Phosphinooxazolines (often abbreviated PHOX) are a class of

chiral ligand Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecul ...

s used in

asymmetric catalysis Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of Chirality (chemistry), chirality are formed ...

. Colorless solids, PHOX ligands feature a tertiary phosphine group, often diphenyl, and an oxazoline ligand in the ortho position. The oxazoline, which carries the stereogenic center, coordinates through nitrogen, the result being that PHOX ligands are P,N-chelating ligands. Most phosphine ligands used in asymmetric catalysis are

diphosphine Diphosphane, or diphosphine, is an inorganic compound with the chemical formula . This colourless liquid is one of several binary phosphorus hydrides. It is the impurity that typically causes samples of phosphine to ignite in air. Properties, ...

s, so the PHOX ligands are distinctive. Some evidence exists that PHOX ligands are hemilabile.

Synthesis

The synthesis of phosphinooxazolines is modular. Methods exist for installing the

phosphine ligand A metal-phosphine complex is a coordination complex containing one or more phosphine ligands. Almost always, the phosphine is an organophosphine of the type R3P (R = alkyl, aryl). Metal phosphine complexes are useful in homogeneous catalysis. Prom ...

before the

oxazoline Oxazoline is a five-membered heterocyclic organic compound with the formula . It is the parent of a family of compounds called oxazolines (emphasis on plural), which contain non-hydrogenic substituents on carbon and/or nitrogen. Oxazolines are the ...

and the reverse. Commonly a phenyloxazoline is combined with a source of diphenylphosphine. Methods for doing this depend on the nature of the substituent in the X position: PHOX ligand synthesis 2

* When X = fluorine coupling involves anionic displacement with a alkali metal diphenylphosphide. * 2-Bromoaryl oxazolines can be converted into a

Grignard reagent Grignard reagents or Grignard compounds are chemical compounds with the general formula , where X is a halogen and R is an organic group, normally an alkyl or aryl. Two typical examples are methylmagnesium chloride and phenylmagnesium bromi ...

, which react with

chlorodiphenylphosphine Chlorodiphenylphosphine is an organophosphorus compound with the formula (C6H5)2PCl, abbreviated Ph2PCl. It is a colourless oily liquid with a pungent odor that is often described as being garlic-like and detectable even in the ppb range. It is ...

. Alternatively, the aryl bromide can be coupled with

diphenylphosphine Diphenylphosphine, also known as diphenylphosphane, is an organophosphorus compound with the formula (C6H5)2PH. This foul-smelling, colorless liquid is easily oxidized in air. It is a precursor to organophosphorus ligands for use as catalysts. Syn ...

via a

copper iodide Copper(I) iodide is an inorganic compound with the chemical formula . It is also known as cuprous iodide. It is useful in a variety of applications ranging from organic synthesis to cloud seeding. Copper(I) iodide is white, but samples often appe ...

-catalysed reaction. * Aryl oxazolines undergo directed ortho lithiation, and the resulting 2-lithio derivative then can be treated with

. Of these methods, the

catalysed reaction method is popular.

Catalysis

Phosphinooxazoline complexes have been widely tested in

homogeneous catalysis In chemistry, homogeneous catalysis is catalysis where the catalyst is in same phase as reactants, principally by a soluble catalyst in a solution. In contrast, heterogeneous catalysis describes processes where the catalysts and substrate are in d ...

Allylic substitutions

PHOX-based

palladium Palladium is a chemical element; it has symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1802 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas (formally 2 Pallas), ...

complexes catalyse enantioselective allylic substitutions. Symmetric vs asymmetric

Substitutions include allylic alkylations ( Tsuji-Trost reaction), aminations, and sulfonylations.

Heck Reaction

Palladium complexes containing chiral phosphinooxazolines are efficient catalysts for the

Heck reaction The Heck reaction (also called the Mizoroki–Heck reaction) is the chemical reaction of an unsaturated halide (or triflate) with an alkene in the presence of a base and a palladium catalyst to form a substituted alkene. It is named after T ...

. Pd-PHOX catalysts have also been used for intramolecular Heck reactions and examples exist where they have been shown to be superior to more common ligands such as

BINAP BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl) is an organophosphorus compound. This Optical isomerism, chiral diphosphines, diphosphine ligand is widely used in chiral synthesis, asymmetric synthesis. It consists of a pair of 2-diphe ...

Asymmetric Hydrogenation

asymmetric hydrogenation 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 oth ...

iridium Iridium is a chemical element; it has the symbol Ir and atomic number 77. This very hard, brittle, silvery-white transition metal of the platinum group, is considered the second-densest naturally occurring metal (after osmium) with a density ...

complexes of phosphinooxazolines catalyse 'classic'

hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to redox, reduce or Saturated ...

. Related

ruthenium Ruthenium is a chemical element; it has symbol Ru and atomic number 44. It is a rare transition metal belonging to the platinum group of the periodic table. Like the other metals of the platinum group, ruthenium is unreactive to most chem ...

and

catalysts effect

transfer hydrogenation In chemistry, transfer hydrogenation is a chemical reaction involving the addition of hydrogen to a compound from a source other than molecular . It is applied in laboratory and industrial organic synthesis to saturate organic compounds and re ...

. In addition to theoretical studies, the structural and kinetic properties

References