Iodophenol derivative

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

Hong and Overman reported the intramolecular termination of cascade reactions by oxygen nucleophiles in their studies on a novel synthesis of morphine (Scheme Starting from an iodophenol derivative tethered with an iodophenol silyl ether, intramolecular carbopalladation provided a bicycUc Tr-allylpalladium intermediate, which in turn was attacked by the oxygen functionality (Scheme 37). 

Similarly, iodoaniline and iodophenol derivatives react with phenylacetylene under carbonylative conditions to give (Z)-lOa and (Z)-lOb (77%)f ° respectively,... 

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]. 

CL reaction can be catalyzed by enzymes other than HRP (e.g., microperoxidase and catalase) and by other substances [hemoglobin, cytochrome c, Fe(III), and other metal complexes]. The presence of suitable molecules such as phenols (p-iodophenol), naphthols (l-bromo-2-naphthol), or amines (p-anisidine) increases the light production deriving from the HRP-catalyzed oxidation of luminol and produces glow-type kinetics [6, 7], The use of other enzymes, such as glucose-6-phosphate dehydrogenase [38-41], P-galactosidase [42], and xanthine oxidase [43-46], as CL labels has been reported. 

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>. 

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. 

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. 

In an alternative strategy functionalized phenols, such as iodophenol, were involved in palladium-catalyzed carbonylation of alkynes or allenes, producing coumarin or chromone derivatives (Scheme 23) [130-133]. After oxidative addition of the iodoarene to the Pd(0) catalyst the order of insertion of either CO or the unsaturated substrate mainly depends on the nature of the substrate. In fact, Alper et al. reported that CO insertion occurs prior to allene insertion leading to methylene- or vinyl-benzopyranone derivatives [130]. On the contrary, insertion of alkynes precedes insertion of CO, affording couma-rine derivatives, as reported by Larock et al. According to the authors, this unusual selectivity can be explained by the inability of the acyl palladium species to further react with the alkyne, hence the decarbonylation step occurs preferentially [131-133]. 

The same reaction, the conversion of 2-iodophenol to 2-arylbenzofuranes was also accomplished in the presence of a copper-phenantroline catalyst and caesium carbonate. Different arylacetylenes and iodophenols were coupled to give the corresponding benzofurane derivatives in good to excellent yield (3.55.)71... 

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... 

Benzofurans and dihydrobenzofurans have been prepared on polymeric supports by the palladium-mediated reaction of 2-iodophenols with dienes or alkynes (Entries 1 and 2, Table 15.9). This reaction is closely related to the synthesis of indoles from 2-iodoanilines, and probably proceeds via an intermediate palladacycle (Figure 15.3). Benzofuran and isobenzofuran derivatives have also been prepared on cross-linked polystyrene by intramolecular addition of aryl radicals to C=C double bonds and by intramolecular Heck reaction. 

Unfortunately, length restrictions did not permit us to consider in detail the tremendous amount of information available on heteroleptic complexes, which are briefly reviewed in Chapter 7. The reviews do not consider a broad group of autocomplexes — derivatives of nitro-, aminophenols, ketoenols, and also chloro-, bromo-, and iodophenols that are stable to hydrolysis and are only formal analogs of alkoxides and phenoxides. 

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... 

The effect of the halogen substituent (fluoro, chloro, bromo and iodo) on the yield and mechanism of 4-halophenol photolysis was investigated by Durand et al. [24], Transient spectroscopy in aerated aqueous solutions indicated the formation of p-benzoquinone O-oxide from each derivative except 4-iodophenol for which no transients were detected p-benzoquinone and hydroquinone were found as photoproducts for all four compounds. It was concluded that the carbene mechanism was valid for the whole series. Under continuous irradiation, the 4-halophenol degradation quantum yields were determined to be

fluorescence lifetimes decreased in the same order, from 2.1 ns for 4-fluorophenol to 0.4 ns for 4-chlorophenol and < 0.1 ns for 4-bromophenol. 

Since the emission spectra of enhanced and unenhanced luminol oxidations are similar, it seems clear that emission is from the excited-state aminophthalate derived from luminol itself and not from the enhancer. The enhancement is also specific for peroxidase i.e., it does not occur under conditions in which the heme would dissociate from the enzyme. Furthermore, luminol chemiluminescence triggered by heme-containing compounds, such as hemoglobin or cytochrome c, is actually reduced by enhancers such as p-iodophenol (T7). This latter phenomenon explains the potential usefulness of enhanced chemiluminescence, i.e., an amplified signal combined with a reduced background and reduced interference from the reagents as well as from endogenous heme compounds. 

A tandem RCM - DA sequence applied to enynes derived from 1 -iodophenol leads to... 

Carbonylation and carboxylation. Araldehydes are derived from the Pd-catalyzed reaction of ArX with CO and HCOONa. The Suzuki coupling under CO leads to diaryl ketones. Chromones and quinolones are similarly acquired by carbonylation of o-iodophenols and anilines in the presence of alkynes. 2-Aryl-benzimidazoles and -benzothiazoles are produced from o-arenediamines and o-mercaptoanilines, respectively. 

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