Is DFT Accurate Enough to Calculate Regioselectivity? The Case of 1,3-Dipolar Cycloaddition of Azide to Alkynes and Alkenes.

The importance of regioselectivity in 1,3-dipolar cycloadditions (DCs) makes it surprising that no benchmarking study on this problem has appeared. We investigated whether DFT calculations are an accurate tool to predict the regioselectivity of uncatalyzed thermal azide 1,3-DCs. We considered the reaction between HN and 12 dipolarophiles, comprising ethynes HC≡C-R and ethenes H C=CH-R (R=F, OH, NH , Me, CN, CHO), which cover a broad range of electron demand and conjugation ability.

Enantiopure β-isocyano-boronic esters: synthesis and exploitation in isocyanide-based multicomponent reactions.

Various boron-containing isocyanides have been efficiently synthesized from the corresponding enantiopure β-substituted β-amino boronic acid pinacol esters, without need for protecting group interconversion, through a two-step, purification-free procedure. They were employed in a variety of isocyanide-based multicomponent reactions, proving to be reliable components for all of them and allowing the efficient synthesis of unprecedented, boron-containing peptidomimetics and heteroatom-rich small molecules, including biologically relevant cyclic boronates. Jointing together the β-amido boronic acid moiety, deriving from the isocyanide component, with prominent pharmacophoric rings emerging from the multicomponent process, a successful application of the molecular hybridization concept could be realized.

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines.

Addressing the asymmetric synthesis of oxindole-based α-aminoboronic acids, instead of the expected products we disclosed the efficient homocoupling of oxindole-based --butanesulfinyl imines, with the generation of chiral, quaternary 1,2-diamines in a mild and completely stereoselective way. The obtained 3,3'-bisoxindole derivatives were fully characterized by NMR and single-crystal X-ray diffraction analysis and proved to be single diastereoisomers and atropisomers. A plausible mechanism for the one-pot Cu(II)-catalyzed Bpin addition to the isatin-derived ketimine substrate and subsequent homocoupling is described.

Highly diastereoselective entry to chiral oxindole-based β-amino boronic acids and spiro derivatives.

We here describe the first Cu-catalysed, diastereoselective 1,2-addition of 1,1-diborylmethane to chiral ketimines for the synthesis of quaternary stereocenters and spiro compounds. The method provides easy access to a range of chiral, highly functionalized compounds, namely oxindole-based β,β'-disubstituted β-amino boronates, boron-containing peptidomimetics and six-, seven-membered spirocyclic hemiboronic esters. Such unprecedented compounds are mostly obtained in high yields and easily isolated as single diastereoisomers, paving the way to a more intense exploitation of boron-containing compounds in diversity-oriented chemistry and drug-discovery programs.

The Azide-Allene Dipolar Cycloaddition: Is DFT Able to Predict Site- and Regio-Selectivity?

The site- and regio-selectivity of thermal, uncatalysed 1,3-dipolar cycloadditions between arylazides and mono- or tetra-substituted allenes with different electronic features have been investigated by both conceptual (reactivity indices) and computational (M08-HX, ωB97X-D, and B3LYP) DFT approaches. Both approaches show that these cycloadditions follow a nonpolar one-step mechanism. The experimental site- and regio-selectivity of arylazides towards methoxycarbonyl- and sulfonyl-allenes as well as tetramethyl- and tetrafluoro-allenes was calculated by DFT transition state calculations, achieving semiquantitative agreement to both previous and novel experimental findings.

Adenosine Triphosphate-Binding Cassette Transporters Are Not Involved In the Detoxification of Extracts In Larvae.

Detoxifying pathways of mosquitoes against the neem () extracts are still unclear. The aim of the present study was to investigate the role of adenosine triphosphate-binding cassette (ABC) transporters in this process in , one of the main malaria vectors in southern Asia. Third-stage larvae of were fed with fish food alone or in combination with neem extract at 0.

Site- and Regioselectivity of Nitrile Oxide-Allene Cycloadditions: DFT-Based Semiquantitative Predictions.

Nitrile oxide 1,3-dipolar cycloaddition to arylsulfonyl- and dialkylaminoallenes have been investigated within the framework of the Kohn-Sham density functional theory (DFT) at the B3LYP/6-31G(d,p) level. The hitherto-unexplained experimental behavior of sulfonylallenes was rationalized by transition-state calculations which enabled a semiquantitative treatment of the cycloaddition site- and regioselectivity. The reliability of DFT computations was further established by predicting the complete selectivity of the nitrile oxide cycloaddition to dialkylaminoallenes according to previous experimental findings.

The Nitrilimine-Alkene Cycloaddition Regioselectivity Rationalized by Density Functional Theory Reactivity Indices.

Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine-alkene cycloaddition. We considered that conceptual density functional theory (DFT) could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine-alkene cycloadditions were analyzed, for which we could find regioselectivity data in the literature.

One-step synthesis and functionalization of hydroxyl-decorated magnetite nanoparticles.

Magnetite nanoparticles covered by a layer of omega-hydroxycarboxylic acid were synthesized in one step by high-temperature decomposition of iron(III) omega-hydroxycarboxylates in tri- and tetra-ethylene glycol. The nanoparticles were characterized by TEM, XRD, IR, XPS and NMR techniques in order to show that they comprise a crystalline magnetite core and actually bear on the outer surface terminal hydroxy groups. The latter ones are convenient "handles" for further functionalization as opposed to the chemically-inert aliphatic chains which cover conventionally synthesized nanoparticles.

The electronic structure of nitrilimine: absence of the carbenic form.

The electronic structure of nitrilimine HCNNH is shown to essentially be propargylic by CASSCF and Spin-Coupled (modern VB) calculations; in contrast to a recent claim, the carbenic resonance form is absent.

DFT-HSAB prediction of regioselectivity in 1,3-dipolar cycloadditions: behavior of (4-substituted)benzonitrile oxides towards methyl propiolate.

The regioselectivity of 1,3-dipolar cycloadditions between (4-substituted)benzonitrile oxides and methyl propiolate cannot be rationalized on the basis of the electron demand of the reactants or frontier molecular-orbital theory. To this problem, we have applied a quantitative formulation of the hard-soft acid-base principle developed within the density functional theory. Global and local reactivity indices were computed at B3LYP/6-311+G(d,p) level.