Copper Catalyzed Synthesis Of Alkyne Propylamines Derivatives

The development of convenient and efficient methods for the synthesis of propargylamines derivatives has attracted considerable attention. Propargylamines derivatives can be utilized as the key synthetic intermediates for the preparation of some natural products and bioactive compounds. There are three main methods have been developed for the preparation of propargylamines derivatives. One involves the substitution reactions of functionalized tertiary amines with alkynyllithium. The second involves the transition-metal-catalyzed three-component one-pot coupling reactions (A3-coupling reactions) of aldehydes, alkynes, and secondary amines. The third involves the copper- or iron-catalyzed activation of C-H bonds with tertiary amines. Among these methods, the third one is the most economical and practical. However, the requirement of external oxidants is disadvantageous because of the sensitivity of some alkynes. In addition, aliphatic alkynes usually have low reactivity. Therefore, we intend to explore a method which not only have good functional group tolerance, but also can activate aliphatic alkynes.In the present study, oxidant-dependent Cu-catalyzed alkynylation and aminomethylation reactions have been achieved under facile and mild conditions. TMEDA coupled with various terminal alkynes via C-H bond cleavage in good yields using atmospheric oxygen as oxidant. Switching from air to tert-butyl hydroperoxide (TBHP) afforded aminomethylation products of terminal alkynes through C-C bond cleavage of TMEDA. The optimized reaction conditions:anhydrous copper chloride (10 mol%) used as catalyst, DMSO as solvent, oxygen or TBHP as oxidant at 80℃ for 5 h. This new method showed a broad substrates scope and high functional tolerance. In conclusion, we have developed a novel and environment friendly strategy to prepare propargylamines and these results have good value in academy and application.