Synthesis of δ- and α‑Carbolines via Nickel-Catalyzed [2 + 2 + 2] Cycloaddition of Functionalized Alkyne-Nitriles with Alkynes

A new method for the synthesis of δ- and α-carbolines through Ni-catalyzed [2 + 2 + 2] cycloaddition of ynamide-nitriles or alkyne-cyanamides with alkynes has been developed. The catalytic system of NiCl₂(DME)/dppp/Zn with a low-cost Ni­(II)-precursor was first utilized in Ni-catalyzed [2 + 2 + 2] cycloaddition reactions, and the in situ generated Lewis acid may play an important role for the successful transformation. Not only internal alkynes but also terminal alkynes undergo the desired cycloaddition reactions efficiently to furnish the carboline derivatives with wide diversity and functional group tolerance

Gold(I)-Catalyzed Formal Intramolecular Dehydro-Diels–Alder Reaction of Ynamide-ynes: Synthesis of Functionalized Benzo[<i>b</i>]carbazoles

A gold-catalyzed cycloisomerization of ynamide-ynes via a formal dehydro-Diels–Alder reaction has been developed, providing an attractive route to diversely substituted benzo­[<i>b</i>]­carbazoles. The reaction likely proceeds via regioselective attack of the pendant alkyne moiety to a keteniminium ion intermediate followed by benzannulation. The method offers several advantages such as high efficiency, mild reaction conditions, and wide functional group tolerance and serves as a highly useful complement to the thermal DDA reactions of ynamide-ynes

Gold-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with 4,5‑Dihydro-1,2,4-oxadiazoles: Synthesis of Functionalized 4‑Aminoimidazoles

A gold-catalyzed formal [3 + 2] cycloaddition of ynamides with 4,5-dihydro-1,2,4-oxadiazoles has been developed. The reaction provides a concise and regioselective access to highly functionalized 4-aminoimidazoles likely via the formation of an α-imino gold carbene intermediate followed by cyclization. 4,5-Dihydro-1,2,4-oxadiazole was found to act as an efficient <i>N</i>-iminonitrene equivalent in these reactions

DNA-Compatible Cyclization Reaction to Access 1,3,4-Oxadiazoles and 1,2,4-Triazoles

DNA-encoded chemical library (DECL) technology is a commonly employed screening platform in both the pharmaceutical industry and academia. To expand the chemical space of DECLs, new and robust DNA-compatible reactions are sought after. In particular, DNA-compatible cyclization reactions are highly valued, as these reactions tend to be atom economical and thus may provide lead- and drug-like molecules. Herein, we report two new methodologies employing DNA-conjugated thiosemicarbazides as a common precursor, yielding highly substituted 1,3,4-oxadiazoles and 1,2,4-triazoles. These two novel DNA-compatible reactions feature a high conversion efficiency and broad substrate scope under mild conditions that do not observably degrade DNA