A. S. Abel

Palladium-Catalyzed Amination of Dichloroquinolines with Adamantane-Containing Amines

Pd-catalyzed amination of isomeric 2,6-, 2,8-, 4,8- and 4,7-dichloroquinolines was studied using adamantane-containing amines in which substituents at the nitrogen atom differ in bulkiness. The selectivity of the amination of 2,6-dichloroquinoline was very low, substantially better results were obtained with 2,8-dichloroquinoline, and 4,8- and 4,7-dichloroquinolines provided the best yields of the amination products. Diamination of 4,8- and 4,7-dichloroquinolines was carried out with two amines which differ strongly in the bulkiness of the alkyl group. In the majority of cases BINAP ligand was successfully applied, however, it had to be replaced with DavePhos in certain reactions when using the most sterically hindered amine as well as for the diamination reactions.

Arylation of adamantanamines: VII. Copper(I)-catalyzed N-heteroarylation of adamantane-containing amines with halopyridines

Copper(I)-catalyzed N-heteroarylation of a wide series of adamantane-containing amines with 2-bromo- and 2- and 3-iodopyridines was studied. The corresponding N-pyridyl derivatives were formed in all cases, but iodopyridines were considerably more reactive. The best results were obtained with the catalytic system CuI-2-(2-methyl-1-oxopropyl)cyclohexanone-DMF which ensured up to 90% yield of the target products. The yield of N-pyridyl derivatives also depended on the steric environment of the amino group in the initial adamantane-containing amine. The yield of the heteroarylation products can be considerably increased using excess iodopyridine. The reaction of 2-(adamantan-1-yl)ethanamine with 2,6-dibromopyridine successfully afforded the corresponding diamine, and N,N′-dipyridyl derivatives were obtained in high yields from 2,2′-(adamantane-1,3-diyl)diethanamine.

Arylation of adamantanamines: V. Palladium-catalyzed amination of isomeric chloroquinolines with diamines of the adamantane series

Palladium-catalyzed arylation of diamines of the adamantane series with isomeric 2-, 4-, and 6-chloroquinoline was studied, and optimal conditions for the synthesis of the corresponding N,N′-diaryl derivatives were found. N,N-Diarylation products of primary amino groups in the diamines bearing 2-aminoethyl and 4-aminophenyl substituents were readily formed.

Arylation of adamantanamines: IV. Palladium-catalyzed arylation of amines of adamantane series with isomeric chloroquinolines

Palladium-catalyzed arylation of diverse amines of the adamantane series with isomeric chloroquinolines was investigated. The 2-chloroquinoline is the most reactive, however the best yields of the N-arylation products are most frequently obtained in the reaction with the less reactive 6-chloroquinoline. The applicability of the reaction is limited by the size of the substituent at the amino group. In some instances the noncatalytic amination of chloroquinolines was possible.

Oxaazamacrocycles incorporating the quinoline moiety: synthesis and the study of their binding properties towards metal cations

Novel dioxa- and trioxadiazamacrocycles have been synthesized by the Pd(0)-catalyzed amination of 4,6- and 4,7-dichloroquinolines with linear di- and trioxadiamines. Macrocyclization reaction was shown to be more successful for 4,6-dichloroquinoline, providing the corresponding macrocycles with yields of up to 32%. 4,6-Di(2-methoxyethylamino)quinoline was obtained in 88% yield for comparative studies. The synthesis of macrocycles comprising two 4,7-disubstituted quinoline moieties and two oxadiamine linkers has been accomplished. The binding properties of 4,6-diamino derivatives of quinoline have been studied with 17 metal cations using UV-vis and fluorescence spectroscopy. UV, fluorescence, and NMR spectral data demonstrated the formation of complexes of different compositions depending on the nature of the ligand and the metal cation. One of the macrocycles (5c) was shown to be applicable as a selective fluorescent and colorimetric chemosensor for Cu(II). Macrocyclic ligands 5 clearly showed a different behavior in the presence of metal cations compared to the non-cyclic derivative 10.

Arylation of adamantanamines: VI. Palladium-catalyzed arylation of amines and diamines of the adamantane series with 3-bromopyridine

Palladium-catalyzed amination of 3-bromopyridine with amines of the adamantane series in the presence of Pd(dba)2/L [L = 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl or 2-dimethylamino-2′-dicyclohexylphosphinobiphenyl] gave the desired N-(pyridin-3-yl)-substituted amines in 74–97% yields. Diamines of the adamantane series reacted with 2 equiv of 3-bromopyridine in a complicated fashion to produce mono- and triaryl-substituted derivatives as by-products, while the yields of N,N′-diarylation products were 18–56%.

Arylation of adamantanamines: VIII. Optimization of the catalytic system for copper-catalyzed arylation of adamantane-containing amines

Arylation of adamantane-containing amines with iodobenzene in the presence of copper(I) and copper(II) compounds and various N,N-, N,O- and O,O-bidentate ligands was studied. The best results were obtained using the catalytic system CuI–rac-BINOL [1,1′-bi(naphthalen-2-ol)] (10/20 mol %). Reactions with iodobenzene derivatives containing electron-donor and electron-withdrawing substituents in the para position to the iodine atom were carried out under the optimal conditions.

CuI-catalyzed hetarylation of natural di- and polyamines with halopyridines

Copper(i)-catalyzed hetarylation of natural diamines (putrescine, cadaverine, and hexane-1,6-diamine), their analogs (propane-1,3-diamine and decane-1,10-diamine), as well as natural tri- (spermidine) and tetraamines (spermine) with 2-bromo, 2-iodo-, and 3-iodopyridines was studied. The CuI—2-isobutyrylcyclohexanone (10—20 mol.%) catalytic system provides the best results in the synthesis of target N,N´-dipyridinyl diamine derivatives. In some cases, an increase in the catalyst loading leads to an increase in the yields of the dihetarylated compounds. In the case of tri- and tetraamines, this catalytic system favors the predominant hetarylation of the primary amino groups with 2-bromopyridine and 3-iodopyridine.

Catalyst-free amination of 2-fluoropyridine and 2-fluoro-5-halopyridines with adamantane amines

Catalyst-free reactions of 2-fluoropyridine with amines and diamines bearing the adamantyl moiety at either the N atom or in the side chain were studied. Amines, which do not contain secondary alkyl substituents at the amino group, react with an excess of 2-fluoropyridine to give N-(pyridin-2-yl) derivatives in the yields from moderate to good. 2-Fluoro-5-halopyridines were found to be more reactive than 2-fluoropyridine.

Arylation of adamantanamines: IX. Copper(I)-catalyzed arylation of adamantane-containing amines

Copper(I)-catalyzed arylation of 14 adamantane-containing amines with iodobenzene, 1-fluoro-4-iodobenzene, 1-iodo-4-(trifluoromethyl)benzene, and 1-iodo-4-methoxybenzene has been studied under the conditions optimized previously. The yields of the N-arylation products have been shown to depend in a complicated manner on the amine structure, steric environment of the amino group, and substituent nature in iodobenzene.