atoms in SiO help the delocalisation of the negative charge of
NMR δC (300 MHz, CDCl ) 145.62, 139.50, 128.81, 128.67,
2
3
the alkoxide generated after the nucleophilic attack on the silica
gel complexed epoxide. Thus, the free alkoxide anion is not
available for subsequent elimination of the chloride anion.
In conclusion, this study demonstrates that chromatographic
silica gel (60–120 mesh) is a highly efficient, mild, and reusable
catalyst for opening of epoxides with amines. The mild reaction
conditions, excellent regio-, diastereo-, and chemo-selectivity,
and applicability for aromatic and aliphatic amines offer
specific advantages. The low cost and apparent non-toxic
nature of silica gel and the solvent-free reaction conditions are
127.55, 126.56, 122.23, 114.90, 66.86 and 59.93; m/z (EI) 247
ϩ
(M ) and 216 (100%). C H ClNO requires: C, 67.88; H, 5.70;
14
14
N, 5.65%; found: C, 67.86; H, 5.71; N, 5.64%.
13a,15
1-Phenoxy-3-phenylaminopropan-2-ol (Table 3, entry 1)
IR (neat): 3391, 3056, 2926, 2872, 1600, 1495, 1243 and 1041;
NMR δC (300 MHz, CDCl ) 158.22, 147.86, 129.37, 129.12,
3
1
2
21.01, 117.75, 114.37, 113.14, 69.80, 68.44 and 46.45; m/z (EI)
43 (M ) and 106 (100%).
ϩ
25
consistent with increasing environmental concerns and will
make the present method potentially useful for industrial
applications.
1
-tert-Butoxy-3-phenylaminopropan-2-ol (Table 3, entry 2)
IR (neat): 3385, 3051, 2973, 1601, 1500, 1243 and 1078; NMR
δH (300 MHz, CDCl ) 7.16 (m, 2 H), 6.70 (m, 1 H), 6.62 (d,
J 8.2, 2 H), 3.93 (m, 1 H), 3.44–3.49 (dd, J 3.9 and 8.9, 1 H),
3
Typical procedure. trans-2-(phenylamino)cyclohexanol (3a)
3
1
.35–3.41 (dd, J 6.3 and 8.9, 1 H), 3.24–3.30 (dd, J 4.2 and 12.5,
H), 3.09–3.15 (dd, J 6.9 and 12.5, 1 H) and 1.20 (s, 9 H).
Silica gel (60–120 mesh, 25 mg, 10% w/w) was added to a mag-
netically stirred mixture of 1 (0.25 ml, 2.5 mmol) and 2a (0.225
ml, 2.5 mmol) at rt under nitrogen. After completion of the
reaction (3 h, GCMS), the reaction mixture was diluted with
NMR δC (300 MHz, CDCl ) 148.34, 129.14, 117.52, 113.09,
3
ϩ
7
1
3.33, 69.20, 64.02, 46.86 and 24.43. m/z (EIMS) 223 (M ) and
06 (100%). C H NO requires: C, 69.92; H, 9.48; N, 6.27%;
13
21
2
Et O (15 ml) followed by addition of a few drops of water
2
found: C, 69.90; H, 9.49; N, 6.26%.
(
to settle down the catalyst). The catalyst was separated by
decantation of the supernatant ethereal solution, was washed
8
1
-Chloro-3-phenylaminopropan-2-ol (Table 3, entry 3)
with Et O (10 ml) and the combined ethereal solutions were
2
dried (Na SO ) and concentrated under vacuum to afford trans-
IR (neat): 3404, 3062, 2952, 1602, 1505, 1318, 1259, 1090 and
2
4
2
3
-(phenylamino)cyclohexanol 3a (0.428 g, 90%); IR (neat):
354, 2931, 2858, 1601, 1500, 1448, 1319 and 1067; NMR
753; NMR δ (300 MHz, CDCl ) 7.19 (m, 2 H), 6.75 (m, 1 H),
H
3
6.66 (d, J 7.9, 2 H), 4.05–4.10 (m, 1 H), 3.61 (m, 2 H), 3.36–3.41
(dd, J 4.4 and 13.3, 1 H) and 3.20–3.27 (dd, J 7.1 and 13.3, 1 H);
δH (300 MHz, CDCl ) 6.7–7.2 (m, 5 H), 3.33 (ddd, J 4.2, 10.4
3
and 10.5, 1 H), 3.13 (ddd, J 3.9, 10.0 and 10.1, 1 H), 2.9 (m,
NMR δC (300 MHz, CDCl ) 147.31, 129.20, 118.23, 113.35,
3
ϩ
D O exchangeable, 2 H), 2.10–2.16 (m, 2 H), 1.72–1.78 (m, 2 H)
69.47, 47.25 and 42.02; m/z (EI) 185 (M ), 168 and 106 (100%).
2
and 1.03–1.42 (m, 4 H); NMR δ (300 MHz, CDCl ) 147.81,
C
3
1
2
29.34, 118.38, 114.40, 74.55, 60.17, 33.15, 31.62, 25.02 and
ϩ 1 13
References and notes
4.27; m/z (EI) 191 (M ); identical ( H and C NMR, and MS)
12h
with an authentic sample. The recovered catalyst was activ-
ated by heating at 100 ЊC under vacuum (∼5 mmHg) for 10 h
and reused for the reaction of a fresh batch of 1 (2.5 mmol) and
1
(a) D. R. Gehlert, D. J. Goldstein and P. A. Hipskind, Annu. Rep.
Med. Chem., 1999, 201; (b) E. J. Corey and F. Zhang, Angew. Chem.,
Int. Ed. Engl., 1999, 38, 1931; (c) C. W. Johannes, M. S. Visser,
G. S. Weatherhead and A. H. Hoveyda, J. Am. Chem. Soc., 1998,
2
a (2.5 mmol) affording 3a in 86% yields. This general
1
20, 8340; (d ) B. L. Chng and A. Ganesan, Bioorg. Med.
procedure was followed for the other reactions. On each
occasion, the product was identified by comparing the spectral
data (IR, NMR, MS) with those reported in the literature,
wherever applicable. New spectral data were obtained in the
following cases.
Chem. Lett., 1997, 7, 1511; (e) G. A. Rogers, S. M. Parsons, D. C.
Anderson, L. M. Nilsson, B. A. Bahr, W. D. Kornreich,
R. Kaufman, R. S. Jacobs and B. Kirtman, J. Med. Chem., 1989, 32,
1
217; ( f ) J. De Cree, H. Geukens, J. Leempoels and H. Verhaegen,
Drug Dev. Res., 1986, 8, 109.
2
(a) P. O’Brien, Angew Chem., Int Ed. Engl., 1999, 38, 326; (b) G. Li,
H.-T. Chang and K. B. Sharpless, Angew Chem., Int Ed. Engl., 1996,
12d
2
-(4-Methylphenyl)aminocyclohexanol (3b)
3
5, 451.
IR (neat): 3389, 2932, 2859, 1616, 1517, 1298 and 1067; NMR
3 D. J. Ager, I. Prakash and D. R. Schaad, Chem. Rev., 1996, 96, 835.
4
(a) S. C. Bergmeier, Tetrahedron, 2000, 56, 2561; (b) D. M. Hodgson,
A. R. Gibbs and G. P. Lee, Tetrahedron, 1996, 52, 14361; (c)
R. M. Hanson, Chem. Rev., 1991, 91, 437; (d ) O. Mitsunobu, in
Comprehensive Organic Synthesis, ed. E. Winterfeldt, Pergamon
Press, New York, 1996, Vol 6, Pt 1.3.4.1; (e) A. S. Rao,
S. K. Paknikar and J. G. Kirtane, Tetrahedron, 1983, 39, 2323.
δ (300 MHz, CDCl ) 6.98 (d, J 7.7, 2 H), 6.62 (d, J 7.7, 2 H),
H
3
3
(
(
.26–3.34 (m, 1 H), 3.01–3.10 (m, 1 H), 2.23 (s, 3 H), 2.07–2.12
m, 2 H), 1.67–1.75 (m, 2H), 1.23–1.42 (m, 3 H) and 0.94–1.06
m, 1 H); δ (300 MHz, CDCl ) 145.06, 129.25, 126.57, 114.15,
C
3
7
3.38, 59.75, 32.99, 30.83, 24.34, 23.86 and 19.93; m/z (EI) 205
ϩ
(
M ), 162, 146 (100%).
5 (a) P. A. Crooks and R. Szyudler, Chem. Ind. (London), 1973, 1111;
(b) J. A. Deyrup and C. L. Moyer, J. Org. Chem., 1969, 34, 175;
(c) M. Freifelder and G. R. Stone, J. Org. Chem., 1961, 26, 1477;
(d ) M. Mousseron, J. Jullien and Y. Jolchine, Bull. Soc. Chim. Fr.,
26
2
-(4-Chlorophenyl)aminocyclohexanol (3c)
1
952, 757; (e) R. E. Lutz, J. A. Freekand and R. S. Murphy, J. Am.
IR (neat): 3386, 2931, 2858, 1511, 1242 and 1035; NMR δ (300
C
Chem. Soc., 1948, 70, 2015.
MHz, CDCl ) 146.15, 128.82, 122.23, 115.13, 73.93, 59.86,
3
6
7
G. H. Posner and D. Z. Rogers, J. Am. Chem. Soc., 1977, 99, 8208.
3
2.23, 31.09, 24.55 and 24.02.
(a) Et AlNHR: L. E. Overman and L. A. Flippin, Tetrahedron Lett.,
2
1
981, 22, 196; (b) silicon amides: A. Papini, I. Ricci, M. Taddei,
G. Seconi and P. Dembach, J. Chem. Soc., Perkin Trans. 1, 1984,
261; (c) R NMgBr: M. C. Carre, J. P. Houmounou and P. Caubere,
9
c
2
-Pyrrolidin-1-yl-cyclohexanol (3d)
2
2
IR (neat): 3422, 2938, 1640, 1484, 1085 and 738; NMR δ (300
Tetrahedron Lett., 1985, 26, 3107; (d ) RЈ PbNR : J.-I. Yamada,
C
3 2
MHz, CDCl ) 69.97, 65.35, 47.94, 33.33, 24.55, 24.00, 23.42
and 22.15; m/z (EI) 169 (M ), 140 and 110 (100%).
M. Yumoto and Y. Yamamoto, Tetrahedron Lett., 1989, 30, 4255;
e) Cu amide: Y. Yamamoto, N. Asao, M. Meguro, N. Tsukade,
H. Nemoto, N. Adayari, J. G. Wilson and H. Nakamura, J. Chem.
3
ϩ
(
Soc., Chem. Commun., 1993, 1201; ( f ) LiNTf : J. Cossy, V. Bellosta,
2
2
-(4-Chlorophenyl)amino-2-phenylethanol (6c)
C. Hamoir and J.-R. Desmurs, Tetrahedron Lett., 2002, 43, 7083.
8
9
M. Chini, P. Crotti and F. Macchia, Tetrahedron Lett., 1990, 31,
IR (neat): 3396, 2931, 1600, 1496, 1314 and 813; NMR δ (300
MHz, CDCl ) 7.13–7.39 (m, 5 H), 7.00 (d, J 8.8, 2 H), 6.46 (d,
J 8.8, 2 H), 4.41–4.45 (dd, J 4.1 and 6.9, 1 H), 3.90–3.95 (dd,
J 4.1 and 10.8, 1 H) and 3.71–3.77 (dd, J 6.9 and 10.8, 1 H);
H
4
661.
3
(a) Ph SbOTf: M. Fujiwara, M. Imada, A. Baba and H. Matsuda,
4
Tetrahedron Lett., 1989, 30, 739; (b) Ln(OTf ) : M. Chini, P. Crotti,
3
L. Favero, F. Machhia and M. Pineschi, Tetrahedron Lett., 1994, 35,
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 2 7 7 – 1 2 8 0
1279