And alkene radical cations

The mechanistic aspects of aromatic and alkene radical cation reactions have been reviewed. A second review article covers the structure and properties of hydrocarbon radical cations, as revealed by low-temperature ESR and IR spectroscopy. A review of the reactivity of trivalent phosphorus radical cations has appeared which discusses ionic and SET processes and their kinetics. " The structure and reactivity of distonic radical cations have been reviewed, including experimental and calculated heats of formation, structures, reactivity, and mechanisms. ... 

Crich D, Brebion F, Suk D-H (2006) Generation of Alkene Radical Cations by Heterolysis of -Substituted Radicals Mechanism, Stereochemistry, and Applications in Synthesis. 263-. 1-38... 

Phosphorylated derivatives of /3-nitroalcohols, upon exposure to Bu3SnH and AIBN, afford /3-(phosphatoxy)alkyl radicals. These radicals undergo heterolytic cleavage of the phosphate group to afford an alkene radical cation which is trapped intramolecularly in a tandem polar/radical crossover sequence. Derivative 37 (Scheme 13), through a 6-exol 5-exo overall cyclization, afforded the indolizidine derivative 38 as an equimolecular mixture of two diastereoisomers <2003JA7942, 2002OL2573>. 

At one time considered as two distinct reactions occurring by different mechanisms [51], the fragmentations of Scheme 2 and the rearrangments of Scheme 5 are now seen as different facets of the same fundamental heterolysis of -substituted alkyl radicals into alkene radical cations, with the eventual outcome determined by the reaction conditions [52],... 

Nelsen and coworkers determined a barrier to inversion through the planar form in 2 and 3 to be approximately 2 kcalmol-1 by variable temperature ESR spectroscopy [59]. Gerson and coworkers found, also by ESR spectroscopy, that the frequency of electron exchange between the two sites in 4, which is equivalent to rotation about the central bond, can vary between < 106 and > 109 s-1 depending the degree of steric hindrance to planarity [60]. Recent calculations also provide very small barriers to inversion through the planar form [56,57]. It is apparent, therefore, that for most synthetic purposes most alkene radical cations can be considered as essentially planar with effective delocalization over the two sp2-hybridized C atoms, and they will be considered as such in this chapter. 

Further evidence for the formation of alkene radical cations derives from the work of Giese, Rist, and coworkers who observed a chemically induced dynamic nuclear polarization (CIDNP) effect on the dihydrofuran 6 arising from fragmentation of radical 5 and electron transfer from the benzoyl radical within the solvent cage (Scheme 6) [67]. 

Scheme 9 Cyclization and deprotonation of an alkene radical cation...

Although cycloaddition reactions have yet to be observed for alkene radical cations generated by the fragmentation method, there is a very substantial literature covering this aspect of alkene radical cation chemistry when obtained by one-electron oxidation of alkenes [2-16,18-26,28-31]. Rate constants have been measured for cycloadditions of alkene and diene radical cations, generated oxidatively, in both the intra- and intermolecular modes and some examples are given in Table 4 [91,92]. 

The regiochemistry of nucleophilic addition to alkene radical cations is a function of the nucleophile and of the reaction conditions. Thus, water adds to the methoxyethene radical cation predominantly at the unsubstituted carbon (Scheme 3) to give the ff-hydroxy-a-methoxyethyl radical. This kinetic adduct is rearranged to the thermodynamic regioisomer under conditions of reversible addition [33]. The addition of alcohols, like that of water, is complicated by the reversible nature of the addition, unless the product dis-tonic radical cation is rapidly deprotonated. This feature of the addition of protic nucleophiles has been studied and discussed by Arnold [5] and Newcomb [84,86] and their coworkers. 

Using alkene radical cations generated under photostimulated electron-transfer conditions, Arnold and coworkers showed that the addition of an-... 

The suprafacial shift along the carbon framework is not restricted to cyclic systems but may also prevail in acyclic cases. In the example given in Scheme 11, minimization of dipolar repulsion between the two C-0 bonds mandates a preferred conformation of the initial radical, leading to a stereo-chemically defined alkene radical cation and, ultimately, to a single diastere-omer of the product [119]. 

In the gluco case (Scheme 13) the radical cyclization, with its requirement for the formation of a czs-fused ring junction [129,130], takes place uneventfully on the opposite face of the alkene radical cation to the one shielded by the phosphate anion, whereas in the manno series cyclization is severely retarded by the presence of the phosphate group above the face of the radical cation on which cyclization must occur. This steric retardation of the cyclization step results in a breakdown of chain propagation and results in the longer reaction times observed. Furthermore, the retardation of the radical cyclization step in the manno case enables the alkene radical cation to take... 

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]. 

A y-lactone was formed in excellent yield by the nucleophilic cyclization of a carboxylic acid onto an alkene radical cation generated from a (i-nilrophosphale under tin hydride conditions (Scheme 21) [139]. Related experiments employing the acetate group and an internal carboxylate nucleophile failed, emphasizing the very rapid collapse of the alkene radical cation/acetate ion pair [127]. 

An example of a 6-endo cyclization of an alcohol onto an alkene radical cation/phosphate anion pair has also been described (Scheme 22). In order to bring about fragmentation of the primary alkyl phosphate bond in this reaction it was necessary to work in a 1 1 mixture of benzene and acetonitrile [139,140],... 

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. 

The contrast between the lack of enantioselectivity in Scheme 39 and the moderate to excellent diastereoselectivity seen with alcohol nucleophiles in Schemes 19 and 33 can be attributed to the difference in leaving groups (diphenyl phosphate vs diethyl phosphate) and to the differences in the radical cations themselves, all of which impinge on the rate of equilibration of the contact alkene radical cation/anion pair. 

A series of N-allyl sulfamates, phosphoramides, and phosphorimidates was prepared to explore the possibility of O- N rearrangements via the intermediacy of the contact alkene radical cation/anion pair, followed by 5-exo-trigonal radical cyclizations (Fig. 4) [142],... 

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