Furan ring systems

Acid-catalyzed hydrogen exchange is used as a measure of the comparative reactivity of different aromatic rings (see Table 5). These reactions take place on the neutral molecules or, at high acidities, on the cations. At the preferred positions the neutral isoxazole, isothiazole and pyrazole rings are all considerably more reactive than benzene. Although the 4-position of isothiazole is somewhat less reactive than the 4-position in thiophene, a similar situation does not exist with isoxazole-furan ring systems. 

A review of Claisen rearrangements in aqueous solution has appeared. The synthesis of natural products utilizing tandem Diels-Alder additions with sigmatropic rearrangement processes has been reviewed, and a brief review of the regioselective synthesis of coumarins, quinolones and thiocoumarins with 3,4-fused pyran or furan ring systems by the Claisen rearrangement has been presented. ... 

The chemistry of fiiians and benzofurans was a Held of lively research in the last year. There are a number of reasons for this activity. The furan ring system - both in its native as well as in its reduced form - occurs in a great number of natural products and a wide variety of these compounds has been isolated from natural sources. This subject is treated regularly with care and accuracy in Heterocycles and will not be repeated here. Therefore only a few examples will be given in this chapter. Several new furan derivatives were isolated from natural sources (-)-wistarin 1 from the marine sponge Ircinia sp. <99TA3869>,... 

The importance of the benzo[6]furan ring system in natural substances and in synthetic products with pharmacodynamic applications explains the large number of papers published. Our aim is not to make an exhaustive study, but rather to underline the important aspects of the modem chemistry of benzo[6]furan and its derivatives ... 

The furo[3,4-c]furan ring system of lignan, ( )-paulownin (51) was constructed stereoselectively by Kraus et al. [16] by the photocyclization of 50, as shown in Scheme 8.15... 

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). 

Excluding the solubility limitations imposed by the substituents that may be bonded to the furan ring system, the compounds are readily soluble in the chlorinated solvents normally utilized as NMR solvents (CCI4 and CDCI3). 

The aromatic furan ring system, though not found in animal metabolism, occurs widely in secondary plant metabolites, especially in terpenoids perillene is a simple example. Vitamin C, ascorbic acid, is at the oxidation level of a trihydroxyfuran, though it assumes an unsaturated lactone tautomeric form. Though one normally associates thiols with unpleasant odours, furfuryl thiol is present in the aroma of roasted coffee. Some 5-nitrofurfural derivatives are important in medicine, Nitrofurazone, a bactericide, is a simple example. Ranitidine is one of the most commercially successful medicines ever developed it is used for the treatment of stomach ulcers. 

Scheme 4.28 TMG (1) mediated intramolecular cyclization to furan ring system...

The Feist-Benary and Paal-Knorr syntheses are commonly employed in the preparation of furan ring systems. In special cases where furan derivatives are difficult to prepare by other methods, Diels-Alder and retro-Diels-Alder reactions have become important methods for their synthesis. Finally, transition metal-catalyzed cyclization and cycloisomerization reactions have recently gained significant attention for their utility in the synthesis of highly functionalized furans. Key examples of these syntheses are highlighted in the sections below. 

In general, the furan ring system appears to far less reactive than the thiophene system, and it is therefore much less toxic. This is most likely due to the higher electronegativity of the oxygen atom, which reduces the reactivity of the ring toward oxidation. 

The first total synthesis of ( )-furoscrobiculin B (18.9) was accomplished by K. Kanematsu 160) through a novel construction of the azuleno [6,7-c] furan ring system by base catalysed pinacol-type rearrangement of the isonaphthofuran derivatives 26.122 (Schemes 37... 

The inverted porphyrins (also called N-confused porphyrins) 289 were discovered accidentally as by-products of the well-known acid-catalyzed pyrrole aldehyde cyclocondensation route to porphyrins (Scheme 58) (see Chapter 14 by Latos-Grazynski). Rational multistep synthetic approaches to inverted porphyrins have t peared recently. Dolphin and coworkers. s have reported a method for the preparation of porphyrin 292 involving acid-catalyzed MacDonald-type (2 -I- 2) condensation of an a,j8-dipyrromethane 291 and a,a-dipyrromethane dialdehyde 290. Lee and coworkers have reported a (3 -I- 1) approach to porphyrin analogues with an inverted pyrrole and a thiphene, or a furan ring system 293 (Scheme 59). Pandey et reported the preparation of dibromo-a, c-... 

Synthesis of furans has been carried out via three-component reactions involving intermolecular carbonyl ylide formation. Johnson and co-workers have revealed [65] the consequence of intermolecular carbonyl ylide generation followed by trapping with a selective dipolarophile to obtain furan ring systems. On the basis of this approach, the diazosulfone 8 underwent intermolecular reaction with aldehydes in the presence of Rh2 (oct)4 to form carbonyl ylide intermediates, which could be trapped by alkynes in an inter-or intramolecular manner to yield substituted dihydrofurans 9 or 11, which were later converted to furans 10 and 12, respectively (Scheme 2). 

The most common form of heterocyclic oxygen is in furan ring systems. Substituted furan rings have been reported in coal extracts, pyrolysis tars, and oxidative degradation products (Duty et al., 1980 Bodzek and Marzek, 1981 see also White, 1983). However, to exactly what extent the diben-zofuran system exists in the parent coal is not clear. The isolation of dibenzofuran from oxidative degradation products and low-C temperature coal extracts supports the view that it is present in the parent coal. 

Carbene complexes have proven to be highly useful in the constmction of pyrrole and furan ring systems. Very often these processes result in unique disconnections to these ring systems that have no parallel in classical organic chemistry. Specific examples are depicted in the following sections. 

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