M. K. Patil, M. Keller, B. M. Reddy, P. Pale, J. Sommer
FULL PAPER
350 °C for 3 d under a nitrogen flow, quantitatively yielding CuI-
USY.
General Procedure for the CuI-Zeolite-Catalyzed Condensation of
Amines, Aldehydes, and Terminal Alkynes: Amines 1a–d (1.0 mmol,
1.0 equiv.), aldehydes 2a–f (1.0 mmol, 1.0 equiv.), and then alkynes
3a,b (1.2 mmol, 1.2 equiv.) were successively added to CuI-USY
(20 mg, 0.07 equiv.). After stirring at 80 °C for 15 h, the mixture
was diluted with dichloromethane (5 mL). After removing the cata-
lyst by filtration, solvent evaporation provided the resulting crude
product usually at ca. 95% purity as judged by NMR spectroscopy.
Column chromatography was then performed. Most of the adducts
thus formed are known compounds, and propargylamines
4a,[10a,10b] 4b,[9a,10a] 4c,[10f,16] 4d,[9e] 4e,[9e,10f] 4f,[9k,10a] 4g,[9k]
4h,[10a,10d] 4i,[10c] 4j,[9k] 4l,[9k,10b] 4n,[10c] and 4o[9k,10b] have been re-
ported previously.
4-Methyl-3-(piperidin-1-yl)-1-phenyltridec-1-yne (4k): A 1:1 mixture
Scheme 4. Proposed mechanism for the MCR catalyzed by CuI-
USY.
of diastereoisomers as a yellowish oil. IR (neat): ν = 2360, 2340,
˜
1
1465, 1376, 1157, 754 cm–1. H NMR (CDCl3): δ = 7.44–7.50 (m,
2ϫ2 H), 7.27–7.33 (m, 2ϫ3 H), 3.09 and 3.13 (2 d, J = 9 Hz, 2ϫ1
H), 2.63–2.71 (m, 2ϫ2 H), 2.43–2.50 (m, 2ϫ2 H), 1.78–1.86 (m,
2ϫ3 H), 1.58–1.70 (m, 2ϫ4 H), 1.42–1.52 (m, 2ϫ2 H), 1.21–1.40
(br. s, 2ϫ16 H), 1.04 and 1.13 (2d, J = 6 Hz, 2ϫ3 H), 0.92–0.95
(m, 2ϫ3 H) ppm. 13C NMR (CDCl3): δ = 131.73, 128.18, 127.76,
123.93, 88.05, 86.04, 64.56, 64.38, 51.19, 51.06, 50.86, 35.50, 34.87,
34.38, 33.19, 32.01, 30.24, 29.74, 29.25, 26.98, 26.58, 26.39, 24.83,
23.92, 22.78, 21.77, 17.50, 16.58, 14.18 ppm. MS: m/z (%) = 354
(100) [M + 1]+, 283 (4), 240 (2). HRMS: calcd. 354.3155; found
354.3148.
Conclusions
Cu-modified zeolites, especially Cu-USY, proved to be
very efficient catalysts for the synthesis of propargylamines
from aldehydes, amines, and alkynes. Moreover, no solvent
is required for this reaction, and upon filtration the adduct
is usually obtained as a single compound. Therefore, with
a heterogeneous catalyst, which can be reused, this multi-
component reaction fulfills most of the principles of green
chemistry. Preliminary mechanistic investigations suggest
that this reaction proceeds via an iminium intermediate,
probably assisted by zeolite, and that this formation is com-
bined with the formation of acetylide within the zeolite
pores, leading to an efficient reaction.
1-(4-Fluorophenyl)-1-(piperidin-1-yl)-3-(p-tolyl)prop-2-yne
(4m):
Yellowish oil. IR (neat): ν = 2360, 2320, 1604, 1506, 1222, 1154,
˜
1
815 cm–1. H NMR (CDCl3): δ = 7.64 (br. dd, J = 9, 6 Hz, 2 H),
7.44 (d, J = 7 Hz, 2 H), 7.15 (d, J = 7 Hz, 2 H), 7.05 (br. dd, J =
9, 8 Hz, 2 H), 4.78 (s, 1 H), 2.56 (br. t, J = 6 Hz, 4 H), 2.38 (s, 3 H),
1.52–1.70 (m, 4 H), 1.42–1.51 (m, 2 H) ppm. 13C NMR (CDCl3): δ
= 162.14 (JC,F = 244 Hz, C), 138.16 (C), 134.46 (JC,F = 2.5 Hz, C),
131.62 (CH), 129.98 (JC,F = 8 Hz, CH), 128.99 (CH), 120.03 (C),
114.72 (JC,F = 20.9 Hz, CH), 88.14 (C), 84.49 (C), 61.60 (CH),
50.51 (CH2), 26.19 (CH2), 24.38 (CH2), 21.40 (CH3) ppm. MS: m/z
(%) = 308 (100) [M + 1]2+, 223 (45). HRMS: calcd. 308.1736; found
308.1897.
Experimental Section
General: All starting materials were commercial and were used as
received. The reactions were monitored by thin-layer chromatog-
raphy carried out on silica plates (silica gel 60 F254, Merck) using
UV light and p-anisaldehyde for visualization. Column chromatog-
raphy was performed on silica gel 60 (0.040–0.063 mm, Merck) by
using mixtures of ethyl acetate and cyclohexane as eluents. Solvents
were removed by evaporation under reduced pressure at tempera-
tures below 30 °C unless otherwise noted. IR spectra were recorded
with a Perkin-Elmer FTIR 1600 spectrometer (KBr disc), and val-
Acknowledgments
The authors thank the CNRS and the French Ministry of Research
for financial support. M. P. thanks the French Embassy in New
Delhi, India, for support of his stay in France under a sandwich
Ph. D. and Post-Doctoral Research Programme.
ues are reported in cm–1. H and 13C NMR spectra were recorded
1
with a Bruker Avance 300 spectrometer at 300 and 75 MHz, respec-
tively. Chemical shifts (δ) and coupling constants (J) are given in
ppm and Hz, respectively. The chemical shifts are reported relative
to the residual solvent as an internal standard ([D1]chloroform:
[1] I. Marek, Tetrahedron 2005, 61, 11309–11519.
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δ
=
7.26 ppm
for
1H
and
77.0 ppm
for
13C;
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[D4]methanol: δ = 3.31 ppm for 1H and 49.15 ppm for 13C). Carbon
multiplicities were determined by DEPT 135 experiments. Electron
impact (EI) and electrospray (ESI) low- and high-resolution mass
spectra were recorded at the mass spectrometry department of the
Institut de Chimie, Strasbourg.
Preparation of CuI-USY: Commercial NH4-USY was loaded in an
oven and heated at 550 °C for 4 h to give H-USY. H-USY (1 g)
and CuCl (475 mg, 1.1 equiv.) were mixed by using a mortar and
charged in a closed reactor. The mixture of powders was heated at
[4] For a review, see: L. Zani, C. Bolm, Chem. Commun. 2006,
4263–4275.
[5] a) M. Konishi, H. Ohkuma, K. Matsumoto, T. Tsuno, H. Ka-
mei, T. Miyaki, T. Oki, H. Kawaguchi, G. D. VanDuyne, J.
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