Dienes intramolecular photocycloaddition

One of the exciting areas that has gained importance over the recent decade is the photochemical cyclization of non-conjugated dienes in the presence of species that can act as templates. One such species that has been used is copper(I) salts. The earliest example of the use of copper salts in the intramolecular photocycloaddition of non-conjugated dienes is that described for cycloocta-1,5-diene. When this is irradiated in the presence... 

Other examples of favored formation of cyclobutanes include photocycloadditions of tri-fluoromethyl-substituted coumarins with dienes,and of 5-(trifluoromethyl)-l,3-dioxin-4-ones, e.g. 3, with alkenes, " - - " as well as intramolecular photocycloadditions, such as those of bicyclo[2.2.2]octadiene and tricyclononadiene derivatives. 

Functionalized substituted cyclopentanes and spirocyclopentanes were easily accessed by intramolecular photocycloaddition of dihydrofuran based dienes catalyzed by Cu(i) salts. Thus, tricyclic compound 39 was synthesized in 60% yield starting from 38 (Scheme 2.22). Notably, 39 can be easily transformed upon treatment with triflic acid into substituted cyclopentanones, which are important building blocks in the total synthesis of natural products. ... 

The photocycloadditions of 2,3-dimethyl-l,3-diene with 4-(alk-l-ynyl)-substituted coumarins (5) produced a mixture of 4 + 2- and 4 + 4-cycloadducts (6) and (7), respectively. However, the corresponding thiocoumarins (8) yielded a single 4 + 2-cycloadduct (9) (Scheme 2)." The intramolecular photocycloadditions (>290nm) of 1,3-enynes with 2-pyridone yielded 2 + 2- and 4 + 4-cycloadducts. The Rh(I)-catalysed formal 5+l-/2 + 2 + 2-cycloaddition of 1-yne-vinylcyclopropanes (10) with two carbon monoxide units produced multifunctional angular tricyclic 5/5/6 compounds (11) in a one-step mechanism (Scheme 3). ... 

The importance of precoordination is also evident in the CuOTf-promoted27T + 2 r photocycloaddition of endo-dicyclopentadiene. This diene forms an isolable 2 1 complex with CuOTf involving evo-monodentate coordination with the 8,9-C=C bond of two molecules of diene. Consequently, intermolecular 2 r + 27r photocycloaddition involving exo addition to the 8,9-C=C bond is strongly favored over intramolecular reaction between the 8,9- and 3,4-C=C bonds (eq 11). This contrasts with the intramolecular photocycloaddition that is promoted by high energy triplet sensitizers. ... 

Copper (I)-catalyzed intramolecular photocycloaddition between two acycHc double bonds was first observed by Evers and Mackor in 1978. They demonstrated that although 3-oxabicyclo[3.2.0]heptane 26 is formed from diallyl ether 25 (Scheme 8), 4-hydroxy-1,6-heptadiene 27 produces an endo,exo (3 2) mixture of 3-hydroxy bicyclo[3.2.0]heptanes 28 (Scheme 9) on irradiation in presence of CuOTf. The generahty and scope of this reaction were investigated in great detail by Salomon et al. The acyclic dienes... 

Al-Qaradawi, S. Y., Cosstick, K. B., and Gilbert, A., Intramolecular photocycloaddition of 4-phenoxybut-l-enes a convenient access to the 4-oxatricyclo[7.2.0.0 ]undeca-2,10-diene skeleton, /. Chem. Soc., Perkin Trans.1,1145,1992. 

Stereochemical scrambling in intramolecular photocycloadditions of cyclohexenones with tethered alkene moieties has also been extensively investigated. Becker and Haddad found that the isomeric 5-ltnked l-acyl-l,6-heptadienes 5 and 6 (R = CH3) give a 1 1 mixture of stereoisomeric cycloadducts 7 and 8,but the dienes do not isomerize during the irradiation process ... 

Schultz carried out extensive studies exploiting the rich photochemistry of 2,5-cyclohexadienones to generate complex multi-cyclic systems amenable to further synthetic elaboration. These studies have explored the intramolecular photocycloadditions of 2,5-cyclohexadienone with alkene and diene traps appended to the 4-position of the ring. This work has been previously reviewed. This chapter focuses on the ability to capture the transient oxyallyl species. 

Sieburth, S. McN. and Zhang, F., Intramolecular photocycloaddition of 1,3-dienes with 2-pyri-dones. Tetrahedron Lett., 40, 3527-3530,1999. 

Intramolecular photocycloadditions of l,n-dienes can be achieved by the use of Cu ions. Cu serves as a removable tether to preorganize the ene chromophores. Cu triflate-catalyzed photoreactions of alkenes involve light absorption by preformed alkene-Cu complexes. The Cu -alkene triflate complex generally shows two strong absorption bands (230-240 nm and 260-290 nm) while the uncomplexed alkenes are nearly transparent in this region. Because of this effect even if only a small percentage of alkene exists in the complexed state, only the complex will react. This cycloaddition reaction is run most often under catalytic conditions. 

As was mentioned in Section 13.2, the [27t + 27i] photocycloaddition of alkenes is an allowed reaction according to orbital symmetry considerations. Among the most useful reactions in this categoty, from a synthetic point of view, are intramolecular [27t + 2ti] cycloadditions of dienes and intermolecular [2ti + 2ti] cycloadditions of alkenes with cyclic a, -unsaturated carbonyl compounds. These reactions will be discussed in more detail in Section 6.4 of Part B. 

Intramolecular [2 + 2] photocycloadditions of alkenes is an important method of formation of compounds containing four-membered rings.184 Direct irradiation of simple nonconjugated dienes leads to cyclobutanes.185 Strain makes the reaction unfavorable for 1,4-dienes but when the alkene units are separated by at least two carbon atoms cycloaddition becomes possible. 

The literature of diene and polyene photochemistry provides many cases of synthetically useful reactions. As a result, certain arbitrary decisions have been made regarding what is covered in this chapter. For example, intramolecular [2 + 2]-photocycloaddition reactions of a, >-dienes can be formally included under the general rubric of diene photochemistry. However, we have chosen to restrict our discussion to dienes and polyenes which constitute a self-contained chromophore, viz. conjugated, cross-conjugated and 1,4-diene systems. Likewise, arene-olefin photocycloadditions will not be considered. These two broad classes of photoreactions have been applied extensively in synthesis, and have been the subject of recent reviews3,4. 

Only a trace of the corresponding cubane 167 is formed on irradiation of the tricy-clooctadiene 168 in pentane at ambient temperatures using a 125-watt mercury arc lamp. The principal product 169 is the result of rearrangement within a biradical intermediate79. A review of the synthetic approaches to cubane and to its reactions has been published77. The diene 170 photochemically converts on irradiation in pentane solution at 254 nm to yield a photostationary mixture of the cubane 171, the starting material 170 and the isomeric diene 17280. Other additions of this type have been used for synthesis of the propellaprismane 173, essentially a heavily substituted cubane, by the intramolecular (2 + 2)-photocycloaddition of the diene 17481. 

The first total synthesis of a racemic dolastane (rac-llO) was apparently published by Pattenden as a short communication 1986 followed in 1988 by a full paper [77, 78]. Pattenden s strategy is based on an intramolecular [2+2]-photocycloaddition/cyclobutane fragmentation to transform the diene 133 into the hydroazulene 136 (Scheme 20). In between the cycloaddition... 

Intramolecular [2 + 2] photocycloadditions have been used successfully for the syntheses of (polycyclic) cage compounds. Recent examples of such reactions are the formation of pentacyclo[5.4.0.02 6.031°.05 9]undecane-8,ll-dione-4-spiro-l-cyclopentane,55 hexacy-clo[7.4.2.01,9.03,7.04 14.061s]pentadeca-10,12-diene-2,8-dione-5-spiro-l -cyclopropane,56 pen-tacyclo[5.4.0.02 6.031°.04 8]undecane57 and pentacyclo[6.4.0.02 7.03 12.06 9Jdodeca-4,10-diene.58 Irradiation of benzoquinone tetrahydropentalene adducts afford cage compounds which are easily converted to angular tetraquinanes.59... 

Para photocycloaddition of arenes to the benzene ring was first reported in 1971 by Wilzbach and Kaplan [7] as a minor process accompanying ortho and meta photocycloaddition. Since that time, relatively few cases of para photocycloaddition have been described. Para adducts were found as minor products from benzene with cyclobutene [8], ra- 3,4 - dimethyIcycIobu(ene [9], vinylene carbonate [10], 2,3-dihydropyran [11,12], and 1,3-dioxole [13,14] and from a,a,a-tri-fluorotoluene with vinylene carbonate [15], Intermolecular para photocycloadducts were major products from the irradiations of benzene and allene [16,17], benzene and cyclonona-1,2-diene [16,17], and from fluorobenzene and cyclopentene [18], Intramolecular para photocycloadducts were found as major products from the irradiations of phenethyl vinyl ether [19-21] (Scheme 3) and 2,3-dimethyl-6-phenylhex-2-ene [22], No detailed mechanistic investigations have been published. 

In Table 5, the ortho adducts are collected, which have been reported to be formed by intermolecular photocycloaddition of benzene and derivatives of benzene to simple alkenes. Ortho photocycloadditions of alkenes to perfluorinated benzenes are separately collected in Table 6. Intramolecular ortho photocycloadditions have been grouped in Table 7. (The many intramolecular ortho photocycloadditions proceeding via the triplet state of the arene moiety are found in Table 4.) All adducts shown in the tables are the primary ortho adducts. Many of these bicyclo[4.2.0]octa-2,4-diene derivatives are, however, unstable and not all of... 

In the formation of tetraenes from bicyclo[4.2.0]octa-2,4-dienes, two bonds are broken. This may occur in one concerted reaction which can be regarded as a retro [2 + 2] cycloaddition. It is also possible that the central bond, being part of a cyclohexadiene system, is the first one to break in a thermal, concerted disrota-tory process that leads to a 1,3,5-cyclooctatriene derivative. Ring opening of the cyclooctatriene then might take place photochemically, again disrotatory, to produce a tetraene. This two-step sequence was first observed by Mirbach et al. [114] in their study of the photocycloaddition of the two parent molecules benzene and ethene. The same explanation for the formation of a tetraene was given by Nuss et al. [160] in their report on the intramolecular ortho photocycloaddition of ( )-6-(2-methoxyphenyl)-5,5-dimethyl-2-hexenenitrile (see Scheme 40). 

The dimerization of thioformylketene was investigated by B3LYP and G3MP2B3 methods. The 4 + 4-pathway has the lowest energy barrier and calculations suggest that the reaction is pseudopericyclic.231 The stereospecific intramolecular 4 + 4-cycloaddition reaction between cyclohexadiene iron tricarbonyl complex and appended dienes (198) generates cyclooctadiene tricyclic adducts (199) (Scheme 56).232 The first example of an asymmetric intermolecular 4 + 4-photocycloaddition reaction in solution between 9-cyanoanthracene and chiral 2-methoxy-l-naphthamides has been reported. The frozen chirality is effectively transferred to the optically active product.233... 

CONTENTS Preface, Mark Lautens. Photocyclization and Photocycloaddition Reactions of 4- and 2-Pyrones, Frederick G. West. Intramolecular [4+3] Cycloaddition Reactions, Michael Harmata. Lewis Acid Catalyzed [2+2] Cycloaddition Reactions of Vinyl Sulfides and Their Analogues Catalytic Asymmetric [2+2] Cycloaddition Reactions, Koichi Narasaka and Yujiro Hayashi. Vinylboranes as Diels-Alder Dienophiles, Daniel A. Singleton. Preparation and Exo-Selective [4+2] Cycloaddition Reactions of Cobaloxime-Substituted 1,3-Dienes, P... 

A [2 + 2] photocycloaddition with two alkenes can also be induced by photochemical electron transfer [16,17]. In such cases, sensitizers are frequently used and the reactions therefore occur under photocatalysis [18]. Under photochemical electron transfer (PET) conditions, the diene 10 yielded in an intramolecular reaction the cyclobutane 11 (Scheme 5.2) [19], such that in this reaction a 12-membered cyclic polyether is built up. The reaction starts with excitation of the sensitizer 1,4-dicyanonaphthalene (DCN) only 0.1 equivalents of the sensitizer are added to the reaction mixture. Electron transfer occurs from the substrate 10 to the excited sensitizer, leading to the radical cation I. This intermediate then undergoes cycli-zation to the radical cation of the cyclobutane (II). Electron transfer from the radical anion of the sensitizer to the intermediate II leads to the final product 11, and regenerates the sensitizer. In some cases, for example the cydodimerization of N-vinylcarbazole, the effidency is particularly high because a chain mechanism is involved [20]. 

Copper(I) catalysis is very well established to promote intramolecular [2+2] photocycloaddition reactions of l,n-dienes (review [351]). The methodology recently enjoyed a number of applications [352-354], It is assumed that CuOTf, which is commonly applied as the catalyst, coordinates the diene and in this way mediates a preorganization. The Ghosh group recently reported a number of CuOTf-catalyzed photochemical [2+2] cycloaddition reactions, in which an organocopper radical complex was proposed as a cyclization intermediate (which should, however, have a formal Cu(II) oxidation state) (selected references [355-357]). A radical complex must, however, not be invoked, since the process may either proceed by a [2+2] photocycloaddition in the coordination sphere of copper without changing the oxidation state or according to a cycloisomerization/reductive elimination process. 

Sensitized intramolecular reaction of two 1,3-dienes (86) (Sch. 17) yields predominantly the [2+2] adduct 87, with small amounts of [4+4] adduct 89 and little, if any, [4+2] product 88 [58,59], consistent with Hammond results for intermolecular reactions of acyclic dienes (Sch. 4). Benzophenone-sensitized reaction yields a mixture of two isomers of 87. Heating this mixture to 200 °C converts both isomers of 87 to cyclo-octadiene 89 [58]. Unsensitized photoreaction of 86 in the presence of copper(I) triflate gives a significant amount of [4+2] adduct 88. Extended irradiation time converts much of 87 and 89 into 88, as well as producing secondary products [59]. Copper triflate-mediated photocycloaddition of a related tethered diene-monoalkene, gave only the [2+2] adduct [59]. 

Mattay et al. employed asymmetric copper(I)-catalyzed intramolecular [2 + 2]-photocycloaddition reactions in a synthetic approach to (+)- and (— )-grandisol [56]. Racemic dienol 33 was irradiated in the presence of CuOTf and a chiral ligand to yield mainly cyclobutanes 34 and ent-34 as a mixture of enantiomers. Other 1,6-dienes were also employed. A number of chiral nitrogen-containing bidentate ligands were tested, the most effective of which, (4S,4 S)-4,4 -diisopropyl-2,2 -bisoxazoline (35) and (4R,47 )-4,4 -diethyl-2,2 -bisoxazoline (36), ensured a minor enantiomeric excess of <5% ee (Scheme 12). The coordination of the diene to the chiral Cu(I) complex under formation of a complex of type 37 was proved by CD analysis. The authors suggest a lower reactivity of the chiral complex compared to the copper ion coordinated to solvent molecules as the reason for the low enantioselectivities observed. 

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