Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of Highly Reactive Ketenimines via Photochemical Rearrangement of Isoxazoles.

ABSTRACT: Ketenimines are highly electrophilic species with multiple applications as building blocks in organic synthesis; however, the effective preparation of these versatile entities remains a synthetic challenge. Here we report a continuous photochemical process that generates ketenimines via skeletal rearrangement of trisubstituted isoxazoles. The resulting flow process is noteworthy, as it provides for the first time a straightforward entry into these ketenimines that were previously only observed spectroscopically. The value of this methodology toward heterocyclic transposition reactions is demonstrated by converting isoxazoles via isolable ketenimines into pharmaceutically relevant pyrazoles.

SUBMITTER: Bracken C

PROVIDER: S-EPMC10496124 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of Highly Reactive Ketenimines via Photochemical Rearrangement of Isoxazoles.

Bracken Cormac C Baumann Marcus M

Organic letters 20230824 35

Ketenimines are highly electrophilic species with multiple applications as building blocks in organic synthesis; however, the effective preparation of these versatile entities remains a synthetic challenge. Here we report a continuous photochemical process that generates ketenimines via skeletal rearrangement of trisubstituted isoxazoles. The resulting flow process is noteworthy, as it provides for the first time a straightforward entry into these ketenimines that were previously only observed s ...[more]

PMID: 37616597

Similar Datasets

Continuous Flow Synthesis of Nitrosoarenes via Photochemical Rearrangement of Aryl Imines.

Project description:Nitrosoarenes are versatile organic building blocks; however, their intrinsic instability and limited synthetic accessibility have so far restricted their widespread use. Herein, we present a new continuous flow route toward these entities that is based on a direct photochemical rearrangement process using o-nitrophenylimines as starting materials. Due to the underlying redox mechanism, a new amide group accompanies the formation of the nitroso group. Crucial to the success of this approach is the use of trifluoroethanol as a solvent and high-power light-emitting diodes (365 nm) as light sources that provide uniform irradiation and high efficiency of the resulting continuous flow method. The process is fast and robust, with high functional group tolerance and high throughput. The formation of the nitroso moiety is supported by full spectroscopic analysis, including X-ray crystallography. The scalability of this flow approach allows access to gram quantities of nitroso species for which we highlight a small set of derivatization reactions underlining their synthetic utility.

| S-EPMC10777388 | biostudies-literature

One-pot synthesis of highly functionalized pyridines via a rhodium carbenoid induced ring expansion of isoxazoles.

Project description:A concise one-pot synthesis of highly functionalized pyridines has been developed. The first step in the reaction sequence is the formal insertion of rhodium vinylcarbenoids across the N-O bond of isoxazoles. Upon heating, the insertion products undergo a rearrangement to give 1,4-dihydropyridines. DDQ oxidation then affords the corresponding pyridines in 31-84% yield. The process has proven general with a range of carbenoid and isoxazole components and represents a unique disconnection strategy for the synthesis of functionalized pyridines.

| S-EPMC2921945 | biostudies-literature

Solution phase synthesis of a diverse library of highly substituted isoxazoles.

Project description:The iodocyclization of O-methyloximes of 2-alkyn-1-ones affords 4-iodoisoxazoles, which undergo various palladium-catalyzed reactions to yield 3,4,5-trisubstituted isoxazoles. The palladium-catalyzed processes have been adapted to parallel synthesis utilizing commercially available boronic acid, acetylene, styrene, and amine sublibraries. Accordingly, a diverse 51-member library of 3,4,5-trisubstituted isoxazoles has been generated.

| S-EPMC3750120 | biostudies-literature

The synthesis of highly substituted isoxazoles by electrophilic cyclization: an efficient synthesis of valdecoxib.

Project description:A large number of functionally substituted 2-alkyn-1-one O-methyl oximes have been cyclized under mild reaction conditions in the presence of ICl to give the corresponding 4-iodoisoxazoles in moderate to excellent yields. The resulting 4-iodoisoxazoles undergo various palladium-catalyzed reactions to yield 3,4,5-trisubstituted isoxazoles, including valdecoxib.

| S-EPMC2529460 | biostudies-literature

Copper-catalyzed Z-selective synthesis of acrylamides and polyacrylamides via alkylidene ketenimines.

Project description:It remains very important to discover and study new fundamental intermediates consisting of carbon and nitrogen as the abundant elements of organic molecules. The unique alkylidene ketenimine could be formed in situ under mild conditions by an unexpected copper-catalyzed three-component reaction of alkyne, azide and water involving a successive cycloaddition, N2 extrusion and carbene-assisted rearrangement. Only Z-α,β-unsaturated amides instead of E-α,β-unsaturated amides or triazoles were acquired from alkylidene ketenimines with excellent selectivities and stereospecificities. In addition, a series of "approximate" alternating copolymers (poly (triazole-alt-Z-acrylamides)) with high Mns and yields were efficiently afforded by multicomponent polymerization through a very simple operation basing on this multicomponent reaction.

| S-EPMC9329291 | biostudies-literature

Photochemical production of a highly reactive porphyrin-iron-oxo species.

Project description:Oxidation of 5,10,15,20-tetramesitylporphyrinatoiron(III) perchlorate, (TMP)FeIII(ClO4), with ferric perchlorate in acetonitrile gave a metastable species identified as (TMP)FeIV(ClO4)2 that decayed within seconds to the known isomeric species (TMP*+)FeIII(ClO4)2. Irradiation of the metastable species with 355 nm laser light gave a highly reactive transient that reacts with simple organic reductants (alkenes and arylalkanes) 5 orders of magnitude faster than known Compound I analogues, (TMP*+)FeIV(O)(X-).

| S-EPMC2525790 | biostudies-literature

Toward the Scale-Up of a Bicyclic Homopiperazine via Schmidt Rearrangement and Photochemical Oxaziridine Rearrangement in Continuous-Flow.

Project description:The scale-up of a chiral bicyclic homopiperazine of pharmaceutical interest was investigated. The outcome and safety profile of a key batch ring-expansion step via Schmidt rearrangement was improved using continuous-flow chemistry. The selectivity of nitrogen insertion for the ring expansion was improved via an alternative photochemical oxaziridine rearrangement under mild conditions, which when converted to continuous-flow in a simple and efficient flow reactor allowed the first photochemical scale-up of a homopiperazine.

| S-EPMC7928940 | biostudies-literature

Photochemical 1,3-boronate rearrangement enables three-component N-alkylation for α-tertiary hydroxybenzylamine synthesis.

Project description:Hydroxybenzylamines are prevalent in drugs and bioactive molecules, including various antimalarial and anticancer drugs. α-tertiary alkylation of amines impacts drug-target interactions significantly through their influence on basicity and lipophilicity. Traditional N-alkylation methods, especially for α-tertiary amines, suffer from limitations due to high energy barriers from steric hindrance. In this work, we leverage visible light irradiation to enable the organoboronic acid addition to sterically hindered ketimines in the excited state. Notably, it overcomes the limitations of the well-explored Petasis reaction, which is restricted to aldimines due to the high energy barrier associated with ketimines (51.3 kcal/mol). This three-component coupling of aliphatic amines, o-phenolic ketones, and organoboronic acids delivers diverse α-tertiary o-hydroxybenzylamines (77 examples, yields up to 82%) with broad functional group tolerance. The light-driven 1,3-boronate rearrangement introduces quaternary carbon centers adjacent to the amine moiety to enable late-stage functionalization of complex bioactive molecules. This versatile tool for complex amine synthesis holds significant potential for accelerating advancements in drug discovery, chemical biology, and materials science research.

| S-EPMC11599903 | biostudies-literature

Diarylamine Synthesis via Desulfinylative Smiles Rearrangement.

Project description:Diarylamines are obtained directly from sulfinamides through a novel rearrangement sequence. The transformation is transition metal-free and proceeds under mild conditions, providing facile access to highly sterically hindered diarylamines that are otherwise inaccessible by traditional SNAr chemistry. The reaction highlights the distinct reactivity of the sulfinamide group in Smiles rearrangements versus that of the more common sulfonamides.

| S-EPMC8893360 | biostudies-literature

Synthesis and Antiprotozoal Profile of 3,4,5-Trisubstituted Isoxazoles.

Project description:A series of 60 4-aminomethyl 5-aryl-3-substituted isoxazoles were synthesized by an efficient method and evaluated in vitro against Leishmania amazonensis and Trypanosoma cruzi, protozoa that cause the neglected tropical diseases leishmaniasis and Chagas disease, respectively. Thirteen compounds exhibited a selective index greater than 10. The series of 3-N-acylhydrazone isoxazole derivatives bearing the bithiophene core exhibited the best antiparasitic effects.

| S-EPMC8485799 | 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