Biocatalytic Approaches to the Henry (Nitroaldol) Reaction

Enantiopure β‐nitro alcohols are key chiral building blocks for the synthesis of bioactive pharmaceutical ingredients. The preparation of these target compounds in optically pure form has been the focus of much research and there has been an emergence of biocatalytic protocols in the past decade. For the first time, these biotransformations are the focus of this review. Herein, we describe two principal biocatalytic approaches to the Henry (nitroaldol) reaction. The first method is a direct enzyme‐catalysed carbon–carbon bond formation resulting in either an enantio‐enriched or enantiopure β‐nitro alcohol. The second approach describes the Henry reaction without stereocontrol followed by a biocatalytic resolution to yield the enantiopure β‐nitro alcohol. Enantiopure β‐nitro alcohols are key chiral pool intermediates for the synthesis of a wide array of bioactive molecules. Methods to gain access to these valuable synthons include organo‐, transition metal‐ and bio‐catalysis. In recent years biocatalytic methods have gained momentum in this area. This microreview details these advances, which principally include a direct enzyme‐catalysed C–C bond formation or enzyme‐mediated resolution of the products of the Henry reaction. This approach is reviewed in detail for the first time.