Rüdiger Selke

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.

New carbohydrate bisphosphites as chiral ligands

Abstract The synthesis of the 2,3-bisphosphite derivatives of phenyl 4,6- O -benzylidene-β-D-glucopyranoside leads to new chelating ligands. Their rhodium(I) and platinum(II) complexes have been tested as catalysts for the asymmetric hydroformylation of vinyl acetate, allyl acetate and p -methoxystyrene. Good regioselectivity (>90% branched product), but an enantioselectivity of only ≤36% ee were found under mild reaction conditions (25–40°C, 40–70 bar syngas).

Application of the term “relative enantioselectivity” as useful measure for comparison of chiral catalysts, demonstrated on asymmetric hydrogenation of amino acid precursors☆

Abstract The application of the quotient “relative enantioselectivity” Q = q/q′ in which q and q′ are enantiomeric ratios R/S (or S/R) for two comparable cases of asymmetric synthesis experiments is recommended for comparison of two or more catalysts or other variables like solvents, substrates and cofactors. The importance of this term Q lies in the possibility to form and compare values of enantioselectivity over the whole range from 99,9 % ee (R) to 99,9 % ee (S) in a mathematically correct way and is demonstrated on multiple examples of asymmetric hydrogenation of partly new N-acyl-dehydroamino acid derivatives with a couple of catalysts [Rh(Pb-β-glup)(COD)]BF41 and [Rh(Ph-β-glup-OH)(COD)]BF42. Interesting inversions of Q could be discovered for changes of the type of substrates and in dependence of the polarity of solvents.

Highly Enantioselective Complex‐Catalyzed Reduction of Ketones— Now with Purely Aliphatic Derivatives Too

A breakthrough for the rhodium-catalyzed asymmetric, homogeneous hydrogenation of unfunctionalized ketones was recently achieved by Zhang et al. with the synthesis and use of ligands 1, named PennPhos, which combine high basisity and optimal spatial requirements with sufficient substituent flexibility.

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.

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.

New seven-membered ring chelates with unexpected enantioselectivity induction in asymmetric hydrogenation — hint for a constant relative enantioselectivity Q for pairs of substrates determined by the structure of the catalysts

Abstract A series of new chiral 2,3-bis(diphenylphosphanylmethyl)-[1,4]dioxane-rhodium(1) chelates as catalysts in the asymmetric hydrogenation of ( Z )-2- N -acylamino-acrylate derivatives, induce in the opposite direction compared with similar well-known catalysts possessing the same configuration, and lead to the unexpected product enantiomers. A thorough investigation of some substrate pairs led to the result that the relative enantioselectivity Q = q H / q Me , the quotient of the enantiomeric ratios q for acid substrates ( q H ) and methyl esters ( q Me ), seems to be constant and characteristic for a catalyst with values influenced distinctly by the structure of the ligand. A new reduction of bisacetals to diethers by the reagent couple triethylsilane - tin tetrachloride was developed in order to obtain ligand 5a .

Internal vs. external ionic functionality—a comparative study in the asymmetric hydrogenation in water as solvent

Abstract Coupling of the benzoylsulfonate moiety to chiral hydroxy phosphines by acylation with o -sulfobenzoic anhydride (SBA) affords unique ligands bearing one or two sulfonate groups in distinguished positions in the molecular framework. Rhodium complexes based on the new ligands have been proven in the asymmetric hydrogenation of functionalized chelating olefins in methanol and in water. Results observed are compared to those featured by the corresponding non-sulfonated catalysts. In methanol as solvent only one of the complexes bearing a sulfonate group in a flexible ligand differed significantly from its parent complex, while in water all sulfonated complexes were superior. In the most cases, addition of the amphiphile sodium dodecylsulfate (SDS) improved the catalytic performance of the parent catalysts as well as that of the sulfonated complexes in water. Other ionic additives (e.g., Na 2 SO 4 , camphersulfonate, benzenesulfonate) which do not bear the long alkyl chain gave poor results illustrating the importance of the particular structure of SDS.

A NOVEL COPPER CHELATE CATALYZED RING CLOSURE REACTION OF 1,2-BISKETENES WITH ALCOHOLS TO GIVE 5-ALKOXY-2,3-DIHYDROFURAN-2-ONES

Copper complexes with distorted tetrahedral structure in solution catalyze regioselectively the cyclization of 1,2-bisketenes with alcohols to give 5-alkoxy-2,3-dihydrofuran-2-ones in very high yields (shown on the right). It seems remarkable that these new compounds could remain undiscovered despite having structural similarities with a great number of well-investigated and biologically active butenolides.

Dependence of Enantioselectivity on the Distribution of a Chiral Hydrogenation Catalyst between an Aqueous and a Micellar Phase: Investigations Using Pulsed Field Gradient Spin Echo NMR Spectroscopy

The enantioselectivity obtained from rhodium complex catalyzed hydrogenations conducted in water can often be increased considerably by the addition of amphiphiles. At present the reasons for this increase in selectivity are not fully understood. The application of pulsed field gradient spin echo NMR (PGSE-NMR) spectroscopy to determine the average diffusion coefficients of the catalysts in both known and novel examples of asymmetric hydrogenation shows definitively that the increase in enantioselectivity is coupled with an aggregation of the catalyst to the micelles. This aggregation or solubilization of the catalyst in the micelles leads to the formation of a new colloidal phase in the aqueous solution. This phase has stronger hydrophobic properties, and thus the hydrogenation is more comparable to those conducted in a hydrophobic or less polar organic solvent. In the case of anionic amphiphiles, which form amphiphilic salts with the cationic catalyst, the embedment of the catalyst complex into the micelle is generally complete. The whole hydrogenation then takes place exclusively inside the micelles, leading to high enantioselectivity. If the catalyst is not completely embedded into the micelle, for example in the cases of nonionic or cationic surfactant solutions, the solubility of the substrate plays an important role. For soluble substrates the hydrogenation of the substrate occurs predominately in the aqueous phase itself, leading to very poor enantioselectivities. In these cases, only the use of a large excess of amphiphile, far above the critical micelle concentration (cmc), will lead to higher enantioselectivities due to a shift of the equilibrium towards the micellar bonded forms of catalyst and substrate. In contrast, poorly soluble substrates exhibit a high tendency to be incorporated into micelles, which leads to much higher enantioselectivities if the cmc of the surfactant is small enough. Changes in the cmc of amphiphiles caused by their aggregation with catalysts could also be estimated. The variation in selectivity observed for the catalysts containing seven-membered, flexible chelate rings is apparently due to changes in their conformation in the less polar micellar medium, and this effect is also seen in organic solvents. As expected, catalysts containing smaller chelate rings show this effect to a considerably lower extent since they are conformationally more rigid.