Photocydoaddition

A combined photochemical and biocatalytic approach provided access to bicyclo [4.2.0]octanes via a novel strategy. The Cu-catalyzed [2 + 2] photocydoaddition of... 

The reactions with a.p-unsaturated carbonyl compounds also lead to cyclobutenes (2.102), and there is evidence that, in some cases at least, the mechanism is non-concerted and goes through biradical intermediates that can be trapped by a second molecule of the conjugated alkene (2.103). Intramolecular photocydoadditions offer routes to polycyclic structures, and the cyclobutene unit in the product provides a basis for subsequent chemical transformations such as oxidation 12.104). 

A second major mode of photocydoaddition involves 1.2-addition to the aromatic ring, and this predominates if there is a large difference in electron-donor/acceptor capacity between the aromatic compound and the alkene. It is therefore the major reaction pathway when benzene reacts with an electron-rich alkene such as 1,1-dimethoxyethylene (3.43) or with an electron-deficient alkene such as acrylonitrile (3.441. When substituted benzenes are involved, such as anisole with acrylonitrile (3.45), or benzonitrile with vinyl acetate (3.46), reaction can be quite efficient and regioselective to give products in which the two substituents are on adjacent carbon atoms. 

One of the first reported photocydoaddition reactions of benzene was with the highly electron-deficient alkene, maleic anhydride. 

Somekawa, K. Okuhira, H. Sendayama, M. Suishu, T. Shimo, T. Intramolecular [2 + 2]-photocydoadditions of l-(tw-alkenyl)-2-pyri-dones possessing an ester group on the olefi-nic carbon chain. J. Org. Chem. 1992, 57, 5708-5712. 

Blakemore, D.C. and Gilbert, A. (1994) Intramolecular meta photocydoaddition of 3-benzylazaprop-l-enes. Tetrahedron Letters, 35 (29), 5267-5270. 

More complex ring systems have been built up using the CuOTf-catalyzed [2 + 2] photocydoaddition. For instance, transformation of the cydopentene derivative 21 leads in high yields to the tricyclic compounds 22a,b (Scheme 5.5, reaction 9) [27], with the endo isomer 22a being obtained in excess. The reaction was applied to... 

Many examples of the intramolecular [2 + 2] photocydoaddition of alkenes to benzene derivatives have been reported. The acetophenone derivative 41 undergoes an efficient [2 + 2] photocydoaddition, leading to the cyclobutane derivative 42 (Scheme 5.9, reaction 18) [46, 47]. It was shown that, in this case, a nn triplet state is involved. The presence of a nitrile group in compound 43 induces a [2 + 2] cycloaddition at position 1,2 of the aromatic moiety, leading to intermediate VIII (reaction 19) [48]. Following tautomerization, the final product 44 is formed. 

Due to their reduced aromatic character, naphthalene derivatives more easily undergo [2 + 2] photocydoaddition to give access to cyclobutane derivatives [49]. In some cases, the formal [4 + 2] addition is competitive. In contrast to the ground-state Diels-Alder reaction, the [4 + 2] products from these photochemical reactions result from a multistep reaction. Upon irradiation, the 1-cyanonaphthalene derivative 45... 

Frequently, the intramolecular [2 + 2] photocydoaddition of an alkene to a benzene ring is followed by further pericyclic reactions. Such transformations yield... 

Photochemical reactions provide a classical access to four-membered ring compounds that generate major interest in organic synthesis, notably as intermediates in multistep syntheses. The [2 + 2] photocycloaddition of a,(3-unsaturated carbonyl and carboxyl compounds with alkenes and [2 + 2] photocydoaddition of ketones with alkenes (the Paterno-Buchi reaction) are discussed in Chapters 6 and 7, respectively. Yet, aside from these transformations, a variety of further reactions provides a systematic access to four-membered rings that possess a wide structural variation. Four-membered ring compounds may also be created via less-systematic photochemical transformations, many of which can be carried out without additional chemical activation. As a consequence, such transformations are rendered not only very convenient but also extremely interesting within the context of green chemistry. ... 

New York, pp. 33-100 (d) Bach, T. (1998) Stereoselective intermolecular [2 + 2] photocydoaddition reactions and their application in synthesis. Synthesis, 683-703 (e) Mattay, J., Conrads, R., and Hoffmann, R. (1996) [2 + 2] Photocydoaddtions of a.S-unsaturated carbonyl compounds, in Houben-Weyl, Methods of Organic Chemistry, Vol. E 21 Stereoselective Synthesis (eds G. Helmchen, R.W. Hoffmann, J. Mulzer and E. Schaumann), Thieme Verlag, Stuttgart, pp. 3085-3178. 

Cornelisse, J. andde Haan, R. (2001) Ortho photocydoaddition of alkenes and alkynes to the benzene ring, in Understanding el Manipulating Excited State Processes, Molecular and Supramolecular Photochemistry, Vol. 8 (eds V. Ramamurthy and K.S. Schanze). Marcel Dekker, New York,... 

The formation of exo-products is also the predominant pathway if acyclic alkenes are employed as reaction partners. The reaction of cyclopentenone and ethyl vinyl ether serves as an instructive example (Scheme 6.4) for two reasons. First, it exemplifies the regiochemical outcome (r.r. = regioisomeric ratio) of the [2 + 2]-photocydoaddition with HT-products 7 being predominantly formed (versus HH-products 8). Second, it illustrates the exo-preference with compound 7a prevailing over 7b (d.r. = diastereomeric ratio) [21]. However, it is also clear from this... 

The regioselectivity of intramolecular [2 + 2]-photocydoaddition reactions is predictable if five-membered ring formation is possible in the formation of biradicals of type C or C (rule of five, vide supra). If five-membered ring formation is not feasible, then six-membered rings are most readily formed. The facial diastereo-selectivity is efficiently controlled by a stereogenic center in the cyclopentenone if the intramolecular alkene is attached via a tether to this stereogenic center. The key step 16 —> 17 in the stereoselective synthesis of (—)-incarvilline (18) illustrates the point (Scheme 6.7) [28]. The side chain attached to C-4 in the cyclopentenone 16 carries the terminal alkene, which reacts intramolecularly with perfect regio- and diastereoselectivity to cyclobutane 17. 

Chiral cyclohexenones have been frequently employed in intermolecular [2 + 2]-photocydoaddition reactions directed towards natural product synthesis. A further case in point is the reaction of cydohexenone 32 with trans-1,2-dichloroethylene... 

An intramolecular naphthoquinone [2 + 2]-photocydoaddition (Scheme 6.16) led directly to the formation of the natural product (—J-elecanacin (43a) [51]. Here,... 

The 3(2H)-furanones are - as the other 4-hetero-2-cyclopentenones - normally 2,2-disubstituted to avoid enolization to the respective 3-hydroxyfuran. If one of the substituents is an alkenyl side chain, then intramolecular [2 + 2]-photocydoaddition reactions are possible with the regioselectivity being dependent on the chain length (Scheme 6.20). The allyl-substituted substrate SO (n— 1) gave predominantly the formal straight product SI [62], while the butenyl-substituted substrate 50 (n = 2) resulted in formation of the crossed product 52 [63]. 

The utility of the [2 + 2]-photocydoaddition to 4-aza-2-cyclohexenones has been explored by Comins et at. in synthetic approaches to different alkaloids [71, 72]. As originally reported by Neier et al. the corresponding acyl- and alkoxycarbonyl-substituted 2,3-dihydropyridin-4(lH)-ones are particularly useful substrates [73], In a recent study, the intramolecular reaction of dihydropyridone 61 was found to lead to the tricyclic product 62, which was further converted into the quinolizidine 63... 

Lactams of type A4 have been successfully employed in intramolecular [2 + 2]-photocydoaddition reactions. Direct excitation has been found most useful to achieve sufficient conversion in these reactions. The reaction of [i-substituted a,P-unsatu-rated lactams 95 in CH2C12 gave the expected products 96 of five-membered ring closure in decent yields (Scheme 6.34) [92]. 

Pyridones can react photochemically along several reaction channels [94]. Besides [4 + 4]-photodimerization and 4jt]-ring closure, [2 + 2]-photocydoaddition reactions are possible in an a,P- or in a y,8-mode relative to the carbonyl carbon atom. With regard to the former reaction pathway, the [2 + 2]-photocydoaddition of olefins to 4-alkoxypyridones appears to be synthetically most useful (vide infra). 

Coumarin photochemistry has been recently employed to demonstrate that a frozen axial chirality can be used to induce the absolute configuration of stereogenic centers. Coumarin 103 was obtained as a single atropisomer by spontaneous crystallization (Scheme 6.37). Upon warming powdered crystals of 103 in MeOH to —20 °C, sensitized [2 + 2]-photocydoaddition to ethyl vinyl ether gave the almost enantiomerically pure products 104. The approach to the coumarin double bond occurred preferentially from the less-shielded face to which the amide carbonyl group... 

Maleic anhydride (117) belongs to the first compounds, the [2 + 2]-photocycloaddi-tion reactions of which were extensively explored [112]. It is preferably converted to the corresponding cyclobutanes by irradiation in the presence of a sensitizer, for example, benzophenone, allowing the addition of a plethora of alkenes (Scheme 6.42). In a recent application the photocydoaddition product 118 of maleic anhydride and l,4-dichloro-2-butene was converted into the marine alkaloid ( )-sceptrin (119) [113]. 

Substituted maleic anhydrides have been directly exdted, but sensitization may also be used. In some cases the first method is better, and in some cases the second. In an approach to merrilactone A, which is closely related to the earlier-mentioned synthesis (Scheme 6.30), 2,3-dimethylmaleic anhydride was employed as a starting material in a sensitized [2 + 2]-photocydoaddition to 1,2-dichlorethene [114]. The reaction of tetrahydrophthalic anhydride (120) with alkenols and alkynols was conducted by direct irradiation in a Pyrex vessel. As an example, the reaction with allyl alcohol is depicted. The exo-product 121 was the preferred product with the endo-product cydizing spontaneously to lactone 122 (Scheme 6.43) [115]. Other alkenols reacted similarly. 

Enantioselectivity control in a [2 + 2]-photocydoaddition reaction was achieved in a chiral, self-assembled host. Fluoranthenes and N-cyclohexylmaleimide underwent an intramolecular reaction in a cage made of M6L4, with the metal M being palladium (II) coordinated to a chiral diamine, and the ligand Lbeing2,4,6-tris(4 -pyridyl)-l,3,5-triazine. Up to 50% ee was observed [117]. 

Sulfur analogues of the compounds discussed previously in Sections 4.1.1—4.1.5 have been employed with some success in [2 + 2]-photocydoaddition chemistry. The analogous nonaromatic lactones, such as 125 [118] and 126 [119], have found little use due to the fact that the yields achieved in their cydoaddition reactions remained low (Figure 6.2). Thiophen-2(5H)-one 126 and its 5-substituted derivatives delivered with 2,3-dimethyl-2-butene under direct irradiation conditions (7. = 350 nm in cyclohexane) the corresponding cydoaddition products in yields of only 10-15%. 

Tetronates derived from l,3-divinyl-2-cyclopentanol were employed to study the possibility of a differentiation of enantiotopic or diastereotopic double bonds in their [2 + 2]-photocydoaddition [140]. It was found that tetronate 148 underwent a selective [2 + 2]-photocydoaddition (r.r. = 75/25) at one of the two possible double bonds to deliver product 149 in 67% yield (Scheme 6.52). The reaction was analyzed regarding the preferred conformations of the cyclopentanol, with the notion that the tetronate resides in a pseudoequatorial position, and the vinyl group in a pseudoaxial position of the envelope conformation. Intermediate 149 served as starting material for the first total synthesis of the tetracydic sesquiterpene (T)-punctaporonin C (150) [141]. 

Margaretha, P. (2005) Photocydoaddition of Cycloalk-2-enones to Alkenes, in Organic Photochemistry (Molecular and Supramolecular Photochemistry), Vol. 12 (eds A.G. Griesbeck and J. Mattay), Marcel Dekker, New York, pp. 211-237. 

Broeker, J.L., Eksterowicz, J.E., Belk, A.J., and Houk, K.N. (1995) On the regio-selectivity of photocydoadditions of triplet cyclohexenones to alkenes. Journal of the American Chemical Society, 117, 1847-1848. 

Meyer, L., Alouane, N., Schmidt, K., and Margarefha, P. (2003) Photocydoaddition of cydohex-2-enones to acrylonitrile. Canadian Journal ofChemistry, 81,417—422. 

Shepard, M.S. and Carreira, E.M. (1997) Asymmetric photocydoadditions with an optically active allenylsilane trimethyl-silyl as a removable stereocontrolling group for the enantioselective synthesis of exo-methylenecydobutanes. Journal of the American Chemical Society, 119, 2597-2605. 

Akritopoulou-Zanze, I., Whitehead, A., Waters, J.E., Henry, R.F., and Djuric, S.W. (2007) Synthesis of novel and uniquely shaped 3-azabicydo[4.2.0]octan-4-one derivatives by sequential Ugi/[2 + 2] ene-enone photocydoadditions. Organic Letters, 9, 1299-1302. 

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