Stereoselective Three‐Step One‐Pot Cascade Combining Amino‐ and Biocatalysis to Access Chiral γ‐Nitro Alcohols

The combination of small‐molecule catalysis and enzyme catalysis represents an underexploited area of research with huge potential in asymmetric synthetic chemistry due to both compatibility of reaction conditions and complementary reactivity. Herein, we describe the telescopic synthesis of chiral nitro alcohols starting from commercially available benzaldehyde derivatives through the one‐pot three‐step chemoenzymatic cascade combination of a Wittig reaction, chiral‐thiourea‐catalysed asymmetric conjugate addition, and ketoreductase‐mediated reduction to access the corresponding target compounds in moderate to excellent overall isolated yields (36–80 %) and high diastereomeric and enantiomeric ratios (up to >97 : 3). This represents the first example of the combination of an organocatalysed asymmetric conjugate addition via iminium ion activation and a bioreduction step catalysed by ketoreductases.