2,5-disubstituted furan rings

The early synthetic endeavors in this area focused mainly on the synthesis of various nonactic acid derivatives. The scenario utilized in almost all of these early studies involved the hydrogenation of a 2,5-disubstituted furan ring to give a cis-disubstituted tetrahydrofuran. 

Two sequential electrochemical annulations of an electron-rich 3,4-disubstituted furan ring were employed to generate the fused tricyclic ring system of arteannuins. The second reaction, as depicted below, represented the formation of a quaternary carbon center by a formal 6-endo cyclization under these anodic oxidation conditions <07OL4599>. 

The structures of all these compounds were established by spectral data including 2D NMR techniques. X-ray analysis were performed for compounds 60 (alysine A) and 139 (alysine B) in order to be sure of their stereochemistry. All six compounds had typical substitutions of neo-clerodane diterpenes, only instead of a monosubstituted fiiran, they all have a, P-disubstituted furan ring, which was the first isolation of such type of compounds. 

Five more furanosesquiterpenes have recently been isolated from acetone extracts of the sponge Disidea pallescens, all of which, on a preliminary spectral examination, contain a 2,3-disubstituted furan ring 61). For the major components pallescensin-G and -F, the isomeric structures (43) and (44) have been proposed, respectively, on spectral grounds and biogenetic considerations 46). The spectral arguments are briefly summarized below. 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

As can be seen below, a retro-Diels-Alder strategy was used to prepare 2,3- and 2,4-disubstituted furans with a SF5 group as one of the substituents, which was introduced into furan ring for the first time <06OL5573>. 

A flexible entry into 2,4-disubstituted furan derivatives through condensation of the sulfur ylide derived from 20 with aldehydes, Pd-catalyzed opening of the vinyl oxirane thus formed, and a final oxidative cyclization of the furan ring was reported. Its utility was exemplified by the first total synthesis of the marine natural product ircinin-4 (21) <99SL29>. 

Table 6 lists proton chemical shifts for a selection of monosubstituted furans including some with a metal or other less common heteroatom attached to the ring, but perhaps it should be noted that values are not closely comparable unless obtained in closely comparable conditions. Solvents can have a substantial effect upon chemical shifts (66CR(B)(263)1227>, especially benzene (72JA8854). Table 7 lists some ring interproton coupling constants and Table 8 some shift values for disubstituted furans. Polysubstituted furans are covered in the reviews and compilations mentioned above. 

Disubstituted furans (130) can be obtained by treatment of j8-alkoxy- and j8-arylthio-a,j8-unsaturated ketones, for example 3-methoxy-l-phenyI-2-buten-l-one (128) or 3-ethylthio-l-phenyl-2-buten-l-one (129), with dimethylsulfonium methylide (79JHC815, 69TL679). The possible reaction pathway (Scheme 27) shows the initially formed epoxides as rearranging by ring opening at the tertiary epoxide carbon atom. 

Reaction of vinylcarbenoids with furans offers another level of complexity because the furanocyclo-propanes in this case would be divinylcyclopropanes capable of a Cope rearrangement as well as electro-cyclic ring opening to trienes.27b c As illustrated in Scheme 42, the product distribution was dependent on the furan structure. With 2,5-disubstituted furans [3.2.1 ]-bicyclic systems (202) were exclusively formed, but with furan or 2-substituted furans, trienes (203) were also produced. 

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