Meta benzene-alkene cycloaddition

Remarkable also is the related case of the meta benzene-alkene cycloaddition. Here again, mixtures are formed, but at least when the alkene moiety is tethered to the benzene ring and a preferred conformation exists, regio-selective processes have been found where several new stereocentres are formed in a single step and in a rigorously controlled way—and thus are synthetically highly valued (see Scheme 2.5) [15]. 

To have a rough idea of the potential of the method, please have a look to the syntheses below that are among those considered typical in a recent book (Scheme 1). These are a cyclization to hydroxycyclobutane via H-abstraction, a 2 + 2 alkene cycloaddition, a "meta" benzene-olefin cycloaddition, and a dye sensitized addition of singlet oxygen." Please consider whether there are facile thermal alternatives to these straightforward photochemical reactions. 

The irradiation of benzenes with alkenes provides a fascinating array of photochemical reactions, not least because it converts the aromatic substrates into polycyclic, non-aromatic products. In principle, benzene can undergo reaction across the 1,2-(ortho). 1,3-(meta), or 1,4-(para) positions the 1,3-cycloaddition is structurally the most complex, but it is the predominant mode of reaction for many of the simplest benzene/alkene systems. The products are tricyclic compounds with a fusion of two five-membered rings and one three-membered ring, and an example is the reaction of benzene with vinyl acetate (3.411. For monosubstituted benzenes there can be a high... 

The photochemistry of benzene is in contrast to ground state chemistry and provides a full exploitation in synthetic applications, which is thermally not possible. The addition of an alkenes, dienes, alkynes, amines, alcohols or carboxylic acids to benzene, can occur across the ortho-, meta-, and para-positions to give three distinct products. The addition of alkene gives ortho-, meta- and paro-cycloadditions. All the addition are streospecific with respect to alkene component. 

Cycloaddition of alkenes to the benzene ring does not occur when both molecules are in their ground electronic states. The reaction can only be brought about by photoexcitation of either of the two addends. Three types of photochemical cycloaddition of alkenes to benzene and its derivatives are presently known. Ortho photocycloaddition, also referred to as 1,2-photocycloaddition or [2 + 2] photocycloaddition, leads to bicyclo[4.2.0]octa-2,4-dienes. Meta photocycloaddition, also referred to as 1,3-photocycloaddition or [2 + 3] photocycloaddition, gives triyclo[3.3.0.02 8]oct-3-enes, also named l,2,2a,2b,4a,4b-hexahydrocyclo-propa[crf]pcn(alcnes. Para photocycloaddition, also referred to as 1,4-photocy-cloaddition or [2 + 4] photocycloaddition, results in bicyclo[2.2.2]octa-2,5-... 

The ortho cycloaddition is thermally forbidden in a suprafacial-suprafacial manner and the photochemical reaction is forbidden with S benzene and ground-state alkene. On the basis of these considerations, it could be understood that the ortho addition had only been observed with systems where the alkene is the lowest excited singlet species (as with maleimides [37,74,75] or where either the alkene or the arene has marked acceptor properties (the only examples known at that time were benzene-acrylonitrile [127] and benzonitrile + a mono-olefin [1,73], Benzene-acrylonitrile and benzonitrile-olefin systems do not display charge-transfer absorption, but charge transfer could well follow excitation. Bryce-Smith further stated that irradiation of benzene in the presence of simple mono-olefins normally provides B2u (Si) benzene as the lowest excited singlet species, which leads to meta rather than ortho addition, but the latter process might, in principle, be able to occur under conditions where a Biu (S2) state of benzene is populated. 

A variety of four-membered ring compounds can be obtained with photochemical reactions of aromatic compounds, mainly with the [2 + 2] (ortho) photocycloaddition of alkenes. In the case of aromatic compounds of the benzene type, this reaction is often in competition with the [3 + 2] (meta) cycloaddition, and less frequently with the [4 + 2] (para) cycloaddition (Scheme 5.7) [38-40]. When the aromatic reaction partner is electronically excited, both reactions can occur at the 7t7t singlet state, but only the [2 + 2] addition can also proceed at the %% triplet state. Such competition was also discussed in the context of redox potentials of the reaction partners [17]. Most frequently, it is the electron-active substituents on the aromatic partner and the alkene which direct the reactivity. The [2 + 2] photocycloaddition is strongly favored when electron-withdrawing substituents are present in the substrates. In such a reaction, crotononitrile 34 was added to anisole 33 (Scheme 5.8, reaction 15) [41 ], and only one regioisomer (35) was obtained in good yield. In this transformation, the... 

The competition of ortho and meta photocycloaddition is much more expressed when the mesomeric effects of the substituents are weak [30,31]. A more precise analysis of the products revealed that ortho and even para side products are formed in minor amounts in cases were normally the meta cycloaddition should be observed as dominant reaction [32]. Bichro-mophroric substrates carrying electron donor substituents on the benzene ring and any electron active groups on the alkene moiety range in this category [15,31,33]. 

In contrast to the major developments in the use of [3C + 2C] and [SC + 2C] cycloadditions based on the arene-alkene meta cycloaddition, relatively less is known about the use of the meta cycloaddition as a means to achieve [3C + 4C] and [SC -i- 4C] connections. Nevertheless, these processes have great potential, provided that the factors determining their selectivity could be elucidated. For example, benzene and diene (176) (equation 16) undergo cycloaddition to furnish a [3C + 4C] (or [SC + 4C]) cycloadduct (177) and a [4C + 4C] cycloadduct (178). Cleavage of the former adduct as in the aforementioned cases would provide access to seven- or nine-membered rings. While most dienes react with arenes to give [4C + 4C] cycloadducts, the range of dienes and arenes studied thus far is too limited to rule out the development of [3C -i- 4C] and [SC -i- 4C] cycloadditions as useful synthetic processes. 

The photoreactions of acyclic and cyclic alkenes with benzene depend on the ionization potential of the alkene relative to that of benzene, In general meta cycloaddition to give tricyclo[3.3.0.0 ]oct-3-ene derivatives occurs to some degree in every case and often predominates. ortho Cycloaddition tends mostly to occur with alkenes of lower ionization potential than benzene and gives bicyclo[4.2.0]octa-2,4-diene derivatives para cycloaddition gives bi-cyclo[2.2.2]octa-2,5-diene derivatives to a smaller extent. 

Simple alkenes which have been observed to undergo meta cycloaddition to benzene to give three-membered rings from ring contractions, sometimes in high chemical and quantum yields, are (Z)- and ( )-but-2-ene, cyclobutene, 2,3-dimethylcyclobutene. methylenecy-clobutane, 2,3-dichlorocyclobutene, bicyclo[3.2.0] hepta-2,6-diene, 8,9,10-trinorborn-2-ene (but not 8,9,10-trinorborna-2,5-diene"), 5,6-dichloro-8,9,10-trinorborn-2-ene, cyclo-... 

Intramolecular analogs from the meta cycloaddition of benzene with alkenes are known. Thus, irradiation of 6-phenylhex-2-ene yielded two adducts 4 and 5 in equal amounts from the (Z)-... 

Some years ago Cornelisse reported that deuteration of alkyl benzenes results in a deuterium isotope effect upon the quantum yield of the meta photocycloaddition reaction with alkenes. In a new report the same group has published an analysis describing how the observed isotope effect upon the reaction quantvun yield can be ascribed to a kinetic deuterium isotope effect on the excited state reaction and distinguished from an effect upon the unimolecular photophysical modes of decay of the excited state. In addition, it is reported that when the quantum yield of meta photocycloaddition of cyclopentene to alkyl benzenes is measured using a mixture of deuterated and non-deuterated benzenes, the quantum yield is arene concentration dependent.The authors argue that this arises from competition between cycloaddition and the formation of mixed excimers between deuterated and non-deuterated alkyl benzenes which dissociate to yield excited deuterated alkyl benzene and ground state non-deuterated alkyl benzene preferentially. 

However, they do provide an explanation for the preferred endo mode of cycloaddition for those alkenes giving meta adducts. Most c/.v-disubstitutcd alkenes like cyclopentene1159 give substantially more endo adduct 8.134 than exo 8.135. Because of the good HOMO/ HOMO and LUMO/ LUMO match with simple alkenes, there will be two sets of secondary orbital interactions to consider. One 8.136 will be between the HOMO of the doubly X-substituted alkene, crudely modelled by i >3 of butadiene, and ip 2 of benzene, and the other 8.137 will be between the LUMO of the alkene, modelled by ip4 of butadiene, and ip5 of benzene. In both cases the secondary overlap is in favour of the endo mode of cycloaddition.1157... 

In contrast to the preferred meta mode of intramolecular photoaddition of 5-phenyl-l-pentenes, where the alkene and benzene groups are separated by three atoms, irradiation of the styrene (64) yields a single stereoisomer of the ortho adduct (65). In (64), not only are the reacting units separated by 4 atoms, but also it is the styrene rather than the benzene which is excited. Comparable photoreactivity is seen for phenanthrene-styrene systems such as (66) which yield 2+2 adducts (67) along with products derived from competing Paterno-Btichi reaction of the ester carbonyl with the alkene side chain. The photochemical cycloaddition also proceeds in an intermolecular fashion between the ester of 9-phenanthrene carboxylic acid and para-methoxy-0-methylstyrene. The mechanism of this reaction is shown to involve addition of the styrene to the singlet excited state of the phenanthrene derivative. °... 

The photocycloaddition of ethene and benzene has been studied by CAS-SCF computation using the 6-3IG basis set for energies and 4-3IG orbitals for structural minimization. The structure of the Cl is shown in Figure 12.24. The ortho and meta cycloaddition processes proceed through alternate electron-pairing schemes from a single Cl without barriers. For unsubstituted alkenes, the meta Cl is lower in energy than the ortho, whereas the ortho Cl is stabilized by alkenes with ERG and EWG substituents. Product compositions tend to reflect these differences. ... 

Photoirradiation of benzene and its derivatives with alkenes give ortho-, meta-, para-cycloaddition products. In most cases, either meta- or orr/io-adducts are obtained as major products [5]. Bryce-Smith and Gilbert suggested a prefulvene type diradical intermediate mechanism (Path A) for the weta-adduct [6], whereas Morrison and Srinivasan groups [7, 8] proposed the exciplex mechanism (Path B) for the formation of these adducts (Scheme 9.1). The exciplex intermediates undergo photo-induced electron transfer processes between donor (D) and acceptor (A) to produce radical ion pairs as intermediates, stabilized by coulombic interactions to give adducts [9]. 

Ortho-cycloaddition takes place with a olefin which has low ionization potential in comparison to benzene where polar nature of reaction overpowers the symmetry imposed barrier to this reaction. Polar nature of ortho-cyclo-addition is supported by the fact that in case of doner substituted ethylenes, reaction is promoted by polar solvent, but in meta-addition no solvent effect is there, o-and p-photocycloadditions are disallowed to occur as concerted addition between of benzene and Sq of alkene until mixing of charge-transfer states occurs. 

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