The Radical Approach

It is notable that pyridine is activated relative to benzene and quinoline is activated relative to naphthalene, but that the reactivities of anthracene, acridine, and phenazine decrease in that order. A small activation of pyridine and quinoline is reasonable on the basis of quantum-mechanical predictions of atom localization encrgies, " whereas the unexpected decrease in reactivity from anthracene to phenazine can be best interpreted on the basis of a model for the transition state of methylation suggested by Szwarc and Binks." The coulombic repulsion between the ir-electrons of the aromatic nucleus and the p-electron of the radical should be smaller if the radical approaches the aromatic system along the nodal plane rather than perpendicular to it. This approach to a nitrogen center would be very unfavorable, however, since the lone pair of electrons of the nitrogen lies in the nodal plane and since the methyl radical is... 

Carbon-centered radicals have been shown to undergo addition reactions with azirine-3-carboxylates. Methyl 2-(2,6-dichlorophenyl)azirine-2-carboxylate thus reacts with alkyl and aryl iodides in the presence of triethylborane to give aziridines in good yields. The radical approaches from the opposite face to the aryl substituent, giving the cis products as single diastereoisomers (Scheme 4.43) [63],... 

The radical approach to natural product xylobovide starting from D-glucose was reported (Fig. 48).64... 

Owing to chelation the radical approaches from the side opposite to the substituent and the reaction becomes completely stereospecific. 

Wet chemical procedures for forming covalently bonded monolayer films on H—Si(l 11) are well developed. Among various methods, the radical approach is the most common one. 

In order to solve for the survival and recombination probabilities, p and q in eqn. (126), it is necessary to solve eqn. (122) for p(r, f]r0, f0) and use eqn. (123) to find p or eqn. (125) for q. Again, the boundary and initial conditions are required. Before the pair is formed (f < and ttf is slightly less than f0), the density p is zero, of necessity. The boundary conditions are closely related to the Smoluchowski conditions [eqns. (5), (22), (46) and (47)]. As the radicals approach each other they have a probability of reacting, which can be related to an effective second-order rate coefficient, fcact> f°r the activation-limited process of recombination by... 

When the two transition states are compared, the radical approach angle in the transition state of 5-exo-trig manner is closer to a = 109° than that in 6-endo-trig manner. 

The OH interaction (either via an addition or abstraction route) with toluene has been studied using computational chemistry [26-29]. Uc et al. [28] specifically showed that the mechanism for OH interaction with toluene involves the formation of a stable pre-reactive complex (depicted in Figure 14.1) when the radical approaches the aromatic ring at a van der Waals distance. 

The data available indicate that the radical approaches the substrate along the equatorial direction. In the addition of PhS to tricyclo[4.1.0.0 - ]heptane (7) (equation 85) it was demonstrated that equatorial attack is preferred over axial attack by a factor of at least 27000 " ... 

Unlike the radical approaches mentioned above, Vasella exploited a carbanion approach. Thus, the anomeric carbanion was anticipated to be stabilized by the Cl-carboxylate group. A 1-deoxy derivative of Neu5Ac 198 was treated with LDA, and the resulting anion was reacted with formaldehyde to produce a 3/1 mixture of a- and /3-isomers of 2-hydroxymethyl product 199 (O Scheme 55) [131]. 

In order for the chemical interaction to take place, radicals must come into contact with one another. The dependence of the rate of this reaction on the monomer concentration makes it possible to assume that the transfer of radicals in space is brought about by the propagation reaction, i.e., by the addition of monomer molecules. Assuming that such a transfer in space is of a random nature from the point of view of the radicals approaching each other, and that the radicals react instantaneously at a distance r from each other (the reaction is limited by transfer in space, and not by the chemical interaction), the authors of13) obtained the following equation to describe for the concentration of radicals (R) and the yield of polymer (q) ... 

Hansen and Ugelstad [27,41] proposed that the radical capture efficiencies may not only be different for micelles and particles, but also among particles because of different sizes, surface charges, and monomer and radical concentrations. The rate of absorption of radicals in micelles and small particles may be lower than expected from diffusion-controlled irreversible absorption. Radicals arriving at the surface of the micelles can adsorb, thai desorb back into the bulk or diffuse further into the micelle. Because of the small size of the micelles, desorptirai can take place at a relatively fast rate. For ionic surfactants, the radicals approach the micelles, adsorb and desorb at almost equal rates, and essentially pass through the micelles. For non-ionic micelles, the presence of a condensed layer at the water side of the micelle can cause a higher resistance to radical capture and thus result in an even lower radical capture efficiency than for ionic miceUes. 

The radical approach for C-C bond formation is a popular method within organic chemistry. The use of radical chemistry in carbohydrate synthesis has certain advantages. Firstly the reaction conditions are very mild and tolerant of a range of functional and protecting groups. Anomeric radicals are also stable towards elimination and epimerisation. Most significantly, the chemistry required to incorporate an appropriate substituent at C-1, employed in the initial homolytic cleavage step, is common within carbohydrate chemistry. The use of such radical techniques can be subdivided into two classes, intermolecular and intramolecular reactions. 

The second channel produces OH radicals, which continue the reaction chain, whereas only 20% of the reaction enters the termination channel. However, this nighttime chemistry gains significance only for high NO2 concentrations. Then the radicals approach concentrations typical of daylight conditions. 

In the Minisci protocol, tiie key role is played by the nucleophilic character of the C-centered radical intermediates and the selectivity depends on polar effects and solvents [24a-24e]. Generally, the Friedel-Crafts protocol results in poor yields when applied to protonated heteroaromatic bases, because of their electron deficiency. On the contrary, the substitution takes place efficiently by means of carbon-centered radicals. This behavior is due to the charge-transfer characfer of the transition state in the radical approach (Scheme 13) [25]. 

Another competing reaction is the intermolecular replacement of bromine by hydrogen in the radical translocating group. Additional approaches capitalizing on stereospecific hydrogen translocation to the anomeric radical have been described by Crich [186, 187]. Despite excellent stereoselectivity, the radical approach is rendered impractical by the circuitous methods needed for generation of the key anomeric radical [51]. 

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