A three-component synthesis of homoallylic amines catalyzed by CuI

Article abstract of DOI:10.1016/j.tetlet.2008.07.032

Cuprous iodide is a very effective catalyst for the three-component condensation of an aldehyde, benzylamine and allyltributylstannane in DMF to produce homoallylic amines in high yields.

Full text of DOI:10.1016/j.tetlet.2008.07.032

Tetrahedron Letters 49 (2008) 5495–5497
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Tetrahedron Letters
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A three-component synthesis of homoallylic amines catalyzed by CuI
*
Pabitra Kumar Kalita, Prodeep Phukan
Department of Chemistry, Gauhati University, Guwahati 781 014, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Cuprous iodide is a very effective catalyst for the three-component condensation of an aldehyde, benzyl-
amine and allyltributylstannane in DMF to produce homoallylic amines in high yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 31 May 2008
Revised 26 June 2008
Accepted 5 July 2008
Available online 9 July 2008
Keywords:
CuI
Aldehyde
Benzyl amine
Allyltributylstannane
Homoallylic amine
The nucleophilic addition of allyl metal reagents to aldimines
has emerged as an important carbon–carbon bond forming reac-
tion in organic synthesis.1 The resulting homoallylic amines are
useful intermediates that can be converted to synthetically and
biologically important compounds such as statin,2 conine,3 epothi-
lone,4 b-amino acids5 and many others.6 These amino compounds
are synthesized by nucleophilic addition of organoallyl reagents of
several metals such as Mg, Si, Sn, Sm, Li, Zn, Ce, Cr, B or Cr to an
imine.7 Allyltributylstannane is one of the most common reagents
used for the synthesis of homoallylic amines. Generally, strong
Lewis acids such as TiCl4 and BF3ÁOEt2, and other metal complexes
the synthesis of homoallylic amines, wherein reactive organo-
metals are generated in situ.1,14 Very recently, Roy developed a
method for the Barbier-type allylation of sulfonimines using
Pd(dba)3ÁCHCl3 as the catalyst.15 The major drawback of this meth-
od was that the palladium catalyst is very expensive. Moreover,
this method is only applicable to highly reactive sulfonimines in
the presence of 1.5 equiv of SnCl2 and 2 equiv of allyl bromide
for in situ generation of the allylstannane. Therefore, the develop-
ment of new, general, less expensive, high yielding and practical
catalytic methods is of interest. CuI has emerged as a very effective
catalyst for various organic transformations.16 In continuation of
our work on CuI-catalyzed reactions,16h,i we report herein a
three-component synthesis of homoallylic amines using CuI as
the catalyst (Scheme 1).
In order to find optimum reaction conditions, a screen was per-
formed varying several parameters including concentration of the
catalyst, amount of substrate, solvent and temperature. The results
are summarized in Table 1. In a typical reaction, allyltri(n-
butyl)stannane (1 equiv) was added to a mixture of benzaldehyde
(1 equiv), benzylamine (1 equiv) and CuI (10 mol % based on the
amount of benzaldehyde) in DMF at room temperature. The reac-
tion was monitored by TLC. After 24 h, the yield of the homoallyl
amine was found to be just 60%. Hence, the reaction was evaluated
by varying the concentration of the catalyst (5–20 mol %) keeping
the reaction time (24 h) constant. Although the optimal amount
of catalyst was found to be 15 mol %, the yield was not satisfactory.
Thereafter, we examined the reaction by changing the concentra-
tions of the amine and allyltributylstannane. An improvement in
the yield was observed when the amount of allylating agent was
increased from 1 equiv to 1.1 equiv (based on benzaldehyde) but
such as PdCl2(PPh3)2, PtCl2(PPh3)2, bis-p-allyl palladium complex,
lanthanide salts and LiClO4 are used for the preparation of homo-
allylic amines.8 However, these reactions cannot be carried out in
a one-pot operation with a carbonyl compound, an amine and an
allyl metal reagent because the amines and water that exist during
imine formation can decompose or deactivate the Lewis acid.9 In
order to overcome these problems, several lanthanide triflates
are used as catalysts;10 however, metal triflates are highly expen-
sive. Lectka has reported a method for the addition of allylsilane
to N-tosyl iminoesters catalyzed by CuClO4.11 A similar method
has been reported by Jørgensen for the addition of allylstannane
to N-tosyl iminoesters using CuPF6.12 Kobayashi employed a 1,2-
diphenyl-diamine/Cu(II) complex for addition of a functionalized
allylsilane to N-acyliminoesters.13 However, these methods can
only be utilized in the case of highly active iminoesters. Several
attempts have been made to modify the Barbier-like protocol for
* Corresponding author. Tel.: +91 361 2674360; fax: +91 361 2700311.
E-mail address: pphukan@yahoo.com (P. Phukan).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.032

5496
P. K. Kalita, P. Phukan / Tetrahedron Letters 49 (2008) 5495–5497
Ph
HN
CuI (0.15 mmol)
CHO
+
NH2
SnBu3
+
DMF, RT, 24 h
R
R
Scheme 1.
Table 1
procedure works well for a variety of aromatic aldehydes to pro-
duce the corresponding homoallylic amines. The reaction time
can be shortened significantly by increasing the reaction tempera-
ture up to 50 °C; however, the yield was not improved. Aromatic
substrates bearing functional groups such as –CH3, –OMe, –Cl,
NO2 and –F all reacted successfully to give the corresponding
homoallylic amine in good to high yields irrespective of the substi-
tuent position on the aromatic ring. The presence of an –NO2 group
on the aromatic ring lowers the yield of the product. Although the
present method works well with aromatic aldehydes, the reaction
was sluggish with aliphatic aldehydes (Table 2, entries 10 and 11),
giving lower yields after much longer reaction times.
The merits of this method are (a) a very simple, one-pot and
high yielding room temperature process; (b) CuI is very cheap
and is easily available and (c) a low amount of the catalyst
(15 mol %) is needed.
In conclusion, we have developed an efficient protocol for the
three-component synthesis of homoallylic amines using CuI as
the catalyst. The workup procedure for this method is very simple.
This method has wide scope for further applications as the catalyst
is cheap and easily available commercially.
Synthesis of homoallylic amines from benzaldehyde under various reaction
conditionsa
Entry PHCH2NH2 CuI
Solvent Temp Time Yieldb
SnBu3
(mmol)
(mmol)
(°C)
(h)
(%)
(mmol)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1
1
1
1
1
1
1
1.1
1
1
1
1
1
1
1
0.05
0.1
0.15
0.2
0.25
0.3
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
0.15
1
1
1
1
1
1
1.1
1.1
1.2
1.1
1.1
1.1
1.1
1.1
1.1
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
MeCN
DCM
DMSO
THF
25
25
25
25
25
25
25
25
25
50
25
25
25
25
25
24
24
24
24
24
24
24
24
24
8
24
24
24
24
24
10
60
70
58
40
35
81
77
78
70
0
20
0
0
H2O
0
a
1 mmol of benzaldehyde was used.
Isolated yield after chromatographic purification.
b
Acknowledgement
the yield did not improve with a further increase to 1.2 equiv.
Increasing the benzylamine concentration did not improve the
yield. Hence, the optimum conditions were 0.15 equiv (15 mol %)
of CuI and 1.1 equiv of allyltributylstannane (based on benzalde-
hyde) (Table 1, entry 7). We also studied the effect of various sol-
vents such as MeCN, DMSO, THF and H2O on the yield of the
product (Table 1), and DMF was found to be the solvent of choice
in terms of yield and reactivity.
Financial Support from DST (Grant No. SR/S1/RFPC-07/2006) is
gratefully acknowledged.
References and notes
1. (a) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763; (b) Marshall, J. A. Chem.
Rev. 2000, 100, 3163; (c) Li, C.-J. Chem. Rev. 2005, 105, 3095.
Next, we examined the scope of the reaction using various alde-
2. Yamamoto, Y.; Schmid, M. J. Chem. Soc., Chem. Commun. 1989, 1310.
3. Yamaguchi, R.; Moriyasu, M.; Kawanisi, M. J. Org. Chem. 1985, 50, 287.
4. Borzilleri, R. M.; Zheng, X.; Schmidt, R. J.; Johnson, J. A.; Kim, S.-H.; DiMarco, J.
D.; Fairchild, C. R.; Gougoutas, J. Z.; Lee, F. Y. F.; Long, B. H.; Vite, G. D. J. Am.
Chem. Soc. 2000, 122, 8890.
hydes and the results are summarized in Table 2.17 In general, this
5. Laschat, S.; Kunz, H. J. Org. Chem. 1991, 56, 5883.
Table 2
6. (a) Wright, D. L.; Schulte, J. P., II; Page, M. A. Org. Lett. 2000, 2, 1847; (b) Felpin,
F.-X.; Girard, S.; Vo-Thanh, G.; Robins, R. J.; Villiéras, J.; Lebreton, J. J. Org. Chem.
2001, 66, 6305; (c) Jain, R. P.; Williams, R. M. J. Org. Chem. 2002, 67, 6361; (d) Di
Fabio, R.; Alvaro, G.; Bertani, B.; Donati, D.; Giacobbe, S.; Marchioro, C.; Palma,
C.; Lynn, S. M. J. Org. Chem. 2002, 67, 7319; (e) Ramachandran, P. V.; Burghardt,
T. E.; Bland-Berry, L. J. Org. Chem. 2005, 70, 7911; (f) Ryan, S. J.; Zhang, Y.;
Kennan, A. J. Org. Lett. 2005, 7, 4765; (g) Besada, P.; Mamedova, L.; Thomas, C. J.;
Costanzi, S.; Jacobson, K. A. Org. Biomol. Chem. 2005, 3, 2016.
7. (a) Enders, D.; Reinhold, U. Tetrahedron: Asymmetry 1997, 8, 1895; (b) Jones, P.;
Knochel, P. J. Org. Chem. 1999, 64, 186; (c) Wang, D.-K.; Zhou, Y.-G.; Hou, X.-L.;
Dai, L.-X. J. Org. Chem. 1999, 64, 4233; (d) Nakamura, K.; Nakamura, H.;
Yamamoto, Y. J. Org. Chem. 1999, 64, 2614; (e) Nakamura, H.; Nakamura, K.;
Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 4242; (f) Yamamoto, Y.; Asao, N.
Chem. Rev. 1993, 93, 2207; (g) Wang, D.-K.; Dai, L.-X.; Hou, X.-L.; Zhang, Y.
Tetrahedron Lett. 1996, 37, 4187; (h) Negoro, N.; Yanada, R.; Okaniwa, M.;
Yanada, K.; Fujita, T. Synlett 1998, 835; (i) Itsuno, S.; Yokoi, A.; Kuroda, S. Synlett
1999, 1987; (j) El-Shehawy, A. A.; Omara, M. A.; Ito, K.; Itsuno, S. Synlett 1998,
367; (k) Yanada, R.; Negoro, N.; Okaniwa, M.; Ibuka, T. Tetrahedron 1999, 55,
13947; (l) Fang, X.; Johannsen, M.; Yao, S.; Gatherhood, N.; Hazel, R. G.;
Jørgensen, K. A. J. Org. Chem. 1999, 64, 4844; (m) Akiyama, T.; Iwai, J. Synlett
1998, 273.
CuI-catalyzed three-component synthesis of homoallylic amines
Entry
1
R
Temp (°C)
Time (h)
Yield (%)
H
25
50
25
50
25
50
25
50
25
50
25
50
25
50
25
50
25
50
25
50
25
50
24
8
81
70
88
78
82
78
85
80
88
85
65
55
68
59
78
72
79
75
70
50
73
52
2
3
4-OMe
4-Cl
24
6
24
7
4
3-Cl
24
5
5
2-Cl
24
5
6
4-NO2
2-NO2
4-Me
24
9
24
8
24
6
7
8
9
4-F
24
5
8. (a) Keck, G. E.; Enholm, E. J. J. Org. Chem. 1985, 50, 146; (b) Itsuno, S.; Watanabe,
K.; Ito, K.; El-Shehaway, A. A.; Sarhan, A. A. Angew. Chem., Int. Ed. 1997, 36, 109;
(c) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118, 6641;
(d) Nakamura, H.; Nakamura, K.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120,
4242; (e) Kobayashi, S.; Nagayama, S. J. Am. Chem. Soc. 1997, 119, 10049; (f)
Chaudary, B. M.; Chidara, S.; Sekhar, C. V. R. Synlett 2002, 1694; (g) Aspinall, H.
C.; Bissett, J. S.; Greeves, N.; Levin, D. Tetrahedron Lett. 2002, 43, 323; (h) Yadav,
10
11
n-Octanal
3-Phenylpropanal
72
24
72
24

P. K. Kalita, P. Phukan / Tetrahedron Letters 49 (2008) 5495–5497
5497
J. S.; Reddy, B. V. S.; Reddy, P. S. R.; Rao, M. S. Tetrahedron Lett. 2002, 43, 6245;
(i) Veenstra, S. J.; Schmid, P. Tetrahedron Lett. 1997, 38, 997.
1990, 31, 3023; (f) Tanaka, H.; Nakahara, T.; Dhimane, H.; Torii, S. Tetrahedron
Lett. 1989, 30, 4161; (g) Tanaka, H.; Yamashita, S.; Ikemoto, Y.; Torii, S. Chem.
Lett. 1987, 673.
9. Kobayashi, S.; Araki, M.; Yasuda, M. Tetrahedron Lett. 1995, 36, 5773.
10. (a) Colombo, F.; Annunziata, R.; Benaglia, M. Tetrahedron Lett. 2007, 48, 2687;
(b) Kalita, H. R.; Phukan, P. Synth. Commun. 2005, 35, 475; (c) Kulkarni, N. A.;
Yao, C.-F.; Chen, K. Tetrahedron 2007, 63, 7816; (d) Ollevier, T.; Ba, T.
Tetrahedron Lett. 2003, 44, 9003; (e) Kobayashi, S.; Busujima, T.; Nagayama,
S. Chem. Commun. 1998, 19.
11. (a) Ferraris, D.; Dudding, T.; Young, B.; Drury, W. J., III; Lectka, T. J. Org. Chem.
1999, 64, 2168; (b) Ferraris, D.; Young, B.; Cox, C.; Dudding, T.; Drury, W. J., III;
Lectka, T. J. Am. Chem. Soc. 2002, 124, 67.
15. Roy, U. K.; Roy, S. Tetrahedron Lett. 2007, 48, 7177.
16. (a) Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421; (b)
Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 14844; (c) Äirakovic, J.
C.; Driver, T. G.; Woerpel, K. A. J. Org. Chem. 2004, 69, 4007; (d) Zhu, W.; Ma, D.
Chem. Commun. 2004, 888; (e) Patil, N. T.; Yamamoto, Y. J. Org. Chem. 2004, 69,
5139; (f) Li, J.-H.; Wang, D.-P.; Xie, Y.-X. Tetrahedron Lett. 2005, 46, 4941; (g)
Taniguchi, N. J. Org. Chem. 2006, 71, 7874; (h) Chen, Y.-J.; Chen, H.-H. Org. Lett.
2006, 8, 5609; (i) Kalita, H. R.; Phukan, P. Catal. Commun. 2007, 8, 179; (j) Kalita,
H. R.; Borah, A. J.; Phukan, P. Tetrahedron Lett. 2007, 48, 5047.
12. Fang, X.; Johannsen, M.; Yao, S.; Gathergood, N.; Hazell, R. G.; Jørgensen, K. A. J.
Org. Chem. 1999, 64, 4844.
17. General procedure: To
a solution of aldehyde (1 mmol) in DMF (1 mL),
13. Kiyohara, H.; Nakamura, Y.; Matsubara, R.; Kobayashi, S. Angew. Chem., Int. Ed.
2006, 45, 1615.
benzylamine (1.1 mmol), CuI (0.15 mmol) and allyltributylstannane (1 mmol)
were added successively at room temperature. After stirring the reaction for
24 h at room temperature, water was added and the mixture was extracted
with diethyl ether. The organic phase was dried over sodium sulfate, filtered
and evaporated. The crude product was purified by column chromatography
over silica gel (60–120 mesh) using ethyl acetate–petroleum ether (5:95) as
eluent.
14. (a) Wang, D.-K.; Dai, L.-X.; Hou, X.-L.; Zhang, Y. Tetrahedron Lett. 1996, 37,
4187; (b) Giammaruco, M.; Taddei, M.; Ulivi, P. Tetrahedron Lett. 1993, 34,
3635; (c) Bhuyan, P. J.; Prajapati, D.; Sandhu, J. Tetrahedron Lett. 1993, 34, 7975;
(d) Benchet, P.; Le Marrec, N.; Mosset, P. Tetrahedron Lett. 1992, 33, 5959; (e)
Tanaka, H.; Inoue, K.; Pokorski, U.; Taniguchi, M.; Torii, S. Tetrahedron Lett.