O-Alkylation of oxime with N-vinyl lactams induced by radical cation

Article abstract of DOI:10.1016/j.tetlet.2008.01.048

Radical cation promoted O-alkylation of oxime with N-vinyllactam was achieved under base free condition by using catalytic tris(4-bromophenyl)aminium cation radical (TBPA^{+ {radical dot}} SbCl₆^-) as an initiator to produce the corresponding oxime ether in high yields.

Full text of DOI:10.1016/j.tetlet.2008.01.048

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 1786–1789
O-Alkylation of oxime with N-vinyl lactams induced by radical cation
a,
a
a
b
b
*
Xiao-dong Jia , Yu-xia Da , Cai-xia Yang , Li Yang , Zhong-li Liu
a College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, PR China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
Received 2 December 2007; revised 28 December 2007; accepted 10 January 2008
Available online 15 January 2008
Abstract
Radical cation promoted O-alkylation of oxime with N-vinyllactam was achieved under base free condition by using catalytic
tris(4-bromophenyl)aminium cation radical (TBPAþÅSbCl6ꢀ) as an initiator to produce the corresponding oxime ether in high yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Oxime ethers are valuable nucleophilic reagents, with
both nitrogen and oxygen atoms as the nucleophile. The
addition of organometallic or radical species to oxime
ethers becomes more and more important in organic syn-
theses.1,2 Recently, the utility of oximes in transition-
metal-catalyzed allylic substitution3 and Michael addition4
has attracted more attention. Generally oxime ethers were
prepared from O-alkyl hydroxylamine and the correspond-
ing aldehyde. The direct preparation of oxime ethers from
oximes has been commonly limited to the reaction of oxi-
mes with alkyl halides under basic conditions,5 while under
acidic conditions byproducts of N-alkylation were inevita-
bly produced.3b Therefore, it is desirable to develop new
synthetic protocol for the preparation of oxime ethers
under neutral or acidic conditions.
On our ongoing research program on synthetic poten-
tials of cation radical induced reactions,6 we found recently
that aza-Diels–Alder reactions could be efficiently induced
by tris(4-bromophenyl)aminium cation radical (TBPAþÅ
SbCl6ꢀ) to accomplish the [4+2] cycloaddition of aromatic
imines with electron-rich olefins,6f,j the [3+2] cycloaddition
of chalcone epoxides with electron-rich olefins,6g and [3+2]
cycloaddition of chalcone epoxides with imines.6h We
report herein that TBPA+Å can also efficiently initiate the
O-alkylation of oximes with N-vinyl lactams producing
the corresponding oxime ethers in excellent yields.
An anhydrous CH2Cl2 solution (20 mL) of oxime (1,
1 mmol), N-vinyllactam (2, 1 mmol), and 2,6-di-tert-
butyl-pyridine (4, 0.1 mmol as base to inhibit acid-induced
reactions.) was added dropwise to a stirred solution of a
catalytic amount of tris(4-bromophenyl)aminium hexa-
chloroantimonate (TBPAþÅSbCl6ꢀ, 0.05 mmol) suspended
in anhydrous CH2Cl2 (20 mL) at ambient temperature.
The reaction completed within 10–15 min, giving exclu-
sively the corresponding oxime ethers 3 in excellent yield.
In the reaction, the oxygen of oxime 1 was added regio-
selectively to the double bond of N-vinyllactam 2. Simple
column chromatographic purification (silica gel, hexane/
acetone 10:1) gave the pure products 3 (Scheme 1), which
was fully identified by MS, 1HNMR, 13CNMR, and
HRMS.7 The results are listed in Table 1.
Diversified oximes 1 with either electron-withdrawing or
electron-donating substituent were synthesized to test the
generality of this methodology. It is seen from Table 1 that
all the oximes reacted with 2 smoothly giving exclusively
the corresponding O-alkyl oxime ethers in excellent yield,
and no N-alkylation products were detected. Electron-
donating groups (CH3, CH3O, entries 7–10) seem pro-
pitious to the addition giving extremely high yield, since
they increase the nucleophilicity of the oxime, and hence
facilitate its addition to the N-vinyllactam radical cation
(vide infra).
*
Corresponding author. Tel.: +86 931 797 1533; fax: +86 931 7971 989.
E-mail address: jiaxd1975@163.com (X. Jia).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.048

X. Jia et al. / Tetrahedron Letters 49 (2008) 1786–1789
1787
n
n
TBPA+.
R
O
R
N
O
CH2Cl2, r.t.
N
N
base 4
N
OH
O
1
2
3
2a, n=1
2b, n=3
Scheme 1.
Table 1
TBPAþÅSbCl6 initiated addition of oxime 1 with N-vinyllactam 2
chain addition with 2 as the electrophile and the catico-
gen10 as depicted in Scheme 2. In Scheme 2, 2 is preferen-
tially oxidized by TBPA+Å giving the corresponding
cation radical 2+Å. The oxygen of 1 adds regioselectively
to the a-carbon of the C@N bond of 2+Å, affording a dis-
tonic cation radical adduct 5. Cation radical 6 undergoes
the second electron transfer with 2 to produce product 3.
This second electron transfer produces a new 2+Å to prop-
agate the radical chain reaction.
ꢀ
Entry
Substrates
R
Products
Yielda (%)
2
1
2
3
4
5
6
7
8
9
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
H
H
NO2
NO2
Cl
2a
2b
2a
2b
2a
2b
2a
2b
2a
2b
3a
3b
3c
3d
3e
3f
84
82
84
87
89
85
96
98
94
92
Cl
To extend the generality of this reaction, ketone oxime
7, 2-furaldehyde oxime 8, and 2-pyridinecarboxaldehyde
oxime 9 were chosen to react with 2 (Scheme 3, Table 2).
It was found that acetophenone and 2-furaldehyde oximes
could smoothly react with N-vinyllactams 2a and 2b, but
the reaction of 2-pyridinecarboxaldehyde oxime (9) with
2 was relatively slow and the yield was lower. It is because
of the fact that the presence of the pyridine ring can accel-
erate the rate of decomposition of TBPAþÅSbCl6ꢀ, presum-
ably by removing protons from cation radicals generated in
the reaction of 9 and 2.11
CH3
CH3
CH3O
CH3O
3g
3h
3i
10
a
3j
Isolated yields based on 1.
We have reported previously that the oxidation poten-
tial of the substrates exerts remarkable effect on the radical
cation reaction.6f,j The smooth reaction of 1 with 2 again
supports this criterion because the oxidation potential of
2 (ꢁ1.12 V vs SCE)6i is significantly lower than the oximes
(1.77–2.14 V vs Ag/AgCl electrode).8 We also tried the
reaction of 1 with other alkenes, such as a-methylstyrene
(Eox = 1.72 V vs SCE)6f and cyclohexene,9 whose oxida-
tion potentials are significantly higher than 2. No reaction
took place but a little bit of decomposition products of 1
were isolated. In case excessive N-vinyllactam 2 was used,
small amount of the dimer of 2 would be isolated. There-
fore, this reaction can be rationalized as a cation radical
In conclusion, TBPAþÅSbCl6 can effectively initiate the
ꢀ
addition of oxime with N-vinyllactams, producing the
corresponding oxime ethers in excellent yield. In compari-
son with the previously reported methods, this approach is
superior in terms of using catalytic amount of initiator
(5 mol %), mild reaction conditions (ambient temperature
and completed within 10–15 min), high yields, and espe-
cially avoiding the use of strong base. Further extension
of this protocol is in progress.
n
n
+.
TBPA
TBPA
O
HO
N
1
O
N
Ar
N
2+.
2
n
n
O
2
2+.
O
N
N
- H+
Ar
N
3
Ar
N
+ H
O
O
H
5
6
Scheme 2.

1788
X. Jia et al. / Tetrahedron Letters 49 (2008) 1786–1789
n
O
n
N
TBPA+.
O
O
O
N
N
N
O
OH
Base 4, CH2Cl2, r.t.
10
7
2
n
n
O
N
TBPA+.
N
N
OH
N
O
O
O
N
Base 4, CH2Cl2, r.t.
O
11
8
2
n
n
O
N
TBPA+.
N
N
OH
N
Base 4, CH2Cl2, r.t.
N
12
9
2
Scheme 3.
Table 2
4. Bhuniya, D.; Moban, S.; Narayanan, S. Synthesis 2003, 1018.
5. (a) Bull, S. D.; Davies, S. G.; Domingez, S. H.; Jones, S.; Price, A. J.;
Sellers, T. G. R.; Thomas, G. R.; Smith, A. D. J. Chem. Soc., Perkin
Trans. 1 2002, 2141; (b) Davis, S. G.; Fox, J. F.; Jones, S.; Price, A. J.;
Sanz, M. A.; Sellers, T. G. R.; Smith, A. D.; Teixeira, F. C. J. Chem.
Soc., Perkin Trans. 1 2002, 1757; (c) Koenig, S. G.; Leonard, K. A.;
Lowe, R. S.; Austin, D. J. Tetrahedron Lett. 2000, 41, 9393.
6. (a) Jin, M. Z.; Yang, L.; Wu, L. M.; Liu, Y. C.; Liu, Z. L. Chem.
Commun. 1998, 2451; (b) Mao, Y.-Z.; Jin, M. Z.; Liu, Z. L.; Wu, L.
M. Org. Lett. 2000, 2, 741; (c) Jin, M. Z.; Zhang, D.; Yang, L.; Liu,
Y. C.; Liu, Z. L. Tetrahedron Lett. 2000, 41, 7357; (d) Zhang, W.; Jia,
X. D.; Yang, L.; Liu, Z. L. Tetrahedron Lett. 2002, 43, 9433; (e)
Zhang, J.; Jin, M. Z.; Zhang, W.; Yang, L.; Liu, Z. L. Tetrahedron
Lett. 2002, 43, 9687; (f) Jia, X. D.; Lin, H. C.; Huo, C. D.; Zhang,
TBPAþÅSbCl6 initiated addition of ketone and hetero-aromatic aldehyde
ꢀ
oxime 7–9 with N-vinyllactam 2
Entry
Substrates
2
Products
Yielda (%)
1
2
3
4
5
6
a
7
7
8
8
9
9
2a
2b
2a
2b
2a
2b
10a
10b
11a
11b
12a
12b
87
81
90
92
82
61
Isolated yields based on 1.
W.; Lu, J. M.; Yang, L.; Zhao, G. Y.; Liu, Z. L. Synlett 2003, 1707;
(g) Huo, C. D.; Jia, X. D.; Zhang, W.; Yang, L.; Lu, J. M.; Liu, Z. L.
¨
¨
References and notes
Synlett 2004, 251; (h) Huo, C. D.; Wei, R.; Zhang, W.; Yang, L.; Liu,
Z. L. Synlett 2005, 161; (i) Zhang, W.; Guo, Y. P.; Liu, Z. G.; Jin, X.
L.; Yang, L.; Liu, Z. L. Tetrahedron 2005, 61, 1325; (j) Jia, X. D.;
Han, B.; Zhang, W.; Jin, X. L.; Yang, L.; Liu, Z. L. Synthesis 2006,
2831.
1. (a) Miyabe, H.; Yamaoka, Y.; Naito, T.; Takemoto, Y. J. Org. Chem.
2003, 68, 6745; (b) Hanessian, S.; Lu, P. P.; Sanceau, J. Y.; Chemla,
P.; Gohda, K.; Fonne-Pfiser, R.; Prade, L.; Cowan-Jacob, S. W.
Angew. Chem., Int. Ed. 1999, 38, 3159; (c) Bernardi, L.; Cere, V.;
Femoni, C.; Pollicino, S.; Ricci, A. J. Org. Chem. 2003, 68, 3348; (d)
Kakiya, H.; Yagi, K.; Shinokubo, H.; Oshima, K. J. Am. Chem. Soc.
2002, 124, 9032; (e) Moody, C. J.; Lightfoot, A. P.; Gallagher, P. T.
Synlett 1997, 659; (f) Marco, J. A.; Carda, M.; Murga, J.; Gonzalez,
F.; Falomir, E. Tetrahedron Lett. 1997, 38, 1841.
2. (a) Kim, S.; Song, H. J.; Choi, T. L.; Yoon, J. Y. Angew. Chem., Int.
Ed. 2001, 40, 2524; (b) Miyabe, H.; Ueda, M.; Yashioka, N.;
Yamakawa, K.; Naito, T. Tetrahedron 2000, 56, 2413; (c) Miyabe, H.;
Ueda, M.; Nishimura, A.; Naito, T. Org. Lett. 2002, 4, 131; (d)
Miyabe, H.; Ushiro, C.; Naito, T. Chem. Commun. 2000, 1789; (e)
Miyabe, H.; Ueda, M.; Naito, T. Synlett 2004, 1140; (f) Mcnabb, S.
B.; Ueda, M.; Naito, T. Org. Lett. 2004, 6, 1911; (g) Ryu, I.;
Kuriyama, H.; Minakata, S.; Komatsu, M.; Yoon, J.-Y.; Kim, S. J.
Am. Chem. Soc. 1999, 121, 12190.
7. General procedure for TBPA+Å induced reaction of oximes 1 and N-
vinyl lactams 2: An anhydrous CH2Cl2 solution (20 mL) of oxime (1,
1 mmol), N-vinyl lactam (2, 1 mmol) and 2,6-di-tert-butylpyridine (4,
0.1 mmol) was added dropwise to a CH2Cl2 solution (20 mL) of a
catalytic amount of tris-(4-bromophenyl)aminium hexachloroanti-
monate (TBPAþÅSbCl6ꢀ, 0.05 mmol) at ambient temperature under
stirring. After completion of the reaction as monitored by TLC
(10 min), the reaction was quenched with sodium carbonate meth-
anol solution. The mixture was poured into a separator funnel with
the addition of excess methylene chloride, and then the crude
organic solution was extracted three times with water to remove
inorganic salts. The organic phase was then dried over anhydrous
magnesium sulfate, filtered, and the solvent was removed under
reduced pressure and the products were separated by silica gel
column chromatography eluted with hexane/acetone (v/v 10:1) to
afford the pure oxime ether as the unique product. Representative
spectral data of the products (E)-O-1-(2-Oxopyrrolidin-1-yl)-ethyl-4-
methyl-benzaldehyde oxime (3g): Colorless oil. 1H NMR (300 MHz,
CDCl3): d 1.35 (d, J = 6.3 Hz, 3H), 1.82–1.92 (m, 2H), 2.23 (s, 3H),
3. (a) Miyabe, H.; Matsumura, A.; Yoshida, K.; Yamauchi, M.;
Takemoto, Y. Synlett 2004, 2123; (b) Miyabe, H.; Yoshida, K.;
Reddy, V. K.; Matsumura, A.; Takemoto, Y. J. Org. Chem. 2005, 70,
5630; (c) Miyabe, H.; Matsumura, A.; Moriyama, K.; Takemoto, Y.
Org. Lett. 2004, 6, 4631.

X. Jia et al. / Tetrahedron Letters 49 (2008) 1786–1789
1789
2.27–2.32 (m, 2H), 3.30–3.34 (m, 2H), 6.02 (q, J = 6.3 Hz, 1H), 7.04
(d, J = 7.5 Hz, 2H), 7.36 (d, J = 7.5 Hz, 2H), 7.92 (s, 1H). 13C NMR
(100 MHz, CDCl3): d 16.7, 17.8, 21.2, 31.4, 41.3, 80.0, 126.9, 128.9,
129.1, 140.0, 149.2, 175.3. EI-MS m/z (rel. int., %): 135 (4.4), 113
(7.9), 112 (100). HR-ESI-MS: Calcd for C14H18N2O2H+: 247.1441;
found: 247.1439.
8. De Lijser, H. J. P.; Hsu, S.; Marquez, B. V.; Park, A.; Sanguantrakun,
N.; Sawyer, J. R. J. Org. Chem. 2006, 71, 7785.
9. Yoshida, K.; Kanbe, T.; Fueno, T. J. Org. Chem. 1977, 42, 2313.
10. Bauld, N. L. Tetrahedron 1989, 45, 5307.
11. Gassman, P. G.; Singleton, D. A. J. Am. Chem. Soc. 1984, 106,
7994.