Amines aryl halide double carbonylation

For the preparation of a-ketoamides, palladium-catalyzed double carbonylation of aryl halides with carbon monoxide and secondary amines is also a useful reaction Kobayashi, T. Tanaka, M. J. Organomet. Chem. 1982, 233, C64 Ozawa, F. Soyama, H. Yamamoto, T. Yamamoto, A. Tetrahedron Lett. 1982, 23, 3383. 

As with ester formation, carbonylation of aryl halides under amide-forming conditions and high carbon monoxide pressures leads to synthetically useful yields of a-ketoamides via double carbonylation916- 21. In these reactions the amine must be a fairly strong nucleophile and it is noteworthy that primary amines often give imines as the final product. Aryl chlorides do not normally undergo this reaction but specialized palladium catalysts may facilitate this process890. Alternatively, reaction may be possible via a first-formed... 

Reduction of nitro groupsThe lithium anion of phthalocyaninecobalt(I), Li[Co(I)Pc], selectively reduces aliphatic and aromatic nitro compounds to primary amines at room temperature in 65-95% yield. Double bonds, nitriles, carbonyl groups, and aryl halides are not reduced. 

Before discussing the double carbonylation processes it may be helpful to understand the mechanism of the single carbonylation of aryl halides into carboxylic acid derivatives (Heck processes). The first step in the catalytic process is oxidative addition of an aryl halide to Pd(0) species formed from a catalyst precursor to yield an arylpal-ladium halide intermediate (A) in Scheme 1. Insertion of carbon monoxide into the aryl-palladium bond in A gives an acylpalladium halide complex (B). Attack of a nucleophile such as alcohol, amine, and water assisted by a base on the acylpalladium complex yields carboxylic ester, amide, and carboxylic acid, although details of the mechanism have not been unequivocally established. The palladium(O) species regenerated in the process further undergoes oxidative addition to carry out the catalytic cycle (Scheme 1). 

Detailed mechanistic studies on the elementary processes putatively involved in the catalytic double carbonylation process established that the latter mechanism involving the reductive elimination of the bis-acyl ligands most reasonably accounts for the features of the double carbonylation. Scheme 2 presents the proposed mechanisms for generation of the a-keto amide and amide in the reaction of an aryl halide with CO in the presence of a secondary amine and a catalytic amount of a palladium complex (yide infra). Table 1 summarizes the representative results of the double carbonylation with various aryl halides. 

TABLE 1. Double Carbonylation of Aryl Halides in the Presence of Amine"... 

On the left hand of Scheme 2 is shown the catalytic cycle to produce a-keto amide (Cycle 1), whereas the right-hand catalytic cycle shows the route to amide (Cycle II). The process common to both processes is oxidative addition of aryl halide to give arylpalladium halide. Further CO coordination to the arylpalladium intermediate gives a CO-coordinated complex. If CO insertion into the aryl-palladium bond takes place, an acylpalladium complex is produced to drive the double carbonylation cycle. Further coordination of CO followed by attack of amine on the carbonyl ligand produces the aroyl(carbamoyl)palladium species as the bis-acyl-type intermediate. Reductive elimination of the a-keto amide by combination of the benzoyl ligand with the carbamoyl ligand regenerates the Pd(0) species that carries the catalytic cycle. 

In parallel, Xia and coworkers have made an important contribution to the carbonylation area (Scheme 8.17) [46]. The double carbonylation of aryl iodides vyith amines highlighted [Cu(I)(IPr)j as the best choice for this reaction. Nevertheless, the combination of a NHC salt and [Cu(X)(NHC)j is required to reach high conversion. The influence of the halides clearly depicted a trend (I > Cl > Br). The reaction also occurred in the presence of [Cu(IPr)2] [BF4] alone [47]. When Nal is used as cocatalyst, the transformation is almost quantitative. The bis-NHC-copper complex is believed to be the active species. 

It seems probable that the mechanism of ester aminolysis is similar to that of the reaction between amines and aryl halides, a reaction which also exhibits general base catalysis (see section III.C). The reaction would then involve the formation of a tetrahedral intermediate (2) by addition of amine across the carbonyl double bond in an equilibrium step, which can then decompose via two independent pathways, one catalysed by base (A ) and the other not (/ 3). Whether... 

However, gas substrates such as carbon monoxide (CO) can be easily introduced in a packed-bed reactor. ThanesNano researchers reported aminocarbonylation of aryl halides with amines and CO gas at high pressure and high temperature under flow conditions, which afforded the corresponding amides in moderate-to-high yield (Scheme 7.24) [101]. In this paper, they described that reaction parameters (solvent, base, catalyst, pressure, temperature, and so on) were rapidly optimized in the reactions, which required less than 2 min. As a continuous study, the authors reported a double carbonylation reaction of iodobenzene to give a-ketoamides in a flow reactor [102]. 

Several papers deal with the products of (formally) "double carbonylation" reactions. The carbonylation product of styrene oxide in the presence of a Co2(C0)g/MeI catalyst under phase-transfer conditions contains two CO derived carbons (eqn.17). Two groups report the synthesis of a-keto esters from aryl iodides, CO, alcohols and tertiary amines the selectivity depends on Replacement of alcohol by water leads to a-keto acids. a-Keto-amides are prepared similarly from secondary amines. In this case the mechanism has been studied in detail oxidative addition of the aryl halide is the rate-determining step (Scheme 5). °... 

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