Enantioselective direct aldol reaction of α-keto esters catalyzed by (Sa)-binam-D-prolinamide under quasi solvent-free conditions

(Sa)-Binam-D-prolinamide (20 mol%), instead of (Sa)-binam-L-prolinamide, in combination with chloroacetic acid (100 mol%) is an efficient organocatalyst for the direct aldol reaction between α-keto esters as electrophiles and alkyl and α-functionalised ketones, under quasi solvent-free conditions, providing access to highly functionalised chiral quaternary γ-keto α-hydroxyesters with up to 92% ee.

Kinetic study of thermal 1,3-dipolar cycloaddition of azomethine ylides using differential scanning calorimetry as monitoring window

Kinetics of 1,3-dipolar cycloaddition involving azomethine ylides, generated from thermal [1,2]-prototropy of the corresponding imino ester, employing differential scanning calorimetry (DSC), is surveyed. Glycine and phenylalanine derived imino esters have different behavior. The first one prefers reacting with itself at 75 ºC, rather than with the dipolarophile. However, the α-substituted imino ester gives the cycloadduct at higher temperatures. The thermal dynamic analysis by 1H NMR of the neat reaction mixture of the glycine derivative reveals the presence of signals corresponding to the dipole in very small proportion. The non-isothermal and isothermal DSC curves of the cycloaddition of phenylalaninate and diisobutyl fumarate are obtained from freshly prepared samples. The application of known kinetic models and mathematical multiple non-linear regressions (NLR) allow to determine and to compare Ea, lnA, reaction orders, and reaction enthalpy. Finally a rate equation for each different temperature can be established for this particular thermal cycloaddition.

Binap-silver salts as chiral-catalysts for the enantioselective 1,3-dipolar cycloaddition of azomethine ylides and alkenes

Binap-AgSbF6 catalyzed 1,3-dipolar cycloadditions between azomethine ylides and electrophilic alkenes are described and compared with analogous transformations mediated by other Binap-silver(I) salt complexes. Maleimides and 1,2-bis(phenylsulfonyl)ethylene are suitable dipolarophiles for obtaining very good enantioselectivities, even better values are generated by a multicomponent version. There are some very interesting applications of the disulfonylated cycloadducts in the total synthesis of cis-2,5-disubstituted pyrrolidines, precursors of natural products, or valuable intermediates in the synthesis of antiviral compounds.

Microwave-assisted multicomponent diastereoselective 1,3-dipolar cycloaddition of ethyl glyoxylate derived azomethine ylides

The thermal multicomponent 1,3-dipolar cycloaddition (1,3-DC) of diethyl aminomalonate or α-amino esters (derived from glycine, alanine, phenylalanine, and phenylglycine) with ethyl glyoxylate and the corresponding dipolarophile such as maleimides, methyl acrylate, methyl fumarate, (E)-1,2-bis(phenylsulfonyl)ethylene, and electron deficient alkynes allows the diastereoselective synthesis of new polysubstituted pyrrolidine derivatives. Microwave-assisted heating processes give better results than conventional heating ones, affording endo-cycloadducts as major stereoisomers. In general, 2,5-cis-cycloadducts are preferentially formed according to the previous formation of the W-shaped dipole. Only in the 1,3-DC of the disulfone with phenylglycine and ethyl glyoxylate the corresponding exo-trans-cycloadduct was isolated. The compound endo-cis-4b, derived from phenylalanine, ethyl glyoxylate and N-benzylmaleimide, has been further transformed into a very complex diazabicyclo[2.2.1]octane skeleton with potential biological activity.

Proline and pyrrolidine derivatives: new drug cadidates for hepatitis C treatment

The more advantageous hepatitis C virus (HCV) inhibitors (most of them incorporating polysubstituted prolines or pyrrolidines) are detailed in this paper. The improvement of current treatments by combination of antiviral drugs is the driving force of this race to reduce the fast proliferation of this virus. The enhancement of efficiency in short periods of treatment is crucial in the economical point of view and for the hope of all infected people. New protease or polymerase inhibitors have been recently developed in order to substitute the traditional highly toxic PEG-interferon α-2b/ribavirin tandem. The contribution of our group in this field concerns the elaboration of the first and second generation GSK polymerase inhibitors through enantioselective processes based on silver(I)- and gold(I)-catalyzed 1,3-dipolar cycloadditions of azomethine ylides.

Asymmetric aldol reaction with BINAM-sulfonyl polymeric organocatalyst

The BINAM-sulfonyl polymeric organocatalysts was prepared by the AIBN-promoted copolymerization of BINAM-derived sulfonamide, styrene and divinylbenzebe. The polymer catalyzed the asymmetric aldol reaction of aliphatic ketones with aromatic aldehydes to give the aldol products in up to 83% yield and with up to 95% ee. The catalysts could be recovered upt to 6 times with only a slight decrease on its activity.

Phosphoramidite-Cu(OTf)2 complexes as chiral catalysts for 1,3-dipolar cycloaddition of iminoesters and nitroalkenes

Chiral complexes formed by phosphoramidites such as (Sa,R,R)-9 and Cu(OTf)2 are excellent catalysts for the general 1,3-dipolar cycloaddition between azomethine ylides and nitroalkenes affording the corresponding tetrasubstituted proline esters mainly as exo-cycloadducts in high er at room temperature. The exo-cycloadducts can be obtained in enantiomerically pure form just after simple recrystallization. DFT calculations support the stereochemical results.

Spin alignment of extra electrons in K-phenanthrene clusters taken from the crystalline tripotassium-intercalated phenanthrene structure

The appearance of ferromagnetic correlations among π electrons of phenanthrene (C14H10) molecules in the herringbone structure is proven for K doped clusters both by ab initio quantum-chemistry calculations and by the direct solution of the many-body Pariser-Parr-Pople Hamiltonian. Magnetic ground states are predicted for one or three additional electrons per phenanthrene molecule. These results are a consequence of the small overlap between the lowest unoccupied molecular orbitals (and lowest unoccupied molecular orbitals + 1) of neutral neighboring phenanthrene molecules, which makes the gain in energy by delocalization similar to the corresponding increase due to the Coulomb interaction.

Exponential decay of spin-spin correlation between distant defect states produced by contour hydrogenation of polycyclic aromatic hydrocarbon molecules

The first few low-lying spin states of alternant polycyclic aromatic hydrocarbon (PAH) molecules of several shapes showing defect states induced by contour hydrogenation have been studied both by ab initio methods and by a precise numerical solution of Pariser-Parr-Pople (PPP) interacting model. In accordance with Lieb's theorem, the ground state shows a spin multiplicity equal to one for balanced molecules, and it gets larger values for imbalanced molecules (that is, when the number of π electrons on both subsets is not equal). Furthermore, we find a systematic decrease of the singlet-triplet splitting as a function of the distance between defects, regardless of whether the ground state is singlet or triplet. For example, a splitting smaller than 0.001 eV is obtained for a medium size C46H28 PAH molecule (di-hydrogenated [11]phenacene) showing a singlet ground state. We conclude that π electrons unbound by lattice defects tend to remain localized and unpaired even when long-range Coulomb interaction is taken into account. Therefore they show a biradical character (polyradical character for more than two defects) and should be studied as two or more local doublets. The implications for electron transport are potentially important since these unpaired electrons can trap traveling electrons or simply flip their spin at a very small energy cost.

Palladium and organocatalysis: an excellent recipe for asymmetric synthesis

The dual activation of simple substrates by the combination of organocatalysis and palladium catalysis has been successfully applied in a variety of different asymmetric transformations. Thus, the asymmetric a-allylation of carbonyl compounds, a-fluorination of acyl derivatives, decarboxylative protonation of β-dicarbonyl compounds, cyclization reactions of alkynyl carbonyl compounds and β-functionalization of aldehydes have been efficiently achieved employing this double-catalytic methodology.

Multicomponent synthesis of unnatural pyrrolizidines using 1,3-dipolar cycloaddition of proline esters

The synthesis of unnatural pyrrolizidines has been studied using a multicomponent-domino process involving proline or 4-hydroxyproline esters, an aldehyde and a dipolarophile. The formation of the iminium salt promotes the 1,3-dipolar cycloaddition affording highly substituted pyrrolizidines under mild conditions and high regio- and diastereoselectivities.

Structural Determination of Organic Compounds Units

Units and slides for the Structural Determination of Organic Compounds subject

Synthetic scope and DFT analysis of the chiral binap-gold (I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

The 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(Sa)-Binap·AuTFA]2. The alanine-derived oxazolone only reacts with tert-butyl acrylate giving anomalous regiochemistry, which is explained and supported by Natural Resonance Theory and Nucleus Independent Chemical Shifts calculations. The origin of the high enantiodiscrimination observed with maleimides and tert-butyl acrylate is analyzed using DFT computed at M06/Lanl2dz//ONIOM(b3lyp/Lanl2dz:UFF) level. Several applications of these cycloadducts in the synthesis of new proline derivatives with a 2,5-trans-arrangement and in the preparation of complex fused polycyclic molecules are described.

Chemistry for Biologists

Material docente en inglés de la asignatura de Química del Grado de Biología.

Chiral β-amino alcohols as ligands for the ruthenium-catalyzed asymmetric transfer hydrogenation of N-phosphinyl ketimines

Some chiral β-amino alcohols have been evaluated as potential ligands for the ruthenium-catalyzed asymmetric transfer hydrogenation (ATH) of N-phosphinyl ketimines in isopropyl alcohol. The ruthenium complex prepared from [RuCl2(p-cymene)]2 and (1S,2R)-1-amino-2-indanol has shown to be an efficient catalyst for the ATH of several N-(diphenylphosphinyl)imines, affording the reduction products in very good isolated yields and enantiomeric excesses up to 82%. The inherent rigidity of the indane ring system present in the ligand seems to be very important to achieve good enantioselectivities.