John Crosby

Efficient rhodium and iridium-catalysed asymmetric transfer hydrogenation using water-soluble aminosulfonamide ligands

Abstract A range of aromatic ketones was reduced asymmetrically under transfer hydrogenation conditions using enantiomerically pure catalysts derived from water-soluble diamine ligands and [Cp*MCl 2 ] 2 (Cp*=pentamethylcyclopentadienyl, M=Rh, Ir). High catalytic activity and enantioselectivity were observed in systems containing up to 51% water.

Synthesis of water-soluble aminosulfonamide ligands and their application in enantioselective transfer hydrogenation

Abstract Water-soluble analogues of Noyoris (1S,2S)-N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine and Knochels (1R,2R)-N-(p-tolylsulfonyl)-1,2-diaminocyclohexane, containing an additional sulfonic acid group, have been synthesised. The ruthenium catalysed reduction of aromatic ketones using enantiomerically pure catalyst derived from water soluble ligands and [RuCl2(p-cymene)]2 has been examined. High enantioselectivity and moderate activity were observed in the 2-propanol/base system. The addition of water is necessary to stabilise the catalyst.

Enantioselective alkylation of alanine-derived imines using quaternary ammonium catalysts

Application of N-anthracenylmethyl dihydrocinchonidinium bromide as a catalyst for the enantioselective alkylation of a series of alanine-derived imines is reported. Using solid K2CO3KOH as the stochiometric base such alkylations can be achieved with enantiomeric excesses up to 87% allowing rapid access to α,α-dialkyl-α-amino acid esters.

Studies on the enantioselective synthesis of α-amino acids via asymmetric phase-transfer catalysis

Abstract In this paper, we describe investigations into the use of cinchona alkaloid-derived quaternary ammonium phase-transfer catalysts for the asymmetric alkylation of a benzophenone-derived glycine-imine. Utility of this process is demonstrated by the enantioselective synthesis of a range of α-amino acid esters.

Structure–selectivity studies on catalysts for the phase-transfer catalysed asymmetric alkylation of glycine imine esters

Abstract In this paper, we describe the synthesis of a series of chiral quaternary ammonium salts with core structures that are closely related to the cinchona alkaloid, cinchonine. By employing these salts as asymmetric phase-transfer agents in the benzylation of a glycine imine, an optimal catalyst structure is identified.

Asymmetric alkylation of glycine imines using in situ generated phase-transfer catalysts

In this paper we report an investigation into the possibility of effecting the asymmetric alkylation of glycine imines using chiral quaternary ammonium salt catalysts that are generated in situ. It is demonstrated that O-alkyl N-alkyldihydrocinchonidinium salts can be assembled from the parent alkaloid under the reaction conditions required for the liquid–liquid phase-transfer alkylation of glycine imines, and that reactions performed in this way give enantioselectivities comparable to those obtained using pre-prepared catalysts. Utilization of this methodolgy in the generation and screening of catalyst libraries is also demonstrated.

A practical synthesis of a disulfonated phosphine and its application to biphasic catalysis

Abstract A convenient synthesis of TPPDS (disodium P-phenyl-3,3′-phosphinediyl-bis(benzenesulfonate)) from triphenylphosphine is described. This represents a quick and reliable way to prepare a water-soluble phosphine with essentially no phosphine oxide formation.

Yeast Catalysed Reduction of β-Keto Esters (1): Factors Affecting Whole-Cell Catalytic Activity and Stereoselectivity

Six yeasts were studied for their ability to reduce ethyl 4-chloroacetoacetate (ethyl 4-chloro-3-oxobutanoate) stereoselectively. Five species reduced the substrate to ethyl (S)-4-chloro-3-hydroxybutanoate of high (92–99%) optical purity. With glucose-grown cells, substrate reduction could only be demonstrated when growth was oxygen-limited, whereas xylose-grown Pichia capsulata could be grown under conditions of oxygen excess without losing its reducing ability. Zygosaccha-romyces rouxii exhibited high enantioselectivity (≥98% ee (S)-enantiomer) under all conditions tested, whilst in P. capsulata, a novel switch was observed from producing mainly the (R)-enantiomer using glucose as co-substrate to producing mainly the (R)-enantiomer using 2-propanol as co-substrate. This switch was correlated with a change in reduction predominantly from an NADPH-dependent dehydrogenase system to an NADH-dependent system. In the production of ethyl (R)-4-chloro-3-hydroxybutanoate with P. capsulata, the enantioselectivity...

An enantioselective approach to bis-α-amino acids

Abstract In this paper, we describe details of a study into the asymmetric synthesis of bis-α-amino acids via alkylation of a benzophenone-derived glycine imine under phase-transfer conditions. By employing chiral quaternary ammonium salts derived from cinchona alkaloids it was found that the target bis-amino acids can be produced in good overall yield, and with high levels of stereoselectivity.

Yeast Catalysed Reduction of β-Keto Esters (2): Optimisation of the Stereospecific Reduction by Zygosaccharomyces Rouxii

Zygosaccharomyces rouxii catalysed the reduction of ethyl 4-chloroacetoacetate (ethyl 4-chloro-3-oxobutanoate) to the corresponding (S)-hydroxy ester (ethyl (S)-4-chloro-3-hydroxybutanoate) in high enantiomeric excess. The productivity of non-immobilised cells was compared to cells immobilised on a range of organic and inorganic supports. Cells immobilised in calcium alginate displayed a catalytic activity significantly higher than that of non-immobilised cells. A time dependent fall in the enantiomeric purity of the product was observed with the use of this matrix. This phenomenon was not seen in the reduction catalysed by non-immobilised cells.