Electrochemical Cross-Dehydrogenative Coupling of Isochroman and Unactivated Ketones

An unprecedented electrochemical cross-dehydrogenative coupling reaction between isochroman and unactivated ketones to directly synthesize a-substituted isochromans has been developed. This strategy provides a facile and efficient procedure to the direct activation of C(sp(3))-H bond adjacent to the O atom of isochroman. The method features high atom economy, chemical oxidant-free, and mild conditions, in which methanesulfonic acid (MsOH) acts as both electrolyte and catalyst, making the process more convenient and environmentally friendly. Gram-scale experiment and synthesis of antitumor active compounds demonstrate the great potential of this protocol for practical applications.

Automated summary

An unprecedented electrochemical cross-dehydrogenative coupling reaction has been developed for the direct synthesis of α-substituted isochromans by coupling isochroman with unactivated ketones. This method allows for the direct activation of the C(sp(3))-H bond adjacent to the O atom of isochroman and features high atom economy, chemical oxidant-free conditions, and mild reaction conditions. Methanesulfonic acid (MsOH) serves as both electrolyte and catalyst, making the process more convenient and environmentally friendly. Gram-scale experiments and synthesis of antitumor active compounds demonstrate the practical potential of this protocol.