Organic Letters
Letter
released and trapped by the nucleophilic primary and
secondary amines to yield the corresponding amides.
Scheme 5. Formation of the Acyl Species
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
Detailed experimental procedures and compound
characterization data (PDF)
with phenylacetylene to regenerate the vinylidene 5 and release
4-picoline.21
The previously mentioned stoichiometric results reveal that
(i) complex CpRuCl(PPh3)2 is the catalytic precursor, whereas
the vinylidene derivative 5 is the true catalyst of the amidation;
(ii) the catalysis takes place via Ru(η2-CO)-ketene inter-
mediates, which are formed by oxygen transfer from 4-picoline
N-oxide; (iii) 4-picoline, which is generated from the oxidation
of the vinylidene, displaces the ketene from the ruthenium
coordination sphere; and (iv) the formation of the amide is an
outer-sphere process involving the capture of the released
ketene by the amine. The cycle shown in Scheme 6
summarizes these features.
AUTHOR INFORMATION
Corresponding Authors
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ORCID
́
Notes
The authors declare no competing financial interest.
Scheme 6. Mechanism Proposed for the Ru-Catalyzed
Oxidative Amidation of Terminal Alkynes with Amines
ACKNOWLEDGMENTS
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This work has received financial support from MINECO
(projects CTQ2014-59015R, CTQ2017-87939R, and
CTQ2017-82935-P and the ORFEO−CINQA network
CTQ2016-81797-REDC), the Xunta de Galicia (project
GRC2014/032, ED431C 2018/04, Centro singular de
́
investigacion de Galicia accreditation 2016−2019, ED431G/
09), DGA (No.E06_17R), and the European Union (Euro-
́
pean Regional Development Fund - ERDF). A.A.-P. thanks the
Spanish MICINN for a predoctoral FPI fellowship. We thank
Prof. J. Granja (CiQUS) for a generous gift of aminoester
derivatives.
REFERENCES
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In conclusion, efficient ruthenium-catalyzed oxidative
amidations of alkynes to primary and secondary amides have
been developed using 4-picoline N-oxide as external oxidant.
Remarkably, the catalysis not only takes place in chlorinated
solvents but also in aqueous media, which opens challenging
applications in peptide chemistry. The process occurs by
conversion of terminal alkynes to Ru-ketenes via oxidation of
the initially formed Ru-vinylidene intermediates. Ketenes are
D
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