Substitution 2,3-disubstituted benzofurans

In contrast to the 5-endo-trig anionic cyclization reactions, rarely observed, there are several examples in which 5-endo-dig processes are involved. Hence 2,3-disubstituted benzofurans, benzothiophenes and indoles 374 have been synthesized starting from triflu-oroethyl ethers, thioethers and anilines 373, respectively, and alkyllithium compounds. A 5-endo-dig carbolithiation reaction on 375, generated by two successive eliminations, one substitution and one ortho-lithiation reactions, is proposed to account for the formation of the corresponding 2-lithiated heterocycles. Further reaction of these intermediates with electrophiles affords compounds 374 (Scheme 98)159. In the case of thioether 373 (X = S) a bromine substituent must be present at the ortho position. 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

Electrophilic substitution and metallation reactions of [l]benzothieno[3,2-3][l]benzofuran 63 were studied <2000CCC58>. Bromination, acetylation, benzoylation, formylation, and nitration usually afforded inseparable mixtures of 2- and 7-substituted derivatives as the main products. Disubstitution reactions preferably led to 2,7-disubstituted derivatives. [l]Benzothieno[3,2-3][l]benzofuran-10,10-dioxide 64 and [l]benzothieno[3,2-3][l]ben-zofuran-lO-oxide 65 can be selectively obtained by oxidation of 63. Mononitration of 64 and 65 led selectively to corresponding 7-nitro derivatives, respectively. Only sulfoxide 65 was successfully reduced. 

A Pd-catalyzed tandem reaction was developed to synthesize a group of interesting benzo[fc] furans as depicted below <05CC271>. The Pd-catdyzed cyclization of propargylic carbonates was also applied to make 2,3-dihydrofurans and benzofurans <05T4381>. Furthermore, an oxidative cyclization procedure catalyzed by Pd(II) and pyridine in the presence of molecular oxygen was carried out on a variety of 2-allylphenols to form 2-substituted as well as 2,2-disubstituted benzo[fc]furans <05JA17778>. 

If A,A-disubstituted amides are used as starting material, the corresponding 3-dialkylamino-benzofurans are obtained <73JOCl746>. Suitably substituted allyl phenyl ethers can be cyclized to 2,3-dihydrobenzo[Z>]furans <94H(38)177>. 

Tin Derivatives. A regiocontrolled method for construction of substituted benzofurans, dibenzofurans, benzothiophenes, and dibenzothiophenes uses 4-chloro-2,3-disubstituted-2-cyclobutenones as reactants together with a heterocycle (Scheme 17). In the construction... 

The 2-methyl-dihydrobenzofuran 12 was the most active. The aromatic benzofurans 2Q were less active. Comparable in activity were the 2,2-dimethyl, the substituted aryl and parent dihydrobenzofuran. The 6-membered pyran ring 24 was less active than the 5-membered ring 22 and the multiple substituted, in this case the 2,3-disubstituted compounds (25) were the least active. All of these sulfonylureas were herbicidal. 

Shen in 2012 reported an Ir/Cu synergistic catalytic C—H bond activation for the one-pot trifluoromethylation reaction (Scheme 9.19). This catalytic process involves sequential iridium-catalyzed C—activation borylation and copper-catalyzed trifluoromethylation of arenes with a variety of functional groups. This tandem procedure was successfully applied to the 2,6-disubstituted pyridine, benzofuran, benzothiazole, indole, and substituted quinoline systems. 

New synthetic methods have been described for the preparation of l-hydroxy-2,3-disubstituted naphthalenes (292) and l,4-dihydroxy-2,3-di-substituted naphthalenes, as illustrated in Scheme 38. l//-2-Benzofuran-l-one-3-(phenylsulphone) (294 Ar = Ph, R = H) may be similarly converted into... 

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