Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regio- and Enantioselective Bromocyclization of Difluoroalkenes as a Strategy to Access Tetrasubstituted Difluoromethylene-Containing Stereocenters.

ABSTRACT: Difluoromethylene-containing compounds have attracted substantial research interest over the past decades for their ability to mimic biological functions of traditional functional groups while providing a wide variety of pharmacological benefits bestowed by the C-F bond. We report a novel strategy to access RCF₂Br-containing heterocycles by regio- and enantioselective bromocyclization of difluoroalkenes enabled by chiral anion phase-transfer catalysis. The utility of this methodology was highlighted through a synthesis of an analogue of efavirenz, a drug used for treating HIV. Additionally, the synthetic versatility of the CF₂Br intermediates was showcased through functionalization to a variety of enantioenriched α,α-difluoromethylene-containing products.

SUBMITTER: Miller E

PROVIDER: S-EPMC7508160 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Regio- and Enantioselective Bromocyclization of Difluoroalkenes as a Strategy to Access Tetrasubstituted Difluoromethylene-Containing Stereocenters.

Miller Edward E Kim Suhong S Gibson Katarina K Derrick Jeffrey S JS Toste F Dean FD

Journal of the American Chemical Society 20200430 19

Difluoromethylene-containing compounds have attracted substantial research interest over the past decades for their ability to mimic biological functions of traditional functional groups while providing a wide variety of pharmacological benefits bestowed by the C-F bond. We report a novel strategy to access RCF<sub>2</sub>Br-containing heterocycles by regio- and enantioselective bromocyclization of difluoroalkenes enabled by chiral anion phase-transfer catalysis. The utility of this methodology ...[more]

PMID: 32352775

Similar Datasets

Enantioselective Narasaka-Heck cyclizations: synthesis of tetrasubstituted nitrogen-bearing stereocenters.

Project description:The first examples of highly enantioselective Narasaka-Heck cyclizations are described. A SPINOL-derived P,N-ligand system enables Pd-catalyzed 5-exo cyclization of a range of oxime esters with sterically diverse trisubstituted alkenes to generate dihydropyrroles containing tetrasubstituted nitrogen-bearing stereocenters in 56 to 86% yield and 90 : 10 to 95 : 5 e.r. These processes are rare examples of reactions that proceed via enantioselective migratory insertion of alkenes into Pd-N bonds, and the first where trisubstituted alkenes are used to generate tetrasubstituted stereocenters with high enantioselectivity.

| S-EPMC5390761 | biostudies-literature

Pd-catalyzed enantioselective access to hydrocarbazolones containing contiguous quaternary and tertiary stereocenters.

Project description:The hydrocarbazole scaffold represents the core structure of numerous monoterpenoid indole alkaloids. The development of catalytic methods that provide efficient access to enantioenriched hydrocarbazole derivatives is central for the synthesis of these bioactive alkaloids. We report here a palladium-catalyzed enantioselective formal 5-endo arylative cyclization of enaminones, facilitating the construction of hexahydrocarbazol-4-ones containing contiguous C4a-quaternary and C9a-tertiary stereocenters with high enantioselectivities (86.5 : 13.5-99 : 1 er) and diastereoselectivities (>20 : 1 dr). Notably, enaminone substrates bearing an α-allyl group undertake an arylation/Cope rearrangement cascade, offering a unique route to C1-substituted tetrahydrocarbazol-4-ones. A stereodivergent approach to all four stereoisomers of the quaternary/tertiary chiral center set is achieved by combining the catalyst with Z/E allyl substituents, yielding excellent enantioselectivity. The N-methyl group of the hydrocarbazolone products is readily removed under oxidation conditions. The utility of the method is demonstrated by the access to a variety of hydrocarbazole derivatives and the efficient syntheses of four Aspidosperma alkaloids/analogs, (+)-N-methyl aspidospermidine, (+)-C20-epi-N-methyl aspidospermidine, (+)-N-methyl fendleridine, and (+)-N-methyl limaspermidine from a hexahydrocarbazol-4-one in 3-5 steps.

| S-EPMC11912222 | biostudies-literature

Enantioselective Copper(I)-Catalyzed Alkynylation of Oxocarbenium Ions to Set Diaryl Tetrasubstituted Stereocenters.

Project description:An enantioselective, copper(I)-catalyzed addition of terminal alkynes to isochroman ketals to set diaryl, tetrasubstituted stereocenters has been developed. The success of this reaction relies on identification of a Cu/PyBox catalyst capable of distinguishing the faces of the diaryl-substituted oxocarbenium ion. This challenging transformation enables efficient conversion of readily available, racemic ketals into high-value enantioenriched isochroman products with fully substituted stereogenic centers. High yields and enantiomeric excesses are observed for various isochroman ketals and an array of alkynes.

| S-EPMC4819992 | biostudies-literature

Enantioselective, Copper-Catalyzed Alkynylation of Ketimines To Deliver Isoquinolines with α-Diaryl Tetrasubstituted Stereocenters.

Project description:An enantioselective, copper-catalyzed alkynylation of cyclic α,α-diaryl ketiminium ions has been developed to deliver isoquinoline products with diaryl, tetrasubstituted stereocenters. The success of this reaction relied on identification of Ph-PyBox as the optimal ligand, i-Pr2NEt as the base, and CHCl3 as the solvent. A broad scope and functional group tolerance were observed. Notably, the use of both aryl and silyl acetylenes results in high yields and enantioselectivities. Mechanistic experiments are consistent with a dimeric or higher order catalyst.

| S-EPMC5161116 | biostudies-literature

Direct catalytic enantioselective amination of ketones for the formation of tri- and tetrasubstituted stereocenters.

Project description:Herein, we report a Zn-ProPhenol catalyzed direct asymmetric amination reaction of unactivated aryl and vinyl ketones using di-tert-butyl azodicarboxylate as a cheap and practical electrophilic nitrogen source. Importantly, this methodology works with both α-branched and unbranched ketones for the construction of tri- and tetrasubstituted N-containing stereocenters. The reaction can be run at gram-scale with low catalyst loadings and features a recoverable and reusable ligand. Finally, the enantioenriched hydrazine products can be readily converted into versatile building blocks such as α-amino carbonyl compounds and β-amino alcohols.

| S-EPMC5897889 | biostudies-literature

Access to enantioenriched compounds bearing challenging tetrasubstituted stereocenters via kinetic resolution of auxiliary adjacent alcohols.

Project description:Contemporary asymmetric catalysis faces huge challenges when prochiral substrates bear electronically and sterically unbiased substituents and when substrates show low reactivities. One of the inherent limitations of chiral catalysts and ligands is their incapability in recognizing prochiral substrates bearing similar groups. This has rendered many enantiopure substances bearing several similar substituents inaccessible. Here we report the rationale, scope, and applications of the strategy of kinetic resolution of auxiliary adjacent alcohols (KRA*) that can be used to solve the above troubles. Using this method, a large variety of optically enriched tertiary alcohols, epoxides, esters, ketones, hydroxy ketones, epoxy ketones, β-ketoesters, and tetrasubstituted methane analogs with two, three, and four spatially and electronically similar groups can be readily obtained (totally 96 examples). At the current stage, the strategy serves as the optimal solution that can complement the inability caused by direct asymmetric catalysis in getting chiral molecules with challenging fully substituted stereocenters.

| S-EPMC8213810 | biostudies-literature

Catalytic Asymmetric Mannich Reaction of α-Fluoronitriles with Ketimines: Enantioselective and Diastereodivergent Construction of Vicinal Tetrasubstituted Stereocenters.

Project description:Diastereodivergent and enantioselective conversion of isatin ketimines to α-fluoro-β-aminonitriles with vicinal tetrasubstituted stereocenters is achieved by a chiral copper complex/guanidine base catalyzed Mannich reaction with proper choice of the bisphosphine ligand. The reaction is broad in scope, scalable, and provides efficient access to a series of 3-aminoindolinones exhibiting a quaternary carbon-fluorine stereocenter with high yields and stereoselectivities. Selective transformations of the Mannich reaction products into multifunctional 3-aminooxindoles without erosion of enantiomeric and diastereomeric purity highlight the synthetic utility.

| S-EPMC6449049 | biostudies-literature

Regio- and enantioselective remote hydroarylation using a ligand-relay strategy.

Project description:The design of a single complicated chiral ligand to well-promote each step of an asymmetric cascade reaction is sometimes a formidable challenge in transition metal catalysis. In this work, a highly regio- and enantioselective Ni-catalysed migratory hydroarylation relay process has been achieved with the combination of two simple ligands, one which accomplishes chain-walking and the other causing asymmetric arylation. This formal asymmetric C(sp3)-H arylation provides direct access to a wide range of structurally diverse chiral 1,1-diarylalkanes, a structural unit found in a number of bioactive molecules. The value of this strategy was further demonstrated by the Ni-catalysed migratory asymmetric 1,3-arylboration.

| S-EPMC9072428 | biostudies-literature

Palladium-Catalyzed Enantioselective Redox-Relay Heck Alkynylation of Alkenols To Access Propargylic Stereocenters.

Project description:An enantioselective redox-relay Heck alkynylation of di- and trisubstituted alkenols to construct propargylic stereocenters is disclosed using a new pyridine oxazoline ligand. This strategy allows direct access to chiral β-alkynyl carbonyl compounds employing allylic alcohol substrates in contrast to more traditional conjugate addition methods.

| S-EPMC5528850 | biostudies-literature

Regio- and Stereoselective 1,2-Oxyhalogenation of Non-Conjugated Alkynes via Directed Nucleopalladation: Catalytic Access to Tetrasubstituted Alkenes.

Project description:A catalytic 1,2-oxyhalogenation method that converts non-conjugated internal alkynes into tetrasubstituted alkenes with high regio- and stereoselectivity is described. Mechanistically, the reaction involves a PdII /PdIV catalytic cycle that begins with a directed oxypalladation step. The origin of regioselectivity is the preference for formation of a six-membered palladacycle intermediate, which is facilitated by an N,N-bidentate 2-(pyridin-2-yl)isopropyl (PIP) amide directing group. Selectivity for C(alkenyl)-X versus -N (X=halide) reductive elimination from the PdIV center depends on the identity of the halide anion; bromide and iodide engage in C(alkenyl)-X formation, while intramolecular C(alkenyl)-N reductive elimination occurs with chloride to furnish a lactam product. DFT calculations shed light on the origins of this phenomenon.

| S-EPMC9588632 | 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