Bisoxazoline ligand

In chemistry, bis(oxazoline) ligands (often abbreviated BOX ligands) are a class of privileged chiral ligands containing two oxazoline rings. They are typically C2‑symmetric and exist in a wide variety of forms; with structures based around CH2 or pyridine linkers being particularly common (often generalised BOX and PyBOX respectively). The coordination complexes of bis(oxazoline) ligands are used in asymmetric catalysis. These ligands are examples of C2-symmetric ligands. In chemistry, bis(oxazoline) ligands (often abbreviated BOX ligands) are a class of privileged chiral ligands containing two oxazoline rings. They are typically C2‑symmetric and exist in a wide variety of forms; with structures based around CH2 or pyridine linkers being particularly common (often generalised BOX and PyBOX respectively). The coordination complexes of bis(oxazoline) ligands are used in asymmetric catalysis. These ligands are examples of C2-symmetric ligands. The synthesis of oxazoline rings is well established and in general proceeded via the cyclisation of a 2‑amino alcohol with any of a number of suitable functional groups. In the case of bis(oxazoline)s, synthesis is most conveniently achieved by using bi-functional starting materials; as this allows both rings to be produced at once. Of the materials suitable, dicarboxylic or dinitrile compounds are the most commonly available and hence the majority bis(oxazoline) ligands are produced from these materials. Part of the success of the BOX and PyBOX motifs lies in their convenient one step synthesis from malononitrile and dipicolinic acid, which are commercially available at low expense.Chirality is introduced with the amino alcohols, as these are prepared from amino acids and hence are chiral (e.g. valinol). In general, for methylene bridged BOX ligands the stereochemical outcome is consistent with a twisted square planar intermediate that was proposed based on related crystal structures. The substituent at the oxazoline's 4-position blocks one enantiotopic face of the substrate, leading to enantioselectivity. This is demonstrated in the following aldol-type reaction, but is applicable to a wide variety of reactions such as Mannich-type reactions, ene reaction, Michael addition, Nazarov cyclization, and hetero-Diels-Alder reaction. On the other hand, two-point binding on a Lewis acid bearing the meridially tridentate PyBOX ligand would result in a square pyramidal complex. A study using (benzyloxy)acetaldehyde as the electrophile showed that the stereochemical outcome is consistent with the carbonyl oxygen binding equatorially and the ether oxygen binding axially. Metal complexes incorporating bis(oxazoline) ligands are effective for a wide range of asymmetric catalytic transformations and have been the subject of numerous literature reviews. The neutral character of bis(oxazoline)s makes them well suited to use with noble metals, with copper complexes being particularly common. Their most important and commonly used applications are in carbon–carbon bond forming reactions. bis(oxazoline) ligands have been found to be effective for a range of asymmetric cycloaddition reactions, this began with the very first application of BOX ligands in carbenoid cyclopropanations and has been expanded to include 1,3-Dipolar cycloaddition and Diels-Alder reactions. Bisoxazoline ligands have also been found to be effective for Aldol, Michael and Ene reactions, amongst many others The success of bis(oxazoline) ligands for carbenoid cyclopropanations led to their application for aziridination. Another common reaction is hydrosilylation, which dates back to the first use of PyBOX ligands. Other niche applications include as fluorination catalysts and for Wacker-type cyclisations. Oxazoline ligands were first used for asymmetric catalysis in 1984 when Brunner et al. showed a single example, along with a number of Schiff bases, as being effective for enantioselective carbenoid cyclopropanation. Schiff bases were prominent ligands at the time, having been used by Ryōji Noyori during the discovery of asymmetric catalysis in 1968 (for which he and William S. Knowles would later be awarded the Nobel Prize in Chemistry). Brunner's work was influenced by that of Tadatoshi Aratani, who had worked with Noyori, before publishing a number of papers on enantioselective cyclopropanation using Schiff bases.