Radicals photocycloaddition

If the triplet energy of the carbonyl compound is below that of the diene, triplet-triplet transfer will become inefficient and photocycloaddition may occur. For example, the triplet energy of 1,4-benzo-quinone is about 50 kcal mole - V41 and photocycloaddition to dienes can indeed occur.42 The products are spiro-pyrans 13 (not vinyl oxetanes), which may arise via the allylic radical intermediate 12. 

The photocycloaddition of carbonyl compounds to unsymmetrical olefins (electron rich) can give two products however, usually one predominates. For example, the photocycloaddition of benzophenone to isobutylene gives a mixture of the two oxetanes 30 and 31 in the ratio of 9 1.17 This ratio is consistent with the preferential formation and/or closure of the intermediate 30a relative to 31a. The diradical 30a is more stable than 3la since a tertiary radical is more stable than a primary radical by about 8 kcal.62 Many of the examples listed in Section VII are consistent with this apparent generalization there are, however, exceptions. 

The photocycloaddition of benzaldehyde to cyclohexene (p. 309) afforded a moderate yield of the oxetane along with the radical coupling products.17,37 Compare this result with the photocycloaddition of benzophenone to cyclohexene where the oxetane was a minor product.17,66 This indicates that the kaiijkabs is higher for benzaldehyde than for benzophenone. 

Photocycloadditions of higher order than 2 + 2) are sometimes encountered, but they are not so general as the (2 +2) reactions. Often they arise in reactions that occur by way of radical cations 2.83), when electrophilic attack on an aromatic ring may divert the reaction from cyclobutane formation, or in those that are promoted... 

The overall course of reaction depends on the relative rate constants for the various secondary radical processes. Aliphatic ketones are often photoreduced to secondary alcohols (4.121, but although there are interesting features in the stereochemistry of the reduction, the method is not a worthwhile alternative to thermal reduction using hydride reagents, except in cases where the substrate is sensitive to basic conditions. Photoaddition of methanol is promoted in the presence of titaniurnfiv) chloride, both for acyclic and cyclic (4.33) ketones the titanium involvement probably starts in the early steps of the reaction, but the detailed mechanism is not known. Addition may also be a major pathway when cyclohexene is used as hydrogen source (4.341 unlike many other simple alkenes, cydohexene does not readily give oxetanes by photocycloaddition (see p. 126). 

The Paterno-Biichi photocycloaddition to glycals occurs with a total regioselectivity according to the stability of the supposed intermediate radicals. Acetone in presence... 

A schematic representation of the possible processes in arene-olefin photocycloaddition according to Leismann et al. [182] is given in Scheme 35. Increasing charge separation in the exciplex, caused by decreasing ionization potentials of the olefins, can lead to zwitterionic intermediates, which are able to form ortho adducts. Increasing solvent polarity can reduce the formation of adducts by propagating the formation of radical ion pairs. The possibility that the ortho adduct may be formed directly or via a different short-lived intermediate was not incorporated in the scheme. 

Photocycloaddition and photoaddition can be utilized for new carbon-carbon and carbon-heteroatom bond formation under mild conditions from synthetic viewpoints. In last three decades, a large number of these photoreactions between electron-donating and electron-accepting molecules have been appeared and discussed in the literature, reviews, and books [1-10]. In these photoreactions, a variety of reactive intermediates such as excimers, exciplexes, triplexes, radical ion pairs, and free-radical ions have been postulated and some of them have been detected as transient species to understand the reaction mechanism. Most of reactive species in solution have been already characterized by laser flash photolysis techniques, but still the prediction for the photochemical process is hard to visualize. In preparative organic photochemistry, the dilemma that the transient species including emission are hardly observed in the reaction system giving high chemical yields remains in most cases [11,12]. 

The reactive species generated by the photoexcitation of organic molecules in the electron-donor-acceptor systems are well established in last three decades as shown in Scheme 1. The reactivity of an exciplex and radical ion species is discussed in the following sections. The structure-reactivity relationship for the exciplexes, which possess infinite lifetimes and often emit their own fluorescence, has been shown in some selected regioselective and stereoselective photocycloadditions. However, the exciplex emission is often absent or too weak to be identified although the exciplexes are postulated in many photocycloadditions [11,12], The different reactivities among the contact radical ion pairs (polar exciplexes), solvent-separated radical ion pairs, and free-radical ions as ionic species... 

We will discuss briefly the reactive species such as an exciplex and radical ion species generated by the excitation of organic molecules in the electron-donor (D)-acceptor (A) system. An exciplex is produced usually in nonpolar solvents by an interaction of an electronically excited molecule D (or A ) with a ground-state molecule A (or D). It is often postulated as an important intermediate in the photocycloaddition between D and A. In the case of D = A, an excimer is formed as an excited reactive species to cause photodimerization. In some cases, a ter-molecular interaction of an exciplex with another D or A generates a triplex, which is also a reactive intermediate for photocycloaddition. The evidence for the formation of excimers, exciplexes, and triplexes are shown in the fluorescence quenching. Excimer and exciplex emission is, in some cases, observed and an emission of triplex rarely appears. 

Farid et al. reported the formation of two types of (4 + 2) photocycloadduct of 9,10-dicyanoanthracene (DCA) with 3-carbomethoxy-l,2-diphenylpropene [192,193], The product ratio depends on the solvent polarity. In benzene, exo-125 is selectively obtained via exciplex (Scheme 38). In acetonitrile, endo-125 is obtained as a sole product via the radical ion pair. Photochemical reactions of DCA with 1,2-diarylcyclopropanes gave (4 + 3) cycloadducts [194,195], In degassed acetonitrile solution, (4 + 3) photocycloaddition occurred to give cis and trans cycloadducts in a 3 1 ratio in good chemical yields, although the quantum yields... 

The photochemical addition of cyclic 1,3-diones such as dimedone, 1,3-cylohexandione 62, or their respective silyl enol ethers leads to the formation of two fused furanylfullerenes, (1) achiral 63 and (2) chiral 64 [244], The latter having an unusual bis-[6,5] closed structure. In the initial step of this reaction, [2 + 2] photocycloaddition across a [6,6] bond to form cyclobutanols or the corresponding TMS ethers is involved (Scheme 26). Oxidation with 02 yields in the formation of the radical 65a. Cleavage to 66a followed by cyclization gives furanyl radical 67a. H abstraction by 102 or a peroxy radical finally leads to product 63. In competition, formation of fullerene triplets by absorption of a... 

A PET reaction between excess phthalimide (in equilibrium with its conjugate base) and an alkene led to a clean phthalimidation of nonactivated double bonds. Here, the singlet excited state of phthalimide acts as the oxidant and a radical ion pair is formed. The olefin cation radical is trapped by the phthalimide anion, and back electron transfer, followed by protonation, affords the photoaddition products [40], Protected phenethylamines are readily accessible in this way. This reaction has been carried out by using NaOH as the base it has been shown that the amounts (usually equimolar with the alkene) must be carefully chosen in order to avoid the undesired competition with [2 + 2] photocycloaddition. 

A [2 + 2] photocycloaddition with two alkenes can also be induced by photochemical electron transfer [16,17]. In such cases, sensitizers are frequently used and the reactions therefore occur under photocatalysis [18]. Under photochemical electron transfer (PET) conditions, the diene 10 yielded in an intramolecular reaction the cyclobutane 11 (Scheme 5.2) [19], such that in this reaction a 12-membered cyclic polyether is built up. The reaction starts with excitation of the sensitizer 1,4-dicyanonaphthalene (DCN) only 0.1 equivalents of the sensitizer are added to the reaction mixture. Electron transfer occurs from the substrate 10 to the excited sensitizer, leading to the radical cation I. This intermediate then undergoes cycli-zation to the radical cation of the cyclobutane (II). Electron transfer from the radical anion of the sensitizer to the intermediate II leads to the final product 11, and regenerates the sensitizer. In some cases, for example the cydodimerization of N-vinylcarbazole, the effidency is particularly high because a chain mechanism is involved [20]. 

Substrates A3 (Q = O) have been employed not only as starting materials for fragmentation reactions but also to probe novel stereoselectivity concepts. The photochemical transformation of axial chirality into central chirality was achieved by Carreira et al., who employed chiral, enantiomerically pure allenes in intramolecular [2 + 2]-photocycloaddition reactions (Scheme 6.27) [79]. The reaction of enantiomerically pure (99% ee) cyclohexenone 71, for example, yielded the two diastereomeric products 72a and 72b, which differed only in the double bond configuration. Apparently, the chiral control element directs the attack at the allene to its re face. The double bond isomerization is due to the known configurational liability of the vinyl radical formed as intermediate after the first C—Cbond formation step (see Scheme 6.2, intermediate C). 

Recent interest in the use of N-unsubstituted 2-quinolones stems from the fact, that they coordinate effectively to chiral lactam-based templates via two hydrogen bonds. The prototypical template to be used in photochemical reactions is compound 115, which can be readily prepared from Kemp s triacid [108]. The template is transparent at a wavelength X > 290 nm, and can be nicely used in stoichiometric amounts for enantioselective photochemical and radical reactions [109]. Conditions which favor hydrogen bonding (nonpolar solvent, low temperature) are required to achieve an efficient association of a given substrate. The intramolecular [2 + 2]-photocycloaddition of 4-alkylquinolone 114 proceeded in the presence of 115 with excellent enantioselectivity, and delivered product 116 as the exclusive stereoisomer (Scheme 6.41) [110]. Application of the enantiomer ent-115 ofcomplexing agent 115 to the reaction 111 —> 112 depicted in Scheme 6.40 enabled enantioselective access to (+ )-meloscine [111]. 

Copper(I) catalysis is very well established to promote intramolecular [2+2] photocycloaddition reactions of l,n-dienes (review [351]). The methodology recently enjoyed a number of applications [352-354], It is assumed that CuOTf, which is commonly applied as the catalyst, coordinates the diene and in this way mediates a preorganization. The Ghosh group recently reported a number of CuOTf-catalyzed photochemical [2+2] cycloaddition reactions, in which an organocopper radical complex was proposed as a cyclization intermediate (which should, however, have a formal Cu(II) oxidation state) (selected references [355-357]). A radical complex must, however, not be invoked, since the process may either proceed by a [2+2] photocycloaddition in the coordination sphere of copper without changing the oxidation state or according to a cycloisomerization/reductive elimination process. 

Bach and coworkers investigated the photocycloaddition of 7V-acyl, 7V-alkyl enamines 125 with benzaldehyde [125]. The 3-amido oxetanes 126 were formed with excellent regioselectivity (analogous to reactions with enolethers—vide supra) and good diastereoselectivity (Sch. 41). Enamines, not deactivated by acylation at the nitrogen atom are poor substrates for Paterno-Buchi reactions due to preferred electron transfer reactivity (formation of the corresponding enamine radical cation and subsequent reactions). 

Scheme 2 Photocycloaddition via radical/cation and radical/anion pathway.

---