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DuPhos is a class of 
Other chiral
In the original scope the metal catalyst was 
Duphos is also applied in the synthesis of tryptophan derivatives.
DuPhos is a class of organophosphorus compound
Organophosphorus chemistry is the scientific study of the synthesis and properties of organophosphorus compounds, which are organic compounds containing phosphorus. They are used primarily in pest control as an alternative to chlorinated hydrocarbo ...
that are used ligand
In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
s for asymmetric synthesis
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 ...
. The name DuPhos is derived from (1) the chemical company that sponsored the research leading to this ligand's invention, DuPont
Dupont, DuPont, Du Pont, duPont, or du Pont may refer to:
People
* Dupont (surname) Dupont, also spelled as DuPont, duPont, Du Pont, or du Pont is a French surname meaning "of the bridge", historically indicating that the holder of the surname re ...
and (2) the compound is a diphosphine ligand
Diphosphines, sometimes called bisphosphanes, are organophosphorus compounds most commonly used as bidentate phosphine
Phosphine (IUPAC name: phosphane) is a colorless, flammable, highly toxic compound with the chemical formula , classed as a ...
type. Specifically it is classified as a C2-symmetric ligand, consisting of two phospholanes rings affixed to a benzene ring.
The ligand was introduced in 1991 by M.J. Burk and first demonstrated in 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 ...
of certain enamide esters to amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
precursors:
:
Other chiral diphosphine ligand
Diphosphines, sometimes called bisphosphanes, are organophosphorus compounds most commonly used as bidentate phosphine
Phosphine (IUPAC name: phosphane) is a colorless, flammable, highly toxic compound with the chemical formula , classed as a ...
s were known at the time of invention, e.g. DIOP
DIOP (2,3-''O''-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane) 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.
DIOP is prepared fr ...
, DIPAMP
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 ...
, CHIRAPHOS, but DuPhos was found to be more effective.
Description
The ligand consists of two 2,5-alkyl-substituted phospholane rings connected by a 1,2-phenyl bridge. The alkyl group can bemethyl
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...
, ethyl, propyl
In organic chemistry, a propyl group is a three-carbon alkyl substituent with chemical formula for the linear form. This substituent form is obtained by removing one hydrogen atom attached to the terminal carbon of propane. A propyl substituent ...
, or isopropyl
In organic chemistry, a propyl group is a three-carbon alkyl substituent with chemical formula for the linear form. This substituent form is obtained by removing one hydrogen atom attached to the terminal carbon of propane. A propyl substituent ...
. In the closely related bis(dimethylphospholano)ethane or BPE ligand the ''o''-phenylene bridge is replaced by a 1,2-ethylene bridge. Both compounds can be obtained from the corresponding chiral diol
A diol is a chemical compound containing two hydroxyl groups ( groups). An aliphatic diol may also be called a glycol. This pairing of functional groups is pervasive, and many subcategories have been identified. They are used as protecting gro ...
through conversion to the cyclic sulfate
The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...
and reaction with lithiated phenylbisphosphine. In DuPhos the phosphorus atoms are electron-rich making the resulting metal complexes reactive. The phosphorus atoms also introduce a kind of pseudo-chirality making enantioselection independent of the overall chemical conformation
In chemistry, rotamers are chemical species that differ from one another primarily due to rotations about one or more single bonds. Various arrangements of atoms in a molecule that differ by rotation about single bonds can also be referred to as ...
Another early application is the synthesis of unnatural chiral amino acids
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...
in a formal reductive amination
Reductive amination (also known as reductive alkylation) is a form of amination that converts a carbonyl group to an amine via an intermediate imine. The carbonyl group is most commonly a ketone or an aldehyde. It is a common method to make amine ...
for example starting from benzophenone
Benzophenone is a naturally occurring organic compound with the formula (C6H5)2CO, generally abbreviated Ph2CO. Benzophenone has been found in some fungi, fruits and plants, including grapes. It is a white solid with a low melting point and ros ...
and the hydrazone
Hydrazones are a class of organic compounds with the structure . They are related to ketones and aldehydes by the replacement of the oxygen =O with the = functional group. They are formed usually by the action of hydrazine on ketones or aldehydes. ...
of benzoyl chloride
Benzoyl chloride, also known as benzenecarbonyl chloride, is an organochlorine compound with the formula . It is a colourless, fuming liquid with an irritating odour, and consists of a benzene ring () with an acyl chloride () substituent. It is ...
:
:
In the original scope the metal catalyst was rhodium
Rhodium is a chemical element; it has symbol Rh and atomic number 45. It is a very rare, silvery-white, hard, corrosion-resistant transition metal. It is a noble metal and a member of the platinum group. It has only one naturally occurring isot ...
but catalysis by 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 ...
was introduced in 1995 with the hydrogenation of the ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
group in β-keto esters:
:
Applications
An application of an asymmetric synthesis with a DuPhos ligand is the hydrogenation of dehydrowarfarin towarfarin
Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...
:
:
Duphos is also applied in the synthesis of tryptophan derivatives.
In polymerization catalysis
DuPhos ligands are used in metal catalyzed alpha-olefin/carbon monoxide
Carbon monoxide (chemical formula CO) is a poisonous, flammable gas that is colorless, odorless, tasteless, and slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the si ...
copolymerization
In polymer chemistry, a copolymer is a polymer derived from more than one species of monomer. The polymerization of monomers into copolymers is called copolymerization. Copolymers obtained from the copolymerization of two monomer species are som ...
to form chiral isotactic
Tacticity (from , "relating to arrangement or order") is the relative stereochemistry of adjacent chiral centers within a macromolecule. The practical significance of tacticity rests on the effects on the physical properties of the polymer. The ...
polyketones. The first publication in this field dates back to 1994 with catalyst system d(Me-DuPhos(MeCN)2)BF4)2
BozPhos ligand
Mono oxidation of (R,R)-Me-Duphos usingborane dimethylsulfide
Borane dimethylsulfide (BMS) is a chemical compound with the chemical formula . It is an adduct between borane molecule () and dimethyl sulfide molecule (). It is a complexed borane reagent that is used for hydroborations and reductions. The adv ...
as protective group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In man ...
and hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...
as oxidizing agent gives bozPhos This ligand is useful in copper-catalyzed asymmetric addition of diorganozinc
Organozinc chemistry is the study of the physical properties, synthesis, and reactions of organozinc compounds, which are organometallic compounds that contain carbon (C) to zinc (Zn) chemical bonds.The Chemistry of Organozinc Compounds' (Patai S ...
reagents to N-diphenylphosphinoylimines.
References
{{Reflist Diphosphines DuPont products