Cyclopentyl radicals, reactions

Cycloalkanes may be pyrolized in a manner similar to that for alicyclic alkanes. Cyclopentane, for instance, yields methane, ethane, propane, ethylene, propylene, cyclopentadiene, and hydrogen at 575°C. Analogous to cracking of alicyclic alkanes, the reaction proceeds by abstraction of a hydrogen atom followed by p scission. The cyclopentyl radical may undergo successive hydrogen abstractions to form cyclopentadiene. 

Our next idea was to utilize diazo compounds as radical acceptors. The radical cyclization of diazo compound 9 would initially give intermediate 11 which should release nitrogen gas to generate cyclopentyl radical 12 (Scheme 3). However, the diazo compounds were very labile to the tributyltin radical and the radical reaction of diazo compounds under normal radical conditions (BujSnH/AIBN) gave tributyltin addition products with the release of nitrogen gas. Alkyl... 

More recently, Hasebe and Tsuchiya found that the photochemical decomposition of oxime esters provides a reasonably efficient method of alkylating pyridine when the latter is employed as the solvent <86TL3239>. The reaction gives all three regioisomers and the proportion of each was influenced to some extent by the nature of the radical intermediate. Thus, while the homobenzyl radical gave the C4 addition product as a minor constituent, both cyclopentyl radical and cyclohexyl radical gave C2 and C4 addition products in almost equal proportion (Scheme 8). 

The stereoselectivity in addition and abstraction reactions of cyclopentyl radicals has been reviewed recently3. It has been concluded that /f-substituents at the radical, as well as the alkene substituents, have a large influence on the selectivity, however only small solvent effects have been found. 

Cyclopentyl radicals substituted in the /1-position relative to the radical center are formed during the solvomercuration/reductive alkylation reaction of cyclopentene34. The organomer-curial produced in the first solvomercuration step is reduced by sodium borohydride and yields free cyclopentyl radicals in a radical chain mechanism. Addition of alkenes can then occur tram or cis to the / -alkoxy substituent introduced during the solvomercuration step. The adduct radical is finally trapped by hydrogen transfer from mercury hydrides to yield the tram- and ris-addition products, The transicis ratio depends markedly on the alkene employed and it appears that the addition of less reactive alkenes occurs with higher trans selectivity. In reactions of highly substituted alkenes, this reactivity control is compensated for by steric effects. Therefore, only the fnms-addition product is observed in reactions of tetraethyl ethenetetracarboxylate. The choice of alcohol employed in the solvomercuration step has, however, only a small influence on the stereoselectivity. 

Cyclopentyl radicals flanked with /1-substituents on both sides are formed in reactions of 3-alkyl-2-phenylselenocyclopentanones36. After photochemical initiation, the cyclopentyl radical is formed through abstraction of the phenylseleno group. Addition to tributyl(2-propenyl)stannane occurs preferentially trans to the / -alkyl substituent and consecutive elimination of the stannyl radical gives the final allylation product. It has also been reported37 that addition of the /1-methyl cyclopentyl radical to 2-propenenitrile occurs with d.r. (transjeis) 92 8, hence it seems likely that the carbonyl group adjacent to the radical center reduces the selectivity. 

Heterocyclic cyclopentyl radicals formed in the solvomercuration/reductivc alkylation reaction of dihydrofuran give products with tram- selectivity in a slightly higher ratio than the corresponding carbocyclic analogs34. This is attributed to anomeric effects, which lead to a more pronounced axial orientation of the /J-alkoxy substituent in the tetrahydropyranyl radical. 

Similar lo the effect of ring oxygen atoms is the influence of a carbonyl group adjacent to the radical center 6. In allylation reactions of 2-oxocyclohexyl radicals, the formation of an axial product is slightly enhanced compared to the corresponding cyclohexyl radicals. This is in contrast lo the situation in cyclopentyl radicals, where the introduction of adjacent carbonyl groups leads to a lowering of cisjtrans selectivity in allylation reactions (see this section Cyclopentyl Radicals),... 

Annulated ring systems have as /1,7-substituents, when compared to annulated cyclopentyl radical systems, a stronger effect on the stereoselectivity than the corresponding combination of acyclic substituents. In all cases, attack tram to the /J.y-m-annulated ring is preferred. The stereoselectivity depends, furthermore, on additional substituents at the radical and the alkene, but it appears that the reactions of cyclohexyl radicals proceed less selectively than their cyclopentyl analogs. One frequently used route to these systems is sequential cyclization/ addi-tion reactions, in which the primary radical cyclizes to form the bicyclic ring system, followed by intermolecular addition to an alkene45,47 74. 

The effect of /(-substituents on the stereoselective trapping of cyclopentyl radicals has been studied in reduction reactions of organomercurialsla-16. /(-Hydroxy or /J-methoxy substituents lead mainly to the /rau.s-addition product as a result of steric effects. 

Another class of cyclopentyl radicals, in which high stereoselectivity in hydrogen-abstraction reactions is observed, are bridged systems. The 2-norbornyl radical, without15-16 and with37 substituents at C-2 has been investigated in detail. In the reduction of 2-norbornylmercury halides or acetates with sodium borodeuteride the intermediate 2-norbornyl radical is trapped from the toco-side predominantly. 

Most of the useful iodine transfer radical reactions arise from the addition of alkyl iodides, which have been activated by one or more adjacent carbonyl or nitrile substituents, to unactivated olefins. This both labilizes the initial iodide, facilitating chain initiation, and helps ensure that the atom transfer step is exothermic. The requisite iodides are typically synthesized by deprotonation with EDA or NaH, followed by iodination with I2 or A-iodosuccinimide. Cyclization of an iodoester yields primarily lactone product, proceeding through the intermediacy of the I-transfer products as shown in Scheme 5 [19]. Reactions in which a-iodoesters cyclized with alkynes also proved efficient. Similar ketones yielded less synthetically useful mixtures of cyclopentyl and cyclohexyl (arising from 6-endo transition states) products. 

The contribution of the transition state position is usually not discussed as a main factor in controlling the stereochemistry of a radical reaction. However, its importance was recently raised in several publications. Moreover, the reactivity-selectivity principle proposed by Giese to rationalize the influence of the radical trap on the stereochemical outcome of 2-substituted cyclopentyl radicals [39] could also be considered as an influence of the transition state position (Scheme 15) in early transition states (reactive olefins such as fumarodinitrile) the reagent is far away from the radical center and the face discrimination is low. With less reactive olefins such as styrene, a later transition state is occurring and the product stability starts to influence the stereoehemical outcome. Therefore, the most stable trans di-substituted cyclopentanes are produced with a higher degree of stereocontrol. 

The Arrhenius parameters for the reactions of cyclopentyl radicals with HI and I2 were obtained from kinetic data for the reverse reactions combined with thermodynamic estimates of the equilibrium constants. 

The year under review has seen a number of applications of e.s.r. spectroscopy to confirm the formation of radicals postulated in a variety of reactions. Thus, in the reaction of t-butoxyl radicals with triethyl phosphite in cyclopentane solution, both phosphoranyl radicals and cyclopentyl radicals were detected (Scheme 1). By comparison with... 

Ring opening in radicals 13 depends upon the value of n (Scheme 12). Radical 13 n = 0) can be observed by EPR at low temperatures but 13 (n = 1) rearranges to the 3-cyclopentyl radical too rapidly to be observed. Although at low temperatures 13 with n = 2-5 rearranges preferentially to the cycloalkenylmethyl radicals, chemical reactions at higher temperature indicate that both decomposition pathways occur for n = 2. Photochlorination of bicyclo[3.1.0]hexane with t-BuOCl at 70-85 °C produces only the... 

The next discussion concerns the formation of propylene, 1-butene and butadiene which are the other main primary products of the reaction. The hot allyl (or 4-pentenyl) radical generated in reaction 29 (or 30) may abstract hydrogen from ethylene to form propylene (or 1-pentene) and a vinyl radical. From the highly endothermic nature of the vinyl radical formation, the postulation of a hot radical is again reasonable in this step. A similar reaction of a cyclopentyl radical with ethylene, i.e., + C=C... 

C=C, was excluded from the whole scheme by the following reasons. Firstly, no cyclopentane was detected experimentally. Secondly, the cyclopentyl radical may have released its energy in the course of cyclization reaction, reaction 33. A hot 4-pentenyl radical itself may partly be quenched by reaction 36. 

Turning from 5 1 to a possible 5 2 process, it is observed that homolytic fission of a Co-C bond can be brought about by attack at the carbon atom by an alkyl radical. The thermal decomposition in CCI4 of hex-5-enyl(pyridine)cobaloxime and in particular its 5-methyl derivative leads to cyclopentyl products reaction (18) is though to occur (R = H or Me) ... 

Baldwin et al. used a radical-mediated ring expansion of 3-stannylcyclohexanones to provide efficient routes to cis-and trans-cyclononenones. Thus, bromo ketone 109 underwent a radical reaction to generate cyclopentyl aUcoxy radical 110. Fragmentation and elimination of a stannyl radical led to cyclononenone 111, which was further elaborated to rac-phoracantholide I (Scheme 25.52), originally isolated from the metastemal secretion of the eucalypt lon-gicom Phoracantha synonyma. 

It is worth mentioning that in a few cases the (3-elimination of the silyl radical from the a-silyl alkoxyl radical (47) with the formation of corresponding carbonyl derivative was observed [63,64]. Evidently the fate of a-silyl alkoxyl radical depends on the method of radical generation and/or the nature of the substrate. Two examples that delineate the potentialities of this rearrangements are reported in Reactions (5.33) and (5.34). In the former, the 5-exo cyclization of secondary alkyl radical on the carbonyl moiety followed by the radical Brook rearrangement afforded the cyclopentyl silyl ether [65], whereas Reaction (5.34) shows the treatment of an a-silyl alcohol with lead tetracetate to afford the mixed acetyl silyl acetal under mild conditions [63]. 

The reaction (equation 76) of the hexenyl radical 47 forming cyclopentyl-methyl radical was discovered independently in several laboratories and has been of pervasive utility in both synthetic and mechanistic studyThe competition between formation of cyclopentylcarbinyl and cyclohexyl radicals favors the former even though the latter is more stable, and this kinetic preference is explained by more favourable transition state interaction. The effects of substituents on the double bond, heteroatoms in the chain, and many other factors on the partitioning between these two paths have been examined. In the gas phase above 300°C, methylcyclopentane has been observed to form cyclohexane via isomerization of cyclopentylmethyl radicals into the more stable cyclohexyl radicals. ... 

The initial transient formed, rearranges in a reaction that involves the ring contraction step in reaction (74). The lifetime of this intermediate is considerably longer than that reported for any other intermediate with a copper(II)-carbon bond in aqueous solution (85-87,101,136), suggesting the stabilized structure featuring the metallocycle. This intermediate decomposes via heterolysis of one of the copper(II)-carbon -bonds followed by homolysis of the second to form the cyclopentyl-methanol radical in reactions (75) and (76), which reacts with Cu + to form the final product cyclopentanecarbaldehyde (89). 

After cyclization has taken place, the only reaction available to the cyclopentyl metiiyl radical is hydrogen abstraction. Thus it remains in solution until it reacts widi dibutyltin hydride to produce methylcyclopentane and a dibutyltin radical which continues die chain. 

Naito has also described analogous tandem radical addition-cyclization processes under iodine atom-transfer reaction conditions [16,32], Treatment of 186 with z-PrI (30 eq.) and triethylborane (3x3 eq.) in toluene at 100 °C gave, after cleavage from the resin, the desired lactam product 190 in 69% yield (Scheme 46). Similar reactions involving cyclohexyl iodide, cyclopentyl iodide, and butyl iodide were also reported as well as the reaction with ethyl radical from triethylborane [16,32], The relative stereochemistry of the products was not discussed. 

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