Cyclobutane ring dimerization

In the crystal of 1,4-dicinnamoylbenzene (1,4-DCB) (see Fig. 12), the distances between the intermolecular photoadductive carbons are 3.973 and 4.086 A for one cyclobutane ring, and 3.903 and 3.955 A for the other. The two topochemical pathways may occur competitively in a single crystal of 1,4-DCB at the initial stage of reaction. Then, both intramolecular photodimerization and intermolecular photopolymerization of the diolefinic mono-cyclobutane intermediate occur competitively to give tricyclic dimer 21,22,23,24-tetraphenyl-l,4,ll,14-tetraoxo-2(13),12(13-diethanol, [4.4] para-cyclophane or oligomers (Hasegawa et al., (1985). On photoirridation at room temperature the 1,4-DCB crystal gives >90% of the tricylic... 

Scheme 1 UV-light induced formation of the two major photo lesions in DNA. T=T cyclobutane pyrimidine dimer. (6-4)-photo product (6-4)-lesion, formed after ring opening of an oxetane intermediate, which is the product of a Paterno-Buchi reaction...

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... 

It may be suspected that the genuinely topotactic (as secured by the molecular precision of the AFM [18]) photodimerization of 2-benzyl-5-benzyli-denecyclopentanone [118] might be a good candidate for a quantitative preparative photo dimerization to give the head-to-tail anti-[2+2] dimer. Early quantitative solid-state [2-1-2] photodimerizations (most of the published mechanistic interpretations of which can no longer be accepted) are listed in [110]. These deal with the anti dimerization of acenaphthylene-1,2-dicarboxylic anhydride, the head-to-head syn dimerization of acenaphthylene-1-carboxylic acid, the syn dimerization of 5,6-dichloroacenaphthylene, and the thermally reversible head-to-tail anti dimerization of seven ( )-2,6-di-f-butyl-4-(2-aryl-ethenyl)pyrylium-trifluoromethanesulfonates. All of these reactions proceed fully specific. On the other hand, quantitative photoconversions of a 1 1 mixed crystal of ethyl and propyl a-cyano-4-[2-(4-pyridyl)ethenyl]cinnamates gives mixtures of diesters with one (A>410 nm) or two cyclobutane rings (no cutoff filter). 

The initial dimerization presumably leads to a [2.2.2]propellane derivative that undergoes thermolysis to the diene that is the observed product. The dimerization occurs in dilute solutions, but at higher concentrations, polymers are found. This finding is in accord with the proposal that these reactions occur via initial formation of a 1,4-diyl, which closes to form the cyclobutane ring. In this way, the reaction avoids an orbital symmetry disallowed pathway. The diyl could react with the alkene at higher concentrations to give a polymer. 

Allene ketene cycloadditions are of greater synthetic utility than cither mixed allene dimerization or mixed ketene dimerization. In this class of reaction the ketene is the more reactive species and homodimerization of ketene can be minimized by use of excess allene. Such cycloadditions always result in 2-alkylidenecyclobutanones with the sp carbons of both moieties forming the initial bond. In substituted allenes and ketenes, mixtures of stereoisomers of 2-alkylidenecyclobutanones are obtained with very little stereoselectivity, the stereoisomers arise from cisUrcins isomerism in the cyclobutane ring and EjZ isomerism of the exocyclic double bond. In unsymmetrically substituted allenes some regiochemical preference for ketene cycloaddition is observed. Examples of dimethylketene allene cycloadditions are summarized in Table 1,2... 

Among the catalysts used are Lewis acids991 and phosphine-nickel complexes.992 Certain of the reverse cyclobutane ring openings can also be catalytically induced (8-40). The role of the catalyst is not certain and may be different in each case. One possibility is that the presence of the catalyst causes a forbidden reaction to become allowed, through coordination of the catalyst to the -it or a bonds of the substrate.993 In such a case the reaction would of course be a concerted 2S + 2S process. However, the available evidence is more consistent with nonconcerted mechanisms involving metal-carbon a-bonded intermediates, at least in most cases.994 For example, such an intermediate was isolated in the dimerization of nor-bornadiene, catalyzed by iridium complexes.995... 

Cycloaddition is, in general, an effective way of generating cyclobutane rings. The lactone (304) is converted in this way on irradiation into both head-to-tail (305) and head-to-head (306) dimers.248 Direct irradiation of 5,7-dimethoxycoumarin in acetonitrile or benzene similarly affords the syn head-to-tail dimer via the singlet excited state, whereas... 

In the anti head-to-head dimer of thiocoumarin 70, the cyclobutane ring is puckered and the thiopyran rings adopt conformations between half-chair and twist-boat. Bond lengths and angles have been reported <1994AXC1922, 1995HCA1079>. 

One of the best-studied solid-state reactions is the photopolymerization of distyrylpyrazine (9) and related compounds to give crystalline polymers containing cyclobutane rings (Scheme 10). This reaction is reminiscent of Schmidt s early work on cinnamic acids, although the presence of two double bonds per monomer can lead to oligomeric or polymeric rather than solely dimeric products. The four-center reaction of 9, and other related polymerizations, have been reviewed in detail by Hasegawa, who has played a central role in the study of these systems... 

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.

Cycloadditions of fluorinated dienes are known to give cyclobutane rings. The original suggestion of the structure of the dimer of perfluoro-1,3-butadiene was perfluorotricyclo[4,2,0,02 5]octane [727]. The compound did not react with potassium permanganate. Fifteen years later, another formula was found correct based on physical methods. Instead of three four-membered rings, the product consists of three five-membered rings. Its name is perfluorotricyclo[3,3,0,02 6]octane [128],... 

Exposure of DNA to ultraviolet light induces a [2 + 2] cycloaddition reaction between the double bonds of adjacent thymines. The resulting thymine dimer, containing a cyclobutane ring, prevents DNA reproduction and can lead to the development of skin cancer. 

Bis(p-chlorostyryl)pyrazine (321) underwent self-condensation to the dicyclobutane dimer (322) in which (as shown by X-ray analysis) the pyrazine rings lay parallel on one side of the nearly coplanar cyclobutane rings and the benzene rings lay on the other side thereof [solid substrate suspended in H20,... 

All the photopolymerizable monomers discussed in this review contain two conjugated olefinic double bonds. Since the rr-electron conjugation of the monomer (A) is interrupted by the formation of a cyclobutane ring to produce a molecule larger than a dimer (B), the n-n electronic transition of B is shifted to a higher energy level than that of A. 

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