title: Application of sequential Cu(I)/Pd(0)-catalysis to solution-phase parallel synthesis of combinatorial libraries of dihydroindeno[1,2-c]isoquinolines.
abstract: Parallel solution-phase synthesis of combinatorial libraries of dihydroindenoisoquinolines employing a sequential Cu(I)/Pd(0)-catalyzed multicomponent coupling and annulation protocol was realized. The scope and limitations of the protocol with respect to the substitution pattern in the aryl ring of the indene core, as well as the N-substituent have been defined, revealing that the methodology is compatible with a wide-range of aliphatic linear, branched, and ester functionalized N-substituents. Unexpectedly, the formation of regioisomers featuring a 1,2,3-contiguous substitution pattern in the aromatic ring of the indene core was observed. Three distinct combinatorial libraries with a total of 111 of members were synthesized, and 80 highly substituted dihydroindenoisoquinolines structurally related to known medicinal agents including some consisting of mixtures of two regioisomers were made available for biological activity testing.
authors.affiliation: Department of Chemistry, The University of Kansas, Lawrence, 66045, United States.
authors.forename: Sarvesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Painter
authors.forename: Benoy K
authors.initials: BK
authors.lastname: Pal
authors.forename: Benjamin
authors.initials: B
authors.lastname: Neuenswander
authors.forename: Helena C
authors.initials: HC
authors.lastname: Malinakova
mesh_terms: D002384:Catalysis; D060326:Chemistry Techniques, Synthetic; D003300:Copper / Q000737:chemistry*; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions; D013237:Stereoisomerism
chemical_list: D007192:Indenes; D007546:Isoquinolines; D054852:Small Molecule Libraries; D012996:Solutions; D010165:Palladium; D003300:Copper