Catalytic Coupling of Arene C?H Bonds and Alkynes for the Synthesis of Coumarins: Substrate Scope and Application to the Development of Neuroimaging Agents

摘要

C−H bond functionalization offers strategicallynnovel approaches to complex organic compounds. However, manynC−H functionalization reactions suffer from poor compatibilitynwith Lewis basic functional groups, especially amines, which arenoften essential for biological activity. This study describes a systematicnexamination of the substrate scope of catalytic hydroarylationnin the context of complex amino coumarin synthesis.nThe choice of substrates was guided by the design and developmentnof the next generation of fluorescent false neurotransmittersn(FFNs), neuroimaging probes we recently introduced for opticalnimaging of neurotransmission in the brain. Comparison of twonmild protocols using catalytic PtCl4 or Au(PPh3)Cl/AgSbF6nrevealed that each method has a broad and mutually complementary substrate scope. The relatively less active platinum systemnout-performed the gold catalyst with indole substrates lacking substitution at the C-3 position and provided higher regioselectivity innthe case of carbazole-based substrates. On the other hand, the more active gold catalyst demonstrated excellent functional groupntolerance, and the ability to catalyze the formation of strained, helical products. The development of these two protocols offersnenhanced substrate scope and provides versatile synthetic tools required for the structure−activity examination of FFNnneuroimaging probes as well as for the synthesis of complex coumarins in general.