A Furan Synthesis

Treatment of methyl vinyl ketone with sodium benzyloxide (1 esq.) followed by bromine (1 eq.) gave the expected alkoxy bromo ketone. Reaction of the latter with DBU in benzene at room temperature gave a 70% yield of 5-acetyl-3-benzyloxymethyl-2-methylfuran. 

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Separately, Paal and Knorr described the initial examples of condensation reactions between 1,4-diketones and primary amines, which became known as the Paal-Knorr pyrrole synthesis. Paal also developed a furan synthesis in related studies. The central theme of these reactions involves cyclizations of 1,4-diketones, either in the presence of a primary amine (Paal-Knorr pyrrole synthesis), in the presence of a sulfur(II) source (Paal thiophene synthesis), or by dehydration of the diketone itself (Paal furan synthesis). 

Furanes. In a furane synthesis described recently the a-bromo acetal (1) and silyl enol ethers (2) react, in the presence of TiCU, to form alkoxy-7-bromoketones (3). The products undergo dehydrohalogenation and loss of CH3OH when heated in toluene for 5-8 hr. to form furanes (4). The furanes (4) are sometimes accompanied by (5), formed by elimination of only CH3OH. 

In 2003, the Uemura group reported a diversity-oriented approach to highly substituted furans based on ruthenium- and platinum-catalyzed intramolecular annulation of propargylic alcohols 59 and ketones 60 (Scheme 19.28) [22]. This reaction is related to the aforementioned pyrrole synthesis (Scheme 19.13). Based on the time profile of the reaction, in which rapid formation/consumption of the alk-4-yn-l-one 63 was seen but only gradual formation/consumption of the diketone 122 was observed, they proposed a mechanism including alkyne hydration and subsequent cyclization of the resulting diketones. However, this reaction can be considered as a furan synthesis by formal reaction between the C=0 and alkyne groups. 

H-Benzo[a]carbazole, 4,4a,5,l 1,1 la,l Ib-hexahydro-synthesis, 4, 283 Benzo[b]carbazole, N-acetyl-photochemical rearrangements, 4, 204 Benzo[/]chroman-4-one, 9-hydroxy-2,2-dimethyl-synthesis, 3, 851 Benzochromanones synthesis, 3, 850, 851, 855 Benzochromones synthesis, 3, 821 Benzocinnoline-N-imide ring expansion, 7, 255 Benzocinnolines synthesis, 2, 69, 75 UV, 2, 127 Benzocoumarins synthesis, 3, 810 Benzo[15]crown-5 potassium complex crystal stmcture, 7, 735 sodium complex crystal stmcture, 7, 735 Benzo[ 18]cr own-6 membrane transport and, 7, 756 Benzo[b]cyclohepta[d]furans synthesis, 4, 106 Benzocycloheptathi azoles synthesis, 5, 120... 

FEIST - SENARY Furan Synthesis Synthesis ol lurans by condensation ol an a-halocarbonyl compound with an enol. 

Badger and coworkers devised a sequential synthesis of [ 18]annulene-l,4 7,10 l 3,16-trioxide which is formally the condensation product of three furan molecules and three ethylenes . The synthesis is illustrated below in Eq. (3.25). The [18]annulene trioxide was obtained as a red solid (mp 215—216 °d) whose proton nmr spectrum showed two peaks of equal area at 8.66 and 8.68 ppm. 

A novel synthesis of nornicotyrine has been described by Lions and Ritchie, who condensed ethyl nicotinylacetate hydrochloride with a -dichlorodiethyl ether in presence of ammonia at — 10° to — 13° and then at room temperature, producing mainly ethyl 2-(3 -pyridyl)furan-3-carboxylate, but also some ethyl 2-(3 -pyridyl)pyrrole-3-carboxylate,... 

The Feist-Benary furan synthesis occurs when an a-halocarbonyl (1) reacts with a P-dicarbonyl (2) in the presence of a base. The resulting product (3) is a 3-furoate that incorporates substituents present in the two starting materials. ... 

Several modifications of the Feist-Benary furan synthesis have been reported and fall into two general classes 1) reactions that yield furan products 2) reactions that yield dihydrofuran products. One variant that furnishes dihydrofiirans uses substrates identical to the traditional Feist-Benary furan synthesis with a slight modification of the reaction conditions. The other transformations covered in this section involve the combination of P-dicarbonyls with reagents that are not simple a-halocarbonyls. Several reactions incorporate a-halocarbonyl derivatives while others rely on completely different compounds. 

Treatment of 1,4-dicarbonyls (1) with catalytic acid yields substituted furans (2) and is called the Paal-Knorr furan synthesis. This method is used extensively to produce a variety of mono-, di-, tri-, and tetrasubstituted furans. ... 

Ibers used the Paal-Knorr furan synthesis to prepare a key intermediate for the synthesis of novel porphyrin-like aromatic macrocycles. Bis yrolyljfuran 27 was available in good yield via the acid catalyzed condensation of diketone 26. ... 

A biarylpropionic acid derivative containing a furan ring as a prominent feature has antiinflammatory activity. The patented synthesis involves a straightforward organometal1ic addition of ethyl lithioacetate to aldehyde 12 followed by saponification... 

Two sequential pericyclic reactions are involved in the following furan synthesis. Identify them, and propose a mechanism for the transformation. 

Scheme 3b). It is instructive at this point to reiterate that the furan nucleus can be used in synthesis as a progenitor for a 1,4-dicarbonyl. Whereas the action of aqueous acid on a furan is known to provide direct access to a 1,4-dicarbonyl compound, exposure of a furan to an alcohol and an acid catalyst should result in the formation of a 1,4-diketal. Indeed, when a solution of intermediate 15 in benzene is treated with excess ethylene glycol, a catalytic amount of / ara-toluenesulfonic acid, and a trace of hydroquinone at reflux, bisethylene ketal 14 is formed in a yield of 71 %. The azeotropic removal of water provides a driving force for the ketalization reaction, and the presence of a trace of hydroquinone suppresses the formation of polymeric material. Through a Finkelstein reaction,14 the action of sodium iodide on primary bromide 14 results in the formation of primary iodide 23, a substance which is then treated, in crude form, with triphenylphosphine to give crystalline phosphonium iodide 24 in a yield of 93 % from 14.

The add-catalyzed cyclodehydration of (Z)- and ( )-6-hydroxy-a,p-unsaturared ketones offers a mild synthesis of substituted furans. In the case of ( )-olefins, photochemical isomerisation was found to accelerate the reaction <96TL6065>. Reaction of alkynyl(phenyl)iodonium tetrafluoroborates with tropolone in the presence of a base yields 2-substituted furotropones (Scheme 16, <96TL5539>). 

Formation of a 6-hydroxydihydropyran-3-one by the oxidative rearrangement of a furan followed by its conversion to a pyrylium ylide forms part of a synthesis of the taxane skeleton <96T14081>. 

The approach also allows the synthesis of furans by employing ethoxymethylene malonate, followed by an eliminative decarboxylation. This method was used by Balme for a formal synthesis of the antitumor lignan burseran (6/1-294), starting from 6/1-290,6/1-291 and 6/1-292 via the furan 6/1-293 (Scheme 6/1.78) [139], Furans as 6/1-298 can also be obtained by Pd-catalyzed reaction of 2-propynyl-l,3-dicarbonyls 6/1-295 with aryl halides 6/1-296 in DMF, using potassium carbonate as base, as shown by Arcadi, Cacchi and coworkers (Scheme 6/1.79) [140]. 

Individual substitutions may not necessarily be true electrophilic aromatic substitution reactions. Usually it is assumed that they are, however, and with this assumption the furan nucleus can be compared with others. For tri-fluoroacetylation by trifluoroacetic anhydride at 75 C relative rates have been established, by means of competition experiments 149 thiophene, 1 selenophene, 6.5 furan, 1.4 x 102 2-methylfuran, 1.2 x 105 pyrrole, 5.3 x 107. While nitrogen is usually a better source of electrons for an incoming electrophile (as in pyrrole versus furan) there are exceptions. For example, the enamine 63 reacts with Eschenmoser s salt at the 5-position and not at the enamine grouping.150 Also amusing is an attempted Fischer indole synthesis in which a furan ring is near the reaction site and diverted the reaction into a pyrazole synthesis.151... 

Gold as an efficient catalyst has widely been used in furan synthesis. One example is shown below, in which the double hydroarylation of unactivated alkyne using 2-methylfuran afforded a difuranylmethane derivative in a moderate yield <06EJOC4340>. 

As can be seen in the scheme below, the catalytic activity of gold species was also shown in a multi-substituted furan synthesis. Cyclization of allenones in the presence of Au(III)-porphyrin gave rise to the corresponding substituted furan in good to high yields. The catalyst can be recycled several times and still maintain the same catalytic activity <06OL325>. 

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