Enzymatic Synthesis of 3‐Hydroxy Bisindoles and Further C‐3 Sulfenylation via Combining a Carbocatalytic Approach in the Same Pot

Herein, we report the selective synthesis of 3‐hydroxy bisindoles via an engineered myoglobin‐catalyzed Friedel–Crafts reaction of isatin and indole. Initially, the reaction was carried out using wild‐type myoglobin as a catalyst, but the conversion was low. Therefore, a library of Mb‐variants was generated utilizing a site‐directed mutagenesis technique and obtained the double‐mutated Mb(H64V, V68A) variant as a highly reactive and selective biocatalyst for this transformation. Additionally, the robustness and generality of this protocol have been demonstrated by setting up scale‐up reactions of variously substituted isatins and indoles which produce the desired 3‐hydroxy bisindoles in 66–93 % isolated yield. Next, the enzymatic approach was combined with an carbocatalytic protocol by using graphene oxide as a catalyst to generate C‐3 sulfenylated bisindole derivatives in a one‐pot manner.