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.

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.

Support effects in a Rh diamine complex heterogenized on carbon materials

The Rh diamine complex [Rh(COD)NH2(CH2)2NH(CH2)3Si(OCH3)3] BF4 was heterogenized by covalent bonding on two carbon xerogels and on carbon nanofibers, with the objective of preparing hydrogenation hybrid catalysts. Gas adsorption, SEM, TEM, DTP, ICP-OES and XPS were used for characterization. The results indicate that the active molecule is mainly located in supermicropores and produces microporosity blockage. The hybrid catalysts are more active than the homogeneous complex, but the Rh complex is partially reduced upon reaction. This modification is related to the nature of the support, which also shows effects in the stabilization against sintering of the Rh particles formed. The support porosity is a key factor in the selectivity differences between the catalysts.

Steam reforming of ethanol over bimetallic RhPt/La2O3: Long-term stability under favorable reaction conditions

Recently, the steam reforming of biofuels has been presented as a potential hydrogen source for fuel cells. Because this scenario represents an interesting opportunity for Colombia (South America), which produces large amounts of bioethanol, the steam reforming of ethanol was studied over a bimetallic RhPt/La2O3 catalyst under bulk mass transfer conditions. The effect of temperature and the initial concentrations of ethanol and water were evaluated at space velocities above 55,000 h−1 to determine the conditions that maximize the H2/CO ratio and reduce CH4 production while maintaining 100% conversion of ethanol. These requirements were accomplished when 21 mol% H2O and 3 mol% C2H5OH (steam/ethanol molar ratio = 7) were reacted at 600 °C. The catalyst stability was assessed under these reaction conditions during 120 h on stream, obtaining ethanol conversions above 99% during the entire test. The effect of both H2 and air flows as catalyst regeneration treatments were evaluated after 44 and 67 h on stream, respectively. The results showed that H2 treatment accelerated catalyst deactivation, and air regeneration increased both the catalyst stability and the H2 selectivity while decreasing CH4 generation. Fresh and spent catalyst samples were characterized by TEM/EDX, XPS, TPR, and TGA. Although the Rh and Pt in the fresh catalyst were completely reduced, the spent samples showed a partial oxidation of Rh and small amounts of carbonaceous residue. A possible Rh–Pt–Rh2O3 structure was proposed as the active site on the catalyst, which was regenerated by air treatment.

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.

Non-covalent immobilization of RhDuphos on carbon nanotubes and carbon xerogels

The immobilization of the chiral complex RhDuphos, by electrostatic or π–π (adsorption) interactions, on carbon nanotubes and carbon xerogels is investigated. To promote such interactions, the supports were either oxidized or heat treated to create carboxylic type surface groups or an apolar surface, respectively. The catalysts were tested in the hydrogenation of methyl 2-acetamidoacrylate. The prepared hybrid catalysts are less active than the homogeneous RhDuphos, but most of them show a high enantioselectivity and the one prepared with the oxidized carbon xerogel is also reusable, being able to give a high substrate conversion, keeping as well a high enantioselectivity. The anchorage by electrostatic interactions is more interesting than the anchorage by π–π interactions, as the π–π adsorption method produces a modification of the metal complex structure leading to an active hybrid catalyst but without enantioselectivity. The creation of carboxylic groups on the support surface has led to some hindering of the complex leaching.

Enantioselective Synthesis of exo-4-Nitroprolinates from Nitro­alkenes and Azomethine Ylides Catalyzed by Chiral Phosphor­amidite·Silver(I) or Copper(II) Complexes

Chiral complexes formed by privileged phosphoramidites derived from chiral binol and optically pure Davies’ amines, and copper(II) triflate, silver(I) triflate or silver(I) benzoate are excellent catalysts for the general 1,3-dipolar cycloaddition between nitroalkenes and azomethine ylides generated from α-amino acid derived imino esters. These three methods can be conducted at room temperature to afford the exo-cycloadducts (4,5-trans-2,5-cis-4-nitroprolinates) with high diastereoselectivity and high enantioselectivity. In general, the three procedures are complementary but silver catalysts are more versatile and less sensitive to sterically congested starting materials.

Synthesis of Chromen[4,3-b]pyrrolidines by Intramolecular 1,3-Dipolar Cycloadditions of Azomethine Ylides: An Experimental and Computational Assessment of the Origin of Stereocontrol

Azomethine ylides, generated from imine-derived O-cinnamyl or O-crotonyl salicylaldeyde and α-amino acids, undergo intramolecular 1,3-dipolar cycloaddition, leading to chromene[4,3-b]pyrrolidines. Two reaction conditions are used: (a) microwave-assisted heating (200 W, 185 °C) of a neat mixture of reagents, and (b) conventional heating (170 °C) in PEG-400 as solvent. In both cases, a mixture of two epimers at the α-position of the nitrogen atom in the pyrrolidine nucleus was formed through the less energetic endo-approach (B/C ring fusion). In many cases, the formation of the stereoisomer bearing a trans-arrangement into the B/C ring fusion was observed in high proportions. Comprehensive computational and kinetic simulation studies are detailed. An analysis of the stability of transient 1,3-dipoles, followed by an assessment of the intramolecular pathways and kinetics are also reported.

1,3-Dipolar cycloadditions of azomethine imines

Azomethine imines are considered 1,3-dipoles of the aza-allyl type which are transient intermediates and should be generated in situ but can also be stable and isolable compounds. They react with electron-rich and electron-poor olefins as well as with acetylenic compounds and allenoates mainly by a [3 + 2] cycloaddition but they can also take part in [3 + 3], [4 + 3], [3 + 2 + 2] and [5 + 3] with different dipolarophiles. These 1,3-dipolar cycloadditions (1,3-DC) can be performed not only under thermal or microwave conditions but also using metallo- and organocatalytic systems. In recent years enantiocatalyzed 1,3-dipolar cycloadditions have been extensively considered and applied to the synthesis of a great variety of dinitrogenated heterocycles with biological activity. Acyclic azomethine imines derived from mono and disubstituted hydrazones could be generated by prototropy under heating or by using Lewis or Brønsted acids to give, after [3 + 2] cycloadditions, pyrazolidines and pyrazolines. Cyclic azomethine imines, incorporating a C–N bond in a ring, such as isoquinolinium imides are the most widely used dipoles in normal and inverse-electron demand 1,3-DC allowing the synthesis of tetrahydro-, dihydro- and unsaturated pyrazolo[1,5-a]isoquinolines in racemic and enantioenriched forms with interesting biological activity. Pyridinium and quinolinium imides give the corresponding pyrazolopyridines and indazolo[3,2-a]isoquinolines, respectively. In the case of cyclic azomethine imines with an N–N bond incorporated into a ring, N-alkylidene-3-oxo-pyrazolidinium ylides are the most popular stable and isolated dipoles able to form dinitrogen-fused saturated and unsaturated pyrazolopyrazolones as racemic or enantiomerically enriched compounds present in many pharmaceuticals, agrochemicals and other useful chemicals.

Regio and diastereoselective multicomponent 1,3-dipolar cycloadditions between prolinate hydrochlorides, aldehydes and dipolarophiles for the direct synthesis of pyrrolizidines

A general synthesis of highly substituted pyrrolizidines can be performed by a multicomponent 1,3-dipolar cycloaddition using proline ester hydrochlorides, aldehydes and dipolarophiles, at room temperature without catalysts or in the presence of AgOAc (5 mol %). In the case of (2S,4R)-4-hydroxyproline derivatives it is possible to obtain enantioenriched pyrrolizidines with high control of the regio- and diastereoselectivity affording the adducts 2,4-trans-2,5-trans according to an endo-approach and a S-dipole geometry of the in situ generated azomethine ylide. For proline esters a similar regioselectivity and endo-diastereoselectivity are observed when the dipole promotes an α-attack. However, when ethyl glyoxylate is used as aldehyde component the γ-attack of the S-ylide takes place preferentially giving rise the opposite regioselectivity for acrylic dipolarophiles, being crucial the role of silver acetate. In this case, the exo-adducts with a 2,3-cis-2,5-trans relative configuration are diastereoselectively obtained. In addition, computational studies have also been carried out to shed light on the origins of the diastereo- and regioselectivity observed for the described 1,3-dipolar cycloadditions.

Copper Nanoparticles in Click Chemistry

Conspectus: The challenges of the 21st century demand scientific and technological achievements that must be developed under sustainable and environmentally benign practices. In this vein, click chemistry and green chemistry walk hand in hand on a pathway of rigorous principles that help to safeguard the health of our planet against negligent and uncontrolled production. Copper-catalyzed azide–alkyne cycloaddition (CuAAC), the paradigm of a click reaction, is one of the most reliable and widespread synthetic transformations in organic chemistry, with multidisciplinary applications. Nanocatalysis is a green chemistry tool that can increase the inherent effectiveness of CuAAC because of the enhanced catalytic activity of nanostructured metals and their plausible reutilization capability as heterogeneous catalysts. This Account describes our contribution to click chemistry using unsupported and supported copper nanoparticles (CuNPs) as catalysts prepared by chemical reduction. Cu(0)NPs (3.0 ± 1.5 nm) in tetrahydrofuran were found to catalyze the reaction of terminal alkynes and organic azides in the presence of triethylamine at rates comparable to those achieved under microwave heating (10–30 min in most cases). Unfortunately, the CuNPs underwent dissolution under the reaction conditions and consequently could not be recovered. Compelling experimental evidence on the in situ generation of highly reactive copper(I) chloride and the participation of copper(I) acetylides was provided. The supported CuNPs were found to be more robust and efficient catalyst than the unsupported counterpart in the following terms: (a) the multicomponent variant of CuAAC could be applied; (b) the metal loading could be substantially decreased; (c) reactions could be conducted in neat water; and (d) the catalyst could be recovered easily and reutilized. In particular, the catalyst composed of oxidized CuNPs (Cu2O/CuO, 6.0 ± 2.0 nm) supported on carbon (CuNPs/C) was shown to be highly versatile and very effective in the multicomponent and regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles in water from organic halides as azido precursors; magnetically recoverable CuNPs (3.0 ± 0.8 nm) supported on MagSilica could be alternatively used for the same purpose under similar conditions. Incorporation of an aromatic substituent at the 1-position of the triazole could be accomplished using the same CuNPs/C catalytic system starting from aryldiazonium salts or anilines as azido precursors. CuNPs/C in water also catalyzed the regioselective double-click synthesis of β-hydroxy-1,2,3-triazoles from epoxides. Furthermore, alkenes could be also used as azido precursors through a one-pot CuNPs/C-catalyzed azidosulfenylation–CuAAC sequential protocol, providing β-methylsulfanyl-1,2,3-triazoles in a stereo- and regioselective manner. In all types of reaction studied, CuNPs/C exhibited better behavior than some commercial copper catalysts with regard to the metal loading, reaction time, yield, and recyclability. Therefore, the results of this study also highlight the utility of nanosized copper in click chemistry compared with bulk copper sources.