Furan ring system preparation

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. 

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-... 

The asymmetric synthesis of a galanthamine alkaloid relies also on the intramolecular Heck reaction for the preparation of the benzo[h]furan-based key intermediate with a crucial chiral quaternary center, which eventually leads to the synthesis of (-)-galanthamine <00JA11262>. A similar approach towards the construction of galanthamine ring system via an intramolecular Heck reaction has also been investigated <00SL1163>. 

Cycloadditions of dienes with oxyallyl offer the opportunity to prepare seven-membeted ring systems. This reaction has also proved to be of importance in Ae furan series. A few examples may illustrate the value of this methodology. A tandem Pummerer rearrangement and intramolecular [4-i3]-cycloaddition with a fiiran derivative has been reported <99TL545>. For a similar reaction see <99T13999>. 

Amino acid-modified furocoumarins were prepared by condensation of the T-hydroxysuccinimide ester of 3-(2,3,5-trimethyl-7-oxofuro[3,2-g]chromen-6-yl)propanoic acid 51 with amino acids <2003JPH177>. Ethyl 3-(7-hydroxy-4-methyl-2-oxo-2/7-3-chromenyl)propanoate 49, prepared in 56% yield by Pechmann condensation of resorcinol and diethyl 2-acetylglutarate in the presence of HCl, was condensed with 3-chlorobutan-2-one in the presence of base to give propanoate 50 (Scheme 4). The MacLeod method was then used to fuse a furan ring to the benzopyran-2-one system. Heating 50 with NaOH solution (1 M) readily cyclized it into the corresponding psoralen furocoumarin 51 with simultaneous hydrolysis of the ester. 

Paal-Knorr synthesis can also be used to synthesize furan and thiophene ring systems. A simple dehydration of a 1,4-dicarbonyl compound provides the furan system, whereas thiophene or substituted thiophenes can be prepared by treating 1,4-dicarbonyl compounds with hydrogen sulphide (H2S) and hydrochloric acid (HCl). 

Double cyclizations to butenolides and furanes. Radicals can undergo intramolecular addition to triple bonds when separated by three carbons. This strategy can be used for synthesis of butenolides (equation 1) and -substituted furanes (equation II). Cyclization of vinyl bromides." Fused and bridged ring systems can be prepared... 

Dicarbonyl compounds are valuable intermediates in the preparation of natural products and related compounds containing pyrrole, thiophene, furan or cyclopentenone ring systems. 

The intramolecular Diels-Alder reaction of furans, often designated as IMDAF,15 helps to overcome the sluggishness of this heteroaromatic ring system toward [4+21-cycloaddition. Not only do IMDAF reactions allow for the preparation of complex oxygenated polycyclic compounds, but they also often proceed at lower temperatures than their intermolecular counterparts.9 Even more significantly, unactivated rc-bonds are often suitable dienophiles for the internal cycloaddition. Indeed, the submitters discovered that the IMDAF reaction of a series of furanamide derivatives occurred... 

In the domino Michael/alkylation reaction applied to the synthesis of 3-(2H)-furanones, the ethyl 4-bromoacetoacetate 203 and nitrostyrene 204 were first trialed with a range of catalysts. In this instance, the so-called modified Feist Binary reaction was completed with an I-threonine bifunctional tertiary amine/thiourea catalyst 205 to produce the furanone 206 in excellent yield and high enantioselec-tivity (Scheme 7.42) [107]. In another report, the furan ring as part of other bicyclic or tricyclic systems was also prepared through an enantioselective Michael addi-tion/nucleophilic substitution reaction (Scheme 7.43) [108]. When diketones and ( )-P,P-bromonitrostyrenes 207 were stirred, again with a bifunctional thiourea... 

The reactivity of this class of carbenes has also been explored in order to prepare novel tricyclic fiised-ring systems 23-24 (azepine derivatives) by a multicomponent procedure employing ortfto-dialdehydes, such as phthalaldehydes [19] or furan(thiophene)-3,4-dicarbaldehydes [20] (Scheme 5.17). 

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