A theoretical review for novel Lewis base amine/imine-catalyzed reactions
Recent advances in computational investigations of Lewis base amine/imine-catalyzed reactions have been systematically summarized and reviewed for the first time.
Optical purity, enantiomeric excess and the Horeau effect
Optical purity (op) and enantiomeric excess (ee) become equal when either heterochiral dimerization constant is twice that of homochiral dimerization constant or specific rotations of monomer and dimer are equal.
Synthetic and mechanistic aspects of sulfonyl migrations
Sulfonyl migrations, frequently described as ‘unusual’ or ‘unexpected’, from the last 20 years, including 1,2-, 1,3-, 1,4-, 1,5-, 1,6- and 1,7-sulfonyl shifts, through either radical or polar processes, either inter- or intramolecularly are reviewed.
Mechanistic knowledge and noncovalent interactions as the key features for enantioselective catalysed multicomponent reactions: a critical review
This critical short review focuses on some key features which determine successful enantioselective catalysed multicomponent reactions (MCRs) and are typically underappreciated in the literature.
The importance of N-heterocyclic carbene basicity in organocatalysis
This review highlights the importance of N-heterocyclic carbene (NHC) basicity for transformations in which NHCs are used as catalysts.
On the reciprocal relationship between σ-hole bonding and (anti)aromaticity gain in ketocyclopolyenes
σ-Hole bonding interactions (e.g., tetrel, pnictogen, chalcogen, and halogen bonding) can polarize π-electrons to enhance cyclic [4n] π-electron delocalization (i.e., antiaromaticity gain) or cyclic [4n + 2] π-electron delocalization (i.e., aromaticity gain).
Divergent pathway and reactivity control of intramolecular arene C–H vinylation by vinyl cations
A computational study revealed the mechanistic details and controlling factors of reactivity in intramolecular C–H vinylation through a vinyl cation intermediate.
The optimal DFT approach in DP4 NMR structure analysis – pushing the limits of relative configuration elucidation
What computational methods should be used to achieve the most reliable result in computational structure elucidation? A study on the effect of quality and quantity of geometries on computational NMR structure elucidation performance is reported.
Mechanism of nitrones and allenoates cascade reactions for the synthesis of dihydro[1,2-a]indoles
Quantum mechanical calculations (DLPNO-CCSD(T) and M06-2X) are employed to gain insights into the mechanism and selectivity in the catalytic synthesis of dihydropyrido[1,2-a]indoles from the cascade reaction between nitrones and allenes.
A Viedma ripening route to an enantiopure building block for Levetiracetam and Brivaracetam
A simple route to enantiomerically pure (S)-2-aminobutyramide – the chiral component of the anti-epileptic drugs Levetiracetam and Brivaracetam has been developed. This approach is based on the rational design and application of a Viedma ripening process. The practical potential of the process is demonstrated on a large scale.
Superelectrophilic activation of 1-nitronaphthalene in the presence of aluminum chloride. Reactions with benzene and cyclohexane
Aluminum chloride was successfully used instead of liquid superacids to mediate selective reactions of 1-nitronaphthalene with benzene and cyclohexane.
Experimental evidence for the formation of cationic intermediates during iodine(III)-mediated oxidative dearomatization of phenols
Hammett analysis reveals iodine(III)-mediated oxidative dearomatization reactions proceed through cationic intermediates and not direct nucleophilic attack on an activated phenol.
On the dual reactivity of a Janus-type mesoionic dipole: experiments and theoretical validation
A mesoionic bicycle, easily synthesized from a proteinogenic amino acid, L-leucine, behaves as both thiazolium-olate and diazolium-olate dipoles, as unveiled by its dipolar cycloadditions.
A “cross-stitched” peptide with improved helicity and proteolytic stability
Peptide “cross-stitching” maintains binding affinity and can enhance helical and proteolytic stability.
A mechanistic study on Cu(I) catalyzed carboxylation of the C–F bond with CO2: a DFT study
Cu(I) catalyzed carboxylation of the C–F bond is an excellent method for construction of complex fluoroacrylate compounds with high regioselectivity. Here, theoretical calculations were carried out to investigate the detailed mechanism and origin of regioselectivity.
Regioselectivity in the adiabatic photocleavage of DNA-based oxetanes
Raise the anchor! Synthesis, X-ray and NMR characterization of 1,3,5-triazinanes with an axial tert-butyl group
N-t-Bu-N′,N′′-Disulfonamide-1,3,5-triazinanes were synthesized and studied by X-ray single crystal structure analysis and dynamic low-temperature NMR.
How the combination of PhIO and I2 provides a species responsible for conducting organic reactions through radical mechanisms
This contribution provides an answer to the long-standing question of how organic radicals are produced by the PhIO/I2 system and how the ensuing radicals are oxidized by the same system to yield the organic products.
Experimental and computational evidence on gold-catalyzed regioselective hydration of phthalimido-protected propargylamines: an entry to β-amino ketones
Gold-catalyzed regioselective hydration of phthalimido-protected propargylamines.
Microwave-assisted nucleophilic degradation of organophosphorus pesticides in propylene carbonate
Degradation of organophosphorus pesticides was achieved by using microwaves, an ionic liquid and propylene carbonate.
Guest-induced supramolecular chirality transfer in pseudorotaxanes: experimental and computational study
We constructed several pseudorotaxanes via chiral binaphthalene crown ethers and achiral ammonium salts, and found that the binaphthalene groups can induce new CD signals only in the pseudorotaxane between the hosts and the guest with anthryl.
How inverting β-1,4-galactosyltransferase-1 can quench a high charge of the by-product UDP3− in catalysis: a QM/MM study of enzymatic reaction with native and UDP-5′ thio galactose substrates
The function of Asp252 in the catalysis of β-1,4-galactosyltransferase-1 may be the stabilization of a high charge of the by-product UDP3− by a substrate-assisted proton transfer reaction.
Influence of a 4′-substituent on the efficiency of flavonol-based fluorescent indicators of β-glycosidase activity
Fluorescent probes for glycosidases, based on the excited-state intramolecular proton transfer (ESIPT) phenomenon, are presented.
A simpler method affords evaluation of π stabilization by phenylalanine of several biochemical carbocations
Simple models based on measurements taken from X-ray structures of relevant active sites are used to evaluate π stabilization by phenylalanine of several biochemical carbocations.
Computational investigations of NHC-backbone configurations for applications in organocatalytic umpolung reactions
Computational modeling and orbital analyses reveal enhanced catalytic properties based on N-heterocyclic carbene backbone modifications.
The effect of bisimidazolium-based ionic liquids on a bimolecular substitution process. Are two head(group)s better than one?
Bisimidazolium-based ionic liquids generally result in greater rate constants than the corresponding monocationic salts. The effect depends on the length of the bridging chain; likely due to a change in the mode of interactions in solution.
Oxidative damage of proline residues by nitrate radicals (NO3˙): a kinetic and product study
Kinetic studies in acetonitrile revealed that proline residues in peptides are considerably protected against radical-induced oxidative damage by the neighbouring peptide bonds, compared with the single amino acid.
Deconvolution of fast exchange equilibrium states in NMR spectroscopy using virtual reference standards and probability theory
DFT–GIAO calculations combined with probability theory enable accurate prediction of fast exchange equilibrium states based on one experimental NMR dataset.
Mechanistic insights into Smiles rearrangement. Focus on π–π stacking interactions along the radical cascade
The synthesis of new arene and heteroarene scaffolds of therapeutic interest has generated a renewed interest in the domino radical cyclisation–Smiles.
Decomplexation as a rate limitation in the thiol-Michael addition of N-acrylamides
Experimental and computational agreement highlights rate-limiting “product decomplexation” and functional group effects in the thiol-Michael addition, utilized for sequence-defined oligomers.
A fully diastereoselective oxidation of a mesoionic dipole with triplet molecular oxygen
A metal-free oxidation of a mesoionic dipole with atmospheric oxygen triggers a complex cascade reaction through spin intercrossing, as supported by computation, and leading to polycycles with complete diastereoselection.
The effect of solvation in torquoselectivity: ring opening of monosubstituted cyclobutenes
The paradigmatic electrocyclic ring opening of monosubstituted cyclobutenes has been used to diagnose possible solvation effects tuning the torquoselectivity observed in these reactions.
Influence of phenylpropanoid units of lignin and its oxidized derivatives on the stability and βO4 binding properties: DFT and QTAIM approach
The interference of the phenylpropanoid units (S, G and H) on the properties of the βO4 bond was investigated by the topological analysis via QTAIM and the stability of the lignin and its oxidized structure were studied by the gap analysis
The chemical gymnastics of enterocin: evidence for stereodivergence in Nature
Stereodivergence in Nature encapsulates both enzymatic (biosynthetic) and non-enzymatic (chemical) diversification of natural product scaffolds arising from a single biosynthetic pathway.
Palladium-catalyzed C–H activation of anisole with electron-deficient auxiliary ligands: a mechanistic investigation
In this work, the experimentally observed site-selectivity and ligand choice of Yu's meta-arylation reaction were rationalized through DFT calculations.
Understanding the mechanism and reactivity of Pd-catalyzed C–P bond metathesis of aryl phosphines: a computational study
Computational study revealed the mechanistic details and reactivity profile of the Pd/PhI-cocatalyzed C–P bond metathesis of aryl phosphines.
Monophenolase and catecholase activity of Aspergillus oryzae catechol oxidase: insights from hybrid QM/MM calculations
Monophenolase and diphenolase activities of the [Cu2O2]2+ active site of Aspergillus oryzae catechol oxidase are revealed by hybrid QM/MM calculations.
Photochemical [2 + 2] cycloaddition reaction of carbonyl compounds with Danishefsky diene
An efficient oxetane formation has been developed in the photochemical [2 + 2] cycloaddition reaction of benzophenone with Danishefsky diene.
Cross-linking of aromatic phenolate groups by cytochrome P450 enzymes: a model for the biosynthesis of vancomycin by OxyB
Aromatic cross-linking by cytochrome P450 enzymes was studied computationally. P450 Compound I rapidly abstracts two weak phenolic H-atoms that link up via a rate-determining C–O bond formation.
Understanding the structures and aromaticity of heteroporphyrins with computations
Different heteroporphyrins go through two different aromatic pathways, either 18π-annulene or 22π-electron model.
Meisenheimer complexes as hidden intermediates in the aza-SNAr mechanism
In this work we report a computational study about the aza-SNAr mechanism in fluorine- and chlorine-containing azines with the aim to unravel the physical factors that determine the reactivity patterns in these heterocycles towards propylamine.
Chemical transformations of push–pull fluorenones: push–pull dibenzodicyanofulvenes as well as fluorenone– and dibenzodicyanofulvene–tetracyanobutadiene conjugates
We report push–pull fluorenones (FOs) that can be transformed into dibenzodicyanofulvenes (DBDCFs). These FOs and DBDCFs, which contain a CC bond, can subsequently be converted into tetracyanobutadiene conjugates.
The intermolecular anthracene-transfer in a regiospecific antipodal C60 difunctionalization
The topochemically controlled regiospecific antipodal C60 difunctionalization proceeds via an ‘inverted sandwich’ with double-decker π–π-stacking interactions.
Controlling the liberation rate of the in situ release of a chemical fuel for the operationally autonomous motions of molecular machines
Aminolysis of the anhydride of 2-cyano-2-phenylpropanoic acid can be employed to conveniently regulate the liberation rate of the related acid which, in turn, can be used as a fuel for acid–base operated molecular machines.
Origin of the ligand effect in the cobalt catalyzed regioselective hydroboration of 1,3-diene
The detailed mechanism and the origin of the ligand-controlled regioselectivity in the cobalt catalyzed hydroboration of 2-substituted 1,3-diene have been investigated.
Enhanced reactivity of the pyrimidine peroxyl radical towards the C–H bond in duplex DNA – a theoretical study
The peroxyl radical exhibits a much stronger reactivity towards C1′–H1′ in duplex DNA with respect to single-stranded DNA.
Chemo- and regioselective click reactions through nickel-catalyzed azide–alkyne cycloaddition
Nickel-catalyzed [3 + 2] cycloaddition reactions of unsymmetrical alkynes and organic azides afford substituted 1,2,3-triazoles with high levels of chemo- and regioselectivity.
The quasi-irreversible inactivation of cytochrome P450 enzymes by paroxetine: a computational approach
The potency of paroxetine as a P450 inhibitor is mainly attributed to the availability of two active sites on its structure, its compatibility with P450's active site and the ease of its tight coordination to heme iron.
Proof of concept for poor inhibitor binding and efficient formation of covalent adducts of KRASG12C and ARS compounds
Comprehensive molecular modeling and kinetic analysis reveal a novel mechanism of the inhibition of the oncogenic mutant of the “undruggable” KRAS protein.
Free-base porphyrins with localized NH protons. Can substituents alone stabilize the elusive cis tautomer?
The localization of central NH protons in antipodally tetrasubstituted tetraphenylporphyrins suggested that suitable substitutions might also stabilize a porphyrin cis tautomer, a possibility that appears to be supported by DFT calculations.
Examination of pinanediol–boronic acid ester formation in aqueous media: relevance to the relative stability of trigonal and tetrahedral boronate esters
The “inverted” order of stabilities Ktrig > Ktet is observed for pinanediol boronate esters in spite of the existence of the usual strain release effect in the O–B–O angle of the cyclic diol ester.
Elucidation of the atroposelectivity in the synthesis of axially chiral thiohydantoin derivatives
A DFT study is carried out in order to elucidate the racemization and cyclization mechanism as well as the atroposelectivity during the synthesis of 2-thiohydantoins. Computational data shows that the racemization occurs after cyclization with the assistance of triethyl amine.
Base-catalyzed C-alkylation of potassium enolates with styrenes via a metal–ene reaction: a mechanistic study
Base-catalyzed, C-Alkylation of potassium (K) Enolates with Syrenes (CAKES) enables practical synthesis or elaboration of pharmaceutical cores via a thusfar elusive mechanism. Herein, computational (DFT) and kinetic studies back a metal-ene reaction.
Establishing linear-free-energy relationships for the quadricyclane-to-norbornadiene reaction
The kinetics of the thermal quadricyclane-to-norbornadiene (QC-to-NBD) isomerization follows a linear-free-energy relationship when using Creary radical values for a selection of aryl/cyano disubstituted derivatives.
Amplification of the chiroptical response of UV-transparent amines and alcohols by N-phthalimide derivatization enabling absolute configuration determination through ECD computational analysis
Transformation of chiral UV-transparent amines and alcohols to phthalimides enhances their chiroptical response allowing their absolute configuration assignment by ECD computation.
The pKa values of N-aryl imidazolinium salts, their higher homologues, and formamidinium salts in dimethyl sulfoxide
The effects of substitution, ring size and cyclisation on the pKa values of imidazolinium salts, higher homologues and formamidinium salts in DMSO are quantified, considering structural and electronic motifs along with crystallographic analyses.
How does cross-conjugation influence thiol additions to enones? A computational study of thiol trapping by the naturally occurring divinyl ketones zerumbone and α-santonin
DFT calculations show how the kinetics and thermodynamics of thiol additions to enones are affected by incorporation of the enone into a cross-conjugated divinyl ketone moiety.
Kinetic modelling of acyl glucuronide and glucoside reactivity and development of structure–property relationships
Detailed kinetic and transition structure modelling to rationalise the differences in reactivity observed between the acyl glucuronide and glucoside metabolites of a series of phenylacetic acid analogues.
Mechanistic investigation into phenol oxidation by IBX elucidated by DFT calculations
Density functional theory (DFT) at the SMD/M06-2X/def2-TZVP//SMD/M06-2X/LANL2DZ(d),6-31G(d) level was used to explore the regioselective double oxidation of phenols by a hypervalent iodine(V) reagent (IBX) to give o-quinones.
Looking at the big picture in activation strain model/energy decomposition analysis: the case of the ortho–para regioselectivity rule in Diels–Alder reactions
The regioselectivity of the DA reaction is predicted by the ortho–para rule which has been explained from FMO theory. Using DFT calculations and ASM/EDA, we found that the results vary depending the position where it is performed.
The phosphorylation mechanism of mevalonate diphosphate decarboxylase: a QM/MM study
Combined MD and QM/MM studies suggested that mevalonate diphosphate decarboxylase requires two magnesium ions for a phosphorylation reaction.
Mechanism and stereoselectivity of benzylic C–H hydroxylation by Ru–porphyrin: a computational study
Density functional theory calculations of an asymmetric benzylic C–H hydroxylation revealed the steric repulsion between the phenyl group of ethylbenzene and the bulky substituent of the D4-symmetric chiral Ru–porphyrin accounts for the stereoselectivity.
The impact of cation structure upon the acidity of triazolium salts in dimethyl sulfoxide
The effect of structure on the pKa value of triazolium salts in dimethyl sulfoxide is quantified, considering common structural and electronic motifs. Included is the first pKa measurement of a triazolium salt that generates a mesionic carbene.
Electronic effects in tautomeric equilibria: the case of chiral imines from D-glucamine and 2-hydroxyacetophenones
Hammett plots show straightforward relationships for tautomeric equilibria in a new class of chiral imine–enamine structures.
(3S,4R)-3,4-Dihydroxy-N-alkyl-L-homoprolines: synthesis and computational mechanistic studies
This is the first synthetic report of (3S,4R)-dihydroxy-N-alkyl-L-homoprolines described so far.
Systematic characterisation of the structure and radical scavenging potency of Pu'Er tea () polyphenol theaflavin
Resolving the functional 3D structural poses of Pu'Er tea antioxidant theaflavin.
Gold(I)-catalyzed nucleophilic cyclization of β-monosubstituted o-(alkynyl)styrenes: a combined experimental and computational study
The diastereospecific 5-endo cyclization of β-monosubstituted o-(alkynyl)styrenes to 1-functionalized-1H-indenes is reported. The regiospecific generation of a cyclopropyl gold carbene intermediate is also supported by DFT calculations.
Theoretical insights into the E1cB/E2 mechanistic dichotomy of elimination reactions
Modeling the E1cB, E2, and E1cB/E2 borderline mechanisms in terms of carbanion stabilization.
Mechanism of fatty acid decarboxylation catalyzed by a non-heme iron oxidase (UndA): a QM/MM study
QM/MM calculations reveal that the fatty acid decarboxylase UndA employs the FeIII–OO˙− complex to initiate the β-H abstraction with the monodentate coordination mode. The iron center accepts the extra electron of the substrate radical.
An efficient synthesis of benzothiazole using tetrabromomethane as a halogen bond donor catalyst
A CBr4 catalyzed simple, mild, and efficient protocol has been developed for the synthesis of 2-substituted benzothiazole from 2-aminothiophenols and N-methylthioamides under solvent free conditions.
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The latest articles published in Organic and Biomolecular Chemistry related to mechanistic, computational & physical organic chemistry research.