Journal of the American Chemical Society
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ered to result from D1, the product of cleavage of
1
2
3
4
5
6
7
8
AI along bonds 1,3 (Scheme 3): D3 and D1’, the
latter as a precipitate which started to show up
after about 8 hours reaction time. Both have been
identified by mass spectrometry. D3 increased
gradually from 0 to 3.9 mM in 42 hours and re-
mained the same even after 5 days. It could be iso-
lated from the reaction mixture by column chro-
ASSOCIATED CONTENT
Supporting Information.
This material is available free of charge via the Internet at
Experimental details, NMR spectra, and synthetic proce-
dures, including Schemes S1-S3, Tables S1, S2 and Figures S1−
S15 (PDF)
1
9
matography. Its spectral features (clear H NMR
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and mass spectra) agree with a structure D3 (see
Figures S13a-c for characterization of D3), a possi-
ble product derived from of D1 (Scheme S3). The
1H NMR and mass spectral data of the precipitate
correspond to those expected for D1’, the tautomer
of D1 (see Figures S14a-c for the characterization
of D1’).
AUTHOR INFORMATION
Corresponding Author
*lehn@unistra.fr
ORCID
Jean-Marie Lehn: 0000-0001-8981-4593
Notes
The authors declare no competing financial interests.
Only trace amounts of 2, 4-dinitrobenzaldehyde
(< 3%), the hydrolysis product of D1, could be ob-
served after 5 days. The decomposition scheme of
AI, the corresponding kinetic curves and the data
for the decomposition products are described in
the SI (Schemes S2 and S3, Figure S12-S15).
ACKNOWLEDGMENT
We thank Dr. Jean-Louis Schmitt for discussions of the NMR
and Mass spectral data. We thank in particular one of the
referees for detailed comments. We also thank the ERC (Ad-
vanced Research Grant SUPRADAPT 290585), the ANR
DYNAFUN grant N° ANR-15-CE29-0009-01, the USIAS and
the University of Strasbourg for financial support. RRG grate-
fully acknowledges a doctoral scholarship from the China
Scholarship Council. KF thanks the ERC for post-doctoral
fellowship support. We also thank Wende Hu (Shanghai) for
the computational results.
3. CONCLUSIONS
The present work establishes that the C=C/C=N
exchange reaction between a barbiturate-derived
Knoevenagel compound and an imine proceeds in
organic solvents through an associative mecha-
nism of organo-metathesis type (Scheme 1) with-
out intervention of a metal or proton catalysis.
Structural effects are in line with the influence of
different parameters on the reaction equilibria,
such as conjugation within the Knoevenagel com-
pounds, nucleophilicity of the imine nitrogen and
polarity of solvent. The results obtained also do
not agree with an alternative dissociative mecha-
nism which would proceed by hydrolysis of one or
both components followed by recondensation.
Moreover, the four-membered ring azetidine in-
termediate AI could be stabilized and character-
ized by NMR and HRMS spectroscopies. In a more
general context, the present Knoevenagel metath-
esis process between (strongly) polarized C=C
bonds and C=N bonds with a nucleophilic N site
provides a novel, efficient tool for the creation of
dynamic covalent libraries and for the generation
of dynamic polymers by C=C/C=N recombination.
It has also further potential in other fields such as
complex molecule synthesis, organic materials and
catalysis.
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