Construction of alkyl-substituted 7-norbornenones through Diels-Alder cycloaddition of electron-deficient olefins and a cyclopentadienone derivative generated in situ

Dimeric sesquiterpenoids possessing densely substituted 7-norbornenone/7-norbornenol motifs pose a considerable challenge for chemical synthesis. From a strategic perspective, one could envision intermolecular Diels-Alder cycloaddition as a straightforward method for assembling alkyl-substituted 7-norbornenones. However, this approach is hindered by lability of the required dienes, namely alkylsubstituted cyclopentadienones. Here we report a one-pot protocol for construction of alkyl-substituted...     

Density functional theory study of the cycloaddition reaction of furan derivatives with masked o-benzoquinones. Does the furan act as a dienophile in the cycloaddition reaction?

The molecular mechanism for the cycloaddition reaction between 2-methylfuran and a masked o-benzoquinone has been characterized using quantum mechanical calculations at the B3LYP/6-31G theory level. An analysis of the results on the reaction pathway shows that the reaction takes place along a polar stepwise mechanism. The first and rate-determining step corresponds to the nucleophilic attack of the furan ring on the doubly conjugated position of the 2,4-dienone system present at the masked o-benzoquinone to give a zwitterionic intermediate. Closure of this intermediate affords the formally [2 + 4] cycloadduct. For the second step two reactive channels have been characterized corresponding to the formation of the formally [2 + 4] and [4 + 2] cycloadducts. Analysis of the energetic results indicates that while the first is the meta regiocontrolling and endo stereocontrolling step, the second one is responsible for the formation of the unexpected formally [2 + 4] cycloadduct. The global and local electrophilicity/nucleophilicity power of the reactants and intermediate have been evaluated to rationalize these results. Density functional theory analysis for these cycloadditions is in complete agreement with the experimental outcome, explaining the reactivity and selectivity of the formation of the formally [2 + 4] cycloadducts.     

Molecular hybridization-guided one-pot multicomponent synthesis of chromanone-fused 3,3′-pyrrolidinyl-dispirooxindoles through a 1,3-dipolar cycloaddition reaction

A new methodology was developed for the synthesis of 3,3′-pyrrolidinyl-dispirooxindoles 3 through a 1,3-dipolar cycloaddition event of isatylidenyl-chromanones 2 with azomethine ylides (thermally generated in situ from isatins and sarcosine). The method gives an easy access to a series of highly functionalized products containing three consecutive stereocenters and vicinal spiroquaternary stereocenters fused in one ring structure with 15 examples in high yields (up to 82% yield) and good diastereoselectivity (up to >20:1), which makes possible the synthesis of libraries under similar circumstances. Moreover, the current method provides a convenient approach for the efficient incorporation of two biologically important scaffolds (chromanone and 3,3′-pyrrolidinyl-dispirooxindoles). X-ray diffraction studies of one of the cycloadducts proved the structure and regiochemistry of the cycloaddition. In particular, their biological activity against human leukemia cells K562 and normal L929 cells has been evaluated. These results suggested that 3,3′-pyrrolidinyl-dispirooxindoles 3 may be potential leads for further biological screenings.     

New materials with high π conjugation by reaction of 2-oxazoline containing phenols with polyamidines and inorganic base

The non-covalent interactions between 2-oxazoline containing phenols and an aliphatic polyamidines as well as an inorganic base were studied. The reaction of a weak acid with a strong base results in the formation of the deprotonated species and subsequently in the formation of a new electronic structure. A bathochromic shift of the wavelength of the absorption maxima of the chromophores bounded to polyamidine was observed. Depending on the structure of the chromophore, the shift of the absorption maxima is 40-100 nm. The changes in photochemical behavior can be explained by the higher portion of quinoid structures in the conjugated π-system. The degree of deprotonation is dependent on the molar ratio of the chromophore and the polymeric base. Analogous results were obtained with an inorganic base.     

One-pot multicomponent construction of chromanone-fused pyrrolidinyl spirooxindole collections through a decarboxylative 1,3-dipolar [3 + 2] cycloaddition reaction

Abstract

A new method was developed for the facile one-pot multicomponent construction of heterocycle-fused spiro compounds containing chromanone and pyrrolidinyl spirooxindoles, two potential pharmacophores, in one molecule through a decarboxylative 1,3-dipolar [3?+?2] cycloaddition reaction of carboxylic acid group-activated chromones 1 with isatin-derivated azomethine ylides based on molecular hybridization strategy. A wide variety of products with three contiguous stereocenters including a spiro quaternary stereocenter were smoothly prepared with high efficiency (up to 87% yield and 20:1?diastereomeric ratio). This method could offer libraries of architecturally diverse and multiple pharmacore collections, potentially useful in medicinal chemistry.     

Synthesis of functionalized pyrroles and fused pyrroles through intermolecular [3 + 2] cycloaddition reaction

A facile and efficient synthesis of pyrrole and pyrrole-fused heterocyclic compounds has been demonstrated. The current protocol involves the in situ generation of azomethine ylides which undergoes intermolecular cycloaddition reaction and subsequent treatment with DDQ provides the pyrrole and fused heterocyclic compounds in good yields.     

Convenient synthesis of ferrocenyl β-C-glycosydic spiropyrrolidines and pyrrolizidines through 1,3-dipolar cycloaddition reaction

An expedient method for the synthesis of ferrocene grafted β-C-glycosydic spiroheterocycles is reported through 1,3-dipolar cycloaddition reaction (1,3-DC reaction). The novel C-glycosyl dipolarophiles derived from d-glucose, d-mannose, and d-ribose underwent neat [3+2] cycloaddition reaction with the azomethine ylides generated from 1,2-diketones and secondary amino acids to give the corresponding β-C-glycosidic heterocycles in good yields. The electrochemical behavior of the cycloadducts is also described.     

Quantum chemical study on the thermal Diels-Alder reaction of cyclohexadiene and methyl crotonate

AM1 molecular orbital method using the unrestricted Hartree-Fock(UHF) calculations has been applied to investigate the thermal reaction of cyclohexadiene and methyl crotonate. The calculated results indicate that the thermal Diels-Alder reaction proceeds to product through the concerted path and two radical pathways.     

A relation between different scales of electrophilicity: are the scales consistent along a chemical reaction?

In this paper, a relationship is established between three electrophilicity scales, namely, the electrophilicity index defined by Parr, Liu, and von Szentpaly; the electron affinity; and the energy of the lowest unoccupied molecular orbital (LUMO). Profiles of electrophilicity index and LUMO energies for different kinds of chemical reactions are compared to verify if they remain consistent during a whole chemical process. It appears that the electrophilicity index and the LUMO energies are linearly correlated in almost all the cases. Besides electrophilicity scales, profiles provide valuable information about the charge-transfer stage of a chemical process.     

Intramolecular Diels-Alder cycloaddition/rearrangement cascade of an amidofuran derivative for the synthesis of (±)-minfiensine

An efficient synthesis of (±)-minfiensine has been accomplished employing an intramolecular Diels-Alder cycloaddition/rearrangement cascade of an amidofuran derivative. Thermal reorganization of the initially formed [4+2]-cycloadduct affords the critical tetrahydroiminoethanocarbazole skeleton of the alkaloid in high yield.     

Diversity-oriented one-pot multicomponent synthesis of chromanone-based 3,3′-pyrrolidinyl-spirooxindoles via a 1,3-dipolar cycloaddition reaction

A new methodology was developed for the highly efficient one-pot multicomponent synthesis of chromanone-based 3,3′-pyrrolidinyl-spirooxindoles via a 1,3-dipolar cycloaddition reaction of chromones 1 with azomethine ylides (thermally generated in situ from isatins and proline or thioproline). Another valuable application of this method was for the less reactive chromone through a carboxylic acid-activation and then decarboxylation strategy, which enabled diversity-oriented synthesis of complex pirooxindoles bearing four contiguous stereocenters (one of which is a spiro quaternary stereocenter) with high efficiency and stereoselectivity (up to 90% yield and 20:1 d.r.). This protocol could provide libraries of stereochemically rich and multiple pharmecore collections, that will help in search for new drug-like molecules.     

Synthesis of pyrroles through a 4π-electrocyclic ring-closure reaction of 1-azapentadienyl cations

1-Azapenta-1,4-diene-3-ols 4a-m are easily accessible from 1-azapenta-1,4-dien-3-ones 3a-i and organolithium compounds. Treatment of the compounds 4a-m with strong acid (triflic acid) generates 1-azapentadienyl cations in situ upon protonation at the hydroxyl oxygen atom and subsequent water elimination. The intermediate cations undergo facile 4π-electrocyclization under ambient condition to give diversely substituted pyrroles 6a-m in moderate to good yield. The product pyrrole 6k could be characterized by X-ray diffraction. Quantum chemical calculations were performed to elucidate the mechanism of this reaction with respect to starting compounds, transition states, and products. They support the proposed mechanism of a 4π-conrotatory M?bius-type electrocyclic ring-closure reaction.     

Direct construction of novel exo′-selective spiropyrrolidine bisoxindoles via a three-component 1,3-dipolar cycloaddition reaction

An efficient synthesis of novel exo′-selective spiropyrrolidine bisoxindoles has been achieved via a three-component 1,3-dipolar cycloaddition reaction. The azomethine ylides generated in situ from substituted isatin and primary α-amino acid methyl ester (or primary α-amino acids) reacted with the Knoevenagel adducts of substituted isatin to furnish novel spiropyrrolidine bisoxindoles in high yields (up to 99%). The structure and relative stereochemistry of cycloadducts were confirmed by single crystal X-ray diffraction. The possible mechanism was proposed and the cycloaddition proceeded via exo′-transition state.     

Concentration and temperature dependency of regio- and stereoselectivity in a photochemical [2 + 2] cycloaddition reaction (the Paternò-Büchi reaction): origin of the hydroxy-group directivity

A set of photochemical oxetane formation reactions, i.e., the Paterno?-Bu?chi (PB) reactions, of tetrahydrobenzofuranol derivatives 1a-d with benzophenone (BP) was investigated to examine poorly understood hydroxy-group directivity on regio- and stereoselectivity. The selectivities of the PB reactions for allylic alcohols 1a,d were found to be largely dependent upon the concentration of the allylic alcohols and the reaction temperature. The temperature-dependent change of the regioselectivity at high concentrations of allylic alcohols was similar to that of the hydroxy-protected methyl ether 1b and tetrahydrobenzofuran (1c). The effect of concentration on regioselectivity can be explained by the hydrogen-bonded aggregates, which mimic the selectivities observed during the PB reaction of 1b,c. The hydroxy-directed cis-selectivity of the higher-substituted oxetane 3a,d formed at low concentration of 1a,d was found to be larger than that at the higher concentration of 1a,d. The cis-selectivity of 3a,d was found to be higher than that of the lower-substituted oxetane 2a,d. The regioselectivity of the cis-configured oxetanes was higher than that of the trans-configured oxetanes. These experimental results strongly suggest that hydroxy-group directivity, induced by hydrogen-bonding stabilization, plays a role in controlling the regio- and stereoselectivity of the PB reactions. The steric effect was also responsible for the diastereoselectivity, as shown by the fact that the cis selectivity in 3d was higher than that in 3a. Computational studies at the (U)MP2 and (U)DFT level of theory revealed that hydrogen-bonding stabilization becomes important only in the excited complex (exciplex) between the triplet excited state of carbonyls and alkenes, in which the charge transfer occurs from the alkene to the excited carbonyl to make the carbonyl oxygen nucleophilic. No significant stabilization energy was found in the intermediary triplet state of biradicals. The combined experimental and computational studies have clarified the origin of the poorly understood hydroxy-group effect on a high degree of regio- and stereoselectivity, i.e., the cooperative effect of hydrogen-bonding stabilization in exciplexes and the steric bulk of the substituents.     

Approach to the aklavinone series through a new high pressure-induced [bcd → abcd] cycloaddition strategy

The high pressure-induced cycloaddition of diene 3 with tricyclic enone $\text{2}$ led to the tetracyclic adduct $\text{4}$.     

“Matrix effects” in the activation of compounds with a system of conjugation in the inhibition of oxidative processes

Russian Chemical Bulletin -     

Explicit definition of the reaction coordinate for the Jackels–Gu–Truhlar projection technique to compute harmonic vibrational frequencies along the intrinsic reaction path

It is shown that the Jackels–Gu–Truhlar projection technique for computing harmonic frequencies along the intrinsic reaction path is equivalent to use of a new, enormously broad family of the so-called hyperplanar-vibrational-surface (HVS) reaction coordinates, namely, for any arbitrarily chosen set of internal variables , the appropriate HVS reaction coordinate, s, is implicitly defined via the requirement that it remains constant on any so-called orthogonal-to-path hyperplane in the coordinate space spanned by variables . It is proven that s defined in such a way satisfies the local Hofacker–Marcus conditions and therefore there is no linear term in a Taylor expansion of the potential in terms of vibrational coordinates Q. Since the transformation from Q and s to is explicitly defined, one can use a standard technique to account for potential anharmonicities along the reaction path.     

Lateral sol–gel cross-linking of polyurethane using the a grafted triethoxysilyl group

3-Triethoxysilylpropyl isocyanate was used to graft a triethoxysilyl group to polyurethane (PU), and the grafted triethoxysilyl groups were used to cross-link PU chains through a sol–gel process. The soft segment melting temperature and enthalpy change were not significantly altered by the sol–gel cross-linking. The sol–gel cross-linked PUs exhibited significantly increased tensile strength and better tensile strain compared to the plain linear PU: the maximum stress and strain increased to 41 MPa and 1,972 %, respectively. Control series containing tetraethyl orthosilicate, a series without cross-linking, was also prepared for comparison with the sol–gel cross-linked PU series. The control series did not exhibit the increased tensile strength shown by the sol–gel cross-linked PU series. The cyclic shape memory tests demonstrated that the shape recovery was as high as 97 %, and both shape recovery and shape retention remained high after the four repeated tests. The sol–gel cross-linked PU series exhibited enhanced low-temperature flexibility compared to the plain linear PU due to the flexible silyl cross-linking group.