Amination reactions aryl electrophiles

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

Accordingly, many reactions can be performed on the sidewalls of the CNTs, such as halogenation, hydrogenation, radical, electrophilic and nucleophilic additions, and so on [25, 37, 39, 42-44]. Exhaustively explored examples are the nitrene cycloaddition, the 1,3-dipolar cycloaddition reaction (with azomethinylides), radical additions using diazonium salts or radical addition of aromatic/phenyl primary amines. The aryl diazonium reduction can be performed by electrochemical means by forming a phenyl radical (by the extrusion of N2) that couples to a double bond [44]. Similarly, electrochemical oxidation of aromatic or aliphatic primary amines yields an amine radical that can be added to the double bond on the carbon surface. The direct covalent attachment of functional moieties to the sidewalls strongly enhances the solubility of the nanotubes in solvents and can also be tailored for different... 

A three-component reaction based on the umpolung of re-allylpalladium (II) complexes indium metal was reported by Grigg and co-workers (Scheme 8.31) [74]. In this reaction, the electrophilic nature of the n-allyl palladium species generated from aryl halides and allenes is reversed by transmetallation with indium metal. The resultant nucleophilic allylindium reagent subsequently adds to the third component - aldehyde [75] or imine [76] - to give the corresponding homo-allylic alcohol 64 or amine 65 respectively. 

The electrophiles in catalytic amination reactions can be either aryl halides or triflates possessing electron-rich, neutral, or electron-poor ring systems, whereas amines can range from aliphatic to aromatic and primary to secondary amines. The Pd-catalyzed C—N bond formation works both inter- and intramolecularly. 

Hii reported an aminophosphine ligand similar to Amphos [118]. This ligand is prepared in four steps, starting from N-methylaniline and bromoacetic acid ethyl ester. An elevated temperature of 110°C was required to achieve aminations of aryl bromides with secondary amines. Surprisingly, the order of reactivity is reported to be reversed to that usually encountered for palladium-catalyzed couplings, and consequently electron-deficient aryl bromides were aminated in lower yields than the corresponding electron-rich electrophiles. The ligand metal ratio was identified as one of the key parameters for the reaction. 

Aryl iodides have not been used extensively in palladium-catalyzed aminations, mainly because they are unattractive from an economical point of view, and do not perform exceptionally well in amination reactions, with dehalogenation often being a significant competing side reaction [98,101,118,152,153], Rather, a recent report indicated that the greater proportion of aminations performed thus far has used aryl bromides and aryl chlorides as electrophiles [3]. 

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,... 

III.3.2 Pd-CATALYZED AMINATION OF ARYL HALIDES AND RELATED REACTIONS 1071 B.X. Additional Aryl Electrophiles... 

The same group also developed the asymmetric synthesis of 3-amino 8-lactams 91 by phosphoric acid-catalyzed cyclization reactions involving azlactones 90 as both nucleophiles and electrophiles (Scheme 2.27) [38]. In addition to aromatic amines, substituted aryl ethylamines 92 participated well in such cyclization reactions to afford products 91a, which can be converted to benzo[a]quinolizidine derivatives 93 after being treated with trifluoroborane in high overall yields with excellent enan-tioselectivity, ranging from 90 to 97% ee [38]. 

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