Vanadium(III) Chloride-Catalyzed Preparation of β-Amino Alcohols from Epoxides

Article abstract of DOI:10.1055/s-2003-41070

Vanadium(III) chloride was found to catalyze the cleavage of epoxides with aromatic amines in an efficient way to afford the corresponding β-amino alcohols in very good yields. The reactions are completely anti-stereoselective, highly regioselective and p

Full text of DOI:10.1055/s-2003-41070

2298
SHORT PAPER
Vanadium(III) Chloride-Catalyzed Preparation of -Amino Alcohols from
Epoxides
P
reparationof -A
o
mino Alcoho
w
ls
f
rom Epoxide
s
ravaram Sabitha,* G. S. Kiran Kumar Reddy, K. Bhaskar Reddy, J. S. Yadav
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)27160512; E-mail: sabitha@iict.ap.nic.in
Received 26 May 2003; revised 21 July 2003
The use of vanadium(III) chloride as catalyst in organic
Abstract: Vanadium(III) chloride was found to catalyze the cleav-
age of epoxides with aromatic amines in an efficient way to afford
the corresponding -amino alcohols in very good yields. The reac-
tions are completely anti-stereoselective, highly regioselective and
proceed at room temperature.
transformations11 is not much explored. As a first example
the opening reaction of cyclohexene oxide (Table 1, entry
2) with aniline was studied in the presence of a catalytic
amount of VCl3 in dichloromethane. The reaction was
found to proceed rapidly at room temperature and com-
plete conversion was observed in 2.5 hours to afford the
corresponding trans- -amino alcohol in 87% yield. The
trans stereochemistry of the product was deduced from
the relevant coupling constants of the peaks at = 3.15
(ddd, J = 10.8, 10.5, 3.9 Hz, HNHPh) and 3.35 (ddd,
J = 10.5, 10.5, 4.5 Hz, CHOH) in the 1H NMR spectra.
Key words: epoxides, amines, VCl3, amino alcohols
Epoxides are valuable intermediates in organic synthesis.
The strain of the epoxide ring makes them prone to react
with a large number of organic compounds. The ring
opening of epoxides by amines is an important route for
the preparation of -amino alcohols.1,2 The amino alcohol
moiety is found in a wide variety of biologically active al-
kaloids, peptides,3 and is a building block in the synthesis
of natural products.4 The importance of vicinal amino al-
cohols is also well recognized in asymmetric synthesis, as
many chiral auxiliaries and ligands contain this substruc-
ture.5 The most straightforward route for the preparation
of amino alcohols involve the ring opening of epoxides
with an excess of amine at elevated temperatures,6 which
is not only detrimental to functional groups, but also to the
control of regioselectivities. To overcome these problems
many activators and promoters have been reported for
the ring opening of epoxides with amines. These include
Ti(i-PrO)4, SmI2, SmCl3, metal triflates, BiCl3 and ionic
liquids.7 Even though a number of reagents are reported
for this transformation most of them suffer from draw-
backs such as use of excess reagent, reflux temperature,
and poor regioselectivity. Moreover, epoxides frequently
undergo rearrangement to produce allylic alcohols as a
major product when metal amides are employed.8 A sto-
ichiometric amount of LiClO4 is necessary to promote the
ring opening of epoxides with amines.9 In continuation of
our recent studies on the use of VCl3,10 we herein report
for the first time the ring opening of epoxides with aro-
matic amines using VCl3 as catalyst (Scheme 1).
Encouraged by this result, we extended this ring-opening
reaction to several epoxides with different substituted ar-
omatic amines and the results are summarized in Table 1.
For example, cyclopentene oxide and cyclohexene oxide
(entries 1 and 2) were treated with various amines to iso-
late the corresponding amino alcohols (Scheme 1) in good
yields. The opening of styrene oxide (entry 3) with aniline
gave the corresponding amino alcohol 5 (entry 3 in
Table 1, Scheme 2) in 86% yield in 4 hours. The reaction
was found to be highly regioselective and afforded a sin-
gle product, which was obtained by the attack of the
amine at the benzylic carbon (internal attack). However,
the presence of a small quantity of the other isomer 6
(Scheme 2) was also observed in the NMR spectrum of
the crude product in the case of a ring-opening reaction of
styrene oxide with m-nitroaniline. The VCl3-catalyzed
ring opening of epoxides is quite effective with sterically
hindered amines such as o-methoxy- and o-fluoroaniline
(entry 1d and entry 2b), which are known to undergo the
reaction only at 80 °C. Using the optimized conditions,
the scope of the reaction was established by variation of
the aromatic amines and epoxides (Table 1). The reaction
gave consistently good results with deactivated amine
such as m-nitroaniline (entry 3b). The glycidyl aryl ethers
(entries 4 and 5) reacted smoothly with aryl amines to af-
ford the corresponding amino alcohols in good yields. The
reaction was highly reagioselective where ring opening
took place exclusively at the less hindered epoxide carbon
as 6 (Scheme 2) was the only detectable by-product
(Scheme 2). All reactions were clean at room temperature
and highly regioselective affording high yields of prod-
ucts in a shorter reaction time. All products were charac-
terized by 1H NMR, IR, and mass spectrometric data and
also by comparison with authentic samples. The uncata-
lyzed ring opening reaction of epoxides require excess of
Scheme 1
SYNTHESIS 2003, No. 15, pp 2298–2300
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Advanced online publication: 25.09.2003
DOI: 10.1055/s-2003-41070; Art ID: Z0703SS.pdf
© Georg Thieme Verlag Stuttgart · New York

SHORT PAPER
Preparation of -Amino Alcohols from Epoxides
2299
Table 1 VCl3-Catalyzed Synthesis of -Amino Alcohols from Ep-
oxides
amino alcohols by the ring opening of epoxides with aro-
matic amines using vanadium trichloride as a catalyst.
The notable features of this procedure are mild reaction
conditions, greater selectivity, cleaner reaction products,
improved yields, enhanced rates and manipulative sim-
plicity, that makes it a useful and attractive process for the
synthesis of amino alcohols.
En- Epoxide 1
Amino Alcohol 3
Time Yieldb
(h)
(%)
trya
1
a: R = H, Ar = Ph
2.5
3
87
85
80
83
85
b: R = H, Ar = 4-FC6H4
c: R = Et, Ar = Ph
Ring opening of Epoxides with Amines Catalyzed by Vanadi-
um(II) Chloride; General Procedure
3
To a mixture of epoxide 1 (1 mmol) and amine 2 (1.1 mmol) in
CH2Cl2 (1 mL) was added VCl3 (0.10 mmol) and the mixture was
stirred at r.t. for the time given in Table 1. After complete conver-
sion, as indicated by TLC, the CH2Cl2 solution was washed with
H2O, dried and evaporated in vacuo. The crude product was purified
by chromatography on a silica gel column (eluent: hexane–EtOAc,
3:7) to afford -amino alcohols 3 in 76–88% yields. Some selected
NMR data are given below.
d: R = H, Ar = 2-MeC6H4
e: R = Me, Ar = Ph
3
2.5
2
a: R = H, Ar = Ph
2.5
3
85
82
78
76
80
Entry 2a
Solid; mp 59–60 °C.
1H NMR (300 MHz, CDCl3): = 1.15–1.46 (m, 4 H), 1.68–1.82 (m,
2 H), 2.08–2.20 (m, 2 H), 2.80 (br s, 1 H, OH), 3.15 (ddd, 1 H,
J = 10.8, 10.5, 3.9 Hz), 3.35 (ddd, 1 H, J = 10.5, 10.5, 4.5 Hz),
6.60–6.75 (m, 3 H), 7.10–7.20 (m, 2 H).
b: R = H, Ar = 2-FC6H4
c: R = Me, Ar = Ph
2.5
3
d: R = H, Ar = 4-MeOC6H4
e: R = Et, Ar = Ph
3
EI-MS: m/z = 191 (M+).
3
4
5
Entry 3a
Oil.
a: Ar = Ph
4
86
1H NMR (300 MHz, CDCl3): = 1.90 (br s, 1 H, OH), 3.80 (dd, 1
H, J = 6.9, 10.8 Hz), 3.95 (dd, 1 H, J = 4.0 10.8 Hz), 4.65 (dd, 1 H,
J = 6.9, 10.8 Hz), 6.55 (d, 2 H, J = 8.2 Hz), 6.70 (t, 1 H, J = 7.8 Hz),
7.15 (t, 2 H, J = 8.0 Hz), 7.30–7.40 (m, 5 H).
b: Ar = 3-O2NC6H4
4.5
80 (2)c
EI-MS: m/z = 213 (M+).
a: Ar = Ph
4
88
85
Entry 5a
Oil.
b: Ar = 4-ClC6H4
4.5
1H NMR (200 MHz, CDCl3): = 3.10 (br s, 1 H, OH), 3.35 (dd, 1
H, J = 9.5, 14.2 Hz), 3.50 (dd, 1 H, J = 4.8, 14.2 Hz), 4.20 (d, 2 H,
J = 4.8 Hz), 4.39 (m, 1 H, CHOH), 6.62 (d, 2 H, J = 9.5 Hz), 6.68
(t, 2 H, J = 9.5 Hz), 7.18 (t, 2 H, J = 9.5 Hz) 7.30–7.55 (m, 4 H),
7.80 (t, 1 H, J = 4.8 Hz), 8.20 (t, 1 H, J = 4.8 Hz).
a: Ar = Ph
5
80
78
EI-MS: m/z = 293 (M+).
b: Ar = 2-ClC6H4
4.5
a All products were characterized by 1H NMR, IR and mass spectros-
Acknowledgment
copy.
b Isolated products.
GSKK thanks CSIR, and KBR thanks UGC, New Delhi for the
award of fellowships.
c Yield in parenthesis refers to the other isomer (cf. Scheme 2).
References
(1) Hadgson, D. M.; Gibbs, A. R.; Lee, G. P. Tetrahedron 1996,
25, 14361.
(2) Bergmeier, S. C. Tetrahedron 2000, 56, 2561.
(3) Kobayashi, S.; Ishitani, H.; Ueno, M. J. Am. Chem. Soc.
Scheme 2
1998, 120, 431.
(4) Castefon, P.; Moyano, A.; Riera, A. Tetrahedron 1996, 52,
the amine at reflux temperatures (e.g. 60 °C)6b and long
reaction times (20–48 h).6a,b,12
7063.
(5) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96,
835.
In conclusion, we have demonstrated a novel, regioselec-
tive and highly efficient method for the synthesis of -
Synthesis 2003, No. 15, 2298–2300 © Thieme Stuttgart · New York

2300
G. Sabitha et al.
SHORT PAPER
Lavie-Campin, G. Tetrahedron Lett. 2002, 43, 7891.
(i) Ionic Liquids: Yadav, J. S.; Reddy, B. V. S.; Basak, A. K.;
Narasaiah, A. V. Tetrahedron Lett. 2003, 44, 1047.
(8) Kissel, C. L.; Rickborn, B. J. Org. Chem. 1972, 37, 2060.
(9) Chini, M.; Crotti, P.; Macchia, F. T. Tetrahedron Lett. 1990,
31, 4661.
(10) Sabitha, G.; Reddy, G. S. K. K.; Reddy, K. B.; Yadav, J. S.
Tetrahedron Lett. 2003, 44, 6497.
(11) (a) Inokuchi, T.; Kawafuchi, H.; Torii, S. Synlett 1992, 510.
(b) Ho, T. L.; Olah, G. A. Synthesis 1977, 170.
(c) Bukietynska, K.; Krot-Lacina, K. Polyhedron 2001,
2353.
(6) (a) Deyrup, J. A.; Moher, C. L. J. Org. Chem. 1969, 34, 175.
(b) Crooks, P. A.; Szyudler, R. Chem. Ind. (London) 1973,
1111.
(7) (a) Ti(i-PrO)4: Sagava, S.; Abe, H.; Hase, Y.; Inaba, T. J.
Org. Chem. 1999, 64, 4962. (b) SmI2: Van de Weghe, P.;
Collin, J. Tetrahedron Lett. 1995, 36, 1649. (c) SmCl3: Fu,
X.-L.; Wu, S.-H. Synth. Commun. 1997, 27, 1677.
(d) LiOTf: Auge, J.; Leroy, F. Tetrahedron Lett. 1996, 37,
7715. (e) La(OTf)3: Chini, M.; Crotti, P.; Favero, L.;
Macchia, F.; Pineschi, M. Tetrahedron Lett. 1994, 35, 433.
(f) Yb(OTf)3: Meguro, M.; Asao, N.; Yermamoto, Y. J.
Chem. Soc., Perkin Trans. 1 1994, 2597. (g) Ph4SbOTf:
Fugiwara, Y.; Imada, M.; Baba, A.; Matsuda, H.
Tetrahedron Lett. 1989, 30, 739. (h) BiCl3: Ollerry, T.;
(12) For a review, see: Smith, J. G. Synthesis 1984, 629.
Synthesis 2003, No. 15, 2298–2300 © Thieme Stuttgart · New York