Alkenes radical attack

In a rare example of the use of phenylselenides as radical precursors in the generation of alkene radical cations by the fragmentation approach, Giese and coworkers generated a thymidine C3/,C4/ radical cation by expulsion of diethyl phosphate. Trapping experiments were conducted with methanol and with allyl alcohol (Scheme 16), when nucleophilic attack was followed by radical cyclization [66]. 

In an extensive investigation of the stereochemical memory effect, a series of six diastereomeric pairs of substrates was prepared to probe the effect of single, then multiple substituents on the 5-exo cyclization of amines onto alkene radical cations [144,145]. Overall, these cyclizations were highly dia-stereoselective and were accounted for by a transition-state model employing a chairlike transition state with attack of the nucleophilic amine on the opposite face of the alkene radical to the one shielded by the phosphate anion in the initial contact ion pair (Scheme 34), as exemplified in Schemes 35 and 36. 

There are a number of other mechanisms by which alkenes can undergo photochemical f2 + 2) cycloaddition, one of which works well for electron-rich alkenes and electron-acceptor sensitizers. The pathway is through the radical cation of the alkene, which attacks a second, ground-state alkene molecule and then cydizes and accepts an electron to give the product cyclobutane. Typical of this group of reactions is the formation of 1,2-dialkoxycydobutanes from alkoxy-ethylenes with drcyanonaphthalene as sensitizer 12.78). 

The central bond of [l.l.l]propellanes (1) is the center of their reactivity, and in many ways, it is useful to think of it as somewhat akin to the n bond in an alkene. The strengths of the two are comparable, and both are susceptible to electrophilic and radical attack. The main difference is that the central bond in la is apparently somewhat susceptible to nucleophilic attack as well, whereas the n bond in unsubstituted ethylene is not. In both cases, introduction of electron-withdrawing groups enhances reactivity towards nucleophiles. 

Substituent effects on cyclizations of simple nucleophilic hexenyl radicals have been well studied, and much quantitative rate data is available.12 The trends that emerge from this data can often be translated to qualitative predictions in more complex settings. Once the large preference for S-exo cyclization is understood, other substituent effects can often be interpreted in the same terms as for addition reactions. For example, electronegative substituents activate the alkene towards attack, and alkyl substituents retard attack at the carbon that bears them. The simple hexenyl radical provides a useful dividing point = 2 x 10s s-1. More rapid cyclizations are easily conducted by many methods, but slower cyclizations may cause difficulties. Like the hexenyl radical, most substituted analogs undergo irreversible S-exo closure as the predominate path. However, important examples of kinetic 6-endo closure and reversible cyclization will be presented. 

The reaction pathway for substituted alkenes proceeds by hydrolysis. The OH radical attacks the C=C bond to form a positive transition state complex. This positive transition state complex corresponds to the negative slope of the Hammett correlation in Figure 5.30. The reaction proceeds until both carbons of the C=C bond have been hydroxylated. 

Enantioselective synthesis of 2-substituted piperidines with 60% ee has been reported via radical precursors being trapped in an intramolecular reaction (Scheme 17) <2003OL3767>. These cyclizations were rationalized in terms of chair-like transition states, with the maximum number of pseudoequatorial substituents, in which the nucleophilic amine attacks the alkene radical cation on the face opposite to the phosphate anion. 

Yates and Wright, 1967). Bimolecular nucleophilic attack on an acetylene (Miller, 1956) (158) or radical attack on an alkene (Readio and Skell, 1966) (159) are illustrative of both stepwise processes and overall stereoselectivity. 

Arenesulfonyl iodide and bromide are rather unstable compounds because of low bond dissociation energies of their S02-I and S02-Br. Therefore, treatment of p-tosyl bromide (47) with alkene or allene (48) produces 1,2-adduct (49) through the addition of the formed p-tosyl radical onto the allene as shown in eq. 4.19 [52]. Here, the p-tosyl radical attacks the central sp carbon of the allene group to generate the stable allylic radical, and then it reacts with p-tosyl bromide to give 1,2-adduct (49) and a p-tosyl radical again, i.e., chain pathway. So, this is also an atom(group)-transfer reaction. 

Tandem radical addition/cydization reactions have been performed using unsaturated tertiary amines (Scheme 9.11) [14,15]. Radical attack is highly stereoselective anti with respect to the 5-alkoxy substituent of 2-(5f-J)-furanones, which act as the electron-deficient alkenes. However, the configuration of the a position of the nitrogen cannot be controlled. Likewise, tandem addition cyclization reactions occur with aromatic tertiary amines (Scheme 9.12) in this case, acetone (mild oxidant) must be added to prevent the partial reduction of the unsaturated ketone [14]. 

Nucleophilic addition reaction is one of the most common reaction pathway available to organic cation radicals. Therefore, as expected alkene radical cations are also attacked by a variety of nucleophiles to give anti-Markonikov addition products. In this context the pioneering work of Arnold [60, 61] may be cited here by illustrating (Scheme 12) the addition of alcohol or cyanide ion... 

Selectivity between hydrogen atom abstraction and addition to an alkene [see (Section 7.3) page 281] is dependent upon the structures of the radical and of the substrate. Simple alkyl radicals attack H Sn bonds competitively with their conjugate addition to Z-substituted alkenes, showing that there is a fairly delicate balance, even though the H Sn bond is notably weak. fert-Butoxy radicals remove allylic hydrogens faster than they add to the terminus of simple alkenes, but quite small changes, to perfluoroalkoxy radicals for example, reverse this selectivity. 

In contrast, for electrophilic radicals attacking an X-substituted alkene, adding an X-substituent like methyl to the Z-substituted radicals 7.20 lowers the rate of attack on 1-decene 7.21. Thus the radical 7.20 (R1 R2 H) reacts 4 times faster than 7.20 (R1 = Me, R2 = H), and the radical 7.20 (R1 = R2 = Cl) reacts 2.5 times faster than 7.20 (R1 = Me, R2 = Cl). The other numbers here are not so easy to interpret, since the chlorine atoms, although re-donating, are also -withdrawing, and it is more than likely that steric effects are also contributing to these results. 

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