TaCl5-catalyzed cleavage of epoxides with aromatic amines

Article abstract of DOI:10.1055/s-2000-8240

Tantalum(V) chloride has been demonstrated as an efficient catalyst in ring opening of epoxides with aromatic amines for the synthesis of β-amino alcohols for the first time.

Full text of DOI:10.1055/s-2000-8240

SHORT PAPER
1817
TaCl5-Catalyzed Cleavage of Epoxides with Aromatic Amines
S. Chandrasekhar,* T. Ramachandar, S. Jaya Prakash
Indian Institute of Chemical Technology, Hyderabad-500 007, India
E-mail: srivaric@iict.ap.nic.in
Received 23 June 2000; revised 11 August 2000
good yields. All the compounds are fully characterised by
1H NMR, IR and mass spectral data by comparison with
the known compounds.9 The trans stereochemistry of the
amino alcohol 3b was determined by the coupling con-
stants of the peaks at 3.15 ppm (CHNHPh) (ddd, J = 10.9,
9.3 and 4.1 Hz) and 3.35 ppm (CHOH) (ddd, J = 9.6, 9.6
and 3.9 Hz) in 1H NMR spectra.9
Abstract: Tantalum(V) chloride has been demonstrated as an effi-
cient catalyst in ring opening of epoxides with aromatic amines for
the synthesis of b-amino alcohols for the first time.
Key words: epoxide, aromatic amine, tantalum(V) chloride, b-ami-
no alcohol
Other epoxides viz., cyclopentene oxide and cyclooctene
oxide also responded well with excellent yields. Interest-
ing to note in the above studies is that aliphatic amines fail
to open the epoxides even after prolonged hours of reac-
tion. This unusual behavior of the reaction is previously
reported with metal triflate3 as catalyst. Mechanistic im-
plications of this selectivity are not understood to the best
of our knowledge.
Introduction of amino functionality into an organic mole-
cule has highest prominence. This may be attributed to the
fact that more than 75% of drugs and drug intermediates
possess amino functionality.1 Of the several methods
available in the literature for this transformation, epoxide
opening with amines catalyzed by metal amides2 and
triflates3 provides direct access to this class, while liberat-
ing a free hydroxy group as an efficient handle for further
manipulations. The resultant trans-1,2-amino alcohols
play a major role as intermediates in the synthesis of un-
usual amino acids4 and chiral auxiliaries5 in asymmetric
synthesis.
In summary we have demonstrated a novel, mild and effi-
cient method for the ring opening of epoxides with aro-
matic amines using TaCl5–SiO2 as a Lewis acid catalyst.
This novel method is applicable to a wide range of sub-
strates.
Several clinically useful skeletons, which exhibit a broad
range of activities as anti-obesity drugs6 and anti-hyper-
tensive agents, 7 also contain the 1,2-amino alcohol func-
tionality. Interest in exploring the usefulness of TaCl5 as
an efficient catalyst in organic synthesis8 en route to the
total synthesis of clinically useful amino alcohols prompt-
ed us to explore the possibility of opening epoxides with
aromatic amines in the presence of TaCl5−SiO2. The re-
sults are disclosed herein (Equation).
Cleavage of Epoxides with Aromatic Amines: General Proce-
dure
Epoxide (10 mmol) and amine (12 mmol) were added to a stirred so-
lution of TaCl5–SiO2 (10mol%) 8 in anhyd CH2Cl2 (20 mL). The
mixture was stirred at r.t. under N2. The reaction upon completion
(TLC) was diluted with H2O (15 mL) and extracted with CH2Cl2
(3 × 20 mL). Combined organic layers were washed with brine and
dried (Na2SO4). The solvent was removed under vacuum and the
crude product was column chromatographed on a silica gel column
to afford pure b-amino alcohol.
We first examined the reaction of cyclohexene oxide with
aniline and TaCl5–SiO2 in anhydrous CH2Cl2 at ambient
temperature to give the corresponding amino alcohol 3a in
85% yield (entry 1). This success has encouraged us to ex-
ploit the generality of the reaction to a few other epoxides
with various amines (Table). For example cyclohexene
oxide is treated with sterically hindered aromatic amines
such as 2-methylaniline (entry 3), 2-acetylaniline (entry 4)
to uniformly isolate the corresponding amino alcohols in
Physical data of unknown compounds 3d: Semi solid.
IR (neat): ν = 3130–3610 cm–1.
1H NMR (CDCl3): δ = 1.0 (m, 1H), 1.2–1.4 (m, 3H), 1.6–1.8 (m,
2H), 2.0–2.15 (m, 2H), 2.5 (s, 3H), 3.05–3.2 (m, 1H), 3.25–3.4 (m,
1H), 6.8 (d, J = 8.83 Hz, 1H), 7.1–7.25 (m, 3H).
MS: m/z 233 (M+).
OH
10 mol% TaCl5-SiO2
O
H2N
R
+
n
n
CH2Cl2, r.t.
R
NH
n = 1, 2, 4
1
3
2
Equation
Synthesis 2000, No. 13, 1817–1818 ISSN 0039-7881 © Thieme Stuttgart · New York

1818
S. Chandrasekhar et al.
SHORT PAPER
Table TaCl5-Silica gel catalysed epoxide opening with aromatic
amines
(dt, J = 7.2, 0.6 Hz, 1H), 6.8 (d, J = 8.7 Hz, 1H), 7.23 (m, 2H); MS:
m/z 192 (M+1).
Anal Calcd for C12H17NO: C, 75.35, H, 8.96, N, 7.32. Found C,
75.39, H, 8.99, N, 7.34.
Entry
Amino alcohols 3
Yield (%)
OH
Acknowledgement
NRAr
Two of us (TRC and SJP) thank CSIR, New Delhi for financial sup-
port.
1
2
3
4
5
6
7
3a
3b
3c
3d
3e
3f
R=H, Ar= Ph
85
82
79
78
75
77
73
R=H, Ar= C6H4-p-OCH3
R=H, Ar= C6H4-o-CH3
R=H, Ar=C6H4-o-COCH3
R=H, Ar= C6H4-p-Cl
R=H, Ar=C6H4-p-Br
R=Et, Ar=C6H5
References
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OH
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NRAr
8
9
3h
3i
3j
3k
3l
3m
3n
R=H, Ar= Ph
83
80
76
76
74
75
72
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R=H, Ar= C6H4-p-OCH3
R=H, Ar= C6H4-o-CH3
R=H, Ar=C6H4-o-COCH3
R=H, Ar= C6H4-p-Cl
R=H, Ar=C6H4-p-Br
R=Et, Ar=C6H5
10
11
12
13
14
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OH
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15
16
3o
3p
R=H, Ar=Ph
R=H, Ar= C6H4-p-OCH3
80
78
(6) Gehlert, D. R.; Goldstein D. J.; Hipskind, P. A. Annual
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Anal Calcd for C14H19NO2: C, 72.07, H, 8.21, N, 6.01. Found C,
72.12, H, 8.26, N, 6.05.
Compound 3g: viscous liquid.
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S.; Rama Rao, C.; Reddy, K. V. Tetrahedron 1997, 53, 14997.
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1H NMR (CDCl3): δ = 0.9–1.0 (m, 1H), 1.2 (t, J = 4.65, 3H), 1.25–
1.5 (m, 3H), 1.7–1.8 (m, 2H), 2.15–2.25 (m, 2H), 2.9 (s, 1H), 3.2–
3.4 (m, 3H), 3.55–3.7 (m, 1H), 6.8 (t, J = 4.5 Hz, 1H), 6.95 (d,
J = 9.0 Hz, 2H), 7.25 (t, J = 4.5 Hz, 2H).
(c) Chandrasekhar, S.; Ramachandar, T.; Takhi, M.
Tetrahedron Lett. 1998, 39, 3263.
MS: m/z = 219 (M+).
(9) (a) Sekar, G.; Singh, V. K. J. Org. Chem. 1999, 64, 287.
(b) Hou, X. l.; Wu, L.; Dai, L. X.; Xia, L. J.; Tang, M. H.
Tetrahedron: Asymmetry 1998, 9, 1747.
Anal Calcd for C14H21NO: C, 76.67, H, 9.65, N, 6.39. Found C,
76.72, H, 9.72, N, 6.42.
Compound 3j: viscous liquid.
1H NMR (CDCl3): δ = 1.35–1.5 (m, 1H), 1.55–1.85 (m, 3H), 2.2–
2.45 (m, 2H), 2.80 (s, 3H), 3.9–3.95 (m, 1H), 4.2–4.3 (m, 1H), 6.64
Article Identifier:
1437-210X,E;2000,0,13,1817,1818,ftx,en;Z06100SS.pdf
Synthesis 2000, No. 13, 1817–1818 ISSN 0039-7881 © Thieme Stuttgart · New York