Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Origins of regioselectivity of Diels-Alder reactions for the synthesis of bisanthraquinone antibiotic BE-43472B.

ABSTRACT: The regioselectivities of several Diels-Alder reactions utilized en route to bisanthraquinone antibiotic BE-43472B are examined using density functional theory calculations. These reactions involve highly substituted dienes and juglone dienophiles, and there is an opposite regiochemical outcome for Diels-Alder reactions with beta-aryl substituted juglones when compared to reactions of unsubstituted juglone. In this article, the effect of an aromatic conjugating group bonded to juglone is explored.

SUBMITTER: Hayden AE

PROVIDER: S-EPMC2813957 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Origins of regioselectivity of Diels-Alder reactions for the synthesis of bisanthraquinone antibiotic BE-43472B.

Hayden Amy E AE Paton Robert S RS Becker Jochen J Lim Yee Hwee YH Nicolaou K C KC Houk K N KN

The Journal of organic chemistry 20100201 3

The regioselectivities of several Diels-Alder reactions utilized en route to bisanthraquinone antibiotic BE-43472B are examined using density functional theory calculations. These reactions involve highly substituted dienes and juglone dienophiles, and there is an opposite regiochemical outcome for Diels-Alder reactions with beta-aryl substituted juglones when compared to reactions of unsubstituted juglone. In this article, the effect of an aromatic conjugating group bonded to juglone is explore ...[more]

PMID: 20027998

Similar Datasets

Regioselectivity of Diels-Alder Reactions Between 6,7-Dehydrobenzofuran and 2-Substituted Furans.

Project description:We describe the first report of the generation of 6,7-dehydrobenzofuran (6,7-benzofuranyne) from 6,7-dihalobenzofurans via metal-halogen exchange and elimination, in a manner similar to our previous work with 6,7-indole arynes. This benzofuranyne undergoes highly regioselective Diels-Alder cycloadditions with 2-substituted furans.

| S-EPMC4179875 | biostudies-literature

Diels-Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene.

Project description:Reversing the regioselectivity of the renowned Diels-Alder reaction by overriding the usual thermodynamic and kinetic governing factors has always been a formidable challenge to synthetic organic chemists. Anthracenes are well-known to undergo [4 + 2]-cycloadditions with dienophiles at their 9,10-positions (central ring) over 1,4-positions (terminal ring) guided by the relative aromatic stabilization energy of the two possible products, and also by harboring the largest orbital coefficients of the highest occupied molecular orbital (HOMO) at the 9,10-positions. We, herein, report a 1,4-selective [4 + 2]-cycloaddition strategy of 9,10-unsubstituted anthracenes by installing electron-donating substituents on the terminal rings which is heretofore unprecedented to the best of our knowledge. The developed synthetic strategy does not require any premeditated engagement of the 9,10-positions either with any sterically bulky or electron-withdrawing substituents and allows delicate calibration of the regioselectivity by modulating the electron-donating strength of the substituents on the terminal rings. Likewise, the regioselective functionalization of the terminal anthracene ring in electrophilic substitution reactions is demonstrated. A mechanistic rationale is offered with the aid of detailed computational studies, and finally, synthetic applications are presented.

| S-EPMC9814106 | biostudies-literature

Two novel 1,2,4,5-tetrazines that participate in inverse electron demand Diels-Alder reactions with an unexpected regioselectivity.

Project description:[reaction: see text] Two new unsymmetrical 1,2,4,5-tetrazines, 3-methylsulfinyl-6-methylthio-1,2,4,5-tetrazine (4) and 3-(benzyloxycarbonyl)amino-6-methylsulfinyl-1,2,4,5-tetrazine (5), were prepared, and the scope of their participation in intermolecular inverse electron demand Diels-Alder reactions was defined. As anticipated, sulfoxides 4 and 5 (4 > 5) display a reactivity that is substantially greater than that of their corresponding sulfides (2 and 3), being derived from their enhanced electron-deficient character and resulting in a wider range of potential dienophile choices or the use of milder reaction conditions. The cycloaddition reactions were expectedly regioselective, typically producing a single cycloadduct, ensuring their synthetic utility, but both were found to proceed with a regioselectivity opposite what would be anticipated and complementary to that observed with 2 and 3.

| S-EPMC2525609 | biostudies-literature

How Ionization Catalyzes Diels-Alder Reactions.

Project description:The catalytic effect of ionization on the Diels-Alder reaction between 1,3-butadiene and acrylaldehyde has been studied using relativistic density functional theory (DFT). Removal of an electron from the dienophile, acrylaldehyde, significantly accelerates the Diels-Alder reaction and shifts the reaction mechanism from concerted asynchronous for the neutral Diels-Alder reaction to stepwise for the radical-cation Diels-Alder reaction. Our detailed activation strain and Kohn-Sham molecular orbital analyses reveal how ionization of the dienophile enhances the Diels-Alder reactivity via two mechanisms: (i) by amplifying the asymmetry in the dienophile's occupied π-orbitals to such an extent that the reaction goes from concerted asynchronous to stepwise and thus with substantially less steric (Pauli) repulsion per reaction step; (ii) by enhancing the stabilizing orbital interactions that result from the ability of the singly occupied molecular orbital of the radical-cation dienophile to engage in an additional three-electron bonding interaction with the highest occupied molecular orbital of the diene.

| S-EPMC9400981 | biostudies-literature

Synthesis of bistetrahydroquinolines as potential anticholinesterasic agents by double Diels-Alder reactions.

Project description:The tetrahydroquinoline ring system is a unit found in many biologically active natural products and pharmacologically relevant therapeutic agents. A new series of bistetrahydroquinolines (bis-THQs) was synthesized using imino Diels-Alder reactions between dialdehydes, anilines and N-vinyl-2-pyrrolidone (NVP). The notable features of this procedure are mild reaction conditions, greater selectivity and good yields of products. In addition, the inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) of some selected derivatives is reported. The feasible binding modes of these active compounds, within AChE and BuChE binding sites, were predicted by molecular docking experiments and their binding affinity was estimated by means of free energy calculations through the MM-GBSA approximation.

| S-EPMC6270290 | biostudies-literature

Dual Activation of Aromatic Diels-Alder Reactions.

Project description:The unusually fast Diels-Alder reactions of [5]cyclophanes were analyzed by DFT at the BLYP-D3(BJ)/TZ2P level of theory. The computations were guided by an integrated activation-strain and Kohn-Sham molecular orbital analysis. It is revealed why both [5]metacyclophane and [5]paracyclophane exhibit a significant rate enhancement compared to their planar benzene analogue. The activation strain analyses revealed that the enhanced reactivity originates from 1)?predistortion of the aromatic core resulting in a reduced activation strain of the aromatic diene, and/or 2)?enhanced interaction with the dienophile through a distortion-controlled lowering of the HOMO-LUMO gap within the diene. Both of these physical mechanisms and thus the rate of Diels-Alder cycloaddition can be tuned through different modes of geometrical distortion (meta versus para bridging) and by heteroatom substitution in the aromatic ring. Judicious choice of the bridge and heteroatom in the aromatic core enables effective tuning of the aromatic Diels-Alder reactivity to achieve activation barriers as low as 2?kcal?mol-1 , which is an impressive 35?kcal?mol-1 lower than that of benzene.

| S-EPMC6771859 | biostudies-literature

Intramolecular Diels-Alder reactions of cyclopropenone ketals.

Project description:The first intramolecular cycloaddition reactions of cyclopropenone ketals with tethered electron-deficient, electron-rich, and neutral 1-substituted dienes are reported, constituting inverse electron demand, normal, and neutral Diels-Alder reactions, that provide exclusively the exo [4 + 2] cycloaddition products without the intervention of [1 + 2], [3 + 2], or [3 + 4] cycloadducts in reactions whose courses do not depend on the reaction conditions, the diene activating substituent, or the nature of the tethering.

| S-EPMC2912946 | biostudies-literature

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

Synthesis of tetrasubstituted 1-silyloxy-3-aminobutadienes and chemistry beyond Diels-Alder reactions.

Project description:Electron-rich dienes have revolutionized the synthesis of complex compounds since the discovery of the legendary Diels-Alder cycloaddition reaction. This highly efficient bond-forming process has served as a fundamental strategy to assemble many structurally formidable molecules. Amino silyloxy butadienes are arguably the most reactive diene species that are isolable and bottleable. Since the pioneering discovery by Rawal, 1-amino-3-silyloxybutadienes have been found to undergo cycloaddition reactions with unparalleled mildness, leading to significant advances in both asymmetric catalysis and total synthesis of biologically active natural products. In sharp contrast, this class of highly electron-rich conjugated olefins has not been studied in non-cycloaddition reactions. Here we report a simple synthesis of tetrasubstituted 1-silyloxy-3-aminobutadienes, a complementarily substituted Rawal's diene. This family of molecules is found to undergo a series of intriguing chemical transformations orthogonal to cycloaddition reactions. Structurally diverse polysubstituted ring architectures are established in one step from these dienes.

| S-EPMC4411301 | biostudies-literature

Origins of stereoselectivity in the trans Diels-Alder paradigm.

Project description:The regioselectivity and stereoselectivity aspects of the Diels-Alder/radical hydrodenitration reaction sequence leading to trans-fused ring systems have been investigated with density functional calculations. A continuum of transition structures representing Diels-Alder and hetero-Diels-Alder cycloadditions as well as a sigmatropic rearrangement have been located, and they all lie very close in energy on the potential energy surface. All three pathways are found to be important in the formation of the Diels-Alder adduct. Reported regioselectivities are reproduced by the calculations. The stereoselectivity of radical hydrodenitration of the cis-Diels-Alder adduct is found to be related to the relative conformational stabilities of bicyclic radical intermediates. Overall, the computations provide understanding of the regioselectivities and stereoselectivities of the trans-Diels-Alder paradigm.

| S-EPMC2908589 | 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