[reaction: see text] Ruthenacycles obtained by cyclometalation of enantiopure aromatic primary or secondary amines with [(eta6-benzene)RuCl2]2 or with [(eta6-p-cymene)RuCl2]2 are efficient catalysts for asymmetric transfer hydrogenation (TOF up to 190 h(-1) at room temperature). Enantioselectivities in the transfer hydrogenation of acetophenone ranged from 38% to 89%. It is possible to prepare the catalysts in situ, which allows the use of high throughput experimentation.

Real-time nuclear magnetic resonance (NMR) spectroscopy measurements carried out with a bench-top system installed next to the reactor inside the fume hood of the chemistry laboratory are presented. To test the system for on-line monitoring, a transfer hydrogenation reaction was studied by continuously pumping the reaction mixture from the reactor to the magnet and back in a closed loop. In addition to improving the time resolution provided by standard sampling methods, the use of such a flow setup eliminates the need for sample preparation. Owing to the progress in terms of field homogeneity and sensitivity now available with compact NMR spectrometers, small molecules dissolved at concentrations on the order of 1 mmol L(-1) can be characterized in single-scan measurements with 1 Hz resolution. Owing to the reduced field strength of compact low-field systems compared to that of conventional high-field magnets, the overlap in the spectrum of different NMR signals is a typical situation. The data processing required to obtain concentrations in the presence of signal overlap are discussed in detail, methods such as plain integration and line-fitting approaches are compared, and the accuracy of each method is determined. The kinetic rates measured for different catalytic concentrations show good agreement with those obtained with gas chromatography as a reference analytical method. Finally, as the measurements are performed under continuous flow conditions, the experimental setup and the flow parameters are optimized to maximize time resolution and signal-to-noise ratio.

Chirality is one of the most intriguing features of natural compounds. It determines, for instance, whether a molecule has a beneficial biological function. Consequently, it is of paramount importance in drug discovery to master asymmetric synthesis. For this reason, a number of methods have been developed in modern organic chemistry to obtain enantiopure compounds from racemic mixtures, for example, chemoenzymatic dynamic kinetic resolution (DKR).[1] In this process, the enzymatic kinetic resolution of a racemic compound is combined with the in situ chemical racemization of the chiral center of the substrate. While the theoretical yield in a normal kinetic resolution process is limited to 50 %, which corresponds to total conversion of the preferred enantiomer, in DKR quantitative substrate conversion and high optical purity (> 99 % ee) can be obtained.Despite the numerous asymmetric methods in organic synthesis, concepts for making chiral synthetic polymers are still limited. One obvious reason is the need for optically pure monomers. Possible sources are naturally occurring optically pure monomers such as l-lactide, which, however, limits the range of available monomer building blocks.An alternative is the direct resolution polymerization from synthetic racemic monomers.[2] While most chemical polymerization catalysts are nonstereoselective and therefore not suited for the direct resolution of racemic monomer mixtures, enzymes can be be employed successfully in kinetic resolution polymerizations. In the recent past we and others have shown this for the ring-opening polymerization (ROP) of chiral caprolactones. [2c-e] This process yields polymers with molecular weights of up to 5000 g mol À1 and with over 98 % ee. However, due to the maximum conversion of 50 % in kinetic resolutions it cannot be applied in the polycondensation of racemic diols and dicarboxylic acid derivatives. The reason is that in a typical polycondensation, significant molecular weights can be realized only at an almost quantitative monomer conversion. We anticipated that for chiral monomers this can be achieved by a process analogous to the DKR of small molecules.Here we report on our investigation of a novel concept for the synthesis of chiral polyesters, a lipase-catalyzed dynamic kinetic resolution polymerization of racemic monomers. As shown in Scheme 1, a mixture of stereoisomers of a secondary diol is enzymatically polymerized with a difunctional acyl donor (dicarboxylic acid derivative). Because of its enantioselectivity the lipase converts only the hydroxy groups at the R-configured centers. In situ racemization of the hydroxysubstituted stereocenters from the S to the R configuration allows the polymerization to proceed to high conversion. We recently reported the combination of racemization and enzymatic ring opening of chiral lactones; the two reaction steps were conducted alternating in separate reaction vessels and low-molecular-weight oligomers were obtained (degree of polymerization 3-5).[3] In contrast, our goal here is the ...

Iterative tandem catalysis is presented as a flexible tool for obtaining chiral macromolecules from racemic or prochiral monomers. Here, we combine lipase-catalyzed ring-opening of omega-substituted lactones with ruthenium-catalyzed racemization. In a two-pot system, enantioenriched oligomers of 6-methyl-epsilon-caprolactone were synthesized, which could not have been obtained by enzymatic ring-opening alone. A one-pot experiment proved highly promising in developing a novel route toward enantiopure polyesters.