Carbonyl direct arylation, palladium-catalyze

Since Wakamatsu serendipitously discovered amidocarbonylation while performing the cobalt-catalyzed hydroformyla-tion of olefins in 1971, this unique carbonylation reaction, affording a-amino acids directly from aldehydes, has been extensively studied.More recently, palladium-catalyzed processes have been developed to expand the scope of this reaction.The Pd-catalyzed amidocarbonylation has been applied to aldehydes,aryl halides, and imines. As a related reaction, lactamization " of aryl halides catalyzed by a rhodium complex has also been developed. 

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. 

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]. 

Biaryl structures are found in a wide range of important compounds, including natural products and organic functional materials [8,80,81]. One of the most common and useful methods for preparing biaryls is the palladium-catalyzed coupling of aryl halides with arylmetals (Scheme 1, mechanism A). On the other hand, aryl halides have been known to couple directly with aromatic compounds as formal nucleophiles under palladium catalysis. While the intramolecular cases are particularly effective, certain functionalized aromatic compounds such as phenols and aromatic carbonyl compounds, as well as... 

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. 

Cunico and Maity published another example of palladium-catalyzed CO-free carbonylation of aryl halides [121]. Depending on the substrate, 2 mol% of either Pd(PPh3)4 or Pd(P Bu3)2 was used to catalyze the reaction of heteroaryl and aryl bromides with A,A -dimethyl-carbamoyl(trimethyl)silane (Scheme 2.10). Tertiary amides were prepared in good yields by direct carbamoylation under their conditions. Remarkably, chlorobenzene, 1-chloro -methoxybenzene, and iodoben-zene gave the desired products in 74, 78, and 60 % yields, respectively. 

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. 

Also exploiting an intramolecular C—S bond formation, Bryan et al. extended their investigation of gem-dihalovinylarene substrates in the synthesis of heterocycles to encompass a thiol analogue (Scheme 34.38, disconnection D-2). The combination of an unusual palladium-catalyzed S-alkenylation with a second cross-coupling process, such as a Suzuki, Heck, or Sonogashira reaction led to diversely functionalized benzothiophenes such as 67, produced in excellent yield (Scheme 24.40) [132], Routes incorporating a tandem carbonylation step [133] and a direct arylation [117] process have subsequently been reported. 

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