal surface reactions that were carried out under free-radical conditions. The description will be circumscribed to the reactions with molecular oxygen and monounsaturated compounds. Mechanistic information for these reactions is scarce mainly due to the complexity of the system, and mechanistic schemes are often proposed in analogy with radical chemistry of organosilane molecules. H—Si(lll) has a band gap of about 1.1 eV while the HOMO LUMO gap in (Me3Si)3SiH is within 8-11 eV and, therefore, has very important consequences for the reactions with nucleophilic and electrophilic species where frontier orbital inter-... 

Nucleophilic and electrophilic substitutions in anion- and cation-radical, respectively, have been considered throughout the book, including the problem of a choice between addition and electron-transfer reactions. Therefore, only some unusual cases are discussed here. 

The first intermediate to be generated from a conjugated system by electron transfer is the radical-cation by oxidation or the radical-anion by reduction. Spectroscopic techniques have been extensively employed to demonstrate the existance of these often short-lived intermediates. The life-times of these intermediates are longer in aprotic solvents and in the absence of nucleophiles and electrophiles. Electron spin resonance spectroscopy is useful for characterization of the free electron distribution in the radical-ion [53]. The electrochemical cell is placed within the resonance cavity of an esr spectrometer. This cell must be thin in order to decrease the loss of power due to absorption by the solvent and electrolyte. A steady state concentration of the radical-ion species is generated by application of a suitable working electrode potential so that this unpaired electron species can be characterised. The properties of radical-ions derived from different classes of conjugated substrates are discussed in appropriate chapters. 

The origin of the difference lies in the fact that triplet carbenes are biradicals (or diradicals) and exhibit chemistry similar to that exhibited by radicals, while singlet carbenes incorporate both nucleophilic and electrophilic sites, e.g., for singlet and triplet methylene. 

The energy of the HOMO (EHomo) is directly related to the ionization potential and characterizes the susceptibility of the molecule to attack by electrophiles. On the other hand, EHOMO is directly related to the electron affinity and characterizes the susceptibility of the molecule toward attack by nucleophiles. Both the E, IOMO and LUMO energies are important in radical reactions. The concept of hard and soft nucleophiles and electrophiles has... 

Competition studies from Szwarc s group provided excellent quantitative insights into the relative affinities of methyl and trifluoromethyl radicals for a host of alkenes [86-88], and from this work came the first general recognition that substituted alkyl radicals could exhibit polar characteristics ranging from nucleophilic to electrophilic. On the basis of such early work, methyl and trifluoromethyl were taken to be the prototypical nucleophilic and electrophilic radicals, respectively, characterizations which it turns out are somewhat exaggerated in both cases. 

Compared with SnI or Sn2 reactions, relatively few examples of radical nucleophilic substitutions have been reported [6-8,16, 22-25]. This suggests that the structural requirements of nucleophile and electrophile for such processes are more stringent than for non-radical nucleophilic substitutions. In the following sections the focus will be on the more generally applicable non-radical SnI and Sn2 reactions. 

Both nucleophilic and electrophilic reactions are known, and the reaction sequence can be directed by a suitable choice for a heteroligand [41,52], As suggested by Scheme 6.11a, the ability of the heteroligand to direct electrophilic or nucleophilic attack by the peroxocomplex can provide an important tool in oxidative reactions, where selectivity of action is required. A second mode of electrophilic reaction chemistry is available through attack of sulfur electrons at the vanadium center to give a transient anion/cation radical pair via formation of V(TV) and S-+ (Scheme 6.1 lb). 

This interpretation is consistent with the nucleophilic properties which are generally associated with the methyl radical. In passing, note that Canadell s rule states that any radical, nucleophilic or electrophilic, reacts with an alkene at the site having the largest HOMO coefficient.62 Canadell and co-workers argue that the three-electron SOMO-HOMO interaction is stabilizing, due to the energetic proximity of these orbitals. See, however, p. 12. 

Besides spectroscopic methods, quenching processes have been utilized to differentiate between various types of radical ion pairs, too. These chemical methods make use of the different reactivities of CIP and SSIP which are caused by the unequal solvation and distance of the charged species in the ion pairs. Depending on the ambivalent character of radical ions, these intermediates may be scavenged either by electron transfer quenchers (Q) or by nucleophilic and electrophilic scavengers (Scheme 7 and Eqs. (5—7)). 

Most of the reactions presented in previous chapters involved nucleophiles and electrophiles and occurred in several steps involving cationic, anionic, or, in the last chapter, radical intermediates. In this chapter a group of concerted (one-step) reactions, called pericyclic reactions, that involve none of these intermediates is discussed. The mechanisms of these reactions are exceedingly simple because they consist of a single step. Yet, as we shall see, pericyclic reactions are amazingly selective, both in terms of when they occur and also in their stereochemical requirements. 

Eberson and co-workers have recently discussed the probability that the interaction of ion-radicals with nucleophiles and electrophiles is subject to orbital symmetry constraints.31,32 This follows the observation that with perylene the cation-radical (18) the preferred course of reaction with halide ions is electron transfer rather than nucleophilic addition, whereas with the phenothiazine cation-radical (19) nucleophilic attack by Cl" and Br occurs. 

Nucleophilic and electrophilic radicals abstract different hydrogen atoms from butyrolactone 7.10 the ferf-butoxy radical selectively abstracts a hydrogen atom from the methylene group adjacent to the oxygen atom, whereas a boryl radical abstracts a hydrogen atom from the methylene group a to the carbonyl group. 

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