workers have reported the direct conversion of activated alcohols
into imines and amines using stoichiometric amounts of MnO2
(oxidizing agent) and polymer-supported cyanoborohydride
(reducing agent).5 On the other hand, the borrowing hydrogen
approach is a strategy for the N-alkylation of amines since there
is no net hydrogen gain or loss.6 In this regard ruthenium7 and
iridium8 catalysts have been successfully employed to achieve
this oxidation, imination, and reduction sequence. However,
these methods are mainly focused on the synthesis of amines
even though imines are the intermediates. We have recently
developed a heterogeneous palladium catalyst, Pd/AlO(OH)
(1),9a that is composed of palladium nanoparticles entrapped in
boehmite nanofibers. The catalyst has shown high activity and
excellent efficiency in the aerobic oxidation of alcohols and
racemization of amines for chemoenzymatic dynamic kinetic
resolution and R-alkylation of ketones with alcohols.9 During
the course of our investigation, we found that this system could
be effective for the C-N coupling reaction of various alcohols
with amines to couple imines or amines without any additives.
Moreover, this reaction promises an attractive green chemistry,
as water is the only byproduct. We first examined the reaction
of benzyl alcohol (1.0 mmol) with 2-phenylethylamine (1.2
mmol) in the presence of 1 (2.0 mol % of Pd) for 20 h at 90 °C
under oxygen atmosphere and obtained N-benzylidene-2-phen-
ethylamine in 90% yield.10 Meanwhile, the same reaction under
argon gave a 80:20 mixture of N-benzyl-2-phenylethanamine
and N-benzylidene-2-phenethylamine after 12 h. Subsequently,
we could convert the mixture to pure N-benzyl-2-phenyletha-
namine (92% yield) at 25 °C under hydrogen atmosphere
(Scheme 1).
One-Pot Synthesis of Imines and Secondary
Amines by Pd-Catalyzed Coupling of Benzyl
Alcohols and Primary Amines
Min Serk Kwon,‡ Sungjin Kim,† Sungho Park,†
William Bosco,† Ravi Kumar Chidrala,† and Jaiwook Park*,†
Department of Chemistry, Pohang UniVersity of Science and
Technology (POSTECH), San 31 Hyojadong,
Pohang, Kyeongbuk 790-784, Republic of Korea, and
Electrical Steel Research Group, Technical Research
Laboratories, POSCO, Pohang, Kyeongbuk 790-300,
Republic of Korea
ReceiVed December 10, 2008
Imines and secondary amines were synthesized selectively
by controlling reaction conditions for the Pd-catalyzed one-
pot reactions of benzyl alcohols with primary amines. The
reactions did not require any additives and were effective
for a wide range of alcohols and amines.
The efficacy of 1 for the coupling of benzyl alcohol with
2-phenethylamine was compared with those of various com-
mercial catalysts (Table 1). The catalyst 1 exhibited the highest
activity among the commercial palladium catalysts such as Pd/
C, Pd/Al2O3, Pd/CaCO3, Pd/BaCO3, and PdEnCat (entries 2-6).
Other metal catalysts such as Ru/Al2O3 and Rh/Al2O3 were
found to be feeble under the same conditions (entries 7 and 8).
The carbon-nitrogen bond-forming reaction is one of the
significant transformations in organic synthesis.1 In particular,
imines are highly desirable, owing to their applications as
electrophiles in many organic reactions such as reduction,
addition, condensation, and cycloaddition.2 Traditionally, imines
are synthesized via the addition of amines and carbonyl
compounds with azeotropic distillation to expel the liberated
water.3 Furthermore, condensation reactions carried out in the
presence of Lewis acids have also been documented in the
literature.4 As a related C-N coupling reaction, Taylor and co-
(4) (a) Billman, J. H.; Tai, K. M. J. Org. Chem. 1958, 23, 535. (b) White,
W. A.; Weingarten, H. J. Org. Chem. 1967, 32, 213. (c) Weingarten, H.; Chupp,
J. P.; White, W. A. J. Org. Chem. 1967, 32, 3246. (d) Moretti, I.; Torre, G.
Synthesis 1970, 141. (e) Jennings, W. B.; Lovely, C. J. Tetrahedron Lett. 1988,
29, 3725. (f) Branchaud, B. P. J. Org. Chem. 1983, 48, 3531. (g) Texier-Boullet,
F. Synthesis 1986, 679. (h) Armstrong, J. D.; Wolfe, C. N.; Keller, J. L.; Lynch,
J.; Bhupathy, M.; Volante, R. P. Tetrahedron Lett. 1997, 38, 1531. (i) Liu, G.;
Gogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64,
1278. (j) Chakraborti, A. K.; Bhagat, S.; Rudrawar, S. Tetrahedron Lett. 2004,
45, 7641.
(5) Blackburn, L.; Taylor, R. J. K. Org. Lett. 2001, 11, 1637.
(6) Hamid, M. H. S. A.; Slatford, P. A.; Williams, J. M. J. AdV. Synth. Catal.
2007, 349, 1555.
(7) Tillack, A.; Hollmann, D.; Michalik, D.; Beller, M. Tetrahedron Lett.
2006, 47, 8881.
† Department of Chemistry, Pohang University of Science and Technology
(POSTECH).
‡ Electrical Steel Research Group, Technical Research Laboratories, POSCO.
(1) (a) Shafir, A.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 8742. (b)
Balraju, V.; Iqbal, J. J. Org. Chem. 2006, 71, 8954. (c) Djakovitch, L.; Dufaud,
V.; Zaidi, R. AdV. Synth. Catal. 2006, 348, 715. (d) Cacchi, S.; Fabrizi, G. Chem.
ReV. 2005, 105, 2873. (e) Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz,
U. AdV. Synth. Catal. 2006, 348, 23.
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Chem. Soc. 1996, 118, 4916. (b) Co´rdova, A. Acc. Chem. Res. 2004, 37, 102.
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S. I.; Komiya, N.; Nakae, T. J. Am. Chem. Soc. 2003, 125, 15312. (e) Drury,
W. J.; Ferraris, D.; Cox, C.; Young, B.; Lectka, T. J. Am. Chem. Soc. 1998,
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(3) (a) Schiff, H. Annals 1864, 131, 118. (b) Moffett, R. B. In Organic
Syntheses; Rabjohn, N., Ed.; John Wiley & Sons, Inc: New York, 1963; Collect.
Vol. IV, pp 608-611. (c) Castellano, J. A.; Goldmacher, J. E.; Barton, L. A.;
Kane, J. S. J. Org. Chem. 1968, 33, 3501. (d) Taguchi, K.; Westheimer, F. H.
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(9) (a) Kwon, M. S.; Kim, N.; Park, C. M.; Lee, J. S.; Kang, K. Y.; Park, J.
Org. Lett. 2005, 7, 1077. (b) Kwon, M. S.; Kim, N.; Seo, S. H.; Park, I. S.;
Cheedrala, R. K.; Park, J. Angew. Chem., Int. Ed. 2005, 44, 6913. (c) Kim,
M. J.; Kim, W. H.; Han, K.; Choi, Y. K.; Park, J. Org. Lett. 2007, 9, 1157. (d)
Kim, S.; Bae, S. W.; Lee, J. S.; Park, J. Tetrahedron 2009, 65, 1461.
(10) The reaction of benzyl alcohol (1.0 mmol) with 2-phenylethylamine
(1.2 mmol) was carried out in toluene, ethyl acetate, and dichloromethane in
the presence of 1 (2.0 mol % of Pd) for 12 h at 90 °C under argon to give the
products in 90% (amine:imine ) 80:20), 63% (70:30), and 0% yield, respectively.
10.1021/jo8026609 CCC: $40.75
Published on Web 03/05/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 2877–2879 2877