Photocycloaddition aldehyde-furan

In contrast to the diastereoselectivity of the 2,3-dihydrofuran photocycloaddition, the photocycloaddition of furan with aromatic as well as aliphatic aldehydes proceeded with unusually high exo-diastereo-selectivity to give the bicyclic oxetanes 119 in good yield (Sch. 39) [123]. The diastereoselectivity of reaction of furan with acetaldehyde and benzaldehyde (iexo/endo) were 19 1 and 212 1, respectively. 

High selectivity has been obtained in the Paterno-Biichi reaction of aldehydes with furans and this reaction has formed the basis of a number of total syntheses. Thus, photocycloaddition of furan with nonanal gave the exo product 170, which was converted to the antifungal metabolite avenaciolide (3.115). 

A recent application of the furan-carbonyl photocycloaddition involved the synthesis of the mycotoxin asteltoxin (147)." Scheme 16 shows the synthetic procedure that began with the photoaddition of 3,4-dimethylfuran and p-benzyloxypropanal to furnish photoaldol (148), which was epoxidized with MCPBA to afford the functionalized product (149) in 50% overall yield. Hydrolysis (THF, 3N HCl) provided the monocyclic hemiacetal which was protected as its hydrazone (150). Chelation-controlled addition of ethylmagnesium bromide to the latent a-hydroxy aldehyde (150) and acetonide formation produced compound (151), which was transformed through routine operations to aldehyde (152). Chelation-controlled addition of the lithium salt of pentadienyl sulfoxide (153) followed by double 2,3-sigma-tropic rearrangement provided (154) as a 3 1 mixture of isomers (Scheme 17). Acid-catalyzed cyclization of (154) (CSA/CH2CI2) gave the bicyclic acetal (155), which was transformed in several steps to ( )-asteltoxin (147). ... 

One limitation encountered in synthetic studies of this reaction is the lack of chemoselectivity in the addition of aldehydes to unsymmetrically substituted furans. For example, the photochemical addition of benzaldehyde to 2-methylfuran provides a 1 3 1 mixture of oxetanes resulting from the exo addition of aldehyde to the more and less substituted alkenes, respectively. Ketone photocycloadditions are more selective. For instance, irradiation of 2-butanone and furan forms a 7 1 mixture of regioisomeric oxetanes (167) and (168) (1 1 mixture of epimers). 

In addition to furan, other heterocycles have been examined." Thiophene undergoes efficient photocycloaddition with benzaldehyde to afford a single exo photoproduct (183) in 60% yield. As reported by Jones and coworkers,the photolysis of IV-methylpyrrole in the presence of aldehydes or ketones yields the corresponding 3-hydroxyalkyl derivative (184), even when the reaction mixture is free from any trace of acid. In order to use the pyrrole nucleus for stereoselective alkaloid synthesis (cf. caesalpinine, 185) in the fashion developed with the furan nucleus, pyrrole substituents that stabilize the presumed intermediate bicyclic oxetane must be discovered. 

The Patemo-Buchl reaction of furan and various aldehydes was shown to be a highly stereoselective photochemical version of the aldol reaction by S.L. Schreiber and co-workers in which the furan serves as an enolate equivalent. This strategy was applied to the total synthesis of the antifungal metabolite (+)-avenaciolide. The photocycloaddition of nonanal with excess furan proceeded in nearly quantitative yield, and the two out of the three required stereocenters were created in a single step. The photocycloadduct was first hydrogenated then hydrolyzed under acidic conditions. 

Table 3 Examples of Regioselectivity in Photocycloadditions between Substituted Furans and Aldehydes...

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. 

---