Mechanism, radical cyclopropane addition

The free radical chain mechanism of the addition reaction of bromodicyanomethane to alkenes has been corroborated by inhibition experiments with oxygen and t-butylcatechol. The mechanism of equation 66 has been postulated. The ring-closure of the 2-bromoalkylmalononitriles gives rise to mixtures of cis- and trans-cyclopropanes. 

In this paperthe relative stabilities of various small-ring propellanes are discussed in terms of enthalpies of hydrogenolysis of the conjoining bond and dissociation energies of this bond in the various substrates. This is perhaps the place to state that the mechanism of addition of bromine, in the dark, to the conjoining bond of several [m.n.l]propellanes, has been discussed in generaF. It is concluded that thermally initiated low temperature radical chain addition to the cyclopropane rings is involved. 

The possibility of a radical mechanism is supported by the observation of the accelerating effect of molecular oxygen on the cyclopropanation. Miyano et al. discovered that the addition of dioxygen accelerated the formation of the zinc carbenoid in the Furukawa procedure [24a, b]. The rate of this process was monitored by changes in the concentration of ethyl iodide, the by-product of reagent formation. Comparison of the reaction rate in the presence of oxygen with that in the... 

While a large number of studies have been reported for conjugate addition and Sn2 alkylation reactions, the mechanisms of many important organocopper-promoted reactions have not been discussed. These include substitution on sp carbons, acylation with acyl halides [168], additions to carbonyl compounds, oxidative couplings [169], nucleophilic opening of electrophilic cyclopropanes [170], and the Kocienski reaction [171]. The chemistry of organocopper(II) species has rarely been studied experimentally [172-174], nor theoretically, save for some trapping experiments on the reaction of alkyl radicals with Cu(I) species in aqueous solution [175]. 

In qualitative terms, the rearrangement reaction is considerably more efficient for the oxime acetate 107b than for the oxime ether 107a. As a result, the photochemical reactivity of the oxime acetates 109 and 110 was probed. Irradiation of 109 for 3 hr, under the same conditions used for 107, affords the cyclopropane 111 (25%) as a 1 2 mixture of Z.E isomers. Likewise, DCA-sensitized irradiation of 110 for 1 hr yields the cyclopropane derivative 112 (16%) and the dihydroisoxazole 113 (18%). It is unclear at this point how 113 arises in the SET-sensitized reaction of 110. However, this cyclization process is similar to that observed in our studies of the DCA-sensitized reaction of the 7,8-unsaturated oximes 114, which affords the 5,6-dihydro-4//-l,2-oxazines 115 [68]. A possible mechanism to justify the formation of 113 could involve intramolecular electrophilic addition to the alkene unit in 116 of the oxygen from the oxime localized radical-cation, followed by transfer of an acyl cation to any of the radical-anions present in the reaction medium. 

Free-radical additions to cyclopropanes have been studied much less, but it is known that Br2 and Cl2 add to cyclopropanes by a free-radical mechanism in the presence of uv light. The addition follows Markovnikov s rule, with the initial radical attacking the least-substituted carbon and the second group going to the most-substituted position. Several investigations have shown that the reaction is stereospecific at one carbon, taking place with inversion there, but nonstereospecific at the other carbon.130 A mechanism that accounts for this behavior is131... 

Cyclopentenes behave differently and often act through radical mechanisms this can lead to photoreduction to cyclopentanes, or photoaddition of the kind exemplified by norborneneand propan-2-ol 12.57). The photoadduct in this process is linked through the carbon atom of the alcohol, and not the oxygen atom. A related addition to acetonitrile 12.58) takes place when norbornene is irradiated in the presence of a silver(i) compound. It is likely thal a metal complex of the alkene is the real irradiation substrate, and the same may be true for copper(i)-promoted additions of haloalkanes to electron-deficient alkenes (2.59). When dichloromelhane is used in such a reaction the product can be reduced electrochemically to a cyclopropane (2.60), which is of value because the related thermal addition of CH.I, to alkenes in the presence of copper does not succeed with electron-poor compounds. 

When S( D) atoms react with C2H6, CgHg, iso-CgHio, cyclopropane, cyclobutane, or cyclopentane, only one type of product—the corresponding mercaptan—is detected in photolysis experiments with the mercury arc. Specific search in careful studies has failed to reveal the presence of any additional products in these systems. This fact can be taken as compelling evidence that in the mechanism of mercaptan formation, no free-radical species are involved. The only exception to this pattern is... 

A homolytic cyclopropane C-C bond rupture that would furnish in turn a 1,3-diradical is also conceivable. However, it is always difficult to establish whether a purely diradical or ionic mechanism is in operation. Between these two extremes there exists a graded continuum of polarized diradicals of which the zwitterion represents the end of the spectrum. In addition, the continuous development of radical character during the formation of the transition state of a homolytic bond scission, called the continuous diradical, has been postulated to explain the behavior of some reactions. Alternatively, the contribution of a truly concerted transformation cannot be overlooked. ... 

Many radical cations derived from cyclopropane (or cyclobutane) systems undergo bond formation with nucleophiles, typically neutralizing the positive charge and generating addition products via free-radical intermediates [140, 147). In one sense, these reactions are akin to the well known nucleophilic capture of carbocations, which is the second step of nucleophilic substitution via an Sn 1 mechanism. The capture of cyclopropane radical cations has the special feature that an sp -hybridized carbon center serves as an (intramolecular) leaving group, which changes the reaction, in essence, to a second-order substitution. Whereas the SnI reaction involves two electrons and an empty p-orbital and the Sn2 reaction occurs with redistribution of four electrons, the related radical cation reaction involves three electrons. 

Unsaturated groups, however, can shift by a two-step addition-fragmentation mechanism via a discrete cyclopropane radical intermediate. Phenyl groups are especially good at undergoing radical 1,2-shifts 1,2-shifts of acyl, alkenyl, and, to a lesser extent, alkynyl and cyano groups are also seen. 

Bromination of methylenecyclopropane with A -bromosuccinimide in dimethyl sulfoxide in the presence of water afforded different products depending on the ratio methylenecyclopropane/ Wbromosuccinimide and the amount of water available. Two equivalents of iV-bromosuc-cinimide predominantly gave l-bromo-l-(bromomethyl)cyclopropane (80%) in addition to some cyclobutanone (20%) derived from 1-(bromomethyl)cyclopropanol (Table 1, entry 7). With equimolar amounts of the alkene and AT-bromosuccinimide in aqueous solution (Table 1, entry 8), the bromohydrin, 1-bromo-l-hydroxymethylcyclopropane, was formed as the main product (70%).The reaction conditions suggest the addition of a positively charged bromine rather than a radical mechanism. 

Cyclopropanes without electron-withdrawing substituents usually resist the attack of nucleophiles. Exceptions are strained systems and a-halo-substituted derivatives which undergo homoallylic substitution reactions.[l.l.l]Propellane structures, though usually formed only as intermediates, underwent addition of benzenethiol with cleavage of the central cyclopropyl bond. This addition possibly follows a radical chain mechanism. 

Optically active l-halo-l-mefhyl-2,2-diphenylcyclopropanes 61 are used as probes to investigate the mechanisms of calcium reduction [39]. Treatment of 61 with calcium biphenyl (Ca(BPh)2) or calcium naphthalene (Ca(NPh)2) then addition of CO2 gives a mixture of cyclopropane derivative 62 and the corresponding carboxylic acid 63 (Scheme 4.17). Walborsky and Hamdouchi have provided evidence showing that these reactions occur by single electron transfer to yield free radicals... 

The synthesis of carbocyclic compounds from acyclic precursors can be accomplished by a sequence of radical reactions, where thiyl radicals act as catalysts. As an example, the generation of homoallyl radicals through the addition of phenyl-thiyl radical to the double bonds of vinyl cyclopropanes results in the multi-step synthesis of cyclopentanoids [62]. The mechanism is shown in Scheme 13. Feldman and coworkers have demonstrated that the success of this strategy is based on the coupling of vinyl cyclopropanes with the electronically complementary functionalized alkenes. A judicious choice of substituents R and X accelerates the rate limiting step (c). 

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