Cross-coupling furan

The oxidative coupling of thiophene, furan[338] and pyrrole[339,340] is also possible. The following order of reactivity was observed in the coupling of substituted furans[338] R = H > Me > CHO > CO Me > CH(OAc)i > CO2H. The cross-coupling of furans and thiophenes with arene is possible, and 4-phenylfurfural (397) is the main product of the cross-coupling of furfural and benzene[341]. 

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. 

Dihydrobenzo[b]furans can be synthesized by using Pd(dba)2/PhsFcP(r-Bu)2 as an efficient catalyst at room temperature, and some interesting discussions related to this catalyst discovery are also addressed <00JA10718>. Buchwald also shows that bulky, electron-rich o-biarylphosphines are effective in PdfOAcfe-catalyzed cross-coupling reactions for the generation of 2,3-dihydrobenzo[6]furans <00JA12907>. 

The Pd-catalysed cyclisation of ( >3-alkyny]-3-tnfluoromethyl allylic alcohols 2, derived from a cross coupling reaction between terminal alkynes and the 3-iodo alcohols 1, yields the pyrans 3 rather than the expected furan derivatives (Scheme 1). It appears that the electron-withdrawing properties of the CF3 group assist the 6-endo-dig cyclisation . 

A distannation product of 2-butyne-l,4-diol oxidatively cyclizes to provide 3,4-bis(stannyl)furan, which then undergoes palladium-catalyzed cross-coupling with an aryl iodide to give 3,4-diarylfuran (Scheme 31).152,153... 

Both vinyl- and aryl triflates have been cross-coupled with 2-furylzinc chloride [26-28]. Since vinyl triflates are easily obtained from the corresponding ketones, they are useful substrates in Pd-catalyzed reactions. In the following example, a Negishi coupling of 2-furylzinc chloride and indol-5-yl triflate (22) provided an expeditious entry to 2-(5 -indolyl)furan (23). Protection of the NH in the indole ring was not required. A similar reaction was successful with pyridyl- and quinolinyl triflates. 

Under the Suzuki reaction condition and in the presence of 2,3-bis(bro-momethyOquinoxaline 149, Song unexpectedly discovered that 140 was able to provide the self-coupling product, namely bifuran 150 in excellent yield (Scheme 31). Similarly, 150 produced quaterfuran 152 via 151, from which taliiran 153 was also obtained via a cross-coupling with 144 under identical conditions (Scheme 31). A variety of symmetrical and unsymmetrical furan-3,4-diyl oligomers were... 

Vilsmeier reaction of 2-oxindole (830) afforded 2-chloroindole-3-carbaldehyde (891). Suzuki cross-coupling of 891 with furan-3-boronic acid (1124), followed by protection of the indole nitrogen with benzyloxymethyl (BOM) chloride, led to... 

Chloro-P-carboline (25) has served as a common intermediate in palladium-catalyzed cross-coupling reactions, offering easy access to several pyridine alkaloids. In Bracher s total synthesis of perlolyrine (27), a P-carboline alkaloid, the Suzuki reaction of 25 with 5-formylfuranyl-2-boronic acid (26) formed the C-C bond between the pyridine and the furan rings <92LA1315>. Reduction of the resulting Suzuki adduct with NaBIL subsequently... 

Furane derivatives, like pyrroles, couple effectively with acetylenes. In case both the a-, and / -position are available for the reaction, like in the case of 4,5-dibromo-furfural in 6.45., the cross-coupling takes place preferentially in the former position65 The observed selectivity is in line with other palladium catalyzed transformations of dihalofuranes, such as their Stifle coupling.66... 

The scope of the coupling of furane derivatives with acetylens was extended to alkynyltrifluoroborates too. These compounds are attracting increased attention due to their ready availability, chemical stability and willingness to participate in cross-coupling reactions. The furane derived bromo compound shown in 6.46. for example reacted readily with a series of alkynyltrifluoroborates in the presence of a palladium-dppf catalyst to give the coupled products in excellent yield67... 

The bis-iodonium acetylene 198 is even more reactive than 189 and undergoes Diels-Alder reaction with cyclopentadiene, furan and 1,3-diphenylisoben-zofuran in acetonitrile under very mild conditions (Scheme 71) [139]. All adducts (62,199) are isolated in the form of stable microcrystalline solids products 62 can be reacted further with nucleophiles or combined in a cross-coupling reaction with lithiated or stannylated alkynes [52,53,61]. 

Oxidative cross-coupling with alkenes is possible with Pd(OAc)2 [109], The reaction proceeds by the palladation of benzene to form phenylpalladium acetate (164), followed by alkene insertion and elimination of /1-hydrogen. Heteroaromatics such as furan and thiophene react more easily than benzene [109]. Stilbene (177) is formed by the reaction of benzene and styrene. The complex skeleton of paraberquamide 179 was obtained in 80% yield by the Pd(II)-promoted coupling of the indole ring with the double bond in 178, followed by reduction of the intermediate with NaBELt [110]. 

Dyker, G. Palladium-catalyzed C-H activation at methoxy groups for cross-coupling reactions a new approach to substituted benzo[h]-furans./. Org. Chem. 1993, 58, 6426-6428. 

Unsymmetrical 2,5-disubstituted alkynylfurans could be prepared from 2,5-bis(butyltelluro)furan by sequential palladium-catalyzed cross-couplings. As represented in Scheme 26, the use of THE, a less effective solvent than MeOH for the symmetrical bis-coupling to alkynes, enabled the first monocoupling to occur <2003TL1387>. 

As depicted in Equation (97), oxidative cross-coupling of a-aryl-/3,/3-difluoroenol silyl ether with unfunctionalized benzo[ ]furan 82 in the presence of Cu(OTf)2 in wet acetonitrile proceeded smoothly to give benzo[/ ]furan difluoromethyl aryl ketone in 50% yield <2004OL2733>. 

Allenyl ketones can also be cross-coupled with allenoic acids to give 2,4-disubstituted furans <2002AGE1775> or with allenamides to yield 4-(3 -furanyl)-2(5//)-furanimines <2005JOC6291>. With chiral allenoic acid derivatives, 4-(3 -furanybbutenolides can be synthesized stereoselectively with complete chirality transfer (Equation 47) <2004CEJ2078>. 

Another method of benzannulation to a furan ring uses precursors of type 59, which are available by cross-coupling reaction with the corresponding 3-bromofuran. Upon treatment with ethyl chloroformate and triethylamine, a pyrocarbonate is formed which acylates the furan nucleus in an intramolecular reaction. With an excess base the 7-hydroxybenzofurans are obtained (Equation 123) <1998TL5609>. 

A Ni-catalyzed cyclization cross-coupling reaction of iodoalkenes with alkyl zinc halides has been employed for the synthesis of various tetrahydrofuran derivatives <2007AGE-ASAP>. The TiCU-catalyzed anti-Markovnikov hydration of alkynes has been applied to the synthesis of various benzo[3]furans <2007JOC6149>. 

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). 

Symmetrical and unsymmetrical 2,5-fc/s-acetylenic furan derivatives were produced in high yield using Pd-catalyzed cross-coupling reaction of 2,5-/7M(butyltelluro)furan, which was prepared from furan through lithiation-transmetallation and alkylation <03TL1387>. 

Cationic palladium-catalyzed addition of arylboronic acids to nitriles for the formation of benzo[h]furans was reported <06OL5987>, an example of which is illustrated in the following scheme. The palladium-catalyzed cross coupling of alkynes with appropriately substituted aryl iodides for the synthesis of substituted dibenzofurans in moderate to excellent yields was also achieved <06JOC5341>. The benzo[fc]furan core of heliannuls G and H were constructed by a palladium-catalyzed Ji-allyl cyclization reaction <06TL7353>. The palladium-catalyzed oxidative activation of arylcyclopropanes was applied to the synthesis of 2-substituted benzo[Z>]furans <06OL5829>. 

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