Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Vinylazaarenes as dienophiles in Lewis acid-promoted Diels-Alder reactions.

ABSTRACT: Described are the first examples of Lewis acid-promoted Diels-Alder reactions of vinylpyridines and other vinylazaarenes with unactivated dienes. Cyclohexyl-appended azaarenes constitute a class of substructures of rising prominence in drug discovery. Despite this, thermal variants of the vinylazaarene Diels-Alder reaction are rare and have not been adopted for synthesis, and Lewis acid-promoted variants are virtually unexplored. The presented work addresses this gap and in the process furnishes increased scope, dramatically higher yields, improved regioselectivity, and high levels of diastereoselectivity compared to prior thermal examples. These reactions provide scalable access to druglike scaffolds not readily available through other methods. More broadly, these studies establish a useful new class of dienophiles that, based on preliminary mechanistic studies, should be amenable to conventional strategies for enantioselective catalysis.

SUBMITTER: Davis AE

PROVIDER: S-EPMC8672738 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

How Lewis Acids Catalyze Diels-Alder Reactions.

Project description:The Lewis acid(LA)-catalyzed Diels-Alder reaction between isoprene and methyl acrylate was investigated quantum chemically using a combined density functional theory and coupled-cluster theory approach. Computed activation energies systematically decrease as the strength of the LA increases along the series I2 <SnCl4 <TiCl4 <ZnCl2 <BF3 <AlCl3 . Emerging from our activation strain and Kohn-Sham molecular orbital bonding analysis was an unprecedented finding, namely that the LAs accelerate the Diels-Alder reaction by a diminished Pauli repulsion between the π-electron systems of the diene and dienophile. Our results oppose the widely accepted view that LAs catalyze the Diels-Alder reaction by enhancing the donor-acceptor [HOMOdiene -LUMOdienophile ] interaction and constitute a novel physical mechanism for this indispensable textbook organic reaction.

| S-EPMC7187354 | biostudies-literature

Lewis Acid-Catalyzed Diels-Alder Reactions: Reactivity Trends across the Periodic Table.

Project description:The catalytic effect of various weakly interacting Lewis acids (LAs) across the periodic table, based on hydrogen (Group 1), pnictogen (Group 15), chalcogen (Group 16), and halogen (Group 17) bonds, on the Diels-Alder cycloaddition reaction between 1,3-butadiene and methyl acrylate was studied quantum chemically by using relativistic density functional theory. Weakly interacting LAs accelerate the Diels-Alder reaction by lowering the reaction barrier up to 3 kcal mol-1 compared to the uncatalyzed reaction. The reaction barriers systematically increase from halogen<hydrogen<chalcogen<pnictogen-bonded LAs, i. e., the latter have the least catalytic effect. Our detailed activation strain and Kohn-Sham molecular orbital analyses reveal that these LAs lower the Diels-Alder reaction barrier by increasing the asynchronicity of the reaction to relieve the otherwise destabilizing Pauli repulsion between the closed-shell filled π-orbitals of diene and dienophile. Notably, the reactivity can be further enhanced on going from a Period 3 to a Period 5 LA, as these species amplify the asynchronicity of the Diels-Alder reaction due to a stronger binding to the dienophile. These findings again demonstrate the generality of the Pauli repulsion-lowering catalysis concept.

| S-EPMC8360170 | biostudies-literature

Hetero-Diels-Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles.

Project description:Selected hetaryl and aryl thioketones react with acetylenecarboxylates under thermal conditions in the presence of LiClO4 or, alternatively, under high-pressure conditions (5 kbar) at room temperature yielding thiopyran derivatives. The hetero-Diels-Alder reaction occurs in a chemo- and regioselective manner. The initially formed [4 + 2] cycloadducts rearrange via a 1,3-hydrogen shift sequence to give the final products. The latter were smoothly oxidized by treatment with mCPBA to the corresponding sulfones.

| S-EPMC4464410 | biostudies-literature

Unveiling the Lewis Acid Catalyzed Diels-Alder Reactions Through the Molecular Electron Density Theory.

Project description:The effects of metal-based Lewis acid (LA) catalysts on the reaction rate and regioselectivity in polar Diels-Alder (P-DA) reactions has been analyzed within the molecular electron density theory (MEDT). A clear linear correlation between the reduction of the activation energies and the increase of the polar character of the reactions measured by analysis of the global electron density transfer at the corresponding transition state structures (TS) is found, a behavior easily predictable by analysis of the electrophilicity ω and nucleophilicity N indices of the reagents. The presence of a strong electron-releasing group in the diene changes the mechanism of these P-DA reactions from a two-stage one-step to a two-step one via formation of a zwitterionic intermediate. However, this change in the reaction mechanism does not have any chemical relevance. This MEDT study makes it possible to establish that the more favorable nucleophilic/electrophilic interactions taking place at the TSs of LA catalyzed P-DA reactions are responsible for the high acceleration and complete regioselectivity experimentally observed.

| S-EPMC7321097 | biostudies-literature

Intramolecular Diels-Alder reactions of cycloalkenones: stereoselectivity, Lewis acid acceleration, and halogen substituent effects.

Project description:The intramolecular Diels-Alder reactions of cycloalkenones and terminal dienes occur with high endo stereoselectivity, both thermally and under Lewis-acidic conditions. Through computations, we show that steric repulsion and tether conformation govern the selectivity of the reaction, and incorporation of either BF3 or α-halogenation increases the rate of cycloaddition. With a longer tether, isomerization from a terminal diene to the more stable internal diene results in a more facile cycloaddition.

| S-EPMC3965351 | biostudies-literature

Chiral cyclopropenyl ketones: reactive and selective Diels-Alder dienophiles.

Project description:The synthesis and Diels-Alder reactions of cyclopropenyl ketones are described. Cyclopropenyl ketones are highly reactive dienophiles that can engage a range of cyclic dienes and 2,3-dimethylbutadiene. The strategy of using cyclopropenyl ketones to facilitate Diels-Alder reactions is not limited to products that contain three-membered rings, as reductive opening by SmI2 can be used to produce a product that lacks a cyclopropane but retains a quaternary stereogenic center.

| S-EPMC3908886 | biostudies-literature

Acylammonium salts as dienophiles in Diels-Alder/lactonization organocascades.

Project description:α,β-Unsaturated acylammonium salts, generated in situ from commodity acid chlorides and a chiral isothiourea organocatalyst, comprise a new and versatile family of chiral dienophiles for the venerable Diels-Alder (DA) cycloaddition. Their reactivity is unveiled through a highly diastereo- and enantioselective Diels-Alder/lactonization organocascade that generates cis- and trans-fused bicyclic γ- and δ-lactones bearing up to four contiguous stereocenters. Moreover, the first examples of DA-initiated, stereodivergent organocascades are described delivering complex scaffolds found in bioactive compounds. The origins of stereoselectivity are rationalized through computational studies. In addition, the utility of this methodology is demonstrated through a concise approach to the core structure of glaciolide and formal syntheses of fraxinellone, trisporic acids, and trisporols.

| S-EPMC3985498 | biostudies-literature

Lewis acid catalyzed inverse-electron-demand Diels-Alder reaction of tropones.

Project description:Lewis acid catalyzed inverse-electron-demand Diels-Alder reaction of tropone derivatives was developed. Up to 97% ee was obtained for the chiral dinucleus BINOL-aluminum complex catalyzed reaction between tropones and ketene diethyl acetal to give bicyclo[3.2.2] ring structures, which opens up a unique way of making chiral seven-membered rings.

| S-EPMC2810398 | biostudies-literature

Halocycloalkenones as Diels-Alder dienophiles. Applications to generating useful structural patterns.

Project description:Halocycloalkenones are demonstrated to function as potent dienophiles in inter- and intramolecular Diels-Alder cycloadditions. We have found 2-brominated cycloalkenone dienophiles to be both highly endo selective and significantly more reactive than their nonhalogenated parent compounds. A method for the facile conversion of brominated cyclobutanone DA adducts to synthetically useful cyclopropyl functional handles is described.

| S-EPMC3543988 | biostudies-literature

Diels-Alder reactions using 4,7-dioxygenated indanones as dienophiles for regioselective construction of oxygenated 2,3-dihydrobenz[f]indenone skeleton.

Project description:Regioselective construction of 4,8,9-trioxygenated 2,3-dihydrobenz[f]indenones, key intermediates for the synthesis of kinamycin antibiotics, was achieved via Diels-Alder reactions (DAR) using 4,7-dioxygenated indanone-type compounds as dienophiles. Reaction of indanetrione with 1-methoxybutadiene gave a 1 : 1 mixture of undesired 4,5,9-trioxygenated 2,3-dihydrobenz[f]indenone and [4.4.3]propellane. The addition of Lewis acid did not affect the product ratio, whereas the use of the 6-bromoindanetrione exclusively afforded the latter propellane. On the other hand, DAR of benzyne derived from bromoindan and furan gave 5,8-epoxy-2,3-dihydrobenz[f]indene, which was subjected to acid-induced ring opening to give 2,3-dihydrobenz[f]indenone with undesired 4,5,9-trioxy functions.

| S-EPMC2486486 | 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