Trisoxazolines (Often abbreviated TRISOX or TOX) are a class of tridentate, chiral ligands composed of three oxazoline rings. Despite being neutral they are able to form stable complexes with high oxidation state metals, such as rare earths, [1] due to the chelate effect. The ligands have been investigated for molecular recognition and their complexes are used in asymmetric catalysts and polymerisation.
Trisoxazolines can either be synthesised directly, from suitable tripodal starting materials, or built up in a modular manner. [2] These approaches can be used to give ligands of differing symmetries, with the direct synthesis route giving homochiral ligands with C3 rotational symmetry and the modular approach typically being used to give asymmetric compounds (C1 symmetry), which are either heterochiral or possess a mix of both chiral and achiral groups. These differences in symmetry can significantly effect the coordination chemistry of the ligands [3] and the catalytic activity of their complexes, with C3 symmetric ligands often being better for asymmetric catalysis. [4] [5]
Suitable tripodal compounds, such as trimesic acid [6] and nitrilotriacetic acid, [7] can be converted directly to trisoxazolines. The simplicity of this approach is beneficial, however it only allows a limited variety of structures to be produced, due to the limited range of available starting materials.
Modular synthesis allows for a more diverse range of structures, however the multi-step reactions can result in lower overall yields. In general synthesis involves the generation of separate mono‑oxazoline (typically halogenated) and bis-oxazoline units, which are then coupled using a strong base such as tBuLi [8] or KN(SiMe3)2.
In addition to the inclusion of heterochirality, modular synthesis also allows for the synthesis of 'lopsided' structures which have application as scorpionate ligands. [9]
Trisoxazolines have been used for the copper catalysed Friedel–Crafts alkylation of indoles, largely with alkylidene malonates, with good yields and ee's reported. A number of interesting solvent effects have also been observed, including a relationship between enantioselectivity and the steric bulk of the solvent when using of alcohols [10] and a reversal of enantioselectivity when changing the reaction solvent from coordinating solvents to weakly coordinating solvents. [11]
Rare-earth complexes incorporating TRISOX ligands have been found to be highly effective catalysts for the polymerisation of α-alkenes and are notable for producing polyolefins with very high tacticities. [12] [13] Computational modelling of the polymerisation mechanism indicates that kinetic factors likely account for the high tacticity. [14]
Trisoxazolines baring a benzene backbone have been investigated for molecular recognition and have shown promising selectivity for the recognition of ammonium [15] alkylammonium and sugar species, [16] including examples of chiral recognition.
Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction in which one or more new elements of chirality are formed in a substrate molecule and which produces the stereoisomeric products in unequal amounts."
Salen refers to a tetradentate C2-symmetric ligand synthesized from salicylaldehyde (sal) and ethylenediamine (en). It may also refer to a class of compounds, which are structurally related to the classical salen ligand, primarily bis-Schiff bases. Salen ligands are notable for coordinating a wide range of different metals, which they can often stabilise in various oxidation states. For this reason salen-type compounds are used as metal deactivators. Metal salen complexes also find use as catalysts.
In chemistry, transfer hydrogenation is a chemical reaction involving the addition of hydrogen to a compound from a source other than molecular H2. It is applied in laboratory and industrial organic synthesis to saturate organic compounds and reduce ketones to alcohols, and imines to amines. It avoids the need for high-pressure molecular H2 used in conventional hydrogenation. Transfer hydrogenation usually occurs at mild temperature and pressure conditions using organic or organometallic catalysts, many of which are chiral, allowing efficient asymmetric synthesis. It uses hydrogen donor compounds such as formic acid, isopropanol or dihydroanthracene, dehydrogenating them to CO2, acetone, or anthracene respectively. Often, the donor molecules also function as solvents for the reaction. A large scale application of transfer hydrogenation is coal liquefaction using "donor solvents" such as tetralin.
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.
DIPAMP is an organophosphorus compound that is used as a ligand in homogeneous catalysis. It is a white solid that dissolves in organic solvents. Work on this compound by W. S. Knowles was recognized with the Nobel Prize in Chemistry. DIPAMP was the basis for of the first industrial scale asymmetric hydrogenation, the synthesis of the drug L-DOPA.
Asymmetric hydrogenation is a chemical reaction that adds two atoms of hydrogen to a target (substrate) molecule with three-dimensional spatial selectivity. Critically, this selectivity does not come from the target molecule itself, but from other reagents or catalysts present in the reaction. This allows spatial information to transfer from one molecule to the target, forming the product as a single enantiomer. The chiral information is most commonly contained in a catalyst and, in this case, the information in a single molecule of catalyst may be transferred to many substrate molecules, amplifying the amount of chiral information present. Similar processes occur in nature, where a chiral molecule like an enzyme can catalyse the introduction of a chiral centre to give a product as a single enantiomer, such as amino acids, that a cell needs to function. By imitating this process, chemists can generate many novel synthetic molecules that interact with biological systems in specific ways, leading to new pharmaceutical agents and agrochemicals. The importance of asymmetric hydrogenation in both academia and industry contributed to two of its pioneers — William Standish Knowles and Ryōji Noyori — being awarded one half of the 2001 Nobel Prize in Chemistry.
Oxazoline is a five-membered heterocyclic organic compound with the formula C3H5NO. It is the parent of a family of compounds called oxazolines, which contain non-hydrogenic substituents on carbon and/or nitrogen. Oxazolines are the unsaturated analogues of oxazolidines, and they are isomeric with isoxazolines, where the N and O are directly bonded. Two isomers of oxazoline are known, depending on the location of the double bond.
Jacobsen's catalyst is the common name for N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) chloride, a coordination compound of manganese and a salen-type ligand. It is used as an asymmetric catalyst in the Jacobsen epoxidation, which is renowned for its ability to enantioselectively transform prochiral alkenes into epoxides. Before its development, catalysts for the asymmetric epoxidation of alkenes required the substrate to have a directing functional group, such as an alcohol as seen in the Sharpless epoxidation. This compound has two enantiomers, which give the appropriate epoxide product from the alkene starting material.
Cyclodiphosphazanes are saturated four membered P2N2 ring systems and one of the major classes of cyclic phosphazene compounds. Bis(chloro)cyclodiphosphazanes, (cis-[ClP(μ-NR)]2) are important starting compounds for synthesizing a variety of cyclodiphosphazane derivatives by nucleophilic substitution reactions; are prepared by reaction of phosphorus trichloride (PCl3) with a primary amine (RNH2) or amine hydrochlorides (RNH3Cl).
DuPhos is a class of organophosphorus compound that are used ligands for asymmetric synthesis. The name DuPhos is derived from (1) the chemical company that sponsored the research leading to this ligand's invention, DuPont and (2) the compound is a diphosphine ligand type. Specifically it is classified as a C2-symmetric ligand, consisting of two phospholanes rings affixed to a benzene ring.
Organogold chemistry is the study of compounds containing gold–carbon bonds. They are studied in academic research, but have not received widespread use otherwise. The dominant oxidation states for organogold compounds are I with coordination number 2 and a linear molecular geometry and III with CN = 4 and a square planar molecular geometry.
Within the area of organocatalysis, (thio)urea organocatalysis describes the use of ureas and thioureas to accelerate and stereochemically alter organic transformations. The effects arise through hydrogen-bonding interactions between the substrate and the (thio)urea. Unlike classical catalysts, these organocatalysts interact by non-covalent interactions, especially hydrogen bonding. The scope of these small-molecule H-bond donors termed (thio)urea organocatalysis covers both non-stereoselective and stereoselective applications.
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A metal salen complex is a coordination compound between a metal cation and a ligand derived from N,N′-bis(salicylidene)ethylenediamine, commonly called salen. The classical example is salcomine, the complex with divalent cobalt Co2+, usually denoted as Co(salen). These complexes are widely investigated as catalysts and enzyme mimics.
In chemistry, metal-catalysed hydroboration is a reaction used in organic synthesis. It is one of several examples of homogeneous catalysis.
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Andreas Pfaltz is a Swiss chemist known for his work in the area of coordination chemistry and catalysis.
DIOP is an organophosphorus compound that is used as a chiral ligand in asymmetric catalysis. It is a white solid that is soluble in organic solvents.
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