Search

Synthesis of amino acids with isolated saturated (hetero)carbocyclic scaffold was disclosed. The method relied on Suzuki cross-coupling reaction of heteroacycloalkene triflates and N-Boc-tetrahydropyridine boron pinacolates followed by catalytic hydrogenation of the conjugated dienes thus obtained, which proceeded with good diastereoselectivity for scaffolds with two six-membered cycles and low diastereoselectivity for a five-membered analog. Several amino acid derivatives have also been obtained, i.e. amino esters, NH- and N-Boc-substituted amino acids – promising building blocks for medicinal and synthetic chemistry. [ABSTRACT FROM AUTHOR]

A series of seven palladium-containing composites, i.e., four Pd/C and three Pd(OH)2/C (Pearlman's catalysts), was prepared using modified common approaches to deposition of Pd or hydrated PdO on charcoal. All the composites were tested in the catalytic hydrogenation of diene carboxylates with the isolated-ring scaffold, e.g., 5,6-dihydropyridine-1(2H)-carboxylates with 2-(alkoxycarbonyl)cyclopent-1-en-1-yl and hex-1-en-1-yl substituents at the C(4)-position. The performance of the composites was also studied via the hydrogenation of quinoline as a model reaction. The composites were characterized by transmission and scanning electron microscopy (TEM and SEM), powder X-ray diffraction, and low-temperature N2 adsorption. It was found that the composites containing Pd nanoparticles (NPs) of 5–40 nm size were the most efficient catalysts for the hydrogenation of dienes, providing the reduced products with up to 90% yields at p(H2) = 100 atm, T = 30 °C for 24 h. The method of Pd NPs formation had more effect on the catalyst performance than the size of the NPs. The catalytic performance of Pearlman's catalysts (Pd(OH)2/C) in the hydrogenation of dienes was comparable to or lower than the performance of the Pd/C systems, though the Pearlman's catalysts were more efficient in the hydrogenation of quinoline. [ABSTRACT FROM AUTHOR]

A set of 20 composites was prepared by pyrolysis of Co2+ complexes with 1,10‐phenanthroline, melamine and 1,2‐diaminobenzene. These composites were tested as the catalysts for the hydrogenation of quinolines. As shown by powder X‐ray diffraction and TEM, the composited contained Co particles of several dozen nm sizes. The composition (elements content), Raman spectra X‐ray photoelectron spectra parameters of the composites were analyzed. It was found that there was no distinct factor that controlled the yield of 1,2,3,4‐tetrahydroquinolines in the investigated process. The yields of the respective products were in the range 90–100 %. The three most active composites were selected for scale‐up and hydrogenation of a series of substituted quinolines. Up to 97 % yield of 1,2,3,4‐tetrahydroquinoline was obtained on a 50 g scale. Five representative substituted quinolines were synthesized on a 10–20 grams scale using the Co‐containing composites as the catalysts. [ABSTRACT FROM AUTHOR]

Difluorocyclopropanation of N‐vinylazoles with the CF3SiMe3–NaI system was studied. It was found that N‐vinylpyrazoles could be transformed into the corresponding N‐difluorocyclopropyl‐substituted derivatives. The method was efficient on a 100 g scale and could be applied for the preparation of various functionalized regioisomeric pyrazole derivatives bearing a gem‐difluorocyclopropane moiety, such as amines, carboxylic acids, aldehydes, bromides, and boronic esters. It was found that N‐difluorocyclopropylpyrazole moiety tolerated many common reagents including nitrating mixture, bromine, aqueous acids and alkali, KMnO4, LiBH4, and Pd0 complexes; it was unstable towards AlCl3, catalytic hydrogenation and lithiation conditions. The products obtained are advanced building blocks which of potential importance to medicinal and agrochemistry. [ABSTRACT FROM AUTHOR]

An efficient approach towards introducing (cyclo)alkyl substituents at C‐2, C‐3 or C‐4 positions of the piperidine ring was described. The method relied on the straightforward two‐step reaction sequence based on the formal sp3–sp3 retrosynthetic disconnection. The procedure commenced with selective directed ortho metalation of 2‐ and 3‐bromopyridine, followed by reaction with aldehydes or ketones. The optimized methods were developed for all three isomers of hydroxyalkyl‐substituted pyridines, which were synthesized in 28–84 % overall yield (20 examples). Catalytic hydrogenation of these adducts could be performed selectively with or without retention of the hydroxyl group in their molecules, so that either (cyclo)alkylpiperidines (14 examples) or the corresponding saturated amino alcohols (16 examples) were obtained (28–96 % and 82–96 % yield, respectively). After minor modifications, the developed method was also implemented in a flow reactor and a 5 L autoclave, which allowed for the preparation of up to 0.5 kg of the representative (cyclo)alkylpiperidines. [ABSTRACT FROM AUTHOR]

An approach to the synthesis of 7-methyl-4-azaindole, which is a valuable building block for drug discovery programs, is described. The method relies on using a bromine atom as a 'place holding group' for one of the carbon atoms of the pyridine ring throughout the reaction sequence, and it is removed only upon the final reductive cyclization leading to the azaindole ring. Exhaustive hydrogenation of the target product proceeds in a diastereoselective manner and leads to a bicyclic conformationally restricted diamine derivative. [ABSTRACT FROM AUTHOR]

The idea of introducing (cyclo)alkyl substituents at the C-3 atom of the piperidine ring, that is, formal sp3-sp3 retrosynthetic disconnection, is implemented through a two-step reaction sequence including directed ortho metalation of a pyridine derivative and the subsequent quenching with a carbonyl compound, followed by catalytic hydrogenation. This robust but very efficient method allows for multigram preparation of sp3-rich 3-(cyclo)alkylpiperidines, which are valuable building blocks for medicinal chemistry and other areas. [ABSTRACT FROM AUTHOR]

Abstract: An approach to the synthesis of all possible tetrahydropyrido[d]pyridazinones has been developed. The method relies on the catalytic hydrogenation of the corresponding aromatic counterparts, which were obtained by cyclization of the relevant dibromomethyl-substituted pyridinecarboxylates with hydrazine. The synthetic schemes include 4–5 steps starting from commercially available materials. The tetrahydropyrido[d]pyridazinone scaffolds are combinations of a saturated heterocycle (piperidine) and a privileged aromatic heterocycle (pyridazinone); hence they are promising starting points for the design in medicinal chemistry. [Copyright &y& Elsevier]

• An approach to 3-substituted piperidines bearing partially fluorinated alkyl groups is developed. • The strategy is based on deoxofluorination of 2-bromopyridin-3-yl derivatives with DAST followed by hydrogenation. • The major limitation of the approach is hydrodefluorination which occurred at the hydrogenation step. • Despite this limitation, the method is efficient for the preparation of 3-(1,1-difluoroalkyl)piperidines. An approach to the synthesis of 3-substituted piperidines bearing partially fluorinated alkyl groups was proposed. The method was based on the DAST-mediated nucleophilic fluorination of easily available 2-bromopyridin-3-yl alcohols and ketones affording 2-bromo-3-(1-fluoroalkyl)pyridines and 2-bromo-3-(1,1-difluoroalkyl)pyridines, respectively, followed by catalytic hydrogenation. The hydrogenation step was studied with common heterogeneous Pd-, Pt-, and Rh-based catalyst. It was found that in the case of fluoroalkyl derivatives, the pyridine core reduction was accompanied by hydrodefluorination, which became a limitation of the strategy. Nevertheless, the method worked well with 1,1-difluoroalkyl derivatives [ABSTRACT FROM AUTHOR]