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Direct Access to Cinnoline-4-carbaldehydes: Iridium(III)-Catalyzed C-H [4 + 2] Annulation Using 2-Chloromalonaldehyde
Chao Zhang1, Guan-Yu Qiao1, Lin Dong1
1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Abstract:
Herein we report a concise synthesis of diazaheterocycle-fused cinnolines via an Ir(III)-catalyzed [4 + 2] annulation between 1-aryl-1,2-dihydropyridazine-3,6-diones and 2-chloromalonaldehyde. This strategy is characterized by three key features: (i) the first employment of 2-chloromalonaldehyde as a C2 synthon in metal-catalyzed cyclization reactions; (ii) the direct and efficient installation of an aldehyde group, a versatile synthetic handle and reactive motif enabling subsequent functionalization; and (iii) a subsequent dephthaloylation step that affords synthetically valuable cinnoline-4-carbaldehyde derivatives.
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