title: C-H bond functionalization under metalation-deprotonation process: regioselective direct arylation of 3-aminoimidazo[1,2-a]pyrazine.
abstract: Concerted metalation deprotonation (CMD) approach with appropriate proton shuttle precursor, base, and solvent (PivOH-K(2)CO(3)-toluene) has rendered a regioselective Pd-catalyzed C6-arylation of 3-aminoimidazo[1,2-a]pyrazine, a therapeutically relevant scaffold accessible by multicomponent reaction. The arylation of this heteroarene suffers from competing C5 and C2'-arylation reactions, while the developed process has virtually eliminated these competing arylations. Density functional calculations for CMD C-H activation at C6, C5, C8, and C2' sites imply that the energy barrier with distortion energy penalty as major contributing component influences the regioselectivity.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), S. A. S. Nagar, Mohali, 160062, Punjab, India. skguchhait@niper.ac.in
authors.forename: Sankar K
authors.initials: SK
authors.lastname: Guchhait
authors.forename: Somnath
authors.initials: S
authors.lastname: Kandekar
authors.forename: Maneesh
authors.initials: M
authors.lastname: Kashyap
authors.forename: Nikhil
authors.initials: N
authors.lastname: Taxak
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D002384:Catalysis; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011522:Protons; D011719:Pyrazines / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C579748:3-aminoimidazo(1,2-a)pyrazine; D007093:Imidazoles; D008670:Metals; D011522:Protons; D011719:Pyrazines; D012997:Solvents; D010165:Palladium