Intermolecular photocycloaddition

Intermolecular photocycloadditions of alkenes can be carried out by photosensitization with mercury or directly with short-wavelength light.179 Relatively little preparative use has been made of this reaction for simple alkenes. Dienes can be photosensitized using benzophenone, butane-2,3-dione, and acetophenone.180 The photodimerization of derivatives of cinnamic acid was among the earliest photochemical reactions to be studied.181 Good yields of dimers are obtained when irradiation is carried out in the crystalline state. In solution, cis-trans isomerization is the dominant reaction. 

The presence of Cu(I) salts promotes intermolecular photocycloaddition of simple alkenes. Copper(I) triflate is especially effective.182 It is believed that the photoreactive species is a 2 1 alkene Cu(I) complex in which the two alkene molecules are brought together prior to photoexcitation.183... 

The synthetic applications 440) and mechanistic aspects 4411 of intermolecular photocycloaddition reactions of arenes to olefins have been reviewed recently. Intramolecular cycloadditions442a,b) have been studied in the context of the photochemical behaviour of bichromophoric molecules, as to investigate interchromophoric interactions in polyfunctional molecules. Three types of addition products can be formed in the photocycloaddition of benzene to an alkene (4.37)441. ... 

The fact that all approaches employing the intermolecular photocycloaddition key step used the same precursor for the construction of the four-membered ring renders enone 6 the key intermediate of the different synthetic strategies. It is therefore sensible to compare first the different strategies to synthesize precursor 6. Afterwards, the different ways to complete the syntheses of kelsoene will be discussed. 

In conclusion, the three groups which applied the intermolecular photocycloaddition as the key step in their approach to kelsoene (1) reported different strategies to synthesize the irradiation precursor 6 in racemic or enantiomerically pure form. After the photocycloaddition step the syntheses of kelsoene were completed in different ways. The next section describes the different strategies employed in the second half of the way to kelsoene. 

Schuster s and Weedon s results support Bauslaugh s proposed mechanism that emphasizes the effect of the ratio between cyclization and the alternative fragmentation pathway of the diradical intermediate, on the regioselectivity in the intermolecular photocycloadditions, and propose not to consider the oriented 7r-complex (exciplex) as an intermediate in the mechanistic pathway of the [2 + 2] photocycloaddition of enones to alkenes. 

Prediction of the regioselectivity in the intermolecular photocycloaddition of enones to alkenes following this method provides similar results to those rationalized by the oriented -complex. However, it is in contrast with Weedon s previously discussed trapping results which indicate no selectivity in the first bond formation at the a- or /J-carbon positions in cyclic enones. 

The intermolecular photocycloaddition of alkenes to cyclic enones was found to afford cis- and trans-fused bicyclic systems. This stereoselectivity and the diastereofacial selectivity of chiral alkenes and/or enones is discussed below. 

Cis,anti,cis products are favored in the intermolecular photocycloaddition of cyclopentenones with cyclic alkenes87 (Scheme 34). However, intermolecular photoaddition of some cyclohexenones provided preferred /raw. -fused product as the major product with cyclic alkenes60. From the large number of examples presented in Schemes 37, 42, 43, 45, 46, 48 and other examples, it could be concluded that cis -fused products are usually preferred. 

Further studies, on the same principle, were carried out by Lange and coworkers on the intermolecular photocycloadditions of cyclohexenones 167 to alkene 168, possessing different chiral auxiliaries at the enone91 or alkene92. Diastereomeric mixtures of cis,anti,cis 169 and cis,syn,cis isomers were obtained in low to moderate diastereomeric excess (Scheme 37). 

In Table 5, the ortho adducts are collected, which have been reported to be formed by intermolecular photocycloaddition of benzene and derivatives of benzene to simple alkenes. Ortho photocycloadditions of alkenes to perfluorinated benzenes are separately collected in Table 6. Intramolecular ortho photocycloadditions have been grouped in Table 7. (The many intramolecular ortho photocycloadditions proceeding via the triplet state of the arene moiety are found in Table 4.) All adducts shown in the tables are the primary ortho adducts. Many of these bicyclo[4.2.0]octa-2,4-diene derivatives are, however, unstable and not all of... 

However, Kubo et al. found the unusual (3 + 2) intermolecular photocycloaddition of alkenes to the naphthalene ring at the 1,8-position. The same group also reported the (3 + 2) photocycloaddition of alkenes to phenanthrene ring at the 8,9-position. 

A phase-selective photochemical reaction of 2-pyridones is observed. Irradiation of 225 in benzene gives mainly rearrangement products 226, whereas, in the solid state, [4+4] photocycloaddition to the photodimer 227 occurred in quantitative yield (Scheme 39) <20040L683>. The stereochemistry of the photodimer was exclusively the trans- /+configuration, as shown. This is presumably due to Jt-rt-stacking and dipole-dipole interactions between the pyridones. Intermolecular photocycloaddition of 2-pyridone mixtures can be selective and lead to useful quantities of [4+4] cycloaddition cross-products <1999JOC950>. 

Ghosh, S., Raychaudhuri, S.R., and Salomon, R.G. (1987) Copper(I) catalysis of olefin photoreactions. 15. Synthesis of cyclobutanated butyrolactones via copper(I)-catalyzed intermolecular photocycloadditions of homoallyl vinyl or diallyl ethers. Journal of Organic Chemistry,... 

A recent example of intermolecular photocycloaddition between acephenanthrylene demonstrates the role of 7i-stacking [26], The singlet excited state gives only the cis dimer that the authors suggest arises from an excimer state. The triplet excited state results in formation of both cis and trans cyclobutanes. Interestingly, in the presence of oxygen the cis dimer is the only product due to quenching of the triplet excited state. 

Recent synthetic applications of intermolecular photocycloadditions have dealt with the question of chemoselective additions of alkenes to one (out of two) reactive excited double bonds (Sch. 25). In this context, it is of interest that 2,3-dimethylbut-2-ene adds selectively to benzodipyran 90 (affording 91) and thiopyranobenzopyran 92 to give 93, respectively [52,85]. 

Similarly, Cantrell observed intermolecular photocycloaddition of vinylogous imide 44 with cyclopentene on irradiation through Pyrex to give cyclobutane 45 (equation 13)30. 

Intermolecular photocycloaddition also occurs between alkenes and simple phenols. The swing from meta addition illustrated above in the [3 + 2]-mode to ortho-addition is a result of charge-transfer interactions between the alkene and the phenol and a greater charge transfer favours the ortto-addition mode. These aspects have been the subjects of reviews . This reaction mode is exemplified by the addition of acrylonitrile... 

In the host-guest complex of template 60 with substrate 61, the two enantio-faces of quinolone 61 are distinctly discriminated. As one of the enantiofaces of 61 is blocked by the benzotriazole moiety of 60, photochemical attack to the substrate is expected to occur from the open face. Indeed, in the presence of 60 and its enantiomer (ent-60), highly enantioselective intramolecular [2 + 2] photocycloaddition of allyl quinolonyl ether 62 [134] and intermolecular [2 + 2] photocycloaddition of quinolone 61 to alkenes 63 [135] were reported to occur in solution (Scheme 23). The intermolecular photocycloaddition of 63 to 61, as well as the intramolecular photocycloaddition of 62 proceeded with excellent enantioselectivities (81-98% ee) and in high yields (61-89%). 

Regiochemical and stereochemical control can be excellent in many examples of the intermolecular photochemical [2 + 2] cycloaddition, but the frequency of cases where selectivity is low, or worse, unpredictable, has inhibited the use of this powerful reaction. While the major disadvantage of the intermolecular photocycloaddition is its low selectivity in some systems, this problem can be substantially overcome by incorporating the two sites of unsaturation into Ae same molecule. Although many of the early examples of the [2 + 2] photocycloaddition were /nrromolecular, this variation of the reaction saw only limited use until the 1970s when its potential for the rapid construction of complex polycyclic carbon skeleta was recognized by Oppolzer, Pattenden and others. 

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