Arylamines palladium-catalyzed

Arylamines display electronic properties that are favorable for materials science. In particular, arylamines are readily oxidized to the aminium form, and this leads to conductivity in polyanilines, hole-transport properties in triarylamines, stable polyradicals with low energy or ground-state, high-spin structures, and the potential to conduct electrochemical sensing. The high yields of the palladium-catalyzed formation of di- and triarylamines has allowed for ready access to these materials as both small molecules and discrete oligomeric or polymeric macromolecules. 

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. 

This review covers palladium-catalyzed amination of aryl halides and sulfonates. The nickel-catalyzed process [82-85] requires much higher catalyst loads and has a narrower substrate scope. Thus, it is not reviewed. Sections 4.2 to 4.5 cover the development of different palladium catalysts for the synthesis of arylamines and related structures. This work has... 

The palladium-catalyzed formation of diarylamines has been used in several contexts to form molecules of biological relevance. The ability to prepare haloarenes selectively by an ortfio-metalation-halogenation sequence allows the selective delivery of an amino group to a substituted aromatic structure. Snieckus has used directed metalation to form aryl halides that were subsequently allowed to react with anilines to form diarylamines (Eq. (34)) [209]. Frost and Mendonqa have reported an iterative strategy to prepare, by the palladium-catalyzed chemistry, amides and sulfonamides that may act as peptidomimetics. Diaryl-amine units were constructed using the DPPF-ligated palladium catalysts, and the products were then acylated or sulfonated with 4-bromobenzoyl or arylsulfonyl chlorides [210]. Le-miere has coupled primary arylamines with 4-chloro-3(2H)-pyridazinones to form compounds with possible analgesic and antiinflammatory properties. 

Palladium-catalyzed amination has also been used to prepare small arylamines that can function as sensors, nonlinear optical materials, magnetic materials, electrode modifiers, hole-transport materials, and dyestuffs. N-Arylpolyamines that have the potential for multiple applications have also been prepared. 

A -Arylaziridines were synthesized in very good yield by palladium-catalyzed N-arylamination reactions utilizing BINAP or xantphos as suitable ligands and either CS2CO3 or NaO/-Bu as a base <07S243>. 

Phosphinoether PPF-OMe (3) is an effective supporting ligand in the palladium-catalyzed coupling of aryl bromides and arylamines [37]. For example, reaction of the hindered aniline below proceeded in 94% yield with as little as 0.5 mol% Pd, Eq. (87). 

Wolfe and Buchwald first reported the palladium-catalyzed arylation of primary amines with aryl iodides in 1996 [67]. The (o-tolljP/Pd-system effected the reaction in moderate yields. Both aliphatic and arylamines were coupled in moderate yield, Eq. (96). 

Louie, J., Hartwig, J. F. Palladium-catalyzed synthesis of arylamines from aryl halides. Mechanistic studies lead to coupling in the absence of tin reagents. Tetrahedron Lett. 1995, 36, 3609-3612. 

The palladium catalyzed asymmetric hydroamination of cyclohexadiene with arylamines utilizing a variant of Trost s ligand R,R) 61 proceeds with high enantio selectivities under mild conditions (Scheme 11.19) [21]. The mechanism is believed to follow a similar pathway as proposed for palladium catalyzed hydroamination of vinyl arenes (Scheme 11.2) [17]. 

One of the most versatile approaches to highly functionalized carbazoles is the sequential palladium-catalyzed C-N/C-C coupling for assembly of the central pyrrole moiety. Many total syntheses of naturally occurring carbazole alkaloids are following this route. The initial C-N bond formation by a palladium(0)-cata-lyzed Buchwald-Hartwig amination of aryl halides or triflates 94 with arylamines 31 affords the diarylamines 95 (Scheme 24) [139,140]. Oxidative cyclization of the diarylamines 95 to the carbazoles 32 proceeds via a double C-H bond activation and is achieved in the presence of palladium(ll) compounds. 

The palladium-catalyzed approach to carbazomadurin A (96a) and B (96b) requires the aryl triflate 97 and arylamine 98 as precursors. The former was... 

Palladium-catalyzed aminations of aryl chlorides required reaction times ranging from hours to 1 day however, it can proceed in few minutes to give higher yield of products by MWI. Rapid palladium-catalyzed aminations of azaheteroaryl chlorides 168 with arylamines have been achieved using temperature-controlled MW heating. 

The Buchwald-Hartwig reaction has been widely used in organic chemistry for the palladium-catalyzed cross-coupling of amines with aryl halides. In particular, it has been used in conjunction with benzothiophenes for arylamination of the thiophene. The final diarylamine product below demonstrated anti-fungal activity against dermatophytes, yeasts, and the Aspergillus species. ... 

For the synthetic application of this method to Erythrina alkaloids, Anh Tuan and Kim [56] reinvestigated the palladium catalyzed cyclization of the requisite precursor which could be formed from the condensation of ketoester 43 and bromo-arylamine 44. In the reaction, two main products were formed. When the intermediate 45 was treated with Pd(OAc)2 in DBU, an enol intermediate (46) was formed in 30% yield through y-lactam enolate formation followed by cyclization. Some amoimt of the eorresponding ketal compound, the precursor of the enol intermediate, could be obtained if the reaction process was quenched earlier. Treatment of 46 with TsOH in acetone afforded compound 47 in 71% yield. Reduction of the carbonyl compound 47 under Luche condition, affording a mixture of diasteromers in a 2.6 1 ratio, was followed by elimination to afford the known intermediate (48) for erysotramidine (49) in 64% yield. 

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. ... 

Scheme 13.3 Competition experiment of dialkyl- and arylamines in the palladium-catalyzed...

Y. Liang, T. Meng, H.-J. Zhang, Z. Xi, Synlett 2011,911-914. Palladium-catalyzed, one-pot, three-component approach to a-aUcynyl indoles from c -bromo-(2,2-dibromovinyl)benzenes, terminal alkynes and arylamines. 

Transition Metal-Catalyzed Coupling Reactions Synthesis of Aryl Amines. LHMDS was first used as a base to de-protonate alkylamines in the palladium-catalyzed synthesis of arylamines. This base is mild enough such that the alkyl-amide is generated at the transition metal center. Earlier examples reported that the reaction of an aryl bromide with cyclo-hexylamine and LHMDS in the presence of 5 mol % of (tri-o-tolylphosphine)2PdCl2 in toluene at 100 °C produced the desired arylamine in 89% yield after 2 h (eq 19). ... 

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