LiClO4-catalyzed three-component-coupling reactions: A facile synthesis of homoallylic amines

Article abstract of DOI:10.1016/S0040-4039(02)01324-2

Lithium perchlorate catalyzes efficiently the three-component condensation of aldehydes, amines and allyltributylstannane under mild and neutral reaction conditions to afford the corresponding homoallylic amines in excellent yields.

Full text of DOI:10.1016/S0040-4039(02)01324-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 6245–6247
LiClO -catalyzed three-component-coupling reactions: a facile
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synthesis of homoallylic amines
J. S. Yadav,* B. V. S. Reddy, P. S. R. Reddy and M. Shesha Rao
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500007, India
Received 25 March 2002; revised 20 June 2002; accepted 28 June 2002
Abstract—Lithium perchlorate catalyzes efficiently the three-component condensation of aldehydes, amines and allyltributylstan-
nane under mild and neutral reaction conditions to afford the corresponding homoallylic amines in excellent yields. © 2002
Elsevier Science Ltd. All rights reserved.
The stereoselective addition of allylmetal reagents to
aldehydes and imines is one of the most important
carbonꢀcarbon bond forming reactions in organic syn-
development of a neutral alternative like lithium per-
chlorate would extend the scope of this transformation.
1
thesis. In particular, Lewis acid-catalyzed car-
In recent years, LiClO in diethyl ether (LPDE) has
4
bonꢀcarbon bonding forming reactions are of great
emerged as a mild Lewis acid imparting high regio-,
chemo- and stereoselectivity to various organic trans-
formations. The LPDE medium provides a convenient
importance in organic synthesis because of their high
2
8
reactivity, selectivity and mild reaction conditions.
Generally, homoallylic amines are prepared either by
addition of organometallic reagents to imines or by
procedure to carry out reactions under neutral reaction
and work-up conditions. Furthermore, LPDE is found
to retain its activity even in the presence of amines and
has also been found to activate effectively nitrogen
3
nucleophilic addition of allylsilane, allyltin, allylboron
or allylgermane reagents to imines in the presence of
4
9
acid catalysts. Lewis acids such as TiCl , BF ·OEt ,
containing compounds such as imines and nitrones.
4
3
2
and PdCl (PPh ) or PtCl (PPh ) have been employed
2
3 2
2
,5
3 2
4
for this transformation.
However, these reactions
In continuation of our interest on the catalytic applica-
tions of lithium perchlorate for various organic trans-
formations, we herein describe a simple and efficient
protocol for the synthesis of homoallylic amines using a
catalytic amount of lithium perchlorate under neutral
reaction conditions (Scheme 1).
cannot be carried out in a one-pot operation with a
carbonyl compound, amine and allyl metal reagent
because the amines and water that exist during imine
formation can decompose or deactivate the Lewis
10
6
acids. In order to circumvent these problems one-pot
procedures have been developed for this conversion
recently using lanthanide triflates as catalysts. In fact,
these procedures do not require the isolation of the
unstable imines prior to the reactions. Metal triflates
are strongly acidic and highly expensive, and so the
7
The reaction of benzaldehyde, aniline and allyltributyl-
stannane in the presence of 10 mol% lithium
perchlorate in acetonitrile at ambient temperature
resulted in the formation of the homoallylic amine in
11
Scheme 1.
Keywords: lithium perchlorate; allylstannane; coupling reaction; homoallylic amines.
*
Corresponding author. Fax: 91-40-7160512; e-mail: yadav@iict.ap.nic.in
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01324-2

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J. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 6245–6247
9
0% yield. Similarly various imines (formed in situ from
within 2.5–5.5 h. Both aromatic and aliphatic aldehydes
afforded excellent yields of products (75–90%) in a
short period whereas ketones did not yield any product
even after a long reaction times (10–15 h). This method
is effective even with aldehydes bearing electron-with-
aldehydes and amines) reacted smoothly with the allyl-
stannane to afford the corresponding homoallylic
amines in high yields.
1
2
The reactions proceeded
smoothly at ambient temperature and were completed
a
Table 1. Lithium perchlorate-catalyzed synthesis of homoallylic amines

J. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 6245–6247
6247
drawing substituents in the aromatic ring. Furthermore,
acid-sensitive aldehydes, such as furfuraldehyde and
cinnamaldehyde, worked well without any decomposi-
tion or polymerization under the reaction conditions.
Enolizable aldehydes, such as cyclohexanecarboxalde-
hyde and decanal, also produced the corresponding
homoallylic amines in good yields. In all cases, no
homoallylic alcohol (an adduct between the aldehyde
and allyltributylstannane) was obtained under these
reaction conditions. This is because of the rapid forma-
tion and activation of imines in the presence of lithium
5. (a) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am.
Chem. Soc. 1996, 118, 6642; (b) Nakamura, K.; Naka-
mura, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996, 118,
6642.
6. Kobayashi, S.; Araki, M.; Yasuda, M. Tetrahedron Lett.
1995, 36, 5773.
7. (a) Kobayashi, S.; Busujima, T.; Nagayama, S. Chem.
Commun. 1998, 19; (b) Kobayashi, S.; Nagayama, S. J.
Am. Chem. Soc. 1997, 119, 10049; (c) Aspinall, H. C.;
Bissett, J. S.; Greeves, N.; Levin, D. Tetrahedron Lett.
2002, 43, 323.
1
perchlorate. All the products were characterized by H
NMR, IR, and mass spectral analysis. There are several
8. Sankara Raman, S.; Nesakumar, J. E. Eur. J. Org. Chem.
2000, 2003.
advantages in the use of LiClO as catalyst for this
9. (a) Ipaktschi, J.; Heydari, A. Chem. Ber. 1993, 126, 1905;
(b) Heydari, A.; Larijani, H.; Emami, J.; Karami, B.
Tetrahedron Lett. 2000, 41, 2471.
10. (a) Yadav, J. S.; Reddy, B. V. S.; Murthy, Ch. V. S. R.;
Kumar, G. M.; Madan, Ch. Synthesis 2001, 783; (b)
Yadav, J. S.; Reddy, B. V. S.; Srinivas, R.; Madhuri, Ch.;
Ramalingam, T. Synlett 2001, 240; (c) Yadav, J. S.;
Reddy, B. V. S.; Jyothirmai, B.; Murthy, M. S. R. Synlett
2002, 53.
4
transformation, which include mild reaction conditions,
cleaner reaction profiles, high yields of products,
greater selectivity and compatibility with acid labile
substrates. The scope and generality of this process is
illustrated with respect to various amines and aldehydes
including aromatic, a,b-unsaturated, heterocyclic, and
aliphatic aldehydes and the results are presented in
Table 1.
1
1. Caution: Although, solid lithium perchlorate is stable up
to its melting point, solutions in organic solvents should
be prepared and handled with the utmost care.
In conclusion, lithium perchlorate is found to be a mild
and efficient Lewis acid in promoting three-component-
coupling reactions of aldehydes, amines and allyl-
tributylstannane under neutral conditions. In addition
to its simplicity, efficiency and mild reaction conditions,
this method provides high yields of products in a short
period, which makes it a useful and attractive process
for the synthesis of homoallylic amines of synthetic
importance.
12. A mixture of aldehyde (5 mmol), amine (5 mmol), allyl-
tributylstannane (5 mmol) and anhydrous LiClO4 (10
mol%) in acetonitrile (10 mL) was stirred at ambient
temperature for the appropriate time (Table 1). After
completion of the reaction as indicated by TLC, the
reaction mixture was quenched with water (10 mL) and
extracted with ethyl acetate (2×15 mL). The combined
organic layers were washed with water (3×15 mL) and
dried over anhydrous Na SO , concentrated in vacuo and
2
4
Acknowledgements
purified by column chromatography on silica gel (Merck,
00–200 mesh, ethyl acetate–hexane, 1:9) to afford pure
1
homoallyl amine. The aqueous layer was quenched with
saturated sodium bicarbonate solution to destroy lithium
perchlorate.
B.V.S. and P.S.R. thank the CSIR, New Delhi, for the
award of fellowships.
Spectral data for selected products: Compound 4b: liquid,
1
H NMR (CDCl ): l 2.30 (s, 3H), 2.50–2.65 (m, 2H),
3
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3
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3
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