Cycloaddition reactions diradical

Steady-state approximation product ratios. The cycloaddition reaction between ben-zyne and cis-1,2-dichloroethene proceeds to a mixture of cis and trans products according to the following scheme, in which the two diradicals are steady-state intermediates 37... 

It must be emphasized once again that the rules apply only to cycloaddition reactions that take place by cyclic mechanisms, that is, where two s bonds are formed (or broken) at about the same time. The rule does not apply to cases where one bond is clearly formed (or broken) before the other. It must further be emphasized that the fact that the thermal Diels-Alder reaction (mechanism a) is allowed by the principle of conservation of orbital symmetry does not constitute proof that any given Diels-Alder reaction proceeds by this mechanism. The principle merely says the mechanism is allowed, not that it must go by this pathway. However, the principle does say that thermal 2 + 2 cycloadditions in which the molecules assume a face-to-face geometry cannot take place by a cyclic mechanism because their activation energies would be too high (however, see below). As we shall see (15-49), such reactions largely occur by two-step mechanisms. Similarly. 2 + 4 photochemical cycloadditions are also known, but the fact that they are not stereospecific indicates that they also take place by the two-step diradical mechanism (mechanism... 

The substitution of the exo-methylene hydrogen atoms of MCP with halogens seems to favor the [2 + 2] cycloaddition reaction by stabilizing the intermediate diradical. Indeed, chloromethylenecyclopropane (96) reacts with acrylonitrile (519) to give a diastereomeric mixture of spirohexanes in good yield (Table 41, entry 2) [27], but was unreactive towards styrene and ds-stilbene. Anyway, it reacted with dienes (2,3-dimethylbutadiene, cyclopentadiene, cyc-lohexadiene, furan) exclusively in a [4 + 2] fashion (see Sect. 2.1.1) [27], while its... 

Exciplexesn6,nl) can be formed if the excitation energy B - B is higher than the one for A -> A in (1.8). Such an excited complex is associative in the excited state only, the corresponding ground state complex between A and B being dissociative (Fig. 9). Such exciplexes are important intermediates in e.g. cycloaddition reactions as precursors of diradicals 118) which are themselves precursors of the cyclized photoproducts. 

Cycloaddition reactions (see Table I) involving unsaturated carbohydrates are regio- and stereo-selective. These selectivities can be understood by assuming that the photochemical interaction between the two 7r-systems results in formation of the more stable 1,4-diradical. The reaction between 3,4,6-tri-O-acetyl-D-glucal (1) and acetone pro-... 

Cycloaddition reactions between alkenes and noncarbohydrate, carbonyl compounds have been described in discussing the reactions of alkenes (see Table I and Scheme 1). The depiction of the excited carbonyl given in Scheme 6 is useful in understanding the regiochem-istry of the cycloaddition process, as it suggests that the electron-deficient oxygen atom in the excited carbonyl will react with the alkene to produce the (more-stable) 1,4-diradical. Table VIII lists cycloaddition reactions in which the excited carbonyl is part of a carbohydrate. 

The cycloaddition reaction of dipoles has been known since the late eighteenth century however, before Huisgeris introduction of the concept of a 1,3-dipole, these reactions were considered to proceed via a diradical mechanism [16]. One of the earhest examples of metal-catalyzed 1,3-dipole formation involved the controlled decomposition of an a-dia-... 

The complete stereoselectivity of the reaction, however, is difficult to reconcile with a two-step process. This earlier controversy, however, has long since been resolved. For example, when considering results of the cycloaddition of p-nitrobenzonitrile oxide with cis- and trani-l,2-dideuterioethylene (111), the experiments clearly established that, within experimental limits of detection, the reaction is > 98% stereoselective. If diradical intermediates were operative, significant scrambling of configuration should be observed in the products. These and other results confirm a concerted mechanism for the 1,3-dipolar cycloaddition reaction (15). 

If the motion had been disrotatory, this would still have been evidence for a cyclic mechanism. If the mechanism were a diradical or some other kind of noncyclic process, it is likely that no stereospecificity of either kind would have been observed. The reverse reaction is also conrotatory. In contrast, the photochemical cyclobutene—1,3-diene interconversion is disrotatory in either direction.368 On the other hand, the cyclohexadiene—1,3,5-triene interconversion shows precisely the opposite behavior. The thermal process is disrotatory, while the photochemical process is conrotatory (in either direction). These startling results are a consequence of the symmetry rules mentioned in Chapter 15 (p. 846).Vl,As in the case of cycloaddition reactions, we will use the frontier-orbital and Mdbius-HQckel approaches.37"... 

An alternative two-step mechanism involving a spin-paired diradical intermediate has also been considered for 1,3-cycloadditions.18,68,69 However, ab initio calculations70-72 on a wide variety of 1,3-dipoles and dipolarophiles are found to coincide essentially with a synchronous 1,3-cycloaddition mechanism.15,17 On the other hand, a two-step mechanism passing through two transition states separated by an intermediate has been derived using the MINDO/3 method, and found to be compatible with substituent and solvent effects as well as stereospecificity observed in 1,3-cycloadditions.73 However, several factors beyond FMO interactions, such as closed shell repulsions, geometrical distortions, polarization, and secondary orbital interactions, all influence mechanisms, rates, and regioselectivities in cycloaddition reactions.74... 

Olefins are also susceptible to cycloaddition reactions (Fig 105) (150). In particular, some olefin-containing APIs can dimerize with another molecule of API to form a 2+2 cycloaddition product under photo conditions (151). A classic example of such a 2+2 cycloaddition catalyzed by UV radiation is that of the nucleoside thymidine (Fig. 106) (152,153). These reactions are proposed to go through more than one mechanism concerted, diradical, electron transfer, and radical ion pairs. 

The stereochemical results are consistent with a 1,4-diradical intermediate such as 63 with a lifetime sufficiently long to permit loss of stereochemistry by rotation for the cycloaddition reaction. At most, however, the same diradical can be an intermediate in only a portion of the ene reaction. 

The lack of stereospecificity in the cycloaddition reaction and the partial stereospecificity in the ene reaction (Table 3) indicate that at least a portion of the ene reaction occurs via a reaction pathway different from the pathway leading to cycloadducts. A probable intermediate in the pathway to cycloadducts is a long-lived diradical such as 63 which randomizes olefin stereochemistry. The long-lived diradical may also be an intermediate in the stereorandom component of the ene reaction. 

From organic chemistry it is known that cycloaddition reactions leading to cyclobutanes are required to be stepwise reactions, according to the Woodward-Hoffmann rules [131]. A bond is formed between the two olefins, leading to a tetramethylene intermediate (T). In a subsequent step, the second bond is formed, yielding the cycloadduct. Depending on the reactants, either zwitterionic or diradical tetramethylenes can be proposed as intermediates [132, 133]. 

The cycloaddition reactions of captodative olefins all are considered to proceed through the intermediacy of a 1,4-diradical, due to the captodative stabilization of the terminal radicals. In cross-cycloadditions captodative olefins easily give cyclobutanes when heated with fluoroolefins [141]. They also react with allenes to give methylenecyclobutanes [142], and with methylenecyclopropane to give spiro[2.3]hexanes [143]. 

We now propose that the diradical intermediates in the cycloaddition reactions of captodative olefins are also the initiators in the observed spontaneous polymerizations of these olefins. Tail-to-tail combination of captodative olefins are expected to provide a low but constant concentration of diradicals, which are capable of initiation. Whether or not polymerization ensues must depend on the experimental conditions, propagation equilibria and rates. 

The most important competing process to the bond-formation is the complete electron transfer to form ion-radicals, which occurs where no bond formation is possible, for example, for aromatic donor-acceptor pairs. For vinyl copolymerizable pairs, the bond will form between the components to give a diradical tetramethylene. For the ionic homopolymerization system, on the other hand, it is difficult to distinguish the ion-radicals from zwitterionic tetramethylenes by the kinetic analysis. In this case, the accompanying cycloaddition reaction offers powerful evidence for the zwitterion formation, i.e., the bond-formation. 

Cycloaddition reactions of a,p-unsaturated carbonyl compounds to olefins have been studied in detail. Cyclic enones, undergo rapid and efficient intersystem crossing thereby providing easy access to the triplet state through direct excitation. The following cycloaddition reaction is proposed to involve a diradical intermediate formed directly or from an exciplex [102, 103] (see (29)). 

The reaction pathway has been rationalized in terms of an attack of the triplet oxygen at the 5-position of (76) to produce the diradical (77) which may add to a second molecule of (76). The resulting peroxide (78) fragments to the dithiobenzoic acid derivative (79) which may act as a dipolarophile in the last step of the [3 + 2] cycloaddition reaction of (76). The structure of the final product (80) was established by X-ray analysis (81CB285). 

The present chapter is dedicated to the cycloaddition reactions of enamines, which include transformations that, independently of the mechanism, create a new ring1. The cycloadditions may proceed via a concerted mechanism (following Woodward-Hoff-mann rules) or a two-step mechanism which may involve zwitterionic or diradical intermediates. Due to their low ionization potentials and asymmetric molecular orbital... 

Examples of 1,3-dipoles include diazoalkanes, nitrones, carbonyl ylides and fulminic acid. Organic chemists typically describe 1,3-dipolar cycloaddition reactions [15] in terms of four out-of-plane 71 electrons from the dipole and two from the dipolarophile. Consequently, most of the interest in the electronic structure of 1,3-dipoles has been concentrated on the distribution of the four Jt electrons over the three heavy atom centres. Of course, a characteristic feature of this class of molecules is that it presents awkward problems for classical valence theories a conventional fashion of representing such systems invokes resonance between a number of zwitterionic and diradical structures [16-19]. Much has been written on the amount of diradical character, with widely differing estimates of the relative weights of the different bonding schemes. 

Due to the electrophilic character of carbenes, they are not expected to easily react with electron-poor alkenes, and the only reported examples concern reactions with diazo compounds (i.e., diazomethane, 56 157 diazofluorenc.158 ethyl diazoacetate,159 and phenyldiazomethane160). However, depending on the reaction conditions, carbenes arc not always the reactive species. Cyclopropanes are often obtained by decomposition of pyrazolines which arise from 1,3-dipolar cycloaddition reactions (see Section 2.1.1.6.2.3.1.). Even when reactions are performed under irradiation, pyrazolines can be obtained as the result of a diradical addition.156... 

Cyclobutanes may be converted to alkenes thermally, the reverse of the [2 + 2] cycloaddition reaction. These retroaddition or cycloreversion reactions have important synthetic applications and offer further insights into the chemical behavior of the 1,4-diradical intermediates involved they may proceed to product alkenes or collapse to starting material with loss of stereochemistry. Both observations are readily accommodated by the diradical mechanism. Generation of 1,4-tetramethylene diradicals in other ways, such as from cyclic diazo precursors, results in formation of both alkenes and cyclobutanes, with stereochemical details consistent with kinetically competitive bond rotations before the diradical gives cyclobutanes or alkenes. From the tetraalkyl-substituted systems (5) and (6), cyclobutane products are formed with very high retention stereospecificity,while the diradicals generated from the azo precursors (7) and (8) lead to alkene and cyclobutane products with some loss of stereochemical definition. ... 

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