Construction of Nitrogen Spirocycles in a Tandem Co(III)‐catalyzed C−H Activation/Dipolar Cycloaddition Reaction

Abstract

Complex spirocyclic isoindolines and pyrrolidines are formed in a tandem process involving Co(III)‐catalyzed dienylation of cyclic C‐aryl nitrones with 2,3‐butadien‐1‐ol carbonates, followed by intramolecular 1,3‐dipolar cycloaddition. The nitrone moiety serves both as a directing group for the C(aryl)−H activation and the dipole in the cycloaddition step. High regioselectivity of the fused vs. bridged product can be obtained by adjusting the reaction temperature. Reactions with substituted allenic substrates provide heterocycles with additional stereocenters usually with complete diastereoselectivity. The reaction products were readily transformed further into other complex nitrogen‐containing spirocyclic systems.

Synthesis of Quinolinoneylnitrones and Coumarinylnitrones via a Cascade Hydroamination and Aza-MBH-Type Reaction

“…Nitrones have high reactivity and ideal stability and are often used as organic building blocks for the synthesis of many nitrogen-containing heterocyclic compounds . This intermediate has been successfully applied to construct complex natural products, alkaloids, and drug molecules. − In recent years, with the discovery of new reactions and biological activities, nitrones have attracted more widespread attention from organic chemists and medicinal researchers. − For example, N - tert -butyl-α-phenylnitrone [PBN (Scheme A)] is a common free radical trapping agent, which can scavenge free radicals and inhibit cyclooxygenase-2 (COX-2) . Triazole-substituted nitrone, compound I (Scheme A), was reported to be an antiproliferative agent with an IC 50 value of 8.1 μM against PC-3 cells .…”