2-iodophenols carbonylation

Thiourea was used as stabilising agent for zerovalent Pd species [117]. The Pd-thiourea (H2NCSNH2) catalysed carbonylation of terminal alkynes and allylic alcohols has been described by Chiusoh [118]. More recently, Pd-thiourea-catalysed carbonylative annulation was studied. The reaction proceeds between alkynes, iodophenol acetates and carbon monoxide, in the presence of dppp, thiourea (H2NCSNH2) and base at 40 °C. Flavones have been obtained in good yields (Scheme 30) [119]. 

First, oxidative addition of 2-iodophenol to a Pd(0) species gives rise to an arylpal-ladium complex, which in turn undergoes carbonylation followed by insertion of allene to generate a 2-acyl-jt-allylpalladium complex. Attack by an internal hydroxyl group gives an a-exo-methylene ketone (Scheme 16.11). 

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]. 

Scheme 23 Pd-catalyzed carbonylation of iodophenol with alkynes and allenes...

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... 

Iodophenyl acetates undergo palladium-catalyzed carbonylation in the presence of aryl alkynes to yield flavones (Equation 309) <20000L1765>. 2-Iodophenols can similarly undergo a palladium-catalyzed carbonylation in the presence of terminal alkynes to afford chromones (Equation 310) <2005JOC6097>. 

A one-pot chroman-4-one synthesis-azomethine ylide cycloaddition can be performed using 2-iodophenol, carbon monoxide, allene and imine 1099 to furnish a mixture of exo- and OTr/o-cycloadducts 1100 (Equation 431) <2000TL7129>. Other nucleophiles are viable alternatives for this process <2000TL7125>. Synthesis of chroman-4-one 1101 is possible using a palladium catalyzed carbonylative cyclization of o-allyloxyliodobenzene (Equation 432) <2001JOC2175>. 

Iodophenol has been carbonylated in the presence of norbornadiene to give a reasonable yield of coumarin, which is formed by a spontaneous retro Diels-Alder reaction from the initially formed product (equation 158)891. 

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]. 

Palladium-catalyzed carbonylative addition reactions of 2-iodophenols 3 to norbornadiene lead to coumarin systems 4 via stereoselective cis-exo addition and retro-Diels-Alder elimination of cyclopentadiene12, l3. Intramolecular versions of this reaction type have been reported34 35, which include the use of nickel36-42-4 3 and rhodium3 catalysts. 

Heterocycles. Many different heterocycles are synthesized via a carbonylation process hydantoins from aldehydes and urea, flavones from ethynylarenes and o-iodophenol acetates, and a-substituted a,p-unsaturated lactones from iodoalkenols. ... 

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. 

The Pd-catalysed carbonylation of o-iodophenols with allenes is regioselective and generally yields 3-methylenechroman-4-ones <97JOC1566>, which are also formed via cyclisation of the acyl radicals generated by the decomposition of the allyloxybenzoyl diazonium salts (39) in the presence of Nal <97JOC5982>. 

The carbonylation of o-iodophenol in the presence of norbornene leads to a mixture of chromanone (40) and dihydrocoumarin (41). The relative proportions of the regioisomers can be controlled by varying the reaction conditions and the Pd catalyst <97SL97>. 

Carbonylation of 2-iodophenol (91) in the presence of 1,2-nonadiene (95) afforded 2-(n-hexyl)-3-methylene-2,3-dihydro-4/f-l-benzopyran -one (97) in 74% yield, showing that selective attack of phenoxy group at the substituted terminus of r-allylpalladium intermediate 96 occurred. Uses of DPPB and K2CO3 were important [43]. 

Formation of flavone 116 and aurone 117 by carbonylation of 2-iodophenol (91) in the presence of terminal alkyne is known [50]. Also l,4-dihydro-4-oxoquinoline 119 is obtained by the reaction of 2-iodoaniline with CO and terminal alkynes [51]. These reactions proceed via the formation of the aryl alkynyl ketones 118 as intermediates. 

Okuro, K. and Alper, H. (1997) Palladium-catalyzed carbonylation of < -iodophenols with allenes. J. Org. Chem., 62, 1566-7. 

In 2000 Yang and Miao reported a novel method for the preparation of flavones [64]. Various flavones are easily synthesized via palladium-catalyzed carbonylative annulation of iodophenol acetates with terminal acetylenes in high yields (Scheme 5.29). This novel reaction provides the possibility of a combinatorial synthesis of flavones on solid supports. 

Yang reported another example of carbonylations of o-iodophenols with terminal acetylenes to obtain flavones. Their reaction proceeded under 1 bar of CO in ionic liquids based on phosphonium salt (PS1L102, Ci4H29(C6Hi3)3)P r ) [66]. It should be noted that by using PSIL102 as an ionic liquid, no phosphine ligand was required (Scheme 5.31). 

In 1997, Alper and colleagues applied allenes as a special family of alkenes in palladium-catalyzed carbonylative reactions with o-iodophenols [25]. Remarkably,... 

Scheme 7.7 Palladium-catalyzed carbonylative coupling of o-iodophenols with allenes...

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

The carbonylative cyclization of 2-iodophenol with phenyl acetylene will provide 3-phenyl-l-(2-hydro) henyl)-2-propyn-l-one as the intermediate, and flavone and aurone are the two theoretically possible products. In 1991, Ortar and co-workers performed a systematic study on the reaction selectivity between these two possible products. In their carbonylative reaction between 2-iodophenols and terminal alkynes, the nature and position of substituents significantly affected the overall yield as well as the ratio between flavone and aurone. For the regiochemical outcome of this carbonylative coupling procedure, thq did a study on the cyclization of... 

The carbonylative cyclization of 2-iodophenols with norbornadiene or norbornene was also carried out. In 1989, Catellani s group studied the annulation of 2-iodophenol with norbornadiene to coumarin (Scheme 3.11a). ° In this method, the elimination of cyclopentadiene via retro-Diels-Alder reaction was involved in the formation of the terminal product. Fiaud and co-workers reported the palladium-catalyzed carbonylative cyclization of 2-iodophenol with norbornene in 1997 (Scheme 3.11b). They reported that the selectivity for the production of the two regioisomers can be controlled. Catellani and co-workers studied the intramolecular cyclization of ort/zo-iodophenyl 3-butenoate to 4-methylcoumarin with a palladium catalyst. 85% of 4-methylcoumarin was produced in the presence of benzonitrile and carbon monoxide, which is compulsory (Scheme 3.12a). Silva, Costa and their co-workers reported a tandem process for the synthesis of coumarins from 2-iodophenols and enoates with the assistance of a palladium catalyst (Scheme 3.12b). The general scope of this Heck-lactonization involves E- and Z-enoates as substrates. It was shown that this reaction is sensitive to steric hindrance around the double bound in... 

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