A mild and efficient synthesis of β-amino alcohols from epoxides using a mesoporous aluminosilicate catalyst

Article abstract of DOI:10.1016/j.tetlet.2007.07.030

Mesoporous aluminosilicates catalyze efficiently the ring-opening reactions of a range of epoxides with aromatic amines to produce β-substituted alcohols in high yields under mild reaction conditions.

Full text of DOI:10.1016/j.tetlet.2007.07.030

Tetrahedron Letters 48 (2007) 6249–6251
A mild and efficient synthesis of b-amino alcohols from
epoxides using a mesoporous aluminosilicate catalyst
Mathew W. C. Robinson, David A. Timms, Sarah M. Williams and Andrew E. Graham*
Department of Chemistry, University of Wales Swansea, Singleton Park, Swansea SA2 8PP, UK
Received 7 June 2007; accepted 5 July 2007
Available online 30 July 2007
Abstract—Mesoporous aluminosilicates catalyze efficiently the ring-opening reactions of a range of epoxides with aromatic amines
to produce b-substituted alcohols in high yields under mild reaction conditions.
ꢀ
2007 Elsevier Ltd. All rights reserved.
The formation of b-amino alcohols from epoxides and
amines is an important reaction in medicinal and organ-
ic chemistry as they are useful synthetic intermediates
for the preparation of b-amino acids, natural products
zirconium sulfophenyl phosphonates, zeolites and clays
for the formation of b-amino alcohols from epoxides
5
and aromatic amines at room temperature. These pro-
cesses have greatly improved the atom efficiency of the
transformation, however, prolonged reaction times or
an inert atmosphere are still required.
1
and chiral auxiliaries. Classically, the reaction has been
carried out using an excess of the amine and high tem-
peratures, however, these conditions are far from ideal
2
as they are not tolerated by certain functional groups.
We recently reported that mesoporous aluminosilicates
are efficient heterogeneous catalysts for the preparation
Therefore, new methods which utilize mild Lewis acid
promoters and which work at low temperatures with
stoichiometric amounts of amine have continued to be
6
of b-alkoxy alcohols from epoxides and alcohols. We
have extended our studies in this area to show that such
catalysts are active for the preparation of b-amino alco-
hols from aromatic amines and epoxides under extre-
mely mild reaction conditions. The mesoporous
aluminosilicate material (Si/Al ratio = 14) was synthe-
sized according to previously reported procedures and
3
of interest (Scheme 1). The use of ultrasound, micro-
wave irradiation, ionic liquids, solvent free conditions
and under aqueous conditions in the absence of a cata-
4
lyst has been reported. These processes are useful, how-
ever, they suffer from disadvantages such as the use of
expensive or air sensitive reagents, extended reaction
times, the requirement for protracted work-up proce-
dures, or are limited in the range of amines.
6
used for all subsequent transformations. Our initial
experiments with 50 mg/mmol of catalyst utilized simple
alkylamines, such as ethylamine or diisopropylamine,
with styrene oxide, however, these reactions resulted in
no conversion to the b-amino alcohol and the starting
material was recovered unchanged. These observations
are attributed to a competing interaction of the nitrogen
and of the amine with the Lewis acid sites of a catalyst
reducing the catalytic activity of the material. To inves-
tigate this point further, we next considered the addition
reactions of the less nucleophilic aromatic amines under
similar conditions. The decreased nucleophilicity of
these substrates and the subsequent reduced interaction
with the catalyst was expected to free-up the catalytic
sites. We were gratified to observe that the reaction of
styrene oxide with aniline in dichloromethane at room
temperature provided moderate conversion with good
selectivity for the expected Markovnikov product pro-
Recent developments have focussed on the application
of heterogeneous catalysts such as heteropolyacids,
NR2
O
H
Lewis acid
+
N
OH
Ph
R
R
Ph
Scheme 1.
Keywords: Epoxide ring-opening; Mesoporous aluminosilicates;
Heterogeneous catalysis; b-Amino alcohols.
*
Corresponding author. Fax: +44 (0)1792 295747; e-mail:
A.E.Graham@swansea.ac.uk
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.030

6250
M. W. C. Robinson et al. / Tetrahedron Letters 48 (2007) 6249–6251
Table 1. Mesoporous aluminosilicate promoted aminolysis of epoxides
a,b
Yield (%)
Entry
1
Epoxide
Aniline
Time (h)
24
Product
HO
NH2
NH2
O
c,d
68
Ph
Ph
Ph
Ph
N
H
HO
O
O
e
2
3
4
6
6
6
70
Ph
N
H
HO
Br
NH2
e
65
Ph
N
H
Br
NHPh
O
NH2
NH2
OH
e
79
OH
H
N
5
O
6
85
OH
NH2
H
N
6
7
O
O
O
6
65
69
57
Br
Br
NH2
OH
OH
H
N
NO2
12
NO2
CO Me
NH2
2
H
N
8
9
12
8
CO Me
2
NH2
OH
O
f
80
PhO
PhO
NHPh
a
b
c
d
e
f
Isolated yield after column chromatography.
Reactions in CH Cl at room temperature utilizing 120 mg/mmol of catalyst unless otherwise stated.
0 mg/mmol of catalyst used.
Product is an 80:20 mixture of regioisomers as determined by H NMR analysis. Major isomer shown.
Products isolated in a 95:5 ratio of regioisomers. Major isomer shown.
2
2
5
1
Products isolated in an 85:15 ratio of regioisomers. Major isomer shown.
7
duced by attack at a more stable benzylic position. The
decreased interaction of the substrate with a catalyst,
and the subsequent improvement in the activity, is anal-
ogous to the ‘hard-soft acid–base’ theory for homo-
naphthalene oxide underwent a facile transformation to
give the anti-substituted product in good yield with only
trace amounts of the corresponding regioisomer. Utiliz-
ing this protocol, the aminolysis of cyclohexene oxide
also proceeded with a range of anilines to produce the
corresponding anti-b-amino alcohols in short times
and high yields further demonstrating the synthetic
utility of this process. Disappointingly, reactions utiliz-
ing 4-nitroaniline with these epoxides resulted in no con-
version to the desired b-amino alcohol. The application
of extended reaction times had no effect on the conver-
sion, and in the case of cyclohexene oxide, the utilization
of reflux temperatures led to the production of cyclohex-
anone produced by a competing Meinwald rearrange-
8
geneous Lewis acid catalysis. In general alkylamines are
harder Lewis bases than aromatic amines and compete
more efficiently with the epoxide for the catalytic sites
resulting in the requirement for longer reaction times
9
and greater amounts of catalyst.
Increasing the quantity of catalyst to 120 mg/mmol led
to an improvement in regioselectivity and a subsequent
reduction in reaction times for the addition aniline to
styrene oxide, and this quantity was used in all subse-
quent reactions (Table 1). Similarly, 1,2-dihydro-
1
0
ment process.
This is attributed to the further

M. W. C. Robinson et al. / Tetrahedron Letters 48 (2007) 6249–6251
6251
reduced nucleophilicity of the para-substituted aniline
References and notes
compared to aniline and indeed, experiments utilizing
the same reaction conditions but with no amine pro-
vided the rearrangement product in high yield. In accor-
1. (a) Cepanec, I.; Litvi c´ , M.; Mikulda sˇ , H.; Bartolin cˇ i c´ , A.;
Vinkovi c´ , V. Tetrahedron 2003, 59, 2435–2439; (b) Ager,
D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96,
5
d
dance with literature reports, the addition of aniline to
,2-epoxy-3-phenyoxypropane resulted in the formation
8
3
35–875; (c) O’Brien, P. Angew. Chem., Int. Ed. 1999, 38,
26–329; (d) Li, G.; Chang, H. T.; Sharpless, K. B. Angew.
1
of the product derived from the addition of the amine to
the least hindered carbon of the epoxide with good
regioselectivity.
Chem., Int. Ed. 1996, 35, 451–455; (e) Joossens, J.; Van der
Veken, P.; Lambeir, A. M.; Augustyns, K.; Haemers, A. J.
Med. Chem. 2004, 47, 2411–2413; (f) Williams, P. G.;
Yoshida, W. Y.; Moore, R. E.; Paul, V. J. J. Nat. Prod.
2002, 65, 29–31; (g) Rogers, G. A.; Parsons, S. M.;
Anderson, D. C.; Nilsson, L. M.; Bahr, B.; Kornreich, W.
D.; Kaufman, R.; Jacobs, R. S.; Kirtman, B. J. Med.
Chem. 1989, 32, 1217–1230.
In conclusion, we have demonstrated that mesoporous
aluminosilicates efficiently catalyze the formation of b-
amino alcohols from aromatic amines and epoxides in
short reaction times and in high yields under mild reac-
tion conditions. The facile synthesis of these materials,
their benign nature, the ease of handling and the simpli-
fied reaction and isolation procedures make them a
highly attractive alternative to current methodologies.
2
3
. Chini, M.; Crotti, P.; Macchia, F. J. Org. Chem. 1991, 56,
5
939–5942.
. (a) Pach o´ n, L. D.; Gamez, P.; van Brussel, J. J. M.;
Reedijk, J. Tetrahedron Lett. 2003, 44, 6025–6027; (b)
Bradley, D.; Williams, G.; Lawton, M. Tetrahedron Lett.
2
006, 47, 6557–6560; (c) Mai, E.; Schneider, C. Chem. Eur.
Typical procedure for aminolysis of epoxides: Cyclo-
hexene oxide (98 mg, 1.0 mmol) and aniline (102 mg,
J. 2007, 13, 2729–2741; (d) Carr e´ e, F.; Gil, R.; Collin, J.
Tetrahedron Lett. 2004, 45, 7749–7751; (e) Yadav, J. S.;
Reddy, A. R.; Narsaiah, A. V.; Reddy, B. V. S. J. Mol.
Catal. A: Chem. 2007, 261, 207–212; (f) Placzek, A. T.;
Donelson, J. L.; Trivedi, R.; Gibbs, R. A.; De, S. K.
Tetrahedron Lett. 2005, 46, 9029–9034.
. (a) Kamal, A.; Adil, S. F.; Arifuddin, M. Ultrason.
Sonochem. 2005, 12, 429–431; (b) Kureshy, R. I.; Singh, S.;
Khan, N. H.; Abdi, S. H. R.; Agrawal, S.; Mayani, V. J.;
Jasra, R. V. Tetrahedron Lett. 2006, 47, 5277–5279;
1
.1 mmol) were dissolved in dichloromethane (5 mL) at
room temperature. The mesoporous catalyst (120 mg)
was added and the reaction mixture stirred at room
temperature and monitored by TLC. Upon completion
of the reaction, the catalyst was removed by filtration
through a Celite plug which was washed with dichloro-
methane (2 · 5 mL) and the combined solvents were
removed under reduced pressure to give a yellow oil
which was purified by column chromatography (hex-
ane!20% ethyl acetate–hexane) to give the product
4
(
c) Fringuelli, F.; Pizzo, F.; Toroolli, S.; Vaccaro, L.
J. Org. Chem. 2004, 69, 7745–7747; (d) Horv a´ th, A.;
Skoda-F o¨ ldes, R.; Mah o´ , S.; Berente, Z.; Koll a´ r, L.
Steroids 2006, 71, 706–711; (e) Yadav, J. S.; Reddy, B. V.
S.; Basak, A. K.; Venkat Narsaiah, A. Tetrahedron
Lett. 2003, 44, 1047–1050; (f) Fringuelli, F.; Pizzo, F.;
Toroolli, S.; Vaccaro, L. J. Org. Chem. 2004, 69, 7745–
2
-(phenylamino)cyclohexanol (162 mg, 85%) as white
4
e
1
solid; mp = 59–61 ꢁC (lit. 60–61 ꢁC ); H NMR (CDCl ;
4
3
2
3
00 MHz) d = 7.11–7.07 (2H, m), 6.68–6.60 (3H, m),
.30–3.22 (1H, m), 3.10–2.80 (2H, m), 2.75 (1H, br s),
.07–1.99 (2H, m), 1.72–1.57 (2H, m), 1.37–1.14 (3H,
7
747; (g) Azizi, N.; Saidi, M. R. Org. Lett. 2005, 7, 3649–
1
3
3651.
m), 1.00–0.89 (1H, m); C NMR (CDCl ; 100 MHz)
3
5
. (a) Azizi, N.; Saidi, M. R. Tetrahedron 2007, 63, 888–891;
d = 148.3, 129.8, 129.7, 118.7, 118.6, 114.7, 74.9, 60.5,
(
b) Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.
ꢀ
1
3
3.6, 32.0, 25.4, 24.7; mmax (film)/cm (neat) = 3394,
Eur. J. Org. Chem. 2001, 4149–4152; (c) Kureshy, R. I.;
Singh, S.; Khan, N. H.; Abdi, S. H. R.; Suresh, E.; Jasra,
R. V. J. Mol. Catal. A: Chem. 2006, 264, 162–169; (d)
Chakraborti, A. K.; Kondasar, A.; Rudrawar, S. Tetra-
hedron 2004, 60, 9085–9091.
3
053, 2923, 1599, 1497, 1321, 1054, 740, 688; MS(EI)
+
m/z 192.1 (M+H) ; HRMS (ES) calculated for
C H NO (M+H) , 192.1383, found (M+H) 192.1384.
+
+
1
2
18
6
. (a) Robinson, M. W. C.; Buckle, R.; Mabbett, I.; Grant,
G. M.; Graham, A. E. Tetrahedron Lett. 2007, 48, 4723–
Acknowledgements
4
725; (b) Robinson, M. W. C.; Graham, A. E. Tetrahedron
Lett. 2007, 48, 4727–4731.
The authors thank the Engineering and Physical Sci-
ences Research Council (EPSRC) for financial support
7
. Lewars, E. G. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Rees, C. W., Lwowski, W., Eds.;
Pergamon: Oxford, 1984; Vol. 7, pp 100–113.
. Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89,
(
MWCR), the EPSRC National Mass Spectrometry ser-
vice, University of Wales Swansea, UK and the EPSRC
Solid-State NMR Service, University of Durham, UK.
We also wish to thank Mr. Peter Davies (School of
Engineering, University of Wales Swansea) for his
assistance in obtaining EDX data and Dr. S. H. Taylor
8
9
1
827–1836.
. Bradley, D.; Williams, G.; Lawton, M. Tetrahedron Lett.
006, 47, 6557–6560.
2
10. Our initial results for the mesoporous aluminosilicate
promoted Meinwald rearrangement of epoxides will be the
subject of a subsequent publication.
(
Cardiff University) for his continued interest in this
work.