Non-covalent interactions in the diastereoselective synthesis of cis-2,3-dihydrobenzofurans: experimental and computational studies.

The diastereoselective synthesis of 2,3-DHBs has been previously reported via an intramolecular Michael addition reaction using alkali bases such as Cs2CO3 and K2CO3. However, no systematic study has been performed to understand the possible role of bases in the mechanism of the reaction and factors behind the stereoselective outcome of the reaction. Herein, from experimental and theoretical points of view, we disclose the role of the cesium salt in the rate-determining step along the catalytic cycle and the key role of stabilizing non-covalent interactions in the stereoselective outcome of the reaction.

Selective reduction of nitroarenes using Ru/C and CaH2.

Herein, we report an efficient and highly selective method for the reduction of aromatic, heteroaromatic and halonitro compounds using the readily available and cost-effective Ru/C as a catalyst along with unconventional CaH2 as a source of hydride. In most cases the corresponding anilines can be obtained by simple filtration without further purification. The use of 2-MeTHF and the simple operational work-up constitute a valid alternative to previous methodologies.

Reduction Over Condensation of Carbonyl Compounds Through a Transient Hemiaminal Intermediate Using Hydrazine.

Reduction of carbonyl moieties to the corresponding alcohol using simply hydrazine hydrate has been considerably unfeasible until now due to the well-known condensation reaction. However, herein, we report that using an excess of 20-fold equivalents, the reduction proceeds in excellent yields. 1H NMR study of the reaction and density functional theory (DFT) calculations indicate that the final fate of the hemiaminal intermediate is crucial to obtain the alcohol or the hydrazone.

Influence of Non-Covalent Interactions in the Exo- and Regioselectivity of Aza-Diels-Alder Reactions: Experimental and DFT Calculations.

A systematic experimental and theoretical study of the intermolecular Aza-Diels-Alder reaction using 5-aminopyrrole as a building block shows that the commonly accepted endo selectivity, ruled by controversial secondary orbital interactions, are overcome by non-covalent interactions affording to the unusual exo adduct. Additionally, the regioselectivity is also influenced for such interactions. The starting materials are easily prepared, and the use of water as the solvent is a great achievement for the development of cleaner synthetic methodologies.

3-Methoxalylchromone--a novel versatile reagent for the regioselective purine isostere synthesis.

The first synthesis of 3-methoxalylchromone was described. The reaction of the latter with electron-rich aminoheterocycles afforded a set of heteroannelated pyridines bearing a CO(2)Me substituent located at the α-position of the pyridine core.

2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors.

2-Arylthiomorpholine and 2-arylthiomorpholin-5-one derivatives, designed as rigid and/or non-basic phenylethylamine analogues, were evaluated as rat and human monoamine oxidase inhibitors. Molecular docking provided insight into the binding mode of these inhibitors and rationalized their different potencies. Making the phenylethylamine scaffold rigid by fixing the amine chain in an extended six-membered ring conformation increased MAO-B (but not MAO-A) inhibitory activity relative to the more flexible alpha-methylated derivative. The presence of a basic nitrogen atom is not a prerequisite in either MAO-A or MAO-B. The best K(i) values were in the 10(-8)M range, with selectivities towards human MAO-B exceeding 2000-fold.

Naphthylisopropylamine and N-benzylamphetamine derivatives as monoamine oxidase inhibitors.

A series of naphthylisopropylamine and N-benzyl-4-methylthioamphetamine derivatives were evaluated as monoamine oxidase inhibitors. Their potencies were compared with those of a series of amphetamine derivatives, to test if the increase of electron richness of the aromatic ring and overall size of the molecule might improve their potency as enzyme inhibitors. Molecular dockings were performed to gain insight regarding the binding mode of these inhibitors and rationalize their different potencies. In the case of naphthylisopropylamine derivatives, the increased electron-donating capacity and size of the aromatic moiety resulting from replacement of the phenyl ring of amphetamine derivatives by a naphthalene system resulted in more potent compounds. In the other case, extension of the arylisopropylamine molecule by N-benzylation of the amino group led to a decrease in potency as monoamine oxidase inhibitors.

One-pot, three-component synthesis of 7-azaindole derivatives from N-substituted 2-amino-4-cyanopyrroles, various aldehydes, and active methylene compounds.

An efficient and practical route to 7-azaindole framework has been developed by one-pot, three-component cyclocondensation of N-substituted 2-amino-4-cyanopyrroles, various aldehydes, and active methylene compounds in ethanol or acetic acid at reflux. Reactions involving tetronic acid, indane-1,3-dione, dimedone, and 5-phenylcyclohexane-1,3-dione gave carbocyclic fused 7-azaindoles, whereas Meldrum's acid, benzoylacetonitrile, and malononitrile resulted in the highly substituted 7-azaindole derivatives, making this strategy very useful in diversity-oriented synthesis (DOS).