On the Solvent and Temperature Driven Stereoselectivity of the Diels-Alder Cycloaddition Reactions of Furan with Maleic Anhydride and Maleimide

In quantum chemical calculations, the Diels-Alder cycloaddition reaction of maleic anhydride with furan favors the endo-isomer kinetically in the gas phase. This preference, however, changes in favor of the exo-isomer on inclusion of solvent effects. For example, in acetonitrile, the exo-isomer was calculated to form twice as fast as the endo-isomer at room temperature, an observation that corroborates well with the experiments. The free energy change of the reaction is such that it allows faster reversal of the endo-isomer to the reactants in an equilibrium process and, thus, the predominance of the more stable exo-isomer eventually. The reaction of maleimide with furan is similar to that of maleic anhydride. However, it favors predominantly endo selectivity at temperatures below 320 K which is in excellent agreement with the experimental studies of temperature dependence of this DA reaction. Further, a gedanken calculation of the DA reaction of cyclopropene with furan has been investigated to delineate the effect of the retro-pathway on the stereoselectivity.

On the Solvent and Temperature Driven Stereoselectivity of the Diels-Alder Cycloaddition Reactions of Furan with Maleic Anhydride and Maleimide

In quantum chemical calculations, the Diels-Alder cycloaddition reaction of maleic anhydride with furan favors the endo-isomer kinetically in the gas phase. This preference, however, changes in favor of the exo-isomer on inclusion of solvent effects. For example, in acetonitrile, the exo-isomer was calculated to form twice as fast as the endo-isomer at room temperature, an observation that corroborates well with the experiments. The free energy change of the reaction is such that it allows faster reversal of the endo-isomer to the reactants in an equilibrium process and, thus, the predominance of the more stable exo-isomer eventually. The reaction of maleimide with furan is similar to that of maleic anhydride. However, it favors predominantly endo selectivity at temperatures below 320 K which is in excellent agreement with the experimental studies of temperature dependence of this DA reaction. Further, a gedanken calculation of the DA reaction of cyclopropene with furan has been investigated to delineate the effect of the retro-pathway on the stereoselectivity.

Reaction of 2-Pyridylmethylthiourea Derivatives with [(en)2Co(OSO2CF3)2]+ Induces Hypodentate Coordination of an Ethylenediamine Ligand

Pyridylmethylthiourea derivatives coordinate with [(en)2Co(OSO2CF3)2]+ in a tridentate manner resulting in the formation of a hypodentate ethylenediamine ligand. Four ligands were studied: N-(R)phenyl-N′-2-pyridylmethylthiourea (R = H (1a), CH3 (1b), OCH3 (1c)) and N-benzyl-N′-2-pyridylmethylthiourea (2). These bind through the sulfur, a deprotonated exo nitrogen, and the pyridyl nitrogen atoms forming four and five-membered rings, respectively. The ligand also coordinates in a bidentate manner through the sulfur and deprotonated endo or exo nitrogen atoms, forming two additional coordination isomers. The solid state structure (X-ray) of one of the bidentate isomers of Co-1b2+ (endo isomer) shows that the coordinated thiourea sulfur induces a structural trans effect of 0.035 Å on the trans Co–N bond while that of the tridentate isomer of Co-1a3+ confirms the coordination mode of the ligand and the presence of a protonated hypodentate ethylenediamine ligand as suggested by 1H and 13C NMR spectroscopy.

Analgesic and anticonvulsive activity new compounds with norbornene and adamantane fragments

IntroductionThe present work deals with analgesic and anticonvulsive activity of four novel aminoalcohols C-81, C-78, C-115 and C-120 synthesized on basic glycidylcamphorimide (Gly-CI), exo- and endo-aminomethylnorbornenes, aminoethyladamantan (remantadin) and aminoethylnorbornan (deitiforin).AimsSynthesis cage-like compounds with excellent analgesic and anticonvulsive activity. Methods: Experiments have been carried out on both genders adult white mice at the dozes of 1/10 LD50. Investigated substances were entered intraperitoneally. Preparations have been entered as a water suspension on TWEEN-40. Acute toxicity of compounds (LD50) has been measured by Litchfield & Wilcoxon method in Prozorovsky V.B. modification and amounts 370–1196 mg/kg.ResultsThe most toxic compound is aminoalcohol C-115 with adamantane fragment. Investigation of analgesic activity has been carried out by determination of pain threshold by thermal irritation method (hot plate) at 55°C. Anticonvulsive activity has been studied by corazole spasm test. The activity has been calculated in percentage in relation to control group of animals.ConclusionsAll aminoalcohols have shown analgesic and (except for compound C-81) anticonvulsive activity. For exo-aminoalcohol C-81 the most intense activity are analgesic (195.0%) and for endo-isomer C-78 - anticonvulsive activity (213.3%). Compounds C-115 and C-120 shows medium analgesic (67.1 and 58.5%) and anticonvulsive activity (13.4 and 67.5%).

QTAIM–DI–VISAB computational study on the Diels–Alder reaction of cyclopentadiene — On the nature of the so-called secondary orbital interactions

We have undertaken a QTAIM–DI–VISAB computational study of the dimerization of cyclopentadiene (1), the archetypal example of a Diels–Alder reaction that has been studied experimentally and computationally. Secondary orbital interactions (SOIs) that have gained acceptance in the interpretation of stereoselectivities seen in many cycloaddition reactions have been used to account for the fact that the endo isomer was the kinetic product of the reaction. To this point, “classical” MO analyses along with a variety of arbitrarily assigned solid and dashed lines (solid lines and bold dashes for “primary” interactions and dashed and dotted lines to differentiate between different SOI schemes) have been used in an attempt to describe the bonding of the transition states. Yet, the existence of SOIs has been challenged. Our interest in applying QTAIM to fundamental chemical problems in physical organic chemistry, with the goal of refining our knowledge of the bonding in transition-states and ground-state molecules while obviating the need to use a variety of confusing arbitrarily assigned dashed and dotted lines, led us to a QTAIM–DI–VISAB computational study of the endo and exo dimerizations of 1 at the DFT B3PW91 and MPW1PW91 levels. We have characterized the bonding interactions between cyclopentadiene rings in the various transition states and show that “normal” bonds are present where SOIs have been considered to exist. There is no need to use different types of dashed and dotted lines. An analysis of the changes in atom energies revealed that the significant destabilization of the carbon atoms in achieving the TSs (potentially leading to a very high barrier) is ameliorated by a stabilization of the hydrogen atoms leading to the relatively low barrier for the D–A reaction.Key words: cyclopentadiene dimerization, bispericyclic transition states, DFT calculations, QTAIM–DI–VISAB analysis, bonding, atom energy analysis.

Intramolecular [4 + 3] cycloadditions – Stereochemical issues in the cycloaddition reactions of cyclopentenyl cations – A synthesis of (+)-dactylol

Five cyclopentanones were prepared for the purpose of examining the effects of stereogenic centers on the course of the intramolecular [4 + 3] cycloaddition reactions of cyclopentenyl cations. One substrate reacted with very high levels of diastereoselectivity and was converted to (+)-dactylol. The cyclopentenone without stereogenic centers on the tether or the five-membered ring gave two cycloadducts, the endo isomer being only slightly favored over the exo. Other substrates reacted with generally good to poor stereoselectivity. An epimer of the substrate leading to (+)-dactylol afforded all possible isomers of the cycloadduct with relatively poor stereoselectivity.Key words: cycloaddition, total synthesis, dactylol.

13C magnetic resonance studies. 138. An examination of the [3.2.2.0] → [4.2.1.0] rearrangement via β-enolization and H/D exchange in tricyclic ketones

The behavior of the endo and exo isomers of 7,7-dimethyltricyclo[3.2.2.02,4]nonan-6-one (9, 17) under strongly basic conditions (t-BuO−/t-BuOH/185 °C) has been examined. In both cases rearrangement to the corresponding 8,8-dimethyl-tricyclo[4.2.1.02,4]nonan-7-one (11, 18) was found, with the exo isomer reacting approximately 8 times faster. Experiments in tert-butyl alcohol-O-d1 were carried out to determine the specific sites, the relative rates, and the stereochemistry of deuterium incorporation in the initial ketones. Although H/D exchange occurs most readily at the cyclopropyl methylene carbon in the endo isomer, none of the rearrangement product expected to arise via γ-enolate formation was observed. The results for these ketones are compared with our earlier observations in the related [2.2.2], [3.2.1.0], and [3.3.1.0] systems. Keywords: homoenolization, tricyclic ketones, H/D exchange.