Pyridinium amidate ligands for efficient Pd-catalyzed reductive nitroarene cyclization using formate as CO surrogate.
Publisher DOI
Abstract
The field of reductive cyclization of substituted nitroarenes by CO is dominated by the use of palladium
complexes with phenanthroline ligands due to their, up to now, unrivalled combination of resistance to
oxidation by the nitroarene and ability to stabilize both Pd(II) and Pd(0) complexes. Recently developed
pyridinium amidate and pyridinium amide (PYA) ligands are shown here to play the same role. We tested
several N,N-bidentate PYAs in the reductive cyclization of methyl o-nitrocinnamate to 2-
carbomethoxyindole using either phenyl formate or the formic acid/acetic anhydride combination as a
suitable CO surrogate. This approach avoids high-pressure setups for CO handling, allowing the reactions
to be performed in standard pressure tubes. Two of the tested ligands, viz. a quinoline-substituted parapyridinium
amide and a pyridine-functionalized ortho-pyridinium amidate gave excellent results that were
comparable to those achieved using phenanthroline, even at a low catalyst loading (0.25 mol%). However,
the results obtained with the pyridyl-PYA ligand strongly depend on the acidity of the reaction mixture and
the reason was identified as its protonation in an acidic environment. Lower activity observed with other
ligands was attributed to either an ortho-palladation of the pyridinium N-Me moiety or to an insufficient
stabilization of key palladium(0) intermediates.
complexes with phenanthroline ligands due to their, up to now, unrivalled combination of resistance to
oxidation by the nitroarene and ability to stabilize both Pd(II) and Pd(0) complexes. Recently developed
pyridinium amidate and pyridinium amide (PYA) ligands are shown here to play the same role. We tested
several N,N-bidentate PYAs in the reductive cyclization of methyl o-nitrocinnamate to 2-
carbomethoxyindole using either phenyl formate or the formic acid/acetic anhydride combination as a
suitable CO surrogate. This approach avoids high-pressure setups for CO handling, allowing the reactions
to be performed in standard pressure tubes. Two of the tested ligands, viz. a quinoline-substituted parapyridinium
amide and a pyridine-functionalized ortho-pyridinium amidate gave excellent results that were
comparable to those achieved using phenanthroline, even at a low catalyst loading (0.25 mol%). However,
the results obtained with the pyridyl-PYA ligand strongly depend on the acidity of the reaction mixture and
the reason was identified as its protonation in an acidic environment. Lower activity observed with other
ligands was attributed to either an ortho-palladation of the pyridinium N-Me moiety or to an insufficient
stabilization of key palladium(0) intermediates.
Date Issued
2025
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
Fouad, Manar Ahmed | |
Ferretti, Francesco | |
Ragaini, Fabio |
Additional Credits
Journal
Pyridinium Amidate Ligands for Efficient Pd-Catalyzed Reductive Nitroarene Cyclization Using Formate as CO Surrogate.
Publisher
Wiley
ISSN
1867-3880
1867-3899
Funding(s)
Access(Rights)
open.access