Synthesis of 5-arylhistidines via a Suzuki-Miyaura cross-coupling

Microwave irradiation efficiently promoted the Suzuki-Miyaura reaction of a 5-bromohistidine with various arylboronic acids in the presence of a palladium catalyst. This methodology allowed the synthesis of histidines substituted at position 5 of the imidazole ring with a phenyl, a substituted phenyl, a pyridyl or a thienyl ring. The corresponding 5-arylhistidines were obtained in moderate to good yields.     

Synthesis of biphenylamines via Suzuki-Miyaura cross-coupling reactions

A small library of meta- and para-biphenylamines substituted by various alkyl, alkoxy, phenoxy, or halogeno groups on their aromatic rings was synthesized via Suzuki-Miyaura cross-coupling between bromoanilines and arylboronic acids using palladium catalysts. The experimental conditions were carefully adjusted to accommodate a wide range of substituents, in terms of electron-withdrawing or -donating ability and steric bulk. In some cases, protection and deprotection of the amine function via its trifluoroacetamide were added to the reaction sequence in order to facilitate the cross-coupling step.     

Synthesis of S-acetyl oligoarylenedithiols via Suzuki-Miyaura cross-coupling

Oligoarylenes with three or four aromatic rings, bearing two S-acetylated mercaptomethyl groups in 1,3 position on one end of the polyaromatic system and presenting various functionalities on the other terminal ring, have been synthesized by the Suzuki-Miyaura cross-coupling reaction. The use of palladium complexes with a Buchwald's phosphine as ligand allowed us to perform this coupling reaction also in the presence of benzylic S-acetyl-protected functionalities on the aromatic halide. The obtained oligoarylenes are potential novel candidates for the generation of self-assembling monolayers on metal substrates.     

2-Arylhydroxytyrosol derivatives via Suzuki-Miyaura cross-coupling

2-Arylhydroxytyrosol derivatives, a new class of hydroxytyrosol derivatives, have been prepared in high to excellent yields from the corresponding 2-chloro precursors via Suzuki-Miyaura cross-coupling with arylboronic acids containing electron-donating, electron-withdrawing, as well as ortho substituents. A remarkable halide effect has been observed. 2-Iodo- and 2-bromohydroxytyrosol derivatives have been found to be ineffective cross-coupling partners in many cases. The acetonide and carbonate protecting groups can be readily removed.     

Synthesis of novel substituted 3,8,11-triazaspiro[5,6]dodecan-7-ones

A synthesis of novel substituted 3,8,11-triazaspiro[5,6]dodecan-7-ones using a combination of solution-phase and solid-phase chemistries is described. A solution-phase approach was used to produce a key piperidine intermediate that was then incorporated into a solid-phase synthesis. The combined synthetic strategy was applied to provide a series of substituted 3,8,11-triazaspiro[5,6]dodecan-7-ones in good yield and high purity.     

Solid-phase synthesis of 5-arylhistidines via a microwave-assisted Suzuki-Miyaura cross-coupling

Microwave irradiation efficiently promoted the solid-phase Suzuki-Miyaura reaction of a 5-bromohistidine with various arylboronic acids in the presence of a palladium catalyst. This methodology allowed the synthesis of peptides bearing a histidine residue substituted at position 5 of the imidazole ring with a phenyl, a substituted phenyl, a pyridyl, or a thienyl ring, as well as with the benzene ring of a tyrosine residue.     

Synthesis of 2-substituted isothiazolopyridin-3-ones

The synthesis of some 2-substituted derivatives 1–4 of all four isomeric isothiazolopyridin-3-ones is described. Several novel 1,2-dithiolopyridin-3-ones and 3-thiones were prepared as intermediates.     

Scope of aminomethylations via Suzuki-Miyaura cross-coupling of organotrifluoroborates

We previously reported the Suzuki-Miyaura reaction of N,N-dialkylaminomethyltrifluoroborates with aryl bromides. Herein, we report a further investigation of the scope and limitations of this palladium-catalyzed aminomethylation reaction. Aryl chlorides, iodides, and triflates coupled in good to excellent yields to give N,N-dialkylbenzylic amines. The aminomethylation of alkenyl bromides was also examined.     

Synthesis of 1,5-disubstituted tetrazoles via Suzuki-Miyaura cross-coupling of 5-chloro-1-phenyltetrazole

Suzuki-Miyaura coupling reactions of 5-chloro-1-phenyl-tetrazole with various functionalized arylboronic acids were investigated. In the presence of catalytic amounts of SPhos/Pd(OAc)₂ or RuPhos/Pd(OAc)₂, the reaction proceeded smoothly to afford 1,5-diaryltetrazoles in good to excellent yields.     

A general strategy for in situ assembly of light-up fluorophores via bioorthogonal Suzuki-Miyaura cross-coupling

Herein we presented a general strategy for in situ assembly of intramolecular charge-transfer (ICT)-based light-up fluorophores via bioorthogonal Suzuki-Miyaura cross-coupling reaction. By introducing iodo group at the appropriate position, five fluorophores with different scaffolds including naphthalimide, coumarin, naphthalene sulfonate, nitrobenzoxadiazole, and acetonaphthone, were designed as bioorthogonal multicolor fluorogenic probes, which could produce significant fluorescence enhancement and high fluorescence quantum yield after Suzuki-Miyaura reaction with aryl boronic acid or boronate. Manipulating the substituents and π scaffold in the fluorophores allows fine-tuning of their photophysical properties. With this strategy, we succeeded in peptide conjugation, no-wash fluorogenic protein labeling, and mitochondria-selective bioorthogonal imaging in live cells.     

Synthesis and biological activity of 2-aminoimidazole triazoles accessed by Suzuki-Miyaura cross-coupling

A pilot library of 2-aminoimidazole triazoles (2-AITs) was synthesized and assayed against Acinetobacter baumannii and methicillin-resistant Staphylococus aureus (MRSA). Results from these studies show that these new derivatives have improved biofilm dispersal activities as well as antibacterial properties against A. baumannii. With MRSA biofilms they are found to possess biofilm inhibition capabilities at low micromolar concentrations.     

Synthesis of some novel 7-substituted quinolonecarboxylic acids via nitroso and nitrone cycloadditions

1-Ethyl-6-fluoro-7-hydroxylamino-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 7 can be either oxidized to the corresponding nitroso intermediate 8 or converted to the methylene nitrone 9. Both intermediates form cycloaddition products with selected dienes and olefins respectively. Also, the preparation of 1-ethyl-6-fluoro-7-(hexahydro-2-methyl-5H-pyrrolo[3,4-d]isoxazol-5-yl)-3-quinolinecarboxylic acid 5 via a nitrone cycloaddition is presented.     

Synthesis of 1,3,4,5-substituted 1,3-dihydro-2h-imidazol-2-ones

It was shown that 3-(1-methyl-2-oxopropyl)-2-benzoxazolones react with primary amines to form the corresponding 1,3-dihydro-2H-imidazol-2-ones in good yields.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1362–1363, October, 1988.     

Synthesis of 2,4-substituted 5,6-benzoquinolines

By the catalytic condensation of azomethines with aliphatic-aromatic and heterocyclic ketones, derivatives of 5,6-benzoquinoline containing thiophene or pyridine rings as substituents have been synthesized.     

Expedient synthesis of 4-O-methylhonokiol via Suzuki-Miyaura cross-coupling

Concise and practical synthesis of 4-O-methylhonokiol was achieved in 34% overall yield. The key features of our synthesis include chemoselective ortho-mono bromination of phenol as well as biaryl formation via Suzuki-Miyaura cross-coupling, in which bromophenol was reacted with potassium aryltrifluoroborate using Pd(OAc)₂ and RuPhos under microwave conditions.     

Synthesis of novel tricyclic pyrimidine-fused 5,6-dihydrobenzodiazepines via a Pictet-Spengler-like cyclization

Novel pyrimidine-fused 5,6-dihydrobenzodiazepines were prepared via a Pictet-Spengler-like cyclization. It was based on the intramolecular electrophilic substitution of the phenyl ring of 5-amino-6-chloro-4-(N-methylanilino)pyrimidine 1 by the iminium intermediate formed with an aldehyde in one pot. The products may be further transformed by subsequent nucleophilic substitution of the chloro atom. This strategy may provide an efficient method to access a library of compounds based on privileged substructures that are of interest in drug discovery.     

Synthesis and cross-coupling reactions of 7-azaindoles via a new donor-acceptor cyclopropane

[reaction: see text] A new type of donor-acceptor cyclopropane has been prepared from commercially available cyclopropane-1,1-diesters. This cyclopropane reacts with triflic anhydride to produce an isolable tristrifloxy intermediate which when treated with primary amines gives 6-trifloxy-7-azaindolines which in turn can be dehydrogenated to the azaindoles. The 6-trifloxy substituent can be used to introduce diversity at this position via a variety of cross-coupling reactions thus preparing potentially interesting compounds based on the important 7-azaindole pharmacophore.     

Synthesis of chalcones from 2-substituted 1-hydroxyindole-5,6-dicarbonitriles

Methods of synthesis of chalcones from 2-substituted 3-acetyl- and 3-formyl-1-hydroxyindole-5,6-dicarbonitriles under acidic conditions have been developed.