Copper-catalyzed 1,2-double amination of 1-halo-1-alkynes. Concise synthesis of protected tetrahydropyrazines and related heterocyclic compounds

Reaction of N,N-di(p-toluenesulfonyl)-1,2-diamine, 1-bromo-1-alkyne, K3PO4, and a catalytic amount of Cul in hot DMF afforded N, N-di(p-toluenesulfonyl)-1,2,3,4-tetrahydropyrazines in good yields. The reaction most likely involves (i) monoalkynylation of the diamine derivative with 1-bromo-1-alkyne, and (ii) 6-endo-dig ring closure between the acetylenic bond and another sulfonylamine moiety of the diamine. When the starting 1,2-diamine derivative was replaced with N,N'-di(p-toluenesulfonyl)-1,3-diamine or N-(p-toluenesulfonyl)-2-amino-1-ethanol, the corresponding seven-membered diazacycle at six-membered N,O-heterocycle was produced. In addition, 1,1-dibromo-1-alkene could be used in place of 1-bromo-1-alkyne.