LETTER
Efficient and Chemoselective Deoxygenation of Amine N-Oxides
351
(9) Den Hertog, H. J.; Overhoff, J. Recl. Trav. Chim. 1950, 69,
468.
(10) McCall, J. M.; TenBrink, R. E. Synthesis 1975, 335.
(11) (a) Homaidan, F. R.; Issidorides, C. H. Heterocycles 1981,
16, 411. (b) George, J.; Chandrasekaran, S. Synth. Commun.
1983, 13, 495.
In conclusion, we have demonstrated that PMHS is a ver-
satile reductive reagent for selective deoxygenation of
amine N-oxides in high yields. We believe that the reagent
system described herein may find wide applicability in or-
ganic synthesis due to its chemoselectivity, efficiency,
economy, simplicity and safety.
(12) Hayashi, E.; Yamanaka, H.; Shimizu, K. Chem. Pharm. Bull.
1958, 6, 323.
(13) Geroge, A.; Olah, G. A.; Arvanaghi, M.; Vankar, Y. D.
Synthesis 1980, 660.
(14) Konwar, D.; Boruah, R. C.; Sandhu, J. S. Synthesis 1990,
337.
(15) Tokitoh, N.; Okazaki, T. Chem. Lett. 1985, 1517.
(16) Balicki, R. Synthesis 1989, 645.
(17) Barton, D. H. R.; Fekih, A.; Lusinchi, X. Tetrahedron Lett.
1985, 38, 4603.
(18) Akita, Y.; Misu, K.; Watanabe, T.; Ohta, A. Chem. Pharm.
Bull. 1976, 24, 1839.
(19) Balicki, R.; Kaczmarek, L.; Malinowski, M. Synth.
Commun. 1989, 19, 897.
General Experimental Procedures for Deoxygenation:
Method A: To a solution of substrate (1 mmol) in THF (10 mL)
were added PMHS (180 mg, 3 mmol) and Pd (PPh3)4 (15 mg, 0.01
mmol).The reaction mixture was stirred at room temperature until
the disappearance of the starting material (monitored by TLC, gen-
erally 20–45 minutes). After completion of the reaction the mixture
was diluted with water (5 mL), extracted with ether (2 15 mL),
washed with brine solution (10 mL) and dried (Na2SO4). Evapora-
tion of the volatiles followed by column chromatography on silica
gel afforded the product in yields as indicated in Tables 1 and 2.
Method B: To a solution of substrate (1 mmol) in THF were added
PMHS (180 mg, 3 mmol) and titanium (IV) isopropoxide (284mg,
1 mmol) and the mixture was stirred at room temperature till com-
pletion of the reaction (monitored by TLC, generally 1.5–2.5
hours). The mixture was cooled and sodium hydroxide solution (3
N, 10 mL) was carefully added dropwise (at first there is vigorous
gas evolution). After stirring for 20 minutes the solution was ex-
tracted with ether (3 15 mL), the combined ether layers were
washed with brine solution (15 mL), dried (Na2SO4) and evaporated
in vacuo to give the amine in essentially pure form.
(20) Kano, S.; Tanaka, Y.; Hibino, S. Heterocycles 1980, 14, 39.
(21) Handa, Y.; Inanaga, J.; Yamaguchi, M. J. Chem. Soc., Chem.
Commun. 1989, 298.
(22) Nicolaou, K. C.; Koumbis, A. E.; Snyder, S. A.; Simonsen,
K. B. Angew. Chem. Int. Ed. 2000, 39, 2529.
(23) Wang, Y.; Espenson, J. H. Org. Lett. 2000, 2, 3525.
(24) Yadav, J. S.; Reddy, B. V. S.; Reddy, M. M. Tetrahedron
Lett. 2000, 41, 2663.
(25) Aoyagi, Y.; Abe, T.; Ohta, A. Synthesis 1997, 891.
(26) Chandrasekhar, S.; Reddy, C. R.; Rao, R. J. Synlett 2001,
1561.
(27) For an exhaustive review on PMHS, see: (a) Lawrence, N.
J.; Drew, M. D.; Bushell, S. M. J. Chem. Soc., Perkin Trans.
1 1999, 3381. (b) Nitzche, S.; Wick, M. Angew Chem. 1957,
69, 96. (c) Mimoun, H.; Laumer, J. Y. S.; Giannini, L.;
Scopelliti, R.; Floriani, C. J. Am. Chem. Soc. 1999, 121,
6158. (d) Verdager, X.; Lange, U. E. W.; Buchwald, S. L.
Angew. Chem. Int. Ed. 1998, 37, 1103. (e) Lopez, R. M.;
Fu, G. C. Tetrahedron 1997, 53, 16349. (f) Breeden, S. W.;
Lawrence, N. J. Synlett 1994, 833. (g) Drew, M. D.;
Lawrence, N. J.; Fontaine, D.; Sehkri, L. Synlett 1997, 989.
(h) Mimoun, H. J. Org. Chem. 1999, 64, 2582; and
references cited therein.
Method C: To a solution of substrate (1 mmol) in ethanol (10mL)
were added PMHS (180 mg, 3 mmol) and 10% Pd/C (~15 mg). The
reaction mixture was stirred at room temperature until completion
of the reaction (monitored by TLC, generally 2–4 hours). The mix-
ture was filtered and the filtrate was evaporated in vacuo. The resi-
due was purified by column chromatography on silica gel to give
the corresponding amine in excellent yields.
Acknowledgement
CRR thanks CSIR and RJR thanks UGC, New Delhi for financial
assistance. SCS thanks CSIR for funding of a research grant (EMR-
0006).
(28) Spectroscopic data of the products(4e): 1H NMR (CDCl3):
2.56–2.38 (m, 4 H), 2.04 (m, 1 H), 1.9 (m, 1 H), 1.78–1.6 (m,
4 H), 1.55–1.15 (broad m, 8 H), 0.96–0.85 (d, 3 H, J = 7 Hz);
IR (Neat): 2927, 2856, 1459, 1283, 772 cm–1; MS (m/z): 167
(M+); Anal. Calcd. for C11H21N: C, 78.98; H, 12.65. Found:
C, 79.01; H, 12.63.(4f1): 1H NMR (CDCl3): 7.41–7.02 (m,
5 H), 6.58–6.44 (d, 1 H, J = 17.6 Hz), 6.3 (m, 1 H), 3.14–3.06
(d, 2 H, J = 6.1 Hz), 2.51–236 (m, 4 H), 1.7–1.54 (m, 4 H);
IR (Neat): 2964, 2856, 143, 1360, 759 cm–1; MS (m/z): 187
(M+); Anal. Calcd. for C13H17N: C, 83.37; H, 9.15. Found: C,
83.34; H, 9.12.(4g1): 1H NMR (CDCl3): 8.3–8.12 (dd, 2 H,
J = 8.4, 16.8 Hz), 7.72–7.46 (dd, 2 H, J = 8.4, 16.8 Hz), 3.68
(s, 2 H), 2.58–2.46 (m, 4 H), 1.88–1.76 (m, 4 H); IR (Neat):
2966, 2797, 1519, 1346, 849 cm–1; MS (m/z): 206 (M+);
Anal. Calcd. for C11H14N2O2: C, 64.06; H, 6.84. Found: C,
64.08; H, 6.86.(4h1): 1H NMR (CDCl3): 7.42–7.3 (m, 5 H),
7.26–7.14 (dd, 2 H, J = 8.2, 14.3 Hz), 6.96–6.8 (dd, 2 H, J =
8.2, 14.3 Hz), 5.2 (s, 2 H), 3.5 (s, 2 H), 2.54–2.4 (m, 4 H),
1.8–1.64 (m, 4 H); IR (Neat): 2963, 2801, 1453, 1232, 771
cm–1; MS (m/z): 267 (M+); Anal. Calcd. for C18H21NO: C,
80.86; H, 7.92. Found: C, 80.85; H, 7.91.
References
(1) IICT Communication No. 4744.
(2) (a) Ochiai, E. J. Org. Chem. 1953, 18, 534. (b) Ochiai, E. In
Aromatic Amine Oxide; Elsevier: Amesterdam, 1967, 184.
(3) Ochiai, E. Proc. Imp. Acad. (Tokyo) 1943, 19, 307; Chem.
Abs. 1947, 41, 5880.
(4) Hayashi, E.; Iijima, C. Yakugaku Zasshi. 1962, 82, 1093.
(5) Hamana, M. J. Pharm. Soc. Jpn. 1952, 71, 263.
(6) (a) Emerson, T. R.; Rees, C. W. J. Chem. Soc. 1962, 1917.
(b) Howard, E.; Olszewski, W. F. J. Am. Chem. Soc. 1959,
81, 1483.
(7) (a) Bonini, B. F.; Maccagnani, G.; Mazzanti, G.; Pedrini, P.
Tetrahedron Lett. 1979, 20, 1799. (b) Olah, G. A.;
Arvanaghi, M.; Vankar, Y. D. Synthesis 1980, 660.
(c) Achremowicz, L. Tetrahedron Lett. 1980, 21, 1675.
(d) Morita, T.; Kuroda, K.; Okamoto, Y.; Sakurai, H. Chem.
Lett. 1981, 921.
(8) (a) Kroehnke, F.; Schaefer, H. Chem. Ber. 1962, 95, 1098.
(b) Abramovitch, R. A.; Adams, K. H. A. Can. J. Chem.
1961, 39, 2134.
Synlett 2002, No. 2, 349–351 ISSN 0936-5214 © Thieme Stuttgart · New York