The asymmetric bioreduction of α,β-unsaturated γ-keto esters using ene-reductases from the Old Yellow Enzyme family proceeds with excellent stereoselectivity and high conversion levels, covering a broad range of acyclic and cyclic derivatives. Various strategies were employed to provide access to both enantiomers, which are versatile precursors of bioactive molecules. The regioselectivity of hydride addition on di-activated alkenes was elucidated by isotopic labeling experiments and showed strong preference for the keto moiety as activating/binding group as opposed to the ester. Finally, chemoenzymatic synthesis of (R)-2-(2-oxocyclohexyl)acetic acid was achieved in high ee on a preparative scale combining enzymatic reduction followed by ester hydrogenolysis. Scheme 1 γ-Oxo acids and esters employed as precursors of biologically active molecules. 1 † Electronic supplementary information (ESI) available: Synthetic procedures and NMR data. See Scheme 4 Access to (R)-2-(2-oxocyclohexyl)acetic acid [(R)-7b] via chemoenzymatic bioreduction-deprotection using NCR. Scheme 5 Elucidation of the anchor group of di-activated substrates (exemplified for 3a) in ene-reductases via incorporation of deuterium.Scheme 6 Baker's yeast catalyzed bioreduction of rac-8b for determination of absolute configuration. 14 Green Chemistry PaperThis journal is

A practical two-stage one-pot synthesis of N-substituted β-amino alcohols using aldehydes and isocyanides as starting materials has been developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon-carbon bond disconnection, this protocol complements traditional approaches that involve amines and various carbon electrophiles (epoxides, α-halo ketones, β-halohydrins). Medicinally relevant products can be prepared in a concise and efficient way from simple building blocks, as demonstrated in the synthesis of the antiasthma drug salbutamol. Upgrading the synthesis to an enantioselective variant is also feasible.

One-Pot Synthesis of N-Substituted -Amino Alcohols from Aldehydes and Isocyanides. -A practical two-stage one-pot synthesis of N-substituted -amino alcohols using aldehydes and isocyanides as starting materials is developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon-carbon bond disconnection, this protocol complements traditional approaches that involve amines and various carbon electrophiles. -(CIOC, R. C.; VAN DER NIET, D. J. H.; JANSSEN, E.; RUIJTER, E.; ORRU*, R. V. A.; Chem. -Eur. J. 21 (2015) 21, 7808-7813, http://dx.doi.org/10.1002/chem.201500210 ; Dep. Chem. Pharm. Sci., Vrije Univ., NL-1081 HV Amsterdam, Neth.; Eng.) -H. Hoennerscheid 42-090