Halides palladium-catalyzed carbonylation

The palladium-catalyzed carbonylation of aryl halides in the presence of various nucleophiles is a convenient method for synthesizing various aromatic carbonyl compounds (e.g., acids, esters, amides, thioesters, aldehydes, and ketones). Aromatic acids bearing different aromatic fragments and having various substituents on the benzene ring have been prepared from aryl iodides at room temperature under 1 atm... 

Scheme 5. Palladium-catalyzed carbonylations of aryl halides and pseudohalides...

The mechanism of palladium-catalyzed carbonylation of organic halides is generally assumed to involve oxidative additon of R-X to a Pd(0) species which is formed from the precursors on the action of CO + OH . Migratory insertion of R onto a coordinated CO followed by reaction with a nucleophile generates the product and gives back the catalytically active palladium(O) species (Scheme 5.4 A). 

Bromophenyl)ethanol undergoes a palladium-catalyzed carbonylation which results in the formation of isochroman-l-one (79H(12)92l). It is considered that the reaction involves formation of an aryl-palladium complex (624) through insertion of the zerovalent palladium complex (623) into the aryl halide. Insertion of carbon monoxide followed by reductive elimination of the metal as a complex species leads to the isochromanone (Scheme 242). 

The palladium-catalyzed carbonylation of isomeric vinylic halides shows the reaction to be reasonably stereospecific and proceed with retention of the original halide structure. The degree of specificity, however, depends somewhat on the reaction conditions. Low reaction temperatures and/or excess triarylphosphine favor the stereospecific reaction (11). 

Amides are produced from the palladium-catalyzed carbonylation of organic halides if primary or secondary amines are present rather than only an alcohol (/5) ... 

Another variation of the palladium-catalyzed carbonylation reaction occurs when hydrogen is added rather than an alcohol or a primary or secondary amine. This variation leads to aldehyde formation the hydrogen reduces the acylpalladium intermediate to aldehyde and metal hydride (76). A basic tertiary amine is also added as in the ester-forming reaction to neutralize the hydrogen halide formed in the dissociation of the hydride ... 

A brief review on the palladium-catalyzed carbonylation of organic halides has appeared.505... 

Ikariya and co-workers reported an efficient palladium-catalyzed carbonylation of aryl halides in sc C02 (eq. 2.10) (Kayaki et al., 1999). 2-Iodobenzyl alcohol was converted to the phthalide in the presence of PdCl2L2 [L = PMe3, PPh3, MeCN, P(OEt)3, P(OPh)3, PPh(OMe)2, PPh2(OMe)] with higher rates in sc C02 than in toluene. 

Palladium-catalyzed carbonylation reactions with aryl halides are powerful methods of generating aromatic amides, hydrazides, esters and carboxylic acids [25]. We have previously reported the exploitation of Mo(CO)6 as a robust carbon monoxide-releasing reagent in palladium-catalyzed carbonylation reactions [26-29]. This stable and inexpensive solid delivers a fixed amount of carbon monoxide upon heating or by the addition of a competing molybdenum coordinating ligand (for example DBU). This allows for direct liberation of carbon monoxide in the reaction mixture without the need for external devices. 

R. Skoda-Foldes, L. Kollar, Synthetic Applications of Palladium Catalyzed Carbonylation of Organic Halides, Curr. Org. Chem. 2002, 6, 1097-1119. 

In 1979 the reaction of benzyl and aryl halides was reported with mechanistic discussions [8, 9]. The first palladium-catalyzed carbonylative coupling of organic halides with organotin compounds was reported by Tanaka in the same year (Scheme 4) [10,11]. 

For the ketone synthesis via the present protocol, acid chlorides are useful precursors, in deed. Nevertheless, carbonylative cross coupling with organic halides is strategically the most simple and direct way to this purpose. The palladium-catalyzed carbonylative cross-coupling reaction with various organic halides has been extensively investigated, because of its merits from synthetic as well as phenomenal point of view. Acid chlorides are not always readily available, and their preparation is not always compatible with many sensitive functionalities. Therefore the development of this type of reaction widens the scope of the ketone synthesis in the present protocol because of the ready availability and storability of organic halides and pseudohalides. 

In the metallic palladium-catalyzed carbonylation of olefins, some hydrogen sources are essential hydrogen halide and molecular hydrogen were found to be the most eflFective. The following sequence of reactions was proposed for the reaction mechanism of the ester and aldehyde formation catalyzed by palladium (23). The first step of the metallic palladium-catalyzed carbonylation seems to be the formation of a palladium-hydrogen bond by the oxidative addition of hydrogen chloride... 

The palladium-catalyzed carbonylative coupling reaction of alkenyl halides with organoboron compounds in the presence of carbon monoxide is a valuable procedure for the synthesis of unsymmetrical ketones. " ... 

Allylic halogenides containing an additional internal functional group in a suitable position, e. g., an alkene moiety or a hydroxy group, produce the corresponding cyclopentenone derivatives or lactones, respectively, via palladium-catalyzed carbonylation [43]. Related cyclocarbonylations of cinnamyl halides or acetates to form polycyclic aromatics such as naphthol derivatives have been reported (eq. (15)). Moreover, the synthetic utility of the method was demonstrated by the synthesis of acetoxybenzofurans, acetoxyindoles, and acetoxycarbazoles [44]. 

P-Lactones can be obtained by oxidative carbonylation of alkenes in the presence of water. Ethylene, for example, is converted to p-propiolactone by carbonylation in aqueous acetonitrile at -20 C using a catalytic amount of PdCh and a stoichiometric quantity of copper(II) chloride (equation 37). Palladium-catalyzed carbonylation of halides can also be used to prepare p-lactones under mild conditions. The reaction takes place at room temperature and pressure in the presence of [PdCl2(PPh3)2] and has been applied to both bromides and chlorides (equations 38 and 39). 

Palladium-catalyzed carbonylation of halides has been applied to the synthesis of natural products such as zearalenone (13 Scheme and curvulin (14 Scheme 23i)P In both cases the yields for the carbonylation steps are 70%. 

Palladium-catalyzed carbonylation of heteroaryl halides provides a quick entry to heteroaryl carbonyl compounds such as heteroaryl aldehydes, carboxylic acids, ketones, esters, amides, a-keto esters, and a-keto amides. In addition, Pd-catalyzed alkoxycarbonylation and aminocarbonylation are compatible with many functional groups, and therefore have advantages over conventional methods for preparing esters and amides [78]. 

Alfhough direct nucleophilic addition is limited because of the low nucleophilicity of fhe fluoride ion, a palladium-catalyzed reaction enables the weak nucleophile to participate fhe addition reaction. In the presence of cesium fluoride, palladium-catalyzed carbonylation of an aryl halide gives fhe acyl fluoride in good yield (Scheme 2.5) [8]. 

The palladium-catalyzed carbonylation of organic halides is a convenient means of synthesizing carbonyl compounds. For example, the single carbonylation of aryl iodides has been applied to synthesize lactones and lactams (eq (69) and (70)) [97,98],... 

Based on the palladium-catalyzed carbonylation of benzylic halides Sheldon and co-workers investigated the functionalization of 5-hydroxymethylfurfural (HMF) to 5-formylfuran-2-acetic acid (FFA) in aqueous medium in the presence of a water-soluble palladium/TPPTS catalyst (Scheme 3) [5], Here, the hydroxy group displays similar reactivity under acidic conditions compared with benzylic halides. 

In general for carbonylations, palladium as catalyst metal is preferable to nickel with respect of catalyst efficiency. Thus, Okano, Kiji, and co-workers described some other efficient palladium-catalyzed carbonylations of allyl chloride and substituted allyl halides (Eqs. 5-10). In greater detail, the water-soluble palladium complex PdCl2[Ph2P(w-C6H4S03Na)]2 has been used in a two-phase system (e.g., aqueous NaOH/benzene medium) at atmospheric carbon monoxide pressure, giving 3-butenoic acids [20], In the carbonylation of allyl chloride a mixture of 2-bute-noic acid, which was formed by base-catalyzed isomerization, and 3-butenoic acid was obtained in up to 90% yield (TON = 135), albeit at moderate selectivity (24 76). Clearly, the isomerization depends on the concentration of the base and was therefore suppressed by a method of continuous addition to the aqueous medium. 

Cassar, L., M. Foa, and A. Gardano, The Use of Phase Transfer Catalysis in Palladium-Catalyzed Carbonylation of Organic Halides, J. Organomet. Chem, 121, C55 (1976). 

The palladium-catalyzed carbonylation reaction with aryl halides is a powerful method for generating aromatic amides, hydrazides, esters, and carboxylic acids... 

Heck carbonylation involving the oxidative addition of aryl halides is not applicable to aliphatic halides, since alkyl halides react directly with nucleophiles. Tsuji developed a process of carbonylating allyl carbonates to form carboxylic esters by palladium-catalyzed carbonylation that is applicable to aliphatic substrates [60]. The process probably involves (a) the oxidative addition of allyl carbonates to Pd(0) species to form r/ -allyl palladium species, (b) CO insertion into the allyl-Pd bond to give acylpalladium species, (c) decarboxylation of the carbonate ligand to give alkoxide, and (d) liberation of butenoate esters by combination with the alkoxides as shown in Scheme 1.21. 

The low melting and liquid halide salts in Table 1 have found utility as ILs. McNulty et al. have reported high yields for palladium cross-coupling reactions using entry 9 (CYPHOS ILlOl) as a recyclable solvent/catalyst system [15], Similarly, Kaufmann et al. have reported that entry 12 can be used repeatedly with the same palladium catalyst to obtain high conversions of Heck coupling products [16]. Ramani has demonstrated that entry 9 can be successfully employed for a variety of reactions such as quantitative Michael addition of amines to acrylate esters [17], palladium-catalyzed carbonylation of iodobenzene to obtain ethyl benzoate [9], and Heck coupling of iodobenzene and ethyl acrylate [19]. 

Other syntheses that have been developed for preparation of triketones include activating the dione portion (to give 14) and coupling this with an aroyl acid (15) in the presence of a Lewis acid catalyst [24] followed by 0-acyl rearrangement, or by palladium-catalyzed carbonylation of an aroyl halide (16) in the presence of a dione (10) [25] and subsequent rearrangement of the 0-acyl product (12) formed into the triketone (13) (Scheme 4.3.2). 

Tanaka and his associates demonstrated for the first time how to use non-volatile ionic liquids (ILs) as solvents in palladium-catalyzed carbonylations [163], In the case of alkoxycarbonylation of bromobenzene, higher yields were obtained when 1-butyl-3-methylimidazolium tetrafluoroborate [bmim][BF4] was used as the reaction medium compared with standard conditions. And the selectivity for the monocarb-onylation of iodobenzene with t -PrOH or Et2NH was significantly enhanced by [bmim][BF4]. After separation of the products, the solvent-catalyst system was easily recycled and exhibited catalytic activity up to seven times. Since then the replacement of traditional solvents with quaternary ammonium halides, imidazoli-um- or pyridinium-derived ILs has gained increasing importance [164—173]. Recently, the phosphonium salt IL trihexyl(tetradecyl)phosphonium bromide has proven to be an effective reaction medium for various carbonylation reactions of aryl and vinyl bromides or iodides under mild conditions (Scheme 2.17) [174]. 

In 1984 Head and colleagues reported a palladium-catalyzed carbonylative synthesis of heterocyclic esters from the corresponding halides [213]. The main substrates are heterocyclic bromides one example of heterocychc chloride was also described. Using PdClaCPPhs) as a catalyst under 7.9 bar of CO at 100 °C in ethanol with NEta as the base, 5-chloroethyInicotinate was produced from 3,5-dichloropyridine. 

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