PAPER
Regioselective, Microwave-Assisted Epoxide Aminolysis
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1H NMR (400 MHz, CDCl3): d = 7.32 (m, 5 Hz), 3.94 (d, J = 12.8
Hz, 1 H), 3.68 (d, J = 12.8 Hz, 1 H), 2.51 (q, J = 6.9 Hz, 1 H), 1.19
(s, 3 H), 1.09 (d, J = 6.9 Hz, 3 H), 1.04 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 140.4, 128.6, 128.3, 127.3, 71.6,
61.9, 52.6, 27.0, 23.0, 15.4.
Electrospray HRMS: m/z calcd for C12H19NO [M + Na+]: 216.1357;
found: 216.1364.
Riera, A.; Verdaguer, X. Tetrahedron: Asymmetry 2004, 15,
2085. (f) Castellnou, D.; Sola, L.; Jimeno, C.; Fraile, J. M.;
Mayoral, J. A.; Riera, A.; Pericas, M. A. J. Org. Chem. 2005,
70, 433. (g) Yamashita, M.; Yamada, K.; Tomioka, K. Org.
Lett. 2005, 7, 2369. (h) Huang, J.; Ianni, J. C.; Antoline, J.
E.; Hsung, R. P.; Kozlowski, M. C. Org. Lett. 2006, 8, 1565.
(i) Schiffers, I.; Rantanen, T.; Schmidt, F.; Bergmans, W.;
Zani, L.; Bolm, C. J. Org. Chem. 2006, 71, 2320.
(4) Two powerful alternate methods for synthesizing b-amino
alcohols are the Sharpless aminohydroxylation and the
Mannich-type reaction. Aminohydroxylation: (a) Li, G.;
Chang, H.-T.; Sharpless, K. B. Angew. Chem. Int. Ed. 1996,
35, 451. (b) O’Brien, P. Angew. Chem. Int. Ed. 1999, 38,
326. Mannich-type reaction: (c) Trost, B. M.; Terrell, L. R.
J. Am. Chem. Soc. 2003, 125, 338; and references cited
therein.
2-Methyl-3-phenylaminobutan-2-ol (13d)
According to the general procedure, MeOH (0.5 mL), aniline (0.19
g, 2.0 mmol), and epoxide 12 (0.17 g, 2.0 mmol) were reacted using
a 30 s ramp time and a 360 min hold time. Chromatography using
hexanes–EtOAc (70:30) afforded the title compound as a pale yel-
low liquid; yield: 0.229 g (64%).
IR (film): 3851, 3439, 1602 cm–1.
(5) For an excellent leading reference listing metal-mediated
epoxide aminolyses published through 2001, see: Cossy, J.;
Bellosta, V.; Hamoir, C.; Desmurs, J.-R. Tetrahedron Lett.
2002, 43, 7083.
1H NMR (400 MHz, CDCl3): d = 7.18 (t, J = 8.2 Hz, 2 H), 6.71 (m,
3 H), 3.41 (br s, NH), 3.40 (q, J = 6.4 Hz, 1 H), 1.29 (s, 3 H), 1.21
(s, 3 H), 1.15 (d, J = 6.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 148.1, 129.4, 118.2, 114.4, 72.7,
58.8, 27.0, 24.7, 16.3.
EI-HRMS: m/z calcd for C11H17NO [M+]: 179.1310; found:
179.1312.
(6) Recent examples: (a) LiClO4: Heydari, A.; Mehrdad, M.;
Maleki, A.; Ahmadi, N. Synthesis 2004, 1563. (b) See also:
Azizi, N.; Saidi, M. R. Can. J. Chem. 2005, 83, 505.
(c) LiBr: Chakraborti, A. K.; Rudrawar, S.; Kondaskar, A.
Eur. J. Org. Chem. 2004, 3597. (d) LiNTf2: see reference 5
(e) Ca(OTf)2: Cepanec, I.; Litvic, M.; Mikuldas, H.;
Bartolincic, A.; Vinkovic, V. Tetrahedron 2003, 59, 2435.
(f) See also: Babic, A.; Sova, M.; Gobec, S.; Pecar, S.
Tetrahedron Lett. 2006, 47, 1733. (g) Al(OTf)3: Fringuelli,
F.; Pizzo, F.; Tortoioli, S.; Vaccaro, L. J. Org. Chem. 2004,
69, 7745. (h) see also: Williams, D. B. G.; Lawton, M.
Tetrahedron Lett. 2006, 47, 6557. (i) BiCl3: Swamy, N. R.;
Kondaji, G.; Nagaiah, K. Synth. Commun. 2002, 32, 2307.
(j) See also: McCluskey, A.; Leitch, S. K.; Garner, J.; Caden,
C. E.; Hill, T. A.; Odell, L. R.; Stewart, S. G. Tetrahedron
Lett. 2005, 46, 8229. (k) Bi(OTf)3 and Bi(TFA)3: Khodaei,
M. M.; Khosropour, A. R.; Ghozati, K. Tetrahedron Lett.
2004, 45, 3525. (l) Sc(OTf)3: Placzek, A. T.; Donelson, J.
L.; Trivedi, R.; Gibbs, R. A.; De S, K. Tetrahedron Lett.
2005, 46, 9029. (m) ZrCl4: Chakraborti, A. K.; Kondaskar,
A. Tetrahedron Lett. 2003, 44, 8315. (n) CoCl2:
Comparison of Microwave Irradiation Versus Oil Bath Heating
for the Synthesis of Amino Alcohol 8a
Microwave method: To a 10 mL microwave reactor vial equipped
with a magnetic stirring bar was added MeCN (1 mL), piperidine
(0.34 g, 4.0 mmol), and styrene oxide (6; 0.48 g, 4.0 mmol). A 10
mL fiber optic internal temperature monitor was placed in the vial,
which was then sealed with the corresponding pressure monitoring
accessory (available from CEM Corporation). The vial was then
placed into the microwave reactor. The reaction was carried out
with the following parameters: temperature: 250 °C; max. pressure:
250 psi; max. power: 300 W. After 15 min and brief cooling period,
the solution was concentrated in vacuo to give amino alcohol 7a in
1
>95% conversion and 8:1 regioselectivity according to H NMR
analysis of the crude reaction mixture.
Oil-bath method: To a 10 mL microwave reactor vial equipped with
a magnetic stirring bar was added MeCN (1 mL), piperidine (0.34
g, 4.0 mmol), and styrene oxide (6; 0.48 g, 4.0 mmol). A 10 mL fi-
ber optic internal temperature monitor was placed in the vial, which
was then sealed with the pressure monitoring accessory and sub-
merged in an oil bath at 185 °C. After 15 min and brief cooling pe-
riod, the solution was concentrated in vacuo to give amino alcohol
Sundararajan, G.; Vijayakrishna, K.; Varghese, B.
Tetrahedron Lett. 2004, 45, 8253. (o) Cu(BF4)2: Kamal, A.;
Ramu, R.; Azhar, M. A.; Khanna, G. B. R. Tetrahedron Lett.
2005, 46, 2675. (p) See also: Yarapathy, V. R.; Mekala, S.;
Rao, B. V.; Tammishetti, S. Catal. Commun. 2006, 7, 466.
(q) ZnCl2: Pachon, L. D.; Gamez, P.; van Brussel, J. J. M.;
Reedijk, J. Tetrahedron Lett. 2003, 44, 6025. (r) Yb(OTf)3:
Shi, M.; Chen, Y. J. Fluorine Chem. 2003, 122, 219.
(s) K5CoW12O40·3H2O and (NH4)8[CeW10O36]·20H2O:
Mirkhani, V.; Tangestaninejad, S.; Yadollahi, B.; Alipanah,
L. Catal. Lett. 2005, 101, 93. (t) See also: Rafiee, E.;
Tangestaninejad, S.; Habibi, M. H.; Mirkhani, V. Synth.
Commun. 2004, 34, 3673. (u) Cyclodextrin: Surendra, K.;
Krishnaveni, N. S.; Rao, K. R. Synlett 2005, 506. (v) Silica
gel: Kotsuki, H.; Hayashida, K.; Shimanouchi, T.;
Nishizawa, H. J. Org. Chem. 1996, 61, 984. (w) See also:
Chakraborti, A.; Rudrawar, S.; Kondaskar, A. Org. Biomol.
Chem. 2004, 2, 1277. (x) Montmorillonite K 10:
1
7a in >95% conversion and 8:1 regioselectivity according to H
NMR analysis of the crude reaction mixture.
Acknowledgment
This research was supported by awards from ACS Petroleum Re-
search Fund (42476-GB1) and Research Corporation (CC6269).
References
(1) Bergmeier, S. C. Tetrahedron 2000, 56, 2561; and
references cited therein.
(2) Lee, H.-S.; Kang, S. H. Synlett 2004, 1673.
(3) For reviews, see: (a) Ager, D. J.; Prakash, I.; Schaad, D. R.
Chem. Rev. 1996, 96, 835. (b) Kolb, H. C.; Sharpless, K. B.
In Transition Metals for Organic Synthesis; Beller, M.;
Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998, 243. (c) Pu,
L.; Yu, H.-B. Chem. Rev. 2001, 101, 757. (d) de Parrodi, A.
C.; Juaristi, E. Synlett 2006, 2699. For recent examples,
see: (e) Garcia-Delgado, N.; Fontes, M.; Pericas, M. A.;
Chakraborti, A.; Kondaskar, A.; Rudrawar, S. Tetrahedron
2004, 60, 9085. (y) [Cr(salen)Cl]: Bartoli, G.; Bosco, M.;
Carlone, A.; Locatelli, M.; Massaccesi, M.; Melchiorre
Sambri, L. Org. Lett. 2004, 6, 2173. (z) See also: Kureshy,
R. I.; Sing, S.; Khan, N.; Abdi, S. H. R.; Agrawal, S.; Jasra,
R. V. Tetrahedron: Asymmetry 2006, 17, 1638.
(aa) Zeolite: Onaka, M.; Kawai, M.; Izumi, Y. Chem. Lett.
1985, 779.
Synthesis 2007, No. 6, 902–910 © Thieme Stuttgart · New York