The asymmetric functionalization of C–H is one of the most attractive strategies in asymmetric synthesis. In the past decades, catalytic enantioselective C­(sp3)–H functionalization has been intensively studied and successfully applied in various asymmetric bond formations, whereas asymmetric C­(sp3)–H alkylation was not well developed. Photoredox catalysis has recently emerged as an efficient way to synthesize organic compounds under mild conditions. Despite many photoinduced stereoselective reactions that have been achieved, the related enantioselective C­(sp3)–C­(sp3) coupling is challenging, especially of the photocatalytic asymmetric C­(sp3)–H radical alkylation. Here, we report a visible light induced Cu catalyzed asymmetric sp 3 C–H alkylation, which is effective for coupling with unbiased primary, secondary, and tertiary alkyl fragments in high enantioselectivities. This reaction would provide a new approach for the synthesis of important molecules such as unnatural α-amino acids and late-stage functionalization of bioactive compounds, and will be useful for modern peptide synthesis and drug discovery.

In the past decades, the Cu-catalyzed asymmetric organic reactions have been well-developed. By contrast, the potential of Cu to serve as a chiral photocatalyst remains underexplored. We here report the visible-lightinduced, Cu-catalyzed photoredox enantioselective cyanofluoroalkylation of alkenes. In the reaction, the Cu-based single catalyst played a dual role, as both the photoredox catalyst for the outer-sphere electron transfer and the asymmetric cross-coupling catalyst for enantioselective C− CN bond formation.

The C-N cross coupling reaction has always been a fundamental task in organic synthesis. However, the direct use of N-H group of aryl amines to generate N-centered radicals which would couple with alkyl radicals to construct C-N bonds is still rare. Here we report a visible light-promoted C-N radical cross coupling for regioselective amination of remote C(sp3)-H bonds. Under visible light irradiation, the N-H groups of aryl amines are converted to N-centered radicals, and are then trapped by alkyl radicals, which are generated from Hofmann-Löffler-Freytag (HLF) type 1,5-hydrogen atom transfer (1,5-HAT). With the same strategy, the regioselective C(sp3)-C(sp3) cross coupling is also realized by using alkyl Hantzsch esters (or nitrile) as radical alkylation reagents. Notably, the α-C(sp3)-H of tertiary amines can be directly alkylated to form the C(sp3)-C(sp3) bonds via C(sp3)-H − C(sp3)-H cross coupling through the same photoredox pathway.

The visible light induced, photocatalysts or photoabsorbing EDA complexes mediated cleavage of pyridinium C-N bond were reported in the past years. Here, we report an ionic compound promote homolytic cleavage of pyridinium C-N bond by exploiting the photonic energy from visible light. This finding is successfully applied in deaminative hydroalkylation of a series of alkenes including naturally occurring dehydroalanine, which provides an efficient way to prepare β-alkyl substituted unnatural amino acids under mild and photocatalyst-free conditions. Importantly, by using this protocol, the deaminative cyclization of peptide backbone N-terminals is realized. Furthermore, the use of Et3N or PPh3 as reductants and H2O as hydrogen atom source is a practical advantage. We anticipate that our protocol will be useful in peptide synthesis and modern peptide drug discovery.

We here report a novel strategy for the visible-light-induced fluoroalkylthiocyanation of alkenes under photocatalyst-free condition. The primary mechanism studies indicated that, in this reaction, an intriguing photochemical activity of electron...