Site-Selective Cross-Coupling of Dichlorinated Benzo-Fused Nitrogen-Heterocycles with Grignard Reagents

• Published in: Chemical & pharmaceutical bulletin Vol. 58; no. 9; pp. 1255 - 1258
• Main Authors: Konishi, Hideyuki, Itoh, Tatsuya, Manabe, Kei
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.09.2010; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: Benzene - chemical synthesis; Benzene - chemistry; Catalysis; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; cross-coupling; Grignard reagent; Halogenation; heterocycle; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Life Sciences & Biomedicine; Nitrogen Compounds - chemical synthesis; Nitrogen Compounds - chemistry; palladium; Palladium - chemistry; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; site-selective; ORTHO-DIRECTING GROUPS; HALOGENATED NITROGEN; ARENES; catalysis; site-selective; heterocycle; REGIOSELECTIVITY; FLUORIDES; OXYGEN; Grignard reagent; cross-coupling; palladium; NONREARRANGED MONOTERPENOID UNIT; SIMPLE INDOLE ALKALOIDS; ELECTRONIC-STRUCTURE
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.58.1255

Site-selective cross-coupling of dihaloarenes constitutes a useful method for synthesis of multi-substituted arenes. In this paper, we report the site-selective cross-coupling of dichlorinated benzo-fused nitrogen-heterocycles having two chloro groups on the benzene ring. These dichlorinated heterocycles reacted with Grignard reagents in the presence of PdCl2(PCy3)2 at the positions ortho to the nitrogen-based substituents with high selectivities. A mechanism in which interaction between Lewis acidic Mg and Cl of the ortho position facilitates C–Cl bond cleavage is proposed.