Furans photocycloaddition reactions

No reaction is observed when 50 and 1,1-dimethoxyethene are allowed to stand in the dark for an equivalent period of time. Irradiation of 50 with 4 equiv. of cyclohexene in methylene chloride solvent gives a 51% isolated yield of the (2 + 2)-cyclo-adduct 52 assigned cis-anti-cis stereochemistry. These two cycloadditions were the first two well defined examples of the (2 + 2)-photocycloaddition reaction of an olefin to a carbon-nitrogen double bond. With furan the (2 + 2)-photocycloadduct 53 is formed, again regiospecifically. 

The Patemo-Btichi photocycloaddition reaction - of various carbonyl compounds to furans was initially investigated by Sakurai in 1963 and was found to afford only the head-to-head photoproducts with high exo relative face selectivity. An NMR study by Whipple and Evanega later confirmed the exo mode of cycloaddition. Since the time of the origin report the photoreaction has been systematically studied by several groups and the 2,7-dioxabicyclo[3.2.0]hept-3-ene ring system has been exploited in several facets of synthesis. 

A recent synthesis of 3-substituted furan derivatives illustrates an important application of the furan-carbonyl photocycloaddition. Zamojski has reported the rearomatization of oxetane (115) in the presence of p-toluenesulfonic acid to 3-furylmethanol derivative (116). Synthesis of (117), itself a substrate for the intramolecular photocycloaddition reaction (Section 2.4.6), involved a similar rearomatization process (PPTS/CHjClj) and capitalized upon the chemoselectivity observed in the ketone-furan photocycloaddition. Similarly, a synthesis of perillaketone (118) by Kawanisi involved irradiation of a carbonyl compound and furan. A complication in the rearomatization is that acid also catalyzes the reversion of the photoadduct to starting materials to circumvent this problem the photoreaction was run in the presence of acid, so that rearomatization would occur in situ and the products of competitive reversion would promptly recombine. 

A further report of the photocycloaddition reactions of benzothiophenes has been made. The two photoproducts (199) and (200) from the benzophenone-sensitized cycloaddition of bromoethene to the 2,3-dichloro-derivative (201a) have been demonstrated to have the stereochemistry shown.The photoaddition of cis-dichloroethene to (201a) is stereoselective and affords predominantly the adduct (202). When 2,3-dibromobenzothiophene (201b) is used with bromoethane, a different reaction path is followed, yeilding (203). Linear products are also obtained with dichloroethene and (201b). [2 + 2] Photocycloaddition of furan or thiophene to the iso-oxazolines (204) affords the adducts... 

Schreiber, S. L., Hoveyda, A. H. Synthetic studies of the furan-carbonyl photocycloaddition reaction. Atotal synthesis of ( )-avenaciolide. J. Am. Chem. Soc. 1984, 106, 7200-7202. 

Griesbeck, A. G. and Stadtmuller, S., Regio- and stereoselective photocycloaddition reactions of aromatic aldehydes to furan and 2,3-dihydrofuran, Chem. Ber., 123, 357, 1990. 

Exceptions due to steric and electronic reasons are known see (a) Carless, H. A. J. and Halfhide, A. F. E., Highly regioselective [2-i-2]-photocycloaddition of aromatic aldehydes to acylfurans, /. Chem. Soc., Perkin Trans. 1, 1081,1992 (b) Schreiber, S. L., Desmaele, D., and Porco, Jr., J. A., On the use of unsymmetrically substituted furans in the furan-carbonyl photocycloaddition reaction synthesis of a kadsurenone-ginkgoKde hybrid. Tetrahedron Lett., 29, 6689,1988. 

Schreiber, S. L. and Satake, K., Studies of the furan-carbonyl photocycloaddition reaction the determination of the absolute stereostructure of asteltoxin. Tetrahedron Lett., 27, 2575,1986. Jarosz, S. and Zamojski, A., Asymmetric photocycloaddition between furan and optically active ketones. Tetrahedron, 38,1453,1982. 

When unsymmetrical carbonyls (R Rj) are used for the photochemical cycloaddition with furans, the inherent stereoselectivity should be considered, i.e., exo-oxetanes vs. endo-oxetanes (Scheme 9). Shima initially investigated the photocycloaddition reaction in 1965 and an NMR study by Whipple and Evanega later provided evidence for the preference of the exo-selective cycloaddition. The exo-selective formation of the bicyclic oxetanes and their chemical transformations are now accepted as powerful tools for preparing the synthetically and biologically important materials. " ... 

Schreiber, S. L., Desmaele, D., and Porco, Jr., J. A., On the use of unsymmetricaUy substituted furans in the furan-carbonyl photocycloaddition reaction synthesis of a kadsurenone-ginkgoHde hybrid. Tetrahedron Lett., 29, 6689,1988. 

A psoralen photoadduct to adenine was also isolated and characterized upon irradiation of a mixture of adenine and psoralen derivative, however, the latter photoadduct does not appear to be generated in cellular DNA. The psoralen adducts within nuclear DNA are formed primarily by a [2 -i- 2] photocycloaddition reaction between the 4, 5 -furan double bond of the psoralen molecule and the 5,6-double bond of thymine. Monoadducts involving the 3,4-pyrone double bond of the psoralen and the pyrimidine 5,6-double bond are also formed, but to a lesser extent (Figure 142.4). Photoisomerization can lead to 4, 5 -monoadducts being converted into 3,4-monoadducts, at least in isolated DNA. Interstrand crosslinks can be generated as the result of photoexcitation of the 4, 5 -monoadduct and its subsequent cycloaddition with the pyrone 3,4 double bond. The structures of the monoadducts and cross-links are shown in Figure 142.4. The cross-linking process depends on the structure of the psoralen derivative. Linear psoralens form cross-links efficiently with a yield, which may reach up to 50% of the overall adducts formed. 

The thermo- and photocycloaddition of alkenes will be discussed in Chapter 12, on pericyclic reactions. On the other hand, transition-metals have effectively catalyzed some synthetically useful cycloaddition reactions in water. For example, Lubineau and co-worker reported a [4 + 3] cycloaddition by reacting a,a-dibromo ketones with furan or cyclopen-tadiene mediated by iron or copper, or a-chloro ketones in the presence of triethylamine (Eq. 3.48).185... 

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