3- Aryl-furans

Aryl furans were prepared in moderate yields by Rh-catalyzed regioselective hydroformylation of substituted propargylic alcohols followed by cyclization, and an example is shown below <06ASC545>. 

In a subsequent investigation by the author (3) arylated furan- and thiophenecarbox-amides, (III), were prepared and were effective in the treatment of atrial fibrillation or atrial flutters. 

As a consequence of the mild reaction conditions in the sequence to 3-halo furans 55 the palladium catalyst should be still intact to trigger another Pd-catalyzed coupling in the sense of a sequentially Pd-catalyzed process [31]. As a consequence, a sequential Sonogashira-deprotection-addition-cyclocondensation-Suzuki reaction, where the same catalyst system is applied in two consecutive significantly different cross-coupling reactions in the same reaction vessel should be feasible. Therefore, upon consecutive reactions of (hetero)aroyl chlorides 7 and THP-protected propargyl alcohols 54, Nal and PTSA, and finally, addition of 1.05 equiv of boronic acids 60 and sodium carbonate, the substituted 3-aryl furans 61 can be obtained in decent yields (Scheme 35). 

Scheme 35 Coupling-transacetalization-addition-cyclocondensation-Suzuki coupling four-component synthesis of 3-aryl furans 61...

The Bayer research group described further heterocyclic diones (Fig. 9.5), which all belong to this chemical class 3-aryl-pyrrolidine-2,4-diones 5 [62, 63], 3-aryl-furan-2,4-diones 6 [64], 2 aryl-cyclopentan-l,3-diones 7 [65] 4-phenyl-[l,2]oxazin-3,5-diones 8 [66]. 

The condensation of furo[3,2- ]pyrrole-type aldehydes 8g and 265-267 with hippuric acid was carried out in dry acetic anhydride catalyzed by potassium acetate as is shown in Scheme 26. The product methyl and ethyl 2-[( )-(5-oxo-2-phenyl-l,3-oxazol-5(4//)-ylidene)methyl]furo[3,2- ]pyrrol-5-carboxylates 268a-d were obtained. The course of the reaction was compared with the reaction of 5-arylated furan-2-carbaldehydes with hippuric acid. It was found that the carbonyl group attached at G-2 of the fused system 8 is less reactive than the carbonyl group in 5-arylated furan-2-carbaldehydes in this reaction <2004MOL11>. The configuration of the carbon-carbon double bond was determined using two-dimensional (2-D) NMR spectroscopic measurements and confirmed the (E) configuration of the products. 

Photolysis of iodohetarenes yields radicals which can arylate furan in the 2-position this method has been used to prepare 3-(2-furyl)pyridine (72CC594) and a variety of 5-(2-furyl)pyrimidines (77JCS(P 1)621). 

A novel one-pot three component synthesis of l,2,4-triazino[3,4-6]thiazolones 60 has been described by condensation of mercaptotriazinones 58, 5-aryl-furan-2-carboxaldehyde 59 and chloroacetic acid <05SC333>. 

Using only sulfur, a 74% yield of phenylfurane could be obtained, while chlor-anil in boiling ethylene glycol furnished the aryl furane in 10% yield. 

A mixture of 2-t-butylfuran and 2,5-di-t-butylfuran is obtained by the action of t-butyl chloride on furan in the presence of mesitylene nolybdenum tricarbonyl." The intermediate in the nitration of furan-2-aldehyde in acetic anhydride has been identified as compound (26). Treatment of 5-bromo-2-furoic acid with sulphur tetrafluoride in hydrogen fluoride yields the dihydrofuran (27). Bromo-furans are converted into aryl-furans by crosscoupling with aryl Grignard reagents in the presence of nickel(II)-phosphine complexes. 2-Furoic acid is lithiated at position 5, 3-furoic acid at C-2. 2-Methylfuran yields the 5-methylthio-derivative by lithiation and subsequent treatment with dimethyl disulphide. The corresponding phenylthio-compound (28) has been converted into a series of 4-substituted 2-methyl-furans (29 R = alkyl, MeaSi, CO2H, or RCHOH) by the sequence bromi-nation, lithiation, treatment with the appropriate electrophile, and, finally, desulphurization with Raney nickel. 2-Lithiofuran reacts with copper(II)... 

The reactions of a-halo-substituted fluorine-containing furans with nucleophilic reagents ° ° are the most studied reactions proceeding with participation of halogen atoms. A fluorine atom in 2-fluoro-3-trifluoromethyl-5-aryl-furans 224 is replaced smoothly by various nucleophiles.The similar reactions were reported for 2-fluoro-3 -trifluoromethyl-5 -aryl-thiophenes. ... 

A large number of new tropanyl esters and other related compounds have been prepared, with the purpose of contributing further structure-pharmacological activity relationships. Inter alia, para-substituted tropanyl benzoates (for studies of the substrate specificity of atropine esterase), benzazocines (narcotic antagonists) from 6-hydroxytropinone, 5-aryl-furan-2-carboxylic esters of pseudotropine (local anaesthetics), 2,4,5-trimethylpyrrole-3-carboxylic acid... 

Cross-coupling Reactions. Two major types of crosscoupling reactions have been reported in conjunction with the synthesis of arylated furans. Thus the photochemical coupling of furan... 

Gharpure and coworkers also found that the oxocarbenium ion from the cyclopropane opening reacts with carbon nucleophiles. C-Aryl furan 41 resulted from the use of 1,3,5-trimethoxybenzene (40) as the nucleophile in the ring opening (Scheme 12). 

Pd(II) salts promote the carbonylation of organomercury compounds. Reaction of phenylmercury chloride and PdCh under CO pressure affords benzophenone (429)[387]. Both esters and ketones are obtained by the carbonylation of furylmercury(Il) chloride in alcohol[388]. Although the yields are not satisfactory, esters are obtained by the carbonylation of aryl- and alkylmercuryfll) chlorides[389,390]. One-pot catalytic carbonylation of thiophene, furan, and pyrrole (430) takes place at the 2-position via mercuration and transmetallation by the use of PdCb, Hg(N03), and CuCl2[391]. 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

The cross-coupling of aromatic and heteroaromatic rings has been carried out extensively[555]. Tin compounds of heterocycles such as oxazo-lines[556,557], thiophene[558,559], furans[558], pyridines[558], and seleno-phenes [560] can be coupled with aryl halides. The syntheses of the phenylo.xazoline 691[552], dithiophenopyridine 692[56l] and 3-(2-pyridyl)qui-noline 693[562] are typical examples. 

Mercapto derivatives of furan, thiophene, selenophene (77ACS(B)198) and pyrrole (72AJC985) all exist predominantly in the thiol form. 2-Mercaptobenzothiophene is also a thiol (70JCS(C)243i) whereas 2-mercaptoindole is mainly indoline-2-thione (89) (69CPB550). The finely balanced nature of this system is indicated by the fact that a 3-aryl, but not a 3-alkyl, substituent will stabilize the 2-thiol form, whereas for 3-aryl-fV-methyl derivatives the 2-thione tautomer is preferred (71CC836). 

There are examples of preferential arylation of Af-substituted pyrroles, thiophenes and furans in the 2-position. A preparatively useful reaction of this type is the o-nitrophenylation of thiophene (Scheme 40). A phase transfer catalytic technique has been recommended for this reaction (77TL1871). 

There are reports of an increasing number of palladium-assisted reactions, in some of which the palladium has a catalytic function. Thus furan and thiophene undergo facile palladium-assisted alkenylation giving 2-substituted products. Benzo[6 Jfuran and TV- acetyl-indole yield cyclization products, dibenzofurans and carbazoles respectively, in addition to alkenylated products (8UOC851). The arylation of pyrroles can be effected by treatment with palladium acetate and an arene (Scheme 86) (81CC254). 

Benzo[b]furan, 3-(anilinoethyl)-4,5,6,7-tetrahydro-synthesis, 4, 671 Benzo[b]furan, 2-aryl-synthesis, 4, 697, 710 Benzo[b]furan, 3-aryl-synthesis, 4, 710... 

Benzo[b]furan, 2-aryl-2,3-dihydro- H NMR, 4, 570 Benzo[b]furan, 2-bromo-nitration, 4, 604 Benzo[b]furan, 5-cinnamoyl-properties, 4, 708 Benzo[b]furan, 2-cyano-photochemical reactions, 4, 636 Benzo[b]furan, 2,3-dialkyl-synthesis, 4, 710 Benzo[b]furan, 2,3-dihydro-aromaticity... 

Furan, 2-alkenyl-3-hydroxytetrahydro-synthesis, 4, 677 Furan, alkyl-reactions, 4, 644 synthesis, 4, 710 Furan, 2-alkyl-mass spectra, 4, 21-22 synthesis, 4, 666 Furan, 3-alkyl-mass spectra, 4, 21-22 synthesis, 4, 665, 710 Furan, 5-alkyl-2-phenylthio-reactions, 4, 80 Furan, 2-alkyltetrahydro-synthesis, 4, 675, 711 Furan, 3-amido-synthesis, 4, 665 Furan, 2-amino-synthesis, 4, 74, 121, 661 tautomerism, 4, 38 Furan, 3-amino-tautomerism, 4, 38 Furan, 2-amino-3-cyano-synthesis, 4, 661, 689, 712 Furan, 3-amino-2-methyl-reaction, 4, 74 Furan, 2-aryl-reactions... 

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