Open AccessGeneral Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides and Lactams
Author(s) -
Ken Yamazaki,
Pablo Gabriel,
Graziano Di Carmine,
Julia Pedroni,
Mirxan Farizyan,
Trevor A. Hamlin,
Darren J. Dixon
Publication year - 2021
Publication title -
acs catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.898
H-Index - 198
ISSN - 2155-5435
DOI - 10.1021/acscatal.1c01589
Subject(s) - pyrrolidine , azomethine ylide , cycloaddition , chemistry , intramolecular force , amide , trimethylsilyl , iridium , catalysis , density functional theory , combinatorial chemistry , medicinal chemistry , 1,3 dipolar cycloaddition , organic chemistry , computational chemistry
An 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 1 mol% Vaska's complex [IrCl(CO)(PPh 3 ) 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-deficient 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.