Copper(ii) triflate-mediated addition reaction of α-oxygenated alkylstannanes to imines for the synthesis of vicinal-amino alcohol derivatives

Article abstract of DOI:10.1246/cl.2003.514

In the presence of copper(II) triflate, a novel addition reaction of α-oxygenated alkylstannanes to various kinds of imines proceeded smoothly to give the corresponding vicinal-amino alcohol derivatives in good yield.

Full text of DOI:10.1246/cl.2003.514

514
Chemistry Letters Vol.32, No.6 (2003)
Copper(II) Triflate-mediated Addition Reaction of ꢀ-Oxygenated Alkylstannanes to Imines
for the Synthesis of vicinal-Amino Alcohol Derivatives
Hirotaka Kagoshimaà and Kohei Shimada
Center for Instrumental Analysis, Ibaraki University, 2-1-1 Bunkyo, Ibaraki 310-8512
(Received March 10, 2003; CL-030213)
In the presence of copper(II) triflate, a novel addition reac-
tion of a-oxygenated alkylstannanes to various kinds of imines
proceeded smoothly to give the corresponding vicinal-amino al-
cohol derivatives in good yield.
At the outset, imine 1a and a-oxygenated alkylstannanes 2a
were chosen as substrates in the search for optimum conditions,
and we examined the effect of Lewis acids in the reaction. The
results are summarized in Table 1. When 1a (1.0 equiv.) and 2a
(1.0 equiv.) were treated with a Lewis acid (1.0 equiv.) such as
BF3ÁOEt2, TMSOTf, Sn(OTf)2, and SnCl4 in CH2Cl2, no alky-
lated product was detected (Entries 1–4). In contrast, use of
either Sc(OTf)3 or AgOTf afforded 3a in moderate yields (En-
tries 5 and 6). Upon screening various Lewis acids, it was found
that yields highly depended on the Lewis acid used and
Cu(OTf)2 was the most effective in this reaction (Entry 7). It
should be noted that the 1-(methoxymethoxy)butyl group was
selectively transferred from the stannane to the imine; no buty-
lated product could be detected in the reaction mixture. In all
cases, disappointingly, negligible diastereoselectivity was ob-
served.
Next, the reactions of 1a with a series of a-oxygenated al-
kylstannanes 2a–d6 were carried out under the influence of
Cu(OTf)2 in order to investigate the effect of the substituent
on the oxygen atom in the stannanes (Entries 7–10). As a result,
it was found that tert-butyldimethylsilyl-substituted stannane 2b
reacted more smoothly with 1a to give 3b and the yield was
comparable to that of 3a (Entry 8). Use of either acetyl- or
methyl-substituted stannanes gave inferior results (Entries 9
and 10). Because variation in the substituent on the oxygen
atom revealed that the tert-butyldimethylsilyl group was super-
ior with regard to reaction rate and yield, tert-butyldimethylsi-
lyl-substituted stannanes were used in further experiments.
a-Oxygenated allylstannanes are useful reagents for intro-
ducing an oxygenated allylic unit upon treatment with electro-
philes.1 For example, Lewis acid-mediated addition reaction of
a-oxygenated allylstannanes to aldehydes offers a general route
to a variety of vicinal-diol derivatives.2 Furthermore, the stereo-
chemistry in these reactions has been well studied by using chir-
al a-oxygenated allylstannanes, and these compounds have
been used for the synthesis of optically active vicinal-diol de-
rivatives.2d,2e In contrast, little has been known about the syn-
thetic utility of a-oxygenated alkylstannanes as nucleophiles
in carbon–carbon bond forming reactions,3 presumably due to
their lower nucleophilicity relative to the corresponding allyl-
stannanes.
As a part of our continuing interest in the development of
synthetic methodology using imines,4 we focused on the reac-
tion of a-oxygenated alkylstannanes with imines leading to vic-
inal-amino alcohol derivatives.5 Herein we would like to report
the first example of the reaction of a-oxygenated alkylstannanes
with imines mediated by Cu(OTf)2, which successfully affords
the corresponding vicinal-amino alcohol derivatives in good
yield.
Table 1. Effects of Lewis acids and substituents R1 and R2 in 2a
HNPMP
R2
NPMP
OR1
SnnBu3
2a-i
Lewis acid
CH2Cl2, rt
+
Ph
R2
Ph
OR1
3a-i
1a
2
3
Entry
Lewis acid
time/h
R1
R2
yield/%
0
syn:antib
—
—
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
BF3ÁOEt2
TMSOTf
Sn(OTf)2
SnCl4
Sc(OTf)3
AgOTf
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
MOM
MOM
MOM
MOM
MOM
MOM
MOM
TBS
Ac
Me
TBS
TBS
nPr
nPr
nPr
nPr
nPr
nPr
nPr
nPr
nPr
nPr
iPr
tBu
H
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
24
24
24
24
24
24
24
12
24
24
12
12
12
6
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
0
0
0
—
—
48
33
61
63
24
27
40
27
6
50:50
53:47
52:48
51:49
53:47
48:52
51:49
70:30
—
TBS
TBS
TBS
2g
2h
2i
3g
3h
3i
Ph
TBSO(CH2)2
42
42
55:45
43:57
12
aPMP = 4-methoxyphenyl; MOM = methoxymethyl; TBS = tert-butyldimethylsilyl; Ac = acetyl. bDetermined by 400 MHz 1H NMR.
Copyright Ó 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.6 (2003)
515
Table 2. Cu(OTf)2-mediated addition reaction of 2b to various imines
O
1) nBu4NF, THF, 83%
HNPMP
nPr
HNR3
NR3
PMPN
Ph
O
OTBS
Cu(OTf)2
nPr
Ph
R4
2) (Cl3CO)2CO, Et3N, CH2Cl2, quant.
+
nPr
SnnBu3
nPr
R4
OTBS
CH2Cl2, rt
H H
trans-4
= 6.2 Hz
OTBS
3b,k-u
syn-3b
1a-l
2b
J
1
3
O
Entry
time/h
R3
R4
yield/% syn:antia
1) nBu4NF, THF, 83%
HNPMP
nPr
1
2
3
4
5
6
7
8
9
4-MeOC6H4 Ph
4-MeC6H4 Ph
1a
1b
1c
12 3b
63
74
80
80
68
68
59
44
37
58
22
82
51:49
49:51
45:55
50:50
48:52
48:52
47:53
51:49
48:52
49:51
51:49
47:53
PMPN
Ph
O
Ph
5
3
3
4
4
5
7
5
8
3k
3l
2) (Cl3CO)2CO, Et3N, CH2Cl2, 86%
nPr
OTBS
anti-3b
4-ClC6H4
Ph
H H
cis-4
= 8.1 Hz
Ph
Ph
Ph
Ph
4-MeOC6H4 1d
4-MeC6H4 1e
4-ClC6H4
Ph
3m
3n
3o
3p
3q
3r
3s
J
1f
1g
1h
1i
1j
1k
1l
Scheme 2. Determination of the relative configurations of 3b.
4-MeOC6H4 2-furyl
4-MeOC6H4 2-thienyl
low yield (Entry 11). Gratifyingly, when an a-imino ester 1l
was used in the reaction with 2b, the highest yield was achieved
(Entry 12). Thus, the present reaction can be applied to the
synthesis of a-amino-b-silyloxy esters.
10 4-MeOC6H4 E-styryl
11 4-MeOC6H4 c-hexyl
12 4-MeOC6H4 EtO2C
18 3t
24 3u
In conclusion, we have developed a copper(II) triflate-
mediated addition reaction of a-oxygenated alkylstannanes to
imines. The present reaction provides new methodology for
the synthesis of vicinal-amino alcohol derivatives. We are cur-
rently investigating the scope of this process using other a-het-
eroatom-substituted alkylstannanes.
aDetermined by 400 MHz 1H NMR.
Several tert-butyldimethylsilyl-substituted stannanes 2e–i6
were prepared and employed in the addition reaction with 1a
(Table 1, Entries 11-15). As can be seen from Entries 8, 11,
and 12, it is clear that yields of the products were lowered as
the alkyl substituent on the a-carbon atom became bulkier. It
is noted that moderate syn diastereoselectivity was observed
when bulky stannane 2f was used (Entry 12). Not only steric
factors but also electronic factors might be important because
sterically less demanding 2g reacted with 1a to give 3g in
low yield (Entry 13), whereas the reaction of sterically hindered
2j6 with 1a proceeded to afford 3j in good yield (Scheme 1).
We anticipated that a; g-dioxygenated alkylstannane 2i would
react with 1a to produce a highly functionalized amino diol de-
rivative. Indeed, the desired product 3i could be obtained in
good yield (Entry 15).
This work was partially supported by the Grant-in-Aid for
Young Scientists (B) from Japan Society for the Promotion of
Science, the Pfizer Pharmaceuticals Award in Synthetic Organic
Chemistry, Japan, and the Mitsubishi Chemical Corporation
Fund.
References and Notes
1
a) J. A. Marshall, Chem.Rev. , 96, 31 (1996). b) J. A. Marshall, in ‘‘Or-
ganometallics in Synthesis, A Manual,’’ ed. by M. Schlosser, John Wi-
ley & Sons, Chichester (2002), Chap. 2, p 353.
2
a) J.-P. Quintard, B. Elissondo, and M. Pereyre, J.Org.Chem. , 48,
1559 (1983). b) J.-P. Quintard, G. Dumartin, B. Elissondo, A. Rahm,
and M. Pereyre, Tetrahedron, 45, 1017 (1989). c) J. A. Marshall and
W. Y. Gung, Tetrahedron Lett., 30, 309 (1989). d) J. A. Marshall
and K. W. Hinkle, J.Org.Chem. , 60, 1920 (1995). e) J. A. Marshall
and K. W. Hinkle, J.Org.Chem. , 61, 105 (1996).
The relative configurations of 3b were determined by con-
version of 3b into the corresponding oxazolidinones 4 and com-
1
parison of their H NMR coupling constants with the values of
analogous oxazolidinones on the basis of the fact that cis-oxa-
zolidinones exhibit larger values than trans-isomers (Scheme
2).8 For other adducts, the relative configurations were deter-
mined by similar derivations and/or on the basis of the 1H
NMR analogy with 3b.
Table 2 summarizes the results of the reactions of various
kinds of imines 1a-l with 2b.9 As can be seen from Table 2,
imines prepared from aromatic aldehydes and aromatic amines
smoothly reacted with 2b to afford the corresponding vicinal-
amino alcohol derivatives in good yields (Entries 1–7). Imines
prepared from heteroaromatic aldehydes also furnished the cor-
responding adducts (Entries 8 and 9). An a; b-unsaturated imine
1j also worked well. Compared with aromatic- and a; b-unsatu-
rated imines, use of an alkyl-substituted imine 1k resulted in
3
4
a) M. Kosugi, T. Sumiya, T. Ogata, H. Sano, and T. Migita, Chem.
Lett., 1984, 1225. b) M. Kosugi, T. Sumiya, K. Ohhashi, H. Sano,
and T. Migita, Chem.Lett. , 1985, 997. c) J. Ye, R. K. Bhatt, and J.
R. Falck, J.Am.Chem.Soc. , 116, 1 (1994).
a) H. Kagoshima and T. Akiyama, J.Am.Chem.Soc. , 122, 11741
(2000). b) H. Kagoshima, T. Okamura, and T. Akiyama, J.Am.Chem.
Soc., 123, 7182 (2001). c) H. Kagoshima, T. Uzawa, and T. Akiyama,
Chem.Lett. , 2002, 298.
5
6
S. C. Bergmeier, Tetrahedron, 56, 2561 (2000).
These a-oxygenated alkylstannanes were prepared by modifications of
the literature procedures for analogous a-oxygenated allyl- and al-
kylstannanes.3c,7
a) R. J. Linderman and A. Ghannam, J.Org.Chem. , 53, 2878 (1988).
b) R. J. Linderman and A. Ghannam, J.Am.Chem.Soc. , 112, 2392
(1990). c) J. A. Marshall, A. W. Garofalo, and K. W. Hinkle, Org.
Synth., 77, 98 (1999).
7
8
9
a) Y. Yamamoto and M. Schmid, J.Chem.Soc,. Chem.Commun.
,
1989, 1310. b) J. A. Marshall, K. Gill, and B. M. Seletsky, Angew.
Chem., Int. Ed., 39, 953 (2000).
SnnBu3
A typical experimental procedure (Table 2, Entry 1): To a mixture of
1a (21 mg, 0.10 mmol) and Cu(OTf)2 (36 mg, 0.10 mmol) in CH2Cl2
(1 mL) was added 2b (48 mg, 0.10 mmol) in CH2Cl2 (0.5 mL) at room
temperature. After being stirred for 12 h at this temperature, the reac-
tion was quenched with saturated aqueous NaHCO3. After a usual work
up, the crude product was purified by TLC (CH2Cl2/hexane = 3/4) to
give the mixture of diastereomers 3b (25 mg, 63%, syn:anti = 51:49).
HNPMP
TBSO
NPMP
Cu(OTf)2
+
Ph
TBSO
Ph
CH2Cl2, rt, 3 h, 56%
3j
1a
2j
Scheme 1. Cu(OTf)2-mediated addition reaction of 2j to 1a.
Published on the web (Advance View) May 13, 2003; DOI10.1246/cl.2003.514