Application of Sequential Cu(I)/Pd(0)-Catalysis to Solution-Phase Parallel Synthesis of Combinatorial Libraries of Dihydroindeno[1,2-c]isoquinolines

作者：Kumar Sarvesh; Painter Thomas O; Pal Benoy K; Neuenswander Benjamin; Malinakova Helena C^*

来源：ACS Combinatorial Science, 2011, 13(5): 466-477.

DOI：10.1021/co200027c

• solution-phase parallel synthesis
• combinatorial libraries of heterocycles
• dihydroindenoisquinolines
• multicomponent reactions
• transition metal-catalyzed reactions

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 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.

• 出版日期2011-10