Cyclobutane adducts

Irradiation of a benzene solution of (267) containing a sixfold excess of l-acetoxybut-l-en-3-one leads to the formation of the two cyclobutane adducts [(278) 47% yield of converted starting material] and [(279) 20% yield], and the acetylcyclobutene [(280) 9 % yield]. The mode of formation of the product (280) is not yet established unambiguously, although it is not formed during workup. 

Fluorinaied dienophiles. Although ethylene reacts with butadiene to give a 99 98% yield of a Diels-Alder adduct [63], tetrattuoroethylene and 1,1-dichloro-2,2-difluoroethylene prefer to react with 1,3-butadiene via a [2+2] pathway to form almost exclusively cyclobutane adducts [61, 64] (equation 61). This obvious difference in the behavior of hydrocarbon ethylenes and fluorocarbon ethylenes is believed to result not from a lack of reactivity of the latter species toward [2+4] cycloadditions but rather from the fact that the rate of nonconcerted cyclobutane formation is greatly enhanced [65]... 

The reaction of methyl or ethyl acrylate with the enamine of an alicyclic ketone results in simple alkylation when the temperature is allowed to rise uncontrolled in the reaction mixture (7,34,35). If the reaction mixture is kept below 30°C, however, a mixture of the simple alkylated and cyclobutane (from 1,2 cycloaddition) products are obtained (34). Upon distillation of this mixture only starting material and simple alkylated product is obtained because of the instability of the cyclobutane adduct. 

In a similar manner diethyl maleate (actually diethyl fumarate since the basic enamine catalyzes the maleate s isomerization upon contact) forms unstable 1,2 cycloadducts with enamines with hydrogens at temperatures below 30°C (37). At higher temperatures simple alkylated products are formed (41). Enamines with no )3 hydrogens form very stable 1,2 cycloadducts with diethyl maleate (36,37,41). The two adjacent carboethoxy groups of the cyclobutane adduct have been shown to be Irons to one another (36,37). 

It was later noted that at low temperatures cyclobutane adduct 48 is formed from this reaction mixture, but as the temperature is increased, the adduct reverts back to starting material and also forms some of simple... 

Nitroolefins also offer the possibilities of 1,2 cycloaddition (37,57) or simple alkylation (57-59) products when they are allowed to react with enamines. The reaction of nitroethylene with the morpholine enamine of cyclohexanone led primarily to a cyclobutane adduct in nonpolar solvents and to a simple alkylated product in polar solvents (57). These products are evidently formed from kinetically controlled reactions since they cannot be converted to the other product under the conditions in which the other... 

The reaction between the pyrrolidine enamine of butyraldehyde (52) and )3-nitrostyrene (53) provides cyclobutane adduct 54 quantitatively in either petroleum ether or acetonitrile solvent, but in the more polar ethanol solvent a 2 1 condensation product occurred. The structure of the product was shown to be 55 (57). 

Methyl vinyl sulfone forms 1,2-cycloaddition adducts with aldehydic enamines, both with and without 3 hydrogens (37). Simple alkylation was reported to take place when phenyl vinyl sulfone was allowed to react with cyclohexanone enamines (58,60), but it has recently been shown that phenyl vinyl sulfone also forms cyclobutane adducts (60a). 

Many if not most furanocoumarln derivatives possess potent photoactive properties. It is generally accepted that the biological actions of furanocoumarins are attributable to the fact that these compounds easily intercalate into the double helix of DNA, where they produce cyclobutane adducts with... 

Psoralens must be photoactivated by long-wavelength ultraviolet light in the range of 320-400 nm (ultraviolet A [UVA]) to produce a beneficial effect. Psoralens intercalate with DNA and, with subsequent UVA irradiation, cyclobutane adducts are formed with pyrimidine bases. Both monofunctional and bifunctional adducts may be formed, the latter causing interstrand cross-links. These DNA photoproducts may inhibit DNA synthesis. The major long-term risks of psoralen photochemotherapy are cataracts and skin cancer. 

Photocycloadditions of naphthalene derivatives to alkcnes have been recently reviewed.60 Examples of such reactions are the photocycloaddition of naphthalene to 2,3-dihy-drofuran,61 of 4-methoxy-l-naphthonitrile to acrylonitrile62 and of 2-trimethylsiloxynaph-thalene to methyl acrylate.63 2-Naphthols undergo cycloaddition with ethene in the presence of aluminum trihalides only.64 Other bicyclic aromatic compounds, e.g. A-acylindoles65-67 and /V-methylphenanthrene-9,10-dicarboximide,68 have also been studied in detail. Irradiation of 5/f-dibenzo[u,i7]cyclohepten-5-one (21) and dimethyl 2-methylfumarate (22) in dioxane gives the cyclobutane adduct 23 in 73% yield.69... 

In the cycloaddition of triisopropylallylsilane to a, /J-unsaturated lactams 197, cyclobutane adducts 198 have been found to be the kinetic products whereas the formation of cyclopentanes 199 is thermodynamically controlled285. Reactions of allenylmethylsilanes with activated unsaturated esters and nitriles (equation 163)286 and allylsilanes with unsaturated esters287 are other examples of using [2+2] cycloaddition to construct cyclobutane derivatives. 

These quenching methods can provide indirect evidence about the involvement of CIP and SSIP in PET reactions. We will briefly discuss the dimerization of 1,3-cyclohexadienes exemplarily, leading either to Diels-Alder products or cyclobutane adducts [37]. 

As an illustration of initiation of a cationic polymerization by a zwitterionic tetramethylene, the polymerization of JV-vinylcarbazole (NVCz) in the presence of dimethyl 2,2-dicyanoethylene-l,l-dicarboxylate was studied in great detail [136] (Scheme 3). The cationic homopolymerization of NVCz could be initiated by adding either the electrophilic olefin or the cyclobutane adduct. The proposed mechanism involves bond formation to the zwitterionic tetramethylene, which closes reversibly to the cyclobutane adduct, and can be trapped with methanol. 

One way around this difficulty is to generate the tetramethylenes from the cyclobutane adducts. The cyclobutane adduct of NVCz and tetracyanoethylene placed in a solution of excess /V-vinylcarbazole causes cationic homopolymerization of the latter [136]. However a cyclobutane whose substitution pattern will lead on cleavage to a tetramethylene diradical at reasonable temperatures has not yet been found. A possible explanation is that a tetramethylene diradical has one less bond than a tetramethylene zwitterion, and so is less stable [137]. Another explanation may be that tetramethylene zwitterions prefer to exist in the cis form for coulombic reasons, but tetramethylene diradicals appear to prefer a trans, extended conformation and are difficult to generate from cyclic precursors. 

Naphthalene and certain of its alkoxy and alkyl derivatives react with AN on irradiation, giving cyclobutane adducts [10,11], An example is given below ... 

Only a few additional examples of intermolecular photochemical vinylations of (hetero)aromatic compounds have been forthcoming. Coupling products are formed in the irradiation of dichloro- and dibromo-A-methylmaleimide in the presence of 1,3-dimethyluracils341 and of 3-bromocoumarin in the presence of naphthalene, phenanthrene, 1-methylpyrrole and other aromatic compounds342. The former reaction is accompanied by cyclobutane adduct formation, which is the mode of reaction of A-methylmaleimide itself. The mechanism of these vinylation reactions is not clear, but most probably an exci-plex (cf equation 20a) or a charge-transfer complex (cf equation 20b) is involved. 

Tetracyanoethylene is unusual in that it reacts with cyclohexanone enamines to give a five-membered ring instead of a cyclobutane adduct. Reaction occurs at the y-position of the enamine and an initial one-electron transfer between the two reactants is... 

Quaternary hexahydroindolium salts 39 are produced from cyclohexanone enamines and a-bromoacrylonitrile. In some cases bicyclic cyclobutane adducts 38 have been isolated, which rearrange thermally to the salts (equation 26)47. 

Returning to the effect of solvents, two reasons for the frequently observed dominance of [2 + 2] cycloadditions in nonpolar solvents can be proposed. Less polar solvents will be less effective in stabilizing the radical cation species, thus giving rise to formation of CIP with the reduced sensitizer and more likely and more exothermic BET. Additionally, forward electron transfer might not favorable in all cases. The thermodynamically disfavored ET in nonpolar solvents increases the probability of a direct photoexcitation of the substrate, leading to the cyclobutane adduct via the normal Woodward-Hoffman dictated excited-state process. ... 

Bauld and coworkers have examined the cation radical cycloadditions of 1,3-dienes with electron-rich alkenes and found that, under photosensitized electron-transfer conditions, [2 -i- 2] cycloaddition is in many cases favored over Diels-Alder addition. Thus, as illustrated in equation (30), 1, T-dicyclopentenyl (186) reacts with p-chloroethyl vinyl ether under electron transfer conditions to afford the cyclobutane adduct (187), which was cleaved to the cyclobutanol (188) in 70% yield upon treatment with n-butyl-iithium. Oxyanion-accelerated VCB rearrangement then provided (189) as a mixture of diastereomers in... 

Similarly, the cyclobutane adducts of phenyl vinyl ether and l,l -dicyclopentenyl are the predominant products under PET conditions, but these rearrange smoothly at -45 °C in the presence of 4+ to Diels-Alder adducts. 

Photocycloaddition of ethoxyethene to the enone (81) at 254 nm in methanol affords the adduct (82). Addition of the same alkene to the enone (83) also proceeds via a cyclobutane intermediate but this is unstable and ring opens to afford the cyclo-octane derivative (84). A study of the addition of the optically active alkene (85) to the enone (86) affords four cyclobutane adducts two from head-to-head addition and two from head-to-tail addition. These cycloadditions load to a double induction giving either increased or decreased diastereoselectivity.The intermolecular cycloaddition of ethylene to the enone (87) yields the two adducts (88) and (89). The photoadducts are apparently susceptible to secondary irradiation and the maximum yields of the adducts was obtained at 50% consumption of the starting material (87). Under these conditions (88) and (89) were obtained in 71 and 23% respectively. The isomer (88) was taken on through several steps to afford ultimately racemic starpuric acid a... 

Photocycloaddition of 1,1-dichloroethene to the quinolone (110) affords the adduct (111). The triplet excited state of the enones (112) are photoreactive and undergo addition to alkenes to afford reasonable yields of the azetidines (113). - Both electron rich and electron deficient alkenes photochemically add to the enone (114) to afford the cyclobutane adducts (115). Normally the C=N Is unreactive to (2+2)-cycloadditions but the authors believe that in this case the C=N system is activated by the trifluoromethyl group. The azetidine-2-ones (116) can be readily prepared by irradiation of the enones (114) in the presence of ketene. ... 

FIGURE 18.3, The formation of cyclobutane dimers, (a) Chemical formula of dimerization. (b) Stereoview of the monomers (black bonds) and the cyclobutane adduct (open bonds). This diagram shows the amount of movement of C=C carbon atoms needed to form a cyclobutane ring. Ph = phenyl (Ref. 28). 

Several examples of isomerism of heavily substituted dienes into cyclobutenes have been reported. The reactions are brought about by the use of quartz filtered light. The reactions are quite efficient and, for example, the bicyclo[4.4.1]undeca-dienes (130) can be converted efficiently into the isomeric products (131) and (132) in the yields shown below the appropriate structure. Ring strain does not adversely affect the reaction since it is also possible to bring about ring closure of the bicyclo[4.2.1]nonadienes (133) to afford the tricyclic products (134) and (135). The (2+2)-photocycloaddition of the lambertianate derivative (136) results in the formation of the cyclobutane adduct (137). ... 

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