DuPhos
Encyclopedia
DuPhos is a class of asymmetric ligands for asymmetric synthesis. The name DuPhos is derived from the chemical company that developed this type of ligand (DuP, DuPont
) and the compound class of phospholanes (Phos) it belongs to. This diphosphine ligand type was introduced in 1991 by M.J. Burk and first demonstrated in asymmetric hydrogenation of certain enamide esters to amino acid
precursors:
Other phosphine asymmetric ligands were known at the time (DIPAMP
, BINOL, CHIRAPHOS
) but the new ligand was found to be more effective.
) connected via a 1,2-phenyl bridge. The alkyl group can be methyl, ethyl
, propyl
or isopropyl
. In the closely related bis(dimethylphospholano)ethane or BPE ligand the phenyl bridge is replaced by an 1,2-ethyl bridge. Both compounds can be obtained from the corresponding chiral diol
through conversion to the cyclic sulfate
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
Another early application is the synthesis of unnatural chiral amino acids in a formal reductive amination
for example starting from benzophenone
and the hydrazone
of benzoyl chloride
:
In the original scope the metal catalyst was rhodium
but catalysis by ruthenium
was introduced in 1995 with the hydrogenation of the ketone
group in β-keto esters:
:
Duphos is also applied in the synthesis of tryptophan derivatives.
copolymerization to form chiral isotactic polyketones. The first publication in this field dates back to 1994 with catalyst system [Pd(Me-DuPhos(MeCN)2)](BF4)2
as oxidizing agent gives bozPhos This ligand is useful in copper-catalyzed asymmetric addition of diorganozinc reagents to N-diphenylphosphinoylimines.
DuPont
E. I. du Pont de Nemours and Company , commonly referred to as DuPont, is an American chemical company that was founded in July 1802 as a gunpowder mill by Eleuthère Irénée du Pont. DuPont was the world's third largest chemical company based on market capitalization and ninth based on revenue in 2009...
) and the compound class of phospholanes (Phos) it belongs to. This diphosphine ligand type was introduced in 1991 by M.J. Burk and first demonstrated in asymmetric hydrogenation of certain enamide esters to amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
precursors:
Other phosphine asymmetric ligands were known at the time (DIPAMP
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 the basis for of the first practical asymmetric...
, BINOL, CHIRAPHOS
Chiraphos
Chiraphos is a chiral diphosphine employed as a ligand in organometallic chemistry. This bidentate ligand chelates metals via the two phosphine groups. Its name is derived from its description — being both chiral and a phosphine...
) but the new ligand was found to be more effective.
Description
The ligand consists of two 2,5-alkyl-substituted phospholane rings (the phosphorus analog of THFThF
Follicular B helper T cells , are antigen-experienced CD4+ T cells found in the B cell follicles of secondary lymphoid organs such as lymph nodes, spleens and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5...
) connected via a 1,2-phenyl bridge. The alkyl group can be methyl, ethyl
Ethyl group
In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5....
, propyl
Propyl
In organic chemistry, propyl is a three-carbon alkyl substituent with chemical formula -C3H7. It is the substituent form of the alkane propane...
or isopropyl
Isopropyl
In organic chemistry, isopropyl is a propyl with a group attached to the secondary carbon. If viewed as a functional group an isopropyl is an organic compound with a propyl group attached at its secondary carbon.The bond is therefore on the middle carbon....
. In the closely related bis(dimethylphospholano)ethane or BPE ligand the phenyl bridge is replaced by an 1,2-ethyl bridge. Both compounds can be obtained from the corresponding chiral diol
Diol
A diol or glycol is a chemical compound containing two hydroxyl groups A geminal diol has two hydroxyl groups bonded to the same atom...
through conversion to the cyclic sulfate
Sulfate
In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
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
Another early application is the synthesis of unnatural chiral amino acids in a formal reductive amination
Reductive amination
Reductive amination is a form of amination that involves the conversion of a carbonyl group to an amine via an intermediate imine...
for example starting from benzophenone
Benzophenone
Benzophenone is the organic compound with the formula 2CO, generally abbreviated Ph2CO. Benzophenone is a widely used building block in organic chemistry, being the parent diarylketone.-Uses:...
and the hydrazone
Hydrazone
Hydrazones are a class of organic compounds with the structure R1R2C=NNH2. They are related to ketones and aldehydes by the replacement of the oxygen with the NNH2 functional group...
of benzoyl chloride
Benzoyl chloride
Benzoyl chloride, also known as benzenecarbonyl chloride, is an organochlorine compound with the formula C6H5COCl. It is a colourless, fuming liquid with an irritating odour...
:
In the original scope the metal catalyst was rhodium
Rhodium
Rhodium is a chemical element that is a rare, silvery-white, hard and chemically inert transition metal and a member of the platinum group. It has the chemical symbol Rh and atomic number 45. It is composed of only one isotope, 103Rh. Naturally occurring rhodium is found as the free metal, alloyed...
but catalysis by ruthenium
Ruthenium
Ruthenium is a chemical element with 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 inert to most chemicals. The Russian scientist Karl Ernst Claus discovered the element...
was introduced in 1995 with the hydrogenation of the ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
group in β-keto esters:
Applications
An application of an asymmetric synthesis with a DuPhos ligand is the hydrogenation of dehydrowarfarin to warfarinWarfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
:
Duphos is also applied in the synthesis of tryptophan derivatives.
In polymerization catalysis
DuPhos ligands are used in metal catalyzed alpha-olefin / carbon monoxideCarbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
copolymerization to form chiral isotactic polyketones. The first publication in this field dates back to 1994 with catalyst system [Pd(Me-DuPhos(MeCN)2)](BF4)2
BozPhos ligand
Mono oxidation of (R,R)-Me-Duphos using borane dimethylsulfide as protective group and hydrogen peroxideHydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
as oxidizing agent gives bozPhos This ligand is useful in copper-catalyzed asymmetric addition of diorganozinc reagents to N-diphenylphosphinoylimines.