Palladium-Catalyzed Carbonylation Reactions

Mizushima, E., Hayashi, T. Tanaka, M (2004). Environmentally benign carbonylation reaction palladium-catalyzed hydroxycarbonylation of aryl halides and benzyl chloride derivatives in ionic hquid media Topics in Catalysis, 29, 3-4, ISSN 1022-5528... 

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]. 

More recently, Morken and colleagues described a rare example of using unsaturated carbonyls for palladium-catalyzed carbonylative coupling reactions with dialkylzinc reagents [81]. 1,4-Diketones were synthesized in good yields... 

Carbonylative Amination Among cross-coupling reactions, palladium-catalyzed aminocarbonylation is an interesting regioselective procedure to prepare amides [73]. The methodology consists of three-component coupling of aryl or alkynyl haUdes, primary/secondary amines, and carbon monoxide. 

Conceptually similar palladium-catalyzed cascade reactions have been developed, involving molecular-queuing cycloaddition, cyclocondensation and Diels-Alder reactions [71], cydization-anion-capture-olefin metathesis [72], carbonylation-allene insertion [73], carbonylation/amination/Michael addition [74], sequential Petasis reaction/palladium-catalyzed process [75], supported allenes as substrates [76], and palladium-ruthenium catalysts [77]. 

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). 

Palladium(O)- and Pd(II)-catalyzed carbonylation reactions have been the subject of several recent articles 32, 116, 119, 124, 173, 228, 232). In one case, the attending CO insertion into a Pd—C bond was shown to proceed with retention of configuration at carbon 131a, 218). 

Thus far, we have discovered and demonstrated a new and effident method for the synthesis of indoles from various carbonyl compounds. This, in conjunction with the use of alkyries in the palladium-catalyzed indolization, widens the spectrum of indoles that can be prepared by these means. The simple procedure, mild reaction conditions, and ready availability of the starting materials render these methods valuable additions to indole chemistry. We next extended this method to the synthesis of the indole core of a PGD2 receptor antagonist, laropiprant 3. 

Later, a nickel-catalyzed cascade conversion of propargyl halides and propargyl alcohol into a pyrone in water was reported. The reaction involved a carbonylation by CO and a cyanation by KCN (Eq. 4.55).96 Recently, Gabriele et al. explored a facile synthesis of maleic acids by palladium catalyzed-oxidative carbonylation of terminal alkynes in aqueous DME (1,2-dimethoxyethane) (Eq. 4.56).97... 

The study on 2,7-di-rerf-butylthiepin has recently been extended to explore more simply substituted thiepins 58). The palladium-catalyzed reaction of the diazo compound 107 lacking a 4-methyl substituent gives exclusively the exo-methylene compound 108 whereas the acid-catalyzed reaction of the same precursor 107 resulted in the formation of 2,7-di-/er/-butyl-4-ethoxycarbonylthiepin (109)58). Due to the substantial thermal stability of 109 it is possible to transform the ethoxy-carbonyl group into the hydroxymethyl (110), trimethylsilyloxymethyl (111) and formyl group (112)58). 

Extension to carbocyclization of butadiene telomerization using nitromethane as a trapping reagent is reported (Eq. 5.48).72 Palladium-catalyzed carbo-annulation of 1,3-dienes by aryl halides is also reported (Eq. 5.49).73 The nitro group is removed by radical denitration (see Section 7.2), or the nitroalkyl group is transformed into the carbonyl group via the Nef reaction (see Section 6.1). 

Another compound 9 with three heterocyclic rings linearly fused (5 5 5) with two heteroatoms has been prepared from 1,1 -carbonyl diindole 297 <2001T5199>. Palladium-mediated coupling of the 2- and 2 -positions of 297 afforded the 1,1 -carbonyl-2,2 -biindolyl 9. 1,1 -Carbonyl diindole 297 was in turn obtained in 41% yield from 1,1 -carbonyldiimidazole 296 by reaction with indole in DMSO at 125 °C. The palladium-catalyzed coupling step afforded the desired product 9 in low yield and required a stoichiometric amount of palladium acetate. Therefore, it was felt prohibitively expensive. Addition of various co-oxidants (Ac20, Mn02, and Cu(OAc)2, etc) to make the reaction catalytic in palladium did not result in any improvement of the yield of 18 (Scheme 53). 

Palladium-catalyzed (PdCl2(PPh3)2) decarboxylative carbonylation reactions for the formation of lactams are known to proceed under carbon monoxide at a pressure of 60 atmospheres. The scheme below highlights a new procedure utilizing a different Pd catalyst, where the formation of lactams 171 from oxazolidinones 172 takes place at atmospheric pressure <06S227>. 

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