Browse
Submit Data
Databases
API
Help

Dataset Information

39 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

α-Functionalization of Cyclic Secondary Amines: Lewis Acid Promoted Addition of Organometallics to Transient Imines.

ABSTRACT: Cyclic imines, generated in situ from their corresponding N-lithiated amines and a ketone hydride acceptor, undergo reactions with a range of organometallic nucleophiles to generate α-functionalized amines in a single operation. Activation of the transient imines by Lewis acids that are compatible with the presence of lithium alkoxides was found to be crucial to accommodate a broad range of nucleophiles including lithium acetylides, Grignard reagents, and aryllithiums with attenuated reactivities.

SUBMITTER: Paul A

PROVIDER: S-EPMC6688489 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

α-Functionalization of Cyclic Secondary Amines: Lewis Acid Promoted Addition of Organometallics to Transient Imines.

Paul Anirudra A Seidel Daniel D

Journal of the American Chemical Society 20190524 22

Cyclic imines, generated in situ from their corresponding N-lithiated amines and a ketone hydride acceptor, undergo reactions with a range of organometallic nucleophiles to generate α-functionalized amines in a single operation. Activation of the transient imines by Lewis acids that are compatible with the presence of lithium alkoxides was found to be crucial to accommodate a broad range of nucleophiles including lithium acetylides, Grignard reagents, and aryllithiums with attenuated reactivitie ...[more]

PMID: 31117670

Similar Datasets

α-C-H Bond Functionalization of Unprotected Alicyclic Amines: Lewis-Acid-Promoted Addition of Enolates to Transient Imines.

Project description:Enolizable cyclic imines, obtained in situ from their corresponding lithium amides by oxidation with simple ketone oxidants, are readily alkylated with a range of enolates to provide mono- and polycyclic β-aminoketones in a single operation, including the natural product (±)-myrtine. Nitrile anions also serve as competent nucleophiles in these transformations, which are promoted by BF3 etherate. β-Aminoesters derived from ester enolates can be converted to the corresponding β-lactams.

| S-EPMC7924990 | biostudies-literature

Diversification of Unprotected Alicyclic Amines by C-H Bond Functionalization: Decarboxylative Alkylation of Transient Imines.

Project description:Despite extensive efforts by many practitioners in the field, methods for the direct α-C-H bond functionalization of unprotected alicyclic amines remain rare. A new advance in this area utilizes N-lithiated alicyclic amines. These readily accessible intermediates are converted to transient imines through the action of a simple ketone oxidant, followed by alkylation with a β-ketoacid under mild conditions to provide valuable β-amino ketones with unprecedented ease. Regioselective α'-alkylation is achieved for substrates with existing α-substituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a SN Ar step.

| S-EPMC7854982 | biostudies-literature

Copper-Nitroxyl-Catalyzed α-Oxygenation of Cyclic Secondary Amines Including Application to Late-Stage Functionalization.

Project description:Cyclic secondary amines are prominent subunits in pharmaceutical compounds. Methods for direct functionalization of N-unprotected/unsubstituted piperidines and related heterocycles have limited precedent despite their potential to impact medicinal chemistry and organic synthesis. Herein, we report a Cu/nitroxyl co-catalyzed method for direct conversion of cyclic secondary amines to the corresponding lactams via aerobic dehydrogenation and oxidative coupling with water. The mild reaction conditions tolerate diverse functional groups, enabling application to molecules that cover broad chemical space. The method is showcased in selective functionalization of building blocks and complex molecules, including late-stage functionalization of bromodomain inhibitors.

| S-EPMC11409824 | biostudies-literature

Rhodium-catalyzed synthesis of branched amines by direct addition of benzamides to imines.

Project description:Rhodium-catalyzed addition of benzamide C-H bonds to a range of aromatic N-sulfonyl aldimines has been developed and proceeds with high functional group compatibility. The synthetic utility of the resulting branched amine products has also been demonstrated by the preparation of isoindoline and isoindolinone frameworks.

| S-EPMC3345069 | biostudies-literature

Direct α-C-H bond functionalization of unprotected cyclic amines.

Project description:Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the α-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.

| S-EPMC5942596 | biostudies-literature

Synergistically activating nucleophile strategy enabled organocatalytic asymmetric P-addition of cyclic imines.

Project description:Herein, we present an attractive organocatalytic asymmetric addition of P-nucleophiles to five-membered cyclic N-sulfonyl imines facilitated by phosphonium salt catalysis, enabling the highly enantioselective synthesis of tri- and tetra-substituted cyclic phosphorus-containing benzosultams. With this protocol, various cyclic α-aminophosphonates were efficiently synthesized with high yields and exceptional enantioselectivities (up to >99% ee) under mild reaction conditions. The utility and practicality of this method were demonstrated through gram-scale reactions and straightforward elaborations. Notably, the success of this approach relies on the deliberate selection of a synergistic organocatalytic system, which helps circumvent foreseeable side effects while handling secondary phosphine oxides (SPOs). Systematic mechanistic studies, incorporating experiments and DFT calculations, have revealed the critical importance of judiciously selecting bifunctional phosphonium salt catalysts for effectively activating P-nucleophiles while stereoselectively controlling the P-attack process.

| S-EPMC11290440 | biostudies-literature

Environmentally Benign Lewis Acid Promoted [2+3]-Dipolar Cycloaddition Reactions of Nitrile Imines with Alkenes in Water.

Project description:Mild and environmentally benign Lewis acid promoted 1,3-dipolar cycloaddition reactions of α-hydrazonyl chlorides with alkenes in water are reported. These α-hydrazonyl chlorides, in the presence of Lewis acids, generate nitrile imines in situ which react with dipolarophiles to furnish the corresponding cycloaddition products. In many cases, the required times for the completion of the Lewis acid promoted 1,3-dipolar cycloaddition reactions in water were comparable to the equivalent reactions performed in an organic solvent. Analogous tetrahexylammonium chloride promoted 1,3-dipolar cycloaddition reactions were also performed. The comparison of reaction times and cycloadduct yields for the aforementioned 1,3-dipolar reactions in aqueous and organic media as well as the proposed role of the Lewis acid in the 1,3-dipolar cycloaddition reaction are described.

| S-EPMC3957226 | biostudies-literature

α-Chiral Amines via Thermally Promoted Deaminative Addition of Alkylpyridinium Salts to Sulfinimines.

Project description:A deaminative reaction of Katritzky alkylpyridinium salts and sulfinimines has been developed to deliver enantiopure α-chiral amines. The success of this method relied on the discovery of a thermally promoted deamination via single-electron transfer of an anion-π complex of the alkylpyridinium cation with potassium carbonate. This method boasts excellent diastereoselectivity over the α-stereocenter as well as broad functional group and heterocycle tolerance.

| S-EPMC8653508 | biostudies-literature

No Transition Metals Required - Oxygen Promoted Synthesis of Imines from Primary Alcohols and Amines under Ambient Conditions.

Project description:The synthesis of imines denotes a cornerstone in organic chemistry. The use of alcohols as renewable substituents for carbonyl-functionality represents an attractive opportunity. Consequently, carbonyl moieties can be in situ generated from alcohols upon transition-metal catalysis under inert atmosphere. Alternatively, bases can be utilized under aerobic conditions. In this context, we report the synthesis of imines from benzyl alcohols and anilines, promoted by KOt Bu under aerobic conditions at room temperature, in the absence of any transition-metal catalyst. A detailed investigation of the radical mechanism of the underlying reaction is presented. This reveals a complex reaction network fully supporting the experimental findings.

| S-EPMC10946877 | biostudies-literature

α-C-H/N-H Annulation of Alicyclic Amines via Transient Imines: Preparation of Polycyclic Lactams.

Project description:Polycyclic lactams are prepared in a single operation from o-toluamides and cyclic amines in a process that involves transient cyclic imines, species that are conveniently obtained in situ from the corresponding lithium amides and simple ketone oxidants. Imines thus generated, such as 1-pyrroline and 1-piperideine, engage lithiated o-toluamides in a facile annulation process. Undesired side reactions such as imine deprotonation and o-toluamide dimerization are suppressed through the judicious choice of reaction conditions.

| S-EPMC8175037 | 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