Browse
Submit Data
Databases
API
Help

Dataset Information

12 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Direct cyclopropanation of activated N-heteroarenes via site- and stereoselective dearomative reactions.

ABSTRACT: A divergent cyclopropanation reaction has been accomplished via the dearomative addition of sulfur ylides to activated N-heteroarenes. A series of biologically significant molecular skeletons was obtained by the direct cyclopropanation of quinolinium zwitterions. Furthermore, a straightforward synthetic route to optically enriched cyclopropane-fused heterocycles was developed using sulfur ylides as chiral nucleophiles in the 1,4-dearomative reaction.

SUBMITTER: Lee J

PROVIDER: S-EPMC7069384 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Direct cyclopropanation of activated N-heteroarenes <i>via</i> site- and stereoselective dearomative reactions.

Lee Jiyoun J Ko Donguk D Park Hyunju H Yoo Eun Jeong EJ

Chemical science 20200110 6

A divergent cyclopropanation reaction has been accomplished <i>via</i> the dearomative addition of sulfur ylides to activated N-heteroarenes. A series of biologically significant molecular skeletons was obtained by the direct cyclopropanation of quinolinium zwitterions. Furthermore, a straightforward synthetic route to optically enriched cyclopropane-fused heterocycles was developed using sulfur ylides as chiral nucleophiles in the 1,4-dearomative reaction. ...[more]

PMID: 32206287

Similar Datasets

Asymmetric dearomative cyclopropanation of naphthalenes to construct polycyclic compounds.

Project description:Catalytic asymmetric dearomatization (CADA) reactions is an important synthetic method for constructing enantioenriched complex cyclic systems from simple aromatic feedstocks. However, the CADA reactions of nonactivated arenes, such as naphthalenes and benzenes, have been far less explored than those of electronically activated arenes, such as phenols, naphthols and indoles. Herein, we disclose an asymmetric dearomative cyclopropanation of naphthalenes for the rapid construction of polycyclic compounds. With chiral dirhodium carboxylate as a catalyst, the dearomative cyclopropanation proceeded smoothly under mild conditions and afforded benzonorcaradiene-containing tetracycles in good yield and high enantioselectivity (up to 99% ee). Three stereogenic centers, including two all-carbon quaternary centers, were created in the dearomatization reaction. Moreover, a variety of functional groups are well-tolerated in the reaction. The products could be readily converted into other complex polycycles while maintaining the high ee value.

| S-EPMC9669881 | biostudies-literature

Stereoselective Intramolecular Cyclopropanation of ?-Diazoacetates via Co(II)-Based Metalloradical Catalysis.

Project description:Co(II) complexes of D2-symmetric chiral porphyrins have been proven to be effective metalloradical catalysts for the asymmetric intramolecular cyclopropanation of allyl ?-diazoacetates. 4-(Dimethylamino)pyridine (DMAP), through positive trans effect, plays an important role in the enhancement of the asymmetric induction for the intramolecular cyclopropanation process. This metalloradical catalytic system is suitable for cyclopropanation of allyl ?-diazoacetates with varied functional groups and substitution patterns, producing bicyclic products with complete diastereocontrol and good enantiocontrol.

| S-EPMC4043383 | biostudies-literature

Highly Stereoselective Synthesis of Fused Cyclopropane-γ-Lactams via Biocatalytic Iron-Catalyzed Intramolecular Cyclopropanation.

Project description:We report the development of an iron-based biocatalytic strategy for the asymmetric synthesis of fused cyclopropane-γ-lactams, which are key structural motifs found in synthetic drugs and bioactive natural products. Using a combination of mutational landscape and iterative site-saturation mutagenesis, sperm whale myoglobin was evolved into a biocatalyst capable of promoting the cyclization of a diverse range of allyl diazoacetamide substrates into the corresponding bicyclic lactams in high yields and with high enantioselectivity (up to 99% ee). These biocatalytic transformations can be performed in whole cells and could be leveraged to enable the efficient (chemo)enzymatic construction of chiral cyclopropane-γ-lactams as well as β-cyclopropyl amines and cyclopropane-fused pyrrolidines, as valuable building blocks and synthons for medicinal chemistry and natural product synthesis.

| S-EPMC7111458 | biostudies-literature

Direct Observation of Aryl Gold(I) Carbenes that Undergo Cyclopropanation, C-H Insertion, and Dimerization Reactions.

Project description:Mesityl gold(I) carbenes lacking heteroatom stabilization or shielding ancillary ligands have been generated and spectroscopically characterized from chloro(mesityl)methylgold(I) carbenoids bearing JohnPhos-type ligands by chloride abstraction with GaCl3 . The aryl carbenes react with PPh3 and alkenes to give stable phosphonium ylides and cyclopropanes, respectively. Oxidation with pyridine N-oxide and intermolecular C-H insertion to cyclohexane have also been observed. In the absence of nucleophiles, a bimolecular reaction, similar to that observed for other metal carbenes, leads to a symmetrical alkene.

| S-EPMC6593763 | biostudies-literature

An Artificial Heme Enzyme for Cyclopropanation Reactions.

Project description:An artificial heme enzyme was created through self-assembly from hemin and the lactococcal multidrug resistance regulator (LmrR). The crystal structure shows the heme bound inside the hydrophobic pore of the protein, where it appears inaccessible for substrates. However, good catalytic activity and moderate enantioselectivity was observed in an abiological cyclopropanation reaction. We propose that the dynamic nature of the structure of the LmrR protein is key to the observed activity. This was supported by molecular dynamics simulations, which showed transient formation of opened conformations that allow the binding of substrates and the formation of pre-catalytic structures.

| S-EPMC6033091 | biostudies-literature

Copper-catalyzed direct alkylation of heteroarenes.

Project description:An efficient and broadly applicable process is reported for the direct alkylation of C-H bonds in heteroarenes, privileged scaffolds in many areas of science. This reaction is based on the copper-catalyzed addition of alkyl radicals generated from activated secondary and tertiary alkyl bromides to a wide range of arenes, including furans, thiophenes, pyrroles, and their benzo-fused derivatives, as well as coumarins and quinolinones.

| S-EPMC5418647 | biostudies-literature

Highly Stereoselective Glycosylation Reactions of Furanoside Derivatives via Rhenium (V) Catalysis.

Project description:A novel approach for the formation of anomeric carbon-functionalized furanoside systems was accomplished through the employment of an oxo-rhenium catalyst. The transformation boasts a broad range of nucleophiles including allylsilanes, enol ethers, and aromatics in addition to sulfur, nitrogen, and hydride donors, able to react with an oxocarbenium ion intermediate derived from furanosidic structures. The excellent stereoselectivities observed followed the Woerpel model, ultimately providing 1,3-cis-1,4-trans systems. In the case of electron-rich aromatic nucleophiles, an equilibration occurs at the anomeric center with the selective formation of 1,3-trans-1,4-cis systems. This anomalous result was rationalized through density functional theory calculations. Different oxocarbenium ions such as those derived from dihydroisobenzofuran, pyrrolidine, and oxazolidine heterocycles can also be used as a substrate for the oxo-Re-mediated allylation reaction.

| S-EPMC8279489 | biostudies-literature

Site-Selective Copper-Catalyzed Amination and Azidation of Arenes and Heteroarenes via Deprotonative Zincation.

Project description:Arene amination is achieved by site-selective C-H zincation followed by copper-catalyzed coupling with O-benzoylhydroxylamines under mild conditions. Key to this success is ortho-zincation mediated by lithium amidodiethylzincate base that is effective for a wide range of arenes, including nonactivated arenes bearing simple functionalities such as fluoride, chloride, ester, amide, ether, nitrile, and trifluoromethyl groups as well as heteroarenes including indole, thiophene, pyridine, and isoquinoline. An analogous C-H azidation is also accomplished using azidoiodinane for direct introduction of a useful azide group onto a broad scope of arenes and heteroarenes. These new transformations offer rapid access to valuable and diverse chemical space of aminoarenes. Their broad applications in organic synthesis and drug discovery are demonstrated in the synthesis of novel analogues of natural product (-)-nicotine and antidepressant sertraline by late-stage amination and azidation reactions.

| S-EPMC5685551 | biostudies-literature

Photoredox-catalyzed stereoselective alkylation of enamides with N-hydroxyphthalimide esters via decarboxylative cross-coupling reactions.

Project description:Stereoselective ?-C(sp2)-H alkylation of enamides with redox-active N-hydroxyphthalimide esters via a photoredox-catalyzed decarboxylative cross-coupling reaction is demonstrated. This methodology features operational simplicity, broad substrate scopes, and excellent stereoselectivities and functional group tolerance, affording a diverse array of geometrically defined and synthetically valuable enamides bearing primary, secondary or tertiary alkyl groups in satisfactory yields.

| S-EPMC6849636 | biostudies-literature

Stereoselective Cyclopropanation of Electron-Deficient Olefins with a Cofactor Redesigned Carbene Transferase Featuring Radical Reactivity.

Project description:Engineered myoglobins and other hemoproteins have recently emerged as promising catalysts for asymmetric olefin cyclopropanation reactions via carbene transfer chemistry. Despite this progress, the transformation of electron-poor alkenes has proven very challenging using these systems. Here, we describe the design of a myoglobin-based carbene transferase incorporating a non-native iron-porphyrin cofactor and axial ligand, as an efficient catalyst for the asymmetric cyclopropanation of electron-deficient alkenes. Using this metalloenzyme, a broad range of both electron-rich and electron-deficient alkenes are cyclopropanated with high efficiency and high diastereo- and enantioselectivity (up to >99% de and ee). Mechanistic studies revealed that the expanded reaction scope of this carbene transferase is dependent upon the acquisition of metallocarbene radical reactivity as a result of the reconfigured coordination environment around the metal center. The radical-based reactivity of this system diverges from the electrophilic reactivity of myoglobin and most of known organometallic carbene transfer catalysts. This work showcases the value of cofactor redesign toward tuning and expanding the reactivity of metalloproteins in abiological reactions and it provides a biocatalytic solution to the asymmetric cyclopropanation of electrodeficient alkenes. The metallocarbene radical reactivity exhibited by this biocatalyst is anticipated to prove useful in the context of a variety of other synthetic transformations.

| S-EPMC7111255 | 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