Fused-furan synthesis

Similar to the Pd-catalyzed pyrrole and thiophene annulations, an intramolecular Heck reaction of substrate 91 resulted in benzofuran 92 [80], Such an approach has become a popular means of synthesizing fused furans. Muratake et al. exploited the intramolecular Heck cyclization to establish the tricyclic core structure en route to the synthesis of a furan analog of duocarmycin SA, a potent cytotoxic antibiotic [81]. Under Jeffery s phase-transfer catalysis conditions, substrate 93 was converted to tricyclic derivatives 94 and 95 as an inseparable mixture (ca. 4 1) of two double bond isomers. 

One of the earliest uses for rhodium(II)-catalyzed dipoles was demonstrated in Davies furan synthesis [22]. Isomiinchnones were also shown to produce substituted furans [115]. Additional furan syntheses have been described using silylacetates [116], unsaturated esters [117], and fluoroalkyl diazo acetates [118]. The synthesis of furofuranones and indenofuranones 35 from a-diazo ketones having pendant alkynes has also been reported (Eq. 6) [119]. Other fused heterocyclic systems include furo[3,4-c]furans [120, 121] furo[2,3-b]furans [122] as well as thiobenzofurans [123], and benzoxazoles[124] have also been synthesized with this methodology. 

The development of schemes for the total synthesis of the carbon skeleton of morphine revealed that the fused furan ring was not necessary for biological activity. More recently it has been found that substitution of a pyran ring for the terminal ali cyclic is also consistent with... 

When the chiral catalyst tetrakis(binaphtholphosphate)dirhodium was used, moderate enantiomeric excess (50%) was obtained in cycloaddition reactions with furans and dihydrofurans (359). This method has been applied to the synthesis of several natural products that contain fused furan rings, e.g., the human platelet... 

Maier and Schoffling (37) extended this intramolecular isomiinchnone cycloaddition to a synthesis of fused furans by employing an alkyne dipolarophile (Scheme 10.9). Thus, the diazo acetylenes (66) are smoothly converted to furans (69) via isomtinchnones (67) with catalytic rhodium acetate. 

The ring closure of o-allyl phenols has been extended to the synthesis of several other types of fused furans. 

Synthesis and reactions of fused furan derivatives 92MI6. 

A synthesis of [3]-fused furans involving a ring enlargement can be effected by the treatment of a-alkynyl-a-cyclopropylcycloalkanones with an electron-rich Au(l) catalyst in the presence of a suitable nucleophile (Equation 18) <2006AGE6704>. The nucleophiles that can be used include alcohols, phenols, carboxylic acids, indole, and 2-pyrrolidone. Open-chain ketones as well as other ring sizes react with comparable yields. Silver and lanthanide triflates are also effective catalysts for this transformation. 

Synthesis of tetrasubstituted furans via an intramolecular version of this methodology was reported by Padwa [206,207]. Alkyne-tethered diazoketones 176 and 178 underwent the Rh( 11)-catalyzed formal [3 + 2] cycloaddition affording fused furans 177 and 179 in good yields (Scheme 8.68). 

Later, Pirrung investigated the employment of cyclic diazo-1,3-dicarbonyl compounds for the Rh(II)-catalyzed synthesis of fused furans (Scheme 8.69) [208]. Diazocyclohexane-1,3-dione 180 underwent a formal [3 + 2] cycloaddition with a variety of terminal alkynes 181 bearing sensitive functional groups in the presence of... 

A palladium-catalyzed reductive cyclization of cyclic endiynal derivatives 142 with formic acid gives fused furans 143 bearing cyclic substituents at the 2-position (Scheme 19.34) [54], This is the furan version of the pyrrole synthesis already described (Scheme 19.15) [24]. 

Scheme 12.56 Synthesis of seven-membered ring-fused furans and thiophene.

An illustrative example of the potency of the second-generation Ru catalyst C is found in Paquette s highly efficient total synthesis of the natural products teubrevin G (122) and teubrevin H (123), which feature a cyclooctane core fused and spiroannulated to smaller oxygen-containing rings [76]. In the retrosyn-thetic analysis, the viability of an RCM step for annulation of a cyclooctenone ring to the furan played a central role. 

A palladium-catalyzed one-step synthesis of dihydrobenzo[fc]furan-based fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes was reported, and an example is provided in the scheme below <060L3601>. 2-Alkyl- or 2-aryl-substituted benzo[ >]furans were synthesized by a copper-TMEDA catalyzed intramolecular annulation from the corresponding ketones <06OL1467>. 

A further neat example of multicomponent reactions in heterocyclic synthesis was reported by Ma et al. <06AG(E)7793>. They prepared the furan-fused 1,4-thiazepine 140 in good yield using the three components 137, 138, and 139 in the one reaction. A range of other furan-fused analogues with different substituent groups in the thiazepine ring were also synthesised. 

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