Arylated furans, cross-coupling, furan

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. 

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. 

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>. 

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). 

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>. 

Unlike normal all-carbon aryl halides, regioselective Negishi couplings of dihalofu-rans and trihalobenzofurans are synthetically useful. Bach and coworkers have studied both systems extensively and use a variety of cross-coupling reactions to produce functionalized furans and benzofurans. In one example of a selective Negishi reaction,... 

Thiophenes and benzothiophenes were used by Ke, Liu, and coworkers to evaluate the efficacy of a group of a-hydroxyimine palladium complexes in direct cross-coupling reactions with aryl and heteroaryl bromides such as 4-bromobenzonitrile (47), 4-bromoanisole (48), and 5-bromopyrimidine (49) (33 examples 50—97% yield) (2015OM4881). In particular, complex 50 operated most efficiently under aerobic conditions and with low catalyst loading (0.55 mol%). This success prompted further exploration of cross-coupling reactions with other heteroaryls such as furans, thiazoles, imidazo[l,2-a]pyridine, and triazoles (19 examples 57—96% yield). 

Scheme 7.5 Palladiumd-catalyzed carbonylative cross-coupling reactions of aryl iodides with alkynones to furans...

One of the first palladium-catalyzed annulation protocols, in which the involvement of paUadium(IV) intermediates had been proposed, was published by Dyker in the early 1990s. A homocoupling of ort/jo-iodoanisole afforded 6//-dibenzo[ >, flpyran, and a cross-coupling of ort/io-iodoanisole with vinyl bromides provided benzo[6] furans (Scheme 2) [2, 3]. The mechanistic rationale put forward for these processes invoked an initial Csp -H activation induced by the paUadium(II) center, followed by the formation of paUadium(IV) intermediates via oxidative addition of aryl iodide or vinyl halide building blocks. Dyker s reports inspired synthetic chemists... 

The C-H/C-X coupling between electron-rich or -neutral heteroarenes such as indoles, thiazoles, furans, and 1,3-azoles with aryl hahdes have been described frequently in the literature (see earlier discussion). However, the couphng of electron-deficient heteroarenes such as pyridines has remained Hmited due to their low reactivity toward electrophilic metalation as well as CMD processes. Furthermore, 2-metallaazines are generally unstable and incompatible with the reaction conditions, although examples of such cross-coupling reactions (C-M/C-X coupling) exist. 

The formation of 2-alkenyl-substituted furans was observed in the palladium-catalyzed cross-coupling reactions between benzyl, aryl, or allyl bromides and conjugated ene-yne-ketones. This reaction involved oxidative addition, alkyne activation-cyclization, palladium carbene migratory insertion, P-hydride elimination, and catalyst regeneration (13JA13502). 

Arylbenzo[b]furans (20) are obtained by iodine-mediated cyclization of (o-hydroxy)stilbenes (17) prepared by selective McMurry cross-coupling of salicylic aldehyde and aryl aldehydes [47] ... 

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