Browse
Submit Data
Databases
API
Help

Dataset Information

29 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Catalytic Asymmetric Synthesis of Chiral ?-Amino Ketones via Umpolung Reactions of Imines.

ABSTRACT: The first direct catalytic asymmetric synthesis of ?-amino ketones was realized by the development of a highly diastereoselective and enantioselective C-C bond-forming umpolung reaction of imines and enones under the catalysis of a new cinchona alkaloid-derived phase-transfer catalyst. In a loading ranging from 0.02 to 2.5 mol %, the catalyst activates a broad range of trifluoromethyl imines and aldimines as nucleophiles to engage in chemo-, regio-, diastereo- and enantioselective C-C bond-forming reactions with acyclic and cyclic enones, thereby converting these readily available prochiral starting materials into highly enantiomerically enriched chiral ?-amino ketones in synthetically useful yields. Enabled by this unprecedented umpolung reaction of imines, conceptually new and concise routes were developed for the asymmetric synthesis of nitrogen-heterocycles such as pyrrolidines and indolizidines.

SUBMITTER: Hu L

PROVIDER: S-EPMC5654742 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Catalytic Asymmetric Synthesis of Chiral γ-Amino Ketones via Umpolung Reactions of Imines.

Hu Lin L Wu Yongwei Y Li Zhe Z Deng Li L

Journal of the American Chemical Society 20161130 49

The first direct catalytic asymmetric synthesis of γ-amino ketones was realized by the development of a highly diastereoselective and enantioselective C-C bond-forming umpolung reaction of imines and enones under the catalysis of a new cinchona alkaloid-derived phase-transfer catalyst. In a loading ranging from 0.02 to 2.5 mol %, the catalyst activates a broad range of trifluoromethyl imines and aldimines as nucleophiles to engage in chemo-, regio-, diastereo- and enantioselective C-C bond-formi ...[more]

PMID: 27960300

Similar Datasets

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

Direct Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Esters/Lactones via Umpolung Strategy.

Project description:Enabled by the discovery of new cinchonium salts and coadditives, a direct and efficient asymmetric access to trifluoromethylated γ-amino esters/lactones has been realized through the enantioselective and diastereoselective umpolung reaction of trifluoromethyl imines with acrylates or α,β-unsaturated lactones as carbon electrophiles. At 0.5-5.0 mol % catalyst loadings, the newly developed catalytic system activates a variety of imine substrates as unconventional nucleophiles to mediate highly chemo-, regio-, diastereo-, and enantioselective C-C bond forming reactions. The developed synthetic protocol represents an excellent strategy to target a series of versatile and enantiomerically enriched γ-amino esters/lactones in good to excellent yields from the readily available starting materials. Additionally, we found that the epi-vinyl catalysts based on cinchonidine and quinine promote a similarly high enantioselective reaction generating the opposite configuration of chiral products in a highly efficient manner, which allows convenient access to either the R- or S-enantiomer of the chiral amine products in high yields and excellent enantioselectivities.

| S-EPMC6467775 | biostudies-literature

Catalytic Asymmetric Synthesis of Trifluoromethylated ?-Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives.

Project description:Novel cinchona alkaloid derived chiral phase-transfer catalysts enabled the highly chemo-, regio-, diastereo-, and enantioselective umpolung addition of trifluoromethyl imines to ?,?-unsaturated N-acyl pyrroles. With a catalyst loading ranging from 0.2 to 5.0?mol?%, this new catalytic asymmetric transformation provides facile and high-yielding access to highly enantiomerically enriched chiral trifluoromethylated ?-amino acids and ?-lactams.

| S-EPMC6408948 | biostudies-literature

Catalytic Asymmetric Mannich Reactions with Fluorinated Aromatic Ketones: Efficient Access to Chiral ?-Fluoroamines.

Project description:Reported herein is a Zn/Prophenol-catalyzed Mannich reaction using fluorinated aromatic ketones as nucleophilic partners for the direct enantio- and diastereoselective construction of ?-fluoroamine motifs featuring a fluorinated tetrasubstituted carbon. The reaction can be run on a gram scale with a low catalyst loading without impacting its efficiency. Moreover, a related aldol reaction was also developed. Together, these reactions provide a new approach for the preparation of pharmaceutically relevant products possessing tetrasubstituted C-F centers.

| S-EPMC4837127 | biostudies-literature

Enantioselective synthesis of α-amino ketones through palladium-catalyzed asymmetric arylation of α-keto imines.

Project description:Chiral α-amino ketones are common structural motifs in natural products and pharmaceuticals, as well as important synthons in organic synthesis. Thus, establishing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones through a chiral palladium-catalyzed arylation reaction of in situ generated challenging α-keto imines from previously unreported C-acyl N-sulfonyl-N,O-aminals, with arylboronic acids. The current reaction offers a straightforward approach to the asymmetric synthesis of acyclic α-amino ketones in a practical and highly stereocontrolled manner. Meanwhile, the multiple roles of the chiral Pd(ii) complex catalyst in the reaction were also reported.

| S-EPMC8966749 | biostudies-literature

Asymmetric synthesis of ?-amino-1,3-dithianes via chiral N-phosphonyl imine-based Umpolung reaction without using chromatography and recrystallization.

Project description:A series of ?-amino-1,3-dithianes have been synthesized via the asymmetric Umpolung reaction of 2-lithio-1,3-dithianes with chiral N-phosphonyl imines in good chemical yields (up to 82%) and good to excellent diastereoselectivities (>99:1). The manner by which chiral N-phosphonyl imines are slowly added into the solution of 2-lithio-1,3-dithiane was found to be crucial for achieving excellent diastereoselectivity. The current synthesis was proven to follow the GAP chemistry (group-assistant-purification chemistry) process, which avoids traditional purification techniques of chromatography or recrystallization, i.e., the pure chiral ?-amino-1,3-dithianes attached with the chiral N-phosphonyl group were readily obtained by washing the solid crude products with hexane or a mixture of hexane-ethyl acetate.

| S-EPMC3074014 | biostudies-literature

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

Project description:Orthogonally protected chiral β-hydroxy-γ-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

Efficient Synthesis of Chiral Trisubstituted 1,2-Allenyl Ketones by Catalytic Asymmetric Conjugate Addition of Malonic Esters to Enynes.

Project description:An N,N'-dioxide/scandium(III) complex catalyzed, highly efficient conjugate addition of malonic esters to enynes is described. A range of trisubstituted 1,2-allenyl ketones were obtained in high yields (up to 99?%) with good d.r. (up to 95/5) and excellent ee values (97?%-99?%). Moreover, the products could be easily transformed into chiral furan and 5-hydroxypyrazoline derivatives, both of which are important skeletons of many biologically active compounds and pharmacologicals.

| S-EPMC4738401 | biostudies-literature

Catalytic asymmetric synthesis of chiral allylic esters.

Project description:Trichloroacetimidate derivatives of prochiral (Z)-2-alken-1-ols react at room temperature with carboxylic acids to give chiral 3-acyloxy-1-alkenes in high enantiopurity in the presence of di-mu-acetatobis[(eta5-(S)-(pR)-2-(2'-(4'-methylethyl)oxazolinyl)cyclopentadienyl,1-C,3'-N)(eta4-tetraphenylcyclobutadiene)cobalt]dipalladium (COP-OAc) or its enantiomer. This reaction has broad scope, proceeds with predictable high stereoinduction, is accomplished at room temperature using high substrate concentrations and low catalyst loadings, and likely proceeds by a novel mechanism.

| S-EPMC2966826 | biostudies-other

Asymmetric organocatalytic decarboxylative Mannich reaction using ?-keto acids: A new protocol for the synthesis of chiral ?-amino ketones.

Project description:The first decarboxylative Mannich reaction employing ?-keto acids, catalyzed by cinchonine-derived bifunctional thiourea catalyst has been described. The desired ?-amino ketones were obtained in excellent yields and with moderate to good enantioselectivities.

| S-EPMC3458749 | 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