Jens Holz

The Synthesis of Chiral Phosphorus Ligands for use in Homogeneous Metal Catalysis

Recent developments in the synthesis of chiral phosphorus ligands are summarized. Main emphasis is given to the multitude of protocols for their synthesis starting from compounds of the chiral pool or by using other easily available chiral starting materials. Besides mono‐ and bidentate P‐ligands hybrid ligands bearing N, O, or olefinic groups as second ligating units are addressed. The syntheses of new P‐chirogenic ligands, as well as ligands with supramolecular structures are likewise reviewed. In appropriate cases structures of related privileged ligands are given for comparison. When available, the efficiency of the new ligands for metal catalyzed reactions are briefly assessed.

Rhodium(I) catalyzed asymmetric hydrogenation of enamines

The asymmetric hydrogenation of prochiral electron-rich enamines with rhodium(I) diphosphine and diphosphinite catalysts is described. The reaction is strongly sensitive to the ligand applied. Good results are observed with catalysts based on (R,R)-DIOP, Kβ+-OH, (R,R)-bdpch and other ligands forming seven-membered chelates with the metal. It is shown, that by conversion of a cyclic imine, which could not be hydrogenated, into the corresponding enamine a substrate is formed which is smoothly reduced at 1 bar initial hydrogen pressure by up to 72% ee.

Impressive Enhancement of the Enantioselectivity for a Hydroxy‐Containing Rhodium(I) Bisphosphine Catalyst in Aqueous Solution by Micelle‐Forming Amphiphiles

A selectivity increase for asymmetric hydrogenation in aqueous solution from 1.5%ee (blank experiment) up to 78%ee (amphiphiles present) may be accounted for by inclusion of the catalyst into micellar aggregates. The relative enantioselectivity Qa/b is distinctly higher for the rhodium chelate 1, carrying a hydroxy group, than for the related DIOP complex 2. The effect is minimized in the presence of increasing amounts of methanol, which is known to prevent micelle formation.

Synthesis of the first water-soluble chiral tetrahydroxy diphosphine Rh(I) catalyst for enantioselective hydrogenation

The synthesis of the first chiral polyhydroxy diphosphine-Rh(I) catalyst for asymmetric hydrogenation is described. Based on a simple synthetic pathway starting from d-mannitol the new metal complex is constructed. A special feature of the approach is the protection of the air-sensitive phosphine groups by the catalytically active metal in the final synthetic steps. Therefore, tedious P-protection-deprotection procedures could be advantageously avoided. The new water-soluble catalyst hydrogenates functionalized olefins by up to 99.6% ee in water as solvent.

Synthesis of Chiral 2,5-Bis(oxymethyl)-Functionalized Bis(phospholanes) and Their Application in Rh- and Ru-Catalyzed Enantioselective Hydrogenations

The synthesis of a series of chiral 2,5-bis(oxymethyl)-substituted bis(phospholanes) 13a−c and 15a,b (BASPHOS) is described, representing functionalized derivatives of the prominent DuPHOS or BPE ligands. D-Mannitol was used as the starting material for these ligands. New bisphospholanes were used as ligands in the enantioselective rhodium(I)-catalyzed hydrogenation of functionalized olefins like unsaturated α- and β-amino acid derivatives, itaconates, and an unsaturated phosphonate. A relevant ruthenium(II) catalyst was used for the reduction of prochiral β-oxo esters. The enantioselectivities, ranging from 8−99% ee, were strongly dependent on the type of the substituent on the oxymethyl group as well on the bridge connecting the phospholane units.

THE FIRST CHIRAL EARLY-LATE HETEROBIMETALLIC COMPLEX : A TITANIUM(IV)-PALLADIUM(II) COMPLEX BASED ON SALENOPHOS

Abstract The synthesis of the chiral polyfunctional diphosphine salenophos 1 is described. The new ligand bearing hard and soft coordination sites chelates titanium(IV) as well as palladium(II) in a defined manner provided a certain order during the introduction of the two metals was kept. In this way the first chiral early-late heterobimetallic complex could be synthesized. It was fully characterized by NMR spectroscopy and X-ray structural analysis. Remarkable features of the heterobimetallic complex are the trans coordination of the phosphine groups on palladium and the distance between Ti and Pd which is more than 4.13 A.

Hydroxyalkylphosphines in asymmetric hydrogenations

Abstract The synthesis of chiral bisphosphines bearing a hydroxyl group in a rigid backbone is described. These compounds which are analogues of the prominent ligand DIOP formed definite rhodium complexes. IR spectra provided evidence that the hydroxyl groups do not participate in the complexation to the metal or to one of the acetal oxygen atoms. The complexes have proven successful in the asymmetric hydrogenation of prochiral functionalized olefins in different solvents. In methanol only small effects could be detected in comparison to parent complexes which do not carry a hydroxyl group. However, when hydrogenations were performed in methylene chloride or toluene significant differences in the enantioselectivities (by up to 17 %ee) were observed, especially in the reaction with itaconic acid or its dimethyl ester, respectively. In the latter cases the effect is contingent on the spatial orientation of the hydroxyl group in the catalyst.

Synthesis and catalytic properties of an acyclic analogue of hydroxy norphos

Abstract The synthesis of (S)-1,2-bis(diphenylphosphino)butane-4-ol 1 an acyclic analogue of hydroxy norphos is described, starting from L-ascorbic acid. Problems which arose during the cleavage of OH-protective groups in the presence of phosphino groups are discussed. The hydrogenation properties of the catalyst derived from the new ligand are compared with those obtained with hydroxy norphos.

Chiral phosphinephosphites having axial and central chirality in asymmetric hydroformylations

Abstract Chiral phosphinephosphites were prepared by the reaction of enantiomerically pure cis - or trans -3-diphenylphosphinotetrahydrofuran-4-ol with atropisomeric chlorophosphites. These ligands were tested in the rhodium catalyzed hydroformylation of allyl acetate. Selectivities up to 44% ee were observed in dependence on the configuration of the applied phosphinephosphites and the bulk of the aromatic groups bound to the phosphorus. The results clearly show that both, central and axial chirality are responsible for the stereochemical outcome of this reaction.

On the enantioselective hydrogenation of isomeric β-acylamido β-alkylacrylates with chiral Rh(I) complexes—comparison of phosphine ligands and substrates

Abstract The rhodium(I)-catalyzed enantioselective hydrogenation of E - and Z -configured β-acylamido β-alkylacrylates as well as of isomeric mixtures has been investigated. As ligands 1,2-bisphospholanes like DuPHOS, BPE and Me 4 -BASPHOS have been tested, but also diphosphines forming seven-membered chelates such as DIOP. The effect of additional oxy groups in the diphosphine ligand on rate and enantioselectivity was likewise elucidated. In general, with all catalysts screened the hydrogenation is strongly sensitive to the E / Z -geometry of the substrate. E -Substrates are converted with good or excellent enantioselectivites into the desired β-amino acid derivatives. The hydrogenation of Z -substrates showed the known H 2 -pressure dependency of the ee.