A facile and efficient deoxygenation of amine-N-oxides with Mo(CO) 6

Article abstract of DOI:10.1016/j.tetlet.2005.10.143

A variety of amine-N-oxides have been found to be selectively deoxygenated to the corresponding amines in high yields with Mo(CO)₆ in ethanol under mild conditions.

Full text of DOI:10.1016/j.tetlet.2005.10.143

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 125–126
A facile and efficient deoxygenation of amine-N-oxides
with Mo(CO)6
Byung Woo Yoo,* Jin Woo Choi and Cheol Min Yoon
Department of Advanced Materials Chemistry, Korea University, Jochiwon, Chungnam 339-700, South Korea
Received 5 September 2005; revised 17 October 2005; accepted 19 October 2005
Available online 15 November 2005
Abstract—A variety of amine-N-oxides have been found to be selectively deoxygenated to the corresponding amines in high yields
with Mo(CO)6 in ethanol under mild conditions.
Ó 2005 Elsevier Ltd. All rights reserved.
The deoxygenation of amine-N-oxides to amines has
oxides with Mo(CO)6. We envisaged that Mo(CO)6
could bring about the deoxygenation of amine-N-oxides
under mild conditions. A variety of amine N-oxides are
selectively deoxygenated to the corresponding amines in
high yields (80–96%) by simply heating the substrate in
the presence of stoichiometric quantity of Mo(CO)6
(Eq. 1) in ethanol.17 The results are presented in Table
1. The reactions proceed readily in all cases with sub-
strates reacting completely within 4 h in refluxing etha-
nol. In order to explore the scope and limitation of
this reagent, we have tested its applicability for selective
deoxygenation of amine-N-oxides bearing other poten-
tially sensitive functional groups in the heteroaromatic
ring. The functional group tolerance of this reagent is
evident from the table, which shows that nitrile, bromo,
chloro, hydroxy, ester and amide substituents remain
unchanged under the reaction conditions. We have been
able to demonstrate the utility of easily accessible
Mo(CO)6 as a convenient reagent for effecting chemo-
selective deoxygenation of various amine-N-oxides. All
the compounds obtained showed IR, NMR and mass
spectral data compatible with the structure. Although
the mechanism of the reaction is not yet clarified, it
can be rationalized as the result of a two-stage process.
A plausible mechanism for the reductive N–O bond
received much attention, being an important step in
the synthesis of heterocycles in many procedures.1
A
number of methods have been developed for the reduc-
tion of amine-N-oxides, including agents such as low-
valent titanium,2 phosphorous compounds,3 Zn/
HCOONH4,4 InCl3,5 tributyltinhydride,6 Pd/C,7 SmI2,8
tetrathiomolybdate,9 indium/NH4Cl.10 However, many
are associated with limitations regarding incompatibility
with other functional groups, low yields, harsh reaction
conditions and intricate procedures. In certain cases, the
reagents required are expensive. Therefore, there is still a
need for introducing selective, simple and cheap re-
agents for the deoxygenation of amine-N-oxides to
amines. We herein wish to report a simple and efficient
deoxygenation method for amine-N-oxides using the
cheap metal carbonyl, molybdenum hexacarbonyl
[Mo(CO)6] under mild conditions. The chemistry of
Mo(CO)6 is one of the current interests in organic syn-
thesis due to the ease of handling, mild reaction condi-
tions and availability (it is commercially available as a
stable crystalline solid).11 Particularly, Mo(CO)6 has
been used to reduce the N–O bonds of isoxazoles,12 isox-
azolines,13 isoxazolidines14 and 1,2-oxazines.15 The
selective reduction of azides, nitro compounds and
deoxygenation of epoxides have also been accom-
plished.16 To the best of our knowledge, there have been
no previous studies on the deoxygenation of amine-N-
Mo(CO)6
N
EtOH, reflux
N
ð1Þ
O
Keywords: Deoxygenation; Amine-N-oxides; Amine; Mo(CO)6.
*
Corresponding author. Tel.: +82 41 860 1338; fax: +82 41 867
5396; e-mail: bwyoo@korea.ac.kr
1
2
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.143

126
B. W. Yoo et al. / Tetrahedron Letters 47 (2006) 125–126
Table 1. Deoxygenation of amine-N-oxides with Mo(CO)6
In conclusion, we believe that the use of Mo(CO)6 offers
an attractive alternative to the currently available meth-
ods for the deoxygenation of amine-N-oxides to the cor-
responding amines. Further studies to develop other
new reactions using Mo(CO)6 are currently in progress.
Entry Substrate
Product
Time Yields
(h)
(%)a
1
2
3
Pyridine-N-oxide
Quinoline-N-oxide
Isoquinoline-N-oxide Isoquinoline
Pyridine
Quinoline
1.0
3.0
4.0
96
92
85
CH3
References and notes
CH3
4
5
6
1.0
2.0
2.0
90
95
92
N
N
1. Ochiai, E. In Aromatic Amine Oxides; Elsevier: Amster-
dam, 1967; pp 184–209.
2. (a) Emerson, T. R.; Ress, C. W. J. Chem. Soc. 1962, 1917;
(b) Howard, E., Jr.; Olszewski, W. F. J. Am. Chem. Soc.
1959, 81, 1483.
3. (a) Malinoswaki, M. Synthesis 1987, 732; (b) Balicki, R.
Chem. Ber. 1990, 647; (c) Balicki, R.; Kaczmarek, L.;
Malinnowski, M. Synth. Commun. 1989, 19, 897; (d) Yoo,
B. W.; Choi, J. W.; Kim, D. Y.; Hwang, S. K.; Choi, K. I.;
Kim, J. H. Bull. Korean Chem. Soc. 2002, 23, 797.
4. Balicki, R.; Cybulski, M.; Maciejewski, G. Synth. Com-
mun. 2003, 23, 4137.
5. Ilias, M. H.; Barman, D. C.; Prajapati, D.; Sandhu, J. S.
Tetrahedron Lett. 2002, 43, 1877.
6. (a) Kozuka, S.; Akasaka, K.; Furumai, T.; Dae, S. Chem.
Ind. (London) 1974, 452; (b) Jousseaume, B.; Chanson, E.
Synthesis 1987, 55.
7. Katritzky, A. R.; Monro, A. M. S. J. Chem. Soc. 1958,
1263.
8. Zhang, Y.; Lin, R. Synth. Commun. 1987, 17, 329.
9. Ilankumaran, P.; Chandrasekara, S. Tetrahedron Lett.
1995, 36, 4881.
O
CN
CN
N
N
O
Br
Br
N
N
O
N
7
8
1.0
2.0
85
83
Cl
Cl
N
N
N
O
OH
OH
N
O
CO2CH3
CONH2
CO2CH3
CONH2
10. Yadav, J. S.; Subba Reddy, B. V.; Muralidhar Reddy, M.
Tetrahedron Lett. 2000, 41, 2663.
N
9
1.0
2.0
82
80
O
11. (a) Harvey, D. F.; Sigano, D. M. Chem. Rev. 1996, 96,
271, and references cited therein; (b) Harvey, D. F.;
Brown, M. F. Tetrahedron Lett. 1990, 31, 2529; (c)
Barluenga, J.; Fananas, F. J. Tetrahedron 2000, 56, 4597;
(d) Shvo, Y.; Green, R. J. Organomet. Chem. 2003, 675,
77.
10
N
N
O
12. Nitta, M.; Kobayashi, T. J. Chem. Soc., Perkin Trans. 1
1985, 1401.
11
12
4.0
2.0
93
88
N
N
O
13. (a) Baraldi, P. G.; Barco, A.; Benneti, S.; Manfredini, S.;
Simoni, D. Synthesis 1987, 276; (b) Trost, B. M.; Li, L.;
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O
O
N
O
N CH3
CH3
a Isolated yields.
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cleavage of amine-N-oxide is outlined in Scheme 1, using
pyridine-N-oxide as the substrate. In the first step,
the reaction was assumed to proceed by loss of CO.
Then the oxygen of the amine-N-oxide coordinates to
Mo(CO)6 to give complex 3 and facilitate the N–O bond
cleavage. In a subsequent step, cleavage of the N–O
bond leads to the formation of the corresponding amine.
The notable advantages of the present procedure are the
ease of manipulation, the high yields, the mild reaction
conditions and the tolerance of several labile functional
groups.
17. A typical procedure for the deoxygenation of amine-N-
oxide is as follows: To a solution of 4-cyanopyridine-N-
oxide (120 mg, 1.0 mmol) in ethanol (10 mL) is added
Mo(CO)6 (264 mg, 1.0 mmol). The mixture was refluxed
for 2 h and monitored by TLC. After completion of the
reaction, the resulting mixture was concentrated under
reduced pressure, extracted with ether, concentrated and
the residue was purified by silica gel column chromato-
graphy (hexane/ethyl acetate = 1:1) to afford 4-cyanopyr-
idine (99 mg, 95%).
_
_
Mo(CO)6
O
O
Mo(CO)5
Mo(CO)5
N
N
O
N
_
_
+
+
CO
3
Scheme 1.