Carbonylation of halides

2 Carbonylation of Halides - Pd(tppts)3-catalysed carbonylation of bromo-benzene (Equation 7) in the presence of NEt3 in an aqueous/toluene (1/1) two phase system at 150°C and 15 bar CO afforded the triethylammonium salt of benzoic acid (100% yield).464,465 Rates were rather low (TOF s of 3.3-17 h ) but no decomposition of Pd(tppts)3 (tppts/Pd 12.5) was observed and the catalyst could be recovered quantitatively and recycled 464 However, in a second recycle extensive decomposition of the catalyst occurred with formation of palladium black. Generally in carbonylation reactions of halides the formation of stoichiometric amounts of either HX or halide salts still remains a problem of environmental concern despite the attractiveness due to the presence of the aqueous solvent. 

Attempted reductive carbonylation of bromobenzene with CO/H2 or with CO/HCOONa in the presence of a Pd/tppts catalyst failed to afford any benzaldehyde 464 

Similarly, PdCl2 modified with the water soluble phosphonated phosphine 105 (Table 5) was used as catalyst in the carbonylation of benzyl chloride to afford phenylacetic acid in 91% yield in an aqueous/organic two phase system under mild reaction conditions (55°C, 8 psi CO).259 

PdCl2(tppts)2 exhibited high catalytic activity (TOF=1860 h-1) for the carbonylation of allyl chloride to the desired product p,y-butenoic acid [Equation (8)] at 40°C and atmospheric CO pressure in an aqueous(NaOH)/toluene two phase system471 By-products were a,P-butenoic acid and allyl alcohol. The yield of butenoic acids was 94% with a 3,y/a, 3 ratio of 21 471 

PdCl2(tppms)2 was also used as a catalyst for the atmospheric pressure carbonylation of allyl halides at 30-50°C in the presence of sodium hydroxide or alkoxides to afford P,y-unsaturated acids or esters in yields up to 93% (P,y/a,p ratio 87/13) in biphasic or monophasic methanolic media.55,56,473,474 

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The benzoic acid derivative 457 is formed by the carbonylation of iodoben-zene in aqueous DMF (1 1) without using a phosphine ligand at room temperature and 1 atm[311]. As optimum conditions for the technical synthesis of the anthranilic acid derivative 458, it has been found that A-acetyl protection, which has a chelating effect, is important[312]. Phase-transfer catalysis is combined with the Pd-catalyzed carbonylation of halides[3l3]. Carbonylation of 1,1-dibromoalkenes in the presence of a phase-transfer catalyst gives the gem-inal dicarboxylic acid 459. Use of a polar solvent is important[314]. Interestingly, addition of trimethylsilyl chloride (2 equiv.) increased yield of the lactone 460 remarkabiy[3l5]. Formate esters as a CO source and NaOR are used for the carbonylation of aryl iodides under a nitrogen atmosphere without using CO[316]. Chlorobenzene coordinated by Cr(CO)j is carbonylated with ethyl formate[3l7]. 

Carbonylation of halides in the presence of primary and secondary amines at I atm affords amides[351j. The intramolecular carbonylation of an aryl bromide which has amino group affords a lactam and has been used for the synthesis of the isoquinoline alkaloid 498(352], The naturally occurring seven-membered lactam 499 (tomaymycin, neothramycin) is prepared by this method(353]. The a-methylene-d-lactam 500 is formed by the intramolecular carbonylation of 2-bromo-3-alkylamino-l-propene(354]. 

Formation of ketones. Ketones can be prepared by the carbonylation of halides and pseudo-halides in the presence of various organometallic compounds of Zn, B, Al, Sn, Si, and Hg, and other carbon nucleophiles, which attack acylpalladium intermediates (transmetallation and reductive elimination). 

Carbonylation of halides in the presence of terminal and internal alkynes produces a variety of products. The substituted indenone 564 is formed by the reaction of o-diiodobenzene. alkyne, and CO in the presence of Zn[414]. 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

Formation of aldehydes. Aldehydes can be prepared by the carbonylation of halides in the presence of various hydride sources. The carbonylation of aryl and alkenyl iodides and bromides with CO and H (1 1) in aprotic solvents in the presence of tertiary amines affords aldehydes[373,374]. Aryl chlorides, as tricarbonylchromium derivatives, are converted into aldehydes at 130 C[366], Sodium formate can be used as a hydride source to afford aldehydes. Chlorobenzene (514) was carbonylated at 150 °C to give benzaldehyde with CO and sodium formate by using dippp as a ligand[375,376]. 

Carbonylation of halides with tetramethyltin This nickel complex is the most efficient catalyst for the synthesis of methyl ketones by reaction of aryl halides with carbon monoxide and tetramethyltin in HMPT at 120°. No reaction occurs when tetraphenyltin is used. A typical reaction is formulated in equation (I). 

Bis(triphenylphosphine)palladium dichloride [(Ph3P)2PdCl2] can also be used as a catalyst for the phase-transfer carbonylation of halides. However, considerably more drastic conditions [95°C, 5 atm] are required when compared with Co2(CO)8 (44). The carbonylation of allyl chlorides can be catalyzed by nickel tetracarbonyl, giving isomeric mixtures of bu-tenoic acids. There is evidence for the intermediacy of polynuclear nickel-ates in this phase-transfer process (45). Acetylene insertion did not occur... 

CuCl2 need to be used to reoxidize the Pd° back to Pd . The carbonylation of halide-containing alcohols is a better reaction as it takes place under mild conditions and often in good yields (equation 25). 

The direct catalytic carbonylation of halides to aldehydes is not readily achieved. Aryl, heterocyclic and vinyl halides, for example, in the presence of [Pd(PPh3)2Ch], a stoichiometric quantity of tertiary amine and synthesis gas (CO/H2), are converted to aldehydes, but the conditions are somewhat drastic (80-100 bar, 80-150 Alkyl halides are even less suitable for this reaction as they tend to undergo dehydrohalogenation to form alkenes, rather than carbonylation. However, using the platinum catalyst [PtCh(PPh3)2], primary alkyl iodides can be successfully carbonylated to aldehydes in good yield under moderate conditions (equation 5). °... 

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). 

The catalytic carbonylation of halides can also be used to synthesize phthalides (equation 46). The reaction will proceed bodi in the presence of palladium and cobal7 catalysts. 

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-catalysed carbonylation of halides, with carbon monoxide, can be used to prepare esters, amides and ketones by trapping the intermediate acylpalladium halide with alcohols,amines and organometal-lics, respectively. Boronic acids are probably the best organometallics for the preparation of ketones, but conditions must be adjusted to give the best selectivity between the acylation reaction and simple Suzuki coupling of the boronic acid with the starting halide. ... 

Under phase transfer conditions, nickel can also catalyze double carbonylation of halide substrates. 2-Halo-l,3-dienes have been converted into a-keto-/3-alkylidene acids or lactones catalyzed by nickel cyanide in the presence of a phase transfer agent (Eq. 

The last reaction discussed in this section will be the carbonylation of halides. 

Chap. 3.2.4, 844-865 Aldrichim. Acta 24, 3, 1991 b) H. Alper, H. des Abbayes - Phase-Transfer Catalyzed Organometallic Chemistry. The Cobalt Carbonyl-Catalyzed Carbonylation of Halides,... 

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