Arylamines palladium complexes

Cross-coupling reaction of aryl halides with arylamines is a straightforward method for forming a carbon-nitrogen bond and is catalyzed by a palladium complex. This methodology was applied by Kanbara, Mullen, and several groups to... 

All of these processes are of limited synthetic utility because of the requirement of the use of stoi chiometric amounts of palladium complexes. However, by judicious choice of reactants and condition the above-mentioned impediments to catalysis can be overcome. For example, an efficient palladium(II) catalyzed cyclization of o-allyl- and o-vinyl-anilines to indoles has been developed (equation 14).28 Be cause arylamines are -106 less basic than aliphatic amines, and because the cyclized product in thi system gave an enamine (indole) stabilized by aromatization, the problems of catalyst poisoning by sub strate or product were circumvented, and catalysis was successfully achieved. The system was quit tolerant of a variety of functional groups and was used to prepare indoloquinones in excellent yieli... 

The transition metal-catalyzed carbonylation reaction is an important pathway to introduce an extra carbon atom in the heterocyclic ring. Lu and Alper used this reaction with recyclable palladium-complexed dendrimers on silica to synthesize 1,4-oxazepines. Remarkably, starting from iodinated arylamine 121, as a substrate for the intramolecular carbonylation, quantitative conversion to the pentacyclic heterocycle 122, containing two oxazepine rings, was achieved (Equation 11) <2005JA14776>. 

The amination of aryl halides and triflates catalyzed by palladium complexes is suitable for use in complex synthetic problems. Many substrates will produce high yields of mixed arylamines with one of the existing catalyst systems. Nevertheless, there are many combinations of substrates for which the amination chemistry may be substantially improved. For the most part, these reactions involve nitrogen centers, such as those in pyrroles, indoles, amides, imidazoles and other heterocyclic groups that are less basic than those in standard alkylamines. Although mild reaction conditions have been developed for many substrates, the harsh conditions used in many of the applications indicate that continued studies on developing mild condi-... 

In addition to the most important 1,2-difunctionalization assisted or catalyzed by palladium(II) complexes, a catalytic 1,1-arylamination process of alkenes, applied to the construction of nitrogen heterocycles from 4-pentenylamides, was realized29,30. The mechanism involves the formation of arylpalladium chloride from alkyl(aryl)stannanes, the addition to the alkene, the isomerization of the adduct to the more stable benzylic palladium complex, and the displacement of palladium by an internal nitrogen nucleophile. In the presence of a substituent, mixtures of diastereomers were generally obtained. 

Kosugi and co-workers reported that palladium complexes with P(o-tolyl)3 as ligand would catalyze the formation of arylamines from aryl halides and aminostannanes (Eq. A subsequent fuU paper demonstrated the scope and limitations of this... 

Hegedus developed an olefin amination process that generates indoles by intramolecular nucleophilic attack of substituted amines on allylarenes (Equation 11.27). In this process, an N-tosyl arylamine attacks the coordinated olefin of an allyl group in the ortho position of the aniline, and p-hydrogen elimination generates a tautomer of indole and a reduced palladium complex. This reduced complex is then re-oxidized by quinone to regenerate the starting palladium(II), and the product tautomerizes to the final indole product. This cycle was one of the earliest catalytic olefin aminations. 

Intramolecular oxidative aminations of olefins have alsobeen studied, and many of these intramolecular processes were observed prior to the analogous intermolecular variants. The oxidative aminations of alkenes with arylamines and arylamine derivatives catalyzed by palladium complexes were shown by Hegedus to form indoles (Equation 16.120). These reactions were conducted with orf/io-allylaniline and ort/zo-allylaniline derivatives as substrate, Pd(NCMe)jCl2 as catalyst, and benzoquinone as oxidant. Intramolecular reactions of N-tosylated aliphatic amines were reported by Larock. ° For example, the tosylamide in Equation 16.121 imdergoes cyclization in high yield in the presence of dioxygen with Pd(OAc)j as catalyst in DMSO. A related reaction (Equation 16.122) was reported recently in toluene solvent with added pyridine. ... 

To access useful arylamines derivatives, the palladium catalyst is usually prepared as a cationic aqua or diaqua palladium(ll) complex or other organopalladium complex. In the Scheme 6.23, a putative catalytic cycle for the Pd-catalyzed asymmetric addition reaction is shown. The hydroxyl-Pd species (A) is formed in the presence of a base or MS that undergo transmettJlation with an organometallic reagent such as ArM to produce the corresponding aryl palladium complex (B). Insertion of an imine substrate into the Ar-Pd bond, followed by hydrolysis, affords the desired product [29b]. 

The arylamine 780b required for the total synthesis of carbazomycin B (261) was obtained by catalytic hydrogenation, using 10% palladium on activated carbon, of the nitroaryl derivative 784 which was obtained in six steps and 33% overall yield starting from 2,3-dimethylphenol 781 (see Scheme 5.85). Electrophilic substitution of the arylamine 780b with the iron-complex salt 602 provided the iron complex 787 in quantitative yield. The direct, one-pot transformation of the iron complex 787 to carbazomycin B 261 by an iron-mediated arylamine cyclization was unsuccessful, probably because the unprotected hydroxyarylamine moiety is too sensitive towards the oxidizing reaction conditions. However, the corresponding 0-acetyl derivative... 

An extensive series of neutral macrocyclic complexes, mainly of nickel(II), copper(II), platinum(II) and palladium(II), has been developed by Dziomko and coworkers. The cyclization step in the template reaction is a nucleophilic aromatic substitution of an arylamine on to a haloaryl azo compound. A variety of aryl and heteroaryl rings can be incorporated in different combinations. For instance, a diaminoazo compound can be combined with a dihaloazo compound (Scheme 58).246 247 Another synthetic strategy involves the dimerization of an aminohaloazo compound and leads to more symmetrical macrocyclic complexes (Scheme 59).248 249 Most recently, dihalodiazo compounds have been synthesized from dihydrazines and pyrazolinediones and undergo template reactions with simple 1,2-diamines (Scheme 60).249 250... 

Scheme 7. Reductive elimination of arylamines from DPPF-ligated palladium amido complexes.

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. 

---