2-iodophenols furans

The reaction of the o-iodophenol 275 with an alkylallene affords the bcnzo-furan derivative 276[184], Similarly, the reactions of the 6-hydroxyallenes 277 and 279 with iodobenzene afford the tetrahydrofurans 278 and 280. Under a CO atmosphere, CO insertion takes place before the insertion of the allenyl bond, and a benzoyl group, rather than a phenyl group, attacks the allene carbon to give 280. Reaction of iodobenzene with 4,5-hexadienoic acid (281) affords the furanone derivative 282[185]. 

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]. 

Some early examples involving microwave-assisted solvent-free Sonogashira couplings using palladium powder doped on alumina/potassium fluoride as catalyst were described by Kabalka and coworkers (Scheme 4.4) [150], In addition, this novel catalytic system has been used in microwave-assisted solvent-free Sonogashira coupling-cyclization of ortho-iodophenol with terminal alkynes, and similarly of ortho-ethynylphenols with aromatic iodides, to generate 2-substituted benzo[b]furans... 

Diastereoselective syntheses of dihydrobenzo[f>]furans have been accomplished by a rhodium-catalyzed regioselective and enantiospecific intermolecular allylic etherification of o-iodophenols as a key step, providing the corresponding aryl ally ether 122, which leads to a dihydrobenzo[b]furan by treatment of the intermediate aryl iodide with tris(trimethylsilyl)silane and triethylborane at room temperature in the presence of air <00JA5012>. 

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. 

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]. 

The Pd-catalyzed electro-cleavage of the C—O bond of allyl aryl ether proceeds smoothly in a DMF-Bu4NBp4-(Mg)-(Stainless Steel) system, giving depro-tected products in 73 99% yield [437]. The sp-sp intermolecular coupling reaction with the Pd water-soluble catalyst prepared in situ from Pd(II) acetate and sul-fonated triphenylphosphine in an MeCN-H2O system yields diynes in 45 65% yields [438]. Similarly, the sp -sp coupling of 2-iodophenols or 2-iodoanilines and terminal alkynes followed by intramolecular cyclization gives indol and furan... 

A formal [4-1-3] cycloaddition leading to products with a core structure similar to that of 220 was found when 2-iodophenols and furan are treated with a mixture of BusSnH, 2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70), and a catalytic amount of diphenyl diselenide, albeit moderate yields have been achieved (Equation 86) <2005OL3625>. 

A palladium-catalyzed annulation of internal alkynes to o-iodophenol derivatives to afford 3-fluoromethyl benzo-furans has also been described (Equation 116) <2004X11695>. 

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]. 

Fluoromethylated benzo[i) furans were made by palladium-catalyzed coupling of fluorine-containing internal alkynes with various 2-iodophenols in the presence of P( Bu>3 as an essential ligand <04T11695>. 

With the advent of palladium(O) catalytic methods, it is now possible to produce the furan ring of a benzofuran by interaction between an ortbo-iodophenol and an alkyne, the two carbon atoms of the triple bond providing carbons 2 and 3 of the furan ring and the larger substituent of the alkyne ending up at the heterocyclic 2-... 

The microwave-assisted solvent-free Sonogashira coupling-cyclization of 0-iodophenols 4 with terminal alkynes 5 and that of o-ethynylphenols 6 with organic iodides 7 to generate 2-substituted benzo[h]furans (8 and 9) has been... 

Hydroalkoxylation of alkynes, or the addition of alcohol to alkynes, is a fundamental reaction in organic chemistry that allows the preparation of enol ethers and a variety of oxygen-containing heterocycles such as furan, pyran, and benzofuran derivatives. Bergbreiter et al. found that a Mnear poly-(A-isopropylacrylamide) (PNIPAM) polymer exhibited inverse temperature solubility in water (i.e., soluble in cold water but insoluble in hot water). A recoverable homogeneous palladium catalyst was prepared based on the polymer. The PNIPAM-bound Pd(0) catalyst was effective for the reaction of 2-iodophenol with phenylacetylene in aqueous THE media to give the target product... 

An efficient approach to two types of 2,3-disubstituted benzo[fe]furans was reported by Rynn. In typical examples, the starting iodophenol was allowed to react with a phenylacetylene and an iodobenzene in the present of Pd(PPh,)jClj and MeMgCI with or without CO to lead to the 3-aroylbenzofuran (as shown) in the presence of CO, or to the 3-arylfuran in its absence <01CC1594>. 

Furan derivatives are prepared by reaction of o-iodophenols. 2-Phenylbenzo-[ >]furan was prepared by the reaction of o-iodophenol (64) with 1-alkyne in one step [40]. It should be noted that similar 2-arylbenzo[i>]furan formation occurred by the use of Pd-free, copper-phosphine complex [41]. Similarly 2-substituted furo[3.2-i ]pyridine 66 was prepared from 2-iodo-3-pyridinol (65) in a one-pot reaction [42]. Naturally occurring ailanthoidol was synthesized by the reaction of 67 and 68 to give the cyclized product 69 [43]. 

One-pot reactions involving acyl chlorides, phosphorus ylides, and o-iodophenols with copper catalysis were established for the rapid synthesis of functionalized benzo[ft]furans (14JOC10599). 

Vinylbenzo[l)]furans were synthesized via copper-catalyzed one-pot, three-component reactions of o-iodophenols, in situ generated aUenes, and dichloromethane (14OL5160). 

Ramon et al. found that impregnated copper on magnetite (CuO-FeaO ) could facilitate the domino Sonogashira-cyclization processes between 2-iodophenol and various alkynes to afford the 2-substituted benzo[fc]furan derivatives (Scheme 4.41) (Cano et al., 2012). 

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 same catalytic system was used for cross-coupling of terminal acetylenes with o-iodophenols and anilines giving the cyclization products, 2-substituted furanes and indoles, in high yields (Scheme 26). ... 

Typical procedure for the synthesis of benzo[Z ]furan. To a screw-capped vial with a stir bar were added 2-iodophenol (110 mg, 0.5 mmol), phe-nylacetylene (56.2 mg, 0.55 mmol), PS-PdONPs (2.9 mg, 1.5 mol% of Pd), triethylamine (152 mg, 1.5 mmol), and H2O (1.0 mL). After stirring at 80 °C for 20 h, the reaction mixture was cooled to room temperature by immediately immersing the vial in water ( 20 °C) for about 10 min. Subsequently, the aqueous phases were removed, and the recovered catalyst was washed with H2O (5x3.0 mL) and diethyl ether (5x3.0 mL), which were then added to the aqueous phase. The aqueous phase was extracted eight times with diethyl ether. The combined organic extracts were dried over MgS04 and concentrated under reduced pressure. The recovered PS-PdONPs was dried in vacuo and reused. The resulting product was purified by PTLC (hexane-CH2Cl2). 

Likewise, Hu, Fathi and coworkers have employed the Sonogashira reaction as a key step in the preparation of a 2,3-diarylbenzo[h]furan library [102]. Five different polymer-bound iodophenols were coupled with seven acetylenic compounds under Sonogashira conditions employing IRORl... 

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