Cyclization radical anion

The formal kinetics and diagnostic criteria for the different mechanistic pathways for intramolecular hydrodimerizations under steady-state conditions (LSV, RDE and polar-ography) have been established [115-117]. For the RS-type mechanisms it is normally assumed that the cyclized radical anion (or the neutral, cyclic radical formed by subsequent protonation) is more easily reduced than the starting material. For the RR-type mechanisms AE (the difference in reduction potential of the two electroactive groups) is normally assumed to equal the statistical difference expected for two electronically isolated groups in the same molecule. 

The electrolysis of adamantylideneadamantane solutions affords the radical cation, which can add molecular (triplet) oxygen to give the peroxide radical anion, which can react with adamantylideneadamantane to give the 1,4-diradical and another molecule of adamantylideneadamantane radical cation. The latter reacts with oxygen, to continue the chain of the reaction, while the former cyclizes to the corresponding 1,2-dioxetane (Scheme 18) (81JA2098). 

The proposed mechanism for the conversion of the furanone 118 to the spiro-cyclic lactones 119 and 120 involves electron transfer to the a -unsaturated methyl ester electrophore to generate an anion radical 118 which cyclizes on the /3-carbon of the furanone. The resulting radical anion 121 acquires a proton, giving rise to the neutral radical 122, which undergoes successive electron transfer and protonation to afford the lactones 119 and 120 (Scheme 38) (91T383). 

Many anodic oxidations involve an ECE pathway. For example, the neurotransmitter epinephrine can be oxidized to its quinone, which proceeds via cyclization to leukoadrenochrome. The latter can rapidly undergo electron transfer to form adrenochrome (5). The electrochemical oxidation of aniline is another classical example of an ECE pathway (6). The cation radical thus formed rapidly undergoes a dimerization reaction to yield an easily oxidized p-aminodiphenylamine product. Another example (of industrial relevance) is the reductive coupling of activated olefins to yield a radical anion, which reacts with the parent olefin to give a reducible dimer (7). If the chemical step is very fast (in comparison to the electron-transfer process), the system will behave as an EE mechanism (of two successive charge-transfer steps). Table 2-1 summarizes common electrochemical mechanisms involving coupled chemical reactions. Powerful cyclic voltammetric computational simulators, exploring the behavior of virtually any user-specific mechanism, have... 

Novi and coworkers124 have shown that the reaction of 2,3-bis(phenylsulfonyl)-l,4-dimethylbenzene with sodium benzenethiolate in dimethyl sulfoxide yields a mixture of substitution, cyclization and reduction products when subjected at room temperature to photostimulation by a sunlamp. These authors proposed a double chain mechanism (Scheme 17) to explain the observed products. This mechanism is supported by a set of carefully designed experiments125. The addition of PhSH, a good hydrogen atom donor, increases the percent of reduction products. When the substitution process can effectively compete with the two other processes, the increase in the relative yield of substitution (e.g., with five molar equivalents of benzenethiolate) parallels the decrease in those of both cyclization and reduction products. This suggests a common intermediate leading to the three different products. This intermediate could either be the radical anion formed by electron transfer to 2,3-bis(phenylsulfonyl)-l,4-dimethylbenzene or the a radical formed... 

The reaction of the unsaturated aldehyde 32 with cat. Cp2 VCl2/Me3SiCl/ Zn is conducted in THF to afford the cyclic alcohol 33 with excellent dia-stereoselectivity (Scheme 19) [21]. The transformation may be explained by 5-exo-cyclization of the corresponding radical anion, followed by chlorination. 

The sonochemistry of the other alkali metals is less explored. The use of ultrasound to produce colloidal Na has early origins and was found to greatly facilitate the production of the radical anion salt of 5,6-benzo-quinoline (225) and to give higher yields with greater control in the synthesis of phenylsodium (226). In addition, the use of an ultrasonic cleaning bath to promote the formation of other aromatic radical anions from chunk Na in undried solvents has been reported (227). Luche has recently studied the ultrasonic dispersion of potassium in toluene or xylene and its use for the cyclization of a, o-difunctionalized alkanes and for other reactions (228). 

Transition state effects communication of orthogonal orbitals in the transition state of radical-anionic cyclizations 23... 

Whitlock et al.14 discovered a reductive cyclization of enediynes promoted by lithium naphthalenide that provides substituted fulvenes and suggested a dianionic mechanism (Scheme 6). However, even now it is still unclear whether the enediyne dianion is indeed the cyclizing species or whether the initially formed acyclic radical-anion cyclizes first to give a fulvene radical-anion which is further reduced by lithium to give the cyclic dianion. 

Fig. 4 The crossings of in-plane and out-of-plane frontier MOs in the radical-anionic Bergman and C1-C5 cyclizations, respectively calculated at the B3LYP/6-31G level. Adapted from reference26.

In this analysis, the activation barrier for both C1-C6 and C1-C5 cyclizations of enediyne radical-anions can be described as the avoided crossing between the out-of-plane and in-plane MOs (configurations). One-electron reduction populates the out-of-plane LUMO of the enediyne moiety. At the TS (the crossing), the electron is transferred between the orthogonal re-systems to the new (in-plane) LUMO. This effect leads to the accelerated cyclization of radical-anions of benzannelated enediynes, a large sensitivity of this reaction to re-conjugative effects of remote substituents and the fact that this selectivity is inverse compared to that of the Bergman cyclization. Similar electronic effects should apply to the other reductive cyclization reactions that were mentioned in the introduction. 

Fig. 19 The reaction energy profiles for thermal (on the left) and radical-anionic (on the right) C1-C6 and C1-C5 cyclizations of the parent enediyne computed at the B3LYP/ 6-31G level.

The only known exception is the fascinating class of radical-anionic and dianionic cyclizations where 7i-effects can be activated through MO crossings... 

The starting points for both C1-C5 and C1-C6 cyclizations are characterized using C1-C6 distances to stress that starting point for both cyclizations is the same enediyne radical-anion. However, for transition states and products of C1-C5 and C1-C6 cyclizations, the respective incipient bond length (C1-C5 or C1-C6) was used as the reaction coordinate... 

Catalysts, alcoholysis of transition metal ion and Ln3 +, see Transition metal ion and Ln3+ catalysts, alcoholysis C1-C5 cyclization, 9, 10/ enediyne radical-anions, 25, 25/ 26/ of enediynes, 5/... 

A radical anion is involved in the samarium iodide-induced cyclization of the pyrrole derivative 58 (Scheme 19) <20030L4305>. 

Vinyllithium cyclizations. The vinyl lithiums formed from trisylhydrazones (9, 486) can participate in intramolecular cyclizations. This anionic cyclization is presently limited to formation of five-membered rings. It has the advantage of greater stereoselectivity than a corresponding radical cyclization. 

Scheme 11.16 Diastereocontrol via chelate effect stereoselective 5-exo-trig cyclization on to a cumulated Jt-bond of a chelated ester-substituted ketyl radical anion 50 [74]. a 94 6 mixture of diastereomers.

This has been applied to the cyclization of dihalides [45, 46], nonconjugated, unsaturated ketones [47] and esters [48], oxoalkylpyridinium salts [49], aldehydes and unsaturated nitriles [50], halides, and unsaturated esters [51], The umpoled acceptors, mostly radical anions or carban-ions (see Scheme 1), can also be used in intermolecular reactions such as acylation, alkylation, or carboxylation (Eq. 5). 

Like the electrohydrodimerization and electrohydrocyclizahon reactions, this process also requires the consumphon of two electrons and two protons. It has been shown to occur via a sequence consisting of electron transfer followed by a ratedetermining protonation of the resulting radical anion, addihon of a second electron to generate a carbanion, cyclization of the carbanion onto the carbonyl acceptor unit and the addition of the second proton [16]. Carbon acids like dimethyl malonate and malononitrile are often used as a proton source. The course of this and other... 

Radicals can be obtained from reduction of molecules followed either by protonation or departure of a nucleophile as illustrated in Schemes 6 [10] and 7 [11], respectively. In the first example, a generally accepted mechanism involves a reduction of a double bond activated by an electron-withdrawing group to a radical anion followed by protonation and cyclization of the resulting radical. The addition of a second electron and proton completes the process. 

The reaction of bornyl and isobornyl bromides with the nucleophile (Scheme 18) is another case where the amount of inversion is small and the rate constant close to that observed with an aromatic anion radical of the same standard potential (Daasbjerg et al., 1989) it can therefore be rationalized along the same lines. Cyclizable radical-probe experiments carried out with the same nucleophile and 6-bromo-6-methyl-1-heptene, a radical clock presumably slower than the preceding one, showed no cyclized coupling product. It should be noted, on the other hand, that, unlike the case... 

The mechanism of the electroreductive cyclization reaction has been studied in some detail [22], The initial thought was that it occurred via the cyclization of the radical anion derived, for example, from 25 in the first reduction step. A moment s reflection, however, reveals that there are many more mechanistically viable pathways, especially when one realizes that the transformation involves five steps - two electron transfers (symbolized below by e and d , the latter corresponding to a homogeneous process), two protonations ( p ), and cyclization ( c ). In principle, these could occur in any order, and with any one of the steps being rate-determining. 

Of hundreds of theoretically possible pathways, the list can be trimmed to four using linear sweep voltammetry (LSV) and chemical arguments [22]. The LSV method is an exceptionally powerful one for analyzing electrochemical processes [24-27]. From LSV studies, it was concluded that a single heterogeneous electron transfer precedes the rate-determining step, cyclization is first order in substrate, and that proton transfer occurs before or in the rate-determining step. The candidates include (a) e-c-P-d-p (radical anion closure). 

---