Iodine as a very powerful catalyst for three-component synthesis of protected homoallylic amines

Article abstract of DOI:10.1021/jo0498462

Iodine catalyzes efficiently the three-component condensation of aldehydes, benzyl carbamate, and allyltrimethylsilane to afford the corresponding protected homo-allylic amines in excellent yields.

Full text of DOI:10.1021/jo0498462

Iod in e a s a Ver y P ow er fu l Ca ta lyst for
Th r ee-Com p on en t Syn th esis of P r otected
Hom oa llylic Am in es
SCHEME 1
Prodeep Phukan*
Department of Chemistry, Gauhati University,
Guwahati - 781014, India
TABLE 1. Syn th esis of Hom oa llylic Am in e 4a u n d er
Differ en t Con d ition sa
b
run
iodine (mol %)
solvent
time (min)
yield (%)
pphukan@yahoo.com
1
2
3
4
5
10
20
10
MeCN
MeCN
MeCN
CH2Cl2
25
10
7
82
80
75
74
Received J anuary 26, 2004
25
a
Abstr a ct: Iodine catalyzes efficiently the three-component
condensation of aldehydes, benzyl carbamate, and allyltri-
methylsilane to afford the corresponding protected homo-
allylic amines in excellent yields.
Reaction conditions: benzaldehyde, 1 mmol; benzyl carbamate,
1.05 mmol; allyltrimethylsilane, 1 mmol; solvent, 2 mL; 25 °C.
Isolated yield after chromatographic purification.
b
developed by Veenstra where a stoichiometric amount
a
The stereoselective addition of allylmetal reagents to
of BF
3
‚OEt
2
was used.6 Yamamoto reported the use of
6
b
aldimines has become an important reaction for carbon-
allyl palladium complex as catalyst, but the main
drawback of this method is the use of 0.5 equiv (based
on reactant) of tetrabutylammonium fluoride as cocata-
lyst. The reaction does not proceed without the use of
cocatalyst. The third method used N-trimethylsilylcar-
bamate as amine source in the presence of a catalytic
amount of triphenylmethyl perchlorate.6 This method
needs prior silylation of carbamate to carry out the
reaction. In addition to the drawback of the use of
expensive catalyst (and cocatalyst), these methods use
stringent dry reaction condition and long reaction time.
Ollevier et. al. reported very recently an one-pot method
for the synthesis of Cbz-protected homoallylamines using
bismuth triflate as catalyst.6d This method has drawback
of long reaction time and use of expensive metal triflate.
In recent years, iodine is emerging as a very effective
1
carbon bond formation. The resulted homoallylamines
are useful intermediates in natural product synthesis.2
Moreover, acylated homoallylic amines are important
3
synthons for many synthetic applications. Usually, al-
lylation of aldimines is carried out using allylstannane
c
in the presence of a Lewis acid such as TiCl
PdCl (PPh , PtCl (PPh , bis-π-allyl palladium complex,
lanthanide triflates, and LiClO
4
, BF
3
‚OEt
2
,
2
3
)
2
2
3 2
)
4
4
. However, use of allyl-
tributylstannane is not a desired reagent from the point
of green chemistry as a result of its toxicity. Other
allylmetal reagents such as allylgermane and allylgalium
were also employed for this important synthetic protocol,5
but the allylic metal is still the reagent of choice. The
use of allylsilanes is more desirable, but because of low
reactivity (as compared to allylstannane) this reagent is
finding limited applications. There are only a few reports
on the use of allylsilane for the synthesis of homoallylic
7
Lewis acid catalyst for various organic transformations.
We recently reported the effectiveness of iodine in
catalyzing Mukaiyama aldol reactions. Herein, we wish
6
8
amine. The first method was a three-component reaction
to report the simplest, rapid and one-pot procedure for
the synthesis of homoallylic amine using iodine as
catalyst (Scheme 1).
*
To whom correspondence should be addressed. Tel: +91-361-
2
570535. Fax: +91-361-2570133.
(1) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(
2) (a) Ovaa, H.; Stragies, R.; van der Marel, G. A.; van Boom, J .
Initially a systematic study was carried out for cata-
lytic evaluation of iodine for benzaldehyde (Table 1). The
reaction was carried out by adding benzyl carbamate and
allyltrimethylsilane to a solution of benzaldehyde and
iodine in acetonitrile at room temperature. Reaction went
into completion in 10 min when 10 mol % of iodine was
used as catalyst. Rate enhancement was observed when
H.; Blechert, S. Chem. Commun. 2000, 16, 1501. (b) Hunt, J . C. A.;
Laurent, P.; Moody, C. J . Chem. Commun. 2000, 18, 1771.
(
3) Hiemstra, H.; Speckamp, W. N. In Comprehensive Organic
Synthesis; Fleming I., Ed.; Pergamon Press. Oxford, 1991; Vol. 2, p
047.
4) (a) Keck, G. E.; Enholm, E. J . J . Org. Chem. 1985, 50, 146. (b)
1
(
Itsuno, S.; Watanabe, K.; Ito, K.; El-Shehaway, A. A.; Sarhan, A. A.
Angew. Chem., Int. Ed. Engl. 1997, 36, 109. (c) Akiyama, T.; Iwai, J .
Synlett 1998, 273. (d) Nakamura H.; Iwama, H.; Yamamoto, Y. J . Am.
Chem. Soc. 1996, 118, 6641. (e) Nakamura H.; Nakamura, K.;
Yamamoto, Y. J . Am. Chem. Soc. 1998, 120, 4242. (f) Kobayashi, S.;
Nagayama, S. J . Am. Chem. Soc. 1997, 119, 10049 (g) Kobayashi, S.;
Busujima, T.; Nagayama, S. (h) Chaudary, B. M.; Chidara, S.; Sekhar,
C. V. R. Synlett 2002, 1694. (i) Aspinall, H. C.; Bissett, J . S.; Greeves,
N.; Levin D. Tetrahedron Lett. 2002, 43, 323 (j) Yadav, J . S.; Reddy,
B. V. S.; Reddy, P. S. R.; Rao, M. S. Tetrahedron Lett. 2002, 43, 6245.
(7) (a) Yadav, J . S.; Reddy, B. V. S.; Rao, C. V.; Reddy, M. S.
Synthesis 2003, 247. (b) Karimi, B.; Golshani, B. Synthesis 2002, 784.
(c) He, Z.; Gao, G.; Hand, E. S.; Kispert, L. D.; Strand, A.; Liaaen-
J ensen, S. J . Phys. Chem. A 2002, 106, 2520. (d) Xu, X.; Zhang, Y.
Synth. Commun. 2002, 32, 2643. (e) Basu, M. K.; Samajdar, S.; Becker,
F. F.; Banik, B. K. Synlett 2002, 319. (f) Yadav, J . S.; Reddy, B. V. S.;
Rao, C. V.; Rao, K. V. J . Chem. Soc., Perkin Trans. 1 2002, 1401. (g)
Ramalinga, K.; Vijayalakshmi, P.; Kaimal, T. N. B.; Tetrahedron Lett.
2002, 43, 879. (h) Yadav, J . S.; Chand, Pratap K.; Anjaneyulu, S.
Tetrahedron Lett. 2002, 43, 3783. (i) Periana, R. A.; Mirinov, O.; Taube,
D. J .; Gamble, S. Chem. Commun. 2002, 20, 2376. (j) Firouzabadi, H.;
Iranpoor, N.; Sobhani, S.; Tetrahedron Lett. 2002, 43, 3653. (k)
Firouzabadi, H.; Iranpoor, N.; Hazarkhani, H. J . Org. Chem. 2001,
66, 7527.
(5) (a) Akiyama, T.; Iwai, J . Synlett 1998, 273. (b) Akiyama, T,; Iwai,
J .; Onuma, Y.; Kagoshima, H. Chem. Commun. 1999, 2191. (b)
Andrews, P. C.; Peatt, A. C.; Raston, C. L. Tetrahedron Lett. 2004, 45,
43
(
b) Nakamura K.; Nakamura, H.; Yamamoto, Y. J . Org. Chem. 1999,
4, 2614. (c) Niimi, L.; Serita, K.; Hiraoka, S.; Yokozawa, T. Tetrahe-
dron Lett. 2000, 41, 7075. (d) Olleiver, T.; Ba, T. Tetrahedron Lett.
2
6) (a) Veenstra, S. J .; Schmid, P. Tetrahedron Lett. 1997, 38, 997.
(
6
2
003, 44, 9003.
(8) Phukan, P. Synth. Commun. 2004, 34, 1065.
1
0.1021/jo0498462 CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/04/2004
J . Org. Chem. 2004, 69, 4005-4006
4005

+
TABLE 2. Syn th esis of Cbz-P r otected Hom oa llylic
Am in e
ence of Me
Si . It is well-known that iodine reacts with
3
9
allyltrimethylsilane to form trimethylsilyliodide. The
a
+
entry
R
product
time (min)
yield (%)
role of Me
catalyzed by Me
documented. These facts support the involvement of
3
Si in the case of allylation of aldehyde
SiI10 and TfOH
+
B(OTf)
-11
is well
3
2
4
a
b
c
d
e
f
g
h
i
Ph
4-NO2-Ph
4-Br-Ph
4-MeO-Ph
3-Cl-Ph
2-Furyl
4a
4b
4c
4d
4e
4f
4g
4h
4i
10
20
10
15
10
10
15
15
15
15
80
69
78
79
82
66
72
72
71
74
+
3
Me Si in the catalytic cycle.
In conclusion, iodine shows a very strong catalytic
activity, which is much faster then any catalyst reported
so far, for the synthesis of Cbz-protected homoallyl-
amines. The merits of this method are that (a) it is a very
simple, one-pot, rapid, and high yielding process; (b)
iodine is very cheap and easily available as compared to
any other catalyst; (c) a catalytic amount of iodine is
required to promote the reaction whereas an equimolar
Ph-CH2
Ph-CH2-CH2
CH3(CH2)6
(CH3)2CH
j
4j
a
Isolated yield after chromatographic purification.
amount of BF
3
2
‚OEt was used in earlier methods; (d) the
2
0 mol % of iodine was used, but relatively lower yield
method is not toxic; and (e) iodine is not moisture-
sensitive and reactions are carried out in air. Moreover,
this method does not require prior isolation of the imine.
The present work demonstrates that iodine is extremely
powerful catalyst for the synthesis of homoallylic alcohols
with excellent yield.
was observed. Moreover, use of dichloromethane as
solvent instead of acetonitrile led to weaker results (74%,
2
5 min).
Encouraged by these results, we have extended the
process to a variety of aldehydes, which are summarized
in Table 2. In general, excellent yields of homoallylamines
were obtained with 10 mol % of iodine at room temper-
ature in acetonitrile. No traces of the corresponding
homoallylic alcohol resulting from direct addition of
allyltrimethylsilane to the aldehyde were observed. Both
aromatic and aliphatic aldehydes undergo homoallylation
with 66-82% yield irrespective of the nature of the
substrate.
Ack n ow led gm en t. The author thanks the Depart-
ment of Science and Technology, New Delhi, India for
financial support (Grant SR/FTP/CSA/-11/2002).
Su p p or tin g In for m a tion Ava ila ble: Analytical data of
the compounds and H and C NMR spectra. This material is
available free of charge via the Internet at http://pubs.acs.org.
1
13
J O0498462
Mechanistically, the reaction proceeds through the
6
a,c
formation of bisurethane at the initial stage.
The
(
9) (a) Grafstein, D. J . Am. Chem. Soc. 1955, 77, 6650. (b) J ung, M.
E.; Blumenkopt, T. A. Tetrahedron Lett. 1978, 3657.
10) Sakurai, H.; Sasaki, K.; Hosomi, A. Tetrahedron Lett. 1981, 22,
45.
11) Davis, A. P.; J aspars, M. J . Chem. Soc., Perkin Trans. 1 1992,
16, 2111.
bisurethane was isolated by quenching the reaction at
an intermediate stage. The reaction proceeds further via
the formation of intermediate acylimine, which undergoes
nucleophilic attack by allyltrimethylsilane in the pres-
(
7
(
4
006 J . Org. Chem., Vol. 69, No. 11, 2004