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 (BF·OEt) 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.