Aryl halides palladium-catalyzed carbonylations

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...

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). 

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. 

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]. 

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],... 

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. 

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]. 

Meyers and colleagues described the palladium-catalyzed carbonylative synthesis of oxazolines as early as 1992 [268]. Aryl or enol triflates made from the corresponding ketones and phenols, and also aryl halides, were used as starting materials and coupled with amino alcohols to give chiral a,)S-unsaturated or aryl oxazolines in good yields. Later on, Perry s group performed systematic studies on this one-pot, two-step process for the preparation of oxazolines (Scheme 2.37) [269, 270]. 

Castanet and his team demonstrated a palladium-catalyzed carbonylative Suzuki reaction of pyridine halides in 2001. Under their conditions, pyridine halides reacted with aryl boronic acids to 2-pyridyl ketones in good yields (81-95 % Scheme 4.8). The proper choice of solvent, catalyst precursor, and CO pressure enabled the selective transformation of mono- and dihalopyridines. Later on, they... 

In 2001 Yun and colleagues used a solid-supported organostannane, which was reacted with aryl halides in a palladium-catalyzed carbonylative coupling reaction [63] to produce a wide range of diaryl ketones. 

Mann et al. showed that various acetophenones can be synthesized by carbonylative coupling of aryl triflates with SnMe4 [65]. Under mild conditions using the catalyst system Pd(OAc)2/dppp, good yields (70-94 %) were obtained (Scheme 4.32). In 2002 Mido and colleagues reported the palladium-catalyzed carbonylative coupling of tributyl(l-fluorovinyl)stannane with aryl halides and aryl triflates [66]. In the presence of a catalytic amount of palladium catalyst and CsF in DMF, aryl 1-fluorovinyl ketones were formed in good yields. 

The first palladium-catalyzed carbonylative Sonogashira coupling was reported in 1981 by Kobayashi and Tanaka [25]. Aryl, heterocyclic, and vinylic halides reacted with CO and terminal acetylenes at 120 °C and 80 bar in the presence of NEta and a catalytic amount of a palladium(II) complex to form alkynones in a 46-93 % yield (Scheme 5.3). Remarkably, aryl bromides and aliphatic alkynes were also included in the range of substrates. But NEts was used as a solvent for this transformation and a relatively high pressure of CO was needed. 

The first report on a palladium-catalyzed carbonylative C-H activation was published in 1986 by Kobayashi and Tanaka [1]. They reported that the carbonylation of organic halides with activated methylene compounds in the presence of NEta under 20 bar of CO produces various ketones in good yields (Scheme 6.1). Aryl iodides, bromobenzene and one example of a vinyl bromide were used as starting materials. But relatively high pressure and high pressure are needed, and tri-ethylamine was used both as a base and solvent. 

Shortly thereafter, a more general palladium-catalyzed carbonylative Heck reaction of aryl halides was able to be developed by our group [34]. For the first time, various aromatic and aliphatic alkenes were used successfully in this system, and good yields of the corresponding a,jS-unsaturated ketones were obtained (41-90 %). Starting from easily available aryl iodides and bromides, interesting building blocks were obtained under mild conditions (Scheme 7.15). With respect to the reaction mechanism, the aryl palladium complex and acyl palladium complex were characterized by X-ray, and the mechanism was studied step by step. The results fit well with DFT calculations. 

Scheme 7.15 Palladium-catalyzed carbonylative Heck reaction of aryl halides...

The first palladium-catalyzed carbonylations of aryl halides were published in 1974 and 1975 (Equation 17.59). ° Heck first reported the synthesis of benzoates by the reaction of an aryl iodide, carbon monoxide, and an alcohol in the presence of a tertiary amine and catalytic amoimts of the combination of palladium acetate and triphenylphosphine. Concurrently, he reported the synthesis of benzamides from an aryl iodide, carbon monoxide, a primary amine, and a tertiary amine as base catalyzed by the same type of palladium complex. The related reactions of vinyl halides were also reported, and these reactions occurred with retention of the olefin geometry. ... 

VI.2.1.1.1 Palladium-Catalyzed Carbonylation of Aryl and Vinylic Halides... 

B.i. Palladium-Catalyzed Carbonylation of Aryl or Vinyl Halide... 

The first example of a microwave-promoted carbonylation was published by Kaiser et al. [13]. In this investigation, the palladium-catalyzed carbonylation of aryl halides... 

An alternative strategy for performing microwave carbonylations without directly using carbon monoxide is to use formic acid derivatives as the source of CO. In fact, common solvents such as DM F or formamide are known to thermally decompose in the presence of a strong base to carbon monoxide and the corresponding amine [40]. The carbon monoxide released in this manner has been used in palladium-catalyzed carbonylation of aryl halides. The nucleophile involved can be either amine derived from the CO source or externally added. 

Palladium-catalyzed carbonylation of aryl halides with nucleophiles such as alcohols, amines, and water can be performed in ionic liquid media. Several systems have been designed so that the ionic phase can be isolated and recycled. Once carbonylation substrates/products form homogeneous mixtures with ionic liquids, the experimental protocols for catalyst/ionic liquid mixture recycling involve separation of the product by either distillation or extraction procedures using organic solvents or supercritical CO2. 

Carbonylation of allylic compounds in alcoholic solvent gives p,y-unsaturated esters, however, these substrates are far less reactive to palladium-catalyzed carbonylation than aryl or alkenyl halides." In general, a large positive pressure of carbon monoxide is necessary to drive these reactions forward. 

Mo(CO)e can be used as a source of carbon monoxide in palladium-catalyzed carbonylations via a ligand-exchange reaction, as reported by Yamazaki and Kondo [22], Two different routes to amides were described, with either the aryl halide or the nucleophile attached to the solid phase (Scheme 3). These methods were subsequently apphed in the synthesis of heterocycles. 

The issue of yields was closely investigated in a series of palladium-catalyzed carbonylations of aryl/heteroaryl halides and triflates with [ C]carbon monoxide, prepared through treatment of well-defined quantities of lithium [ C]formate with concentrated sulfuric acid. The experiments were carried out in a dual-chamber reaction vessel, one section for the generation of CO, the other for the carbonylation reaction. This arrangement eliminated the need to manipulate the CO released but instead relied on its being drawn from the first chamber into the second as it was consumed. The reaction sequence was typically performed with two equivalents of Ba COj, which corresponded... 

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