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A series of optically active β-hydroxy sulfones has been obtained through an oxosulfonylation-stereoselective reduction sequence in aqueous medium. Firstly, β-keto sulfones were synthesized from arylacetylenes and sodium sulfinates to subsequently develop the carbonyl reduction in a highly selective fashion using alcohol dehydrogenases as biocatalysts. Optimization of the chemical oxosulfonylation reaction was investigated, finding inexpensive iron(III) chloride hexahydrate (FeCl3 ⋅ 6H2 O) as the catalyst of choice. The selection of isopropanol in the alcohol-water media resulted in high compatibility with the enzymatic process for enzyme cofactor recycling purposes, providing a straightforward access to both (R)- and (S)-β-hydroxy sulfones. The practical usefulness of this transformation was illustrated by describing the synthesis of a chiral intermediate of Apremilast. Interestingly, the development of a chemoenzymatic cascade approach avoided the isolation of β-keto sulfone intermediates, which allowed the preparation of chiral β-hydroxy sulfones in high conversion values (83-94 %) and excellent optical purities (94 to >99 % ee).

The self-assembly of styrene-type olefins into the corresponding stilbenes was conveniently performed in the Deep Eutectic Solvent (DES) mixture 1ChCl/2Gly under air and in the absence of hazardous organic co-solvents using a one-pot chemo-biocatalytic route. Here, an enzymatic decarboxylation of p-hydroxycinnamic acids sequentially followed by a ruthenium-catalyzed metathesis of olefins has been investigated in DES. Moreover, and to extend the design of chemoenzymatic processes in DESs, we also coupled the aforementioned enzymatic decarboxylation reaction to now concomitant Pd-catalyzed Heck-type C-C coupling to produce biaryl derivatives under environmentally friendly reaction conditions.

Amine transaminases (ATAs) are used to synthesize enantiomerically pure amines, which are building blocks for pharmaceuticals and agrochemicals. R‐selective ATAs belong to the fold type IV PLP‐dependent enzymes, and different sequence‐, structure‐ and substrate scope‐based features have been identified in the past decade. However, our knowledge is still restricted due to the limited number of characterized (R)‐ATAs, with additional bias towards fungal origin. We aimed to expand the toolbox of (R)‐ATAs and contribute to the understanding of this enzyme subfamily. We identified and characterized four new (R)‐ATAs. The ATA from Exophiala sideris contains a motif characteristic for d‐ATAs, which was previously believed to be a disqualifying factor for (R)‐ATA activity. The crystal structure of the ATA from Shinella is the first from a Gram‐negative bacterium. The ATAs from Pseudonocardia acaciae and Tetrasphaera japonica are the first characterized (R)‐ATAs with a shortened/missing N‐terminal helix. The active‐site charges vary significantly between the new and known ATAs, correlating with their diverging substrate scope., Diversifying: The toolbox of R‐selective amine transaminases (ATAs) has been expanded by an ATA containing a motif characteristic for d‐ATAs, two ATAs with a shortened/missing N‐terminal helix and the first ATA with known structure from a Gram‐negative bacterium. Their active site charges vary significantly compared to known ATAs correlating with their diverging substrate scope.

The first application of Deep Eutectic Solvents (DESs) in asymmetric bioamination of ketones has been accomplished. The amine transaminases (ATAs) turned out to be particularly stable in DES-buffer mixtures at a percentage of up to 75% (w/w) neoteric solvent. Moreover, this reaction medium was used to perform a chemoenzymatic cascade toward biaryl amines by coupling a Suzuki reaction sequentially with an enantioselective bioamination catalyzed by the recently discovered ATA from Exophiala xenobiotica (EX-wTA). The solubilizing properties of DESs enabled the metal catalyzed step at 200 mM loading of substrate and the subsequent biotransformation at 25 mM.

One of the pioneering examples of chemoenzymatic cascades in water such as the palladium-catalysed Suzuki-cross coupling followed by an enzymatic reduction has been revisited by the employment of a medium containing Deep Eutectic Solvents (DESs) for the catalytic performance. Thus, the unique properties of these neoteric solvents enabled to reach high substrate concentration for the overall process. Moreover, both isolated enzymes and whole cells exhibited excellent activities which allowed to obtain a set of chiral biaryl alcohols in good yields and very high enantiomeric excess (> 99%).

E. Liardo acknowledges funding from the European Union's Horizon 2020 MSCA ITN‐EID program under grant agreement no. 634200 (Project BIOCASCADES). Authors from the University of Oviedo thank the Ministerio de Ciencia e Innovación of Spain (Project CTQ 2014‐55015) and Principado de Asturias (FC‐15‐GRUPIN‐14‐002) for financial support.

The first application of Deep Eutectic Solvents (DESs) in the asymmetric bioreduction of ketones has been accomplished for purified ketoreductases (KREDs). The performance of the biocatalysts was enhanced by increasing the percentage of neoteric solvent in DES-buffer mixtures. At a buffer content of 50% (w/w) and even 20% (w/w), the combination of either choline chloride (ChCl)/glycerol (Gly) (1 : 2) or ChCl/sorbitol (1 : 1) proved to be most effective for achieving up to >99% conversion and up to >99% enantiomeric excess of the corresponding secondary alcohols. Moreover, this reaction medium was used to perform the first example of a chemoenzymatic cascade process in DES-buffer mixtures, namely the ruthenium-catalysed isomerisation of racemic allylic alcohols coupled with a further enantioselective bioreduction, in both sequential and concurrent modes.

A hybrid organo- and biocatalytic system for the asymmetric conversion of racemic alcohols into amines was developed. Combining an organocatalyst, AZADO, an oxidant, NaOCl, and an enzyme, ω-transaminase, we implemented a one-pot oxidation–transamination sequential process in aqueous medium. The method showed broad substrate scope and was successfully applied to conventional secondary alcohols and sterically hindered β-substituted cycloalkanols, where a highly stereoselective dynamic asymmetric bioamination enabled us to set up both contiguous stereocenters with very high enantio- and diastereomeric ratio (>90% yield, >99% ee, and up to 49:1 dr).

The development of continuous flow processes for the synthesis of chiral enantiopure 1-(2-hydroxycycloalkyl)imidazoles is reported. For the ring-opening reaction microwave batch processes and continuous flow reactions have led to similar results in terms of conversion, although the productivity is clearly improved under flow. The use of continuous flow systems for the lipase-catalyzed kinetic resolution of the racemic 2-(1H-imidazol-yl)cycloalkanols with either immobilized CAL-B or PSL-C has been demonstrated to be significantly more efficient than the corresponding batch processes. The continuous flow biotransformations have allowed us to easily increase the production of these chiral imidazoles, adequate building blocks in the synthesis of chiral ionic liquids.

This paper reports a simple and robust modular synthetic strategy that leads to a large variety of configurationally and structurally diverse imidazole-based chiral ionic liquids (CILs) by lipase-catalyzed resolution. The intimate microscopic interactions of the supramolecular ionic network of these imidazolium chiral salts at the molecular level are investigated both spectroscopically (NMR, FT-IR-ATR) and theoretically, and a topological analysis of the experimental electron densities obtained by X-ray diffraction of single crystals is performed. Our results support the key role played by the relative configuration of the -OR group on the hydrogen-bonding pattern and its strong influence on the final physical properties of the imidazolium salt. We also obtained a reasonable correlation between the observed melting point and the non-covalent interactions. The spectroscopic data and the topological analysis reflect the key role played by hydrogen bonds between the OH and imidazolium C2H groups in both cation–anion and cation–cation interactions, with the presence of an OH group leading to an additional inter-cation interaction. This interaction significantly affects the properties of stereoisomeric salts. Even more interestingly, we also studied the effect of the chirality by comparing enantiopure CILs with their racemic mixtures and found that, with the exception of trans-Cy6-OH-Im-Bn-Br, the melting points of the racemic mixtures are higher than those of the corresponding enantiomerically pure forms. For stereoisomeric examples, we have successfully explained the differences in melting temperatures in light of the corresponding structural data. Chirality should therefore be taken into account as a highly attractive design vector in the preparation of ILs with specifically desired properties., Financial support from the Ministerio de Ciencia e Innovación (MICINN CTQ2007-61126, CTQ2008-04415, and CTQ2008-04309), CSIC-I3 (200780I001), and BANCAIXA (P1 1A2007-11) is gratefully acknowledged. V.G.-F and E.G-V. (Ramón y Cajal Program), and R.P. (FPU) thank the MICINN for personal funding. N.R-L. thanks the FICYT for a pre-doctoral fellowship.

An enzymatic one‐pot process for asymmetric transformation of prochiral ketoximes into alcohols or amines was developed by sequential coupling of a laccase‐catalyzed deoximation either with a ketone reduction (ketoreductase, KRED) or bioamination (ω‐transaminase, ω‐TA) in aqueous medium. An accurate selection of biocatalysts provided the corresponding products in excellent enantiomeric excesses and overall conversions ranging from 83 to >99 % for alcohols and 70 to >99 % for amines. Likewise, the employment of exclusively 1 % (w/w) of Cremophor®, a polyethoxylated castor oil, as co‐solvent enabled to reach concentrations up to 100 mM in the chiral alcohols cascade., Authors acknowledge funding from the European Union's Horizon 2020 MSCA ITN‐EID program (grant agreement No 634200). The authors also thank Dr. Martin Schürmann (InnoSyn) and Prof. Harald Gröger (Bielefeld University) for the generous gift of the KRED of Rhodococcus ruber and Lactobacillus kefir, respectively, as well as Dr. Wolfgang Kroutil for the ω‐TAs Cv, ArS and ArR.