Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Trifluoroethanol Promoted Castagnoli-Cushman Cycloadditions of Imines with Homophthalic Anhydride.

ABSTRACT: Lactams are essential compounds in medicinal chemistry and key intermediates in the synthesis of natural products. The Castagnoli-Cushman reaction (CCR) of homophthalic anhydride with imines is an exciting method for accessing cyclic densely substituted lactam products. Most CCRs need to be catalyzed or heated. Herein, we report a new, efficient, metal and catalyst-free CCR for the synthesis of poly-substituted 3,4-lactams utilizing the unique properties of trifluoroethanol (TFE). This procedure provides high-speed and smooth access to a broad range of densely substituted 3,4-lactams in good yields and a 100% atom-economical fashion.

SUBMITTER: Bayles T

PROVIDER: S-EPMC8839191 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Trifluoroethanol Promoted Castagnoli-Cushman Cycloadditions of Imines with Homophthalic Anhydride.

Bayles Thibault T Guillou Catherine C

Molecules (Basel, Switzerland) 20220127 3

Lactams are essential compounds in medicinal chemistry and key intermediates in the synthesis of natural products. The Castagnoli-Cushman reaction (CCR) of homophthalic anhydride with imines is an exciting method for accessing cyclic densely substituted lactam products. Most CCRs need to be catalyzed or heated. Herein, we report a new, efficient, metal and catalyst-free CCR for the synthesis of poly-substituted 3,4-lactams utilizing the unique properties of trifluoroethanol (TFE). This procedure ...[more]

PMID: 35164109

Similar Datasets

N-methylimidazole promotes the reaction of homophthalic anhydride with imines.

Project description:The addition of N-methylimidazole (NMI) to the reaction of homophthalic anhydride with imines such as pyridine-3-carboxaldehyde-N-trifluoroethylimine (9) reduces the amount of elimination byproduct and improves the yield of the formal cycloadduct, tetrahydroisoquinolonic carboxylate 10. Carboxanilides of such compounds are of interest as potential antimalarial agents. A mechanism that rationalizes the role of NMI is proposed, and a gram-scale procedure for the synthesis and resolution of 10 is also described.

| S-EPMC4136697 | biostudies-literature

The Use of Aryl-Substituted Homophthalic Anhydrides in the Castagnoli-Cushman Reaction Provides Access to Novel Tetrahydroisoquinolone Carboxylic Acid Bearing an All-Carbon Quaternary Stereogenic Center.

Project description:Novel aryl-substituted homophthalic acids were cyclodehydrated to the respective homophthalic anhydrides for use in the Castagnoli-Cushman reaction. With a range of imines, this reaction proceeded smoothly and delivered hitherto undescribed 4-aryl-substituted tetrahydroisoquinolonic acids with remarkable diastereoselectivity, good yields and no need for chromatographic purification. These findings significantly extend the range of cyclic anhydrides employable in the Castagnoli-Cushman reaction and signify access to a novel substitution pattern around the medicinally relevant tetrahydroisoquinolonic acid scaffold.

| S-EPMC9738897 | biostudies-literature

Fluoral Hydrate: A Perspective Substrate for the Castagnoli-Cushman Reaction.

Project description:The reactivity of azomethines based on trifluoroacetaldehyde hydrate in the Castagnoli-Cushman reaction (CCR) was researched. The impact of the nature of anhydrides explored on the reaction route was determined. The preparative procedures for the synthesis of N-substituted (3R*,4R*)-1-oxo-3-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic and (1R*,2R*)-4-oxo-2-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine-1-carboxylic acids in gram scales were elaborated. It was shown that the trifluoromethyl group remarkably decreased the reactivity of azomethines in CCR. The mechanism for the formation of different products depending on the anhydride's nature was proposed.

| S-EPMC7450650 | biostudies-literature

Dimerization and comments on the reactivity of homophthalic anhydride.

Project description:Homophthalic anhydride (HPA) dimerizes under the influence of base to provide, sequentially, the (3-4')-C-acyl dimer, a pair of chiral diastereomeric bis(lactones), 3-(2-carboxybenzyl)isocoumarin-4-carboxylic acid, and finally, 3-(2-carboxybenzyl)isocoumarin. The structures of the bis(lactones) were misassigned in 1970 based on the (presumed) cis thermal decarboxylative elimination reaction of the lower melting one. The preferred pathway should be trans-anti, however, and crystallographic analysis of one of the bis(lactones) reverses the earlier assignment. The formal cycloaddition reaction of HPA with imines occurs in preference to HPA dimerization; the mechanistic implications of this reactivity difference are discussed.

| S-EPMC4481714 | biostudies-literature

Two Annulated Azaheterocyclic Cores Readily Available from a Single Tetrahydroisoquinolonic Castagnoli-Cushman Precursor.

Project description:A novel approach to indolo[3,2-c]isoquinoline and dibenzo[c,h][1,6]naphthyridine tetracyclic systems was discovered based on switchable reduction of 2-methoxy-3-(2-nitrophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid prepared via Castagnoli-Cushman reaction. Reduction with ammonium formate resulted in the expected selective transformation of the nitro group (thus providing access to substituted dibenzo[c,h][1,6]naphthyridine via cyclization and dehydrogenation). However, attempted reduction with sodium sulfide initiated a previously unknown reaction cascade including double reduction, cyclization, and decarboxylation, leading to formation of indolo[3,2-c]isoquinoline polyheterocycle in one synthetic step.

| S-EPMC7248902 | biostudies-literature

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli-Cushman protocol.

Project description:The Castagnoli-Cushman reaction of 3,4-dihydroisoquinolines with glutaric anhydride, its oxygen and sulfur analogues was investigated as a one-step approach to the benzo[a]quinolizidine system and its heterocyclic analogs. An extension towards the pyrrolo[2,1-a]isoquinoline system was achieved with the use of succinic anhydride. The results are evidence of an unexplored method for the access of the aforementioned tricyclic annelated systems incorporating a bridgehead nitrogen atom. The structures and relative configurations of the new compounds were established by means of 1D and 2D NMR techniques. The reactions between 1-methyldihydroisoquinoline and glutaric, diglycolic and succinic anhydrides yielded unexpected isoquinoline derivatives containing an exocyclic double bond. The compounds prepared bear the potential to become building blocks for future synthetic bioactive molecules.

| S-EPMC7323625 | biostudies-literature

Stereodivergent Synthesis of Complex <i>N</i>-Sulfonimidoyl Lactams via the Castagnoli-Cushman Reaction.

Project description:The reactivity between sulfonimidamide-derived imines and cyclic anhydrides has been investigated. Sulfonimidamide imines readily react with homophthalic anhydride under mild conditions in the presence of non-nucleophilic bases to yield complex lactam products with high diastereoselectivity. Furthermore, it was discovered that sulfonimidamide imines react with homophthalic anhydride in the absence of a base to yield distinct diastereomer products with high diastereoselectivity. Density functional theory calculations suggest the existence of an open transition state pathway in the presence of base and a novel cyclic eight-membered transition state in the absence of base.

| S-EPMC11812003 | biostudies-literature

One-Pot Sequence of Staudinger/aza-Wittig/Castagnoli-Cushman Reactions Provides Facile Access to Novel Natural-like Polycyclic Ring Systems.

Project description:Realization of the one-pot Staudinger/aza-Wittig/Castagnoli-Cushman reaction sequence for a series of azido aldehydes and homophthalic anhydrides is described. The reaction proceeded at room temperature and delivered novel polyheterocycles related to the natural product realm in high yields and high diastereoselectivity. The methodology has been extended to three other cyclic anhydrides. These further unravel the potential of the Castagnoli-Cushman reaction in generating polyheterocyclic molecular scaffolds.

| S-EPMC9735558 | biostudies-literature

Fluorogenic Strain-Promoted Alkyne-Diazo Cycloadditions.

Project description:Fluorogenic reactions, in which non- or weakly fluorescent reagents produce highly fluorescent products, are attractive for detecting a broad range of compounds in the fields of bioconjugation and material sciences. Herein, we report that a dibenzocyclooctyne derivative modified with a cyclopropenone moiety (Fl-DIBO) can undergo fast strain-promoted cycloaddition reactions under catalyst-free conditions with azides, nitrones, nitrile oxides, as well as mono- and disubstituted diazo-derivatives. Although the reaction with nitrile oxides, nitrones, and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H-pyrazole derivatives that exhibited an approximately 160-fold fluorescence enhancement over Fl-DIBO combined with a greater than 10,000-fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H-pyrazoles, which are formed by reaction with disubstituted diazo-derivatives, is likely due to the presence of energetically low-lying (n,π*) states. The fluorogenic probe Fl-DIBO was successfully employed for the labeling of diazo-tagged proteins without detectable background signal. Diazo-derivatives are emerging as attractive reporters for the labeling of biomolecules, and the studies presented herein demonstrate that Fl-DIBO can be employed for visualizing such biomolecules without the need for probe washout.

| S-EPMC4712747 | biostudies-literature

Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with methyleneindolinones.

Project description:Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with methyleneindolinones are reported. The spiro[pyrazolin-3,3'-oxindole] products are formed in good yields (up to 98%) and high enantioselectivity (up to 99% ee).

| S-EPMC3876797 | 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