Palladium-Catalyzed Direct Heck Arylation of Dual π-Deficient/π-Excessive Heteroaromatics. Synthesis of C-5 Arylated Imidazo[1,5-a]pyrazines

• Published in: Organic letters Vol. 10; no. 14; pp. 2923 - 2926
• Main Authors: Wang, Jian-Xin, McCubbin, J. Adam, Jin, Meizhong, Laufer, Radoslaw S, Mao, Yunyu, Crew, Andrew P, Mulvihill, Mark J, Snieckus, Victor
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.07.2008; Amer Chemical Soc
• Subjects: Catalysis; Chemistry; Chemistry, Organic; Combinatorial Chemistry Techniques; Hydrocarbons, Brominated - chemistry; Imidazoles - chemical synthesis; Imidazoles - chemistry; Molecular Structure; Palladium - chemistry; Physical Sciences; Pyrazines - chemical synthesis; Pyrazines - chemistry; Science & Technology; Stereoisomerism; CROSS-COUPLING REACTIONS; ACTIVATION; DESIGN; MECHANISM; BIARYL COMPOUNDS; OLEFINS; H BOND FUNCTIONALIZATION; AROMATIC-SUBSTITUTION; ALKENYLATION; INDOLES
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol800761r

A general and efficient synthesis of 5-aryl imidazo[1,5-a]pyrazines by palladium-catalyzed coupling of the corresponding 8-substituted derivatives with aryl halides is described. The scope of this new reaction for the imidazo[1,5-a]pyrazine ring system was explored using three readily available 8-substituted precursors, X = NH2, NMe2, and OMe, as well as 8-aryl derivatives, X = Ar′. On the basis of these results as well as studies using a deuterated derivative, a Heck-like mechanism is proposed for this transformation.