2- silyl-substituted benzofuran

These annulations can be extended bqrond indole syntheses. For example, the analogous reaction with ortho-iodophenols can provide an effective method to build up benzofurans (Scheme 6.50) [67]. Presumably due to the lower nudeophilicity of the phenolic oxygen, these reactions generally require higher reaction temperatures. Nevertheless, similar regioselectivity was found here as with the indole synthesis, and, in particular, 2 -silyl-substituted benzofuran is often obtained with high selectivity. This same approach can be applied to the construction of pyrroles and furans [68]. 

The aryl r-butyl ether 15 and silyl ether 18, prepared by the Pd-catalyzed reaction, can be converted easily to phenols 16, and these reactions offer convenient synthetic methods for phenols 16 from aryl halides 14 and 17. Based on this reaction, the first synthesis of 4-chlorobenzofiiran (18c), which is difficult to synthesize by conventional methods, was carried out. Selective mono-r-butoxylation of 2,6-dichloroacetaldehyde dimethylacetal (18a) using P(r-Bu)3 as a ligand gave the r-butyl ether 18b, and subsequent treatment with aq. HCl afforded 4-chlorobenzofuran (18c) in 51 % overall yield. Further conversion of 18c to various 4-substituted benzofurans is possible by Pd-catalyzed substitutions of the 4-chloro group in 18c [6]. 

Substituting the benzene ring with a double bond, Pd-catalyzed intramolecular alkoxylation of alkyne 122 also proceeded via an alkenyl palladium complex to form furan 123 instead of a benzofurans [99, 100]. In addition, 3-hydroxyalkylbenzo[fc]furans was prepared by Bishop et al via a Pd-catalyzed heteroannulation of silyl-protected alkynols with 2-iodophenol in a fashion akin to the Larock indole synthesis, [101]. 

In summary, the literature survey provides clear evidence for a-carbonyl radical intermediates but no convincing proof for further oxidation to a-carbonyl cation in the vast majority of silyl enol ether radical cation reactions. This suggests that for most cases, silyl enol ethers are more readily oxidized than the corresponding a-carbonyl radicals. Only in oxidations of -aryl substituted silyl enol ethers, a-carbonyl cation intermediates have been invoked. For example, one-electron oxidation of 87d with TTA" " in acetonitrile/MeOH afforded 76 in analogy to the a-Umpolung of ketones via enol radical cations (Scheme 4), and oxidation of 124 with FePHEN provided benzofuran 19 [171]. 

The most popular Pd-catalyzed method for the production of furans and benzofurans involves reactions of alkynols. Acyclic alkynols are converted into furans, while benzene substituted alkynols are transformed into benzofurans. The use of this strategy is widespread for the synthesis of benzofurans however, it is occasionally used for the syntheses of furans. For example, intramolecular alkoxylation of alkyne 189 proceeds via an alkenylpalladium complex and subsequent carbonylation to form furan 190 [156, 157]. In addition, 3 -hydroxyalkyl-benzo[/)J furans were prepared by Bishop et al. via a Pd-catalyzed heteroannulation of silyl-protected alkynols with 2-iodophenol in a fashion akin to the Larock indole synthesis [158]. In a related series of experiments, Qing demonstrated that alkynes 191 could be efficiently converted into furans 192 [159]. 

Pd-catalyzed reaction of o-iodophenol (26) with alkynes offers a good synthetic method of functionalized benzofurans 27. The silyl group in the benzofuran 27, obtained from tri-isopropylsilylalkyne, can be used for electrophilic substitution or desilylation to yield 28 [11]. In the reaction of 26 under CO atmosphere (1 atm), the insertion of 4-octyne occurs in preference to the insertion of CO to generate the alkenylpalladium 29, to which CO insertion occurs to afford the acylpalladium 30. Finally, intramolecular reaction of 30 yields the coumarin 31. The chromone 32 is not obtained [12]. 

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