Titanium-Catalyzed Hydrohydrazination with Monosubstituted Hydrazines: Catalyst Design, Synthesis, and Reactivity

A new titanium catalyst using an ethylene diamine backbone with pyrrolyl-α-methyl groups on the diamine nitrogens has been developed for the hydrohydrazination of alkynes with monosubstituted hydrazines. The catalyst cleanly hydrohydrazinates terminal and internal alkynes with monosubstituted hydrazines bearing both alkyl and aryl substituents. One-pot Fischer indole cyclization led to NH-indoles in moderate to good yield. For example, 2-methyltryptamine was synthesized directly from 5-chloropent-1-yne with phenylhydrazine by hydrohydrazination and Fischer indole cyclization in a one-pot procedure. A variety of heterocycles, including pyrazoles and various hydropyridazines, can be generated using titanium-catalyzed hydrohydrazination. One of the products, 1,2-bis(2-methyl-3-indolyl)ethane, was structurally characterized.