10.1002/chem.201903402
Chemistry - A European Journal
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flash chromatography techniques is simple and straightforward,
providing the pure isomers in preparative amounts. We believe
that the reported protocol offers a practical and unified solution for
the hitherto unresolved direct synthesis of -EWG substituted
acrylonitriles from terminal alkynes, and we are confident that it
will find widespread use in the preparative synthesis of these
important building blocks.
[6] A Scifinder search by reaction, structure and topic only showed this result.
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2370.
Experimental Section
General procedure. Synthesis of
(Z/E)-n-octyl 3-
cyanoacrylate (2c). A solution of n-octyl alkynoate 1c (363 mg;
2.0 mmol), acetone cyanohydrin (178.7 mg; 2.1 mmol) and
DABCO (2.2 mg; 0.02 mmol) in CH2Cl2 (4 mL) was stirred for 1h
at room temperature. Solvent was evaporated under reduced
pressure and the crude residue was flash chromatographed using
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Synthesis 2007, 1465-1470.
v
silica gel. Elution with ethyl acetate-hexanes (10/90 /v) afforded
1
pure (E)-2c (306.3 mg, 73%). Colorless liquid: H NMR (CDCl3,
500 MHz): 0.85 (t, 3H, 3J(H,H) = 6.9 Hz), 1.22-1.35 (m, 10H),
3
1.63-1.69 (m, 2H), 4.20 (t, 2H, J(H,H) = 6.7 Hz), 6.47 (d, 1H,
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3
3J(H,H) = 16.4 Hz), 6.70 (d, 1H, J(H,H) = 16.4 Hz). 13C NMR
(CDCl3, 100 MHz): 14.0, 22.6, 25.6, 28.4, 29.07 (2C), 31.7,
66.2, 112.8, 115.3, 139.9, 163.3 ppm. HRMS (ESI+): m/z [M+Na]+
calculated for C12H19NO2 232.1313, found 232.1319. Further
elution (30/70 v/v) delivered pure (Z)-2c (114.1 mg, 27%).
Colorless liquid: 1H NMR (CDCl3, 400 MHz): 0.86 (t, 3H,
3J(H,H) = 6.9 Hz), 1.25-1.38 (m, 10H), 1.67-1.72 (m, 2H), 4.24 (t,
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inflammatory drug. S. Strickson, D. G.Campbell, C. H. Emmerich, A.
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3
3
2H, J(H,H) = 6.7 Hz), 5.93 (d, 1H, J(H,H) = 11.4 Hz), 6.70 (d,
3
1H, J(H,H) = 11.4 Hz). 13C NMR (CDCl3, 100 MHz): 14.0,
[10] a) For the development of catalytic multicomponent manifolds based on
this reactivity generation principle, see: D. Tejedor, S. López-Tosco, F.
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22.6, 25.8, 28.3, 29.07 (2C), 31.7, 66.1, 110.4, 114.2, 138.4,
162.5 ppm. HRMS (ESI+): m/z [M+Na]+ calculated for C12H19NO2
232.1313, found 232.1315.
Acknowledgements
[11] S. A. Haroutounian. Acetone Cyanohydrin. In Encyclopedia of Reagents
for Organic Synthesis, John Wiley & Sons, 2001.
The authors thank the Spanish Ministries of Economy and
Competitiveness (MINECO), Science, Innovation and Universities
(MICINN), Agencia Estatal de Investigación (AEI) and the
European Regional Development Funds (ERDF) for financial
support (CTQ2015-63894-P and PGC2018-094503-B-C21). S. D.
H. thanks La Laguna University and Cajasiete for a pre-doctoral
contract.
[12] DABCO has shown to be an excellent nucleophilic catalyst for this kind of
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Tejedor, M. A. Maestro, J. González-Platas, Org. Lett. 2001, 3, 1905-1908.
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Keywords: Hydrocyanation • Terminal alkynes • DABCO •
Organocatalysis • acetone cyanohydrin
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