Photoaddition to heterocycles

Photoaddition to heterocyclic systems occurs both as a result of excitation of the heterocycle or of the species undergoing addition. Dimerization will be discussed separately. 

Streith, A. Blind, J. M. Cassal, and C. Sigwalt, Bull. Soc. Chim. France 948 (1969). 

Unlike coumarin, chromone (206) undergoes efficient unsensitized photoaddition to tetramethylethylene, cyclopentene, ketene dimethyl acetal, and but-2-yne.180 The major product of such an addition to tetramethylene is the cis-fused cyclobutane derivative (207) the formation of the two minor products (208 and 209) is easily rationalized. Added benzophenone has no visible effect on this cycloaddition, which is therefore believed to involve the attack of triplet chromone on the ground-state alkene. Photoaddition to furo-chromones has also been studied,179 and the photosensitized cyclo- 

The related oxobicycle (210), on photolysis in carbon tetrachloride, is converted into the isomer (211) in high yield by an intramolecular cycloaddition.186 The same transformation has been observed in norbornadiene, and other intramolecular cycloadditions are known [see, for example, Eq. (50)187]. An intermediate of this type has been postulated188 to account for the photorearrangement of 1,4-epoxy -1,4-dihydronaphthalene to benz[/]oxepin [Eq. (51)]. 

The tetrahydro-2-quinolone (212) affords a very small yield of 1,2-cycloadduct on irradiation with diphenylacetylene in methanol.189 The two major products are the 1,4-dimer and the pentacyclic derivative (213), arising presumably by intramolecular photocycloaddition 

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A wide variety of photoadditions to unsaturated nitrogen containing heterocyclic systems has been reported. It has, however, proved difficult to classify these processes as the reaction mechanisms involved have not always... 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

In certain cases benzene will undergo photocycloaddition to oxygen and sulfur heterocycles. The two major photoproducts of irradiation of a mixture of furan and benzene are adducts 356 and 357, arising, respectively, by [ 2 + 2] and [ 4 + 4] cycloaddition processes.306 Irradiation of benzene and 2,2-dimethyl-l,3-dioxol (358) similarly affords adducts 359 and 360, together with dimer 361.307 Thiochromone 1,1-dioxide also undergoes photoaddition to benzene.308... 

Additions of tetrahydrofuran to dimethylacetylenedicarboxylate395 and to tetracyanoethylene396 and ofxanthene to 3,3-dimethyl-l,2-indanedione397 have also been described. Few systematic investigations of addition to sulfur heterocycles have been made and the topic merits further study. Primary and secondary amines, however, do undergo photoaddition to benzo[h]thiophen (453), as shown in Scheme 30.398... 

In this chapter, we will be concerned with the ortho photocycloaddition of arenes to the benzene ring. This implies that photocycloadditions to larger aromatic systems and to heterocyclic aromatic molecules will not be discussed. The photoadditions of alkynes to benzene and derivatives of benzene, however, are included in this review. The material is organized in sections, according to the pathway that is followed from the ground state of the addends to the ortho photocycloadducts. 

Photoaddition of nucleophiles to heterocycles is often observed.1 Irradiation of acridine and its quaternary salt in ethanol produced 9,9 -bisacridan (151) as the major product besides a little acridan and 9a-hydroxyethylacridan.207 The reaction mechanism is most likely a hydrogen abstraction from the alcohol by the excited molecule, followed by competitive radical combination to yield 151. Irradiation of an aqueous solution of alloxan monohydrate and its derivatives produces an alloxantin-type dimer (152 R = H, Me, Et) by combination (at the 5-position) of a radical intermediate.208... 

A number of examples of photocycloaddition to sulphur-containing heterocycles have been reported. 2,3-Dichlorobenzo(b]thiophene (226) undergoes [ 2 + 2] benzophenone-sensitized photoaddition to vinyl bromide to give the stereoisomeric adducts (227). A potentially more useful cycloaddition has been described for 4-methoxy-l-thiocoumarin (228) which with isobutene, for example, affords the adduct (229). The structures assigned to adducts of... 

Numerous examples of [ 2 -I- 2] photocycloaddition of five-membered oxygen-containing heterocycles to alkenes have been reported, many of which have useful synthetic applications. The regiochemistry and stereochemistry of each adduct has not always been fully established. The lactone (311) undergoes photoaddition to cyclopentene to afford the cis,anti,cis adduct (312), whereas three stereoisomeric adducts were obtained with cyclohexene. Analogous additions of substituted lactones to alkenes have been employed in the syntheses of ( )-dihydrofomannosin acetate and cyclobutane analog of chrysanthemumic acid. The photoaddition of... 

A wide variety of photoadditions to unsaturated oxygen and sulfur heterocycles has been reported. It has, however, proved difficult to classify these processes, especially as the reaction mechanisms are not fully understood in all cases. Most additions of solvent to oxygen heterocycles arise via hydrogen abstraction pathwyas, often initiated by added ketone. Polar addition is relatively rare in these compounds the addition of methanol to... 

Reports of [ 2 + 2] cycloaddition of nitrogen containing heterocycles to alkenes are so numerous that attention can be drawn here to only a few. Recent examples include the acetone-sensitized photoaddition of 4-oxazolin-2-one (248) to ethylene to give the cis-adduct 249,203 the photocycloadditions of N-substituted imidazoles to acrylonitrile204 and of N-methyl-4-hydroxy-quinol-2-one to cyclohexene,205 and the photoaddition of pentafluoro-pyridine to ethylene to give the 1 1- and 1 2-adducts 250 and 251,... 

The iminium salt photoaddition reaction has been applied to the synthesis of N-heterocyclic systems (equation 70)126,127. 

The double bonds in certain heterocyclic compounds, such as furans, Af-acylpyrroles and A-acylindoles are also susceptible to photoaddition of carbonyl compounds to form oxetanes (equation 106) (77JHC1777). A wide range of carbonyl compounds can be used, including quinones, a-diketones, acyl cyanides, perfluorinated aldehydes and ketones and esters. A remarkable case of asymmetric induction in oxetane formation has been reported from optically active menthyl phenylglyoxylate and 2,3-dimethyl-2-butene the oxetane product obtained after hydrolysis of the ester group had an optical purity of 53% (79AG(E)868). 

Other synthetic routes to benzazepines involving ring expansion of six-membered heterocycles include the action of diazomethane (77CPB321), sulfonium ylides (77H(7)37> or acyl halides (75T1991) on quaternary 3,4-dihydroisoquinolines that of sulfoxonium ylides on quaternary quinolines (74IJC(B)1238) and the zinc-acetic acid reduction of quaternary 1-acyltetrahydroisoquinolines (77BSF893). Photoaddition of acyl- or aryl-nitrenes to the exocyclic alkene bond of 2-methylene-1,2-dihydroquinolines results in ring expansion to... 

A series of intramolecular photoadditions of one anthracene nucleus to another resulting in the formation of heterocycles have been reported in certain dianthryl derivatives.273 9-Anthryl-9-anthramide (262), on irradiation in benzene yields the /3-lactam (263) the corresponding carbonate and azo compound undergo analogous cyclizations. 

The photoaddition of alcohols and phenols to alkenes has been observed.404 The equivalent intramolecular process results in cyclization and the formation of oxygen heterocycles. Irradiation of 2-allyl-4-(-butylphenol (388) affords 2,3-dihydro-2-methyl-5-<-butyl-benzofuran (389), whereas o-3-methylbut-2-enylphenol (390) gives 2,2-dimethylchroman (391). In both cases, therefore, the addition can be said to occur in a Markovnikov direction. 

Addition to six-membered oxygen heterocycles is also common. The photocycloaddition of 5,7-dimethoxycoumarin to tetramethylethylene has been described,269 and 4-hydroxycoumarin (326) undergoes facile addition to cyclohexene on direct irradiation to give the cyclobutane (327)270 analogous additions to a variety of other alkenes have been reported, and the cycloaddition of 4-methoxycoumarin to 2-methylpropene has been employed in a synthesis of l,2-dihydrocyclobuta[c]coumarin.271 Photoaddition of the 1,2-bisenol lactone (328) to tran.s-stilbene yields propellane (329),272 and [ 2 + 2] cycloaddition is observed along with other competing photoreactions on irradiation of chromone in the presence of alkenes.273... 

The cycloaddition of a variety of sulfur heterocycles to alkenes has also been reported. Dibromomaleic anhydride undergoes [ 2 + 2] cycloaddition to thiophen295 and to benzo[b]thiophen.296 The photoaddition of benzo-[(>]thiophen 1,1-dioxides to alkenes also affords cyclobutane derivatives.297 Of particular interest is the addition of 3-acetoxybenzo[6]thiophen (350) to cyclohexene to give the adduct (351), which on treatment with base, undergoes a retro-aldol ring opening to benzo[6]thiepinone (352).298 A mixture of stereoisomeric cyclobutane derivatives were obtained on irradiation of 2,6-diphenyl-4//-thiopyran-4-one 1,1-dioxide in cyclohexene.299 The [ 2 + 2] cycloaddition of sulfolen to maleic anhydride and to maleimide has been reported.300... 

There are few new authenticated examples of [ 4 + 4] photoadditions in oxygen- and sulfur-containing heterocycles. 1-Cyanonaphthalene (362), for example, undergoes an addition of this type to furan on irradiation in benzene to give adduct 363 in high yield.309 Addition of 2-cyanonaphthalene... 

A number of cycloadditions have been shown to arise by initial bond homolysis in the heterocycle followed by the addition of the resulting biradical to an alkene. The photoaddition of 2-phenylbenzothiazole (367) to ethyl vinyl ether to give the 1,5-benzothiazepine (368) can be interpreted in this way.313 Similar pathways have been proposed to account for the... 

Organ, M.G., Froese, R.D.J., Goddard, J.D., Taylor, N.J., and Lange, G.L. (1994) Photoadditions and dialkylcuprate additions to 2-tert-butyl-2,6-dimethyl-l,3-dioxin-4-one and related heterocycles. Experimental, ab initio theoretical, and X-ray structural studies of facial seledivity and enone pyramidalization. Journal of the American Chemical Society, 116, 3312-3323. 

Other miscellaneous additions have been reported. Novel three-, five-, and six-membered nitrogen-sulphur heterocycles have been prepared by irradiation of sulphur monochloride in the presence of perfluoroazoalkanes. Photoaddition of hydrogen sulphide to the diallylsilane (232) yields the thiol (233), which readily undergoes cyclization to the l-thia-5-silacyclooctane (234). ... 

Lewis and coworkers have also observed efficient intramolecular photoaddition for several (A,A-dimethylaminoalkyl)styrenes, leading to the formation of nitrogen heterocycles or aminocycloalkanes (Scheme 53) [287]. 

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