Electrochemical Cross-Dehydrogenative Coupling of Isochroman and Unactivated Ketones

An unprecedented electrochemical cross-dehydrogenative coupling reaction between isochroman and unactivated ketones to directly synthesize alpha-substituted isochromans has been developed. This strategy provides a facile and efficient procedure to the direct activation of C(sp3)-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 alpha-substituted isochromans. This method allows for the direct activation of C(sp3)-H bond adjacent to the O atom of isochroman. It has high atom economy, does not require a chemical oxidant, and is carried out under mild conditions using methanesulfonic acid as both electrolyte and catalyst, making it convenient and environmentally friendly. Gram-scale experiments and synthesis of antitumor active compounds demonstrate the practical applicability of this protocol.