135689-93-9Relevant articles and documents
Anchored Pd(0) Nanoparticles on Synthetic Talc for the Synthesis of Biaryls and a Precursor of Angiotensin II Inhibitors
Dos Santos, Beatriz F.,Da Silva, Beatriz A. L.,De Oliveira, Aline R.,Sarragiotto, Maria H.,Domingues, Nelson Luís C.
, p. 933 - 942 (2021)
The palladium-catalyzed Suzuki-Miyaura cross-coupling reaction is one of the most important and efficient reactions to prepare a variety of organic compounds, including biaryls. Despite the overwhelming number of reports related to this topic, some methodological difficulties persist in terms of catalyst handling, recovery, and reuse, as well as the reaction media. This work reports the rational design of new, efficient, cost-effective, and reusable palladium catalysts supported on synthetic talc for the Suzuki-Miyaura reaction. From the results, key points were identified: both designed catalysts accelerated the reaction in EtOH and an open-flask setup, affording moderate to excellent yields within a short time (e.g., 30 min) even for deactivated aryl halides; the protocol can be applied to a great number of both cross-coupling partners, showing an excellent functional group tolerance; the catalysts can be recovered and reused without significant loss of activity. This protocol was used for the synthesis of a precursor of angiotensin II inhibitors such as valsartan, losartan, irbesartan, and telmisartan.
Multi-layered, covalently supported ionic liquid phase (mlc-SILP) as highly cross-linked support for recyclable palladium catalysts for the suzuki reaction in aqueous medium
Gruttadauria, Michelangelo,Liotta, Leonarda Francesca,Salvo, Anna Maria Pia,Giacalone, Francesco,La Parola, Valeria,Aprile, Carmela,Noto, Renato
, p. 2119 - 2130 (2011)
The reaction between an excess of 1,4-bis(3-vinylimidazolium-1-yl) bromide and a mercaptopropyl-modified amorphous silica gel or ordered mesoporous silica SBA-15 in the presence of azobisisobutyronitrile (AIBN) afforded new materials, which have a high loading of imidazolium moieties. These materials, which contain a highly cross-linked polymeric network, have been denoted as multi-layered, covalently supported ionic liquid phase (mlc-SILP) and have been used as support for palladium catalysts containing a high loading of the metal (10 wt%). Such materials were characterized by several techniques ( 13C magic angle spinning nuclear magnetic resonance, the Brunauer-Emmett-Teller technique, small-angle X-ray scattering, X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy). The presence of a homogeneous distribution of palladium nanoparticles was established. The palladium catalysts displayed good activity allowing the synthesis of several biphenyl compounds in high yields working with only 0.1 mol% of palladium loading at mild temperatures (room temperature or 50 °C) in ethanol/water. Reactions carried out on a 10-mmol scale required only 10 mg of catalysts. Good recyclability was observed. Copyright
Design of a Numbering-up System of Monolithic Microreactors and Its Application to Synthesis of a Key Intermediate of Valsartan
Nagaki, Aiichiro,Hirose, Katsuyuki,Tonomura, Osamu,Taniguchi, Satoshi,Taga, Toshiki,Hasebe, Shinji,Ishizuka, Norio,Yoshida, Jun-Ichi
, p. 687 - 691 (2016)
Synthesis of a key intermediate of valsartan was accomplished using five parallel monolithic microreactors connected to a split-and-recombine-type flow distributor. The channel resistances of the flow distributor were designed so as to minimize the flow maldistribution among reactors by using pressure drop compartment model, which is analogous to electrical resistance network.
Chiral Proline-Decorated Bifunctional Pd?NH2-UiO-66 Catalysts for Efficient Sequential Suzuki Coupling/Asymmetric Aldol Reactions
Chen, Jinxi,Cheng, Lin,Li, Yiming,Lou, Yongbing,Zhai, Qingchao,Zhang, Qingsong,Zhao, Kaiyuan
, (2020/06/08)
The design and development of site-isolating and multifunctional catalysts for multistep sequential reactions at the molecular level is a significant challenge. Herein, we first report bifunctional metal NPs?chiral MOFs catalysts for asymmetric sequential reactions. Pd nanoparticles and chiral proline were successfully added to NH2-UiO-66 to construct two chiral bifunctional catalysts, in which active Pd nanoparticles were encapsulated into the frameworks via the "bottle-around-ship" method, and chiral proline was introduced into NH2-UiO-66 by coordination to zirconium nodes and postsynthetic modification (PSM) of the organic linkers. The chiral proline-decorated bifunctional Pd?NH2-UiO-66 catalysts were applied to sequential Suzuki coupling/asymmetric aldol reactions with excellent coupling performance (yields up to 99.9%) and good enantioselectivities (eeanti values up to 97%). The heterogeneous catalyst by coordination of proline can be reused, and the reaction activity was not significantly reduced after four cycles.
Palladium-Catalyzed Late-Stage Direct Arene Cyanation
Zhao, Da,Xu, Peng,Ritter, Tobias
supporting information, p. 97 - 107 (2019/01/21)
Methods for direct benzonitrile synthesis are sparse, despite the versatility of cyano groups in organic synthesis and the importance of benzonitriles for the dye, agrochemical, and pharmaceutical industries. We report the first general late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance. The reaction is enabled by a dual-ligand combination of quinoxaline and an amino acid-derived ligand. The method is applicable to direct cyanation of several marketed small-molecule drugs, common pharmacophores, and organic dyes. Benzonitriles are some of the most versatile building blocks for organic synthesis, in particular in the pharmaceutical industry, but general methods to make them by direct C–H functionalization are unknown. In this issue of Chem, Ritter and coworkers describe a late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance, enabled by a palladium-dual-ligand catalyst system. The reaction may serve for the late-stage modification of drug candidates. Aryl nitriles constitute an important class of organic compounds that are widely found in natural products, pharmaceuticals, agricultural chemicals, dyes, and materials. Moreover, nitriles are versatile building blocks to access numerous other important molecular structure groups. However, no general method for direct aromatic C–H cyanation is known. All approaches to date require either an appropriate directing group or reactive electron-rich substrates, such as indoles, which limit their synthetic applications. Here we describe an undirected, palladium-catalyzed late-stage aryl C–H cyanation reaction for the synthesis of complex aryl nitriles that would otherwise be more challenging to produce. The wide substrate scope and good functional-group tolerance of this reaction provide direct and quick access to structural diversity for pharmaceutical and agrochemical development.
VP1 crystal structure-guided exploration and optimization of 4,5-dimethoxybenzene-based inhibitors of rhinovirus 14 infection
Da Costa, Laurène,Roche, Manon,Scheers, Els,Coluccia, Antonio,Neyts, Johan,Terme, Thierry,Leyssen, Pieter,Silvestri, Romano,Vanelle, Patrice
, p. 453 - 462 (2016/04/19)
Human rhinoviruses (HRV) are the predominant cause of common colds and flu-like illnesses, but are also responsible for virus-induced exacerbations of asthma and chronic obstructive pulmonary disease. However, to date, no drug has been approved yet for clinical use. In this study, we present the results of the structure-based lead optimization of a class of new small-molecule inhibitors that we previously reported to bind into the pocket beneath the canyon of the VP1 protein. A small series of analogues that we designed based on the available structure and interaction data were synthesized and evaluated for their potency to inhibit the replication of HRV serotype 14. 2-(4,5-Dimethoxy-2-nitrophenyl)-1-(4-(pyridin-4-yl)phenyl)ethanol (3v) was found to be a potent inhibitor exhibiting micromolar activity (EC50 Combining double low line 3.4 ± 1.0 μM) with a toxicity for HeLa cells that was significantly lower than that of our previous hit (LPCRW-0005, CC50 Combining double low line 104.0 ± 22.2 μM; 3v, CC50 > 263 μM).
Aryldiazonium Tetrafluoroborate Salts as Green and Efficient Coupling Partners for the Suzuki-Miyaura Reaction: From Optimisation to Mole Scale
Colleville, Aymeric P.,Horan, Richard A. J.,Tomkinson, Nicholas C. O.
supporting information, p. 1128 - 1136 (2015/04/22)
The use of aryldiazonium tetrafluoroborate salts as coupling partners in the Suzuki-Miyaura reaction was investigated from a process chemistry perspective including safety evaluation, solvent and catalyst screening and multivariate factor optimisation. Optimised conditions were applied to a range of substrates to evaluate the scope and limitations of the reaction, and one example was carried out on mole scale to demonstrate the practicality and scalability of the process.
Improved Sommelet reaction catalysed by lanthanum triflate
Xu, Wenhao,Su, Weike
, p. 710 - 714 (2015/03/04)
An improved Sommelet reaction for the synthesis of araldehydes from benzyl halides and hexamethylenetetramine was achieved employing lanthanum triflate (3 mol%) as catalyst in water with sodium dodecyl sulfate (SDS, 2 wt%) as solubiliser. Good to excellent yields were obtained in most of the 18 examples.
Sequential Suzuki/asymmetric aldol and Suzuki/Knoevenagel reactions under aqueous conditions
Gruttadauria, Michelangelo,Bivona, Lucia Anna,Lo Meo, Paolo,Riela, Serena,Noto, Renato
experimental part, p. 2635 - 2642 (2012/06/04)
Here we describe for the first time a sequential Suzuki/asymmetric aldol reaction. Such sequential approach was achieved through the combined use of an ionic liquid supported palladium catalyst and the organocatalyst trans-4-(2,2-diphenylacetoxy)proline. Suzuki and asymmetric aldol reactions were performed under aqueous conditions. The use of a palladium catalyst under basic conditions allowed also the first example of sequential Suzuki/Knoevenagel reaction. Reactions were carried out under aqueous conditions and products were isolated in good to high yields and, in the case of the Suzuki/aldol reaction, with diastereoselectivities up to 91:9 and enantioselectivities up to at least 99%.
Synthesis of valsartan via decarboxylative biaryl coupling
Goossen, Lukas J.,Melzer, Bettina
, p. 7473 - 7476 (2008/02/12)
(Chemical Equation Presented) An efficient synthesis of the angiotensin II inhibitor valsartan (Diovan) is presented. Two routes were evaluated, both making use of an advanced version of our decarboxylative coupling for the construction of the biaryl moiety. Thus, in the presence of a catalyst system consisting of copper(II) oxide, 1,10-phenanthroline, and palladium(II) bromide, 2-cyanocarboxylic acid was coupled with 1-bromo(4-dimethoxymethyl)benzene in 80% yield and with 4-bromotoluene in 71% yield. The valsartan synthesis using 1-bromo(4-dimethoxymethyl)benzene was completed in four steps overall with a total yield of 39%, via a novel route that presents substantial economical and ecological advantages over the literature process, as it is more concise and stoichiometric amounts of expensive organometallic reagents are avoided.
