2,3,4-Tris furan, preparation

Alkynes substituted with one or two trifluoromethyl groups are also highly reactive dienophiles [9] Indeed, hexafluoro-2-butyne is used increasingly as a definitive acetylenic dienophile in "difficult Diels-Alder reactions. It was used, for example, to prepare novel inside-outside bicycloalkanes via its reaction with cir,trnns -l,3-undecadiene [74] (equation 67) and to do a tandem Diels-Alder reaction with a l,l-bis(pyrrole)methane [75] (equation 68) Indeed, its reactions with pyrrole derivatives and furan have been used in the syntheses of 3,4-bis(tri-fluoromethyl)pyrrole [76, 77] (equation 69) and ],4-bis(trifluoromethyl)benzene-2,3-oxide [78] (equation 70), respectively. 

In a series of papers in late 1884 and early 1885, Paal and Knorr demonstrated that several 1,4-dicarbonyls could be transformed into furans, pyrroles, and thiophenes. Paal first discovered this transformation and used it to prepare di-, tri-, and tetrasubstituted furans. For example, dicarbonyl 3 yielded disubstituted furan 4 upon treatment with weak acid. 

The zinc complex of 1,1,1,5,5,5-hexafluoroacetylacetonate forms coordination polymers in reaction with either 2,5-bis(4-ethynylpyridyl)furan or l,2-bis(4-ethynylpyridyl)benzene. The X-ray crystal structures demonstrate an isotactic helical structure for the former and a syndio-tactic structure for the latter in the solid state. Low-temperature 1H and 19F NMR studies gave information on the solution structures of oligomers. Chiral polymers were prepared from L2Zn where L = 3-((trifluoromethyl)hydroxymethylene)-(+)-camphorate. Reaction with 2,5-bis(4-ethy-nylpyridyl)furan gave a linear zigzag structure and reaction with tris(4-pyridyl)methanol a homo-chiral helical polymer.479... 

This methodology was applied to a two-step sequence for the preparation of enantio-merically enriched dihydrobenzo[h]furans (Scheme 10.11) [46]. Rhodium-catalyzed allylic etherification of (S)-47 (>99% ee), with the sodium anion of 2-iodo-6-methyl-phenol, furnished the corresponding aryl allyl ethers (S)-48/49 as a 28 1 mixture of regioisomers favoring (S)-48 (92% cee). Treatment of the aryl iodide (S)-48 with tris(trimethylsilyl)silane and triethylborane furnished the dihydrobenzo[h]furan derivatives 50a/50b as a 29 1 mixture of diastereomers [43]. 

Similar to 136, furan 137 was also prepared via the oxazole route. Yun Yang, a student from Guangzhou Institute of Chemistry, thermolyzed oxazole 139 and bis(tri-n-butylstannyl)acetylene 155 in a sealed tube to afford a separable mixture... 

The furan mono-, di-, tri- and tetra-carbaldehydes are prepared by reduction and subsequent oxidation of the appropriate ester, or by reduction of the appropriate cyanofuran. They may also be prepared from the halofurans by lithiation and treatment of the lithiofurans with N,N- dimethylformamide. Furan-2-carbaldehyde is prepared from pentoses by acid treatment similarly, furan-2,5-dicarbaldehyde is conveniently prepared... 

In a recent report, Padwa [64] disclosed a general method of wide applicability for constructing a variety of heterocyclic systems. It involved an amino furan ester as a more reactive four carbon component vis avis a pyrone in intramolecular Diels-Alder addition to an unactivated olefin. This method as applied to the synthesis of anhydrolycorinone consisted of the preparation of the tertiary amide 240 (Scheme 40) and its subsequent thermolysis to the N-o-bromoaroylindoline 241. It is believed that the initially formed cycloadduct 242 opened to the acyl iminium oxyanion 243, which by prototropy and dehydration generated 241. The latter, on photolysis in the presence of bis (tri-n-butyltin), furnished the tetracyclic ester 244, which was hydrolysed and decafboxylated to anhydrolycorinone as in the previous synthesis. 

Part A illustrates a general method of preparing a,0-unsaturated j8-keto amines (/3-keto imines cf. synthesis 13), a class of weakly acidic bidentate ligands. Part C illustrates the use of chromium(III) chloride-tris(tetrahydro-furan) in the synthesis of a chromium(III) complex under nonaqueous conditions. 

L-Arcanose and L-olimycose have been prepared in enantiomerically pure forms and with high stereoselectivity by Lewis-acid promoted addition of (5)-2-benzyloxypropanal to 1-tri-methylsilyl-2,3-butadiene. Depending on the nature of the Lewis acid either the syn (with TiCl4) or the anti adduct (with BF3 Et20) can be obtained. Epoxidation with lateral control by the allylic alcohol moieties and standard reactions lead to the unprotected monosaccharides [334]. Total syntheses of 2,3-dideoxy-3-C-methyl-D-maw o-heptose and of 2,3-dideoxy-2,3-di-C-methyl-D-gfycero-D-ga(acto-heptose have been realized by addition of 2-(trimethylsiloxy)furan to 2,3-0-isopropylidene-D-glyceraldehyde ((R)-37) [335]. 

Indium enolates, prepared conveniently by transmetalation of hfhium enolates with IriCl j, react wifh aldehydes to give fhe corresponding -hydroxy esters [80]. Ultrasound irradiation promotes fhe Reformatsky reaction of aldehydes and ethyl bromoacetate wifh indium [81]. Indium-mediated Reformatsky reaction of phenyl a-bromoalkanoates wifh ketones or aldehydes gives di-, tri-, and tetrasubstituted -lactones (Scheme 8.57) [82]. Indium-mediated reaction of imines with ethyl bromoacetate gives 3-unsubstituted -lactams (Scheme 8.58) [83]. An indium-Refor-matsky reagent prepared from 2-(chlorodifluoroacetyl)furan couples with aldehydes (Scheme 8.59) [84]. 

Polyhydroxylated indolizidine alkaloids, due to their biological activity, have attracted considerable synthetic interest. The total synthesis of ( —)-l-qp/-swainsonine (250) from the chiral imine 238 (Scheme 58) and the parallel synthesis of (+ )-2,8,8a-tri-qp/-swainsonine (252) from the enantiomeric threose A-benzylimine 251, prepared from natural L-tartaric acid, provide further examples of the utility of tartaric acid in meeting the challenge of complex syntheses. A stereospecific 4 + 4 homologation utilizing 2-(trimethylsiloxy)furan (178) pro-... 

Tris(trifluoromethyl)furan 66 was prepared by the fluorination of acid 67 with sulfur tetrafluoride. The fluorination of acid 68 under similar conditions gives bicyclic product 69. ... 

As a specific example of such syntheses, the preparation of [6]-3,6-oxepinophane starting from furan and cyclooctyne <87CB769> should be noted. The formation of 2,7-diethyl-3,4,5,6-tris(trifluoromethyl)oxepin from 2,5-diethyl-3,4-di(trifluoromethyl)furan and di(trifluoromethyl) ethyne is also of interest <92JHC1 13>. 

The furan reaction was shown to be an equilibrium, and to be catalyzed by mercuric chloride 116). Tris(2-furyl)arsine has also been prepared by Wurtz-Fittig and Grignard procedures 119). The most recent use of mercury compounds has been in the preparation of dichloroperfluorovinyl-arsine 120,121). 

In general it is not advisable to have the palladium-catalysed coupling reaction as last or penultimate step in view of the need to reduce palladium levels in the final product to below 10 ppm. Based on this reasoning, Taiwanese chemists patented an alternative route towards Lapatinib in which the furan ring is coupled to the quinazoline moiety before attachment of the substimted aniline (Scheme 23) [69]. Thus, coupling between the furfural-boronic acid 99 and aryl halide 103 catalysed by a catalyst prepared in situ from palladium acetate and one equivalent of tri-t-butylphosphine (2 mol%) gave the biaryl compound 104 in 98% HPLC yield. 

Another method available for the synthesis of such derivatives is the reaction of the rare earth trichlorides with KC5H5 or TIC5H5 in benzene (E.O. Fischer and H. Fischer, 1965b Manzer, 1976a). This method allows the synthesis of tris(cyclo-pentadienyl) europium, which could not be prepared by the reaction in tetrahydro-furane, because of the decomposition of (CjH5)3Eu THF during sublimation ... 

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