Synthesis of Substituted Imidazo[1,5-a]pyrazines via Mono-, Di-, and Directed Remote Metalation Strategies.

Imidazo[1,5-a]pyrazines 1undergo regioselective C3-metalation and C5/C3-dimetalation to afford a range of functionalized derivatives 2a−2g(Table 1), and 4a−4d(Table 2). Under similar conditions, the C3-methyl derivatives 2aand 5undergo surprising regioselective C5-deprotonation to afford, after electrophile quench, products 4b and 6a−6p(Table 3), results that are rationalized by quantum mechanical calculations. Benzamide 7b, obtained from such metalation chemistry followed by Suzuki cross coupling, undergoes directed remote metalation-cyclization to afford 8, representing the hitherto unknown triazadibenzo[cd,f]azulen-7(6H)-one tricyclic ring system. [ABSTRACT FROM AUTHOR]