A General Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides & Lactams

27 January 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


A new iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3+2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using catalytic Vaska’s complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent, regio- and diastereoselective, inter- and intramolecular, dipolar cycloaddition reactions with variously substituted electron-poor alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures which ultimately control the unusual selectivities observed in certain cases.


Vaska's complex
amide reduction
[3+2] cycloaddition
azomethine ylides
polycyclic amine
density functional calculation

Supplementary materials

SI complete


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