Clara I. Herrerías

Enantioselective cyclopropanation reactions in ionic liquids

Abstract The benchmark enantioselective cyclopropanation of styrene with ethyl diazoacetate, promoted by two different bis(oxazoline)-copper complexes, is studied in three ionic liquids. The nature of both the anion and cation influence the behaviour of the catalysts, which can be recovered and re-used.

Surface-mediated improvement of enantioselectivity with clay-immobilized copper catalysts

The clay surface plays a role in the enantioselectivity of the cyclopropanation reaction, in the case of copper catalysts immobilized on laponite by electrostatic interactions. The effect is different depending on the type of chiral ligand, bis(oxazoline) or pyridineoxazoline. In the first case the clay promotes a reversal of the stereochemical course of the reaction. The pyridineoxazoline-copper complexes lead to very low enantioselectivity in homogeneous phase. However, the asymmetric induction increases when the complexes are immobilized on laponite, showing that it is possible to design good chiral ligands specific for the use in immobilized catalysts.

Immobilisation of bis(oxazoline)–copper complexes on clays and nanocomposites. Influence of different parameters on activity and selectivity

Bis(oxazoline)–copper complexes, immobilised by electrostatic interactions on Laponite and Nafion/silica nanocomposites, have been tested as catalysts in the cyclopropanation of styrene with ethyl diazoacetate. Several factors play a decisive role in the outcome of the reaction. Firstly, the nature of the solid counterion is important, with perfluorosulfonic solids being the best in this regard. Secondly, the nature of the solvent used has a marked influence as some solvents cause the solid support to modify the stereochemical course of the reaction. Finally, the nature of the chiral ligand is also very important, in particular the strength of its copper complex, in order to avoid the formation of non-chiral catalytic copper centres. This particular effect has been highlighted by using a ligand that is able to give strong complexation, namely an iminobis(oxazoline) ligand, and this leads to the best enantioselectivities being obtained for reactions using electrostatically immobilised catalysts.

Reversal of enantioselectivity by change of solvent with clay-immobilized bis(oxazoline)–copper catalysts

Abstract The reduction in the polarity of the solvent induces the approach of the bis(oxazoline)–copper complex to the clay sheet in the immobilized catalyst. This proximity strongly influences the stereochemical course of the cyclopropanation reaction, even leading to a reversal in the enantioselectivity.

Comparison of the immobilization of chiral bis(oxazoline)-copper complexes onto anionic solids and in ionic liquids

Chiral bis(oxazoline)–copper complexes can be easily immobilized onto anionic solids or in ionic liquids and used as catalysts in cyclopropanation reactions. The efficiency and recovery of the catalysts are strongly dependent on the stability of the complex. In the case of a highly stable bis(oxazoline)–copper complex, both solid supports and ionic liquids allow efficient recovery of the catalyst with results quite similar to those obtained in molecular solvents. However, ionic liquids are clearly better when the complex is not so stable. In this case, the nature of both the anion and cation, the presence of water and the method used to synthesize the ionic liquid have a noticeable influence on both catalytic performance and catalyst recovery. Enantioselectivity is also influenced by the ionic liquid/catalyst molar ratio.

Metal-Mediated Cyclization of Aryl and Benzyl Glycidyl Ethers: A Complete Scenario

Enantiomerically pure aryl and benzyl glycidyl ethers undergo stereospecific cyclizations leading to 3-chromanols or to tetrahydrobenzo[c]oxepin-4-ols under mild conditions in the presence of a catalytic amount of FeBr3/3AgOTf. The same processes are also mediated, albeit in a much less efficient manner, by AuCl3/3AgOTf. The set of active mediators in this group of processes (BF3 x Et2O, FeBr3, FeBr3/3AgOTf, AuCl3/3AgOTf) shows its nature as Friedel-Crafts reactions and disfavors the intermediacy of arylgold species.

Polymer immobilization of bis(oxazoline) ligands using dendrimers as cross-linkers

Homopolymers of bis(oxazoline) ligands can be used to prepare efficient catalysts for cyclopropanation reactions. However, the low accessibility to most bis(oxazoline) moieties leads to a low copper loading. As a consequence, the transmission of chiral information from the complexed polymer is not very efficient and only a few chiral cyclopropane molecules are obtained from each molecule of chiral ligand. The use of suitable dendrimers as cross-linkers in the polymerization process allows better copper functionalization. As a consequence the productivity of chiral cyclopropanes per molecule of chiral ligand greatly increases, which improves the ligand economy and the chirality transfer.

Bis(oxazoline)-metal complexes immobilised by electrostatic interactions as heterogeneous catalysts for enantioselective Diels–Alder reactions

Abstract The immobilisation by cationic exchange of complexes of a bis(oxazoline) with Cu(II), Mg(II) and Zn(II) has been studied with two types of anionic solid, a laponite clay and a nafion-silica nanocomposite. The results obtained show that the cationic exchange depends on both the geometry of the complex and the nature of the cation. Whereas the immobilisation of square-planar complexes takes place easily, the situation is not the same for tetrahedral complexes. The solids prepared have been used as catalysts in a benchmark Diels–Alder reaction. These solids are efficient catalysts but the enantioselectivities are low, a fact that is related to the presence of non-chiral catalytic sites and to the nature of both the solid counter-ion and the bis(oxazoline) structure.

Bis(oxazoline)-based coordination polymers: a recoverable system for enantioselective Henry reactions.

An efficient release-capture strategy for the recovery and reuse of enantioselective catalysts in the Henry reaction is described. This strategy is based on the precipitation of an insoluble coordination polymer at the end of each reaction, allowing easy separation from products. The coordination polymer is formed through aggregation of Cu(II) ions with ditopic bisoxazoline-based chiral ligands. Up to 11 catalytic cycles have been conducted keeping good yields and enantioselectivities.

Study of the recycling possibilities for azabis(oxazoline)–cobalt complexes as catalysts for enantioselective conjugate reduction

Azabis(oxazoline)–cobalt(II) complexes have been tested in multiphasic catalytic systems for enantioselective conjugate reduction of (E)-3-phenylbut-2-enoate with NaBH4. Immobilization by electrostatic interactions with laponite clay leads to excellent results in the first run, as a consequence of the role of the clay as an anion. However most of the reaction takes place in solution due to leaching of active complex, and the solids are not reusable. Covalent immobilization to Merrifields resin does not allow the high enantioselectivity obtained in solution to be reached, and heterogeneous catalysts are again not reusable. Only the use of biphasic liquid systems allows an efficient recovery of the catalyst. The combination of a new ditopic ligand and 1,3-bis(2,2,2-trifluoroethoxy)propan-2-ol as a solvent for the catalyst phase is optimal to recycle the catalytic system with 90–96% ee for 5 runs.