Unnatural α-amino acid derivatives are greatly important in pharmaceuticals and biochemicals owing to their diverse biological activities, and usually serve as versatile building blocks in organic synthesis as well. A variety of approaches have been developed to prepare α-amino acid derivatives, among which N—H insertion reactions of diazo compounds are considered to be one of the most direct methods. These N—H insertion reactions typically proceed through carbene active intermediates that derived from diazo compounds by UV-induction or metal catalysis. As a green and powerful avenue to organic synthesis, visible-light-mediated methodology has also been applied to N—H insertion of diazo compounds principally through carbene intermediates. Due to the single reaction mechanism of these reactions, however, the scope of diazo compounds were limited to α-aryl diazoacetates that can directly absorb the visible-light. Therefore, exploring new activation modes is conducive to expanding the applicable scope and reaction type of diazo compounds in visible- light-mediated reactions. Herein we report visible-light-promoted N-alkylation reactions of (aza)aromatic amines with ethyl diazoacetate based on the mechanism of proton-coupled electron transfer (PCET). A series of α-amino acid derivatives were synthesized by the combination of photocatalyst and Lewis-acid catalyst. This method featured in mild reaction conditions, good functional group tolerance and wide range of substrate scope. Mechanism experiments indicated the reaction involved in radical intermediate rather than carbene that engaged in conventional N—H insertion reactions. According to the fluorescence quenching experiment, the alkyl radical intermediate was formed by the PCET step between ethyl diazoacetate and excited photocatalyst. And then radicals cross-coupling occurred under the coordination of Lewis-acid to produce the final N-alkylation products. This new catalytic strategy expands the applications of diazo compounds in visible-light chemical reactions. The general procedure for the visible-light-promoted N-alkylation reactions of (aza)aromatic amines with ethyl diazoacetate is as following: Aniline 1a (0.1 mmol), ethyl diazoacetate 2 (0.2 mmol), Fe(OTf)₂ (0.02 mmol) and photocatalyst [Ir(ppy)₂(NCMe)₂]PF₆ (0.005 mmol) were dissolved in MeOH (2 mL). Then the mixture was degassed via a “freeze-pump-thaw” procedure (3 times). After that, the resulting mixture was stirred under irradiation of 30 W blue LEDs at room temperature. Upon reaction completion, the crude product was purified by flash chromatograph on silica gel to give the final product.

Key words: visible-light, diazo compound, radical, N-alkylation