Benzofuran coupling reactions

Cross-coupling reactions are also possible as an extension of this type of domino process - with excess vinyl bromide 19 either benzofurans 20 or indenes 21 are obtained as mixtures of double-bond isomers [5, 6]. 

A general and convenient route to 2-substituted benzofurans or indoles is based on intramolecular annulation of 2-alkynylphenols or 2-alkynylanilines (Scheme 23), which are in turn readily available via alkynylaryl cross-coupling reactions. In a representative example, base-induced cyclization of the precursors 37 with concomitant elimination of the TMS-moiety affords the indoles 38 in good yields (Scheme 24) <1997JOC6507>. 

The cross-coupling reactions can be combined with catalytic cyclization of 2-alkynylphenols in a one-pot, multi-component coupling procedure leading to 2,3-disubstituted benzofurans 39 as shown in Scheme 25 . 

Finally, ortho- 2,2-dibromovinyl)-aniline or -acetanilide can successfully be applied in a sequential cyclizing amination-cross coupling reaction with diethyl phosphonate to furnish the indolyl phosphonic ester 136 or the N-acetyl 2-aryl indole 137 as recently shown by Bisseret and coworkers [ 105] (Scheme 50). This sequence can be also performed with corresponding phenol derivatives furnishing benzofurans. For the N-acetyl 2-aryl indole 137 it can be shown that the Suzuki coupling occurs prior to the intramolecular animation as a consequence of the gradual difference in reactivity between trans-and czs-carbon-bromine bonds. 

Reactions with aryl halides have been described [79-81] in one case a stannylated benzofuran was allowed to react with an aryl iodide containing sterically demanding trialkylsiloxy groups in positions 3 and 5, but yields remained good to excellent [82]. Yang and Wong have also reported coupling reactions of 3,4-bis(tributylstannyl)furan [83,84] (Scheme 4-28). 

In the laboratory of M. Nilsson, a facile one-pot synthesis of isocumestans (6H-benzofuro[2,3-c][1]benzopyran-6-ones) was developed via a novel extension of the Castro-Stephens coupling utilizing ortho-iodophenols and ethyl propiolate. The reaction can be regarded as an extended Castro-Stephens coupling where an intermediate cuprated benzofuran couples with a second equivalent of ortho-iodophenol, and the product lactonizes to isocumestan. 

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,... 

The oxidative coupling reactions of benzofuran and N-substituted indoles with benzene and derivatives have also been achieved using oxygen as an oxidant (Equation 11.37) [76]. This methodology for synthesizing heterocoupled biaryls... 

Baran et al. developed a radical cross-couphng reaction between arylboronic acids and trifluoroborates, in 2011 (Scheme 5.31) [56]. This methodology was applied to achieve a domino cyclization/coupling reaction. When the aryl boronic acid 144 was subjected to Ag+/S20g , a benzofuran radical was generated, which underwent a radical trap with 1,4-benzoquinone as the terminating radicophile. 

Later on, the annulation of allenes with 2-iodophenols and 2-iodoaniline derivatives were further explored. In 2009, Shi and Li developed an efficient method for the coupling reactions of diarylvinylidenecyclopropanes with 2-iodophenols and N-(2-iodophenyl)-4-methylbenzenesulfonamide. A variety of cyclopropane-containing 2,2-diaiyl-3-(tetramethyl(yclopropylidene)-2,3-(dihydro)benzofuran and 2,2-diaryl-3-(tetramethyl(yclopropylidene)-l-(toluene-4-sulfonyl)-2,3-dihydro-l//-indole derivatives were produced in moderate to good yields with palladium as the catalyst (Scheme 2.48a). 

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