Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rhodium catalysed C-3/5 methylation of pyridines using temporary dearomatisation.

ABSTRACT: Pyridines are ubiquitous aromatic rings used in organic chemistry and are crucial elements of the drug discovery process. Herein we describe a new catalytic method that directly introduces a methyl group onto the aromatic ring; this new reaction is related to hydrogen borrowing, and is notable for its use of the feedstock chemicals methanol and formaldehyde as the key reagents. Conceptually, the C-3/5 methylation of pyridines was accomplished by exploiting the interface between aromatic and non-aromatic compounds, and this allows an oscillating reactivity pattern to emerge whereby normally electrophilic aromatic compounds become nucleophilic in the reaction after activation by reduction. Thus, a set of C-4 functionalised pyridines can be mono or doubly methylated at the C-3/5 positions.

SUBMITTER: Grozavu A

PROVIDER: S-EPMC8163342 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Rhodium catalysed C-3/5 methylation of pyridines using temporary dearomatisation.

Grozavu Alexandru A Hepburn Hamish B HB Bailey Elliot P EP Lindsay-Scott Peter J PJ Donohoe Timothy J TJ

Chemical science 20200810 32

Pyridines are ubiquitous aromatic rings used in organic chemistry and are crucial elements of the drug discovery process. Herein we describe a new catalytic method that directly introduces a methyl group onto the aromatic ring; this new reaction is related to hydrogen borrowing, and is notable for its use of the feedstock chemicals methanol and formaldehyde as the key reagents. Conceptually, the C-3/5 methylation of pyridines was accomplished by exploiting the interface between aromatic and non- ...[more]

PMID: 34123119

Similar Datasets

Rhodium-catalysed <i>ortho</i>-alkynylation of nitroarenes.

Project description:The ortho-alkynylation of nitro-(hetero)arenes takes place in the presence of a Rh(iii) catalyst to deliver a wide variety of alkynylated nitroarenes regioselectively. These interesting products could be further derivatized by selective reduction of the nitro group or palladium-catalysed couplings. Experimental and computational mechanistic studies demonstrate that the reaction proceeds via a turnover-limiting electrophilic C-H metalation ortho to the strongly electron-withdrawing nitro group.

| S-EPMC8597868 | biostudies-literature

Pd-catalyzed allylative dearomatisation using Grignard reagents.

Project description:Pd-catalyzed allylative dearomatisation of naphthyl halides is shown to be feasible by employing Grignard reagents. The high reactivity of the nucleophile allows for fast reactions and low catalyst loading, while a plethora of successfully substituted compounds illustrate the broad scope. Five membered heteroaromatic compounds are also demonstrated to be reactive under similar conditions.

| S-EPMC8577247 | biostudies-literature

Rhodium-catalysed tetradehydro-Diels-Alder reactions of enediynes <i>via</i> a rhodium-stabilized cyclic allene.

Project description:Efficient methods for the synthesis of fused-aromatic rings is a critical endeavour in the creation of new pharmaceuticals and materials. A direct method for preparing these systems is the tetradehydro-Diels-Alder reaction, however this is limited by the need for harsh reaction conditions. A potential, but underdeveloped, route to these systems is via transition metal-catalysed cycloaromatisation of ene-diynes. Herein, tethered unconjugated enediynes have been shown to undergo a facile room-temperature RhI-catalysed intramolecular tetradehydro-Diels-Alder reaction to produce highly substituted isobenzofurans, isoindolines and an indane. Furthermore, experimental and computational studies suggest a novel mechanism involving an unprecedented and complex RhI/RhIII/RhI/RhIII redox cycle involving the formation of an unusual strained 7-membered rhodacyclic allene intermediate and a RhIII-stabilized 6-membered ring allene complex.

| S-EPMC8162385 | biostudies-literature

Rhodium-catalysed syn-carboamination of alkenes via a transient directing group.

Project description:Alkenes are the most ubiquitous prochiral functional groups--those that can be converted from achiral to chiral in a single step--that are accessible to synthetic chemists. For this reason, difunctionalization reactions of alkenes (whereby two functional groups are added to the same double bond) are particularly important, as they can be used to produce highly complex molecular architectures. Stereoselective oxidation reactions, including dihydroxylation, aminohydroxylation and halogenation, are well established methods for functionalizing alkenes. However, the intermolecular incorporation of both carbon- and nitrogen-based functionalities stereoselectively across an alkene has not been reported. Here we describe the rhodium-catalysed carboamination of alkenes at the same (syn) face of a double bond, initiated by a carbon-hydrogen activation event that uses enoxyphthalimides as the source of both the carbon and the nitrogen functionalities. The reaction methodology allows for the intermolecular, stereospecific formation of one carbon-carbon and one carbon-nitrogen bond across an alkene, which is, to our knowledge, unprecedented. The reaction design involves the in situ generation of a bidentate directing group and the use of a new cyclopentadienyl ligand to control the reactivity of rhodium. The results provide a new way of synthesizing functionalized alkenes, and should lead to the convergent and stereoselective assembly of amine-containing acyclic molecules.

| S-EPMC4636455 | biostudies-literature

Dibenzothiophenesulfilimines: A Convenient Approach to Intermolecular Rhodium-Catalysed C-H Amidation.

Project description:A sulfilimine-based Group 9 transition-metal-catalysed C-H amidation procedure is reported. Dibenzothiophene-based sulfilimines were shown to constitute a class of novel amidation reagents which enable the transfer of a wide range of N-sulfonyl and N-acyl moieties. It was demonstrated that sulfilimines, which are easily accessible from cheap reagents, are safe-to-handle and represent broadly applicable amidation reagents. The dibenzothiophene can be recycled after use. The C-H amidation was shown to proceed with high selectivity and gave the mono-amidated products, mostly in good to excellent yields.

| S-EPMC7383884 | biostudies-literature

Rhodium-catalysed selective C-C bond activation and borylation of cyclopropanes.

Project description:Transition metal (TM)-catalysed directed hydroboration of aliphatic internal olefins which facilitates the construction of complex alkylboronates is an essential synthetic methodology. Here, an efficient method for the borylation of cyclopropanes involving TM-catalysed directed C-C activation has been developed. Upon exposure to neutral Rh(i)-catalyst systems, N-Piv-substituted cyclopropylamines (CPAs) undergo proximal-selective hydroboration with HBpin to provide valuable γ-amino boronates in one step which are otherwise difficult to synthesize by known methods. The enantioenriched substrates can deliver chiral products without erosion of the enantioselectivities. Versatile synthetic utility of the obtained γ-amino boronates is also demonstrated. Experimental and computational mechanistic studies showed the preferred pathway and the origin of this selectivity. This study will enable the further use of CPAs as valuable building blocks for the tunable generation of C-heteroatom or C-C bonds through selective C-C bond activation.

| S-EPMC8179453 | biostudies-literature

Exploiting rhodium-catalysed ynamide hydroacylation as a platform for divergent heterocycle synthesis.

Project description:The first examples of ynamide hydroacylation are described. Using rhodium catalysis, linear β-enaminone products are generated in high yield and excellent regioselectivity from the combination of aldehydes and ynamides. The enaminone products are subsequently used as a platform to construct a diverse array of substituted pyrazoles, pyrimidines, and isoxazoles in a two-step, one-pot sequence. It was found that with judicious choice of catalyst system it was possible to overturn the regioselectivity of the hydroacylation reaction to generate α-enaminone products.

| S-EPMC5853270 | biostudies-literature

Photochemical Reactions of Fluorinated Pyridines at Half-Sandwich Rhodium Complexes: Competing Pathways of Reaction.

Project description:Irradiation of CpRh(PMe3)(C2H4) (1; Cp = η5-C5H5) in the presence of pentafluoropyridine in hexane solution at low temperature yields an isolable η2-C,C-coordinated pentafluoropyridine complex, CpRh(PMe3)(η2-C,C-C5NF4) (2). The molecular structure of 2 was determined by single-crystal X-ray diffraction, showing coordination by C3-C4, unlike previous structures of pentafluoropyridine complexes that show N-coordination. Corresponding experiments with 2,3,5,6-tetrafluoropyridine yield the C-H oxidative addition product CpRh(PMe3)(C5NF4)H (3). In contrast, UV irradiation of 1 in hexane, in the presence of 4-substituted tetrafluoropyridines C5NF4X, where X = NMe2, OMe, results in elimination of C2H4 and HF to form the metallacycles CpRh(PMe3)(κ2-C,C-CH2N(CH3)C5NF3) (4) and CpRh(PMe3)(κ2-C,C-CH2OC5NF3) (5), respectively. The X-ray structure of 4 shows a planar RhCCNC-five-membered ring. Complexes 2-5 may also be formed by thermal reaction of CpRh(PMe3)(Ph)H with the respective pyridines at 50 °C.

| S-EPMC3929166 | biostudies-literature

Asymmetric Suzuki-Miyaura coupling of heterocycles via Rhodium-catalysed allylic arylation of racemates.

Project description:Using asymmetric catalysis to simultaneously form carbon-carbon bonds and generate single isomer products is strategically important. Suzuki-Miyaura cross-coupling is widely used in the academic and industrial sectors to synthesize drugs, agrochemicals and biologically active and advanced materials. However, widely applicable enantioselective Suzuki-Miyaura variations to provide 3D molecules remain elusive. Here we report a rhodium-catalysed asymmetric Suzuki-Miyaura reaction with important partners including aryls, vinyls, heteroaromatics and heterocycles. The method can be used to couple two heterocyclic species so the highly enantioenriched products have a wide array of cores. We show that pyridine boronic acids are unsuitable, but they can be halogen-modified at the 2-position to undergo reaction, and this halogen can then be removed or used to facilitate further reactions. The method is used to synthesize isoanabasine, preclamol, and niraparib-an anticancer agent in several clinical trials. We anticipate this method will be a useful tool in drug synthesis and discovery.

| S-EPMC5474734 | biostudies-literature

Stereoisomeric Tris-BINOL-Menthol Bulky Monophosphites: Synthesis, Characterisation and Application in Rhodium-Catalysed Hydroformylation.

Project description:Four stereoisomeric monoether derivatives, based on axially chiral (R)- or (S)-BINOL bearing a chiral (+)- or (-)-neomenthyloxy group were synthesised and fully characterised by NMR spectroscopy and X-ray crystallography. The respective tris-monophosphites were thereof prepared and fully characterised. The coordination ability of the new bulky phosphites with Rh(CO)2(acac), was attested by 31P NMR, which presented a doublet in the range of δ = 120 ppm, with a 1J(103Rh-31P) coupling constant of 290 Hz. The new tris-binaphthyl phosphite ligands were further characterised by DFT computational methods, which allowed us to calculate an electronic (CEP) parameter of 2083.2 cm-1 and an extremely large cone angle of 345°, decreasing to 265° upon coordination with a metal atom. Furthermore, the monophosphites were applied as ligands in rhodium-catalysed hydroformylation of styrene, leading to complete conversions in 4 h, 100% chemoselectivity for aldehydes and up to 98% iso-regioselectivity. The Rh(I)/phosphite catalytic system was also highly active and selective in the hydroformylation of disubstituted olefins, including (E)-prop-1-en-1-ylbenzene and prop-1-en-2-ylbenzene.

| S-EPMC8954005 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data