Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An enantioselective synthesis of ?-alkylated pyrroles via cooperative isothiourea/palladium catalysis.

ABSTRACT: Herein we describe the direct enantioselective Lewis base/Pd catalysed ?-allylation of pyrrole acetic acid esters. This provides high isolated yields of highly enantioenriched products and exhibits broad reaction scope with respect to both reaction partners. The products can be readily elaborated in a manner which points towards potential applications in target directed synthesis.

SUBMITTER: Rush Scaggs W

PROVIDER: S-EPMC6499370 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

An enantioselective synthesis of α-alkylated pyrroles via cooperative isothiourea/palladium catalysis.

Rush Scaggs W W Scaggs Toya D TD Snaddon Thomas N TN

Organic & biomolecular chemistry 20190201 7

Herein we describe the direct enantioselective Lewis base/Pd catalysed α-allylation of pyrrole acetic acid esters. This provides high isolated yields of highly enantioenriched products and exhibits broad reaction scope with respect to both reaction partners. The products can be readily elaborated in a manner which points towards potential applications in target directed synthesis. ...[more]

PMID: 30483696

Similar Datasets

Tandem Palladium and Isothiourea Relay Catalysis: Enantioselective Synthesis of α-Amino Acid Derivatives via Allylic Amination and [2,3]-Sigmatropic Rearrangement.

Project description:A tandem relay catalytic protocol using both Pd and isothiourea catalysis has been developed for the enantioselective synthesis of α-amino acid derivatives containing two stereogenic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succinimide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by the isothiourea benzotetramisole forms syn-α-amino acid derivatives with high diastereo- and enantioselectivity. This methodology is most effective using 4-nitrophenylglycine esters and tolerates a variety of substituted cinnamic and styrenyl allylic ethyl phosphates. The use of challenging unsymmetrical N-allyl-N-methylglycine esters is also tolerated under the catalytic relay conditions without compromising stereoselectivity.

| S-EPMC5579534 | biostudies-literature

Enantioselective Synthesis of α-Aryl-β<sup>2</sup> -Amino-Esters by Cooperative Isothiourea and Bronsted Acid Catalysis.

Project description:The synthesis of α-aryl-β2 -amino esters through enantioselective aminomethylation of an arylacetic acid ester in high yields and enantioselectivity via cooperative isothiourea and Brønsted acid catalysis is demonstrated. The scope and limitations of this process are explored (25 examples, up to 94 % yield and 96:4 er), with applications to the synthesis of (S)-Venlafaxine⋅HCl and (S)-Nakinadine B. Mechanistic studies are consistent with a C(1)-ammonium enolate pathway being followed rather than an alternative dynamic kinetic resolution process. Control studies indicate that (i) a linear effect between catalyst and product er is observed; (ii) an acyl ammonium ion can be used as a precatalyst; (iii) reversible isothiourea addition to an in situ generated iminium ion leads to an off-cycle intermediate that can be used as a productive precatalyst.

| S-EPMC8252622 | biostudies-literature

Cooperative Palladium/Isothiourea Catalyzed Enantioselective Formal (3+2) Cycloaddition of Vinylcyclopropanes and α,β-Unsaturated Esters.

Project description:A protocol for the enantioselective synthesis of substituted vinylcyclopentanes has been realised using cooperative palladium and isothiourea catalysis. Treatment of vinylcyclopropanes with Pd(PPh3 )4 generates a zwitterionic π-allyl palladium intermediate that intercepts a catalytically generated α,β-unsaturated acyl ammonium species prepared from the corresponding α,β-unsaturated para-nitrophenyl ester and the isothiourea (R)-BTM. Intermolecular formal (3+2) cycloaddition between these reactive intermediates generates functionalised cyclopentanes in generally good yields and excellent diastereo- and enantiocontrol (up to >95 : 5 dr, 97 : 3 er), with the use of LiCl as an additive proving essential for optimal stereocontrol. To the best of our knowledge a dual transition metal/organocatalytic process involving α,β-unsaturated acyl ammonium intermediates has not been demonstrated previously.

| S-EPMC9324207 | biostudies-literature

Enantioselective Synthesis of 3,5,6-Substituted Dihydropyranones and Dihydropyridinones using Isothiourea-Mediated Catalysis.

Project description:The scope of dihydropyranone and dihydropyridinone products accessible by isothiourea-catalyzed processes has been expanded and explored through the use of 2-N-tosyliminoacrylates and 2-aroylacrylates in a Michael addition-lactonization/lactamization cascade reaction. Notably, to ensure reproducibility it is essential to use homoanhydrides as ammonium enolate precursors with 2-aroyl acrylates, while carboxylic acids can be used with 2-N-tosyliminoacrylates, delivering a range of 3,5,6-substituted dihydropyranones and dihydropyridinones with high enantioselectivity (typically >90 % ee). The derivatization of the heterocyclic core of a 3,5,6-substituted dihydropyranone through hydrogenation is also reported.

| S-EPMC4755233 | biostudies-literature

Exploring the Scope of Tandem Palladium and Isothiourea Relay Catalysis for the Synthesis of α-Amino Acid Derivatives.

Project description:The scope and limitations of a tandem N-allylation/[2,3]-rearrangement protocol are investigated through the incorporation of a variety of functional groups within an allylic phosphate precursor. This method uses readily accessible N,N-dimethylglycine aryl esters and functionalized allylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequent enantioselective [2,3]-sigmatropic rearrangement, promoted by the chiral isothiourea tetramisole, generates α-amino acid derivatives with two contiguous stereocenters. The incorporation of electron-withdrawing ester and amide groups gave the best results, furnishing the desired products in moderate to good yields (29-70%), with low diastereocontrol (typically 60:40 dr) but high enantioselectivity (up to 90:10 er). These results indicate that substrate-catalyst interactions in the proposed transition state are sensitive to the substitution pattern of the substrates.

| S-EPMC7287902 | biostudies-literature

Enantioselective conjugate additions of α-amino radicals via cooperative photoredox and Lewis acid catalysis.

Project description:We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates.

| S-EPMC4547529 | biostudies-literature

Traversing Steric Limitations by Cooperative Lewis Base/Palladium Catalysis: An Enantioselective Synthesis of ?-Branched Esters Using 2-Substituted Allyl Electrophiles.

Project description:Cooperative catalysis enables the direct enantioselective ?-allylation of linear prochiral esters with 2-substituted allyl electrophiles. Critical to the successful development of the method was the recognition that metal-centered reactivity and the source of enantiocontrol are independent. This feature is unique to simultaneous catalysis events and permits logical tuning of the supporting ligands without compromising enantioselectivity.

| S-EPMC6038818 | biostudies-literature

Distal Alkenyl C-H Functionalization via the Palladium/Norbornene Cooperative Catalysis.

Project description:A distal-selective alkenyl C-H arylation method is reported through a directed palladium/norbornene (Pd/NBE) cooperative catalysis. The key is to use an appropriate combination of the directing group and the NBE cocatalyst. A range of acyclic and cyclic cis-olefins are suitable substrates, and the reaction is operated under air with excellent site-selectivity. Preliminary mechanistic studies are consistent with the proposed Pd/NBE-catalyzed C-H activation instead of the Heck pathway. Initial success on distal alkylation has also been achieved using MeI and methyl bromoacetate as electrophiles.

| S-EPMC7075342 | biostudies-literature

Stereodivergent synthesis of α-fluoro α-azaaryl γ-butyrolactones <i>via</i> cooperative copper and iridium catalysis.

Project description:The development of stereodivergent synthetic methods to access all four stereoisomers of biologically important α-fluoro γ-butyrolactones containing vicinal stereocenters is of great importance and poses a formidable challenge owing to ring strain and steric hindrance. Herein, a novel asymmetric [3+2] annulation of α-fluoro α-azaaryl acetates with vinylethylene carbonate was successfully developed through Cu/Ir-catalyzed cascade allylic alkylation/lactonization, affording a variety of enantioenriched α-fluoro γ-butyrolactones bearing vicinal stereogenic centers with high reaction efficiency and excellent levels of both stereoselectivity and regioselectivity (up to 98% yield, generally >20:1 dr and >99% ee). Notably, all four stereoisomers of these pharmaceutically valuable molecules could be accessed individually via simple permutations of two enantiomeric catalysts. In addition, other azaaryl acetates bearing α-methyl, α-chlorine or α-phenyl group were tolerated well in this transformation. Reaction mechanistic investigations were conducted to explore the process of this bimetallic catalysis based on the results of reaction intermediates, isotopic labelling experiments, and kinetic studies.

| S-EPMC11197661 | biostudies-literature

Sulfenamide-enabled ortho thiolation of aryl iodides via palladium/norbornene cooperative catalysis.

Project description:Poly-substituted aromatic sulfur compounds are widely found in pharmaceuticals, agrochemicals and organic materials. However, the position that a sulfur moiety can be introduced to is largely restricted to a pre-functionalized site; otherwise, use of electronically biased substrates or auxiliary groups that direct catalysis is required. Here we report a general ortho thiolation of common aryl and heteroaryl iodides via palladium-norbornene cooperative catalysis. Using this approach, an aryl or alky sulfur moiety can be site-selectively introduced at the arene ortho position without using sterically or electronically biased substrates. The arene ipso functionalization is simultaneously achieved through Heck, Suzuki or Sonogashira termination. The reaction is enabled by a unique class of electrophiles in palladium-norbornene cooperative catalysis, which are sulfenamides derived from seven-membered lactams. The broad substrates scope and high chemoselectivity could make this method attractive for synthesis of complex sulfur-containing aromatic compounds.

| S-EPMC6685968 | 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