Boron-Catalyzed Formylation of Indoles Using Trimethyl Orthoformate as Carbonyl Source

This study presents a practical, efficient, and scalable approach for the C-H formylation of indoles and their derivatives using alkyl orthoesters as formylating agents. Boron trifluoride diethyl etherate (BF₃·OEt₂) was found to be an effective stoichiometric catalyst, with trimethyl orthoformate (TMOF) acting as a reliable formyl source. This method enables the rapid and efficient synthesis of a wide range of C-formylindoles, including C3, C2, C6, and C7 derivatives, as well as electron-rich aromatic carbaldehydes. Key advantages of the protocol include its operational simplicity, use of inexpensive and readily available reagents, neat conditions, ambient reaction temperatures, short reaction times (typically 1-5 min), broad substrate tolerance, and scalability. These features make the method highly versatile and suitable for diverse synthetic applications.