Synthesis of substituted imidazo[1,5-a]pyrazines via mono-, di-, and directed remote metalation strategies.
Imidazo[1,5-a]pyrazines 1 undergo 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 2a and 5 undergo 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.
Board
Johnathan
J
Department of Chemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Wang
Jian-Xin
JX
Crew
Andrew P
AP
Jin
Meizhong
M
Foreman
Kenneth
K
Mulvihill
Mark J
MJ
Snieckus
Victor
V
D003500:Cyclization; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism
D007093:Imidazoles; D008670:Metals; D011719:Pyrazines; C517813:imidazo(1,5-a)pyrazine