Alkylamines are ubiquitous in pharmaceuticals, materials and agrochemicals. The Mannich reaction is a well-known three-component reaction for preparing alkylamines and has been widely used in academic research and industry. However, the nucleophilic components in this process rely on C(sp2)−H and activated C(sp3)−H bonds while the unactivated C(sp3)−H bonds involved Mannich alkylamination is a long-standing challenge. Here, we report an unprecedented multicomponent double Mannich alkylamination for both C(sp2)−H and unactivated benzylic C(sp3)−H bonds. In this process, various 3-alkylbenzofurans, formaldehyde and alkylamine hydrochlorides assemble efficiently to furnish benzofuran-fused piperidines. Mechanistic studies and density functional theory (DFT) calculations revealed a distinctive pathway that a multiple Mannich reaction and retro-Mannich reaction of benzofuran and dehydrogenation of benzylic C(sp3)−H bonds were key steps to constitute the alkylamination. This protocol furnishes a Mannich alkylamine synthesis from unusual C–H inputs to access benzofuran-fused piperidines with exceptional structural diversity, molecular complexity and drug-likeness. Therefore, this work opens a distinctive vision for the alkylamination of unactivated C(sp3)−H bonds, and provides a powerful tool in diversity-oriented synthesis (DOS) and drug discovery.

The activation of dinitrogen (N 2 ) and direct incorporation of its N atom into C−H bonds to create aliphatic C−N compounds remains unresolved. Incompatible conditions between dinitrogen reduction and C−H functionalization make this process extremely challenging. Herein, we report the first example of dinitrogen insertion into an aliphatic Csp 3 −H bond on the ligand scaffold of a 1,3-propane-bridged [N 2 N] 2− -type dititanium complex. Mechanistic investigations on the behaviors of dinuclear and mononuclear Ti complexes indicated the intramolecular synergistic effect of two Ti centers at a C−N bond-forming step. Computational studies revealed the critical isomerization between the inactive side-on N 2 complex and the active nitridyl complex, which is responsible for the Csp 3 −H amination. This strategy maps an efficient route toward the future synthesis of aliphatic amines directly from N 2 .

Cyclopropanes bearing contiguous all-carbon quaternary centers continue to attract attention due to their bioactivities. However, methods to obtain cyclopropanes with contiguous all-carbon quaternary centers remain largely unexplored due to the high steric hindrance of these compounds. Herein, we report a visible-light-mediated energy-transfer (EnT) strategy to realize in situ donor/donor carbenes from readily available N-tosylhydrazones, facilitating the synthesis of highly congested EWG-free cyclopropanes. Through this approach, cyclopropanes are rapidly installed into complex bioactive molecules, fluorescent molecules, and other useful building blocks that are challenging to synthesize. Detailed mechanistic reactions and DFT studies clearly demonstrated the role of the photosensitizer, the formation of donor/donor carbenes, and the necessity of light and a base in the system.

Splitting of N2 via six-electron reduction and further functionalization to value-added products is one of the most important and challenging chemical transformations in N2 fixation. However, most N2 splitting approaches rely on strong chemical or electrochemical reduction to generate highly reactive metal species to bind and activate N2, which is often incompatible with functionalizing agents. Catalytic and sustainable N2 splitting to produce metal nitrides under mild conditions may create efficient and straightforward methods for N-containing organic compounds. Herein, we present that a readily available and nonredox (n-Bu)4NBr can promote N2-splitting with a Mo­(III) platform. Both experimental and theoretical mechanistic studies suggest that simple X– (X = Br, Cl, etc.) anions could induce the disproportionation of MoIII[N­(TMS)­Ar]3 at the early stage of the catalysis to generate a catalytically active {MoII[N­(TMS)­Ar]3}− species. The quintet MoII species prove to be more favorable for N2 fixation kinetically and thermodynamically, compared with the quartet MoIII counterpart. Especially, computational studies reveal a distinct heterovalent {MoII–N2–MoIII} dimeric intermediate for the NN triple bond cleavage.

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