Catalytic Asymmetric 1,3-Dipolar Cycloaddition/Hydroamination Sequence: Expeditious Access to Enantioenriched Pyrroloisoquinoline Derivatives

A three-step reaction sequence has been developed to prepare a variety of enantioenriched pyrroloisoquinoline derivatives. The process involves a catalytic asymmetric azomethine ylide 1,3-dipolar cycloaddition followed by an intramolecular Au^I-catalyzed alkyne hydroamination and enamine reduction

Enantioselective Synthesis of α‑Heteroarylpyrrolidines by Copper-Catalyzed 1,3-Dipolar Cycloaddition of α‑Silylimines

α-Heteroarylpyrrolidines have been efficiently prepared via 1,3-dipolar cycloaddition between silylimines and activated olefins. In the presence of Cu­(CH₃CN)₄PF₆/Walphos as catalytic system, high levels of enantioselectivity (up to ≥99% ee) and diastereoselectivity were achieved (major formation of C-2/C-4 <i>trans</i>-substituted pyrrolidines). The reaction is compatible with a broad variety of dipolarophiles including maleimides, maleates, fumarates, nitroalkenes, and vinylsulfones. The resulting cycloadducts can be transformed into bioactive pyrrolidine derivatives

Transition-Metal-Free Radical C(sp³)–C(sp²) and C(sp³)–C(sp³) Coupling Enabled by 2‑Azaallyls as Super-Electron-Donors and Coupling-Partners

The past decade has witnessed the rapid development of radical generation strategies and their applications in C–C bond-forming reactions. Most of these processes require initiators, transition metal catalysts, or organometallic reagents. Herein, we report the discovery of a simple organic system (2-azaallyl anions) that enables radical coupling reactions under transition-metal-free conditions. Deprotonation of <i>N</i>-benzyl ketimines generates semistabilized 2-azaallyl anions that behave as “super-electron-donors” (SEDs) and reduce aryl iodides and alkyl halides to aryl and alkyl radicals. The SET process converts the 2-azaallyl anions into persistent 2-azaallyl radicals, which capture the aryl and alkyl radicals to form C–C bonds. The radical coupling of aryl and alkyl radicals with 2-azaallyl radicals makes possible the synthesis of functionalized amine derivatives without the use of exogenous radical initiators or transition metal catalysts. Radical clock studies and 2-azaallyl anion coupling studies provide mechanistic insight for this unique reactivity