Metal-free photoinduced C(sp3)-H/C(sp3)-H cross-coupling to access α-tertiary amino acid derivatives

The cross-dehydrogenative coupling (CDC) reaction is the most direct and efficient method for constructing alpha-tertiary amino acids (ATAAs), which avoids the pre-activation of C(sp(3))-H substrates. However, the use of transition metals and harsh reaction conditions are still significant challenges for these reactions that urgently require solutions. This paper presents a mild, metal-free CDC reaction for the construction of ATAAs, which is compatible with various benzyl C-H substrates, functionalized C-H substrates, and alkyl substrates, with good regioselectivity. Notably, our method exhibits excellent functional group tolerance and late-stage applicability. According to mechanistic studies, the one-step synthesized and bench-stable N-alkoxyphtalimide generates a highly electrophilic trifluoro ethoxy radical that serves as a key intermediate in the reaction process and acts as a hydrogen atom transfer reagent. Therefore, our metal-free and additive-free method offers a promising strategy for the synthesis of ATAAs under mild conditions.

Automated summary

This paper presents a mild, metal-free method for constructing alpha-tertiary amino acids (ATAAs) using the cross-dehydrogenative coupling (CDC) reaction. The method exhibits excellent functional group tolerance and late-stage applicability, and allows for the synthesis of ATAAs under mild conditions.