Transition-Metal-Catalyzed Arylation of 1-Deazapurines via C–H Bond Activation (original) (raw)
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C–H Imidation of 7-Deazapurines
ACS Omega, 2018
We developed and presented here a ferrocenecatalyzed C−H imidation of 7-deazapurines (pyrrolo[2,3-d]pyrimidines) with N-imidyl peroxyesters. The reactions occur regioselectively at position 8 in 7-deazapurines, leading to a series of 8-succinimido-, phtalimido-, or naphthalimido-7-deazapurine derivatives. Attempted hydrazinolysis of resulting 8-imidyl-7deazapurines led to corresponding 8-amino-7-deazapurine, which was very unstable and quickly decomposed.
Tetrahedron, 2008
Highly selective, practical, and efficient protocols for the preparation of 4(5)-aryl-1H-imidazoles 2, 2,4(5)-diaryl-1H-imidazoles 3, and 4,5diaryl-1H-imidazoles 1 are described. A key step of these protocols is the regioselective synthesis of 5-aryl-1-benzyl-1H-imidazoles 9 by Pd-catalyzed direct C-5 arylation of commercially available 1-benzyl-1H-imidazole (8) with aryl halides. The three-step synthesis of compounds 3 from 8 also involves the Pd-catalyzed and Cu-mediated direct C-2 arylation of imidazoles 9 with aryl halides under base-free and ligandless conditions. On the other hand, the four-step synthesis of imidazoles 1 from 8 also involves the regioselective bromination of compounds 9 and a Suzuki reaction of the resulting 5-aryl-1-benzyl-4-bromo-1H-imidazoles 11 with arylboronic acids 5 under phase-transfer conditions, followed by N-debenzylation.
The Journal of Organic Chemistry, 2010
A new method for the synthesis of dihydroimidazo[1,2-a][1,3,5]triazin-4(6H)-ones via copper(I)catalyzed hydroamination was developed. In addition, for the first time iodoalkynes were shown to participate in the copper(I)-catalyzed intramolecular hydroamination reaction with exclusive formation of E-isomers. The unique role that purine and pyrimidine heterocycles play in biology makes them timeless subjects of research in disciplines encompassing the fields of organic synthesis, medicinal chemistry, biotechnology, and materials science.1 Small molecules containing imidazo[1,2-a]-s-triazine fragment, which is an analog of 5-aza-7-deaza-purine, have been identified as promising candidates in the treatment of Type 1 diabetes, rhinovirus infections, and against the Flaviviridae family of viruses.2 Whether the goal is the discovery of compounds with new biological function or expansion of the genetic alphabet, a methodology that allows simple and reliable access to novel purine analogs would be a valuable addition to these fields. Herein, we report a new approach toward dihydroimidazo[1,2-a][1,3,5]triazinone derivatives via a copper-catalyzed hydroamination, delivering a practical, scalable and versatile route to these rarely studied heterocycles. The construction of imidazo[1,2-a]-s-triazine (1) core can commence from 2aminoimidazole (2),1c ; 2a,b 5-azacytosine (3, X=NH 2)2c,d or 1,3,5-triazine heterocycles (3, X=Cl) (Scheme 1).3a,b ; 2e,f However, these methodologies have not proven to be practical due to the low conversions and limited substrate scope. We envisioned assembling the imidazo[1,2-a]-s-triazine ring system via transition metal-catalyzed hydroamination of alkynyl triazinones 4 , 4 which are easily derived from cyanuric chloride (5).
Substrate-Directed C-H Functionalization of 2-Aryl Pyridines by Transition Metal Complexes
ChemistrySelect, 2018
Transition metal mediated CÀH activation is a powerful synthetic tool for the total synthesis of complex natural products and biologically active molecules. The strategy involves mainly CÀH activation, nucleophilic addition and regeneration of the catalyst. It proceeds through a CÀH bond cleavage by ligand coordination to transition metal. Transition metals like Pd, Rh, Ru, Co, and Ir are the most often used catalysts, which form a complex with 2-aryl pyridine and facilitates the functionalization of various CÀH bonds to generate diverse CÀC and CÀX bonds under typically mild reaction conditions with low catalyst loading. In particular, the chelation-assisted cleavage of CÀH bonds at ortho-position of the pyridine directing group has been recognized as one of the most powerful strategies for the functionalization of unreactive CÀH bonds. Recently, transition metal catalyzed CÀH bond activation has received significant interest because it does not require the prefunctionalization of the substrate. Therefore, the metal-catalyzed CÀH activation and functionalization is currently considered as atom economy and simplified procedure in comparison with the traditional strategies. Recent years have witnessed remarkable progress in the development of more atom-and step-economical direct arylations of 2-aryl pyridines. In 2008, Nakamura et al reported a new class of homogeneous iron-catalyzed arylation of 2-aryl pyridines by a C À H bond activation (Scheme 1). [16] The overall synthetic transformation represents a nucleophilic displacement of ortho CÀH bond of 2-aryl pyridine (3) by an arylzinc bromide (4) to give the arylated product (5) in good yield. The reaction took place at 0 8C since C À H bond activation often requires high temperature above 80 8C. The direct crosscoupling reaction of 2-aryl pyridines with Grignard reagent through Co catalyst also well established. [17] Authors observed that the combination of iron, zinc, magnesium, 1,10-phenan-[a] Dr.
Journal of the American Chemical Society, 2011
We report a new catalytic protocol for highly selective C-H arylation of pyridines containing common and synthetically versatile electron-withdrawing substituents (NO 2 , CN, F and Cl). The new protocol expands the scope of catalytic azine functionalization as the excellent regioselectivity at the 3-and 4-positions well complements the existing methods for C-H arylation, Ir-catalyzed borylation, as well as classical functionalization of pyridines. Another important feature of the new method is its flexibility to adapt to challenging substrates by a simple modification of the carboxylic acid ligand or the use of silver salts. The regioselectivity can be rationalized on the basis of the key electronic effects (repulsion between the nitrogen lone pair and polarized C-Pd bond at C2-/C6-positions and acidity of the C-H bond) in combination with steric effects (sensitivity to bulky substitutents).
Molecules (Basel, Switzerland), 2016
1-alkyl aryl-5-amino-4-(cyanoformimidoyl)imidazoles 4 were reacted with malononitrile and 2-amino-1,1,3-propenetricarbonitrile under mild experimental conditions, which led to 5-amino-3-(substituted benzyl)-6,7-dicyano-3H-imidazo[4,5-b]pyridines 5 and 6,8-diamino-3-(4-substituted benzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7,9-dicarbonitrile 6, respectively, when the reaction was carried out in the absence of a base, or to 5,7-diamino-3-(4-alkyl aryl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile 8, and 6,8,9-triamino-3-(4-substitutedbenzyl)-3H-imidazo[4,5-b]-1,8-naphthyridine-7-carbonitrile 10 in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU). Both reactions evolved from an adduct formed by nucleophilic attack of the malononitrile anion or 2-amino-1,1,3-propenetricarbonitrile anion to the carbon of the cyanoformimidoyl substituent. In the case of the malononitrile anion, a 5-amino-1-alkyl aryl-4-(1-amino-2,2-dicyanovinyl)imidazole 7 was isolated when this reaction was carried ...