More than 1000 yields and ee determinations are possible per day using an immunoassay. This highly efficient screening method is based on the remarkable binding specificity of antibodies. It has been employed in the development of straightforward procedures for the direct conversion of α‐keto acids into chiral α‐hydroxy acids, for which the enantioselective reduction of benzoyl formic acid to mandelic acid serves as a model reaction (see scheme).

CF3 -substituted 1,3-diols were stereoselectively prepared in excellent enantiopurity and high yield from CF3 -substituted diketones by using an ansa-ruthenium(II)-catalyzed asymmetric transfer hydrogenation in formic acid/triethylamine. The intermediate mono-reduced alcohol was also obtained in very high enantiopurity by applying milder reaction conditions. In particular, CF3 C(O)-substituted benzofused cyclic ketones underwent either a single or a double dynamic kinetic resolution during their reduction.

[Structure: see text] The asymmetric transfer hydrogenation of fluoroalkyl ketones mediated by [Ru(eta6-arene)((S,S)-R2NSO2DPEN)] catalysts using HCO2H-Et3N afforded the corresponding alcohols with high ee's and in excellent yields.

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published as an Advance Article on the web 13th November 2001 b-(3,4-Dimethoxyphenyl)serine methyl ester was obtained in high diastereomeric and enantiomeric excesses under transfer hydrogenation using chiral Ru(h 6 -arene)-N-perfluorosulfonyl-1,2-diamine catalysts.

Interest is continuously growing in the application of powerful combinatorial approaches to the discovery of new catalysts by combining synthesis and screening of large libraries. [1] Although this area is still in its infancy, several catalysts have already been identified by parallel synthesis and high-throughput-screening (HTS) techniques. [2] However, the factor limiting an efficient extension of this research to asymmetric catalysis remains the lack of efficient methods for rapid screening of enantioselective reactions. [3] To overcome this major obstacle, a first approach consists in screening the catalyst library for activity using an HTS procedure and then testing each lead for enantioselectivity by conventional methods, [4] but this is only amenable if few catalysts from the broad library are active. Clearly, a high-throughput technique allowing quantification of both activity and enantioselectivity would accelerate the rate at which asymmetric catalysts are discovered. Recently, IR thermography, [5] capillary array electrophoresis, [6] CD-HPLC, [2c] and electrospray ionization based on the use of isotopically labeled substrates [7] have emerged as promising but equipment-intensive techniques for the screening of enantioselective catalysts. [8] Herein, we describe a new HTS method for the simultaneous screening of multiple catalysts for the enantioselective reduction of ketones. This procedure, allows quantification of both yields and enatiomeric excess (ee) in an HTS format using inexpensive and commonly available equipment.Our interest in this field was focused on the enantioselective reduction of a-keto acids by hydrogen transfer using chiral metal complexes. Although considerable effort was expended to develop applicable methods for the enantioselective preparation of a-hydroxy acids, [9] only a few papers [10] are devoted to the development of straightforward procedures involving the direct conversion of a-keto acids to chiral a-hydroxy acids. As a model reaction, we chose the enantioselective reduction of benzoyl formic acid (BF) into mandelic acid (MA). The catalyst library was prepared by combining a set of 22 chiral diamine-based ligands and four different metal species (Scheme 1).

A highly efficient enantio- and diastereoselective catalyzed asymmetric transfer hydrogenation via dynamic kinetic resolution (DKR–ATH) of α,β-dehydro-α-acetamido and α-acetamido benzocyclic ketones to ent-trans-β-amido alcohols is disclosed employing a new ansa-Ru(II) complex of an enantiomerically pure syn-N,N-ligand, i.e. ent-syn-ULTAM-(CH2)3Ph. DFT calculations of the transition state structures revealed an atypical two-pronged substrate attractive stabilization engaging the commonly encountered CH/π electrostatic interaction and a new additional O=S=O···HNAc H-bond hence favoring the trans-configured products.

New 3 rd generation designer ansa-ruthenium(II)c omplexes featuring N,C-alkylene-tethered N,N-dialkylsulfamoyl-DPEN/h 6 -arene ligands,e xhibited good catalytic performance in the asymmetric transfer hydrogenation (ATH) of various classes of (het)arylk etones in formic acid/triethylamine mixture.I np articular, benzo-fused cyclic ketones furnished 98 to > 99.9% ee using al ow catalyst loading.Keywords: alcohols;a symmetric catalysis;Nl igands;reduction;ruthenium In asymmetric transfer hydrogenation (ATH)o fa ryl ketones using HCO 2 H/Et 3 Nm ixture, ansa-ruthenium(II)-type complexes with intra-covalently tethered diaminea nd h 6 -arene ligand units (complexes A-D of Figure 1) have displayed improved turnover rates over the untethered version. [1,2] In fact, 2 nd and 3 rd generation designed complexes wherein the h 6 -arene ligand is linked to either SO 2 DPEN terminal( available in both enantiomericf orms, DPEN = trans-1,2-diphenylethylenediamine) demonstratede nhancedl ongevity of the catalytic species.T his aspect is economically attractivep romoting theiri ndustrial implementation for the synthesis of enantioenriched a-substituted arylmethanols. [3] We have recentlyi ntroduced a2 nd generation-type {RuCl[(S,S)-DPEN-SO 2 N(Me)(CH 2 ) n (h 6 -aryl)]}c omplex series (complex B)[4] wherein a para-substituted h 6 -phenyl (e.g., p-Tol, p-i-Pr-C 6 H 4 )t ethered to DPEN with -SO 2 N(Me)(CH 2 ) n -( n= 2o r3 )e xhibited an exceptionally high efficiency in the ATHo fa ryl ketones.[2i,k] Thus,u sing substrate-to-catalystr atios (S/Cs) of 200 to 1000, 1-naphthylk etones, a-tetralone, achloroacetophenone,a nd 1,3-diaryl b-diketones furnished at 40-60 8 8Ci nr easonable times the corresponding alcohols in > 98% to virtually perfect ees with full conversion. Given the higher activity of the known 3 rd generation ansa-Ru(II) complexes versus the 2 nd generation,w ew ere interested to explore this option using our R 2 NSO 2 DPEN [5] ligand. Herein, we present an ansa-Ru(II) complex series 1 in which the h 6 -arene is alkylene-tethered to R 2 NSO 2 DPEN from the N'-terminal( a" transshifted tether" comparedt ot he 2 nd generation version) (Scheme 1), andt heir ATHr esults against various types of prostereogenic aryl ketones.Then ew homochiral (S,S)-R 2 NSO 2 DPEN-(CH 2 ) n (h 6 -p-aryl)-type combined preligands 3,w herein the "(CH 2 ) n " ansa-bridge length and the anchored "h 6 -aryl" para end-substituent have been systematically varied, were preparedb yu sf ollowing an improved