Iron-catalyzed ligand-free three-component coupling reactions of aldehydes, terminal alkynes, and amines

Article abstract of DOI:10.1002/chem.200802643

The results on the ligand-free three-component coupling reactions of aldehydes, terminal alkynes, and amines, catalyzed by highly efficient FeCl ₃ in the absence of any ligand, were reported. Various iron sources were screened in a model reacti

Full text of DOI:10.1002/chem.200802643

COMMUNICATION
DOI: 10.1002/chem.200802643
Iron-Catalyzed Ligand-Free Three-Component Coupling Reactions of
Aldehydes, Terminal Alkynes, and Amines
Pinhua Li,[a] Yicheng Zhang,[a] and Lei Wang*[a, b]
Over the past few years, iron salts as effective, alternative,
and promising transition-metal catalysts have received much
more attention because of their less expensive, readily avail-
able, and environmentally benign properties. Since the pio-
neering research work of Tamura and Kochi,[1] iron-cata-
lyzed oxidation,[2] hydrogenation,[3] hydrosilylation,[4] rear-
rangement,[5] Michael addition,[6] and carbon–carbon bond
forming reactions have been intensively investigated.[7–9]
molecules.[16b,18] Within the past few years, there have been
several noble transition-metal salts or their bimetallic sys-
tems, such as AgI salts,[19] AuI/AuIII salts,[15,20] AuIII–salen
complexes,[21] CuI salts,[22] Ir complexes,[23] Hg2Cl2,[24] and Cu/
RuII bimetallic systems,[25] which can catalyze this atom-eco-
nomical three-component coupling reaction by C–H activa-
tion of terminal alkynes under homogeneous reaction condi-
tions, for which water is the only theoretical by-product. But
all of these transformations suffer from the loss of precious
or hazardous catalysts at the end of the reaction. AuI, AgI,
and CuI in ionic liquids, supported AuIII, AgI, CuII, and CuI
were successfully used to catalyze the three-component cou-
pling reactions under heterogeneous reaction conditions
with recyclability and reusability of the transition-metal cat-
alysts,[26] however, iron-catalyzed three-component coupling
reactions of aldehydes, terminal alkynes, and amines have
not so far been described. Herein, we report our results on
the three-component coupling reactions of aldehydes, termi-
nal alkynes, and amines catalyzed by highly efficient FeCl3
in the absence of any ligand (Scheme 1).
À
Most recently, iron-catalyzed S-arylation of thiols (C S
bond formation),[10] N-arylation of nitrogen nucleophiles
[11]
À
À
(C N bond formation), and O-arylation of phenols (C O
bond formation)[12] with aryl halides, and classic Sonogashira
reactions have been developed.[13] There is a keen interest
from both the academia and industry to expand the applica-
tion scope of iron catalysts in organic transformations be-
cause of their unique and significant advantages.
One-pot multicomponent coupling reactions, which intro-
duce several elements of diversity into a molecule in a
single step, are efficient methods for the preparation of
complex molecules starting from readily available raw mate-
rials in organic synthesis.[14] Three-component coupling of al-
dehydes, alkynes, and amines is one of the best examples of
such a process and has received much attention in recent
years.[15] The resultant propargylamines obtained from the
reactions are frequent skeletons[16] and synthetically versa-
tile key intermediates[17] in the preparation of many nitro-
gen-containing biologically active compounds such as b-lac-
tams, oxotremorine analogues, conformationally restricted
peptides, isosteres, natural products, and therapeutic drug
Scheme 1.
Our initial investigation focused on the effect of iron sour-
ces on the three-component coupling reactions of aldehydes,
terminal alkynes, and amines. Several iron sources were
screened in a model reaction of phenylacetylene (1), isobu-
tyraldehyde (2), and dibenzylamine (3), and the results are
summarized in Table 1. The three-component coupling reac-
tion could be catalyzed by FeIII salts, FeIII oxide, or FeII salts,
[a] P. Li, Y. Zhang, Prof. Dr. L. Wang
Department of Chemistry, Huaibei Coal Teachers College
Huaibei, Anhui 235000 (China)
Fax : (+86)561-309-0518
E-mail: leiwang@hbcnc.edu.cn
[b] Prof. Dr. L. Wang
such as FeCl3·6H2O, Fe
ACHUTNGTNERGUN(NO3)3·9H2O, Fe2ACHTUNTGRNE(NUGN SO4)3, Fe2O3, Fe-
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Shanghai 200032 (China)
AHCTUNGTRENNUNG
uene. It is evident that FeCl3 (anhydrous) was the most ef-
fective catalyst for the reaction (Table 1, entries 1–7). But,
more stable FeII complexes and Fe0, such as FeCp2, and Fe0
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200802643.
Chem. Eur. J. 2009, 15, 2045 – 2049
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2045

Table 1. Screening of catalysts, ligands, and solvents for the iron-cata-
lyzed three-component coupling reactions of phenylacetylene (1), isobu-
tyraldehyde (2), and dibenzylamie (3).[a]
catalyzed three-component coupling reactions of aldehydes,
terminal alkynes, and amines, and conversely, restrained the
reactivity of the catalyst (Table 1, entries 18–21). It should
be noted that no corresponding product was obtained when
1,10-phenanthroline or DMEDA was added to the reaction
and starting materials were recovered. Fortunately, when a
P-ligand such as (C6H5)3P, (C 6H11)3P, or 1,1’-bis(diphenyl-
phosphino)ferrocene (DPPF) was added to the reaction sys-
tems, we found that especially DPPF accelerates the reac-
tion to give 4a in 87% yield (Table 1, entries 22–24). It is
noteworthy that the isolated yield of 4a increased up to
95% when 4 A molecular sieves were added to the reaction
system even in the absence of DFFP (Table 1, entry 25).
However, additional DPPF did not improve the yield of 4a
in the presence of 4 A molecular sieves (Table 1, entry 26).
During the course of our further optimization of the reac-
tion conditions, the reaction was generally completed within
24 h when it was performed at 1208C by using 10 mol% of
FeCl3 in the presence of 4 A molecular sieves
(100 mgmmolÀ1) in toluene without additional DPPF.
To examine the scope of this three-component coupling
reaction, we extended our studies to different combinations
of aldehydes, amines, and alkynes. The results are listed in
Table 2. At the beginning of the search for the suitable al-
kynes, isobutyraldehyde and dibenzylamine were used as
model substrates and a variety of alkynes were examined
for the coupling reactions (Table 2, entries 1–7). As can be
seen from Table 2, aromatic alkynes were much more reac-
tive than aliphatic ones. Aromatic alkynes, such as phenyla-
cetylene, p-methylphenylacetylene, p-chlorophenylacetylene,
p-fluorophenylacetylene, and diphenylacetylene, reacted
with dibenzylamine and isobutyraldehyde smoothly and gen-
erated the corresponding products in excellent yields
(Table 2, entries 1–5). Fortunately, the reactions involving
aliphatic alkynes also gave both higher conversions and iso-
lated yields, leading to the corresponding propargylamines
in good yields (Table 2, entries 6 and 7).
Entry Fe source
Ligand[b]
Solvent[c] 4a [%][d]
1
2
3
4
5
6
7
8
FeCl3·6H2O
none
none
none
none
none
none
none
none
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
26
21
29
34
64
79
74
0
Fe
Fe
ACHTUNGTRENNUNG
CHTUNGTRENNUNG
Fe2O3
Fe(acac)3
ACHTUNGTRENNUNG
FeCl3
FeCl2
FeCp2
9
Fe powder (100 nm) none
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25[e]
26[e]
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
none
none
none
none
none
none
none
none
benzene 70
DCE 44
C2H5OH 40
CH3CN
dioxane
DMSO
DMF
48
39
0
0
DMA
0
DMEDA
1,10-phenanthroline toluene
DCH
TMHD
toluene
0
0
toluene
toluene
toluene
toluene
toluene
toluene
toluene
48
42
82
83
87
95
96
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
DPPF
none
DPPF
[a] Reaction conditions: 1 (1.0 equiv), 2 (1.0 equiv), 3 (1.0 equiv), Fe
source (0.1 equiv), ligand (0.1 equiv), solvent (1.0 mLmmolÀ1), sealed
tube, 1208C, under argon, 24 h. [b] Cp=cyclopentadienyl, acac=acetyla-
cetonate, DMEDA=N,N’-dimethylethylenediamine, DCH=(dl)-trans-
1,2-diaminocyclohexane,
TMHD=2,2,6,6-tetramethyl-3,5-heptadione,
DPPF=1,1’-bis(diphenylphosphino)ferrocene. [c] DMF=N,N-dimethyl-
formamide, DMA=N,N-dimethylacetamide, DMSO=dimethyl sulfox-
ide, DCE=1,2-dichloroethane. [d] Yields of isolated products after flash
chromatography. [e] In the presence of 4 A molecular sieves (100 mg).
To expand the scope of aldehyde substrates, a combina-
tion of phenylacetylene-dibenzylamine-aldehydes was
chosen and various aldehydes were surveyed. The aliphatic
aldehydes, cyclic or acyclic, such as n-butyraldehyde, isobu-
tyraldehyde, isovaleraldehyde, para-formaldehyde, and cy-
clohexanecarboxaldehyde, displayed high reactivity under
the present reaction conditions, and high yields of the de-
sired three-component coupling products were obtained
(Table 2, entries 1, and 8–11). Fortunately, aromatic alde-
hydes with both electron-donating and electron-withdrawing
functionalities, such as methoxy, methyl, and chloro groups,
afforded the corresponding propargylamines in good yields
(Table 2, entries 12–16).
Subsequently, a variety of amines was also examined and
the results listed in Table 2 indicated that cyclic, heterocy-
clic, and acyclic secondary aliphatic amines, such as diben-
zylamine, piperidine, and morpholine, gave high yields of
products under the optimized reaction conditions (Table 2,
entries 1, 13, 17, and 18). However, aromatic secondary
amines, such as N-benzylaniline and N-methylaniline, were
powder (100 nm), failed to catalyze the reaction (Table 1,
entries 8 and 9). The effect of solvent on the reaction by
using FeCl3 as catalyst was also surveyed (Table 1, entries 6,
10–17). Among the solvents tested, toluene and benzene
were the most suitable reaction media for this three-compo-
nent coupling reaction. 1,2-Dichloroethane, ethanol, aceto-
nitrile, and dioxane were inferior and generated 4a in 44,
40, 48, and 39% yields, respectively (Table 1, entries 11–14).
Unfortunately, no desired product was isolated when the re-
actions were carried out in dimethyl sulfoxide (DMSO),
N,N-dimethylformamide (DMF), or N,N-dimethylacetamide
(DMA) (Table 1, entries 15–17). In general, iron-catalyzed
carbon–carbon and carbon–heteroatom bond formation re-
actions could be enhanced by a suitable ligand containing
nitrogen or oxygen atoms.[7–9] However, N-ligands, such as
1,10-phenanthroline, (dl)-trans-1,2-diaminocyclohexane, and
N,N’-dimethylethylenediamine (DMEDA), and O-ligand,
2,2,6,6-tetramethyl-3,5-heptadione, did not assist the iron-
2046
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2045 – 2049

Three-Component Coupling Reactions of Aldehydes, Terminal Alkynes, and Amines
COMMUNICATION
Table 2. Iron-catalyzed three-component coupling reactions of aldehydes,
terminal alkynes, and amines.[a]
Table 2. (Continued)
Entry
Alkyne
Aldehyde
Amine
4 [%][b]
17
84
Entry
1
Alkyne
Aldehyde
Amine
4 [%][b]
18
82
[a] Reaction conditions: aldehyde (1.0 mmol), amine (1.0 mmol), alkyne
(1.0 mmol), FeCl3 (0.1 mmol), 4 A molecular sieves (100 mg), toluene
(1.0 mL), sealed tube, 1208C, under argon, 24 h. [b] Yields of isolated
products after flash chromatography.
95
2
94
96
97
90
85
78
98
79
70
90
84
less reactive in reactions with phenylacetylene and isobutyr-
aldehyde, and only trace amounts of the desired products
were isolated.
A possible mechanism of the iron-catalyzed one-pot
three-component coupling of aldehyde, alkyne, and amine is
shown in Scheme 2. The precatalyst FeCl3, a trivalent iron
3
4
5
6
7
8
Scheme 2. Possible mechanism of iron-catalyzed three-component cou-
pling of aldehyde, alkyne, and amine.
9
salt, would presumably be initially reduced to a low-valent
FeII state, which probably possesses only one alkynyl group
given the notable stability of FeII alkynylate complexes,
compared to Fe0 and FeIII analogues.[27] When FeCl2 was
used instead of FeCl3 under the optimized reaction condi-
tions, 4a was isolated in 91% yield and comparable catalytic
activity of FeII and FeIII was observed. However, Fe0 powder
(freshly prepared, 100 nm) failed to catalyze the reaction.
On the other hand, we hypothesize that the generated HCl
accelerates the formation of the immonium salt from the al-
dehyde and the secondary amine,[28] and that FeCl3, as a
Lewis acid, plays a role in increasing the electrophilic char-
acter of the starting aldehyde and stabilizing the immonium
salt by the coordination of the oxygen or nitrogen lone elec-
tron pair with FeCl3.[29] The resulting FeII alkynylate com-
plex subsequently reacted with the immonium salt generated
in situ to give the corresponding propargylamine and regen-
erate the FeII catalyst for further reactions.
10
11
12
ACHTUGNTERN(NUNG CH2O)n
13
14
15
16
91
92
78
75
In summary, we have successfully developed a novel, eco-
nomical, environmentally friendly, and practical iron-cata-
lyzed ligand-free one-pot three-component coupling reac-
tion of aldehydes, alkynes, and amines. The reactions were
Chem. Eur. J. 2009, 15, 2045 – 2049
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2047

L. Wang et al.
[7] For general reviews on iron catalysis, see: a) A. Correa, O. G. Man-
carried out in the presence of catalytic amounts of FeCl3
and in conjunction with 4 A molecular sieves without any
ligand, and generated the corresponding propargylamines in
good to excellent yields. The reactions were also applicable
to aromatic and aliphatic aldehydes, alkynes, and aliphatic
secondary amines. In addition, the novel FeCl3-catalyzed
ligand-free one-pot three-component coupling reaction
should expand the application scope of iron catalysts as a
versatile tool in organic synthesis. Further investigations on
the application of this kind of catalyst in asymmetric cataly-
sis are underway in our laboratory.
ˇ
cheno, C. Bolm, Chem. Soc. Rev. 2008, 37, 1108–1117; b) S. Enthal-
er, K. Junge, M. Beller, Angew. Chem. 2008, 120, 3363–3367;
Angew. Chem. Int. Ed. 2008, 47, 3317–3321; c) C. Bolm, J. Legros, J.
Le Paih, L. Zani, Chem. Rev. 2004, 104, 6217–6254; d) A. Fꢁrstner,
R. Martin, Chem. Lett. 2005, 34, 624–629.
[8] For recent papers on iron catalysis, see: a) A. Fꢁrstner, A. Leitner,
M. Mꢂndez, H. Krause, J. Am. Chem. Soc. 2002, 124, 13856–13863;
b) A. Fꢁrstner, A. Leitner, Angew. Chem. 2002, 114, 632–635;
Angew. Chem. Int. Ed. 2002, 41, 609–612; c) R. Martin, A. Fꢁrstner,
Angew. Chem. 2004, 116, 4045–4047; Angew. Chem. Int. Ed. 2004,
43, 3955–3957; d) I. Sapountzis, W. Lin, C. C. Kofink, C. Despoto-
poulou, P. Knochel, Angew. Chem. 2005, 117, 1682–1685; Angew.
Chem. Int. Ed. 2005, 44, 1654–1657; e) C. C. Kofink, B. Blank, S.
Pagano, N. Gçtz, P. Knochel, Chem. Commun. 2007, 1954–1956;
f) G. Anilkumar, B. Bitterkich, F. G. Gelalcha, M. K. Tse, M. Beller,
Chem. Commun. 2007, 289–291; g) K. Komeyama, T. Morimoto, K.
Takaki, Angew. Chem. 2006, 118, 3004–3007; Angew. Chem. Int. Ed.
2006, 45, 2938–2941; h) B. Plietker, Angew. Chem. 2006, 118, 6200–
6203; Angew. Chem. Int. Ed. 2006, 45, 6053–6056; i) J. Kischel, I.
Jovel, K. Metins, A. Zapf, M. Beller, Org. Lett. 2006, 8, 19–22; j) H.
Egami, T. Katsuki, J. Am. Chem. Soc. 2007, 129, 8940–8941; k) G.
Cahiez, A. Moyeux, J. Buendia, C. Duplais, J. Am. Chem. Soc. 2007,
129, 13788–13789; l) T. Hatakeyama, M. Nakamura, J. Am. Chem.
Soc. 2007, 129, 9844–9845; m) A. Guꢂrinot, S. Reymond, J. Cossy,
Angew. Chem. 2007, 119, 6641–6644; Angew. Chem. Int. Ed. 2007,
46, 6521–6524; n) Z. Li, L. Cao, C. J. Li, Angew. Chem. 2007, 119,
6625–6627; Angew. Chem. Int. Ed. 2007, 46, 6505–6507; o) Z. Li, R.
Yu, H. Li, Angew. Chem. 2008, 120, 7607–7610; Angew. Chem. Int.
Ed. 2008, 47, 7497–7500; p) C. M. Rao Volla, P. Vogel, Angew.
Chem. 2008, 120, 1325–1327; Angew. Chem. Int. Ed. 2008, 47, 1305–
1307; q) C. Y. Li, X. B. Wang, X. L. Sun, Y. Tang, J. C. Zheng, Z. H.
Xu, Y. G. Zhou, L. X. Dai, J. Am. Chem. Soc. 2007, 129, 1494–1495.
[9] For iron-catalyzed reactions reported by Bolmꢃs group, see: a) J.
Legros, C. Bolm, Angew. Chem. 2003, 115, 5645–5647; Angew.
Chem. Int. Ed. 2003, 42, 5487–5489; b) J. Legros, C. Bolm, Angew.
Chem. 2004, 116, 4321–4324; Angew. Chem. Int. Ed. 2004, 43, 4225–
4228.
Experimental Section
General procedure for the iron-catalyzed ligand-free three-component
coupling reactions of aldehydes, alkynes, and amines: Under an argon at-
mosphere, a sealable reaction tube equipped with a magnetic stir bar was
charged with aldehyde (1.0 mmol), amine (1.0 mmol), alkyne (1.0 mmol),
FeCl3 (0.1 mmol), 4 A molecular sieves (100 mg), and toluene (1.0 mL).
The rubber septum was then replaced by a Teflon-coated screw cap, and
the reaction vessel placed in an oil bath at 1208C. After the mixture had
been stirred at this temperature for 24 h, it was cooled to room tempera-
ture and diluted with dichloromethane. The resulting solution was direct-
ly filtered through a pad of silica gel using a sintered glass funnel, and
concentrated under reduced pressure. The residue was purified by flash
chromatography on silica gel (eluant: hexane/ethyl acetate=3:1, v/v) to
give the desired three-component coupling product. The identity and
1
purity of known products was confirmed by H and 13C NMR spectrosco-
py, and new products were fully characterized. See the Supporting Infor-
mation for full details.
[10] A. Correa, M. Carril, C. Bolm, Angew. Chem. 2008, 120, 2922–2925;
Angew. Chem. Int. Ed. 2008, 47, 2880–2883.
Acknowledgements
[11] a) A. Correa, C. Bolm, Angew. Chem. 2007, 119, 9018–9021; Angew.
Chem. Int. Ed. 2007, 46, 8862–8865; b) A. Correa, C. Bolm, Adv.
Synth. Catal. 2008, 350, 391–394; c) A. Correa, S. Elmore, C. Bolm,
Chem. Eur. J. 2008, 14, 3527–3529.
[12] O. Bistri, A. Correa, C. Bolm, Angew. Chem. 2008, 120, 596–598;
Angew. Chem. Int. Ed. 2008, 47, 586–588.
We are grateful to the National Natural Science Foundation of China
(No. 20772043, 20572031) for financial support. P. L. thanks the Key Proj-
ect of Science and Technology of the Department of Education, Anhui
Province, China (No. ZD2007005–1).
[13] M. Carril, A. Correa, C. Bolm, Angew. Chem. 2008, 120, 4940–4943;
Angew. Chem. Int. Ed. 2008, 47, 4862–4865.
Keywords: alkynes
multicomponent reactions · synthetic methods
·
coupling reactions
·
iron
·
[14] For recent three-component reactions, see: a) S. Kamijo, Y . Yama-
moto, J. Am. Chem. Soc. 2002, 124, 11940–11945; b) S. Kamijo, T.
Jin, Y. Yamamoto, J. Am. Chem. Soc. 2001, 123, 9453–9454; c) F.
Bertozzi, M. Gustafsson, R. Olsson, Org. Lett. 2002, 4, 4333–4336;
d) G. W. Kabalka, Z. Wu, Y. Ju, Org. Lett. 2002, 4, 3415–3417;
e) T. P. Loh, S. L. Chen, Org. Lett. 2002, 4, 3647–3650; f) A. Dçm-
ling, I. Ugi, Angew. Chem. 2000, 112, 3300–3344; Angew. Chem. Int.
Ed. 2000, 39, 3168–3210; g) B. List, P. Pojarliev, W. T. Biller, H. J.
Martin, J. Am. Chem. Soc. 2002, 124, 827–833; h) U. Bora, A.
Saikia, R. C. Boruah, Org. Lett. 2003, 5, 435–438; i) R. Dhawan,
R. D. Dghaym, B. A. Arndtsen, J. Am. Chem. Soc. 2003, 125, 1474–
1475; j) C. Cao, Y. Shi, A. L. Odom, J. Am. Chem. Soc. 2003, 125,
2880–2881; k) S. J. Patel, T. F. Jamison, Angew. Chem. 2003, 115,
1402–1405; Angew. Chem. Int. Ed. 2003, 42, 1364–1367; l) J. R.
Porter, J. F. Traverse, A. H. Hoveyda, M. L. Snapper, J. Am. Chem.
Soc. 2001, 123, 10409–10410; m) D. J. Ramꢄn, M. Yus, Angew.
Chem. 2005, 117, 1628–1661; Angew. Chem. Int. Ed. 2005, 44, 1602–
1634; n) R. W. Armstrong, A. P. Combs, S. D. Brown, T. A. Keating,
Acc. Chem. Res. 1996, 29, 123–131; o) L. Weber, K. Illgen, M. Alm-
stetter, Synlett 1999, 366–374; p) L. Zani, C. Bolm, Chem. Commun.
2006, 4263–4275.
[1] a) M. Tamura, J. K. Kochi, J. Am. Chem. Soc. 1971, 93, 1487–1489;
b) M. Tamura, J. K. Kochi, Synthesis 1971, 303–305.
[2] a) O. G. MancheÇo, C. Bolm, Org. Lett. 2006, 8, 2349–2352; b) M.
Nakanishi, C. Bolm, Adv. Synth. Catal. 2007, 349, 861–864; c) W. D.
Kerber, B. Ramdhanie, D. P. Goldberg, Angew. Chem. 2007, 119,
3792–3795; Angew. Chem. Int. Ed. 2007, 46, 3718–3721.
[3] a) S. C. Bart, E. Lobkovsky, P. J. Chirik, J. Am. Chem. Soc. 2004,
126, 13794–13807; b) C. P. Casey, H. Guan, J. Am. Chem. Soc. 2007,
129, 5816–5817; c) R. M. Bullock, Angew. Chem. 2007, 119, 7504–
7507; Angew. Chem. Int. Ed. 2007, 46, 7360–7363.
[4] a) H. Nishiyama, A. Furuta, Chem. Commun. 2007, 760–762;
b) N. S. Shaikh, S. Enthaler, K. Junge, M. Beller, Angew. Chem.
2008, 120, 2531–2535; Angew. Chem. Int. Ed. 2008, 47, 2497–2501.
[5] G. Zhang, Q. Liu, L. Shi, J. Wang, Tetrahedron 2008, 64, 339–344.
[6] a) C. M. Chu, W. J. Huang, C. Lu, P. Wu, J. T. Liu, C. F. Yao, Tetra-
hedron Lett. 2006, 47, 7375–7380; b) M. Kawatsura, Y. Komatsu, M.
Yamamoto, S. Hayase, T. Itoh, Tetrahedron Lett. 2007, 48, 6480–
6482.
2048
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 2045 – 2049

Three-Component Coupling Reactions of Aldehydes, Terminal Alkynes, and Amines
COMMUNICATION
[15] C. Wei, L. Zhang, C. J. Li, Synlett 2004, 1472–1483, and references
therein.
[16] a) M. A. Huffman, N. Yasuda, A. E. DeCamp, E. J. J. Grabowski, J.
Org. Chem. 1995, 60, 1590–1594; b) M. Konishi, H. Ohkuma, T.
Tsuno, T. Oki, G. D. VanDuyne, J. Clardy, J. Am. Chem. Soc. 1990,
112, 3715–3716.
[17] a) M. Miura, M. Enna, K. Okuro, M. Nomura, J. Org. Chem. 1995,
60, 4999–5004; b) A. Jenmalm, W. Berts, Y. L. Li, K. Luthman, I.
Csoregh, U. Hacksell, J. Org. Chem. 1994, 59, 1139–1148.
[18] a) G. Dyker, Angew. Chem. 1999, 111, 1808–1822; Angew. Chem.
Int. Ed. 1999, 38, 1698–1712; b) T. Naota, H. Takaya, S. I. Muraha-
shi, Chem. Rev. 1998, 98, 2599–2660.
[19] C. Wei, Z. Li, C. J. Li, Org. Lett. 2003, 5, 4473–4475.
[20] C. Wei, C. J. Li, J. Am. Chem. Soc. 2003, 125, 9584–9585.
[21] V. K. Y. Lo, Y. Liu, M. K. Wong, C. M. Che, Org. Lett. 2006, 8,
1529–1532.
[22] a) L. Shi, Y. Q. Tu, M. Wang, F. M. Zhang, C. A. Fan, Org. Lett.
2004, 6, 1001–1003; b) H. Z. Syeda Huma, R. Halder, S. S. Karla, J.
Das, J. Iqbal, Tetrahedron Lett. 2002, 43, 6485–6488; c) G. W. Kabal-
ka, L. Wang, R. M. Pagni, Synlett 2001, 676–678. For enantioselec-
tive syntheses of propargylamines through CuI-catalyzed one-pot
three-component coupling reactions of aldehydes, alkynes, and
amines, see: d) C. Wei, C. J. Li, J. Am. Chem. Soc. 2002, 124, 5638–
5639; e) C. Wei, J. T. Mague, C. J. Li, Proc. Natl. Acad. Sci. USA
2004, 101, 5749–5754; f) N. Gommermann, C. Koradin, K. Polborn,
P. Knochel. Angew. Chem. 2003, 115, 5941–5944; Angew. Chem. Int.
Ed. 2003, 42, 5763–5766; Angew. Chem. Int. Ed. 2003, 42, 5763–
5766; g) F. Colombo, M. Benaglia, S. Orlandi, F. Usuelli, J. Mol.
Angew. Chem. Int. Ed. 2001, 40, 2534–2536; c) S. Sakaguchi, T.
Mizuta, M. Furuwan, T. Kubo, Y. Ishii, Chem. Commun. 2004,
1638–1639.
[24] P. Li, L. Wang, Chin. J. Chem. 2005, 23, 1076–1080.
[25] C. J. Li, C. Wei, Chem. Commun. 2002, 268–269.
[26] a) Z. Li, C. Wei, L. Chen, R. S. Varma, C. J. Li, Tetrahedron Lett.
2004, 45, 2443–2446; b) S. B. Park, H. Alper, Chem. Commun. 2005,
1315–1317; c) B. M. Choudary, C. Sridhar, M. L. Kantam, B. Sreed-
har, Tetrahedron Lett. 2004, 45, 7319–7321; d) M. L. Kantam, B. V.
Prakash, C. R. V. Reddy, B. Sreedhar, Synlett 2005, 2329–2332;
e) K. M. Reddy, N. S. Babu, P. S. S. Prasad, N. Lingaiah, Tetrahedron
Lett. 2006, 47, 7563–7566; f) X. Zhang, A. Corma, Angew. Chem.
2008, 120, 4430–4433; Angew. Chem. Int. Ed. 2008, 47, 4358–4361;
g) P. Li, L. Wang, Tetrahedron 2007, 63, 5455–5459; h) M. Wang, P.
Li, L. Wang, Eur. J. Org. Chem. 2008, 2255–2261; i) P. Li, L. Wang,
Y. Zhang, M. Wang, Tetrahedron Lett. 2008, 49, 6650–6654.
[27] a) L. A. Berben, J. R. Long, Inorg. Chem. 2005, 44, 8459–8468;
b) R. Nast, F. Z. Urban, Z. Anorg. Allg. Chem. 1956, 287, 17–23;
c) C. D. Delfs, R. Stranger, M. G. Humphrey, A. M. McDonagh, J.
Organomet. Chem. 2000, 607, 208–212; d) R. Nast, Coord. Chem.
Rev. 1982, 47, 89–124, and references therein.
[28] a) N. Risch, M. Arend in Houben-Weyl, Vol. E21b, 4th ed. (Eds.: G.
Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann), Thieme,
Stuttgart, 1995, p. 1925; b) L. Kꢁrti, B. Czakꢄ in Strategic Applica-
tions of Named Reactions in Organic Synthesis, Elsevier, London,
2005, p. 274; c) S. J. Benkovic, P. A. Benkovic, D. R. Comfort, J. Am.
Chem. Soc. 1969, 91, 1860–1861; d) N. J. Leonard, J. V. Paukstelis, J.
Org. Chem. 1963, 28, 3021–3024.
Catal.
A
2006, 260, 128–134; h) N. Gommermann, P. Knochel,
[29] R. Bloch, Chem. Rev. 1998, 98, 1407–1438.
Chem. Eur. J. 2006, 12, 4380–4392; i) A. Bisai, V. K. Singh, Org.
Lett. 2006, 8, 2405–2408.
[23] a) C. Fischer, E. M. Carreira, Org. Lett. 2001, 3, 4319–4321; b) S. Sa-
kaguchi, T. Kubo, Y. Ishii, Angew. Chem. 2001, 113, 2602–2604;
Received: December 16, 2008
Published online: January 28, 2009
Chem. Eur. J. 2009, 15, 2045 – 2049
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2049