One of the major advantages of enzymatic reactions over chemical reactions is that they typically occur under mild aqueous reaction conditions at neutral pH, which also facilitates the development of enzymatic cascade reactions without an intermediate work-up step. Having demonstrated the versatility and ebiciency of NR-triggered indazole formation, we decided to further showcase its synthetic utility by developing an enzymatic cascade for the facile synthesis of indazoles from cheap and readily available building blocks. Thus, we envisioned an enzymatic cascade using imine reductases (IREDs) or reductive aminases (RedAms) as well-established biocatalysts to form secondary amines from a carbonyl and a primary amine compound . These enzymes could provide the 2-nitrobenzylamines required for the NR-triggered indazole formation from cheap and readily available 2-nitrobenzaldehyde and a primary amine (Figure ). To prove this concept, IREDs from Mycobacterium smegmatis (IRED10), Actinomadura rifamycini (IRED15), Streptomyces tsukubaensis (IRED20), Streptomyces viridochromogenes (IRED23) and the RedAm from Aspergillus oryzae (AspRedAm) were investigated for the generation of 1b from 2-nitrobenzaldehyde (12) and methylamine (13) (Figure ).