Base-Mediated, Chemo- and Regioselective (4+2) Annulation of Indole-2-carboxamides with 2,3-Epoxy Tosylates toward 1,2-Fused Indoles.

Base-mediated [4+2] annulation of indole-2-carboxamides with 2,3-epoxy tosylates has been explored. The protocol delivers 3-substituted pyrazino[1,2- a ]indol-1-ones in high yields in diastereoselective fashion, and neither 4-substituted pyrazino[1,2- a ]indol-1-ones nor tetrahydro-1 H -[1,4]diazepino[1,2- a ]indol-1-ones are generated, irrespective of whether the distal epoxide C3 substituent is alkyl or aryl, or the epoxide is cis - or trans -configured. This reaction proceeds in one pot via N-alkylation of the indole scaffold with 2,3-epoxy tosylates, concomitantly followed by 6-exo-selective epoxide-opening cyclization. Notably, the process is chemo- and regioselective with respect to both the starting materials. To our knowledge, the process represents the first successful example of one-pot annulation of indole-based diheteronucleophiles with epoxide-based dielectrophiles.