Meta-photocycloaddition

The intramolecular [5 + 2] cycloaddition mode has been studied extensively. The chemistry bears a remarkable similarity to the arene-olefin meta-photocycloaddition [53] reaction (e.g. 114... 

The bicyclic enone 665 (see Scheme IX) has been utilized as a precursor to hirsu-tene The mold metabolite has also been attained in clever fashion from 666 using meta-photocycloaddition methodology... 

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-... 

Meta photocycloaddition was discovered simultaneously and independently by two groups in 1966. Wilzbach and Kaplan [4] found that the adducts from m-but-2-ene, cyclopentene, and 2,3-dimethylbut-2-ene with benzene are substituted tricyclo 3.3.0.02X]oct-3-enes. The adducts were formed by irradiation of solutions (-10%) of the olefins in benzene, at room temperature under nitrogen, with 2537-A light. Bryce-Smith et al. [5] subjected an equimolar mixture of m-cyclooctene at room temperature or in the solid phase at 60°C to ultraviolet radiation of wavelength 235-285 nm. A mixture of 1 1 adducts was obtained from which the main component (-85%) was readily obtained pure by treatment of the mixture with methanolic mercuric acetate. This 1 1 adduct proved to be a meta photocycloadduct (Scheme 2). The minor nonaromatic adduct (10-15%) could, at that time, not yet be obtained completely free from the meta photocycloadduct the structure of a rearranged ortho adduct was provisionally assigned to this isomer. 

Para photocycloaddition of arenes to the benzene ring was first reported in 1971 by Wilzbach and Kaplan [7] as a minor process accompanying ortho and meta photocycloaddition. Since that time, relatively few cases of para photocycloaddition have been described. Para adducts were found as minor products from benzene with cyclobutene [8], ra- 3,4 - dimethyIcycIobu(ene [9], vinylene carbonate [10], 2,3-dihydropyran [11,12], and 1,3-dioxole [13,14] and from a,a,a-tri-fluorotoluene with vinylene carbonate [15], Intermolecular para photocycloadducts were major products from the irradiations of benzene and allene [16,17], benzene and cyclonona-1,2-diene [16,17], and from fluorobenzene and cyclopentene [18], Intramolecular para photocycloadducts were found as major products from the irradiations of phenethyl vinyl ether [19-21] (Scheme 3) and 2,3-dimethyl-6-phenylhex-2-ene [22], No detailed mechanistic investigations have been published. 

Scheme 3 Para and meta photocycloaddition of phenethyl vinyl ether ippara = 0.23, cpmeta = 0.006. (From Ref. 20.)...

In 1977, Scharf and Mattay [123] found that benzene undergoes ortho as well as meta photocycloaddition with 2,2-dimethyl-1,3-dioxole and, subsequently, Leismann et al. [179,180] reported that they had observed exciplex fluorescence from solutions in acetonitrile of benzene with 2,2-dimethyl-l,3-dioxole, 2-methyl-l,3-dioxole, 1,3-dioxole, 1,4-dioxene, and (Z)-2,2,7,7-tetram-ethyl-3,6-dioxa-2,7-disilaoct-4-ene. The wavelength of maximum emission was around 390 nm. In cyclohexane, no exciplex emission could be detected. No obvious correlation could be found among the ionization potentials of the alkenes, the Stern-Volmer constants of quenching of benzene fluorescence, and the fluorescence emission energies of the exciplexes. Therefore, the observed exciplexes were characterized as weak exciplexes with dipole-dipole rather than charge-transfer stabilization. Such exciplexes have been designated as mixed excimers by Weller [181],... 

F. Empirical Rules Ortho Versus Meta Photocycloaddition... 

On the basis of these observations, Bryce-Smith et al. [115] introduced a rule stating that for addition to benzene, Pmeta when 9.6 eV < IP (alkene) <8.65 eV. They concluded that if this rule is correct, ortho addition of ethylenes to Si benzene necessarily involves an element of charge transfer to or from the ethylene. Indeed, a marked effect of polar solvents (methanol or acetonitrile) in promoting the ortho addition of benzene to ethyl vinyl ether and tetramethylethene was observed (portho increased by 20-50%, whereas cpmeta was unaffected. One exception to this rule was found by Heine and Hartmann [10], who discovered that vinylene carbonate (IP = 10.08 eV) undergoes mainly meta photocycloaddition to benzene, accompanied by some para addition. Bryce-Smith and Gilbert [46] commented that their rule referred to quantum yields and not chemical yields, whereas no quantum yields were given for the vinylene carbonate additions. Moreover, quantum yield measurements should be made at low conversions because most ortho cycloadducts are photolabile. 

Intermolecular meta photocycloaddition of cycloalkenes to benzene rings occurs with marked endo stereoselectivity, although the exo process would be favored on purely steric grounds. Because of intramolecular anomalous stereoselectivity, the exo process is often feasible [55] (Scheme 55). 

In recent investigations about the intramolecular meto-addition processes, the effects of heteroatoms in the linking chains are obvious. Blakemore and Gilbert reported the photoreaction of 185 linked by the amide group [240], Pho-toinduced intramolecular electron transfer can be inhibited by /V-acetyl or N-car-bomethoxy groups. Fluorescence is then observed from the arene chromophore and intramolecular meta photocycloaddition occurs through high selectivity. 

Blakemore and Gilbert found that the SiMe2 unit induces high selectivity in the meta photocycloaddition [241], Irradiation (254 nm) of the silicon-tethered bichromophore 186 gives only one photoisomer 187 in 60% yield (Scheme 56). The ability of silicon to stabilize a (3-positive center acts to stabilize the developing positive charge in the ipso carbon hence, the photocycloaddition directs to the 2,6-position of the benzene ring rather than the 1,3-addition. 

To prevent the meta photocycloaddition, the use of rigid face-to-face skeletons is also an effective strategy. Acetone-sensitized excitation of 208 gave only 209 reversibly [262-264] reactions of 210 and 211 gave similar results [265,266] (Scheme 61). X-ray analysis of 210 showed the distance of the aromatic carbons which react is 3.04 A [263],... 

Chappell, D. and Russell, A.T. (2006) From a-cedrene to crinipellin B and onward 25 years of the alkene-arene meta-photocycloaddition reaction in natural product synthesis. Organic tg Biomolecular Chemistry, 4 (24), 4409-4430. 

Blakemore, D.C. and Gilbert, A. (1995) Heteroatom control of isomer formation in the intramolecular meta photocycloaddition of arene-ethene bichromo-phores. Tetrahedron Letters, 36 (13), 2307-2310. 

De Keukeleire, D., Bako, P., and Van der Eycken, E. (2000) Intramolecular ortho and meta photocycloadditions of 4-phenoxybut-l-enes substituted in the arene residue with carbomethoxy, carbomethoxymethyl, and 2-carbo-methoxyethyl groups. Journal of Photochemistry and Photobiology A Chemistry, 133, 135-146 (c) Wender, P.A. and Dore, T.M. (1995) Intra and inter-molecular cycloadditions of benzene derivatives, in CRC Handbook of Organic Photochemistry and Photobiology (eds W.M. Horspool and P-.S. Song), CRC Press, Boca Raton, pp. 280-290. 

Boyd, J.W., Greaves, N., Kettle, J., Russell, A.T., and Steed, J.W. (2005) Alkene-Arene meta photocycloadditions with a four-carbon-atom tetheu efficient approach toward the polycyclic ring systems of aphidicolin and stemodinone. Angewandte Chemie, International Edition, 44, 944—946. 

The last two chapters by Hoffmann and Ramamurthy deal with a collection of photochemical reactions with arenes, the ortho-, meta- and para photocycloadditions and with a conceptually exciting concept in organic photochemistry, the use of contrained media. Retigeranic acid (16, by formal asymmetric synthesis) was synthesized via a fabulous reaction sequence involving an intramolecular meta photocycloaddition as key step [16]. 

While the meta photocycloaddition occurs at the n,n singlet state of the arene [4], different cases must be distinguished for the ortho cycloaddition depending on the structure of the substrates [5] (a) excitation of a ground state charge-transfer complex (b) excitation of the alkene (or alkyne) reaction partner (c) excitation of the arene partner and reaction at the singlet state and (d) excitation of the arene followed by intersystem crossing and reaction with the alkene at the triplet state. 

At the singlet excited state, ortho and meta photocycloadditions are often competitive processes and physicochemical investigations were carried out to rationalize the modes of cycloaddition of arenes with alkenes. In the context of the study of photochemical electron transfer reactions, it has been proposed that the difference of the redox potentials of the reaction partners might play an important role in this competition [10]. Such a discussion involves the intervention of an exciplex as intermediate. The Rehm-Weller equation [11] was used to quantify the relationship. When an electron transfer process is strongly endergonic (AG>1.5eV), the meta cycloaddition should be favored. When such a process is less endergonic (1 < AG< 1.5 eY), the ortho addition dominate [12]. This means that the... 

Recent results revealed that the ortho photocycloaddition frequently occurs concomitantly with the meta photocycloaddition even in cases where only meta derivatives are obtained. Especially in the case or electron-donor substituted benzene derivatives, the competitive ortho cycloaddition is less stereo- or regioselective and the resulting products are less stable. Aside the meta adducts as main products, complex mixtures of ortho products or products resulting from rearrangements of these primary photoproducts have been obtained [15,16], Improved separation techniques recently enabled a better characterization of these products. Furthermore, using particular conditions like an acidic reaction medium, the intermediates resulting from ortho photocycloaddition could be transformed selectively in more stable final products [17]. 

The meta photocycloaddition is frequently observed in cases of alkyl or electron-donor substituted benzene derivatives. Two exo/endo isomeres 2a,b are obtained in high yields in the reaction of anisole 1 with cyclopentene (Sch. 2) [18]. The reaction was also efficiently carried out in an intramolecular way. Two efficient reactions of this type are depicted in Sch. 2. The azatriquinane 3 [19] and the silane derivative 4 [20] were obtained in high yields. The formation of different regioisomers can be controlled by the heteroatoms in the side chain. The longer C-Si bonds particularly favor the formation of compound 4. 

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]. 

Among the variety of terpenes which were synthesized with an intramolecular meta photocycloaddition as key step, triquinane derivatives were particularly well studied. Two isomers of these compounds are readily accessible via intramolecular meta cycloaddition in position 1,3 (Sch. 9). The following cyclopropanation reaction of intermediate O controls which of the angular or linear isomers is formed (Sch. 17) [67]. As this step is almost always unselective, both isomers are concomitantly formed. However, one of the isomers can be obtained predominantly via an additional photochemical equilibration step (compare Sch. 11). The triquinane frame is obtained by rupture of the distant C-C bond of the cyclopropane in connection to the 10-membered ring moiety. 

Eycken and coworkers [121] employed ji-CDx as a chiral template for asymmetric induction in the intramolecular meta-photocycloaddition [126,127] of 4-phenoxy-1-butenes 48 and 50 in the solid state. (Scheme 19.)... 

The photochemical transformations of vinylcyclopropanes are of mechanistic interest, but because of the high energy of the reaction intermediates, especially in the triplet manifold, practical applications are scarce. The regio- and stereo-selective aspects are, however, similar to those of the thermal processes. Additional methods that provide for the cyclopentene rearrangement involve the degenerate photochemical rearrangements observed by Wender during meta-photocycloaddition of arenes and alkenes and utilized extensively in the synthesis of triquinane sesquiterpenes. -" -" (See Section 8.1.9 or ref. 41 for a recent summary.)... 

The meta photocycloaddition of cis-cyclooctene to benzene was one of the first examples of this reaction reported, and the addition of this cycloalkene to low molecular weight polystyrene and mono- and di-aromatic model-compounds has now been described. The results were analysed by mass spectroscopy, and it was reptorted that for polymers having up to six styrene units, more than one phenyl group in each chain had reacted. In the 2 1... 

Wender and co-workers have continued their elegant use of the meta photocycloaddition of ethylenes to arenes as the key step in the synthesis of several naturally occurring compounds. The major product from irradiation of benzene and vinyl acetate is the 1-endo acetate of (36), and using this as the starting material, the total synthesis of the ant defensive secretion, isoiridomyrmecin (50), has been accomplished in seven further steps." There... 

Yamamura has extensively explored the intramolecular [5 - - 2]-cycloaddition mode. This chemistry bears a remarkable similarity to the so-called arene olefin meta-photocycloaddition [64] reaction (e.g., 267 to 268) that has frequently been used in the synthesis of complex bioactive natural products. While different intermediates are involved, the photo-and electrochemical reactions provide access to many of the same basic ring systems. This is nicely demonstrated by comparing key steps and the outcome of an electrochemical approach to the total synthesis of pentalene (53) [65] and a photochemical pathway that ultimately led to cedrene (compare equations 48 and 49). 

The intramolecular (4n + 4ti) photoaddition of furan-pyran-2-one bichromo-phores [e.g. (38) to give (39)] is potentially useful as an approach towards the fusicoccane/ophiobolane skeleton (Chase et al.), and the formation of (40) from the irradiation of (41) constitutes the first example of a (47t + 4ji) photocycloaddition of an enone to the benzene ring (Kishikawa et al.). Wender et al. continue to report elegant new applications of the intramolecular meta photocycloaddition of 5-phenylpent-l-ene derivatives and have described the synthesis of cis,cis,cis, traMi-[5,5,5,5]-fenestrane (42) using the photoreaction of (43) as a key step. Park... 

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