AZA-INDOLIZINE WITH BRIDGEHEAD NITROGEN - METALATION, HALOGEN-METAL EXCHANGE AND DIRECTED ORTHO-LITHIATION IN THE IMIDAZO[1,2-A]PYRAZINE SERIES

The n-BuLi and lithium 2,2,6,6-tetramethylpiperidine (LTMP) metalation of imidazo[1,2-a]pyrazine heterocycles and subsequent quenching with electrophiles is described. Bromine atoms exhibit different behaviours towards lithiation depending on their positions (3 or 6) on the imida zo[1,2-a]pyrazine heterocycle. Halogen-metal exchange occurs readily w ith the bromine on position 3. On the contrary, bromine on position 6 only leads to C-5 substituted derivatives further to an ortho-directin g effect. (C) 1998 Elsevier Science Ltd. All rights reserved.