O IODOPHENOL

In the reaction of aryl and alkenyl halides with 1,3-pentadiene (248), amine and alcohol capture the 7r-allylpalladium intermediate to form 249. In the reactions of o-iodoaniline (250) and o-iodobenzyl alcohol (253) with 1,3-dienes, the amine and benzyl alcohol capture the Tr-allylpalladium intermediates 251 and 254 to give 252 and 255[173-175]. The reaction of o-iodoaniline (250) with 1,4-pen tadiene (256) affords the cyclized product 260 via arylpalladiuni formation, addition to the diene 256 to form 257. palladium migration (elimination of Pd—H and readdition to give 258) to form the Tr-allylpalladium 259, and intramolecular displacement of Tr-allylpalladium with the amine to form 260[176], o-Iodophenol reacts similarly. 

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]. 

The reaction of o-iodophenol, norbornadiene and CO proceeds via alkene and CO insertions to afford the lactone 562, which is converted into coumarin (563) by the retro-Diels-Alder reaction. In this coumarin synthesis, norbona-diene behaves as a masked acetylene[4)3],... 

In a similar way, Aland and coworkers described a three-component Pd-catalyzed domino process of o-iodophenols or o-iodoanilides in the presence of a secondary... 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

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>. 

Palladium-catalyzed cyclization reactions with aryl halides have been used to synthesize pyrazole derivatives. V-Aryl-lV-(c>-bromobenzyl)hydrazines 26 participated in a palladium-catalyzed intramolecular amination reaction to give 2-aryl-2W-indazoles 27 . Palladium-catalyzed cascade intermolecular queuing-cyclocondensation reaction of o-iodophenol (28) with dimethylallene and aryl hydrazines provided pyrazolyl chromanones 29 <00TL7129>. A novel one-pot synthesis of 3,5-disubstituted-2-pyrazolines 32 has been achieved with an unexpected coupling-isomerization sequence of haloarene 30, propargyl alcohol 31, and methylhydrazine <00ACIE1253>. 

A three-component coumarin synthesis involves the Pd-catalysed coupling of o-iodophenols with alkynes and subsequent insertion of carbon monoxide. With internal alkynes, pyridine is the crucial base for successful annulation the regioselectivity with unsymmetrically substituted alkynes is only moderate (Scheme 43) . 

An intramolecular Heck cyclization strategy was developed for the construction of indole and benzofuran rings on solid support [82], enabling rapid generation of small-molecular libraries by simultaneous parallel or combinatorial synthesis. Sn2 displacement of resin-bound y-bromocrotonyl amide 97 with o-iodophenol 96 afforded the cyclization precursor 98. A subsequent intramolecular Heck reaction using Jeffery s ligand-free conditions furnished, after double bond tautomerization, the resin-bound benzofurans, which were then cleaved with 30% TFA in CH2CI2 to deliver the desired benzofuran derivatives 99 in excellent yields and purity. 

Cyclocarbonylation of o-iodophenols 503 with isocyanates or carbodiimides and carbon monoxide in the presence of a catalytic amount of a palladium catalyst (tris(dibenzylideneacetone)dipalladium(O) Pd2(DBA)3) and l,4-bis(di-phenylphosphino)butane (dppb) resulted in formation of l,3-benzoxazine-2,4-diones 504 or 2-imino-l,3-benzoxazin-4-ones 505 (Scheme 94). The product yields were dependent on the nature of the substrate, the catalyst, the solvent, the base, and the phosphine ligand. The reactions of o-iodophenols with unsymmetrical carbodiimides bearing an alkyl and an aryl substituent afforded 2-alkylimino-3-aryl-l,3-benzoxazin-4-ones 505 in a completely regioselective manner <1999JOC9194>. On the palladium-catalyzed cyclocarbonylation of o-iodoanilines with acyl chlorides and carbon monoxide, 2-substituted-4f/-3,l-benzoxazin-4-ones were obtained <19990L1619>. 

The analogous palladium catalyzed reaction of internal acetylenes, 2-iodophenol and carbon monoxide leads to the selective formation of coumarins. The heterocyclic analogues of o-iodophenol are also effective. The o-iodopyridone shown in 4.16. for example gave rise to the formation of azacoumarin in 70% yield.18 In these processes the insertion of the acetylene derivative occurs in advance of the insertion of CO. Interestingly, the change of the acetylene to an alkene reverses the insertion order and leads to flavone formation.19... 

The absorption curves for o-bromophenol and o-iodophenol are similar to those for o-chlorophenol, the shifted peaks lying at 6860 and 6800 cm-1, respectively. Guaiacol, o-methoxyphenol, shows a single peak at 6930 cm- 1, corresponding to the cis configuration... 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichloro-9/T-fluoren-9-yIidene (15) may lead to the formation of fullerene fragments.89 The amiulation reaction, under palladium catalysis, between iodoanflines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck aiylation of cyclic enamides.93... 

Benzofurans. 2-Substituted benzofurans can be obtained in 65-83% yield by reaction of o-iodophenols and 1-alkynes in the presence of Cu20 suspended in pyridine. This synthesis has been conducted in the past by reaction of copper(I) acety-lides with o-halophenols, but yields are somewhat lower. In addition, copper(I) acetylides can be explosive. 

More recently, cationic intermediates have been observed in the Heck reactions of arene diazonium salts catalyzed by triolefinic macrocycle Pd(0) complexes [17,59], o-iodophenols and enoates to form new lactones [60], and o-iodophenols with olefins (the oxa-Heck reaction) [61 ]. In the first case ions were formed by oxidation of the analyte at the capillary, or by association of [NH4] or Na". In the two other cases ionization occurred through the more typical loss of a halide ligand. The oxa-Heck reaction provides a good example of how these experiments are typically performed and the type of information that can be obtained. The oxyarylations of olefins were performed in acetone, catalyzed by palladium, and required the presence of sodium carbonate as base. Samples from the reaction mixtures were diluted with acetonitrile and analyzed by ESI(+)-MS. Loss of iodide after oxidative addition of o-iodophenol to palladium afforded positively-charged intermediates. Species consistent with oxidative addition, such as [Pd(PPh3)2(C6H50)], and the formation of palladacycles of the type seen in Scheme 8 were observed. Based on this, a mechanism for the reaction was proposed (Scheme 8). 

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