Furans reactions with singlet oxygen

A six-step synthesis of hexahydrofuro[3,2-3]oxepin-2(3/7)-one involves cyclization with the formation of an ethereal C-0 bond (Scheme 13). However, its specific peculiarities are that the product skeleton is built from tetrahydrofuran (THF) and furan, the key reactions being the oxidation of a furan ring with singlet oxygen, followed by an intramolecular Michael addition to 2(5/7)-furanone C=C bond <2003TL4467, 2004TL5207>. 

Furans also form cyclic peroxides on reaction with singlet oxygen these undergo some interesting rearrangements as shown by the formation of the 2-aroyl enol esters 226 from the peroxides derived from 2-arylfurans. 

A series of anti-inflammatory hydroxy butenolides was synthesized starting from 55. Thus heating 55 with ethyl phenyl-prop-1-ynoate 141 for 16 h at 210°C afforded 3-phenyl-4-furancarboxylic acid ethyl ester 142 (Fig. 3.42). Functionalization of the ester followed by reaction of the furan ring with singlet oxygen gave the biologically active butenolides, 143. 

Thiophenes. It has been reported that thiophenes, unlike the furans and pyrroles, do not react by sensitized photooxidation however, when thiophene is substituted with alkyl group, it does undergo reaction with singlet oxygen (Matsuura and Saito, 1976). Photosensitized oxidation of 2,5-dimethylthiophene in either chloroform or methanol gives a diketone and a sulfme as shown in Scheme 21 (Skold and Schlessinger, 1970). Three possible pathways which lead to sulfine formation have been proposed (Scheme 21). 

Mass spectrometry has been used to investigate the mechanism of ozonolysis <79JOC3i85,80JA4763) and to study the gas-phase reaction of furans with singlet oxygen in which endoperoxides are intermediates. 

It is known that thiophenes react with singlet oxygen forming endoperoxides, which are thiaozonides, and whose thermal reactions have been investigated. A novel reaction of acylthiophene endoperoxides 213 (photosensitized oxidation with tetraphenylporphyrine at —30 °C) involves their treatment with triphenylphosphine. The nucleophilic attack finally leads to a furan derivative 214 by elimination of O and S atoms bound to phosphorus (Scheme 71) <1995TL7431, 1998JA8914>. 

The oxazoles also display a number of characteristics that are typical of the furans and are explained by the structural similarity of these heterocyclic systems. The ease with which they undergo Diels-Alder reactions with dienophiles and autooxidation with singlet oxygen (see Sections IV, D and E) clearly demonstrates that oxazoles are not fully aromatic. This fact and ultraviolet data (Section III, E) suggest that oxazoles should be considered partly as conjugated dienes. 

Furans also undergo cycloaddition with singlet oxygen this can be made the basis for the synthesis of 5-hydroxy-2(5/f)-furanones (4-hydroxybut-2-eno-lides, see section 15.12), a structural unit which occurs in several natural products. For example, addition to a 3-substituted furan in the presence of a hindered base or addition " to 2-trialkylsilyl-4-substituted furans leads through, as shown, to 4-substituted 5-hydroxy-2(5//)-furanones. A particularly neat example is the reaction of 2-furoic acid, which is converted in quantitative yield, with decarboxj lation, into malaldehydic acid (the cyclic hemiacetal of Z-4-oxobut-2-enoic acid). ... 

Fig. 3.25. Side reaction of a branched furan fatty acid with singlet oxygen (R (CH2)iCOOH)...

The primary interaction of singlet oxygen, produced by energy transfer from the excited sensitizer, with the diene can give rise to an exciplet that then collapses to peroxide, to a 1,4-biradical or to a 1,4-zwitterion alternatively, the adduct is the result of a concerted action without the involvement of an intermediate. Detailed kinetic Diels-Alder investigations of singlet oxygen and furans indicate that the reactions proceed concertedly but are asynchronous with the involvement of an exciplex as the primary reaction intermediate [63]. 

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