Esters palladium catalyzed carbonylation

Oxidative Carbonylation of Ethylene—Elimination of Alcohol from p-Alkoxypropionates. Spectacular progress in the 1970s led to the rapid development of organotransition-metal chemistry, particularly to catalyze olefin reactions (93,94). A number of patents have been issued (28,95—97) for the oxidative carbonylation of ethylene to provide acryUc acid and esters. The procedure is based on the palladium catalyzed carbonylation of ethylene in the Hquid phase at temperatures of 50—200°C. Esters are formed when alcohols are included. Anhydrous conditions are desirable to minimize the formation of by-products including acetaldehyde and carbon dioxide (see Acetaldehyde). 

Scheme 8.15. Synthesis of Ketones, Esters, Carboxylic Acids, and Amides by Palladium-Catalyzed Carbonylation and Acylation... 

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 6.47 Palladium-catalyzed carbonylation reactions yielding acids, esters, and lactones using molybdenum hexacarbonyl as a solid source of carbon monoxide.

Allenic esters can be generated by palladium-catalyzed carbonylation of propargyl compounds (see Section 7.2.6). Under the reaction conditions applied, however, succeeding reactions occur directly in many cases, for instance by introduction of a second ester function. Many examples of such carbonylation reactions of allenic esters were summarized in a review by Tsuji and Mandai [136],... 

The synthesis of pyrimidine carboxylic esters can be achieved by palladium-catalyzed carbonylation of halopyrimi-dines with carbon monoxide and an alcohol < 1999T405, 2001S1098>, as shown by the formation of a variety of esters 271 from 2-chloro-4,6-dimethoxypyrimidine 270 <1999T405>. 

The synthesis of succinic acid derivatives, /3-alkoxy esters, and a,j3-unsaturated esters from olefins by palladium catalyzed carbonylation reactions in alcohol have been reported (24, 25, 26, 27), but full experimental details of the syntheses are incomplete and in most cases the yields of yS-alkoxy ester and diester products are low. A similar reaction employing stoichiometric amounts of palladium (II) has also been reported (28). In order to explore the scope of this reaction for the syntheses of yS-alkoxy esters and succinic acid derivatives, representative cyclic and acyclic olefins were carbonylated under these same conditions (Table I). The reactions were carried out in methanol at room temperature using catalytic amounts of palladium (II) chloride and stoichiometric amounts of copper (II) chloride under 2 atm of carbon monoxide. The methoxypalladation reaction of 1-pentene affords a good conversion (55% ) of olefin to methyl 3-methoxyhexanoate, the product of Markov-nikov addition. In the carbonylation of other 1-olefins, f3-methoxy methyl esters were obtained in high yields however, substitution of a methyl group on the double bond reduced the yield of ester markedly. For example, the carbonylation of 2-methyl-l-butene afforded < 10% yield of methyl 3-methyl-3-methoxypentanoate. This suggests that unsubstituted 1-olefins may be preferentially carbonylated in the presence of substituted 1-olefins or internal olefins. The reactivities of the olefins fall in the order RCH =CHo ]> ci -RCH=CHR > trans-RCH =CHR >... 

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 ... 

The palladium-catalyzed carbonylation reaction of alkenyliodonium salts in the presence of alcohols proceeds at room temperature under one atmosphere of carbon monoxide to afford esters 89 in good yields (Scheme 40) [68]. 

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. 

After separation of the desired major diastereoisomer 154, the removal of the chiral auxiliary furnished vinyl compound 151 in enantiomerically pure form. The latter was directly converted to the 9-membered lactam 144 in 58% yield via a palladium-catalyzed carbonylation (10 atm CO, HCOOH, DME, 150°C). Removal of the methyl ester as previously described furnished (-)-rhazinilam. This elegant work constitutes the first asymmetric total synthesis of the natural product. 

Synthesis of ester 83a and amide 83b was performed by palladium-catalyzed carbonylation starting from iodo lactone 98 to afford products in good yields (Scheme 13, Section 14.10.5.4) <2002JOC4565>. 

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... 

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]. 

Advantage has been taken of the aforementioned observations in the synthesis of a terthiophene natural product, arctic acid (250) [168]. Palladium-catalyzed carbonylation of bromobisthiophene 37, obtained from the Kumada coupling of 2-thienylmagnesium bromide and 2,5-dibromothiophene, gave bithiophene ester 247, which was converted to iodide 248 by reaction with iodine and yellow mercuric oxide. Subsequent propynylation of 248 was then realized using the Sonogashira reaction with prop-l-yne to give bisthienyl alkyne 249, which was subsequently hydrolyzed to 250, a natural product isolated from the root of Arctium lappa. 

Rhone-Poulenc developed ketoprofen [66]. A few synthetic routes have been reported that involving multi-step syntheses [67, 68]. Ketoprofen is produced by similar reaction sequences that were described for naproxen [69]. Transition metal-catalyzed reactions including carbonylations, hydroformylations, and hydrogenations have been applied to the synthesis of ketoprofen. 3-Vinylbenzophenone (4) was obtained from 3-bromo-benzophenone (3) by a Heck reaction. Palladium-catalyzed carbonylation of 4 provided the isopropyl-a-(3-benzoylphenyl)propionate in 95% yield. Ketoprofen was then obtained in 90% yield by hydrolysis of the isopropyl ester [69]. 

Tsuji has employed a palladium-catalyzed carbonylation reaction in a formal synthesis of 110 (Eq. 1.4). Thus reaction of 3,5-dimethoxybenzyl chloride (115) with hydroxy ester 108 in the presence of 10 mole % of PdCl2(Ph3P)2 under a CO atmosphere produced diester 109 in 70% yield. Bycroft had previously converted 109 to the unnatural product 110. 

Palladium-catalyzed carbonylation of chloropyrazines in methanol and in amines yields the pyrazine carboxylic methyl esters and carboxamides, respectively. This procedure has been successfully applied to the synthesis of 2,5-pyrazinedicarboxylic acid derivatives and 3-methoxy-carbonylpyrazine 1-oxide from the corresponding dichloropyrazines and A-oxides <908923 >. 

Palladium-catalyzed carbonylation of aryl triflates in the presence of an alcohol141 or amine1423 provides a good method for preparation of arenecarboxylic esters and amides from phenols (equation 121). However, palladium-catalyzed cyanation of 5,6,7,8-tetrahydro-2-naphthyl triflate with potassium cyanide failed completely whereas the more reactive tetrakis(triphenylphosphine)nickel(0) could catalyze the same reaction which gives the nitrile in a good yield142b (equation 122). 

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]. 

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. 

Palladium-catalyzed carbonylation of organic halides to form esters, amides, ketones, and aldehydes (Equation 17.58) has been studied and reviewed extensively. " These reactions are closely related to the palladium-catalyzed cross-coupling processes presented in Chapter 19. However, the addition of CO to ttiese processes generates organic carbonyl compounds, rather than products from direct cross coupling. 

Palladium-catalyzed carbonylation of allylic and propargylic compounds offers a potential tool of one-carbon homologation. Particularly, pd-catalyzed carbonylation of propargylic compounds further provides synthetically valuable transformations because of the high reactivity of the intermediary allenyl esters. 

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