Palladium-Catalyzed Reaction of o-Ethynylphenols, o-((Trimethylsilyl)ethynyl)phenyl Acetates, and o-Alkynylphenols with Unsaturated Triflates or Halides:  A Route to 2-Substituted-, 2,3-Disubstituted-, and 2-Substituted-3-acylbenzo[b]furans

Abstract

The reaction of o-ethynylphenols 3 with a wide variety of unsaturated halides or triflates 6 in the presence of Pd(OAc)2(PPh3)2, CuI, and Et3N (procedure A) gives 2-vinyl- and 2-arylbenzo[b]furans 7, in good to high yield, through a palladium-catalyzed coupling followed by an in situ cyclization step. Small amounts of 2,3-disubstituted-benzo[b]furans 8 are usually isolated as side products. In some cases, however, compounds 8 are generated in significant yield or even as the main products. The formation of 8 can be prevented by employing alternative procedures (B and C) that use o-((trimethylsilyl)ethynyl)phenyl acetates 5 as starting building blocks. Procedure B is based on the palladium-catalyzed reaction of 5 with 6 in the presence of Pd(PPh3)4, Et3N, and n-Bu4NF, followed by the hydrolysis of the resultant coupling derivative 12 under basic conditions. Procedure C affords 7 through an in situ coupling/cyclization of 5 with 6 in the presence of Pd(PPh3)4 and KOBut. The utilization of o-alkynylphenols 9 as the starting alkynes in the palladium-catalyzed reaction with 6 leads to the formation of 2,3-disubstituted-benzo[b]furans 13 through an annulation process promoted by σ-vinyl- and σ-arylpalladium complexes generated in situ. The best results in this case are obtained by using KOAc and Pd(PPh3)4. In the presence of KOAc and Pd(PPh3)4, and under an atmosphere of carbon monoxide, the reaction of o-alkynylphenols with 6 provides 2-vinyl- and 2-aryl-3-acylbenzo[b]furans 14.

Chemicals from Alkynes with Palladium Catalysts

“…132 Other examples of the synthesis of furans are the palladium-catalyzed internal cyclization of (Z)-2-en-4-ynol, 151 However, it has been more frequent to prepare these kind of benzocondensed systems from o-iodinated phenols and terminal alkynes by the above mentioned in situ palladium-catalyzed Sonogashira coupling (see Section 6.1) followed by intramolecular cyclization. 155,156 An example is the preparation of benzofuran 154 by in situ formation of alkynylphenol intermediate 153 from iodophenol 152 and 2-methylbut-3-yn-2-ol under Sonogashira conditions, followed by intramolecular cyclization. The process is catalyzed by a combination of Pd(OAc) 2 and a water-soluble phosphine such as 3,3′,3′′-phosphinidynetris(benzenesulfonic acid (TPPTS), in the presence of triethylamine as base in aqueous acetonitrile as solvent at room temperature (Scheme 57).…”

The 'one-pot' preparation of substituted benzofurans

“…An alternate approach would achieve the formation of the benzofuran moiety through the ring closure of an o-alkynylphenol, [10][11][12][13][14][15] available through the coupling of an aryl halide and the appropriate aryl acetylene.…”

“…In spite of the large number of publications describing the conversion of 2-halophenols to benzo [b]furans, [10][11][12][13][14][15] the preparation of hydroxylated benzofurans has received only limited attention so far. 12,14,15 By analogy, such a process would start from a halogenated dihydroxybenzene.…”

“…12,14,15 By analogy, such a process would start from a halogenated dihydroxybenzene. These compounds usually fail to undergo Sonogashira coupling 17 and the successful procedures on similar systems usually utilize the selective protection of the different hydroxyl groups or an equimolar amount of preformed organocopper reagent.…”

Acetylenes from Aldehydes. Preparation of Ethynylphenols and Phenylacetylenes by Flash Vacuum Pyrolysis of Isoxazolones

“…The addition of weakly nucleophilic phenols to acetylenes usually requires transition metal catalysis, e.g. with Hg II , [14] Pd II , [15] Au III , [16] or Cu I . [17] We envisage that this unwanted cyclization could be suppressed by protecting the OH group by silylation.…”