BF3-promoted hydrostannation of N-heteroatom-substituted imines for the reduction of C=N bond

Article abstract of DOI:10.1016/S0040-4039(02)00785-2

Hydrostannation of N-heteroatom-substituted imines such as oxime ethers, hydrazones, oximes, nitrones, and N-sulfonyl imines using a combination of Bu₃SnH and BF₃·OEt₂ has been systematically studied. Not only aromatic aldimines but also kitimines and aliphatic imines were reduced to give the corresponding amines.

Full text of DOI:10.1016/S0040-4039(02)00785-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 4369–4371
BF3-promoted hydrostannation of N-heteroatom-substituted
imines for the reduction of CꢀN bond
Masafumi Ueda, Hideto Miyabe, Megumi Namba, Toshiki Nakabayashi and Takeaki Naito*
Kobe Pharmaceutical University, Motoyamakita, Higashinada, Kobe 658-8558, Japan
Received 29 March 2002; revised 15 April 2002; accepted 19 April 2002
Abstract—Hydrostannation of N-heteroatom-substituted imines such as oxime ethers, hydrazones, oximes, nitrones, and N-sulfo-
nyl imines using a combination of Bu3SnH and BF3·OEt2 has been systematically studied. Not only aromatic aldimines but also
kitimines and aliphatic imines were reduced to give the corresponding amines. © 2002 Elsevier Science Ltd. All rights reserved.
Organotin hydrides are known as a mild reagent for the
reduction of aldehydes and ketones by hydrostanna-
tion, and a variety of useful methods have been avail-
able.1,2 In contrast, the corresponding hydrostannation
of imine derivatives has not been widely studied. Baba’s
group have shown, in their series of papers, that the
reduction of N-alkyl or N-aryl imines with organotin
hydrides or dibutyltin halide hydrides was promoted by
the addition of Lewis bases such as HMPA, Bu4NX
and so on. They have successfully extended the reaction
to reductive amination of aldehydes and ketones,
chemoselective reduction of imino group in the pres-
ence of carbonyl group, and tandem reductive amina-
tion-Michael reaction.3 However, the hydrostannation
of imines activated by Lewis acids has not been stud-
ied.4 Herein we wish to report the BF3-promoted
hydrostannation of imines providing a new efficient
method for the reduction of CꢀN bond.
substituted imines is that the resulting N-heteroatom-
substituted amines can be readily converted to primary
amines by cleavage of the nitrogen-heteroatom bond.6
We initially investigated the hydrostannation of benzal-
doxime ether 1a (Scheme 1). Among several Lewis acids
evaluated, BF3·OEt2 was found to be most effective for
the hydrostannation of 1a using Bu3SnH.7 To a solu-
tion of oxime ether 1a in CH2Cl2 were added BF3·OEt2
(1 equiv.) and a commercially available Bu3SnH (2
equiv.), and then the reaction mixture was stirred at
room temperature for 2 h. As expected, the reaction
proceeded smoothly to give the desired alkoxyamine 2a
in 95% yield (Table 1, entry 1). When the reaction was
carried out in the presence of 0.5 equiv. of BF3·OEt2,
alkoxyamine 2a was obtained in 27% yield and 69%
yield of starting material 1a was recovered (entry 2). In
the absence of BF3·OEt2, the reaction did not proceed
(entries 3 and 4); thus, 1 equiv. of BF3·OEt2 is necessary
for completing hydrostannation of 1a, because
BF3·OEt2 is trapped by the nitrogen atom of both the
starting material and the product. When the freshly-dis-
tilled Bu3SnH was employed, the reaction proceeded
smoothly even with 1 equiv. of Bu3SnH to give 2a in
95% yield (entry 5).8
The imines of choice were N-heteroatom-substituted
imines such as oxime ethers, hydrazones, oximes,
nitrones, and N-sulfonyl imines, since they have been
shown to be stable and useful even for aqueous-
medium reaction in our recent studies on radical reac-
tions.5 Additionally, the advantage of N-heteroatom-
We next examined the hydrostannation of hydrazone,
oxime, nitrone, and sulfonyl imine 1b–e in the presence
of BF3·OEt2 (Scheme 2, Table 2).
Bu3SnH
NOBn
Ph
NHOBn
Ph
BF3•OEt2
1a
2a
In the presence of 1 equiv. of BF3·OEt2, the hydrostan-
nation of hydrazone 1b having two nitrogen atoms was
less effective to give the corresponding hydrazine 2b in
65% yield (entry 1). In the case of hydrazone 1b, 2
equiv. of BF3·OEt2 were required for completing the
Scheme 1.
Keywords: reduction; imines; oximes; hydrazones; nitrones.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00785-2

4370
M. Ueda et al. / Tetrahedron Letters 43 (2002) 4369–4371
Table 1. Hydrostannation of oxime ether 1a
Entry
Solvent
Bu3SnH (equiv.)
BF3·OEt2 (equiv.)
Temp. (°C)
Yield (%)a
1
2
3
4
5
CH2Cl2
CH2Cl2
CH2Cl2
MeOH
CH2Cl2
2
2
2
1
0.5
0
0
1
20
20
20
Reflux
20
95
27 (69)
No reaction
No reaction
95
1
1b
a Yields in parentheses were for the starting material.
b The reaction was carried out with freshly-distilled Bu3SnH.
hydrostannation (entries 2 and 3). Only a modest chem-
ical yield was observed in the reaction of oxime 1c,
presumably due to the formation of unidentified com-
plex formed from oxime 1c and Bu3SnH in the presence
of BF3·OEt2 (entry 4). The reaction of nitrone 1d
proceeded smoothly to give the corresponding amine 2d
in 84% yield (entry 5). In contrast, N-sulfonyl imine 1e
exhibited an excellent reactivity toward Bu3SnH even in
the absence of BF3·OEt2, because of the higher reactiv-
ity of CꢀN bond by electron-withdrawing substituent
on nitrogen atom (entry 6).
Ketimine derivatives 3a–d worked well under similar
reaction conditions using BF3·OEt2 (Scheme 3, Table
3). In the case of ketoxime ether 3a and hydrazone 3b,
more than 2 equiv. of BF3·OEt2 were required for
completing the reactions (entries 1 and 2).9 The reaction
of N-sulfonyl ketimine 3d proceeded smoothly even in
the absence of BF3·OEt2 to give the corresponding
amine 4d in 99% yield (entry 4).
We finally investigated hydrostannation of aliphatic
imine derivatives 5 and 7 (Scheme 4). The reactions of
pentanal oxime ether 5 proceeded slowly to give
alkoxyamine 6 in 76% yield,10 accompanied with 23%
yield of the starting compound 5. Modest chemical
yield was obtained in the reaction of aliphatic ketoxime
ether 7.
Bu3SnH
NR
Ph
NHR
Ph
BF3•OEt2
In conclusion, we have developed a new method for
reduction of N-heteroatom-substituted imine deriva-
tives via hydrostannation using Bu3SnH and BF3·OEt2.
The reaction could apply to not only aromatic aldimine
derivatives but also aromatic ketimines, providing a
2b-e
1b-e
Scheme 2.
Table 2. Hydrostannation of N-heteroatom-substituted
imines 1b–ea
Table 3. Hydrostannation of N-heteroatom-substituted
imines 3a–da
Entry
Substrate
BF3·OEt2
(equiv.)
Product
Yield
(%)
Entry
Substrate
BF3·OEt2
(equiv.)
Product
Yield
(%)
1
1b: NR=NNPh2
1b: NR=NNPh2
1b: NR=NNPh2
1c: NR=NOH
1
2
2
1
1
0
2b
2b
2b
2c
65
76
92
48
84
98
1
2
3
4
3a: R=NOBn
3b: R=NNPh2
3c: R=NOH
3d: R=NTs
3
2
1
0
4a
4b
4c
4d
97
99
70
99
2
3b
4
5
6
1d: NR=N+(O−)Bn
1e: NR=NTs
2dc
2e
a The reactions were carried out with Bu3SnH (2 equiv.) in CH2Cl2 at
20°C for 2 h.
a The reactions were carried out with Bu3SnH (2 equiv.) in CH2Cl2 at
20°C for 2 h.
b The reaction was carried out with freshly-distilled Bu3SnH (1
equiv.) in CH2Cl2 at 20°C for 2 h.
Bu3SnH (2 eq)
NOBn
n-Bu
NHOBn
n-Bu
BF3•OEt2 (2 eq)
c Product 2d is PhCH2NH(OH)CH2Ph.
5
6
CH2Cl2
76% (23%)
Bu3SnH (2 eq)
BF3•OEt2 (2 eq)
CH2Cl2
Me
NOBn
Me
NHOBn
Me
Bu3SnH
Ph
NHR
Me
4a-d
Ph
NR
Me
3a-d
BF3•OEt2
Me
7
8
42% (41%)
Scheme 3.
Scheme 4.

M. Ueda et al. / Tetrahedron Letters 43 (2002) 4369–4371
4371
useful route for synthesis of a variety of primary amines
from the corresponding carbonyl compounds.
1998, 54, 11431–11444. Friestad’s group also reported the
hydrostannation of N-acylhydrazone as aside-reaction in
radical reaction: Friestad, G. K.; Qin, J. J. Am. Chem.
Soc. 2000, 122, 8329–8330.
5. (a) Miyabe, H.; Ueda, M.; Naito, T. J. Org. Chem. 2000,
65, 5043–5047; (b) Miyabe, H.; Ueda, M.; Naito, T.
Chem. Commun. 2000, 2059–2060.
Acknowledgements
6. The cleavage of nitrogen–oxygen bond had been carried
This research was supported by a Grant-in-aid for
Scientific Research (C) from the Ministry of Education,
Culture, Sports, Science and Technology of Japan and
the research grant from the Science Research Promo-
tion Fund of the Japan Private School Promotion
Foundation.
out by LiAlH4 , Mo(CO)6 and hydrogenolysisc. (a)
Kiguchi, T.; Tajiri, K.; Ninomiya, I.; Naito, T. Tetra-
hedron 2000, 56, 5819–5833; (b) Miyabe, H.; Ushiro, C.;
Ueda, M.; Yamakawa, K.; Naito, T. J. Org. Chem. 2000,
65, 176–185; (c) Miyabe, H.; Fujii, K.; Goto, T.; Naito,
T. Org. Lett. 2000, 2, 4071–4074.
a
b
7. In the presence of other Lewis acids (InCl3, MgBr2 or
Yb(OTf)3), the hydrostannation of 1a did not proceed
under the similar reaction conditions.
References
8. Procedure for hydrostannation of 1a (Table 1, entry 5):
To a solution of oxime ether 1a (50 mg, 0.24 mmol) in
CH2Cl2 (5 mL) were added BF3·OEt2 (0.03 mL, 0.24
mmol) and Bu3SnH (0.06 mL, 0.24 mmol). After being
stirred under a nitrogen atmosphere at 20°C for 2 h, the
reaction mixture was diluted with saturated aqueous
NaHCO3 and extracted with CH2Cl2. The organic phase
was dried over MgSO4 and concentrated at reduced
pressure. Purification of the residue by preparative TLC
(hexane:AcOEt=15:1) afforded 2a (48.5 mg, 95%) as a
colorless oil.
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9. Spectral data of 4b: 1H NMR (CDCl3): l 1.39 (3H, d,
J=6.0 Hz), 4.04 (1H, q, J=6.0 Hz), 4.16 (1H, br s),
6.92–7.42 (10H, m). 13C NMR (CDCl3): l 21.0, 56.8,
120.3, 122.1, 127.2, 127.3, 128.3, 128.9, 143.3, 147.7.
HRMS: calcd for C20H20N2 (M+) 288.1626, found
288.1637.
1
10. Spectral data of 6: H NMR (CDCl3): l 0.89 (3H, br t,
J=6.0 Hz), 1.20–1.60 (6H, m), 2.93 (2H, t, J=7.0 Hz),
4.71 (2H, s), 7.28–7.40 (5H, m). 13C NMR (CDCl3): l
13.9, 22.4, 26.9, 29.2, 52.1, 76.1, 127.6, 128.2, 137.9.
HRMS: calcd for C12H19NO (M+) 193.1466, found
193.1481.
4. We recently reported the hydrostannation of oxime ether
as a side-reaction in radical reaction: Miyabe, H.; Shi-
bata, R.; Sangawa, M.; Ushiro, C.; Naito, T. Tetrahedron