Amido complexes, amination reactions, aryl halides

The amine-ligated aryl halide complexes react with alkoxide or silylamide bases to form arylamine products (Eq. (48)) [279]. The reaction of Pd[P(o-C6H4Me)3](HNEt2)(p-Bu, )(Br) and LiN(SiMe3)2 occurred immediately at room temperature to form the arylamine in greater than 90 % yield. Low-temperature reactions conducted in the NMR spectrometer probe allowed direct observation of the anionic halo amido complex Pd[P(o-C6H4Me)3](NEt2)(Ar)(Br) [279]. Thus, one experimentally supported mechanism for gen-... 

One of the most versatile and widely employed methods for the construction of aryl C—N bonds is the palladium-catalyzed cross coupling of amines with aryl halides and related electrophiles [4]. These reactions are believed to occur as shown in Scheme 1.1, with the coupling initiated by oxidative addition of the aryl halide to a Pd° complex. The resulting intermediate 1 is converted to a palladium(aryl)(amido) complex 2 through reaction with the amine substrate in the presence of base. Finally,... 

In the original process using tin amides, transmetallation formed the amido intermediate. However, this synthetic method is outdated and the transfer of amides from tin to palladium will not be discussed. In the tin-free processes, reaction of palladium aryl halide complexes with amine and base generates palladium amide intermediates. One pathway for generation of the amido complex from amine and base would be reaction of the metal complex with the small concentration of amide that is present in the reaction mixtures. This pathway seems unlikely considering the two directly observed alternative pathways discussed below and the absence of benzyne and radical nucleophilic aromatic substitution products that would be generated from the reaction of alkali amide with aryl halides. 

An alternative pathway when soluble alkoxide or silylamido bases are used, involves reaction of a palladium amido aryl complex with the alkoxide or silylamide to form an intermediate alkoxide or amide. These complexes can react with amines to form the required amido aryl intermediate. This pathway seems to occur for aryl halide animations catalyzed by complexes with chelating ligands. The inorganic... 

The transition metal catalyzed synthesis of arylamines by the reaction of aryl halides or tri-flates with primary or secondary amines has become a valuable synthetic tool for many applications. This process forms monoalkyl or dialkyl anilines, mixed diarylamines or mixed triarylamines, as well as N-arylimines, carbamates, hydrazones, amides, and tosylamides. The mechanism of the process involves several new organometallic reactions. For example, the C-N bond is formed by reductive elimination of amine, and the metal amido complexes that undergo reductive elimination are formed in the catalytic cycle in some cases by N-H activation. Side products are formed by / -hydrogen elimination from amides, examples of which have recently been observed directly. An overview that covers the development of synthetic methods to form arylamines by this palladium-catalyzed chemistry is presented. In addition to the synthetic information, a description of the pertinent mechanistic data on the overall catalytic cycle, on each elementary reaction that comprises the catalytic cycle, and on competing side reactions is presented. The review covers manuscripts that appeared in press before June 1, 2001. This chapter is based on a review covering the literature up to September 1, 1999. However, roughly one-hundred papers on this topic have appeared since that time, requiring an updated review. 

Phosphines that are tightly chelated to the metal center often achieve high selectivity of secondary over tertiary amine products in reactions of primary alkylamines with unhindered aryl halides. The chelation helps prevent competing /3-hydrogen elimination of the aryl palladium amido intermediate (vide infra). Additionally, the greater steric hindrance of bisphosphine palladium complexes, when compared to mono phosphine palladium complexes, prevents diarylation. Some ligands originally introduced by... 

The arylamines are generally formed in good yields (Table 1). Dehalogenation products are the only by-products observed, which pro-baly arise from base-induced )9-hydride elimination of the amido arylpalladium complex and subsequent reduction. Interestingly, the base employed has a decisive influence on the course of the reaction. In the amination of l-bromo-4-n-butylbenzene with free amines in the presence of silyl amides as base -in contrast to the coupling with tin amides -the rate-determining step in the catalytic cycle is the oxidative addition of bis(tri-o-tolylphosphine)palladium(O) to the aryl halide. However, when LiOrBu is used as base, the formation and reductive elimination of the amido arylpalladium complex is decisive for the rate of the reaction. In the presence of NaOtBu both reaction steps seem to take place at similar rates. [9]... 

Some fundamental inorganic chenustry that is important for understanding which complexes will undergo the aromatic C—and C—O bond-forming processes will be presented before the catalytic transformations. First, the three reaction types involved in the catalytic cycle to form arylanunes are similar to those found in the catalytic cycle for C—C bond formation oxidative addition of aryl halide to Pd(0) complexes, transmetallation that converts an arylpalladium halide complex to an arylpaUadium amido complex, and reductive elimination to form a C—or C—O bond. The oxidative addition step is identical to the addition that initiates C—C bond-fomting cross-couplings,f f but the steps that form the arylpalladium amido complexes and that produce the arylamine product are different. The mechanism for these steps is discussed after presentation of the scope of the amination process. 

Pd(II) complexes formed by oxidative addition of organic electrophiles to Pd(0) may react with amines, alcohols, or thiols in the presence of a base to give the corresponding key amido, aUcoxide, or sulfide complexes. These complexes undergo reductive ehmination to afford the new C-X (X = O, N, S) bond in the final organic product [104, 387] and the paUadium(O) species is regenerated. The palladium-catalyzed cyanation of aryl halides [388] is probably mechanistically related to these reactions. 

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