Asymmetric hydrogenation using monodentate phosphoramidite ligands.
Monodentate phosphoramidites are excellent ligands for Rh-catalyzed asymmetric hydrogenations of substituted olefins. Enantioselectivities between 95 and 99% were obtained in the asymmetric hydrogenation of protected alpha- and beta-dehydroamino acids and esters, itaconic acid and esters, aromatic enamides, aromatic enol esters, aromatic and aliphatic enol carbamates, and alpha-substituted cinnamic acids. An iridium catalyst Ir(L*)(COD)Cl was developed that contains only a single bulky phosphoramidite based on 3,3'-disubstituted BINOL or bisphenol as a chiral ligand. With this catalyst, acetylated dehydroamino acid esters could be hydrogenated with very good enantioselectivity. Most reactions have turnover frequencies of 250-1600 h (-1), depending upon the hydrogen pressure. The enantioselectivity is unaffected by the pressure over a wide range. Because of their modularity and easy synthesis, parallel ligand synthesis is possible. Results obtained with these library ligands deviate only slightly from those obtained with purified ligands. Using this instant ligand library protocol, DSM has developed catalysts for industrial processes. These MonoPhos ligands are currently used in production for pharmaceutical intermediates by DSM. It is possible to use catalysts based on a mixture of two different monodentate ligands, such as two different monodentate phosphoramidites or one phosphoramidite and one achiral phosphine ligand. Dependent upon the substrate, the "mixed" catalyst may lead to higher enantioselectivity and rate than the "homocatalysts".
Minnaard
Adriaan J
AJ
Organic and Molecular Inorganic Chemistry, Stratingh Institute, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
Feringa
Ben L
BL
Lefort
Laurent
L
de Vries
Johannes G
JG
D000475:Alkenes / Q000737:chemistry; D006865:Hydrogenation; D008024:Ligands; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D012238:Rhodium; D054852:Small Molecule Libraries; D013237:Stereoisomerism
D000475:Alkenes; D008024:Ligands; D009943:Organophosphorus Compounds; D054852:Small Molecule Libraries; C434331:phosphoramidite; D012238:Rhodium