Benzo furan 2-substituted derivatives

The synthetic approach to the benzo[fo]furan is similar to that of the thiophenes described in Scheme 39. The synthetic approach was described by Flynn et al. [73], and an example synthesis is given in Scheme 40. The appropriate iodophenol 104 is coupled to the aryl alkyne 111. The intermediate 155 is subsequently cyclized in the presence of an appropriately substituted aryl iodide, e.g., 107 under an atmosphere of carbon monoxide gas, to give the benzo[fr]furan chalcone derivative 156. Deprotection of the hydroxyl produces the target compound 157. 

III. Benzo[f]furan and Its Alkyl- and Monoaryl-Substituted Derivatives.142... 

The commonest five-membered heteroaromatic compounds containing one heteroatom are pyrrole (30), furan (31) and thiophene (32). Their substituted derivatives and the substituted derivatives of the corresponding benzo analogues [indole (33), benzofuran (34) and benzothiophene (35)] are widespread naturally-occurring compounds. 

Synthetically even more versatile trifunctional intermediates result from the addition of carbonyl compounds onto methyl 2-siloxycyclopropanecarboxylates 92). Benzo-phenone, titanium tetrachloride, and 162, for instance, provide an excellent yield of the a-hydroxyalkylated y-oxoester 174, which predominates in the equilibrium with its cyclic hemiacetal 176 (y-lactol). It can undergo elimination to the unsaturated ester 175, but as Scheme 7 illustrates, 174/176 can also serve as the starting material to several highly substituted furan(one) derivatives. 

Diphenylthieno[2,3-c]furan (130) reacted with 7V-4-methylphenylmaleimide at room temperature to give in 73% yield endo adduct (131). In the presence of 4-methylbenzenesulfonic acid the substituted benzo[6]thiophene derivative (132) was obtained. Vinylene carbonate as dienophile led to an endo/exo mixture (133a) and (133b) in the ratio 6 1. The same reaction in the presence of sulfuric and acetic acids afforded compound (134) <89CB1U9). 

The reactions of the lithio derivatives of benzo[A]-fused systems indole, benzo[ ]furan, and benzol/ ]thiophene are similarly diverse. Since indole and benzo[A]thiophene undergo electrophilic substitution mainly in the 3-position, the ready availability of 2-lithio derivatives by deprotonation with -butyllithium is particularly significant. The ready availability of 3-iodoselenophene and hence of 3-lithioselenophene provides a convenient route to 3-substituted selenophenes. 2-Lithiotellurophenes are especially important precursors of tellurophene derivatives because of the restricted range of electrophilic substitution reactions which are possible on tellurophenes. 

Vinyl-substituted benzo[c]furans can be prepared by reaction of n-alkynylbenzaldehydes with chromium Fischer carbene complexes. Initially a benzo[c]furan chromiumtricarbonyl complex is believed to be formed which is converted into an alkylidenephthalan derivative or can be trapped with electron-deficient dienophiles with excellent ( 3 ti-selectivity (Equation 128) <20000L1267>. More elaborate vinylidene Fischer carbene complexes yield dienyl benzo[c]furans that undergo [8-1-2] cycloaddition with DMAD to furnish furanophane derivatives <2003JA12720>. An equilibrium between 7] -(o-ethynylbenzoyl)rhenium complexes and rhenium benzo[f]furyl carbene complexes has been observed. These species behave like other benzo[< ]furans in the reaction with DMAD <20040M4121>. 

Several substituted benzo[ ]furans were synthesized efficiently in one-pot procedures by reaction of salicyaldehydes and ethyl diazoacetate in the presence of HBF/EtjO in high yields as shown below. A plausible mechanism was also given <0681711>. Two types of naphtha[2,3-fc]furan derivatives were made respectively by Lewis acid and HCl catalyzed ring cyclizations <06T8045>. AuBrj-catalyzed [4+2] benzannulation between enynal units and enol ethers was also applied to prepare benzo[Z)]furans <06JOC5249>. 

The synthesis of benzo[i ]furan derivatives has become a very active field because these molecules have been identified as having a variety of biological aaivities. Many syntheses of interesting benzo[f ]furans substituted with carbon, oxygen, nitrogen, or sulfur functional groups at the C-2/C-3 position were reported in 2014. 

Benzo[l)]furan-6-carbonitrile and 6-cyanobenzo[l>]furan-2-boronic acid pinacol ester were prepared in the presence of Cu. (13SC1974) 2-Substituted benzo[ ]furans were synthesized by employing easily accessible A/-tosylhy-drazones and o-hydroxy or o-amino phenylacetylenes as substrates. (13OBC1490) One-pot access to either 2-naphthols or benzo[l>]furans via the aerobic Wacker-type oxidation/intramolecular aldol cyclization was accomplished. (13T1532 ) 5,5-Disubstituted-2,2 -bisbenzofuran derivatives were produced by treatment of 4-substituted-2-(2-trimethylsilylethynyl) phenyl tert-butyldimethylsilyl ether analogues with CuCl as a catalyst (13TL2655). 

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