Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Managing the retro-pathway in direct catalytic asymmetric aldol reactions of thioamides.

ABSTRACT: Thioamides are the preferred pronucleophiles for direct catalytic asymmetric aldol reactions in the context of soft Lewis acid/hard Brønsted base cooperative catalysis. In-depth investigation of this proton-transfer catalysis, which is virtually in equilibrium, revealed that the prominence of the retro-aldol reaction depended on the substrate combination. The retro-aldol reaction is a serious issue in direct aldol reactions because the product distribution, including enantiomers and diastereomers, is governed by thermodynamic parameters, and the aldol products are obtained in much lower stereoselectivity compared with the kinetically controlled process. Herein we report the beneficial effect of an additive with a functional group architecture similar to that of the aldol adduct that suppresses the retro-aldol reaction by competitively binding to the catalyst. Strategic use of the additive led to high stereoselectivity, even when the combination of substrates was prone to the retro-aldol reaction.

SUBMITTER: Bao Y

PROVIDER: S-EPMC6054082 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Managing the retro-pathway in direct catalytic asymmetric aldol reactions of thioamides.

Bao Youmei Y Kumagai Naoya N Shibasaki Masakatsu M

Chemical science 20150807 11

Thioamides are the preferred pronucleophiles for direct catalytic asymmetric aldol reactions in the context of soft Lewis acid/hard Brønsted base cooperative catalysis. In-depth investigation of this proton-transfer catalysis, which is virtually in equilibrium, revealed that the prominence of the retro-aldol reaction depended on the substrate combination. The retro-aldol reaction is a serious issue in direct aldol reactions because the product distribution, including enantiomers and diastereomer ...[more]

PMID: 30090227

Similar Datasets

Direct catalytic enantio- and diastereoselective ketone aldol reactions of isocyanoacetates.

Project description:A catalytic asymmetric aldol addition/cyclization reaction of unactivated ketones with isocyanoacetate pronucleophiles has been developed. A quinine-derived aminophosphine precatalyst and silver oxide were found to be an effective binary catalyst system and promoted the reaction to afford chiral oxazolines possessing a fully substituted stereocenter with good diastereoselectivities and excellent enantioselectivities.

| S-EPMC4678506 | biostudies-literature

Comparison of L-Threonine Aldolase Variants in the Aldol and Retro-Aldol Reactions.

Project description:Most of biochemical and mutagenesis studies performed with L-threonine aldolases were done with respect to natural activity, the cleavage of L-threonine and sometimes L-β-phenylserine. However, the properties of variants and the impact of mutations on the product synthesis are more interesting from an applications point of view. Here we performed site-directed mutagenesis of active site residues of L-threonine aldolase from Aeromonas jandaei to analyze their impact on the retro-aldol activity and on the aldol synthesis of L-β-phenylserine and L-α-alkyl-β-phenylserines. Consequently, reduced retro-aldol activity upon mutation of catalytically important residues led to increased conversions and diastereoselectivities in the synthetic direction. Thus, L-β-phenylserine can be produced with conversions up to 60% and d.e.'s up to 80% (syn) under kinetic control. Furthermorem, the donor specificity of L-threonine aldolase was increased upon mutation of active site residues, which enlarged the pocket size for an efficient binding and stabilization of donor molecules in the active site. This study broadens the knowledge about L-threonine aldolase catalyzed reactions and improves the synthetic protocols for the biocatalytic asymmetric synthesis of unnatural amino acids.

| S-EPMC6546723 | biostudies-literature

Catalytic Asymmetric Direct Aldol Reaction of α-Alkyl Azlactones and Aliphatic Aldehydes.

Project description:An unprecedented highly diastereoselective and enantioselective aldol reaction of α-alkyl azlactones and aliphatic aldehydes was achieved with cinchona alkaloid catalysts. To our knowledge, this reaction provides the first useful catalytic asymmetric access toward β-hydroxy-α-amino acids bearing alkyl substituents, which are structural motifs embedded in many natural products.

| S-EPMC4762611 | biostudies-literature

A catalytic asymmetric vinylogous Mukaiyama aldol reaction.

Project description:A vinylogous Mukaiyama aldol reaction, conducted using 10 mol % of a BITIP catalyst and B(OMe)3 as an additive, effects an enantioselective four-carbon chain extension to give versatile E-alpha,beta-unsaturated thiol esters.

| S-EPMC2516376 | biostudies-literature

Direct Catalytic Asymmetric Mannich Reactions for the Construction of Quaternary Carbon Stereocenters.

Project description:Herein, we report a Zn-ProPhenol catalyzed Mannich reaction using ?-branched ketones as nucleophilic partners for the direct enantio- and diastereoselective construction of quaternary carbon stereocenters. The reaction can be run on a gram-scale with a low catalyst loading without impacting its efficiency. Moreover, the Mannich adducts can be further elaborated with complete diastereocontrol to access molecules possessing complex stereotriads.

| S-EPMC4866641 | biostudies-literature

Enantioselective direct aldol reactions catalyzed by L-prolinamide derivatives.

Project description:l-Prolinamides 2, prepared from l-proline and simple aliphatic and aromatic amines, have been found to be active catalysts for the direct aldol reaction of 4-nitrobenzaldehyde with neat acetone at room temperature. They give moderate enantioselectivities of up to 46% enantiomeric excess (ee). The enantioselectivity increases as the amide N-H becomes a better hydrogen bond donor. l-Prolinamides 3, derived from the reaction of l-proline with alpha,beta-hydroxyamines such that there is a terminal hydroxyl group, show more efficient catalysis and higher enantioselectivities. In particular, catalyst 3h, prepared from l-proline and (1S,2S)-diphenyl-2-aminoethanol, exhibits high enantioselectivities of up to 93% ee for aromatic aldehydes and up to >99% ee for aliphatic aldehydes under -25 degrees C. Model reactions of benzaldehyde with three enamines derived from the condensation of prolinamides with acetone have been studied by quantum mechanics calculations. The calculations reveal that the amide N-H and the terminal hydroxyl groups form hydrogen bonds with the benzaldehyde substrate. These hydrogen bonds reduce the activation energy and cause high enantioselectivity. Our results suggest a new strategy in the design of new organic catalysts for direct asymmetric aldol reactions and related transformations.

| S-EPMC395980 | biostudies-literature

Catalytic asymmetric umpolung reactions of imines.

Project description:The carbon-nitrogen double bonds in imines are fundamentally important functional groups in organic chemistry. This is largely due to the fact that imines act as electrophiles towards carbon nucleophiles in reactions that form carbon-carbon bonds, thereby serving as one of the most widely used precursors for the formation of amines in both synthetic and biosynthetic settings. If the carbon atom of the imine could be rendered electron-rich, the imine could react as a nucleophile instead of as an electrophile. Such a reversal in the electronic characteristics of the imine functionality would facilitate the development of new chemical transformations that convert imines into amines via carbon-carbon bond-forming reactions with carbon electrophiles, thereby creating new opportunities for the efficient synthesis of amines. The development of asymmetric umpolung reactions of imines (in which the imines act as nucleophiles) remains uncharted territory, in spite of the far-reaching impact such reactions would have in organic synthesis. Here we report the discovery and development of new chiral phase-transfer catalysts that promote the highly efficient asymmetric umpolung reactions of imines with the carbon electrophile enals. These catalysts mediate the deprotonation of imines and direct the 2-azaallyl anions thus formed to react with enals in a highly chemoselective, regioselective, diastereoselective and enantioselective fashion. The reaction tolerates a broad range of imines and enals, and can be carried out in high yield with as little as 0.01 mole per cent catalyst with a moisture- and air-tolerant operational protocol. These umpolung reactions provide a conceptually new and practical approach to chiral amino compounds.

| S-EPMC4513368 | biostudies-literature

Practical asymmetric synthesis of ?-hydroxy ?-amino acids via complimentary aldol reactions.

Project description:Orthogonally protected chiral ?-hydroxy-?-amino acids can be accessed in >100 g quantities from readily available starting materials and reagents in 3-4 steps. These chiral synthons contain two adjacent stereocenters along with suitably protected functional groups (O-TBS, N-Boc) for downstream reactivity. Implementation of two existing aldol technologies allows rapid access to all possible stereoisomers of 1. The guiding principles during reaction optimization were reaction scalability and operational efficiency. Conversion of the amino acids to a variety of chiral building blocks in 1-2 steps demonstrates their synthetic utility.

| S-EPMC3150486 | biostudies-literature

Asymmetric Vinylogous Aldol-type Reactions of Aldehydes with Allyl Phosphonate and Sulfone.

Project description:Two catalytic asymmetric vinylogous aldol-type reactions of aldehydes with allyl phosphonate and allyl sulfone have been uncovered in good to high yields for the first time. The bulky ligand-(R)-DTBM-SEGPHOS-was found to be the key to perfectly control both regio- and enantioselectivities. Transformations of the vinylogous products (including Horner-Wadsworth-Emmons and Julia olefinations) were successfully realized by virtue of the phosphonate and sulfone moieties. Moreover, the present methodology was successfully applied in the asymmetric synthesis of natural products.

| S-EPMC6443912 | biostudies-literature

Cooperative catalysis of cellulose nanofiber and organocatalyst in direct aldol reactions.

Project description:Cellulose nanofibers (CNFs) are finding a wide range of applications in the forthcoming sustainable society because of their carbon-neutral renewability and superior physicochemical properties. Here, we first show a cooperative organocatalysis by combining TEMPO-oxidized cellulose nanofiber (TOCN) and proline to enhance the catalytic efficiency in a direct aldol reaction. The yields of proline-catalyzed aldol products drastically increased in the presence of catalytically-inactive TOCN. This effect was also achieved by simply adding the TOCN to the reaction conditions where various proline analogues including structurally simple pyrrolidine and piperidine were used instead of proline. TOCN was superior to physically-pulverized CNF in the organocatalytic efficiency, and the nanofibrillation of cellulose microfibrils in reaction media was essential to induce the drastic enhancement in catalytic activity. The present finding will bring a new entry in the applications of CNFs, and open up a new phase in developing highly efficient molecular transformations in green chemical industries.

| S-EPMC5840413 | 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