Cyclization furans from

The last method for the preparation of 2-quinolones described in this chapter relies on a intramolecular Heck cyclization starting from heteroaryl-amides (Table 2) [57]. These are synthesized either from commercially available pyrrole- and thiophene-2-carboxylic acids (a, Table 2) or thiophene-and furan-3-carboxylic acids (b, Table 2) in three steps. The Heck cyclization is conventionally performed with W,Ar-dimethylacetamide (DMA) as solvent, KOAc as base and Pd(PPh3)4 as catalyst for 24 h at 120 °C resulting in the coupled products in 56-89% yields. As discussed in Sect. 3.4, transition metal-catalyzed reactions often benefit from microwave irradiation [58-61], and so is the case also for this intramolecular reaction. In fact, derivatives with an aryl iodide were successfully coupled by conventional methods, whereas the heteroarylbromides 18 and 19, shown in Table 2, could only be coupled in satisfying yields by using MAOS (Table 2). 

A highly efficient synthesis of l-alkylidene-l,3-dihydrobenzo[f]furans from t>-hydroxymethyl iodoarenes and propargyl alcohols uses a bimetallic Pd/Cu-catalyzed Sonogashira coupling/cyclization reaction (Equation 132) <1999SL456>. Pd/l,4-bis(diphenylphosphino)butane (DPPB)-catalyzed reaction of t>-allylphenols under a CO atmosphere leads to carbonylative cyclization to form benzannulated lactones <2006ASC1855>. A similar carbonylative cyclization leads to the stereoselective formation of 3-alkenyl phthalides <2006T4563>. 

A three-component domino reaction catalyzed by palladium that produces 4,5-disubstituted dihydrobenzo[ ]furans from readily available starting materials has been developed by Pache and Lautens. The reactions of iodobenzenes of type 61 with Bui and tert- mx acrylate, as shown, give good yields of cyclization products (Scheme 96) <2003OL4827>. A reaction mechanism which involves sequential alkylation-alkenylation has been proposed. 

The oxidation of ethylene has been investigated on polycrystalline P UO3 surfaces. Two oxygen containing products were observed acetaldehyde, and furan. Furan desorption which requires a C-C bond formation, most likely is formed via dimerization of two adsorbed ethylene molecules followed by cyclization with available surface oxygen. Both the formation of acetaldehyde and furan from ethylene on UO3 are clear examples of the ease of removing oxygen atoms from UO3 surfaces. The reduction of acetaldehyde was also... 

The above approaches can also be applied to a range of other aromatic heterocycles, including furans, thiophenes and oxazoles [2, 15]. While these protocols typically require the initial assembly of the precursor for cyclization, Trost has demonstrated that palladium catalysis can also be employed to assemble the en-yn-ol 8 for cyclization to furans. (Scheme 6.11) [16]. This reaction, that proceeds via the palladium-catalyzed regioselective addition of terminal alkynes to internal propargyl alcohols, provides a biomolecular method to build up furans from these two alkyne building blocks. 

Substituted naphtho[lr]furans and benzo[fc]furans were easily accessible by treatment of naphthols/substituted phenols with nitroallylic acetates through a substitution-elimination process promoted by cesium carbonate (13CEJ4344). Aminobenzo[l)]furan could be obtained by a one-pot con-densation-cyclization sequence from ethyl glycolate with chloropyridine (13BMCL2781). An intramolecular cyclization of 2-(gem-dibromovinyl) phenols(thiophenols) produced 2-bromobenzo[lr]furans(thiophenes) in the presence of Cu (13OBC4095). 

In a similar way, iminoalkynes containing aryl, alkenyl, and alkyl substituents undergoes Cul-catalyzed cyclization in excellent yields and short reaction times to give isoquinolines, pyridines, and pyrroles via a cycloisomerization (eq 18)4 Copper chloride is preferred, however, for the conversion of cyclic alkynyl imines to pyrrole-containing heterocycles. Copper iodide catalyzes the formation of furans from alkynyl ketones. ... 

A direct synthesis of substituted pyridines in yields of about 50% is found in the treatment of acetylene and an alkyl nitrile in the presence of a cobalt catalyst. A general method for the synthesis of 3- and 3,4-substituted furans from ketones has been developed. A new route to various heterocycles with 2 or more heteroatoms has been presented, as well as a procedure involving 1,3- or 3,3-cyclization on difunctional nucleophiles, such as hydrazine, hydroxylamine, alkyl and aryl-diamines. 76 77... 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

Phenolic oxygen participates in facile oxypalladation. The intramolecular reaction of 2-hydroxychalcone (105) produces the flavone 106[127]. The ben-zofuran 107 is formed from 2-allyIphenol by exo cyclization with Pd(OAc)2, but benzopyran 108 is obtained by endo cyclization with PdChf S], Normal cyclization takes place to form the furan 109 from 2-(l-phenylethenyl)phe-nol[129]. Benzofuran formation by this method has been utilized in the synthesis of aklavinione (110)[130]. 

Alkynyl)oxiranes also react with carbon nucleophiles to afford furan derivatives. Furanes of different types are obtained depending on the structure of the substrates. 7-Methyl-2-ethynyloxirane (95) reacts with acetoacetate to give the furan 97 by the elimination of formaldehyde from the cyclized product 96. The hydroxy ester of the alkylidenefuran 98 and the corresponding lactone 99 are obtained by the reaction of i-methyl-2-(2-propynyI)oxirane[40, 42]. 

A variety of 2,5-dialkylfurans are available via the Paal-Knorr condensation cyclization is possible for both hindered and unhindered 1,4-diketones. Fleming prepared 2-cyclohexyl-5-methylfuran (31) in 91% yield via treatment of dione 30 with catalytic p-toluenesulfonic acid in refluxing benzene. Using the same methodology, Denisenko synthesized furan 33 in 35% yield from the corresponding dione (32). ... 

A recent report demonstrates that trisubstituted furans can be prepared on a solid support using the Paal-Knorr condensation. Raghavan synthesized a variety of triaryl and alkyl diary] furans, one of which is highlighted below. Dione 50 was cyclized using p-toluenesulfonic acid in refluxing toluene followed by cleavage from the solid support to yield furan 51. ... 

A stmple and general synthesis of 2,2,4,5-tetrasubstituted furan-3(2//)-ones from 4-hydroxyalk-2-ynones and alkyl halides via tandem CO, addition-elimination protocol is described <96S 1431>. Palladiuni-mediated intramolecular cyclization of substituted pentynoic adds offers a new route to y-arylidenebutyrolactones <96TL1429>. The first total synthesis of (-)-goniofupyrone 39 was reported. Constmction of the dioxabicyclo[4.3.0]nonenone skeleton was achieved by tosylation of an allylic hydroxy group, followed by exposure to TBAF-HF <96TL5389>. 

---