Copper(II) triflate-mediated addition reaction of α-oxygenated alkylsilanes to imines for the synthesis of vicinal-amino alcohols

Article abstract of DOI:10.1080/00397910600781117

In the presence of copper(II) triflate, the addition reaction of α-oxygenated alkylsilanes to several imines proceeded smoothly to give the corresponding vicinal-amino alcohols in moderate yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600781117

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Copper(II) Triflate–Mediated Addition
Reaction of α‐Oxygenated Alkylsilanes to
Imines for the Synthesis of Vicinal‐Amino
Alcohols
Hirotaka Kagoshima a & Kohtaro Yonezawa a
a Center for Instrumental Analysis , Ibaraki University , Mito, Japan
Published online: 27 Oct 2006.
To cite this article: Hirotaka Kagoshima & Kohtaro Yonezawa (2006) Copper(II) Triflate–Mediated Addition
Reaction of α‐Oxygenated Alkylsilanes to Imines for the Synthesis of Vicinal‐Amino Alcohols, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:17,
2427-2432, DOI: 10.1080/00397910600781117
To link to this article: http://dx.doi.org/10.1080/00397910600781117
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Synthetic Communicationsw, 36: 2427–2432, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600781117
Copper(II) Triflate–Mediated Addition
Reaction of a-Oxygenated Alkylsilanes to
Imines for the Synthesis of Vicinal-Amino
Alcohols
Hirotaka Kagoshima and Kohtaro Yonezawa
Center for Instrumental Analysis, Ibaraki University, Mito, Japan
Abstract: In the presence of copper(II) triflate, the addition reaction of a-oxygenated
alkylsilanes to several imines proceeded smoothly to give the corresponding vicinal-
amino alcohols in moderate yields.
Keywords: Addition reaction, copper(II) triflate, imine, a-oxygenated alkylsilane,
vicinal-amino alcohol
Vicinal-amino alcohols and their derivatives have received considerable
attention because of their versatility as synthetic intermediates in organic
synthesis.[1] We have been interested in the development of new methods
for the synthesis of nitrogen-containing compounds from the reaction
between organometallic compounds and imines[2–6] and recently reported
the addition reaction of a-oxygenated alkylstannanes to imines leading to
vicinal-amino alcohol derivatives [Eq. (1)].[5] The reaction was effectively
mediated by Cu(OTf)2 to afford the addition products in good yields. Here,
if less toxic a-oxygenated alkylsilanes react with imines instead of the
stannanes, the reaction becomes an environmentally benign process. In
addition, our interest in the comparison of reactivity between the silanes
and the stannanes led us to investigate the reaction. We report herein a new
Received in Japan December 19, 2005
Address correspondence to Hirotaka Kagoshima, Center for Instrumental Analysis,
Ibaraki University, 2-1-1 Bunkyo, Mito, Ibaraki 310-8512, Japan. E-mail: hkago@mx.
ibaraki.ac.jp
2427

2428
H. Kagoshima and K. Yonezawa
addition reaction of a-oxygenated alkylsilanes to imines mediated by
Cu(OTf)2, leading to vicinal-amino alcohols.
We initially examined the reaction of 1a with 2a[7,8] under various con-
ditions to optimize the reaction conditions (Table 1). (These a-oxygenated
alkylsilanes were prepared by modifications of the literature procedures
for the analogous silanes.) As shown in entry 1, the reaction did not take
place at all, and 1a and 2a remained unchanged under similar conditions
applied in Eq. (1), suggesting that silane 1a is less reactive than the corre-
sponding stannane.[5] To overcome the low reactivity of 1a, the reaction was
carried out under reflux in CH2Cl2 (entry 2). Although the desired product
3a was obtained in 42% yield with minimal diastereoselectivity, the reaction
was still sluggish (entry 2). Fortunately, the rate of the reaction could be
greatly accelerated by refluxing at higher temperature using 1,2-dichloro-
ethane as a solvent while maintaining moderate yield (entry 3). Next, we
examined the effect of mediators and found that Cu(OTf)2 was the most
Table 1. Effect of mediators and solvents in the reaction of 1a with 2aa
Time
(h)
Yield
(%)
Entry
Solvent
CH2Cl2
CH2Cl2
Mediator
Syn:anti
1b
2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Sc(OTf)3
AgOTf
24
20
3
0
42
46
0
—
54:46
49:51
—
3
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
Benzene
4
6
5
6
0
—
—
.
BF3 OEt2
6
6
0
7
Me3SiOTf
Sn(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
6
0
—
—
8
6
0
9
1.5
2
32
28
7
57:43
54:46
47:53
—
10
11
12
Toluene
Tetrahydrofuran
CH3CN
6
6
0
aMolar ratio 1a–2a–mediator,1.0:1.0:1.0.
bThe reaction was performed at room temperature.

Table 2. Effect of substituents in 1a
1
3
Entry
SiR13
SiMe3
SitBuMe2
SiMe2Ph
SiMe3
R2
R3
Compound
Time (h)
Compound
Yield (%)
Syn:anti
1
2
3
4
5
6
7
H
H
H
nPr
nPr
nPr
nPr
nPr
iPr
1a
1b
1c
1d
1e
1f
3
3a
3a
3a
3a
3a
3b
3c
46
46
39
32
39
21
0
49:51
42:58
57:43
47:53
57:43
54:46
—
3
5
SiMe3
SitBuMe2
4
SiMe3
SiMe3
SiMe3
6
H
H
5
0.25
Ph
1g
aMolar ratio 1–2a–Cu(OTf)2, 1.0:1.0:1.0.

Table 3. Reactions of 1a with imines 2a
2
3
Entry
R4
R5
Compound
Time (h)
Compound
Yield (%)
Syn:anti
1
2
3
4
6
7
p-MeOC6H4
p-MeC6H4
p-ClC6H4
Ph
Ph
Ph
Ph
Ph
2a
2b
2c
2d
2e
2f
3
4
3
4
6
4
3a
3d
3e
3f
46
48
45
47
45
41
49:51
51:49
56:44
56:44
61:39
55:45
Ph
Ph
p-MeC6H4
p-ClC6H4
3g
3h
aMolar ratio 1a–2–Cu(OTf)2, 1.0:1.0:1.0.

Copper(II) Triflate–Mediated Addition Reaction
2431
promising among the mediators examined. The use of other mediators such
.
as Sc(OTf)3, AgOTf, BF3 OEt2, Me3SiOTf, and Sn(OTf)2 gave no product
(entries 4–8). Finally, the optimized conditions were determined after
surveying solvents (entries 3 and 9–12); 1,2-dichloroethane was the best
solvent from the viewpoints of both the reaction rate and yield (entry 3).
We next performed the addition reaction of a series of silanes 1a–g[7,8]
with 2a under the optimized reaction conditions to clarify the scope and limit-
ation of the present reaction. The results are summarized in Table 2. Not only
trimethylsilyl-substituted silane 1a but both t-butyldimethylsilyl- and
dimethylphenyl-substituted silanes, 1b and 1c, reacted with 2a to give 3a in
moderate yields (entries 2 and 3). When O-silylated silanes 1d and 1e were
used, 3a was obtained instead of the corresponding O-silylated products
(entries 4 and 5). Silane 1f, which has an isopropyl group at the a-carbon,
also underwent the addition reaction (entry 6), whereas a reaction using
silane 1g gave no product (entry 7).
The reactions of 1a with several imines 2a–f were carried out under the
optimized conditions (Table 3). As can be seen from Table 3, 1a smoothly
reacted with aromatic imines to give the corresponding vicinal-amino
alcohols in moderate yields.
In summary, we have developed a new addition reaction of a-oxygenated
alkylsilanes to imines in the presence of Cu(OTf)2. The present reaction
provides a new method for the synthesis of vicinal-amino alcohols.
EXPERIMENTAL
General Procedure (Table 3, Entry 1)
To a mixture of 2a (21 mg, 0.10 mmol) and Cu(OTf)2 (36 mg, 0.10 mmol) in
1,2-dichloroethane (1.5 mL) was added 1a (15 mg, 0.10 mmol) in 1,2-
dichloroethane (0.5 mL) at room temperature. After being stirred for 3 h
under reflux, the reaction was quenched with saturated aqueous NaHCO3.
After a usual workup, the crude product was purified by TLC (AcOEt–
hexane 1/5) to give 3a (13 mg, 46%, syn:anti ¼ 49:51).
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