Substituted aryl/heteroaryl amines

Ai-aryl benzamide (1 0.20 mmol), [RuCl2(pcymene)]2 (0.02 mmol), 0-benzoyl hydroxylamine (2 0.60 mmol), and K2CO3 (0.40 mmol) dissolved in acetone (1 mL) was stirred in a 25 mL Schlenk tube at room temperature under argon atmosphere for 36 h. Upon completion, the reaction mixture was diluted with ethyl acetate and filtered through a small pad of Celite. The filtrate was concentrated in vacuo and purified by a silica gel packed flash chromatography column, using ethyl acetate/hexane as the eluent to furnish pure substituted aryl/heteroaryl amine 3. All the products were characterized by spectral methods. 

Keywords Substituted aryl/heteroaiyl benzamides, cyclic N-benzoyloxyamines, [Ru Cl2(p-cymeme)]2 complex as catalyst, potassium carbonate, argon atmosphere, acetone, room temperature, ortho-C-H amination, substimted aryl/heteroaryl amines... 

Aryl- and heteroaryl halides can undergo thermal or transition metal catalyzed substitution reactions with amines. These reactions proceed on insoluble supports under conditions similar to those used in solution. Not only halides, but also thiolates [76], nitro groups [76], sulfinates [77,78], and alcoholates [79] can serve as leaving groups for aromatic nucleophilic substitution. 

Terminal alkynes can be coupled directly to aryl, heteroaryl, and vinyl halides or triflates in the presence of a Pd-catalyst and a base, which frequently is an amine acting both as solvent and as scavanger for the respective acid formed in the reaction. The mechanism appears to involve oxidative addition of the sp2-halide or triflate to Pd(0), followed by alkynylation of the intermediate organopalladium complex and reductive elimination of the substituted alkyne. Copper(I) iodide is a particular effective cocatalyst, allowing the reaction to proceed at room temperature (91MI2). 

Albanese. D. Landini. D. Maia. A. Penso. M. Phase transfer eatalysis Some recent applications in organic synthesis. J. Mol. Catal. A Chem. 1999,150 (1-2). 113- 131. Landini. D. Maia. A. Secci. D. Vlasov. V.M. Os kina. I. Nucleophilic aromatic substitution reactions promoted by aryl and heteroaryl amine nitranions. New J. Chem. 1998. 22 (1), 71-74. 

This system was later used for a systematic study of homocoupling of variously substituted aryl and heteroaryl bromides. The authors conducted a number of experiments to find the best conditions for homocoupling of various aryl halides. The influence of the base (K2CO3, amines) and the reductant (isopropanol) was studied. It was demonstrated... 

A/ -Tosylindole 87 was prepared by the metal-free C—H amination of Af-tosylaniline 86 and DDQ.The reaction is believed to proceed through a radical cation generated from a SET process and a phenonium ion intermediate. Most of the substituted indoles were isolated in very good yields and a variety of aryl, heteroaryl, halogen, and trifluoromethyl substituents were tolerated (14OL3720). 

In addition, complexes of P(/-Bu)3 have been shown to catalyze the formation of diaryl heteroarylamines from bromothiophenes.224 Aminations of five-membered heterocyclic halides such as furans and thiophenes are limited because their electron-rich character makes oxidative addition of the heteroaryl halide and reductive elimination of amine slower than it is for simple aryl halides. Reactions of diarylamines with 3-bromothiophenes occurred in higher yields than did reactions of 2-bromothiophene, but reactions of substituted bromothiophenes occurred in more variable yields. The yields for reactions of these substrates in the presence of catalysts bearing P(/-Bu)3 as ligand were much higher than those in the presence of catalysts ligated by arylphosphines. 

Aminations of five-membered heterocyclic halides, such as furans and thiophenes, are limited. These substrates are particularly electron-rich. As a result, oxidative addition of the heteroaryl halide and reductive elimination of the amine are slower than for simple aryl halides (see Sections 4.7.1 and 4.7.3). In addition, the amine products can be air-sensitive and require special conditions for their isolation. Nevertheless, Watanabe has reported examples of successful couplings between diarylamines and bromothiophenes [126]. Triaryl-amines are important for materials applications because of their redox properties, and these particular triarylamines should be especially susceptible to electrochemical oxidation. Chart 1 shows the products formed from the amination of bromothiophenes and the associated yields. As can be seen, 3-bromothiophene reacted in higher yields than 2-bromothiophene, but the yields were more variable with substituted bromothiophenes. In some cases, acceptable yields for double additions to dibromothiophenes were achieved. These reactions all employed a third-generation catalyst (vide infra), containing a combination of Pd(OAc)2 and P(tBu)3. The yields for reactions of these substrates were much higher in the presence of this catalyst than they were in the presence of arylphosphine ligands. 

Transition-metal-catalysed reactions can be used to introduce aryl or heteroaryl groups onto the ring NH, or attached amino groups, of heterocycles. They can also be used for the displacement of leaving groups by amines in all types of heterocyclic systems, including the use of milder conditions for substitutions at relatively activated positions, such as a- and y-positions in pyridines, where nucleophilic substitutions can be carried out. 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

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