257,478 research outputs found
Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells
Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells
Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells
Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells
Developing and Understanding Iridium-Catalysed Arene Borylation
Iridium catalysed C-H borylation has moved from an interesting observation to an efficient catalytic reaction. This work has developed and improved upon some of the key issues associated with the methodology.
The one-pot conversion of aryl boronates, generated by C-H borylation, to other functionality has been one area of interest. However, reactions typically require a change in reaction solvent to make this possible. This thesis describes a one-pot, single solvent C-H borylation/Suzuki-Miyaura cross-coupling sequence. The key to this transformation is the use of methyl tert-butyl ether (MTBE). This procedure allows efficient synthesis of biaryls by initial C-H borylation of aromatic substrates followed by addition of water, subsequent reagents and aryl halide to complete the Suzuki-Miyaura cross-coupling without the need for change in reaction solvent.
Another issue associated with the C-H borylation reaction is the extended reaction times required for some substrates. This issue was tackled by development of a microwave accelerated C-H borylation reaction. Microwave reactions are conducted at the same temperature as standard heated reactions with accelerations of 2 - 24 times affording comparable product yields. Typically reaction times were reduced from hours to minutes. A microwave accelerated one-pot, single solvent C-H borylation/Suzuki-Miyaura cross-coupling sequence allowed synthesis of biaryls from arene plus aryl halides in reaction times of minutes.
Subsequent work focussed on the borylation of novel substrates classes, in particular quinolines. The borylation of substituted quinolines highlighted interesting electronic selectivity of the reaction. The site of borylation can be directed by changing the nature of the substituent on the ring. DFT calculations have been conducted to gain understanding into the causes of selectivity. A link between C-H acidity, calculated by DFT methods, and the borylation site was observed. Preliminary studies into the borylation of azaindoles are discussed. Studies towards a procedure to convert aryl boronates to trifluoromethyl groups are also been introduced
ONE-POT O-ALKYLATION AND C-C CROSS-COUPLING REACTIONS INVOLVING STABILIZED PHOSPHORANES
This thesis is concerned with the one-pot reactions that are considered to be beneficial to preserve resources, save time, and are deemed a green chemistry strategy. To plan such one-pot reactions, it is important to combine two or more reactions that are compatible with each other and can be run under the same reaction conditions. In this work, possibilities of a combination of Wittig-olefination and Suzuki C-C-cross coupling reactions are explored further. Reaction sequences involve the combination of a Suzuki-reaction / Wittig olefination, a Suzuki reaction / Wittig olefination/hydrolysis, and a Suzuki-reaction / double Wittig olefination. In all cases, stabilized Wittig reagents were used. Also, a novel one-pot O-alkylation / Wittig olefination of hydroxybenzaldehydes to alkoxycinnamates was developed. Furthermore, during the synthesis of starting materials a new approach to arylmaleimides was found, using a modified Appel-type reaction.
Some of the compounds that could be made by one-pot Suzuki and single Wittig olefination are methyl 3-(3’-nitrophenyl) cinnamate, methyl (E, E)-5-(4’-nitro-1,1’- biphen-4-yl)-Penta-2,5-dienoate, methyl (E,E)-5-(3’-nitrobiphenyl)Penta-2,4- dienoate. Moreover, the combination between Suzuki – Wittig olefination and hydrolysis in one pot was performed to obtain 3-(3“-nitrobiphen-3’-yl) acrylic acid. Furthermore, dimethyl biphenyl-4,4’-diacrylate and dimethyl biphenyl-3,4’-diacrylate were synthesized by one-pot Suzuki and double Wittig olefination reactio
Synthesis of Functionalized Benzophenones and Terphenyls based on Site-Selective Suzuki-Miyaura Reactions of Bis(triflates) of various Hydroxylated Benzophenones and Benzoates
The palladium(0)-catalyzed Suzuki cross-coupling reaction of the bis(triflates) of 2,4′-dihydroxybenzophenones afforded 2,4′-diarylbenzophenones. The Suzuki-Miyaura reaction of the bis(triflate) of 3,4-dihydroxybenzophenone with two equivalents of boronic acids gave 3,4-diarylbenzophenones. The Sonogashira cross-coupling reactions of the same substrate display remarkable compatibility with Suzuki reactions.The palladium(0)-catalyzed Suzuki cross-coupling reaction of the bis(triflates) of methyl 2,5-dihydroxybenzoate and methyl 2,4-dihydroxybenzoate afforded p-terphenyls and m-terphenyls respectively
Synthesis of 5-substituted 2'-deoxyuridine-5'-phosphonate analogues and evaluation of their antiviral activity
A small series of 5-(hetero)aryl-modified nucleoside phosphonates was synthesized via an 8-step procedure including a Wittig reaction and Suzuki-Miyaura coupling. An unanticipated anomerization during phosphonate deprotection allowed us to isolate both anomers of the 5-substituted 2'-deoxy-uridine phosphonates and assess their antiviral activity against a broad panel of viruses
Recent developments in the Suzuki-Miyaura reaction: 2010-2014
The Suzuki-Miyaura reaction (SMR), involving the coupling of an organoboron reagent and an organic halide or pseudo-halide in the presence of a palladium or nickel catalyst and a base, has arguably become one of most utilized tools for the construction of a C-C bond. This review intends to be general account of all types of catalytic systems, new coupling partners and applications, including the literature between September 2010 and December 2014
IMPROVING THE SCOPE AND UNDERSTANDING OF THE SYMMETRIC AND ASYMMETRIC SUZUKI COUPLING REACTION
Investigations into the Symmetric and Asymmetric Suzuki cross-coupling
reaction have been described. A new reaction protocol has been developed in which
isolated pre-activated sodium trihydroxyarylborate salts were employed as the
organoboron coupling partner, resulting in a more convenient and stoichiometrically
efficient process. This alternative protocol has been applied to symmetric Suzuki
reactions employing simple electron-rich and electron-poor aryl halide partners, and
to sterically challenging Suzuki reactions employing bulkier substrates. Asymmetric
(atroposelective) Suzuki coupling reactions were also successfully performed using
sodium trihydroxyarylborate salts as coupling substrates. The versatility of these
species as general organoboron reagents was also demonstrated by their successful
application in a rhodium-catalysed 1,4-addition reaction.
Experimental studies of asymmetric Suzuki cross-couplings towards axially
chiral biaryl products have also been detailed. Model reactions towards
configurationally stable biaryl products were found to undergo a successful chiral
induction with the use of chiral ferrocenyl ligand (R)-(S)-PPFA 180, with high
enantiomeric excesses achieved in some cases. Investigations into the possible
influences on the asymmetric induction process exerted by the electronic and steric
properties of the coupling partners were carried out, involving repeat asymmetric
reactions towards the biaryl product 1-(2’-nitrophenyl)-2-phenylnaphthalene 179. In
these reactions, changes to the reacting moiety of the coupling substrates were tested,
with an additional reaction carried out involving the reversal of the organic group
borne by each substrate
Palladium nanoparticles supported on fluorine-doped tin oxide as an efficient heterogeneous catalyst for Suzuki coupling and 4-nitrophenol reduction
Immobilization of palladium nanoparticles onto the fluorine-doped tin oxide (FTO) as support Pd/FTO, resulted in a highly active heterogeneous catalyst for Suzuki-Miyaura cross-coupling reactions and 4-nitrophenol reduction. The Pd/FTO catalyst has been synthesized by immobilization of palladium nanoparticles onto FTO via a simple impregnation method. ICP-MS analysis confirmed that there is 0.11 mmol/g of palladium was loaded successfully on FTO support. The crystallinity, morphologies, compositions and surface properties of Pd/FTO were fully characterized by various techniques. It was further examined for its catalytic activity and robustness in Suzuki coupling reaction with different aryl halides and solvents. The yields obtained from Suzuki coupling reactions were basically over 80%. The prepared catalyst was also tested on mild reaction such as reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP). Pd/FTO catalyst exhibited high catalytic activity towards 4-NP reduction with a rate constant of 1.776 min(-1) and turnover frequency (TOF) value of 29.1 hr(-1). The findings revealed that Pd/FTO also maintained its high stability for five consecutive runs in Suzuki reactions and 4-NP reductions. The catalyst showed excellent catalytic activities by using a small amount of Pd/FTO for the Suzuki coupling reaction and 4-NP reduction
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