Cyclobutane-Forming Photodimerizations

Simple olefins can photodimerize to cyclobutanes in the presence of cuprous salts as sensitizers (4.20) 423 . Copper (I) trifluoromethanesulfonate has been utilized successfully (4.21) 424). 

Stilbene-like olefins can be irradiated directly to afford cyclodimers 

Cyclic a,P-enones photodimerize via the Tt-state, as in (4.23)426) and (4.24)427). By chosing the appropriate substituents the reactions proceed regio- and stereoselectively. In contrast, pyrimidine bases dimerize from the first excited singlet state to afford head to tail products (4.25) 428). 

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Unusual heterocyclic systems can be obtained by photodimerizations and for five-membered heterocycles with two or more heteroatoms such dimerizations need be effected on their ring-fused derivatives. Cyclobutanes are usually obtained as in the photodimerization of the s-triazolo[4,3-a]pyridine (540) to the head-to-head dimer (541). These thermally labile photodimers were formed by dimerization of the 5,6-double bond in one molecule with the 7,8-double bond in another (77T1247). Irradiation of the bis( 1,2,4-triazolo[4,3-a]pyridyl)ethane (542) at 300 nm gave the CK0ifused cyclobutane dimer (543). At 254 nm the cage-like structure (544) was formed (77T1253). 

The second example is an intermolecular crystal-state reaction. Cross-conjugated 1,5-disubstituted 1,4-dien-3-ones in solution undergo both cis-trans photoisomerization and photodimerization, yielding complex mixtures of products, including die all-trans-substituted cyclobutane 2 in the case of 1,5-diphenyl-1,4-pentadien-3-one. In contrast, dienones such as 3a in whose crystals adjacent molecules lie parallel and strongly overlapped react in the solid to give 3b as the sole photoproduct. This isomerically pure tricyclic diketone results, formally, from an eight-center dimerization. It is not formed in the reaction in solution, and could be prepared by other methods only with considerable difficulty (4). 

In a fluid environment the photodimerization of thymine and its derivatives involves cycloaddition at the 5,6-double bond to form one or more of the four possible stereoisomers of the cyclobutane dimer shown... 

Photodimerization behavior of 4-formyl-, 3,4-dichloro-, and several other cinnamic acid derivatives is greatly influenced by other molecules outside of the crystal (9,10). For example, 4-formylcinnamic acid 1 crystallizes in two modifications, photoreactive and photostable forms. The photoreactive crystals of 1 (mp 249 °C), on photoirradiation at room temperature in the presence of even a trace of moisture, dimerize to crystalline dimer 2 containing one molecule of water. The continuous change of the x-ray diffraction pattern during the photodimerization indicates a typical crystal-to-crystal transformation process. On the other hand, the same crystal 1 photodimerizes into amorphous dimer 2 in the absence of water. The same cyclobutane derivative is produced in very high yield in both reactions. However, highly crystalline dimer 2 is obtained only by the photodimerization of 1 in the presence of water and is not regenerated by any attempted recrystallization procedures from various aqueous solutions of 2. 

It should be noted here that thymine photodimerization may occur by a non-concerted mechanism, involving free radical intermediates. Indeed, photoproducts other than cis-syn dimer, such as the next most abundant thymine dimer, so-called 6 4 adduct, were observed in irradiated DNA. However, the quantum yield of cis-syn photodimer formation (r/j 0.02) is more than an order of magnitude higher than that of the 6 4 adduct ( 0.0013) which in turn is an order of magnitude higher than the quantum yields for other thymine isomers [68]. This specificity can lead to the conclusion that the thymine photodimerization occurs predominantly via concerted 2 + 2 cycloaddition mechanism. A time-resolved study of thymine dimer formation demonstrated that thymine cyclobutane dimers are formed on a timescale of less than 200 nsec, while the 6 4 adduct is formed on a timescale of few milliseconds [69]. The delay in the formation of the latter was attributed to the mechanism of its formation through a reactive intermediate. 

The intramolecular photodimerization and [2 + 2]-photocycloaddition in DNA involves thymine or cytosine as the chromophore. This chemistry has been intensively investigated with regards to DNA damage and repair [131]. Despite the fact that the area is of continuous interest [132], the synthetic applications are limited and are not covered here in detail. However, some preparative aspects of 4-pyrimidinone photocycloaddition chemistry will be addressed. Aitken et al. have prepared a plethora of constrained cyclobutane P-amino acids by intra- or intermolecular [2 + 2]-photocycloaddition to uracil and its derivatives [133, 134]. In a chiral adaptation of this method, the uracil-derived enone 140 was employed to prepare the diastereomeric cyclobutanes 141 in very good yield (Scheme 6.49). The compounds are easily separated and were - despite the relatively low auxiliary-induced diastereoselectivity - well suited to prepare the as-2-aminocyclobutanecarboxylic acids 142 in enantiomerically pure form. Enantioselective access to the corresponding trans-products was feasible by epimerization in a-position to the carboxyl group [135],... 

The (Z) isomer (189) of 4-benzylidene-2-phenyl-5(4//)-oxazolone rearranges to the (E) form on irradiation. The photodimerization of compound (190) in solution results in the centrosymmetric cyclobutane derivative (191). A different kind of photodimerization occurs when the oxazolone (192) is irradiated in the solid state, compound (193) being formed (79TL2461, 79TL3139). 

Fig. 8. Photodimerization in o-ethoxy cinnamic acid Two centrosymmetric molecules of the a-form before (full lines) and after (dashed lines) the reaction. Hydrogen atoms other than the hydroxyl are omitted for the sake of clarity. The cinnamoyl double bonds are spaced at —4.3 A and following the cycloaddition, a new pair of bonds is formed which are slightly longer (—1.57 A) than typical C-C bonds. The inset shows the deformation density (at 0.075 ek 3) in the plane of the cyclobutane ring in the a-dimer.

An interesting conversion of a bis(styrene) crown precursor was reported recently <2001MI35>. The [2+21-photodimerization of 16 was found to occur in solution to afford a cyclobutane-containing crown ether. The reaction product was formed only in 10% yield when irradiated at >280 nm in aqueous base solution. However, when 7-cyclodextrin was present, the hydrophobic styryl residues were apparently confined within its interior cavity and the yield rose to 39%. A similar reaction was performed to afford the diaza-18-crown-6 derived cryptand. In the latter case, cyclization failed in the absence of the cyclodextrin (Figure 18). 

The use of crystal-to-crystal [2+2] photodimerizations as a means to construct crystalline polymers has been pioneered by Hasegawa and co-workers [32]. To construct the polymers, reactants with two double bonds in the form of 1,4-divinyl-benzenes, such as methyl 4-[2-(4-pyridyl)ethenyl]cinnamate (Scheme 2.3.2) were employed [33]. One-dimensional chains composed of repeat units of cyclobutane... 

In studies where cholesteric phase order appears to influence the course of bimolecular reactions, solute diffusion and collisional orientations appear to be affected by solvent anisotropy. An example is the stereoselective photodimerization of 1,3-dlmethylthymine(24). While all four possible cis-fused cyclobutane photodimers are produced in isotropic solutions and disordered glasses, the cis-syn dimer is formed almost exclusively in liquid-crystalline media. Furthermore, selectivity of reaction products in the mesophases is greatly decreased upon addition of an isotropic diluent which disturbs local solvent order (e.g., dioxane or DMSO). Since all of the... 

The photodimerization of cinnamic derivatives to form cyclobutane structures is a very well-known photochemical reaction. 

Stilbene and its derivatives, which had been widely investigated in CDs and CAs, can be included in CB[8] cavity to form 2 1 complexes. Two ( )-diaminostilbene dihydrochloride 68 (Scheme 1.13) can insert into CB[8] cavity to give a 2 1 host-guest complex which has a good solubility in water. Photoirradiation of the complex gave [2-h2] photodimerization product la,2o,3)3,4)3-telrakis(4-aminophenyl)cyclobutane 69 as major product, along with a trace amount of la,2)3,3a,4j8-tetrakis(4-aminophenyl)cyclobutane 70. No formation of the isomerization product (Z)-68 was observed, which is significantly different from the photoreaction of ( )-68 in the absence of CB[8]. The stereoselectivity of photodimerization in the presence of CB[8] (synlanti = 95/5) is much better than that obtained with y-CD (synlanti = 80/20). 

Another interesting photochemical reaction that occurs with the monolayers is dimerization. This is exempUfled by the photochemical behaviour of the SAM of 7-(10-thiodecoxy)coumarin (52) on polycrystaUine gold. Irradiation at 350 nm results in the (2 -f 2)-cycloaddition of the coumarin moieties. The photodimerization is a reversible process by irradiating at 254 nm. Better regioselectivity in the cycloaddition is obtained when the solid monolayer is irradiated rather than when it is in contact with benzene. The dimer formed is the yn-head-to-head dimer identified as 53 . Self-assembled monolayers of cis- and frani-4-cyano-4 -(10-thiodecoxy)stilbene (54) are also photochemically reactive. Irradiation of a thin film in benzene solution using A, > 350 nm results in the formation of a photostationary state with 80% of the cis-isomer present. Irradiation in the solid shows that cis.trans isomerism occurs but that trans.cis-isomerism fails. Prolonged irradiation brings about (2 - - 2)-cycloaddition of the stilbene units to afford cyclobutane adducts. Such dimerization is a well established process . The influence of irradiation at 254 nm or 350 nm of self-assembled monolayers of 10-thiodecyl 2-anthryl ether on polycrystaUine... 

Fig. 12.B3 The photodimerization of thymine bases to form either (a) a cyclobutane-thymine dimer or (b) a 6,4 photoproduct.

Alkenes are well-established to be able to undergo [2+2] photodimerization reactions in the solid state if the double bonds are close enough together, and this can happen in coordination networks. Lang and coworkers showed that both silver and cadmium coordination polymers containing tra v-l,2-bis(4-pyridyl)ethylene (bpe) can undergo photodimerization, in the latter case in a SC-SC transformation. Vittal and coworkers showed that compounds such as [Zn(bpe)(bdc)] formed interpenetrated three-dimensional (3D) networks with the double bonds from the two networks <4 A apart. Following UV irradiation, the compounds were converted into the cyclobutane derivatives in SCSC transformations (equation 15). ... 

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