Binap-gold (I) versus Binap-silver trifluoroacetate complexes as catalysts in 1,3-dipolar cycloadditions of axomethine ylides

The 1,3-dipolar cycloaddition between azomethine ylides and alkenes is efficiently catalysed by [{(Sa)-Binap-Au(tfa)}2] (Binap=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl; tfa=trifluoroacetyl). Maleimides, 1,2-bis(phenylsulfonyl)ethylene, chalcone and nitrostyrene were suitable dipolarophiles even when using sterically hindered 1,3-dipole precursors. The results obtained in these transformations improve the analogous ones obtained in the same reactions catalysed by [Binap–Ag(tfa)]. In addition, computational studies have also been carried out to demonstrate both the high enantioselectivity exhibited by the chiral gold(I) complex, and the non-linear effect observed in this transformation.

Enantioselective 1,3-dipolar cycloadditions of azlactones and electrophilic alkenes catalyzed by dimeric BinapAuTFA complexes

Glycine-derived azlactones react with maleimides using (S)- or (R)-dimeric BinapAuTFA complexes affording the corresponding cycloadducts in good yields and high enantioselections (up to 99% ee). The intermediate carboxylic acids are treated with trimethylsilyldiazomethane and isolated as Δ¹-pyrroline methyl esters. These cycloadducts are transformed into exo-proline derivatives by reduction with NaBH3CN in acidic media. On the other hand, N-benzoylalanine-derived oxazolone reacts with tert-butyl acrylate providing the cycloadduct with the ester group at the 3-position with a trans-relative configuration with respect to the methyl ester group.

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.

Spin degree of freedom in two dimensional exciton condensates

We present a theoretical analysis of a spin-dependent multicomponent condensate in two dimensions. The case of a condensate of resonantly photoexcited excitons having two different spin orientations is studied in detail. The energy and the chemical potentials of this system depend strongly on the spin polarization. When electrons and holes are located in two different planes, the condensate can be either totally spin polarized or spin unpolarized, a property that is measurable. The phase diagram in terms of the total density and electron-hole separation is discussed.

Coherent-light emission from exciton condensates in semiconductor quantum wells

We show that a quasi-two dimensional condensate of optically active excitons emits coherent light even in the absence of population inversion. This allows an unambiguous and clear experimental detection of the condensed phase. We prove that, due to the exciton–photon coupling, quantum and thermal fluctuations do not destroy condensation at finite temperature. Suitable conditions to achieve condensation are temperatures of a few K for typical exciton densities and the use of a pulsed and preferably circularly polarized, laser.

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.

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.

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.

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.

Domino 1,3-Dipolar Cycloadditions of N-Alkyl-α-Amino Esters with Paraformaldehyde: A Direct Access to α-Hydroxymethyl α-Amino Acids

N-Alkyl-α-amino esters undergo a domino reaction, based on the iminium cation generation, with paraformaldehyde, followed by a 1,3-dipolar cycloaddition of the stabilized azometh­ine ylide with another equivalent of formaldehyde. The resulting products are oxazolidines, which can be transformed after hydrolysis into α-hydroxymethyl α-amino acid or its derivatives. The diastereoselective 1,3-dipolar cycloaddition was performed using sarcosine (–)-menthyl or (–)-8-phenylmenthyl esters affording the cyclic product with moderate enantiomeric ratio.

Coinage Metal Complexes as Chiral Catalysts for 1,3-Dipolar Cycloadditions

In this account, we describe the experience of our research group in the implementation of chiral coinage metal complexes into the efficient enantioselective 1,3-DC of azomethine ylides derived from α-amino acids and azlactones with different dipolarophiles. The corresponding chiral metallodipoles were generated in situ and next focused on the synthesis of highly substituted prolines. For this purpose, privileged ligands such as phosphoramidites and binap with silver(I), gold(I) and copper(II) salts are described. Depending from the ligand and mainly from the metal salt it can be possible to control the facial endo/exo-diasteroselectivity and the enantioselectivity of these types of processes. The synthetic processes are also supported by DFT calculations in order to elucidate the most plausible mechanism and the stereochemical results.

Asymmetric 1,3-Dipolar Cycloadditons of Stabilized Azomethine Ylides with Nitroalkenes

This review highlights the biological importance of many polysubstituted nitro-prolines and -pyrrolidines. Their preparation using asymmetric 1,3-dipolar cycloadditions of azomethine ylides with nitroalkenes using diastereoselective and enantioselective strategies is described remarking the scope and main features of each one.

Efficient Diastereo- and Enantioselective Synthesis of exo-Nitroprolinates by 1,3-Dipolar Cycloadditions Catalyzed by Chiral Phosphoramidite⋅Silver(I) Complexes

Chiral complexes formed by privileged phosphoramidites and silver triflate or silver benzoate are excellent catalysts for the general 1,3-dipolar cycloaddition between azomethine ylides generated from α-amino acid-derived imino esters and nitroalkenes affording with high dr the exo-cycloadducts 4,5-trans-2,5-cis-4-nitroprolinates in high ee at room temperature. In general, better results are obtained using silver rather than copper(II) complexes. In many cases the exo-cycloadducts can be obtained in enantiomerically pure form just after simple recrystallization. The mechanism and the justification of the experimentally observed stereodiscrimination of the process are supported by DFT calculations. These enantiomerically enriched exo-nitroprolinates can be used as reagents for the synthesis of nitropiperidines, by ester reduction and ring expansion, which are inhibitors of farnesyltransferase.

Binap-silver-catalyzed enantioselective multicomponent 1,3-dipolar cycloaddition of azomethines ylides derived from ethyl glyoxylate

The enantioselective binap–silver catalyzed multicomponent 1,3-dipolar cycloaddition using ethyl glyoxylate, phenylalanine ethyl ester, and maleimides is described. The employment of basic silver carbonate allows the reaction to take place in the absence of an extra base giving high yields and ee. In addition, low-level calculations regarding the importance of the benzyl substituent at the α-position of the amino ester justify the expected absolute configuration of the final cycloadducts and the observed high enantiodiscrimination.