Furans from 1,4-dicarbonyl compound

Disubstituted furans are available from the combination of P-dicarbonyl compounds with bromoacetaldehyde diethyl acetal (44). For example, dibenzoylmethane (45) reacts with acetal 44 to furnish 2,3-disubstituted furan 46 in 77% yield. This two-... 

The ease with which furans may be formed from and hydrolyzed back to 1,4-dicarbonyl compounds, together with ready 5-lithiation of 2-substituted furans. 

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.

As depicted in the following scheme, in the presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzofuran derivatives were synthesized via an oxidation-Michael addition of P-dicarbonyl compounds to catechols in a one-pot procedure <06TL2615 06JHC1673>. A novel additive Pummerer reaction of 2-benzo[fc]furan sulfilimines with carbon nucleophiles derived from P-dicarbonyl compounds was also employed to the synthesis of 2,3-disubstituted benzo[b]furans <06TL595>. 

Substituted furan formation by an indirect cyclization of 1,4-dicarbonyl derivatives has also been adopted as a key step in the synthesis of 3-oxa-guaianolides. Although 1,4-dicarbonyl compounds have been traditionally considered as the direct precursors for furans, treatment of 1,4-dicarbonyl compounds having a tertiary acetoxy group with p-toluenesulfonic acid leads to only 11% yield of an alkenylfurans as derived from a cyclization/acetoxy-elimination route. The following scheme shows an alternative multi-step conversion of the 1,4-dicarbonyl that leads to a more acceptable yield of the acetoxyfuran . 

Aside from alcohols, other oxygen nucleophiles have also participated in hydroalkoxylation reactions with alkynes. The most common of these are 1,3-dicarbonyl compounds, whose enol oxygens are readily available to add to alkynes. Cyclization reactions of this type have been carried out under Pd(0) catalysis with various aryl or vinyl iodides or triflates, often in the presence of CO, affording the corresponding furan derivatives (Equation (95)).337-340 A similar approach employing cyclic 1,3-diketones has also been reported to prepare THFs and dihydropyrans under Pd, Pt, or W catalysis.341 Simple l-alkyn-5-ones have also been isomerized to furans under the influence of Hg(OTf)2.342... 

Furans, from acetylenic sul-fonium salts and 1,3-dicarbonyl compounds, 53, 3... 

On a commercial scale, furan is obtained from 2-formylfuran (furfural, furan-2-carbaldehyde) (see Section 6.2.7) by gas-phase decarbonylation, but in the laboratory, furans can be formed by the cyclodehydration of 1,4-dicarbonyl compounds. Heating in boiling benzene with a trace of /7-toluenesulfonic acid as a catalyst in a Dean-Stark apparatus is often effective (Scheme 6.30a). 

This is often achieved from 1,4-dicarbonyl compounds in a procedure similar to that used to form furans but using phosphorus pentasulfide, or Lawesson s reagent (see below), to cause a transposition from carbonyl to thiocarbonyl groups, prior to cyclization and loss of hydrogen sulfide (Scheme 6.37). 

The first two reactions of the sequence are similar to reactions that occur in acidic medium. The 1,2- and 2,3-enediols, and the unsaturated elimination-products derived from them, are present both in acidic and basic solutions. In general, however, reactions in basic solution are much faster than in acidic solution, because of the greater catalytic effect of the hydroxyl ion on the transformation reactions Mechanistic differences between the media become operative in steps c and d. In acid, further dehydration, if it is possible, occurs rapidly, before equilibrium of the deoxy-enediol with the dicarbonyl compound has been established,17 and the products are furans. In alkaline solution, the rapid formation of the tautomeric dicarbonyl compound permits the benzilic acid rearrangement42 to proceed. 

Pyrans 342 were prepared from furan derivatives 241, readily accessible by the reaction of glucose with /J-dicarbonyl compounds.328 The reaction was accomplished under acidic conditions and probably proceeds according to Eq. (16). 

The reversal of the well-known transformation of sugars into pyrans has been detailed as a method for assembling simple monosaccharides from simple furans (71T1973). A compound of the 2-furylcarbinol type was converted by the Br2/MeOH procedure into a mixture of the cis and trans isomers of the corresponding 2,5-dimethoxy-2,5-dihydrofuran derivative (129). Mild acid hydrolysis of (129) resulted in cleavage of the acetal bonds with formation of the dicarbonyl compound (130) which underwent immediate cyclization to 2,3-dideoxy-DL-alk-2-enopyranos-4-ulose (131 Scheme 29). 

Pyrroles, furans, thiophenes and pyrazolones from dicarbonyl compounds. 

Pyrroles, thiophenes, and furans from 1,4-dicarbonyl compounds... 

Standard heterocyclic syntheses tend to have a name associated with them and it is simply not worth while learning these names. Few chemists use any but the most famous of them we will mention the Knorr pyrrole synthesis, the Hantzsch pyridine synthesis, and the Fischer and Reissert indole syntheses. We did not mention that the synthesis of furans from 1,4-dicarbonyl compounds is known as the Feist-Benary synthesis, and there are many more like this. If you are really interested in these other names we suggest you consult a specialist book on heterocyclic chemistry. 

The acid fission of furans, to yield 1,4-dicarbonyl compounds, is not satisfactory from the preparative point of view. This fission reaction has recently been restudied.169, 287-292 It is preferable to use the route involving 2,5-dialkoxy-2,5-dihydrofurans, which on hydrogenation and acid hydrolysis give the desired 1,4-dicarbonyl compounds. 

Tetrasubstituted furans were obtained by a simple and efficient protocol starting from propargylic alcohols and 1,3-dicarbonyl compounds in the presence of a ruthenium-catalyst and CF3CO2H <07ASC382>. 

Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by Initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from Sn2 displacement at the allylic site.11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable Ai -interaction in the transition state when a substituent group is present at the 2-position ol the dicarbonyl compound. This steric Interaction is not present in the transition state leading to the cyclopentenone ring. 

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