Directed evolution of Pseudomonas aeruginosa lipase by the use of combinatorial active site saturation test (CAST) criteria provided a highly enantioselective mutant (Leu162Phe) for kinetic resolution of an axially chiral allene, p-nitrophenyl 4-cyclohexyl-2-methylbuta-2,3-dienoate (E=111); the high enantioselectivity of the Leu162Phe mutant was rationalized by pi-pi stacking.

Enzyme- and ruthenium-catalyzed dynamic kinetic asymmetric transformation (DYKAT) of bicyclic diols to their diacetates was highly enantio- and diastereoselective to give the corresponding diacetates in high yield with high enantioselectivity (99.9 % ee). The enantiomerically pure diols are accessible by simple hydrolysis (NaOH, MeOH), but an alternative enzyme-catalyzed ester cleavage was also used to give the trans-diol (R,R)-1 b in extremely high diastereomeric purity (trans/cis=99.9:0.1, >99.9 % ee). It was demonstrated that the diols can be selectively oxidized to the ketoalcohols in a ruthenium-catalyzed Oppenauer-type reaction. A formal enantioselective synthesis of sertraline from a simple racemic cis/trans diol 1 b was demonstrated.

Primary alcohols with an unfunctionalized stereogenic center in the b-position undergo an enzyme-and metal-catalyzed dynamic kinetic resolution (DKR). The in situ racemization of the primary alcohol, required for the DKR, takes place via: (i) ruthenium-catalyzed dehydrogenation of the alcohol, (ii) enolization of the aldehyde formed, and (iii) ruthenium-catalyzed readdition of hydrogen to the aldehyde. The present method widens the scope of metal-and enzyme-catalyzed DKR, which has so far been limited to a-chiral alcohol and amine derivatives.Keywords: dynamic kinetic resolution; enzyme catalysis; metal catalysis; primary alcohols The development of efficient protocols for the synthesis of optically active compounds has attracted major attention in organic chemistry, because of the increasing demand for such compounds as building blocks in the pharmaceutical or agrochemical industry.[1] The most common way to prepare enantiomerically pure compounds in the chemical industry is still via resolution and separation of enantiomers from racemic mixtures.[2] In this respect, enzymatic resolution plays an important and dominant role [3] and a number of multi-ton industrial processes are based on enzymatic resolution.[4] A drawback with these kinetic resolutions (KR) is the maximum theoretical yield of 50 % leading to waste of half of the material. A solution to this problem is dynamic kinetic resolution (DKR), [5] which takes advantage of an in situ racemization of the remaining substrate enantiomer (Scheme 1). In this way a yield of up to 100 % of enantiopure material can be achieved.During the past decade, various DKR methods based on the combination of an enzyme and an additional racemization catalyst have been developed. [5d,6] In particular, the combination of an enzyme and a transition metal catalyst has proven to be useful for DKR of secondary alcohols.[5d] In the first efficient system developed, [7] Shvos ruthenium catalyst 1 (Scheme 2) was employed, and this catalyst requires a slightly elevated temperature. This procedure has been successfully applied to the DKR of various substituted secondary alcohols including diols [8] and allylic alcohols.[9] The method was recently extended to amines. [10] Further developments have led to room temperature procedures for DKR of secondary alcohols that employ a new type of racemization catalyst together with an enzyme. [11][12][13] In all these applications, the metal catalyst can be compared with the dehydrogenase/hydrogenase activity by enzymes having NAD(P)/ NAD(P)H as cofactor.All of the protocols for chemoenzymatic DKR of alcohols and amines described to date have been limited to substrates that are chiral at the a-carbon (A, Figure 1). An extension of chemoenzymatic DKR to alcohols and amines with a non-functionalized chiral carbon, for example, B (Figure 1) would significantly broaden the scope of the method. Scheme 1. Principle of a dynamic kinetic resolution (DKR).Adv. Synth. Catal. 2007, 349, 1577 -1581 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim...

Propellants containing nitrocellulose (NC) continuously decompose. The decomposition products released in the process increase the rate of the decomposition and a self‐accelerating behavior is obtained. To prevent the autocatalysis, stabilizers are added to NC/NG‐based propellants. The action of the stabilizers is to trap the nitrous decomposition products and form stable compounds, which prevent or delay further decomposition. The most common stabilizers are aniline derivatives, which can form potentially toxic and/or carcinogenic nitrosamine derivatives during prolonged storage in propellants. This work is the joint effort between the Swedish Defence Research Agency (FOI) and Eurenco Bofors (EuB) to find new stabilizers without any amine moiety to avoid nitrosamine formation, which has resulted in a new class of stabilizers with plasticizing properties. The paper describes the concept of this class of plasticizing stabilizers, the synthesis of these compounds and characterization of their performance as stabilizers. The most promising stabilizer was found to be bis(2,6‐dimethoxyphenyl)triethyleneglycol (Stab‐5). Kilogram scale production of this substance at FOI allowed evaluation of its stabilizing effect in real propellants and its effect on the burning rate in a double‐base rocket motor at EuB. Accelerated ageing of a double‐base propellant stabilized with Stab‐5 was applied in order to identify the compounds that were obtained in the reaction between the stabilizer and the decomposition products.

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