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

• Published in: Organic letters Vol. 11; no. 22; pp. 5118 - 5121
• Main Authors: Board, Johnathan, Wang, Jian-Xin, Crew, Andrew P, Jin, Meizhong, Foreman, Kenneth, Mulvihill, Mark J, Snieckus, Victor
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 19.11.2009; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Cyclization; Imidazoles - chemical synthesis; Imidazoles - chemistry; Metals - chemistry; Molecular Structure; Physical Sciences; Pyrazines - chemical synthesis; Pyrazines - chemistry; Quantum Theory; Science & Technology; Stereoisomerism; ROUTE; QUINOLINES; IMIDAZOLES; PYRIDINES; DERIVATIVES; AZINES; IMIDAZO<1,5-A>PYRAZINES
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol901889e

Imidazo[1,5-a]pyrazines 1 undergo regioselective C3-metalation and C5/C3-dimetalation to afford a range of functionalized derivatives 2a−2g (Table ), and 4a−4d (Table ). 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 ), 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.