Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

DoE-Driven Development of an Organocatalytic Enantioselective Addition of Acetaldehyde to Nitrostyrenes in Water.

ABSTRACT: The development of an enantioselective enamine-catalysed addition of masked acetaldehyde to nitroalkenes via a rational approach helped to move away from the use of chloroform. The presented research allows the use of water as a reaction medium, therefore improving the industrial relevance of a protocol to access very important pharmaceutical intermediates. Critical to the success is the use of chemometrics-assisted 'Design of Experiments' (DoE) optimisation during the development of the presented new synthetic approach, which allows to investigate the chemical space in a rational way.

SUBMITTER: Nori V

PROVIDER: S-EPMC9313880 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

DoE-Driven Development of an Organocatalytic Enantioselective Addition of Acetaldehyde to Nitrostyrenes in Water.

Nori Valeria V Sinibaldi Arianna A Giorgianni Giuliana G Pesciaioli Fabio F Di Donato Francesca F Cocco Emanuele E Biancolillo Alessandra A Landa Aitor A Carlone Armando A

Chemistry (Weinheim an der Bergstrasse, Germany) 20220322 24

The development of an enantioselective enamine-catalysed addition of masked acetaldehyde to nitroalkenes via a rational approach helped to move away from the use of chloroform. The presented research allows the use of water as a reaction medium, therefore improving the industrial relevance of a protocol to access very important pharmaceutical intermediates. Critical to the success is the use of chemometrics-assisted 'Design of Experiments' (DoE) optimisation during the development of the present ...[more]

PMID: 35230722

Similar Datasets

Light-Driven Enantioselective Organocatalytic ?-Benzylation of Enals.

Project description:A photochemical organocatalytic strategy for the direct enantioselective ?-benzylation of ?,?-unsaturated aldehydes is reported. The chemistry capitalizes upon the light-triggered enolization of 2-alkyl-benzophenones to afford hydroxy-o-quinodinomethanes. These fleeting intermediates are stereoselectively intercepted by chiral iminium ions, transiently formed upon condensation of a secondary amine catalyst with enals. Density functional theory (DFT) studies provided an explanation for why the reaction proceeds through an unconventional Michael-type addition manifold, instead of a classical cycloaddition mechanism and subsequent ring-opening.

| S-EPMC5412672 | biostudies-literature

Bioinspired total synthesis of katsumadain A by organocatalytic enantioselective 1,4-conjugate addition.

Project description:Katsumadain A, a naturally occurring in?uenza virus neuraminidase (NA) inhibitor, was synthesized by using a bioinspired, organocatalytic enantioselective 1,4-conjugate addition of styryl-2-pyranone with cinnamaldehyde, followed by a tandem Horner-Wadsworth-Emmons/oxa Michael addition.

| S-EPMC3740603 | biostudies-literature

Photochemical Organocatalytic Regio- and Enantioselective Conjugate Addition of Allyl Groups to Enals.

Project description:We report the first catalytic enantioselective conjugate addition of allyl groups to α,β-unsaturated aldehydes. The chemistry exploits the visible-light-excitation of chiral iminium ions to activate allyl silanes towards the formation of allylic radicals, which are then intercepted stereoselectively. The underlying radical mechanism of this process overcomes the poor regio- and chemoselectivity that traditionally affects the conjugate allylation of enals proceeding via polar pathways. We also demonstrate how this organocatalytic strategy could selectively install a valuable prenyl fragment at the β-carbon of enals.

| S-EPMC9298816 | biostudies-literature

Enantioselective Aldol Addition of Acetaldehyde to Aromatic Aldehydes Catalyzed by Proline-Based Carboligases.

Project description:Aromatic ?-hydroxyaldehydes, 1,3-diols, and ?,?-unsaturated aldehydes are valuable precursors to biologically active natural products and drug molecules. Herein we report the biocatalytic aldol condensation of acetaldehyde with various aromatic aldehydes to give a number of aromatic ?,?-unsaturated aldehydes using a previously engineered variant of 4-oxalocrotonate tautomerase [4-OT(M45T/F50A)] as carboligase. Moreover, an efficient one-pot two-step chemoenzymatic route toward chiral aromatic 1,3-diols has been developed. This one-pot chemoenzymatic strategy successfully combined a highly enantioselective aldol addition step catalyzed by a proline-based carboligase [4-OT(M45T/F50A) or TAUT015] with a chemical reduction step to convert enzymatically prepared aromatic ?-hydroxyaldehydes into the corresponding 1,3-diols with high optical purity (e.r. up to >99:1) and in good isolated yield (51-92%). These developed (chemo)enzymatic methodologies offer alternative synthetic choices to prepare a variety of important drug precursors.

| S-EPMC7045556 | biostudies-literature

Organocatalytic enantioselective dearomatization of thiophenes by 1,10-conjugate addition of indole imine methides.

Project description:Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. This work reports an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition. By suitable stabilization of the thiophenyl carbocation with an indole motif in the form of indole imine methide, excellent remote chemo-, regio-, and stereocontrol in the nucleophilic addition can be achieved with chiral phosphoric acid catalysis under mild conditions. This protocol can be successfully extended to the asymmetric dearomatization of other heteroarenes including selenophenes and furans. Control experiments and DFT calculations demonstrate a possible pathway in which hydrogen bonding plays an important role in selectivity control.

| S-EPMC8361129 | biostudies-literature

Enantioselective organocatalytic Michael addition of aldehydes to nitroethylene: efficient access to gamma2-amino acids.

Project description:Enantioselective organocatalytic Michael addition of aldehydes to nitroethylene catalyzed by (S)-diphenylprolinol silyl ether provides beta-substituted-delta-nitroalcohols in nearly optically pure form (96-99% ee). The Michael adducts bear a single substituent adjacent to the carbonyl and can be efficiently converted to protected gamma2-amino acids, which are essential for the systematic conformational studies of gamma-peptide foldamers.

| S-EPMC3429127 | biostudies-literature

Enantioselective organocatalytic construction of pyrroloindolines by a cascade addition-cyclization strategy: synthesis of (-)-flustramine B.

Project description:Pyrroloindoline and bispyrroloindoline are a subclass of alkaloid structural motifs that commonly exhibit biological activity. An enantioselective organocatalytic approach to the synthesis of pyrroloindoline architecture is described. The addition-cyclization of tryptamines with alpha,beta-unsaturated aldehydes in the presence of imidazolidinone catalysts 1 and 8 provides pyrroloindoline adducts in high yield and excellent enantioselectivities. This transformation is successful for a wide range of tryptamine and alpha,beta-unsaturated aldehyde substrates. This amine-catalyzed sequence has been extended to the enantioselective construction of furanoindoline frameworks. Application of this pyrroloindoline-forming reaction to natural product synthesis has been accomplished in the context of the enantioselective synthesis of (-)-flustramine B.

| S-EPMC397409 | biostudies-literature

Organocatalytic enantioselective olefin aminofluorination.

Project description:Chiral beta-fluoroamines are increasingly prevalent in medicinal compounds, but there are few efficient methods to access them from achiral starting materials. To address this, a multicomponent organocascade reaction was developed in which chiral alpha-fluoro-beta-amino aldehydes were generated in a single flask from achiral alpha,beta-unsaturated aldehydes (2), using catalyst 12a. Conversions up to 85%, dr's up to 98:2 and ee's up to 99% of the corresponding alcohol (9) were achieved in this reaction.

| S-EPMC2946328 | biostudies-literature

Regio- and enantioselective synthesis of acyclic quaternary carbons via organocatalytic addition of organoborates to (Z)-Enediketones.

Project description:The chemical synthesis of molecules with closely packed atoms having their bond coordination saturated is a challenge to synthetic chemists, especially when three-dimensional control is required. The organocatalyzed asymmetric synthesis of acyclic alkenylated, alkynylated and heteroarylated quaternary carbon stereocenters via 1,4-conjugate addition is here catalyzed by 3,3´-bisperfluorotoluyl-BINOL. The highly useful products (31 examples) are produced in up to 99% yield and 97:3 er using enediketone substrates and potassium trifluoroorganoborate nucleophiles. In addition, mechanistic experiments show that the (Z)-isomer is the reactive form, ketone rotation at the site of bond formation is needed for enantioselectivity, and quaternary carbon formation is favored over tertiary. Density functional theory-based calculations show that reactivity and selectivity depend on a key n→π* donation by the unbound ketone's oxygen lone pair to the boronate-coordinated ketone in a 5-exo-trig cyclic ouroboros transition state. Transformations of the conjugate addition products to key quaternary carbon-bearing synthetic building blocks proceed in good yield.

| S-EPMC10787796 | biostudies-literature

Streptavidin-Hosted Organocatalytic Aldol Addition.

Project description:In this report, the streptavidin-biotin technology was applied to enable organocatalytic aldol addition. By attaching pyrrolidine to the valeric motif of biotin and introducing it to streptavidin (Sav), a protein-based organocatalytic system was created, and the aldol addition of acetone with p-nitrobenzaldehyde was tested. The conversion of substrate to product can be as high as 93%. Although the observed enantioselectivity was only moderate (33:67 er), further protein engineering efforts can be included to improve the selectivity. These results have proven the concept that Sav can be used to host stereoselective aldol addition.

| S-EPMC7287710 | 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