Benzofurans oxidative coupling

The synthesis of a new sulfur analogue of angelicin, a thiopyrano[2,3-e]benzofuran, was reported <96JOC4842>. The reaction of 3(2//)-benzofuranone with SjClj yields bis-2-spirocoumaranoylidenetetrathiane instead of oxindigo (an oxidative coupling of a coumaranone) (Scheme 12, <96T1961>). 

The industrial synthesis of vinyl acetate [14] via palladium-catalyzed oxidative coupling of acetic acid and ethene using direct 02 reoxidation has already been mentioned (Scheme 3, d). Some NaOAc is required in the reaction medium, and catalysis by Pd clusters, as alternative to Pd(II) salts, was proposed to proceed with altered reaction characteristics [14]. Similarly, the alkenyl ester 37 (Table 5) containing an isolated vinyl group yields the expected enol acetate 38 [55] whereas allylphenol 39 cyclizes to benzofuran 40 with double bond isomerization [56]. 

As can be seen in the scheme below, a series of substituted 2-(2-aminothiazol-4-yl)-benzo[ ]furans with inhibitory activity for leukotriene B4 were made from benzofurans via acylation, followed by Hantzsch thiazole formation <070BC3083>. 2-Substituted benzo[ ]furans could also be generated via an aerobic oxidative coupling of 2-unsubstituted benzo[ ]furans with arenes through the palladium-catalyzed double C-H activation <07OL3137>. In addition, 2,3-diarylbenzo h I uran could be constructed by a palladium-catalyzed arylation of benzo[6]furan with an aryl chloride in the presence of a bulky, and electron-rich phosphine <07OL1449>. 

The catalytic oxidative coupling of two dissimilar arenes is also possible, for example, iV-acetyl indoles, or benzofurans, with benzene and other simple arenes. The mechanism involves sequential metallations in the two rings. The regioselectivity can be controlled by the choice of oxidant, Cu(OAc)2 favouring C-3 and AgOAc, C-2 substitution in 1-acetylindole. ... 

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... 

Compound 539, in turn, could be formed by oxidative coupling of a biflavone and a benzofuran derivative through a C-I-4 O C-II-3 linkage. 

Interestingly, coupling of phenols and jS-ketoesters under iron-catalysed oxidative conditions leads selectively to the formation of substituted benzofurans. Notably, the iron catalyst acts as a transition-metal catalyst in the oxidative coupling step and as Lewis acid in the condensation step. The presence of water coordinated to the catalyst and/or protic solvents accelerates the process, likely favouring the (final) tautomerisation step (Scheme 13.12). ... 

Scheme 13.12 Iron-catalysed nthesis of polysubstituted benzofuran via an oxidative coupling/annulation tandem process.

The arene substrates are not limited to simple benzene derivatives. A variety of het-eroarenes can also participate in alkene arylations to generate the desired coupling products. Stoichiometric oxidative coupling of aromatic heterocycles such as furan, thiophene, selenophene, A-methylpyrrole, benzofiiran and benzothiophene with a variety of alkenes, including acrylonitrile, styrene and methyl acrylate, have been extensively studied by Fu-jiwara and coworkers [8]. Furan, thiophene, selenophene and A-methylpyrrole are easily alkenylated with alkenes to give 2-alkenylated and 2,5-dialkenylated heterocycles in relatively low yields (3 6%) [8a], while the reactions of benzofuran and benzothiophene with alkenes produced a mixture of 2- and 3-alkenylated products [8b]. 

The C-H/C-H coupling of protected indoles with unactivated arenes takes place using air and copper as oxidants (eq 153). A mixture of C-2 and C-3 arylation is obtained, and the ratio is dependent on the protecting group employed. Benzofuran and its derivatives participate in a similar oxidative coupling under similar reaction conditions.Later, it was demonstrated that switching from acetic acid to 1,4-dioxane as the solvent, selective C-2 arylation could be obtained when Cu(OAc)2 was the oxidant in contrast, use of AgOAc as the oxidant favored arylation at the C-3 position. 

Guo et al. [24] reported iron-catalyzed tandem oxidative coupling and annulation of phenols and p-keto esters, furnishing polysubstituted benzofurans 38 (Scheme 5.20). The combination of FeClj 6HjO and (t-BuO) offers an efficient catalytic oxidative system. The iron catalyst demonstrates dichotomous catalytic behavior in this transformation, which is a transition metal catalyst in the oxidative coupling step and a Lewis acid in the condensation. 

Ortho,ortho -coupling of the phenoxy radical produces V, its further oxidation forms via an arene oxide the benzofuran VI, and the ortho, para -coupling leads after a subsequent Michael addition to the Pummerer ketone VII. 

Diimide reduction of 96, obtained by the enzymatic oxidation of 95 (96% ee) [67], followed by O-acetylation afforded cyclohexene-diol 97 in 47% yield (Scheme 19). Compound 97 was converted into carbamate 98 by S 2 reaction with methylamine and subsequent urethane formation. Regioselective protection of the diol in 98 with TBSC1 afforded 99, which was coupled with bromoisovanillin 54 under the conditions of Mitsunobu to provide 100 (see Sect. 2.2.2). The intramolecular Heck reaction of 100 constructed the benzofuran ring including a quaternary center to afford 101 in 82% yield. Wittig reaction of 101 with Ph3P=CHBr generated vinyl bromide 102 in 49% yield as a mixture of E- and Z-isomers (E Z = ca. 1 2). 

Scheme 18 Pd-catalyzed oxidative cross-coupling of benzofuran with benzene...

---