Copper-Catalyzed 1,2-Double Amination of 1-Halo-1-alkynes. Concise Synthesis of Protected Tetrahydropyrazines and Related Heterocyclic Compounds

Abstract

Reaction of N, N ‘-di( p -toluenesulfonyl)-1,2-diamine, 1-bromo-1-alkyne, K 3 PO 4, and a catalytic amount of CuI 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 or six-membered N, O -heterocycle was produced. In addition, 1,1-dibromo-1-alkene could be used in place of 1-bromo-1-alkyne.