Substitution Reactions of the Furan Ring

Perfluoroalkyl-substituted propynoates and furans react to give Diels-Alder adducts. The success of the subsequent retro process depends on the substitution pattern of the furan ring system. The adducts of unsubstituted furan are thermally relatively stabile, whereas the [4 + 2] cycloadducts of 2,5-dimethylfuran readily undergo a thermally induced retro-Diels-Alder reaction to give the 3-trifluoromethylfuran in high yield [91JFC(53)285] (Scheme 89). 

Quantitative data are available on the effect on electrophilic substitution reactions of the fusion of a benzene ring to the b face of a furan or thiophene ring. The overall effect is to decrease reactivity this decrease is much more pronounced in the case of fusion to a furan than to a thiophene ring. As a consequence the overall reactivities of benzo[Z)]furan and benzo[Z)]thiophene are approximately equal 71AHC(13)235). 

Four years later, we reported an improved iron-mediated total synthesis of furostifoline (224) (689). This approach features a reverse order of the two cyclization reactions by first forming the carbazole nucleus, then annulation of the furan ring. As a consequence, in this synthesis the intermediate protection of the amino function is not necessary (cf. Schemes 5.178 and 5.179). The electrophilic aromatic substitution at the arylamine 1106 by reaction with the iron complex salt 602 afforded the iron... 

Five-Membered Unsaturated Heterocycles 1151 Structures of Pyrrole, Furan, and Thiophene 1152 Electrophilic Substitution Reactions of Pyrrole, Furan, and Thiophene 1153 Pyridine, a Six-Membered Heterocycle Electrophilic Substitution of Pyridine Nucleophilic Substitution of Pyridine Fused-Ring Heterocycles 1158 Nucleic Acids and Nucleotides 1160 Structure of Nucleic Acids 1163 Base Pairing in DNA The Watson-Crick Model Nucleic Acids and Heredity 1166 Replication of DNA 1167... 

Inverse demand Diels-Alder reactions of tetrazines 1 to psoralenes 267 were reported to furnish tetracyclic pyridazine dicarboxylates 268, which were used as the key intermediates in the synthesis of nitrogenated isosteres of potent DNA inhibitors <2003T8171>. In some cases, cycloaddition was followed by opening of the furan ring to give pyridazinyl-substituted coumarins 271 (Scheme 66) <2000JHC907, 2003SL2225>. 

Extrusion of sulfur dioxide from oxidized thiophene derivatives is an exceptional method to prepare cis-dienes as components for Diels-Alder reactions. An example of this approach utilizes the Diels-Alder reactivity of the furan ring in substituted 4//,6ff-thieno[3,4-c]furan-3,S-dioxides to react with a variety of dienophiles such as DMAD, dimethyl maleate and dimethyl fumarate which then lose SO2 to form another reactive diene (Eq. 17) <94H961>. A review of the preparation and use of 4i/,6f/-thieno[3,4-c]furan-S,5-dioxides as well as other heteroaromatic-fused 3-suIfolenes is report <94H1417>. The preparation of dihydrothienooxazole 80 requires the careful control of the reaction time and temperature as well as the reactants molar ratio <94JOC2241>. Specific control of the alkylation conditions for 81 (X = COCH3) allows for the preparation of either 1,4-disubstituted or 1,6-disubstituted 4, 6//-thieno[3,4-c]furan-S,S-dioxides. These molecules could be used as intermediates for the preparation of novel pentacyclic compounds <94JCS(P1)1371>. 

The outcome of the intramolecular reaction between vinylcar-benoids and furans depends on the structure of the vinylcarbenoid and the position of the tether. In the case of the 2-substituted fiiran 126, the triene 127 is formed exclusively (Scheme 43). Presumably, the additional strain in the intramolecular version favors unraveling of the furan ring to the triene rather than forming the [3+4] annulation product. In contrast, reaction of the 3-substituted furans 128 results in the synthesis of novel tricyclic products 129 that contain two formally anti-Bredt double bonds. " ... 

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