Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dearomatization of aryl sulfoxides: a switch between mono- and dual-difluoroalkylation.

ABSTRACT: Herein we describe the dearomatization of aryl sulfoxides with difluoroenol silyl ether (DFESE) using a rearrangement/addition protocol. The selection of the sulfoxide activator determines whether one or two difluoroalkyl groups are incorporated into dearomatized products. Using TFAA can deliberately halt the reaction at the mono-difluoroalkylated dearomatized intermediate formed via a [3,3]-rearrangement, which can be further trapped by external nucleophiles to give mono-difluoroalkylated alicycles. In contrast, switching to Tf₂O enhances the electrophilicity of dearomatized intermediates, thus allowing for the adoption of a second DFESE to produce dual-difluoroalkylated alicycles.

SUBMITTER: Huang X

PROVIDER: S-EPMC8157523 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Dearomatization of aryl sulfoxides: a switch between mono- and dual-difluoroalkylation.

Huang Xin X Zhang Yage Y Liang Weijian W Zhang Qifeng Q Zhan Yaling Y Kong Lichun L Peng Bo B

Chemical science 20200225 11

Herein we describe the dearomatization of aryl sulfoxides with difluoroenol silyl ether (DFESE) using a rearrangement/addition protocol. The selection of the sulfoxide activator determines whether one or two difluoroalkyl groups are incorporated into dearomatized products. Using TFAA can deliberately halt the reaction at the mono-difluoroalkylated dearomatized intermediate formed <i>via</i> a [3,3]-rearrangement, which can be further trapped by external nucleophiles to give mono-difluoroalkylate ...[more]

PMID: 34122809

Similar Datasets

Ni-Catalyzed Borylation of Aryl Sulfoxides.

Project description:A nickel/N-heterocyclic carbene (NHC) catalytic system has been developed for the borylation of aryl sulfoxides with B2 (neop)2 (neop=neopentyl glycolato). A wide range of aryl sulfoxides with different electronic and steric properties were converted into the corresponding arylboronic esters in good yields. The regioselective borylation of unsymmetric diaryl sulfoxides was also feasible leading to borylation of the sterically less encumbered aryl substituent. Competition experiments demonstrated that an electron-deficient aryl moiety reacts preferentially. The origin of the selectivity in the Ni-catalyzed borylation of electronically biased unsymmetrical diaryl sulfoxide lies in the oxidative addition step of the catalytic cycle, as oxidative addition of methoxyphenyl 4-(trifluoromethyl)phenyl sulfoxide to the Ni(0) complex occurs selectively to give the structurally characterized complex trans-[Ni(ICy)2 (4-CF3 -C6 H4 ){(SO)-4-MeO-C6 H4 }] 4. For complex 5, the isomer trans-[Ni(ICy)2 (C6 H5 )(OSC6 H5 )] 5-I was structurally characterized in which the phenyl sulfinyl ligand is bound via the oxygen atom to nickel. In solution, the complex trans-[Ni(ICy)2 (C6 H5 )(OSC6 H5 )] 5-I is in equilibrium with the S-bonded isomer trans-[Ni(ICy)2 (C6 H5 )(SOC6 H5 )] 5, as shown by NMR spectroscopy. DFT calculations reveal that these isomers are separated by a mere 0.3 kJ/mol (M06/def2-TZVP-level of theory) and connected via a transition state trans-[Ni(ICy)2 (C6 H5 )(η2 -{SO}-C6 H5 )], which lies only 10.8 kcal/mol above 5.

| S-EPMC8252015 | biostudies-literature

Dearomatization reactions of aryl-substituted silaaziridines.

Project description:Silaaziridines with an aryl group on either the carbon or the nitrogen atom undergo dearomatization reactions upon treatment with benzaldehyde. The reactions form new bonds ortho to the nitrogen substituents with high diastereoselectivity. These dearomatization processes likely are driven by relief of the considerable ring strain of the silaaziridine.

| S-EPMC2664301 | biostudies-literature

Rapid Photoracemization of Chiral Alkyl Aryl Sulfoxides.

Project description:The photoracemization of chiral alkyl aryl sulfoxides with a photosensitizer has not been sufficiently investigated thus far. Therefore, in this study, a rapid photoracemization reaction of enantiopure alkyl aryl sulfoxides using 1 mol % 2,4,6-triphenylpyrylium tetrafluoroborate (TPT+) was developed. Various substitution patterns were tolerated and every racemization reaction proceeded extremely fast (k2 = 1.77 × 104-6.08 × 101 M-1 s-1, t1/2 = 0.4-114 s). Some chiral sulfoxides with easily oxidizable functional groups are not appropriate for this photoisomerization. The electrochemical potentials of the functional groups, determined via cyclic voltammetry, are useful for predicting the reactive or nonreactive groups in this photoracemization reaction. A theoretical study was conducted to clarify the sp2-like nature of S of the sulfoxide cation radical, which makes photoracemization easier.

| S-EPMC8650104 | biostudies-literature

Dearomative Mislow-Braverman-Evans Rearrangement of Aryl Sulfoxides.

Project description:The Mislow-Braverman-Evans rearrangement, the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenate esters, finds widespread applications in organic synthesis and medicinal chemistry. However, the products of this powerful strategy have primarily been limited to derivatives of allylic alcohols. In contrast, access to structurally similar benzylic alcohols has not yet been established. Described herein is an unprecedented dearomative Mislow-Braverman-Evans rearrangement of aryl sulfoxides to afford benzylic alcohols. A variety of heteroaryl sulfoxides as well as α-naphthyl sulfoxides could be tolerated, and a diverse range of primary, secondary, and tertiary alcohols possessing either alkyl or aryl substituents can be prepared by our protocol with broad functional group tolerance. A patented bioactive molecule could be prepared using our protocol as the key step with exclusive diastereoselectivity, highlighting its potential utility in organic synthesis. Key to the success of the transformation is the dearomative tautomerization to shift the reactive alkene to the exocyclic position enabled by the reversible deprotonation of the benzylic C-H bond, setting the stage for the subsequent [2,3]-sigmatropic rearrangement. Density functional theory (DFT) calculations reveal that protonation of the α-carbon of the sulfoxide is the stereocontrolling step, generating the intermediate that undergoes [2,3]-sigmatropic rearrangement. The full reaction profile is outlined, showing the reversible nature of each step, which causes the observed erosion of the enantiopurity.

| S-EPMC11863165 | biostudies-literature

From perfluoroalkyl aryl sulfoxides to <i>ortho</i> thioethers.

Project description:Access to original ortho thioether derivatives was achieved through a [3,3]-rearrangement in a one-pot two-step protocol. Several aryl-SCF3 compounds are reported by variation of the nitrile or of the trifluoroalkyl sulfoxide starting material. The variation of the perfluoroalkyl chain was also possible.

| S-EPMC11346307 | biostudies-literature

Dearomative di- and trifunctionalization of aryl sulfoxides via [5,5]-rearrangement.

Project description:Aromatic [5,5]-rearrangement can in principle be an ideal protocol to access dearomative compounds. However, the lack of competent [5,5]-rearrangement impedes the advance of the protocol. In this Article, we showcase the power of [5,5]-rearrangement recently developed in our laboratory for constructing an intriguing dearomative sulfonium specie which features versatile and unique reactivities to perform nucleophilic 1,2- and 1,4-addition and cyclization, thus achieving dearomative di- and trifunctionalization of easily accessible aryl sulfoxides. Impressively, the dearomatization products can be readily converted to sulfur-removed cyclohexenones, naphthalenones, bicyclic cyclohexadienones, and multi-substituted benzenes. Mechanistic studies shed light on the key intermediates and the remarkable chemo-, regio- and stereoselectivities of the reactions.

| S-EPMC9372148 | biostudies-literature

Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides.

Project description:The selective incorporation of gem-difluoroalkyl groups into biologically active molecules has long been used as an efficient strategy for drug design and discovery. However, the catalytic C(sp3)-CF2 bond-forming cross-coupling reaction for selective incorporation of difluoromethylene group into diverse alkyl chains, especially more sterically demanding secondary and tertiary functionalized alkanes, still remains as a major challenge. Herein, we describe a cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides, which exhibited high efficiency, broad scope and mild conditions. The synthetic utility of this method is demonstrated by late-stage difluoroalkylation of donepezil, a well-known acetylcholinesterase inhibitor used to treat the Alzheimer's disease. Preliminary mechanistic investigations indicate that a difluoroalkyl radical is involved in a Co(I)/Co(III) catalytic cycle. This cobalt-catalyzed fluoroalkylation thus offers insights into an efficient way for the synthesis of fluoroalkylated bioactive molecules for drug discovery.

| S-EPMC6251884 | biostudies-literature

Highly stereoselective nickel-catalyzed difluoroalkylation of aryl ketones to tetrasubstituted monofluoroalkenes and quaternary alkyl difluorides.

Project description:A nickel-catalyzed difluoroalkylation of α-C-H bonds of aryl ketones to furnish highly stereo-defined tetrasubstituted monofluoroalkenes or quaternary alkyl difluorides from secondary or tertiary ketones, respectively, has been established. Mechanistic investigations indicated that these C-H fluoroalkylations proceed via a Ni(i)/Ni(iii) catalytic cycle. An obvious fluorine effect was observed in the reaction, and this reaction has demonstrated high stereoselectivity, mild conditions, and broad substrate scopes, thus enabling the late-stage fluoroalkylation of bioactive molecules. This method offers a solution for expedient construction of monofluoroalkenes from readily available materials, and provides an efficient approach for the synthesis of bioactive fluorinated compounds for the discovery of lead compounds in medicinal chemistry.

| S-EPMC7003883 | biostudies-literature

Dual-gated mono-bilayer graphene junctions.

Project description:A lateral junction with an atomically sharp interface is extensively studied in fundamental research and plays a key role in the development of electronics, photonics and optoelectronics. Here, we demonstrate an electrically tunable lateral junction at atomically sharp interfaces between dual-gated mono- and bilayer graphene. The transport properties of the mono-bilayer graphene interface are systematically investigated with I ds-V ds curves and transfer curves, which are measured with bias voltage V ds applied in opposite directions across the asymmetric mono-bilayer interface. Nearly 30% difference between the output I ds-V ds curves of graphene channels measured at opposite V ds directions is observed. Furthermore, the measured transfer curves confirm that the conductance difference of graphene channels greatly depends on the doping level, which is determined by dual-gating. The V ds direction dependent conductance difference indicates the existence of a gate tunable junction in the mono-bilayer graphene channel, due to different band structures of monolayer graphene with zero bandgap and bilayer graphene with a bandgap opened by dual-gating. Simulation of the I ds-V ds curves based on a new numerical model validates the gate tunable junction at the mono-bilayer graphene interface from another point of view. The dual-gated mono-bilayer graphene junction and new protocol for I ds-V ds curve simulation pave a possible way for functional applications of graphene in next-generation electronics.

| S-EPMC9418045 | biostudies-literature

Methionine sulfoxides on prion protein Helix-3 switch on the alpha-fold destabilization required for conversion.

Project description:BackgroundThe conversion of the cellular prion protein (PrP(C)) into the infectious form (PrP(Sc)) is the key event in prion induced neurodegenerations. This process is believed to involve a multi-step conformational transition from an alpha-helical (PrP(C)) form to a beta-sheet-rich (PrP(Sc)) state. In addition to the conformational difference, PrP(Sc) exhibits as covalent signature the sulfoxidation of M213. To investigate whether such modification may play a role in the misfolding process we have studied the impact of methionine oxidation on the dynamics and energetics of the HuPrP(125-229) alpha-fold.Methodology/principal findingsUsing molecular dynamics simulation, essential dynamics, correlated motions and signal propagation analysis, we have found that substitution of the sulfur atom of M213 by a sulfoxide group impacts on the stability of the native state increasing the flexibility of regions preceding the site of the modification and perturbing the network of stabilizing interactions. Together, these changes favor the population of alternative states which maybe essential in the productive pathway of the pathogenic conversion. These changes are also observed when the sulfoxidation is placed at M206 and at both, M206 and M213.Conclusions/significanceOur results suggest that the sulfoxidation of Helix-3 methionines might be the switch for triggering the initial alpha-fold destabilization required for the productive pathogenic conversion.

| S-EPMC2628723 | 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