Cycloaddition photodimerization

Cycloadditions are in general an effective way of constructing cyclobutane rings. A wide variety of heterocyclic systems dimerize in this way. 1,3-Diacetylindole, for example, affords the head-to-tail dimer 242 on irradiation in ethanol.185 Ethyl 2-ethoxy-l,2-dihydroquinoline-l-carboxy-late is similarly converted in diethyl ether into the trans head-to-head dimer.186 Notable among many analogous photodimerizations are those reported in 1,4-dihydropyridines,187 in furo[3,2-b]pyridin-2(4//)-ones,188 in 8-methyl-s-triazolo[4,3-a]pyridine,189 and in 2H-2-benzazepine-1,3-diones.190 The [ 2 + 2] dimerization of amidopyrine is the first reported example of a photocycloaddition in a 4-pyrazolin-3-one.191... 

Cycloadditions, although relatively rare, are not unknown in heterocyclic systems. The first documented example was the photodimerization of pyrid-2-one a reinvestigation of this reaction has established that three other isomeric [ 4 + 4] dimers are formed in low yield in addition to the originally reported trans-anti dimer (264).215 Attempts to effect analogous cycloadditions in a series of l,T-polymethylenedipyrid-2-ones were unsuccessful, [ 2 + 2] and [ 4 + 2] additions being preferred.216 Thus,... 

This article will only discuss two particular kinds of photocycloaddition reactions, the photodimerization or cross-cycloaddition of two olefins to yield a cyclobutane derivative, and the photoreaction of an olefin with a carbonyl compound to give an oxetane, Eq. 1 and Eq. 2. The inportance of substituent effects in reactions of these types is pointed... 

As noted above, formation of a furan [4 + 3]-cycloadduct during irradiation of a 4-pyrone was advanced as evidence for the zwitterionic intermediate. This process can be moderately efficient (equation 4)68, and can be envisioned as an approach to substituted cyclooctanoids. Besides the formation of three new carbon-carbon bonds, an additional attractive feature is the complete diastereoselectivity, arising from a compact [4 + 3]-cycloaddition transition state with approach from the face opposite the epoxide. However, the generality of the intermolecular reaction is limited, as competing [2 + 21-photodimerization, solvent trapping and rearrangement often predominate58. 

H-stacking interactions have also been exploited to orientate olefinic moieties in a geometry suitable for photochemical cycloaddition reactions, and have been invoked by Coates et al. to explain the photodimerization and photopolymerization of mono- and diolefins carrying phenyl and perfiuorophenyl groups [43]. Matsumoto et al. reported the photodimerization of 2-pyridone in co-crystals with naphthalene-substituted monocarboxyhc acids, where the stacking of the naphthalene rings provides carbon-carbon distances appropriate for [4+4] cycloaddition [44]. 

Toda et al. reported that the topotactic and enantioselective photodimerization of coumarin and thiocoumarin takes place in single crystals without significant molecular rearrangements [49]. Molecular motion needs to be called upon to explain the photochemically activated cycloaddition reaction of 2-benzyl-5-benzylidenecyclopentanone. The dimer molecules, once formed, move smoothly in the reactant crystal to form the product crystal [50]. Harris et al. investigated the reactivity of 10-hydroxy-10,9-boroxophenanthrene in the solid state and the mechanism of the solid-state reaction was characterized by both X-ray diffraction and thermal analysis [51]. It was demonstrated that the solution chemistry of 10-hydroxy-10,9-boroxophenanthrene is different from that in the solid state, where it undergoes dimerization and dehydration to form a monohydride derivative. 

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... 

A great number of olefinic compounds are known to photodimerize in the crystalline state (1,2). Formation of a-truxillic and / -truxinic acids from two types of cinnamic acid crystals was interpreted by Bernstein and Quimby in 1943 to be a crystal lattice controlled reaction (5). In 1964 their hypothesis on cinnamic acid crystals was visualized by Schmidt and co-workers, who correlated the crystal structure of several olefin derivatives with photoreactivity and configuration of the products (4). In these olefinic crystals the potentially reactive double bonds are oriented in parallel to each other and are separated by approximately 4 A, favorable for [2+2] cycloaddition with minimal atomic and molecular motion. In general, the environment of olefinic double bonds in these crystals conforms to one of three principal types (a) the -type crystal, in which the double bonds of neighboring molecules make contact at a distance of -3.7 A across a center of symmetry to give a centrosymmetric dimer (1-dimer) (b) the / -type crystal, characterized by a lattice having one axial length of... 

Photolysis of 3-methylbenzo[6]thiophene 1-oxide in benzene results in [2+2] cycloaddition-dimerization. Both products (Scheme 191) result from head-to-head dimerization. The yield is increased on using benzophenone sensitization (78TL999). The photodimerization proceeds from a triplet state precursor (81JOC4258). 

Anthracene undergoes a photochemical 9,10,9, 10 -cycloaddition which goes through the excimer as intermediate. Many aromatic molecules follow similar cycloaddition paths. The close approach of the molecules in the excimer is essential for bond formation, and steric hindrance can prevent the reaction unsubstituted anthracene dimerizes so fast that no excimer fluorescence can be detected, 9,10-dimethylanthracene shows both excimer fluorescence and photodimerization, but 9,10-diphenylanthracene shows neither excimer emission nor photodimerization (Figure 4.52). 

The photodimerization of t-1 via a nonfluorescent singlet excimer is analogous to the behavior of anthracene (41,42). A possible explanation for the absence of excimer fluorescence is provided by the high limiting quantum yield for photodimeriza- tion (0.77 0.12) obtained from the intercept of a plot of versus [t-l] l according to eq. 9 (40). Excimer fluorescence is, in general, a slow process (< 1 x 10" s l), which evidently does not compete with cycloaddition in the exciplexes of t-1 or anthracene (42). 

Mechanistic investigations by Chapman and co-workers (99) indicated that these reactions occurred via a nonfluorescent singlet exciplex intermediate. While the rate constant for quenching of - -t5 by 2,3-dimethy 1-2-butene is slower than the rate of diffusion (Table 8), the limiting quantum yield for cycloaddition is 1.0. Thus, highly efficient exciplex cycloaddition may account for the absence of exciplex fluorescence, as in the case of t-1 photodimerization. Photochemical [2+2] cycloaddition reactions have also been observed to occur upon irradiation of the cyclic c-1 analogues diphenylcyclobutane (7) and diphenyl-vinylene carbonate (10) with 2,3-dimethyl-2-butene (96) however, the mechanistic aspects of these reactions have not been investigated. 

Intermolecular and intramolecular photocycloadditions to heterocyclic systems, including the photodimerization of individual heterocycles, are considered in this section. Two types of cycloaddition can readily be effected photochemically, namely [ 2 + 2] and [ 4 + 4],... 

The ability of a linear template to orient two identical pyridyl units in a face-to-face stacked arrangement suggested that a linear template might be used to assemble two unsymmetrical reactants for a head-to-head photodimerization. Since different combinations of hydrogen-bond acceptor sites may be employed for the reaction (i.e. I runs-1 -( -pyndyl)-2-(n/-pyridyl)e(hylene (where n,m =2, 3, or 4 n f m)), a general means to establish regiocontrol of the cycloaddition could be achieved. 

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. 

An interesting head-to-tail photodimerization of 2-phenylbenzoxazoles leading to a [2+2] cycloaddition to furnish 1,3-diazetidines 27 has been studied and the structures have been finally confirmed by X-ray analysis <1987CG578>. 

In an approach to a dihydrooritidine analogue, the intermolecular [2 + 2]-photo-cycloaddition of 2, 3 -0-isopropylideneuridine to chiral and achiral acrylates was found to be unsatisfactory both with respect to regio- and diastereoselectivity. The intramolecular approach was more successful, and uridine 143 produced selectively the single diastereomerically pure product 144. Due to concurrent photodimerization and polymerization reactions, however, the yield was only moderate (Scheme 6.50) [136]. 

Lewis, F.D. and Barancyk, S.V. (1989) Lewis Acid catalysis of photochemical reactions. 8. Photodimerization and cross-cycloaddition of coumarin. Journal of the American Chemical Society, 111, 8653-8661. 

The photodimerization of 2-pyridones is an efficient, regiospecific, and stereoselective [4+ 4]-cycloaddition [56] that converts two achiral aromatics into a highly functionalized tricyclic cyclooctadiene with four stereogenic centers (Scheme 9.34). For tethered pyridones, the trans isomer is usually the major product when one or both pyridine nitrogens are methylated. By contrast, in the unsubstituted systems,... 

The first such reaction published in 1908 by Ciamician and Silber was the light induced carvone —> carvonecamphor isomerization, corresponding to type b [1]. Between 1930 and 1960 some examples of photodimerizations (type c) of steroidal cyclohexenones and 3-alkylcyclohexenones were reported [2-5]. In 1964, Eaton and Cole accomplished the synthesis of cubane, wherein the key step is again a type b) photocycloisomerization [6]. The first examples of type a) reactions were the cyclopent-2-enone + cyclopentene photocycloaddition (Eaton, 1962) and then the photoaddition of cyclohex-2-enone to a variety of alkenes (Corey, 1964) [7,8]. Very soon thereafter the first reviews on photocycloaddition of a,(3-unsaturated ketones to alkenes appeared [9,10]. Finally, one early example of a type d) isomerization was communicated in 1981 [11]. This chapter will focus mainly on intermolecular enone + alkene cycloadditions, i.e., type a), reactions and also comprise some recent developments in the intramolecular, i.e., type b) cycloisomerizations. 

Recent reports detail a computational analysis of the photodimerization of 1,3-butadiene that located conical intersections for concerted [4+4] and [2+2] cycloaddition paths [19,20] and have correlated these results with the products observed experimentally [21]. 

Numerous photodimerization studies of 1,3-cyclohexadiene 36 have been reported (Sch. 9). Thermal cycloaddition yields a 4 1 mixture of endo/ exo [4+2] adducts 37 and 38 in modest yield. Irradiation of the diene in cyclohexane near its 2max of 254 nm yields very little dimer, but irradiation at 313 nm leads to a mixture of dimers, favoring the [2+2] adducts 39 [37]. The use of y-radiation produces similar mixtures [38,39]. A triplet sensitizer leads to largely the [2+2] adducts plus exo 38 and little of the endo [4+2] isomer 37 [40]. When the photochemistry is conducted in the presence of the electron acceptors anthracene 41, LiC104-42 or pyrylium 43, only [4+2]... 

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