Regioselective Allylation of Carbon Electrophiles with Alkenyl-silanes under Dual Catalysis by Cationic Platinum(II) Species

Article abstract of DOI:10.1055/s-0035-1560380

In the presence of catalytic amounts of platinum(II) chloride and silver(I) hexafluoroantimonate, (Z)-alkenylsilanes reacted with various carbon electrophiles (acetals, aminals, carboxylic anhydrides, alkyl chlorides, etc.) at the γ-position to give allylation products. A plausible mechanism for the platinum-catalyzed allylation involves alkene migration of alkenylsilanes to allylsilanes and subsequent allylation of carbon electrophiles, both of which are catalyzed by a cationic platinum(II) species.

Full text of DOI:10.1055/s-0035-1560380

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2016, 48, 520–534
paper
520
H. Kinoshita et al.
Paper
Synthesis
Regioselective Allylation of Carbon Electrophiles with Alkenyl-
silanes under Dual Catalysis by Cationic Platinum(II) Species
Hidenori Kinoshitaa
Ryosuke Kizua
Masahiro Horikoshia
Gen Inoueb
Masayuki Fujimotob
Masanori Saitoa
Junji Ichikawab
Akira Hosomib
Katsukiyo Miura*a
X
X
R1
R1
X
R2
or
cat. PtCl2-AgSbF6
+
SiMe3
or
R3
R3
R2
PtII
PtII
R1
R1
Y
R2
SiMe3
X = OMe, NHCO2Me
Y = OMe, OCOR', Cl
R2
a Department of Applied Chemistry, Graduate School of Science
and Engineering, Saitama University, Sakura-ku, Saitama 338-
8570, Japan
kmiura@apc.saitama-u.ac.jp
b Division of Chemistry, Faculty of Pure and Applied Sciences,
University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
Received: 12.10.2015
Accepted after revision: 05.11.2015
Published online: 16.12.2015
act at the γ-position as allyl donors. This is quite different
from the usual reactivity of alkenylsilanes, which in most
cases react with electrophiles at the α-position as alkenyl
donors.1b,c This unusual reactivity is reasonably explained
by platinum(II)-catalyzed alkene migration leading to allyl-
silane intermediates.13,14 Thus, our interest focused on the
platinum(II)-catalyzed intermolecular allylation of carbon
electrophiles with alkenylsilanes (Scheme 1, lower equa-
tion). Since alkenylsilanes can be easily prepared from ter-
minal alkynes and alkenes,15–17 we envisioned that the tar-
get reaction would make silicon-based nucleophilic allyla-
tion more accessible and atom-economical. We herein
report full details of platinum(II)-catalyzed allylation using
alkenylsilanes.18,19
DOI: 10.1055/s-0035-1560380; Art ID: ss-2015-f0600-op
Abstract In the presence of catalytic amounts of platinum(II) chloride
and silver(I) hexafluoroantimonate, (Z)-alkenylsilanes reacted with vari-
ous carbon electrophiles (acetals, aminals, carboxylic anhydrides, alkyl
chlorides, etc.) at the γ-position to give allylation products. A plausible
mechanism for the platinum-catalyzed allylation involves alkene migra-
tion of alkenylsilanes to allylsilanes and subsequent allylation of carbon
electrophiles, both of which are catalyzed by a cationic platinum(II) spe-
cies.
Key words acetals, alkenylsilanes, allylation, allylsilanes, tandem reac-
tion, platinum catalysis
The nucleophilic allylation of carbon electrophiles is
one of the most important transformations in fine organic
synthesis. Allylsilanes are widely and frequently used for
this purpose since they have several advantages over other
available allylmetals.1 A large number of methods for the
preparation of allylsilanes have been developed because of
the great synthetic utility of allylsilanes;2–11 in recent years,
much attention has been paid to their synthesis from unac-
tivated alkenes.8–10 However, continuous development is re-
quired for more efficient, rapid, and atom-economical al-
lylation by allylsilanes.
previous work: intramolecular allylation
O
R1
OH
cat. PtCl2-AgOTf
SiMe3
R1CHO
+
γ
α
PhMe, r.t. or 45 °C
β
cat. Pt2+
OH
R1CHO
O
R1
cat. Pt2+
SiMe3
SiMe3
this work: intermolecular allylation
cat. PtCl2-AgSbF6
DCE, 70 °C
E
We have previously reported the platinum(II)-catalyzed
annulation of hydroxy-substituted alkenylsilanes with al-
dehydes via intramolecular allylation (Scheme 1, upper
equation).12 Under platinum(II) catalysis, alkenylsilanes re-
+
SiMe3
E X
R2
R2
E = carbon electrophile
Scheme 1 Previous work and this work
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 520–534

521
H. Kinoshita et al.
Paper
Synthesis
We initially attempted the reaction of benzaldehyde
with alkenylsilane 2a under catalysis by platinum(II) chlo-
ride with silver(I) triflate (PtCl2–2AgOTf), however no al-
lylation product was obtained. In contrast, benzaldehyde
dimethyl acetal (1a) smoothly reacted with 2a to give the
allylation product 3aa in 78% yield with syn diastereoselec-
tivity (Table 1, entry 1).20,21 Silver(I) hexafluoroantimonate
also served as an effective cocatalyst although silver(I)
tetrafluoroborate and silver(I) hexafluorophosphate were
not as effective (entries 2–4). Without the cocatalyst, the al-
lylation did not occur (entry 5). Using silver(I) hexafluoro-
antimonate at 40 °C gave 3aa in high yield (entry 8). An effi-
cient allylation was achieved even with reduced amounts of
2a (1.2 equiv), platinum(II) chloride (5 mol%), and silver(I)
hexafluoroantimonate (10 mol%) at 70 °C (entry 9). With-
out platinum(II) chloride, silver(I) hexafluoroantimonate
did not promote the allylation (entry 10). The reaction with
(E)-2a was rather slow and resulted in a low yield of 3aa
with 60% recovery of (E)-2a (entry 11).
ture of products within two hours; this is probably due to
the instability of the allylation product 3ga since the elec-
tron-donating effect of the p-methoxy group makes the
benzylic C–O bond reactive under these Lewis acidic condi-
tions. Shortening the reaction time enabled the isolation of
3ga in low yield (entry 7). The allylation of acetals 1h and
1i, derived from aliphatic aldehydes, proceeded in moderate
yields (entries 8 and 9).
Table 2 Allylation of Various Acetals 1 with Alkenylsilane 2aa
PtCl2 (5 mol%)
AgSbF6 (10 mol%)
OMe
OMe
OMe
SiMe3
(CH2)8Me
+
R1
R1
DCE, 70 °C
(CH2)8Me
1
2a (1.2 equiv)
3
Entry Sub-
R1
Time (h) Product Yieldb
(%)
Ratioa
syn/anti
strate 1
1
1a
1b
1c
1d
1e
1f
Ph
4
10
10
24
24
4
3aa
3ba
3ca
3da
3ea
3fa
84
83
93
92
76
74
26
65
58
63:37
71:29
73:27
70:30
68:32
40:60
47:53
82:18
54:46
2
4-ClC6H4
4-BrC6H4
4-MeO2CC6H4
4-O2NC6H4
4-MeC6H4
4-MeOC6H4
Cy
Table 1 Optimization of Reaction Conditions for Allylation of Acetal 1a
with Alkenylsilane 2aa
3
4
5
PtCl2 (10 mol%)
AgX (20 mol%)
OMe
OMe
OMe
6d
7
SiMe3
(CH2)8Me
+
Ph
3aa
CH2Cl2 or DCE
Ph
1g
1h
1i
0.5
3ga
3ha
3ia
(CH2)8Me
1a
2a (2 equiv)
8
2
1
9d
(CH2)7Me
Entry
AgX
Temp
(°C)
Time
(h)
Isolated
yield (%) syn/anti
Ratiob
a Reaction conditions: 1 (0.5 mmol), 2a (0.6 mmol), PtCl2 (0.025 mmol),
AgSbF6 (0.05 mmol), DCE (1.5 mL), 70 °C.
b Isolated yield.
1
2
AgOTf
AgSbF6
AgPF6
AgBF4
–
r.t.
r.t.
r.t.
r.t.
r.t.
40
70
40
70
70
70
24
24
24
24
24
12
1.5
10
4
78
60
28
8
63:37
73:27
72:28
70:30
–
c Determined by 1H NMR analysis.
d With PtCl2 (0.05 mmol) and AgSbF6 (0.1 mmol).
3
Functionalized alkenylsilanes also served as substrates
in the platinum(II)-catalyzed allylation (Equation 1). γ-Phe-
nyl-substituted alkenylsilane 2b was sufficiently reactive
for the allylation of 1a. The reaction with alkenylsilanes 2c
and 2d, bearing an oxygen functionality, gave ethers 3ac
and 3ad, respectively, in moderate yields.
4
5
0
6
AgOTf
AgOTf
AgSbF6
AgSbF6
AgSbF6
AgSbF6
71
72
89
84
0
64:36
61:39
74:26
63:37
–
7
8
9c
10d
11e
PtCl2 (5 mol%)
OMe
24
24
OMe
OMe
AgSbF6 (10 mol%)
SiMe3
+
25f
61:39
Ph
DCE, 70 °C
R2
Ph
R2
a Reaction conditions: 1a (0.5 mmol), 2a (Z/E >98:2, 1 mmol), PtCl2 (0.05
mmol), AgX (0.1 mmol), CH2Cl2 (1.5 mL, entries 1–5) or DCE (1.5 mL, en-
tries 6–11).
1a
2 (1.2 equiv)
3
2b R2 = Ph
4 h
24 h
24 h
3ab, 75%, syn/anti = 70:30
3ac, 61%, syn/anti = 70:30
3ad, 65%, syn/anti = 69:31
b Determined by 1H NMR analysis.
2c R2 = (CH2)3OMe
2d R2 = (CH2)3OBz
c With 2a (0.6 mmol), PtCl2 (0.025 mmol), and AgSbF6 (0.05 mmol).
d Without PtCl2.
e The E-isomer of 2a [(E)-2a, Z/E 3:97] was used.
f (E)-2a was recovered in 60% yield.
Equation 1 Allylation with alkenylsilanes 2
In the allylation of 1a with 2a (Table 2, entry 1), the for-
mation of allylsilane 4a, a regioisomer of 2a, was observed.
This implies that the allylation proceeds by alkene migra-
tion of 2a14 to 4a and subsequent allylation with 4a.22 To as-
certain this postulation, we first examined alkene migra-
tion of 2a. When 2a was treated with a catalytic amount of
With the optimized conditions (Table 1, entry 9) in
hand, the scope of the acetal was investigated (Table 2).
Acetals 1b–f efficiently underwent the platinum(II)-cata-
lyzed allylation with 2a to afford homoallylic ethers 3ba–fa
(entries 2–6). Acetal 1g was converted into a complex mix-
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522
H. Kinoshita et al.
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Synthesis
either platinum(II) chloride or silver(I) hexafluoroantimon-
ate, the isomerization of 2a to 4a did not occur. The com-
bined use of platinum(II) chloride and silver(I) hexafluoro-
antimonate effectively promoted the isomerization to give
4a (E/Z 86:14) with (E)-2a and other isomers formed by
further alkene migration (Equation 2). We next examined
the allylation of 1a with 4a. A catalytic amount of either
platinum(II) chloride or silver(I) hexafluoroantimonate did
not catalyze the allylation of 1a. In contrast, the combina-
tion of platinum(II) chloride with silver(I) hexafluoroanti-
monate achieved an efficient allylation of 1a with syn selec-
tivity (Equation 3). These results prove that the allylation
mechanism involves a consecutive isomerization–allylation
process, in which a cationic platinum(II) species generated
from platinum(II) chloride and silver(I) hexafluoroantimon-
ate promotes both steps (Scheme 2). The allylation step
would involve the formation of oxocarbenium ion A by acti-
vation of the acetal C–O bond.23
Allylation of acetals with allylsilanes provides good ac-
cess to homoallylic ethers. However, commercially available
acetals are rather limited, and the synthesis of acetals from
aldehydes is usually required. Therefore much attention has
focused on the Lewis or Brønsted acid catalyzed three-com-
ponent coupling of aldehydes, alkoxy donors (silyl ethers,
orthoformates, or alcohols), and allylsilanes as a direct ac-
cess to homoallylic ethers.25,26 For the efficient and rapid
synthesis of homoallylic ethers, the use of aldehydes and a
methoxy donor instead of acetals 1 is also an attractive op-
tion for the present allylation. Thus we investigated the
platinum(II)-catalyzed three-component coupling reaction
using alkenylsilanes as allylsilane equivalents.
We selected trimethyl orthoformate as the methoxy do-
nor and examined the reaction of benzaldehyde (5a),
trimethyl orthoformate, and 2a. Expectedly, under catalysis
by platinum(II) chloride and silver(I) hexafluoroantimona-
te, 5a reacted with trimethyl orthoformate and 2a succes-
sively to give homoallylic ether 3aa in good yield (Table 3,
entry 1). Aromatic aldehydes 5b–e also underwent efficient
three-component coupling (entries 2–5). The reaction of 4-
methoxybenzaldehyde (5g) resulted in a low yield of 3ga
(entry 6). Increasing the reaction time led to a complex
mixture of products by further reaction of 3ga, which
would be promoted by the electron-donating effect of the
p-methoxy group (vide supra). The coupling of an α-
branched aliphatic aldehyde 5h proceeded more efficiently
than that of a linear aldehyde 5i (entries 7 and 8). Function-
alized alkenylsilanes are also available for the platinum(II)-
catalyzed three-component coupling (entries 9–11).
The present allylation is not useful for the stereoselec-
tive synthesis of homoallylic ethers. We expected that the
syn selectivity could be improved by conducting the allyla-
tion step at a low temperature.21 Therefore, a one-pot al-
lylation by a two-step method with an additional Lewis
acid was attempted (Table 4). The first step is the plati-
num(II)-catalyzed isomerization of 2 to 4 in 1,2-dichlo-
roethane at 70 °C, and the second step is the boron trifluo-
ride–diethyl ether complex promoted allylation of 1 with 4
at –30 °C. When the second step was conducted in acetoni-
trile, the allylation of 1a with 2a gave 3aa in 96% yield with
87% syn selectivity (entry 1).23 Retaining the 1,2-dichlo-
roethane solvent from the first step in the second step (no
acetonitrile) results in a drop in the syn selectivity to 81%.
Other acetals, except 1g, underwent efficient allylation
with reasonable stereoselectivity (entries 2, 3, 5, and 6).
The reaction of 1g resulted in a moderate yield of 3ga, but
with good syn selectivity (entry 4). Functionalized alkenyl-
silanes were successfully applied in the stepwise allylation
(entries 7–11). The platinum(II)-catalyzed isomerization of
2b to allylsilane 4b was rather slower than that of other
alkenylsilanes. Under catalysis by platinum(II) chloride
(0.025 mmol) and silver(I) hexafluoroantimonate (0.05
mmol) at 70 °C for 20 hours, the conversion of 2b (1.6
PtCl2 (5 mol%)
AgSbF6 (10 mol%)
SiMe3
(CH2)8Me
2a
SiMe3
+
+
others
(E)-2a
DCE, 70 °C
15 min
(CH2)8Me
4a
2a / (E)-2a / 4a / other isomers / dodec-1-ene =
1.7 : 3.5 : 83.5 : 9.9 : 1.4 (molar ratio of products)
Equation 2 Isomerization of alkenylsilane 2a
PtCl2 (5 mol%)
AgSbF6 (10 mol%)
OMe
OMe
OMe
+
4a*
Ph
DCE, 70 °C, 4 h
Ph
(1 equiv)
(CH2)8Me
3aa, 99%, syn/anti = 70:30
1a
* 80 wt% pure: 2a / (E)-2a / 4a / other isomers / dodec-1-ene =
4.1 : 3.2 : 78 : 7.1 : 7.7 (molar ratio)
Equation 3 Allylation of acetal 1a with allylsilane 4a
OMe
+
Me
H
Pt2+
OMe
OMe
O
MeOPt+
+
R1
R1
R2
R1
R2
+
1
A
3
cat. Pt2+
Me3SiOMe
+
SiMe3
R2
SiMe3
Pt2+
2
4
Scheme 2 A plausible mechanism for the platinum(II)-catalyzed allyla-
tion of acetals 1 with alkenylsilanes 2
The low reactivity of (E)-2a comes from slow isomeriza-
tion of (E)-2a to 4a (Table 1, entry 11). It is known that the
coordinating ability of (Z)-but-2-ene to a platinum(II) com-
plex is 1.9 times higher than that of (E)-but-2-ene.24 The
geometric difference in coordinating ability as well as the
molecular strain caused by the Z-geometry may facilitate
the isomerization of 2a.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 520–534

523
H. Kinoshita et al.
Paper
Synthesis
Table 3 Three Component Coupling of Aldehydes, Trimethyl Ortho-
formate, and Alkenylsilane 2a
Table 4 Stepwise Allylation of Acetals 1 with Alkenylsilane 2a
PtCl2 (2.5 mol%)
AgSbF6 (5 mol%) BF3•OEt2 (1.2 equiv)
R1CH(OMe)2 (1)
OMe
PtCl2 (10 mol%)
OMe
R1CHO (5)
SiMe3
R2
2 (1.6 equiv)
R1
AgSbF6 (20 mol%)
DCE, 70 °C, 2 h
MeCN, –30 °C, 6 h
+
SiMe3
R1
R2
DCE, 70 °C, 0.5–2 h
HC(OMe)3
(1.2 equiv)
3
R2
R2
2 (1.2 equiv)
3
Entry Substrates R1
R2
Product Yieldb Ratioc
1 + 2
(%)
syn/anti
Entry Substrates R1
R2
Product Yieldb Ratioc
5 + 2
(%)
syn/anti
1
1a + 2a
1c + 2a
1e + 2a
1g + 2a
1h + 2a
1i + 2a
1a + 2b
1a + 2c
1a + 2e
1a + 2f
1a + 2g
Ph
(CH2)8Me
3aa
3ca
3ea
3ga
3ha
3ia
96
87:13
87:13
88:12
93:7
1d
2
5a + 2a
5b + 2a
5c + 2a
5d + 2a
5e + 2a
5g + 2a
5h + 2a
5i + 2a
5a + 2b
5a + 2c
5a + 2e
Ph
(CH2)8Me
3aa
3ba
3ca
3da
3ea
3ga
3ha
3ia
78
60:40
63:37
68:32
70:30
72:28
24:76
80:20
70:30
63:37
70:30
74:26
2
4-BrC6H4
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
Ph
95
96
65
94
90
89
90
90
73
93
4-ClC6H4
4-BrC6H4
4-MeO2CC6H4
4-O2NC6H4
4-MeOC6H4
Cy
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
Ph
84
86
88
78
36
69
35
64
50
46
3
4-O2NC6H4
3
4
4-MeOC6H4
4
5
Cy
92:8
5
6
(CH2)7Me
88:12
87:13
87:13
87:13
86:14
89:11
7d
8e
9e
Ph
Ph
Ph
Ph
Ph
3ab
3ac
3ae
3af
6
7
(CH2)3OMe
(CH2)3OAc
(CH2)3Cl
(CH2)3Phth
8
(CH2)7Me
Ph
9
3ab
10
11
10
11
Ph
(CH2)3OMe 3ac
(CH2)3OAc 3ae
3ag
a Reaction conditions: 1st step: 2 (1.6 mmol), PtCl2 (0.025 mmol), AgSbF6
(0.05 mmol), DCE (3 mL), 70 °C, 2 h; 2nd step: 1 (1 mmol), BF3·OEt2 (1.2
mmol), MeCN (3 mL), –30 °C, 6 h.
Ph
a Reaction conditions: 5 (0.5 mmol), HC(OMe)3 (0.6 mmol), 2 (0.6 mmol),
PtCl2 (0.05 mmol), AgSbF6 (0.1 mmol), DCE (1.5 mL), 70 °C. Reaction time:
0.5 h (entries 6 and 7), 1 h (entries 8 and 10), 1.5 h (entry 11), 2 h (other
entries).
b Isolated yield.
c Determined by 1H NMR analysis.
d The reaction time of the first step was 20 h. The second step was carried
out with half amounts of 1a (0.5 mmol) and BF3·OEt2 (0.6 mmol).
e With PtCl2 (0.011 mmol) and AgSbF6 (0.022 mmol).
b Isolated yield.
c Determined by 1H NMR analysis.
d With PtCl2 (0.025 mmol) and AgSbF6 (0.05 mmol).
forded homoallylic amines 7 in good to high yields (entries
1–5). In contrast, aliphatic aminal 6h did not reacted with
2a (entry 6). When boron trifluoride–diethyl ether complex
was used for the allylation of 6h, homoallylic amine 7ha
mmol) into 4b was only 59%. This is the reason for the pro-
longed first step and the increased (relative) amount of 2b
in entry 7.
Our attention next focused on the platinum(II)-cata-
lyzed allylation of aminals. The reaction of aminal 6a, de-
rived from benzaldehyde and methyl carbamate,27 with
alkenylsilane 2a was selected for optimization of the reac-
tion conditions (Table 5). With 10 mol% platinum(II) chlo-
ride and 20 mol% silver(I) hexafluoroantimonate (PtCl2–
2AgSbF6), the allylation of 6a proceeded smoothly at 70 °C
to give homoallylic amine 7aa in good yield (entry 1). Al-
though a decrease in the catalyst loading decelerated the al-
lylation, the yield was retained by increasing the reaction
time (entries 2–4). The use of 2.5 mol% platinum(II) catalyst
gave a satisfying result (entry 3). In comparison with acetal
allylation, smaller amounts of platinum(II) chloride and sil-
ver(I) hexafluoroantimonate are sufficient for aminal al-
lylation. This may result from the thermal stability of 7aa,
which enables prolonged reaction without decomposition
of the product. Both platinum(II) chloride and silver(I)
hexafluoroantimonate are also essential for this allylation
(entries 5 and 6).
Table 5 Optimization of Reaction Conditions for Allylation of Aminal
6a with Alkenylsilane 2aa
cat. PtCl2
cat. AgSbF6
NHCO2Me
NHCO2Me
SiMe3
(CH2)8Me
+
Ph
DCE, 70 °C
Ph
NHCO2Me
6a
(CH2)8Me
2a (1.2 equiv)
7aa
Entry
PtCl2
(mol%)
AgSbF6
(mol%)
Time
(h)
Yieldb
(%)
Ratioc
syn/anti
1
2
3
4
5
6
10
5
20
10
5
5
85
72:28
70:30
72:28
74:26
–
10
24
48
4
90
90
76
0
2.5
1
2
10
0
0
10
48
0
–
a Reaction conditions: 6a (1 mmol), 2a (Z/E >98:2, 1.2 mmol), DCE (3 mL),
With the optimized conditions in hand (Table 5, entry
3), the scope of aminal 6 and alkenylsilane 2 was examined
(Table 6). The allylation of aromatic aminals 6 with 2a af-
70 °C.
b Isolated yield.
c Determined by 1H NMR analysis.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 520–534

524
H. Kinoshita et al.
Paper
Synthesis
was formed in good yield with reasonable syn selectivity
(entry 7). Alkenylsilanes other than 2a are also applicable
to the allylation of 6a (entries 8–10).
ble 7, entry 1). The use of an increased amount of 2a (2
equiv) was quite effective in improving the yield (entry 2).
The reactions of aldehydes 5c and 5e, bearing an electron-
withdrawing group, successfully proceeded under the mod-
ified conditions (entries 3 and 4). Aldehydes 5f and 5g,
bearing an electron-donating group, were coupled with
methyl carbamate and 2a in low to moderate yields (entries
5 and 6). In these cases, the products 7fa and 7ga gradually
decomposed probably due to the reaction of the benzylic
C–N bond activated by the electron-donating groups. Al-
though the reaction of aminal 6h did not result in the for-
mation of 7ha (Table 6, entry 6), the coupling of aldehyde
5h to 7ha was observed (entry 7).
Table 6 Allylation of Various Aminals 6 with Alkenylsilanes 2a
PtCl2 (2.5 mol%)
AgSbF6 (5 mol%)
NHCO2Me
NHCO2Me
NHCO2Me
SiMe3
+
R1
R1
R2
DCE, 70 °C, 24 h
R2
6
7
2 (1.2 equiv)
Entry Substrates R1
R2
Product Yieldb Ratioc
6 + 2
(%)
syn/anti
1
2
3
4
5
6
7d
8
9
6a + 2a
6c + 2a
6e + 2a
6f + 2a
6g + 2a
6h + 2a
6h + 2a
6a + 2b
6a + 2h
6a + 2i
Ph
(CH2)8Me
7aa
7ca
7ea
7fa
90
72:28
70:30
75:25
72:28
62:38
–
4-BrC6H4
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
Ph
93
90
86
74
0
Table 7 Three-component Coupling of Aldehydes, Methyl Carbamate,
and Alkenylsilane 2aa
4-O2NC6H4
4-MeC6H4
PtCl2 (2.5 mol%)
AgSbF6 (5 mol%)
NHCO2Me
R1CHO (5)
4-MeOC6H4
7ga
7ha
7ha
7ab
SiMe3
(CH2)8Me
2a (2 equiv)
+
R1
DCE, 70 °C, 24 h
Cy
Cy
Ph
Ph
Ph
H2NCO2Me
(1.2 equiv)
(CH2)8Me
7
76
60
62
86
85:15
50:50
75:25
70:30
Entry
Substrate R1
5
Product
Yieldb
(%)
Ratioc
syn/anti
(CH2)3OTIPS 7ah
Mee
7ai
10
1d
2
3
4
5
6
7
5a
5a
5c
5e
5f
Ph
7aa
7aa
7ca
7ea
7fa
54
74:26
72:28
72:28
76:24
71:29
54:46
85:15
a Reaction conditions: 6 (1 mmol), 2 (1.2 mmol), PtCl2 (0.025 mmol), AgSbF6
(0.05 mmol), DCE (3 mL), 70 °C.
Ph
83
81
88
58
34
21
b Isolated yield.
4-BrC6H4
4-O2NC6H4
4-MeC6H4
4-MeOC6H4
Cy
c Determined by 1H NMR analysis.
d BF3·OEt2 (1 mmol) was used as an additive.
e With 2i (2 mmol).
5g
5h
7ga
7ha
A plausible mechanism for the platinum(II)-catalyzed
allylation of aminals 6 involves the formation of iminium
ion intermediates B by the action of a cationic platinum(II)
species (Scheme 3). Such active carbon electrophiles bear-
ing a nitrogen functionality can also be generated from al-
dehydes and a nitrogen donor under Lewis acid catalysis.
This pathway is utilized for the three-component coupling
of aldehydes, a nitrogen donor, and allylsilanes, which pro-
vides a direct, convenient route to homoallylic amines.28
We, therefore, examined the three-component coupling re-
action using alkenylsilanes instead of allylsilanes.
a Reaction conditions: 5 (1 mmol), H2NCO2Me (1.2 mmol), 2a (2 mmol),
PtCl2 (0.025 mmol), AgSbF6 (0.05 mmol), DCE (3 mL), 70 °C, 24 h.
b Isolated yield.
c Determined by 1H NMR analysis.
d With 2a (1.2 mmol).
The platinum(II)-catalyzed one-step allylation of ami-
nals 6 as well as that of acetals 1 suffered from low diastere-
oselectivity. We, therefore, conducted a one-pot, two-step
allylation of 6 with alkenylsilanes 2 for highly stereoselec-
tive synthesis of homoallylic amines 7 (Table 8). The step-
wise allylation consists of the platinum(II)-catalyzed isom-
erization of 2 to allylsilanes 4 and subsequent boron tri-
fluoride promoted allylation of 6 at low temperatures. The
allylation of aromatic aminals with 2a proceeded in good to
high yields with reasonable syn selectivity (entries 1–4).
When 6c and 6e were used as substrates, the second step
was carried out in a 2:1 mixture of acetonitrile and 1,2-di-
chloroethane because of their low solubility in acetonitrile.
With the aid of boron trifluoride–diethyl ether, aliphatic
aminals were efficiently allylated with high syn selectivity
(entries 5–8). In the case of 6j, the allylation step using 1,2-
dichloroethane instead of acetonitrile lowered the stereose-
NHCO2Me
+
M
CO2Me
Pt2+
NHCO2Me
NHCO2Me
4 from 2
N
R1
R1
R1
H
R2
7
6
B: M = Pt+, H
Scheme 3 A plausible mechanism for the allylation of aminals
Since carbamates are effective as nitrogen donors in the
known three-component coupling,28 methyl carbamate was
selected for the target reaction. Under the conditions used
for the aminal allylation, the reaction of benzaldehyde (5a),
methyl carbamate (1.2 equiv), and alkenylsilane 2a (1.2
equiv) gave the desired product 7aa in moderate yield (Ta-
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525
H. Kinoshita et al.
Paper
Synthesis
lectivity (entry 7). The aminal allylation using other alke-
nylsilanes showed good compatibility with various func-
tional groups (entries 9–14).
high syn selectivity (entries 5 and 8). In contrast, the same
reaction in 1,2-dichloroethane proceeded with high yield,
but with decreased syn selectivity (entries 7 and 10). The
use of a mixed solvent (MeCN–DCE, 2:1) was successful for
efficient coupling without loss of stereoselectivity (entries
6 and 9).
Table 8 Stepwise Allylation of Aminals 6 with Alkenylsilanes 2a
PtCl2 (1.1 mol%) R1CH(NHCO2Me)2 (6)
AgSbF6 (2.2 mol%) BF3•OEt2 (1.5 equiv)
NHCO2Me
Further effort was made to expand the scope of the car-
bon electrophile; the allylation of carboxylic anhydrides
was examined (Scheme 4 and Table 10).29 The platinum(II)-
catalyzed reaction of acetic anhydride (8a) with alkenylsi-
lane 2a by a one-step method (method A) gave β,γ-unsatu-
rated ketone 9a in good yield (entry 1); contamination with
a trace amount of α,β-unsaturated ketone 9a′ was detected
by 1H NMR analysis. The reaction of 8a was carried out also
by a stepwise method (method B), in which 2a alone was
initially subjected to platinum(II) catalysis, and then 8a was
added to the resultant mixture. This method was not as ef-
fective for the allylation even using boron trifluoride–di-
ethyl ether complex as an additional promoter (entries 2
and 3). Pivalic anhydride (8b) and benzoic anhydride (8c)
were less reactive than 8a (entries 4, 5, 7, and 8). However,
the reaction by method B using boron trifluoride–diethyl
ether complex achieved successful allylation of 8b and 8c
(entries 6 and 9). Hexanoic anhydride (8d) was also allylat-
ed efficiently under similar conditions (entry 10). The al-
lylation of crotonic anhydride (8e) was complicated by the
use of boron trifluoride–diethyl ether complex (entries 11
and 12).
SiMe3
R1
R2
DCE, 70 °C, 2 h MeCN, 0 °C, 24–48 h
R2
7
2 (1.6 equiv)
Entry
Sub-
strates
6 +2
R1
R2
Product Yieldb Ratioc
(%)
syn/anti
1
6a + 2a
6c + 2a
6e + 2a
6g + 2a
6h + 2a
6j + 2a
6j + 2a
6k + 2a
6a + 2b
6j + 2b
6j + 2c
6j + 2e
6j + 2f
Ph
(CH2)8Me
7aa
7ca
7ea
7ga
7ha
7ja
7ja
7ka
7ab
7jb
7jc
90
89:11
87:13
88:12
84:16
93:7
2d,e
3d,e
4d
5f,g
6
4-BrC6H4
(CH2)8Me
(CH2)8Me
77
73
76
94
82
85
93
74
48
82
82
78
81
4-O2NC6H4
4-MeOC6H4 (CH2)8Me
Cy
Et
(CH2)8Me
(CH2)8Me
(CH2)8Me
(CH2)8Me
Ph
95:5
7h
Et
91:9
8f,g
9i
t-Bu
Ph
Et
97:3
71:29
88:12
95:5
10i
Ph
11
12
13d
14
Et
(CH2)3OMe
(CH2)3OAc
(CH2)3Cl
(CH2)3Phth
Et
7je
7jf
92:8j
93:7
Et
6j + 2g
Et
7jg
91:9j
method A:
a Reaction conditions: 1st step: 2 (1.6 mmol), PtCl2 (0.011 mmol), AgSbF6
(0.022 mmol), DCE (3 mL), 70 °C, 2 h; 2nd step: 6 (1 mmol), BF3·OEt2 (1.5
mmol), MeCN (3 mL), 0 °C, 24 h (entries 1–4 and 9) or 48 h (entries 5–8
and 10–14).
PtCl2 (2.5 mol%)
AgSbF6 (5 mol%)
O
(R3CO)2O
SiMe3
(CH2)8Me
+
R3
DCE, 70 °C, time
8
b Isolated yield.
2a (1.4 equiv)
(CH2)8Me
c Determined by GC analysis.
d With PtCl2 (0.025 mmol) and AgSbF6 (0.05 mmol).
e The second step was carried out in MeCN–DCE (2:1, 4.5 mL).
f With 2a (1.8 mmol).
9
method B:
O
+
PtCl2 (2.5 mol%)
AgSbF6 (5 mol%)
8
(BF3•OEt2)
R3
g The second step was carried out at 50 °C.
2a
h The second step was carried out with BF3·OEt2 (1 mmol) in DCE (5 mL).
i The reaction time of the first step was 20 h. The second step was carried
out with half amounts of 6a or 6j (0.5 mmol) and BF3·OEt2 (0.75 mmol).
j Determined by 1H NMR analysis.
(CH2)8Me
9'
DCE, 70 °C, 2 h
70 °C, time
(1.4 equiv)
Scheme 4 Allylation of carboxylic anhydrides
We next examined a stepwise three-component cou-
pling of aldehydes 5, methyl carbamate, and 2a (Table 9).
After allylsilane 4a had been prepared from 2a, it under-
went boron trifluoride promoted coupling with 5 and
methyl carbamate in the same flask. When the second step
was conducted with 5a in acetonitrile, 7aa was obtained in
high yield with reasonable syn selectivity (entry 1). Al-
though the use of 1,2-dichloroethane as the solvent effi-
ciently promoted the second step with a lower amount of
boron trifluoride–diethyl ether complex, the syn selectivity
decreased significantly (entry 2). Similar solvent effects
were also observed in other cases. The coupling reaction of
5i or 5j in acetonitrile resulted in moderate yields, but with
method A:
PtCl2 (2.5 mol%)
AgSbF6 (5 mol%)
R4
10
X
SiMe3
(CH2)8Me
+
DCE, 70 °C, 24 h
R4
2a (1.4 equiv)
method B:
(CH2)8Me
PtCl2 (2.5 mol%)
AgSbF6 (5 mol%)
10
11
(BF3•OEt2)
2a
DCE, 70 °C, 2 h
70 °C, 24 h
(1.4 equiv)
Scheme 5 Allylation of other carbon electrophiles
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526
H. Kinoshita et al.
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Synthesis
Table 9 Stepwise Three-Component Coupling of Aldehydes 5, Methyl Carbamate, and Alkenylsilane 2aa
R1CHO (5)
PtCl2 (2.5 mol%) H2NCO2Me (1.2 equiv)
AgSbF6 (5 mol%) BF3•OEt2 (1.5 equiv)
NHCO2Me
SiMe3
R1
DCE, 70 °C, 2 h Solv, T °C, 24-48 h
(CH2)8Me
2a (1.6 equiv)
(CH2)8Me
7
Entry
Substrate 5
R1
Solvent,b Temp
Product
Yieldc (%)
Ratiod syn/anti
1
2
5a
5a
5h
5h
5i
Ph
MeCN, 0 °C
7aa
7aa
7ha
7ha
7ia
7ia
7ia
7ja
7ja
7ja
95
93
90
90
66
77
90
59
74
84
88:12
83:17
91:9
Ph
DCE, 0 °C
3e
4e
5
Cy
MeCN, 50 °C
DCE, 50 °C
Cy
88:12
93:7
(CH2)7Me
MeCN, 30 °C
MeCN–DCE (2:1), 30 °C
DCE, 30 °C
6
5i
(CH2)7Me
93:7
7
5i
(CH2)7Me
88:12
94:6
8
5j
Et
Et
Et
MeCN, 0 °C
9
5j
MeCN–DCE (2:1), 0 °C
DCE, 0 °C
94:6
10
5j
91:9
a Reaction conditions: 1st step: 2a (1.6 mmol), PtCl2 (0.025 mmol), AgSbF6 (0.05 mmol), DCE (3 mL), 70 °C, 2 h; 2nd step: 5 (1 mmol), H2NCO2Me (1.2 mmol),
BF3·OEt2 [1 mmol (entries 2, 4, 7, and 10) or 1.5 mmol (other entries)], 24 h (entries 1 and 2) or 48 h (entries 3–10).
b MeCN (3 mL), DCE (5 mL), or the mixed solvent (4.5 mL) was used for the second step.
c Isolated yield.
d Determined by GC analysis.
e With 2a (1.8 mmol).
Alkyl electrophiles 10, bearing a methoxy, acetoxy, or
chloro leaving group, also underwent the allylation with 2a
(Scheme 5 and Table 11). Ether 10a and ester 10b were effi-
ciently converted into the allylation product 11a by the
one-step method (method A) (entries 2 and 5). The step-
wise method (method B) was more effective in the allyla-
tion of 10b than method A (entries 4 vs. 6). The reaction of
ester 10c by method A formed a complex mixture of prod-
ucts (entry 7). Allylation of 10c successfully proceeded by
method B when the second step was conducted using bo-
ron trifluoride–diethyl ether complex at 30 °C (entry 8). In-
terestingly, method A completely suppressed the allylation
of chloride 10d, while method B succeeded in quantitative
formation of 11a (entries 9 and 10). Similar results were
obtained in the reactions of alkyl chlorides 10e and 10f (en-
tries 11–14). In these cases, using method A resulted in de-
compostion of the substrates, and the isomerization of 2a
to 4a hardly occurred. This is probably due to fast chloride
abstraction from the substrates by silver(I) hexafluoroanti-
monate, as a result the active platinum(II) catalyst was not
generated. It is also likely that alkyl chlorides deactivate the
active catalyst by chloride donation, thereby preventing the
alkene migration of 2a.
Table 10 Allylation of Carboxylic Anhydridesa (Scheme 4)
Entry Substrate R3
Methodb Time
(h)
Product
Yieldc (%)
(ratio 9/9′)
8
1
8a
8a
8a
8b
8b
8b
8c
8c
Me
A
B
B
A
B
B
A
B
B
B
B
B
4
2
9a + 9a′
9a + 9a′
9a + 9a′
9b
74 (>99:1)
63 (>99:1)
71 (98:2)
61e
2
Me
3d
4
Me
2
t-Bu
24
24
20
24
24
24
3
5
t-Bu
9b
52e
6d
7
t-Bu
9b
95e
Ph
9c + 9c′
9c + 9c′
9c + 9c′
9d + 9d′
9e
43 (97:3)
35 (98:2)
89 (91:9)
84 (97:3)
60e
8
Ph
9d,f 8c
Ph
10d
8d
8e
8e
(CH2)4Me
CH=CHMe
CH=CHMe
11
6
12d
3
9eg
<69
a Reaction conditions: 8 (1 mmol), 2a (1.4 mmol), PtCl2 (0.025 mmol),
AgSbF6 (0.05 mmol), DCE (3 mL), 70 °C.
b See Scheme 4 for methods A and B.
c Isolated as a mixture of 9 and 9′; yields of 9 and 9′ were determined by 1H
NMR analysis of the mixture.
d BF3·OEt2 (1 M in DCE; 0.2 (entries 3, 10, and 12), 0.4 (entry 6), or 0.5 (entry
9) mmol) was used in the second step.
In conclusion, we have succeeded in the allylation of
various carbon electrophiles with (Z)-alkenylsilanes under
catalysis by platinum(II) chloride and silver(I) hexafluoro-
antimonate. In this catalytic system, alkenylsilanes served
e The isomer 9b′ or 9e′ was not detected in the purified product.
f With 2a (1.6 mmol).
g Contaminated with unidentified products.
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527
H. Kinoshita et al.
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Synthesis
Table 11 Allylation of Other Carbon Electrophilesa (Scheme 5)
MeCN were dried by distillation from CaH2. Acetals 1d–f,h,i, aminals
6, and alkenylsilanes 2 were synthesized according to the reported
procedures (see the Supporting Information). Other substrates and
reagents were purchased from chemical suppliers. Purchased alde-
hydes, alkynes, acetals, and HC(OMe)3 were distilled from CaH2.
BF3·OEt2 was simply distilled under reduced pressure. Other reagents
and catalysts were used as received. PtCl2 and silver salts were han-
dled in a glovebox filled with argon. Gas chromatography was carried
out with a Shimadzu GC-17A (DB-1 capillary column, 15 m × 0.25
mm i.d., 0.25 μm, He at 32.5 cm/s, split ratio 15, column flow 1.4
mL/min). Analytical TLC was performed using 0.25 mm silica gel 60
F254 plates (Merck). Silica gel 60 N (spherical, neutral, 63–210 μm,
Kanto Chemical) and hexane–EtOAc (eluent) was used for column
chromatography. Melting points were measured for solid compounds
with a micro melting point apparatus (Yanagimoto) and are uncor-
rected. IR spectra were measured with a Jasco FT/IR 230 spectropho-
tometer. 1H and 13C NMR were recorded on a Jeol JNM-EX270 or a
Bruker Avance (200, 300, 400, or 500). The chemical shifts (δ) are re-
ported with reference at δ = 7.26 (CHCl3, 1H) and δ = 77.0 (CDCl3, 13C).
HRMS were obtained on a Jeol JMS700AM in the Comprehensive
Analysis Center for Science, Saitama University. Microanalyses by
technical staff were performed therein.
Entry
10 R4X
Methodb Product Yieldc (%)
1
2d,e
3
10a Ph2CHOMe
10a Ph2CHOMe
10a Ph2CHOMe
10b Ph2CHOAc
A
A
B
A
A
B
A
B
A
B
A
B
A
B
11a
11a
11a
11a
11a
11a
11c
11c
11a
11a
11c
11c
11f
11f
60
81
43
84
86
94
0
4
5f
10b Ph2CHOAc
6
10b Ph2CHOAc
7
10c 4-MeOC6H4CH2OAc
10c 4-MeOC6H4CH2OAc
10d Ph2CHCl
8g
9
79
0
10d
11
12h
13
14
10d Ph2CHCl
98
0
10e 4-MeOC6H4CH2Cl
10e 4-MeOC6H4CH2Cl
10f MeOCH2Cl
71
0
10f MeOCH2Cl
74
a Reaction conditions: 10 (1 mmol), 2a (1.4 mmol), PtCl2 (0.025 mmol),
AgSbF6 (0.05 mmol), DCE (3 mL), 70 °C.
b See Scheme 5 for methods A and B.
Allylation of Acetals 1 with Alkenylsilanes 2 (Table 2 and Equation
1); General Procedure A (GP A)
c Isolated yield.
Acetal 1 (0.50 mmol) and alkenylsilane 2 (0.60 mmol) were added to
a stirred mixture of PtCl2 (6.7 mg, 0.025 mmol) and AgSbF6 (17.2 mg,
0.050 mmol) in DCE (1.5 mL). The mixture was heated to 70 °C. After
the indicated time, it was cooled to r.t., diluted with Et2O, and passed
through a short silica gel column with a charcoal pad. After evapora-
tion of the filtrate, the residual oil was purified by column chroma-
tography (silica gel).
d With 2a (1.6 mmol).
e With PtCl2 (0.1 mmol) and AgSbF6 (0.2 mmol).
f With PtCl2 (0.011 mmol) and AgSbF6 (0.022 mmol).
g The allylation step was carried out with BF3·OEt2 (1 M in DCE, 1 mmol) at
30 °C for 2 h.
h The allylation step was carried out at 30 °C for 18 h.
as precursors of γ-substituted allylsilanes to achieve com-
pletely regiocontrolled reaction at the γ-position. The good
compatibility with functional groups and easy access to
alkenylsilanes make this allylation synthetically useful. The
platinum(II)-catalyzed three-component coupling is valu-
able for the rapid, convenient synthesis of homoallylic
ethers and amines. The combination of the platinum(II) cat-
alyst with boron trifluoride–diethyl ether complex enabled
good to high levels of diastereoselectivity in the one-pot al-
lylation of acetals and aminals. Besides the synthetic utility,
this study has disclosed a novel type of tandem catalysis by
a cationic platinum(II) species.30 The actual platinum(II)
catalyst promotes both alkene migration of alkenylsilanes
and subsequent allylation of carbon electrophiles. It acts as
a π-Lewis acid in the former step, and activates carbon elec-
trophiles as a σ-Lewis acid in the latter step.31,32 This infor-
mation should induce further study on tandem platinum
catalysis directing towards rapid and efficient transforma-
tion of organic compounds.
Three-Component Coupling to Homoallylic Ethers 3 (Table 3);
General Procedure B (GP B)
Aldehyde 5 (0.50 mmol), HC(OMe)3 (63.7 mg, 0.60 mmol), and alke-
nylsilane 2 (0.60 mmol) were added to a stirred mixture of PtCl2 (13.3
mg, 0.050 mmol) and AgSbF6 (34.4 mg, 0.10 mmol) in DCE (1.5 mL).
The mixture was heated to 70 °C. After the indicated time, it was
cooled to r.t., diluted with Et2O, and passed through a short silica gel
column with a charcoal pad. After evaporation of the filtrate, the re-
sidual oil was purified by column chromatography (silica gel).
3-[Methoxy(phenyl)methyl]dodec-1-ene (3aa)
Following GP A using 1a (76.1 mg) and 2a (144 mg) (Table 2, entry 1)
gave 3aa as a colorless liquid; yield: 121 mg (84%); syn/anti 63:37.
IR (neat): 2925, 2854, 1454, 1103, 912, 700 cm–1
.
1H NMR (270 MHz, CDCl3): δ = 0.86–0.90 (m, 3 H), 1.13–1.33 (m, 15.4
H), 1.59–1.65 (m, 0.6 H), 2.27–2.37 (m, 1 H), 3.19 (s, 1.1 H), 3.21 (s, 1.9
H), 4.01 (d, J = 6.4 Hz, 0.6 H), 4.02 (d, J = 6.7 Hz, 0.4 H), 4.84 (dd,
J = 17.0, 2.0 Hz, 0.6 H), 4.92 (dd, J = 10.3, 2.0 Hz, 0.6 H), 4.94 (dd,
J = 17.0, 2.0 Hz, 0.4 H), 5.06 (dd, J = 10.0, 2.0 Hz, 0.4 H), 5.47 (ddd,
J = 17.0, 10.3, 9.1 Hz, 0.63 H), 5.63 (ddd, J = 17.0, 10.0, 9.0 Hz, 0.37 H),
7.21–7.29 (m, 3 H), 7.29–7.35 (m, 2 H).
13C NMR (67.7 MHz, CDCl3): δ (syn) = 14.1, 22.7, 27.2, 29.3, 29.6 (2 C),
29.7, 30.0, 31.9, 50.9, 57.0, 87.2, 116.2, 127.3, 127.6 (2 C), 127.9 (2 C),
139.0, 140.4.
All reactions and distillation of solvents were carried out under an in-
ert gas (N2 or Ar). Solvents were purchased from chemical suppliers.
Anhyd THF commercially obtained was used as received. DCE and
Anal. Calcd for C20H32O: C, 83.27; H, 11.18. Found: C, 82.97; H, 10.94.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 520–534

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H. Kinoshita et al.
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Synthesis
3-[4-Chlorophenyl(methoxy)methyl]dodec-1-ene (3ba)
1H NMR (270 MHz, CDCl3): δ = 0.85–0.90 (m, 3 H), 1.08–1.40 (m, 15.3
H), 1.52–1.70 (m, 0.7 H), 2.20–2.36 (m, 1 H), 3.23 (s, 3 H), 4.10 (d,
J = 6.6 Hz, 0.72 H), 4.20 (d, J = 5.5 Hz, 0.28 H), 4.81 (dd, J = 17.2, 1.8 Hz,
0.7 H), 4.84 (dd, J = 17.1, 2.0 Hz, 0.3 H), 4.94 (dd, J = 10.2, 1.9 Hz, 0.7
H), 5.04 (dd, J = 10.2, 1.5 Hz, 0.3 H), 5.43 (ddd, J = 17.2, 10.2, 9.3 Hz,
0.7 H), 5.57 (ddd, J = 17.1, 10.2, 9.3 Hz, 0.3 H), 7.38–7.42 (m, 2 H),
8.17–8.21 (m, 2 H).
13C NMR (67.7 MHz, CDCl3): δ (syn) = 14.1, 22.7, 27.0, 29.3, 29.55 (2
C), 29.58, 29.9, 31.9, 51.0, 57.4, 86.4, 117.2, 123.2 (2 C), 128.2 (2 C),
138.0, 147.3, 148.5.
Following GP B using 5b (70.1 mg), HC(OMe)3 (64.0 mg), and 2a (145
mg) (Table 3, entry 2) gave 3ba as a colorless liquid; yield: 135 mg
(84%); syn/anti 63:37.
IR (neat): 2925, 2854, 1491, 1466, 1092, 914 cm–1
.
1H NMR (270 MHz, CDCl3): δ = 0.85–0.89 (m, 3 H), 1.10–1.38 (m, 15.4
H), 1.53–1.67 (m, 0.6 H), 2.20–2.34 (m, 1 H), 3.18 (s, 1.1 H), 3.19 (s, 1.9
H), 3.97 (d, J = 6.6 Hz, 0.63 H), 4.02 (d, J = 6.2 Hz, 0.37 H), 4.83 (dd,
J = 17.1, 2.0 Hz, 0.6 H), 4.87–4.95 (m, 1 H), 5.05 (dd, J = 10.2, 2.2 Hz,
0.4 H), 5.43 (ddd, J = 17.1, 10.2, 9.2 Hz 0.63 H), 5.59 (ddd, J = 17.1,
10.2, 9.1 Hz, 0.37 H), 7.13–7.19 (m, 2 H), 7.26–7.32 (m, 2 H).
Anal. Calcd for C20H31NO3: C, 72.04; H, 9.37. Found: C, 72.18; H, 9.60.
13C NMR (67.7 MHz, CDCl3): δ (syn) = 14.1, 22.7, 27.1, 29.3, 29.5, 29.6,
29.7, 30.0, 31.9, 50.9, 57.0, 86.5, 116.6, 128.1 (2 C), 128.9 (2 C), 132.9,
138.5, 139.0.
3-[Methoxy(4-methylphenyl)methyl]dodec-1-ene (3fa)
Following GP A using 1f (83.9 mg) and 2a (145 mg) (Table 2, entry 6)
gave 3fa as a colorless liquid; yield: 113 mg (74%); syn/anti 40:60.
Anal. Calcd for C20H31ClO: C, 74.39; H, 9.67. Found: C, 74.11; H, 9.66.
IR (neat): 2924, 2854, 1466, 1101, 912 cm–1
.
3-[4-Bromophenyl(methoxy)methyl]dodec-1-ene (3ca)
1H NMR (270 MHz, CDCl3): δ = 0.84–0.89 (m, 3 H), 1.10–1.35 (m, 15.6
H), 1.52–1.65 (m, 0.4 H), 2.29–2.37 [m, 4 H; including 2.35 (s, minor)
and 2.37 (s, major)], 3.17 (s, 1.8 H), 3.19 (s, 1.2 H), 3.97 (d, J = 6.6 Hz, 1
H), 4.85 (dd, J = 17.1, 2.2 Hz, 0.4 H), 4.90–4.98 (m, 1 H), 5.06 (dd,
J = 10.4, 2.0 Hz, 0.6 H), 5.47 (ddd, J = 17.1, 10.4, 9.4 Hz, 0.4 H), 5.63
(ddd, J = 17.0, 10.4, 9.1 Hz, 0.6 H), 7.11–7.16 (m, 4 H).
13C NMR (67.7 MHz, CDCl3): δ (anti) = 14.1, 21.1, 22.7, 27.0, 29.3, 29.5
(2 C), 29.6, 30.5, 31.9, 51.0, 56.8, 87.0, 116.0, 127.5 (2 C), 128.7 (2 C),
136.9, 137.5, 139.7.
Following GP B using 5c (93.3 mg), HC(OMe)3 (64.5 mg), and 2a (144
mg) (Table 3, entry 3) gave 3ca as a colorless liquid; yield: 159 mg
(86%); syn/anti 68:32.
IR (neat): 2925, 2854, 1485, 1105, 1011, 915, 819 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.85–0.90 (m, 3 H), 1.13–1.34 (m, 15.3
H), 1.57–1.65 (m, 0.7 H), 2.21–2.33 (m, 1 H), 3.18 (s, 1 H), 3.19 (s, 2 H),
3.96 (d, J = 6.6 Hz, 0.7 H), 4.00 (d, J = 6.2 Hz, 0.3 H), 4.83 (dd, J = 17.2,
1.9 Hz, 0.7 H), 4.89 (dd, J = 10.2, 1.9 Hz, 0.7 H), 4.91 (dd, J = 17.2, 1.8
Hz, 0.3 H), 5.05 (dd, J = 10.4, 1.8 Hz, 0.3 H), 5.43 (ddd, J = 10.2, 10.2,
17.2 Hz, 0.68 H), 5.59 (ddd, J = 17.2, 10.4, 9.5 Hz, 0.32 H), 7.09–7.13
(m, 2 H), 7.43–7.47 (m, 2 H).
Anal. Calcd for C21H34O: C, 83.38; H, 11.33. Found: C, 83.32; H, 11.03.
3-[Methoxy(4-methoxyphenyl)methyl]dodec-1-ene (3ga)
13C NMR (100.6 MHz, CDCl3): δ (syn) = 14.1, 22.7, 27.1, 29.3, 29.52,
29.6, 29.7, 30.0, 31.9, 50.8, 57.0, 86.53, 116.6, 121.1, 129.3 (2 C), 131.0
(2 C), 138.5, 139.5.
Following GP B using 5g (70.0 mg), HC(OMe)3 (65.1 mg), and 2a (145
mg) (Table 3, entry 6) gave 3ga as a colorless liquid; yield: 58.2 mg
(36%); syn/anti 24:76.
IR (neat): 2924, 2854, 1512, 1249, 1100 cm–1
.
Anal. Calcd for C20H31BrO: C, 65.39; H, 8.50. Found: C, 65.48; H, 8.52.
1H NMR (400 MHz, CDCl3): δ = 0.84–0.90 (m, 3 H), 1.10–1.29 (m, 15.8
H), 1.55–1.70 (m, 0.2 H), 2.24–2.38 (m, 1 H), 3.16 (s, 2.3 H), 3.19 (s, 0.7
H), 3.805 (s, minor) + 3.814 (s, major) (3 H), 3.96 (d, J = 6.8 Hz, 1 H),
4.84 (dd, J = 17.2, 1.2 Hz, 0.24 H), 4.92 (dd, J = 10.4, 2.0 Hz, 0.24 H),
4.96 (dd, J = 17.2, 1.6 Hz, 0.76 H), 5.07 (dd, J = 10.2, 2.2 Hz, 0.76 H),
5.45 (ddd, J = 17.2, 10.2, 9.0 Hz, 0.24 H), 5.63 (ddd, J = 17.2, 10.2, 9.0
Hz, 0.76 H), 6.84–6.90 (m, 2 H), 7.10–7.15 (m, 2 H).
13C NMR (100.6 MHz, CDCl3): δ (anti) = 14.1, 22.7, 27.0, 29.3, 29.5 (2
C), 29.6, 30.5, 31.9, 51.1, 55.2, 56.7, 86.7, 113.4 (2 C), 116.0, 128.6 (2
C), 132.6, 139.8, 158.9.
Methyl 4-(1-Methoxy-2-nonylbut-3-enyl)benzoate (3da)
Following GP B using 5d (81.7 mg), HC(OMe)3 (64.0 mg), and 2a (147
mg) (Table 3, entry 4) gave 3da as a colorless liquid; yield: 152 mg
(88%); syn/anti 70:30.
IR (neat): 2925, 2854, 1726, 1436, 1278, 1103 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 0.85–0.88 (m, 3 H), 1.10–1.35 (m, 15.3
H), 1.58–1.64 (m, 0.7 H), 2.24–2.37 (m, 1 H), 3.20 (s, 0.9 H), 3.21 (s, 2.1
H), 3.90 (s, 2.1 H), 3.91 (s, 0.9 H), 4.05 (d, J = 6.5 Hz, 0.7 H), 4.11 (d,
J = 5.8 Hz, 0.3 H), 4.81 (ddd, J = 17.1, 1.9, 0.5 Hz, 0.7 H), 4.87 (ddd,
J = 1.8, 17.2, 1.8, 0.5 Hz, 0.3 H), 4.92 (dd, J = 10.3, 1.9 Hz, 0.7 H), 5.03
(dd, J = 10.5, 1.8 Hz, 0.3 H), 5.44 (ddd, J = 17.1, 10.3, 9.3 Hz, 0.7 H),
5.59 (ddd, J = 17.2, 10.5, 9.1 Hz, 0.3 H), 7.28–7.35 (m, 2 H), 7.98–8.03
(m, 2 H).
Anal. Calcd for C21H34O2: C, 79.19; H, 10.76. Found: C, 78.91; H, 10.71.
3-[Cyclohexyl(methoxy)methyl]dodec-1-ene (3ha)
Following GP B using 5h (56.2 mg), HC(OMe)3 (64.2 mg), and 2a (144
mg) (Table 3, entry 7) gave 3ha as a colorless liquid; yield: 102 mg
(69%); syn/anti 80:20.
13C NMR (125.8 MHz, CDCl3): δ (syn) = 14.1, 22.6, 27.1, 29.3, 29.5,
29.55, 29.61, 29.9, 31.9, 50.9, 52.0, 57.2, 86.8, 116.6, 127.5 (2 C), 129.2
(2 C), 129.33, 138.5, 146.0, 167.0.
IR (neat): 2925, 2852, 1450, 1107, 910 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 0.87 (t, J = 8.6 Hz, 3 H), 0.90–1.82 (m,
27 H), 2.14–2.21 (m, 1 H), 2.70–2.73 (m, 1 H), 3.41 (s, 3 H), 4.93–5.05
(m, 2 H), 5.59 (ddd, J = 17.3, 10.0, 9.5 Hz, 0.8 H), 5.68 (ddd, J = 17.3,
10.2, 9.5 Hz, 0.2 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 14.1, 22.7, 26.3, 26.58, 26.60,
27.3, 27.4, 29.26, 29.33, 29.6, 29.7, 29.8, 30.8, 31.9, 40.9, 47.2, 61.6,
90.0, 115.2, 141.0.
Anal. Calcd for C22H34O3: C, 76.26; H, 9.89. Found: C, 76.21; H, 9.99.
3-[Methoxy(4-nitrophenyl)methyl]dodec-1-ene (3ea)
Following GP B using 5e (75.5 mg), HC(OMe)3 (65.2 mg), and 2a (140
mg) (Table 3, entry 5) gave 3ea as a colorless liquid; yield: 130 mg
(78%); syn/anti 72:28.
IR (neat): 2925, 2854, 1523, 1346, 1105 cm–1
.
Anal. Calcd for C20H38O: C, 81.56; H, 13.01. Found: C, 81.44; H, 13.07.
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4-Methoxy-3-nonyldodec-1-ene (3ia)
HRMS (EI+): m/z [M]+ calcd for C21H24O3: 324.1725; found: 324.1726.
Following GP B using 5i (67.6 mg), HC(OMe)3 (64.3 mg), and 2a (143
mg) (Table 3, entry 8) gave 3ia as a colorless liquid; yield: 54.0 mg
(35%); syn/anti 70:30.
4-[Methoxy(phenyl)methyl]hex-5-enyl Acetate (3ae)
Following GP B using 5a (55.1 mg), HC(OMe)3 (64.0 mg), and 2e (128
mg) (Table 3, entry 11) gave 3ae as a colorless liquid; yield: 63.2 mg
(46%); syn/anti 74:26.
IR (neat): 2922, 2854, 1466, 1101, 911 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 0.88 (t, J = 7.0 Hz, 6 H), 1.15–1.50 (m,
30 H), 2.13–2.24 (m, 1 H), 2.99–3.06 (m 1 H), 3.346 (s, 2.1 H), 3.354 (s,
0.9 H), 4.95–5.07 (m, 2 H), 5.56–5.67 (m, 1 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 14.1 (2 C), 22.66, 22.69, 25.6,
27.5, 29.31, 29.34, 29.6 (3 C), 29.77, 29.81, 30.1, 30.8, 31.86, 31.91,
47.1, 57.3, 84.3, 115.8, 139.7.
IR (neat): 1739, 1241, 1095, 702 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 1.17–1.80 (m, 4 H), 1.98 (s, 0.78 H),
2.02 (s, 2.22 H), 2.26–2.39 (m, 1 H), 3.19 (s) and 3.21 (s, major) (3 H),
3.93–4.04 (m, 3 H), 4.86 (ddd, J = 17.2, 1.8, 0.6 Hz, 0.74 H), 4.93–4.99
(m, 1 H), 5.09 (dd, J = 10.0, 1.8 Hz, 0.26 H), 5.48 (ddd, J = 17.2, 10.4, 9.6
Hz, 0.74 H), 5.62 (ddd, J = 17.2, 10.0, 9.2 Hz, 0.26 H), 7.20–7.36 (m, 5
H).
Anal. Calcd for C22H44O: C, 81.41; H, 13.66. Found: C, 81.28; H, 13.56.
13C NMR (75.5 MHz, CDCl3): δ (syn) = 20.8, 26.0, 26.2, 50.6, 56.8, 64.4,
86.8, 116.7, 127.3, 127.4 (2 C), 127.8 (2 C), 138.3, 140.0, 170.9.
4-Methoxy-3,4-diphenylbut-1-ene (3ab)
Following GP A using 1a (76.3 mg) and 2b (113 mg) (Equation 1) gave
3ab as a colorless liquid; yield: 89.5 mg (75%); syn/anti 70:30.
Anal. Calcd for C16H22O3: C, 73.25; H, 8.45. Found: C, 73.15; H, 8.60.
IR (neat): 3028, 1454, 1099, 760, 700 cm–1
.
Stepwise Allylation of Acetals 1 with Alkenylsilanes 2 (Table 4);
General Procedure C (GP C)
1H NMR (300 MHz, CDCl3): δ = 3.13 (s, 2.1 H), 3.23 (s, 0.9 H), 3.55 (t,
J = 7.7 Hz, 0.3 H), 3.64 (t, J = 7.8 Hz, 0.7 H), 4.36–4.41 (m, 1 H), 4.84
(ddd, J = 17.1, 1.5, 1.2 Hz, 0.7 H), 4.91–5.03 (m, 1 H), 5.15 (ddd,
J = 10.2, 1.8, 0.9 Hz, 0.3 H), 5.88 (ddd, J = 17.1, 10.2, 8.1 Hz, 0.7 H), 6.27
(ddd, J = 17.1, 10.2, 8.1 Hz, 0.3 H), 7.03–7.32 (m, 10 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 56.9, 57.2, 86.9, 116.4, 126.3,
127.3, 127.7 (2 C), 127.9 (2 C), 128.1 (2 C), 128.6 (2 C), 138.3, 139.9,
141.1.
Alkenylsilane 2 (1.60 mmol) was added to a stirred mixture of PtCl2
(6.7 mg, 0.025 mmol) and AgSbF6 (17.2 mg, 0.050 mmol) in DCE (3
mL). The mixture was heated to 70 °C and stirred for 2 h. The resul-
tant mixture was cooled to r.t. and concentrated under reduced pres-
sure. MeCN (3 mL) and acetal 1 (1.00 mmol) were added to the resi-
due. The mixture was cooled to –30 °C, and BF3·OEt2 (0.148 mL, 1.20
mmol) was added with stirring. After 6 h the mixture was quenched
with water and extracted with Et2O (3 ×). The combined extract were
washed with sat. aq NaHCO3, dried (Na2SO4), and evaporated. The res-
idue was purified by column chromatography (silica gel).
HRMS (EI+): m/z [M]+ calcd for C17H18O: 238.1358; found: 238.1361.
6-Methoxy-3-[methoxy(phenyl)methyl]hex-1-ene (3ac)
Following GP A using 1a (74.5 mg) and 2c (112 mg) (Equation 1) gave
3ac as a colorless liquid; yield: 70.3 mg (61%); syn/anti 70:30.
6-Chloro-3-[methoxy(phenyl)methyl]hex-1-ene (3af)
Following GP C using 1a (154 mg) and 2f (305 mg) (Table 4, entry 10)
gave 3af as a colorless liquid; yield: 177 mg (73%); syn/anti 86:14.
IR (neat): 2926, 1453, 1118, 914. 701 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.19–1.78 (m, 4 H), 2.27–2.38 (m, 1 H),
3.19 (s, 0.9 H), 3.20 (s, 2.1 H), 3.27–3.32 [m, 3.6 H; including 3.27 (s,
minor) and 3.30 (s, major)], 3.34 (t, J = 6.6 Hz, 1.4 H), 4.00 (d, J = 6.9
Hz, 0.7 H), 4.04 (d, J = 6.3 Hz, 0.3 H), 4.85 (ddd, J = 17.1, 2.1, 0.6 Hz, 0.7
H), 4.91–4.97 (m, 1 H), 5.06 (dd, J = 10.2, 1.8 Hz, 0.3 H), 5.45 (ddd,
J = 17.1, 10.2, 9.3 Hz, 0.7 H), 5.62 (ddd, J = 17.0, 10.2, 9.0 Hz, 0.3 H),
7.20–7.34 (m, 5 H).
IR (neat): 2930, 1453, 1101, 918, 702 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 1.23–1.90 (m, 4 H), 2.30–2.40 (m, 1 H),
3.20 (s, 0.4 H), 3.21 (s, 2.6 H), 3.40–3.58 (m, 2 H), 3.99–4.07 (m, 1 H),
4. 86 (ddd, J = 17.2, 2.0, 0.8 Hz, 0.86 H), 4.93–4.99 (m, 1 H), 5.08 (dd,
J = 10.2, 2.1 Hz, 0.14 H), 5.48 (ddd, J = 17.2, 10.2, 9.3 Hz, 0.86 H), 5.62
(ddd, J = 17.1, 10.2, 9.3 Hz, 0.14 H), 7.21–7.38 (m, 5 H).
13C NMR (125.8 Hz, CDCl3): δ (syn) = 26.6, 27.3, 50.8, 56.9, 58.4, 72.9,
13C NMR (75.5 MHz, CDCl3): δ (syn) = 27.4, 30.4, 45.1, 50.5, 57.0, 86.9,
87.0, 116.6, 127.4, 127.6 (2 C), 127.9 (2 C), 138.5, 140.2.
116.9, 127.4, 127.5 (2 C), 128.0 (2 C), 138.3, 140.0.
HRMS (EI+): m/z [M]+ calcd for C15H22O2: 234.1620; found: 234.1622.
Anal. Calcd for C14H19ClO: C, 70.43; H, 8.02. Found: C, 70.33; H, 8.10.
4-[Methoxy(phenyl)methyl]hex-5-enyl Benzoate (3ad)
N-(4-[Methoxy(phenyl)methyl]hex-5-enyl)phthalimide (3ag)
Following GP A using 1a (77.0 mg) and 2d (169 mg) (Equation 1) gave
3ad as a colorless liquid; yield: 106 mg (65%); syn/anti 69:31.
Following GP C using 1a (154 mg) and 2g (481 mg) (Table 4, entry 11)
gave 3ag as a white solid; yield: 329 mg (93%); mp 79–80 °C; syn/anti
89:11.
IR (neat): 1718, 1452, 1275, 1111, 1070, 712 cm–1
.
IR (nujol): 1768, 1715, 1401, 1105, 721, 701 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 1.26–1.43 (m, 1 H), 1.45–1.54 (m, 0.3
H), 1.56–1.71 (m, 1 H), 1.75–1.89 (m, 1.7 H), 2.34–2.43 (m, 1 H), 3.20
(s, 0.94 H), 3.21 (s, 2.06 H), 4.04 (d, J = 6.5 Hz, 0.7 H), 4.05 (d, J = 6.5
Hz, 0.3 H), 4.18–4.32 (m, 2 H), 4.90 (ddd, J = 17.0, 1.5, 0.5 Hz, 0.7 H),
4.96–5.02 (m, 1 H), 5.12 (dd, J = 10.0, 1.8 Hz, 0.3 H), 5.53 (ddd, J = 17.0,
10.0, 9.0 Hz, 0.7 H), 5.66 (ddd, J = 17.0, 10.0, 9.0 Hz, 0.3 H), 7.22–7.28
(m, 3 H), 7.30–7.34 (m, 2 H), 7.40–7.45 (m, 2 H), 7.52–7.57 (m, 1 H),
7.93–7.96 (m, 0.6 H), 8.00–8.02 (m, 1.4 H).
1H NMR (300 MHz, CDCl3): δ = 1.16–1.80 (m, 4 H), 2.29–2.42 (m, 1 H),
3.17 (s, 0.3 H), 3.18 (s, 2.7 H), 3.55–3.66 (m, 2 H), 3.98–4.04 (m, 1 H),
4.85 (ddd, J = 17.1, 1.8, 0.6 Hz, 0.89 H), 4.90–4.98 (m, 1 H), 5.06 (dd,
J = 10.2, 0.8 Hz, 0.11 H), 5.46 (ddd, J = 17.1, 10.2, 9.2 Hz, 0.89 H), 5.61
(ddd, J = 17.1, 10.2, 9.3 Hz, 0.11 H), 7.18–7.32 (m, 5 H), 7.66–7.72 (m,
2 H), 7.78–7.85 (m, 2 H).
13C NMR (75.5 MHz, CDCl3): δ (syn) = 26.2, 27.1, 38.0, 50.6, 56.9, 86.8,
116.8, 123.1 (2 C), 127.4, 127.5 (2 C), 127.9 (2 C), 132.1 (2 C), 133.7 (2
C), 138.2, 140.1, 168.3 (2 C).
13C NMR (125.7 MHz, CDCl3): δ (syn) = 26.2, 26.5, 50.7, 57.0, 65.0,
87.0, 116.8, 127.4, 127.5 (2 C), 128.0 (2 C), 128.2 (2 C), 129.5 (2 C),
130.5, 132.7, 138.5, 140.2, 166.6.
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HRMS (EI+): m/z [M]+ calcd for C22H23NO3: 349.1678; found: 349.1676.
13C NMR (75.5 MHz, CDCl3): δ (syn) = 13.9, 22.5, 27.0, 29.1, 29.2,
29.32, 29.33, 30.9, 31.7, 49.1, 52.1, 57.7, 118.7, 123.1 (2 C), 128.1 (2 C),
137.1, 146.9, 148.1, 156.0.
Allylation of Aminals 6 with Alkenylsilanes 2 (Table 6); General
Procedure D (GP D)
Anal. Calcd for C21H32N2O4: C, 66.99; H, 8.57; N, 7.44. Found: C, 66.95;
H, 8.59; N, 7.44.
Alkenylsilane 2 (1.20 mmol) was added to a stirred mixture of PtCl2
(6.7 mg, 0.025 mmol), AgSbF6 (17.2 mg, 0.050 mmol), and aminal 6
(1.00 mmol) in DCE (3 mL). The mixture was stirred at 70 °C for 24 h.
The product was isolated by GP A.
N-(Methoxycarbonyl)-1-(4-methylphenyl)-2-nonylbut-3-en-1-
amine (7fa)
Following GP D using 6f (253 mg) and 2a (287 mg) (Table 6, entry 4)
gave 7fa as a pale yellow oil to solid; yield: 300 mg (86%); mp 45–
47 °C; syn/anti 72:28.
Three-Component Coupling to Homoallylic Amine 7 (Table 7);
General Procedure E (GP E)
IR (neat): 3326, 2924, 2854, 1701, 1516, 1254 cm–1
.
Aldehyde 5 (1.00 mmol) and alkenylsilane 2a (288 mg, 1.20 mmol)
were added to a stirred mixture of PtCl2 (6.7 mg, 0.025 mmol), AgSbF6
(17.2 mg, 0.050 mmol), and H2NCO2Me (90.3 mg, 1.20 mmol) in DCE
(1.5 mL). The mixture was stirred at 70 °C for 24 h. The product was
isolated by GP A.
1H NMR (400 MHz, CDCl3): δ = 0.85–0.89 (m, 3 H), 1.00–1.48 (m, 16
H), 2.28–2.40 (m, 4 H), 3.60 (s) + 3.62 (s, major) (3 H), 4.46–4.69 (m, 1
H), 4.95–5.27 (m, 3 H), 5.37–5.47 (m, 0.72 H), 5.52–5.61 (m, 0.28 H),
7.04–7.12 (m, 4 H).
13C NMR (75.5 MHz, CDCl3): δ (syn) = 14.0, 20.9, 22.5, 27.1, 29.2,
29.37, 29.42 (2 C), 31.1, 31.8, 49.4, 51.8, 57.6, 117.6, 127.2 (2 C), 128.6
(2 C), 136.5, 137.0, 138.3, 156.0.
N-(Methoxycarbonyl)-2-nonyl-1-phenylbut-3-en-1-amine (7aa)
Following GP D using 6a (238 mg) and 2a (291 mg) (Table 6, entry 1)
gave 7aa as a colorless oil to white solid; yield: 300 mg (90%); mp 50–
55 °C; syn/anti 72:28.
Anal. Calcd for C22H35NO2: C, 76.48; H, 10.21; N, 4.05. Found: C, 76.49;
H, 10.28; N, 4.13.
IR (neat): 3328, 2926, 2698, 1698, 1538, 701 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.85–0.90 (m, 3 H), 0.95–1.51 (m, 16
H), 2.27–2.45 (m, 1 H), 3.61 (s) + 3.63 (s, major) (3 H), 4.50–4.74 (m, 1
H), 5.02–5.30 (m, 3 H), 5.35–5.63 (m, 0.74 H), 5.51–5.48 (m, 0.26 H),
7.15–7.35 (m, 5 H).
13C NMR (100.6 MHz, CDCl3): δ (syn) = 14.1, 22.6, 27.2, 29.2, 29.4, 29.5
(2 C), 31.2, 31.8, 49.5, 52.0, 57.9, 117.9, 127.1, 127.4 (2 C), 128.0 (2 C),
138.2, 140.0, 156.1.
N-(Methoxycarbonyl)-1-(4-methoxyphenyl)-2-nonylbut-3-en-1-
amine (7ga)
Following GP D using 6g (270 mg) and 2a (288 mg) (Table 6, entry 5)
gave 7ga as a pale yellow oil to solid; yield: 271 mg (74%); mp 54–
57 °C; syn/anti 62:38.
IR (neat): 3326, 2925, 2857, 1713, 1515, 1248 cm–1
.
1H NMR (200 MHz, CDCl3): δ = 0.84–0.90 (m, 3 H), 1.09–1.39 (m, 16
H), 2.20–2.45 (m, 1 H), 3.60 (s, 1.14 H), 3.62 (s, 1.86 H), 3.788 (s) +
3.794 (s, major) (3 H), 4.41–4.69 (m, 1 H), 4.92–5.67 (m, 4 H), 6.81–
6.88 (m, 2 H), 7.07–7.18 (m, 2 H).
13C NMR (75.5 MHz, CDCl3): δ (syn) = 13.9, 22.5, 27.1, 29.1, 29.36,
29.39 (2 C), 31.1, 31.7, 49.4, 51.8, 54.9, 57.3, 113.2 (2 C), 117.6, 128.3
(2 C), 133.9, 138.2, 156.0, 158.5.
Anal. Calcd for C21H33NO2: C, 76.09; H, 10.03; N, 4.23. Found: C, 75.96;
H, 10.01; N, 4.05.
1-(4-Bromophenyl)-N-(methoxycarbonyl)-2-nonylbut-3-en-1-
amine (7ca)
Following GP D using 6c (319 mg) and 2a (290 mg) (Table 6, entry 2)
gave 7ca as a pale yellow oil to solid; yield: 383 mg (93%); mp 50–
56 °C; syn/anti 70:30.
Anal. Calcd for C22H35NO3: C, 73.09; H, 9.76; N, 3.87. Found: C, 73.12;
H, 9.81; N, 3.84.
IR (neat): 3317, 2924, 2854, 1698, 1539, 1254 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.84 (t, J = 6.6 Hz, 3 H), 0.98–1.46 (m,
16 H), 2.21–2.39 (m, 1 H), 3.57 (s) + 3.59 (s, major) (3 H), 4.41–4.66
(m, 1 H), 4.99–5.44 (m, 3.7 H), 5.45–5.58 (m, 0.3 H), 7.03 (d, J = 8.4 Hz,
1.4 H), 7.10 (d, J = 8.4 Hz, 0.6 H), 7.37–7.41 (m, 2 H).
13C NMR (75.5 MHz, CDCl3): δ (syn) = 14.0, 22.5, 27.0, 29.1, 29.3, 29.4
(2 C), 30.7, 31.7, 49.1, 51.9, 57.4, 118.1, 120.9, 129.0 (2 C), 131.0 (2 C),
137.7, 139.3, 156.0.
1-Cyclohexyl-N-(methoxycarbonyl)-2-nonylbut-3-en-1-amine
(7ha)
Following GP D using BF3·OEt2 (0.130 mL), 6h (244 mg), and 2a (290
mg) (Table 6, entry 7), with isolation by GP C gave 7ha as a yellow liq-
uid; yield: 257 mg (76%); syn/anti 85:15.
IR (neat): 3322, 2924, 2852, 1700, 1541, 1258 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 0.83–0.89 (m, 4 H), 1.04–1.75 (m, 26
H), 1.99–2.07 (m, 0.85 H), 2.25–2.32 (m, 0.15 H), 3.22–3.30 (m, 0.15
H), 3.39–3.45 (m, 0.85 H), 3.65–3.69 (m, 3 H), 4.40–4.55 (m, 1 H),
4.91–5.08 (m, 2 H), 5.45–5.60 (m, 1 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 14.0, 22.6, 26.0, 26.2, 26.3 (2
C), 27.1, 29.2, 29.47, 29.50, 29.53, 30.1, 30.9, 31.8, 39.5, 46.8, 51.8,
58.6, 115.8, 139.9, 157.3.
Anal. Calcd for C21H32BrNO2: C, 61.46; H, 7.86; N, 3.41. Found: C,
61.51; H, 7.89; N, 3.39.
N-(Methoxycarbonyl)-1-(4-nitrophenyl)-2-nonylbut-3-en-1-
amine (7ea)
Following GP D using 6e (281 mg) and 2a (286 mg) (Table 6, entry 3)
gave 7ea as a pale yellow oil to solid; yield: 335 mg (90%); mp 47–
49 °C; syn/anti 75:25.
Anal. Calcd for C21H39NO2: C, 74.72; H, 11.65; N, 4.15. Found: C, 74.60;
H, 11.71; N, 4.36.
IR (neat): 3318, 2925, 2854, 1708, 1523, 1348 cm–1
.
1H NMR (200 MHz, CDCl3): δ = 0.83–0.91 (m, 3 H), 1.23 (br s, 16 H),
2.27–2.48 (m, 1 H), 3.62 (br s) + 3.64 (br s, major) (3 H), 4.54–4.83 (m,
1 H), 5.02–5.44 (m, 3.75 H), 5.45–5.57 (m, 0.25 H), 7.35 (d, J = 8.7 Hz,
1.5 H), 7.41 (d, J = 8.7 Hz, 0.5 H), 8.14–8.22 (m, 2 H).
N-(Methoxycarbonyl)-1,2-diphenylbut-3-en-1-amine (7ab)
Following GP D using 6a (239 mg) and 2b (231 mg) (Table 6, entry 8)
gave 7ab as a white solid; yield: 168 mg (60%); mp 94–97 °C; syn/anti
50:50.
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IR (nujol): 3381, 1690, 1525, 1250, 700 cm–1
.
N-(Methoxycarbonyl)-4-nonylhex-5-en-3-amine (7ja)
1H NMR (500 MHz, CDCl3): δ = 3.53–3.73 (m, 4 H), 4.90–5.20 (m, 4 H),
5.95 (ddd, J = 17.0, 10.3, 8.3 Hz, 0.50 H), 6.11 (ddd, J = 17.0, 10.3, 8.2
Hz, 0.50 H), 6.98–7.31 (m, 10 H).
Following GP F using 6j (190 mg) and 2a (385 mg) (Table 8, entry 6)
gave 7ja as a white solid; yield: 231 mg (82%); mp 31–32 °C; syn/anti
95:5.
IR (nujol): 3333, 2925, 2854, 1701, 1541, 1246 cm–1
.
13C NMR (75.5 MHz, CDCl3): δ (one isomer) = 52.0, 55.5, 58.6, 117.4,
126.9, 127.15 (2 C), 127.19, 128.0 (2 C), 128.3 (2 C), 128.4 (2 C), 137.2,
139.7, 140.4, 156.0; δ (other isomer) = 52.0, 56.7, 59.1, 117.4, 126.6,
126.9 (2 C), 127.0, 127.9 (2 C), 128.19 (2 C), 128.21 (2 C), 138.2, 140.2,
140.6, 156.2.
1H NMR (500 MHz, CDCl3): δ (syn) = 0.88 (t, J = 6.8 Hz) + 0.90 (t, J = 7.2
Hz) (6 H), 1.12–1.36 (m, 16 H), 1.40–1.46 (m, 1 H), 1.58–1.68 (m, 1 H),
2.04–2.10 (m, 1 H), 3.49–3.53 (m, 1 H), 3.67 (s, 3 H), 4.47 (d, J = 9.5 Hz,
1 H), 5.02 (dd, J = 17.0, 2.0 Hz, 1 H), 5.08 (dd, J = 10.0, 2.0 Hz, 1 H), 5.53
(ddd, J = 17.0, 10.0, 9.5 Hz, 1 H).
Anal. Calcd for C18H19NO2: C, 76.84; H, 6.81; N, 4.98. Found: C, 76.96;
H, 6.84; N, 4.92.
13C NMR (125.8 MHz, CDCl3): δ (syn) = 10.5, 14.0, 22.6, 24.1, 27.3,
29.2, 29.47 (2 C), 29.52, 31.0, 31.8, 49.2, 51.8, 55.7, 117.0, 138.9, 156.9.
N-(Methoxycarbonyl)-1-phenyl-2-[3-(triisopropylsiloxy)pro-
pyl]but-3-en-1-amine (7ah)
HRMS (EI+): m/z [M]+ calcd for C17H33NO2: 283.2511; found: 283.2506.
Following GP D using 6a (238 mg) and 2h (399 mg) (Table 6, entry 9)
gave 7ah as a pale yellow oil to solid; yield: 260 mg (62%); mp 39–
47 °C; syn/anti 75:25.
N-(Methoxycarbonyl)-2,2-dimethyl-4-nonylhex-5-en-3-amine
(7ka)
Following GP F using 6k (221 mg) and 2a (430 mg) (Table 8, entry 8)
gave 7ka as a colorless liquid; yield: 293 mg (93%); syn/anti 97:3.
IR (neat): 3315, 2941, 2866, 1712, 1538, 1107 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.99–1.14 (m, 21 H), 1.22–1.66 (m, 4
H), 2.31–2.47 (m, 1 H), 3.55–3.65 (m, 5 H), 4.49–4.74 (m, 1 H), 5.00–
5.31 (m, 3 H), 5.35–5.48 (m, 0.75 H), 5.51–5.63 (m, 0.25 H), 7.15–7.34
(m, 5 H).
13C NMR (100.6 MHz, CDCl3): δ (syn) = 11.9 (3 C), 18.0 (6 C), 27.6,
30.6, 49.4, 52.0, 58.0, 63.1, 118.1, 126.8, 127.4 (2 C), 128.0 (2 C), 138.0,
139.9, 156.0.
IR (neat): 3331, 2924, 2854, 1697, 1538, 1247 cm–1
.
1H NMR (500 MHz, CDCl3): δ (syn) = 0.88 (t, J = 7.0 Hz, 3 H), 0.94 (s, 9
H), 1.10–1.42 (m, 16 H), 2.15–2.43 (m, 1 H), 3.48 (dd, J = 11.0, 3.5 Hz,
1 H), 3.67 (s, 3 H), 4.63 (d, J = 11.0 Hz, 1 H), 4.94 (dd, J = 17.0, 1.5 Hz) +
4.97 (dd, J = 10.0, 2.0 Hz) (2 H), 5.68 (ddd, J = 17.0, 10.0, 9.5 Hz, 1 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 13.9, 22.5, 27.1, 27.2 (3 C),
29.2, 29.46, 29.50, 29.6, 30.0, 31.8, 35.9, 45.1, 51.9, 62.1, 114.0, 142.1,
157.1.
HRMS (EI+): m/z [M]+ calcd for C24H41NO3Si: 419.2856; found:
419.2843.
HRMS (EI+): m/z [M]+ calcd for C19H37NO2: 311.2824; found: 311.2830.
Anal. Calcd for C24H41NO3Si: C, 68.69; H, 9.85; N, 3.34. Found: C,
68.34; H, 9.95; N, 3.21.
N-(Methoxycarbonyl)-4-phenylhex-5-en-3-amine (7jb)
Following GP F using 6j (95.1 mg) and 2b (306 mg) (Table 8, entry 10)
gave 7jb as a white solid; yield: 56.6 mg (48%); mp 69–71 °C; syn/anti
88:12.
N-(Methoxycarbonyl)-2-methyl-1-phenylbut-3-en-1-amine (7ai)
Following GP D using 6a (238 mg) and 2i (258 mg, 2 mmol) (Table 6,
entry 10) gave 7ai as a white solid; yield: 188 mg (86%); mp 77–
81 °C; syn/anti 70:30.
IR (nujol): 3321, 1694, 1539 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 0.83–0.93 (m, 3 H), 1.00–1.32 (m, 1 H),
1.45–1.70 (m, 1 H), 3.23–3.49 (m, 1 H), 3.61 (s, major) + 3.67 (s) (3 H),
3.85–4.00 (m, 1 H), 4.10–4.49 (m, 1 H), 5.04–5.19 (m, 2 H), 5.99–6.14
(m, 1 H), 7.17–7.35 (m, 5 H).
13C NMR (75.5 MHz, CDCl3): δ (syn) = 10.3, 25.3, 52.0, 54.3, 55.9,
117.2, 126.6, 128.2 (2 C), 128.4 (2 C), 137.8, 140.8, 156.8.
IR (nujol): 3299, 1688, 1545, 1266, 700 cm–1
.
1H NMR (200 MHz, CDCl3): δ = 0.97 (d, J = 6.8 Hz, major) + 0.99 (d,
J = 6.8 Hz) (3 H), 2.50–2.66 (m, 1 H), 3.62 (s) + 3.64 (s, major) (3 H),
4.46–4.70 (m, 1 H), 5.02–5.15 (m, 3 H), 5.50–5.80 [m, 1 H; including
5.61 (ddd, J = 17.6, 9.6, 8.0 Hz)], 7.16–7.36 (m, 5 H).
13C NMR (100.6 MHz, CDCl3): δ (syn) = 16.1, 42.9, 51.9, 58.9, 115.9,
126.6, 127.0 (2 C), 128.0 (2 C), 139.6, 140.3, 156.2.
HRMS (EI+): m/z [M]+ calcd for C14H19NO2: 233.1416; found: 233.1413.
Anal. Calcd for C13H17NO2: C, 71.21; H, 7.81; N, 6.39. Found: C, 71.18;
H, 7.83; N, 6.39.
N-(Methoxycarbonyl)-4-(3-methoxypropyl)hex-5-en-3-amine
(7jc)
Following GP F using 6j (192 mg) and 2c (302 mg) (Table 8, entry 11)
gave 7jc as a colorless liquid; yield: 189 mg (82%); syn/anti 95:5.
Stepwise Allylation of Aminals 6 with Alkenylsilanes 2 (Table 8);
General Procedure F (GP F)
IR (neat): 3323, 2936, 1713, 1538, 1245, 1118 cm–1
.
According to GP C, alkenylsilane 2 (1.6 or 1.8 mmol) was isomerized
to 4 with PtCl2 (2.9 mg, 0.011 mmol) and AgSbF6 (7.6 mg, 0.022
mmol) in DCE (3 mL). MeCN (3 mL) and aminal 6 (1.0 mmol) were
added to the crude allylsilane. The mixture was stirred and treated
with BF3·OEt2 (0.185 mL, 1.50 mmol) at 0 or 50 °C for 24 or 48 h. The
product was isolated by GP C and the ratio syn/anti was determined
by GC or NMR as indicated in Table 8.
1H NMR (500 MHz, CDCl3): δ (syn) = 0.90 (t, J = 7.2 Hz, 3 H), 1.12–1.22
(m, 1 H), 1.24–1.68 (m, 5 H), 2.02–2.15 (m, 1 H), 3.31 (s, 3 H), 3.35 (t,
J = 6.2 Hz, 2 H), 3.48–3.55 (m, 1 H), 3.66 (s, 3 H), 4.48 (d, J = 9.5 Hz, 1
H), 5.04 (dd, J = 17.0, 1.5 Hz, 1 H), 5.10 (dd, J = 10.0, 1.5 Hz, 1 H), 5.53
(dd, J = 17.0, 10.0, 9.5 Hz, 1 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 10.4, 24.2, 27.3, 27.4, 49.0,
51.7, 55.7, 58.3, 72.5, 117.3, 138.6, 156.8.
HRMS (EI+): m/z [M]+ calcd for C12H23NO3: 283.2511; found: 283.2506.
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4-(1-[(Methoxycarbonyl)amino]propyl)hex-5-enyl Acetate (7je)
Allylation of Carbon Electrophiles by Method A (Tables 10 and 11);
General Procedure H (GP H)
Following GP F using 6j (193 mg) and 2e (341 mg) (Table 8, entry 12)
gave 7je as a colorless liquid; yield: 214 mg (82%); syn/anti 92:8.
Carbon electrophile 8 or 10 (1.00 mmol) and 2a (337 mg, 1.40 mmol)
was added to a stirred mixture of PtCl2 (6.7 mg, 0.025 mmol) and
AgSbF6 (17.2 mg, 0.050 mmol) in DCE (3 mL). The mixture was heated
to 70 °C and stirred for the indicated time. The product was isolated
by GP A.
IR (neat): 3331, 2964, 1714, 1538, 1257, 1041 cm–1
.
1H NMR (500 MHz, CDCl3): δ (syn) = 0.90 (t, J = 7.4 Hz, 3 H), 1.12–1.72
(m, 6 H), 2.04–2.14 [m, 4 H; including 2.04 (s)], 3.35–3.54 (m, 1 H),
3.66 (s, 3 H), 4.00–4.07 (m, 2 H), 4.27–4.50 (m, 1 H), 5.04 (dd, J = 17.0,
1.5 Hz, 1 H), 5.12 (dd, J = 10.2, 1.9 Hz, 1 H), 5.52 (ddd, J = 17.0, 10.2,
9.5 Hz, 1 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 10.3, 20.8, 24.3, 26.4, 27.2,
48.9, 51.8, 55.6, 64.1, 117.6, 138.3, 156.9, 171.0.
Allylation of Carbon Electrophiles by Method B (Tables 10 and 11);
General Procedure I (GP I)
Alkenylsilane 2a (337 mg, 1.40 mmol) was added to a stirred mixture
of PtCl2 (6.7 mg, 0.025 mmol) and AgSbF6 (17.2 mg, 0.050 mmol) in
DCE (3 mL). The mixture was stirred at 70 °C for 2 h. Then electro-
phile 8 or 10 (1.00 mmol) was added to the mixture at 70 or 30 °C.
After the indicated time, the product was isolated by GP A. When
BF3·OEt2 (1 M in DCE) was used for the second step, the product was
isolated by GP C.
HRMS (EI+): m/z [M]+ calcd for C13H23NO4: 257.1627; found: 257.1629.
4-(3-Chloropropyl)-N-(methoxycarbonyl)hex-5-en-3-amine (7jf)
Following GP F using 6j (192 mg) and 2f (307 mg) (Table 8, entry 13)
gave 7jf as a colorless liquid; yield: 184 mg (78%); syn/anti 93:7.
IR (neat): 3323, 2962, 1694, 1538, 1462, 1245 cm–1
.
3-Nonylpent-4-en-2-one (9a)
1H NMR (500 MHz, CDCl3): δ (syn) = 0.91 (t, J = 7.4 Hz, 3 H), 1.13–1.22
(m, 1 H), 1.35–1.43 (m, 1 H), 1.60–1.87 (m, 4 H), 2.04–2.18 (m, 1 H),
3.34–3.60 (m, 3 H), 3.66 (s, 3 H), 4.25–4.50 (m, 1 H), 5.05 (dd, J = 17.1,
1.4 Hz, 1 H), 5.12 (dd, J = 10.2, 1.8 Hz, 1 H), 5.53 (ddd, J = 17.1, 10.2,
9.5 Hz, 1 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 10.4, 24.3, 28.2, 30.4, 44.9,
48.7, 51.9, 55.7, 117.8, 138.2, 156.9.
Following GP H using 8a (103 mg) and 2a (336 mg) (Table 10, entry 1)
gave 9a as a colorless liquid; yield: 157 mg (74%); ratio 9a/9a′ >99:1.
IR (neat): 2925, 2855, 1715, 1466, 1355, 919 cm–1
1H NMR (300 MHz, CDCl3): δ = 0.86 (t, J = 6.6 Hz, 3 H), 1.15–1.50 (m,
15 H), 1.63–1.75 (m, 1 H), 2.12 (s, 3 H), 3.05 (td, J = 8.1, 6.9 Hz, 1 H),
5.10–5.17 (m, 2 H), 5.63–5.75 (m, 1 H). The following signals of (E)-
9a′ were detected: δ = 1.87 (d, J = 7.0 Hz, 3 H), 2.28 (s, 3 H), 6.71 (q,
J = 7.0 Hz, 1 H).
.
HRMS (EI+): m/z [M]+ calcd for C11H20ClNO2: 233.1183; found:
233.1180.
13C NMR (75.5 MHz, CDCl3): δ = 14.0, 22.6, 27.0, 28.4, 29.2, 29.4 (2 C),
29.5, 30.7, 31.8, 58.4, 117.8, 136.4, 209.4.
HRMS (EI+): m/z [M]+ calcd for C14H26O: 210.1984; found: 210.1981.
N′-(Methoxycarbonyl)-N,N-phthaloyl-4-vinylheptane-1,5-di-
amine (7jg)
Following GP F using 6j (192 mg) and 2g (479 mg) (Table 8, entry 14)
gave 7jg as a white solid; yield: 281 mg (81%); syn/anti 91:9.
2,2-Dimethyl-4-nonylhex-5-en-3-one (9b)
IR (nujol): 3313, 1710, 1682, 1545, 724 cm–1
.
Following GP I using 8b (190 mg) and 2a (341 mg) with BF3·OEt2 (1.0
M in DCE, 0.40 mL) (Table 10, entry 6) gave 9b as a colorless liquid;
yield: 245 mg (95%).
1H NMR (500 MHz, CDCl3): δ (syn) = 0.84 (t, J = 7.2 Hz, 3 H), 1.09–1.74
(m, 6 H), 2.03–2.18 (m, 1 H), 3.27–3.68 [m, 6 H; including 3.54 (s)],
4.35–4.60 (m, 1 H), 4.99 (d, J = 17.0 Hz, 1 H), 5.05 (d, J = 10.2 Hz, 1 H),
5.45 (ddd, J = 17.0, 10.2, 9.8 Hz, 1 H), 7.65–7.67 (m, 2 H), 7.77–7.79
(m, 2 H).
13C NMR (125.8 MHz, CDCl3): δ (syn) = 10.2, 24.6, 26.1, 27.8, 37.4,
48.6, 51.8, 55.5, 117.7, 123.0 (2 C), 132.0 (2 C), 133.7 (2 C), 138.3,
156.9, 168.3 (2 C).
IR (neat): 2925, 2855, 1705, 1465, 997, 915 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.14 (s, 9 H),
1.20–1.69 (m, 16 H), 3.54–3.60 (m, 1 H), 5.04–5.08 (m, 2 H), 5.64–5.74
(m, 1 H).
13C NMR (75.5 MHz, CDCl3): δ = 14.1, 22.6, 26.1 (3 C), 27.3, 29.3, 29.4,
29.48, 29.53, 31.8, 33.0, 45.0, 51.3, 116.5, 138.2, 216.1.
HRMS (EI+): m/z [M]+ calcd for C19H24N2O4: 344.1736; found:
344.1735.
HRMS (EI+): m/z [M]+ calcd for C17H32O: 252.2453; found: 252.2458.
2-Nonyl-1-phenylbut-3-en-1-one (9c)
Stepwise Three-component Coupling to Homoallylic Amines 7 (Ta-
ble 9); General Procedure G (GP G)
Following GP I using 8c (229 mg) and 2a (385 mg) with BF3·OEt2 (1.0
M in DCE, 0.50 mL) (Table 10, entry 9) gave 9c as a colorless liquid;
yield: 245 mg (89%); ratio 9c/9c′ 91:9.
IR (neat): 2924, 2854, 1682, 1448, 1214, 704 cm–1
1H NMR (500 MHz, CDCl3): δ = 0.87 (t, J = 7.0 Hz, 3 H), 1.18–1.40 (m,
14 H), 1.57–1.64 (1 H), 1.83–1.90 (m, 1 H), 4.03 (dt, J = 8.0, 7.3 Hz, 1
H), 5.13–5.18 (m, 2 H), 5.90 (ddd, J = 17.0, 10.0, 8.5 Hz, 1 H), 7.44–7.48
(m, 2 H), 7.53–7.57 (m, 1 H), 7.97 (dd, J = 8.2, 1.2 Hz, 2 H). The follow-
ing signals of (E)- and (Z)-9c′ (E/Z 72:28) were detected: δ = 2.27–2.33
(m, 0.28 H), 2.48 (t, J = 7.6 Hz, 0.72 H), 6.30 (q, J = 6.9 Hz, 0.72 H), 5.77
(q, J = 6.9 Hz, 0.28 H).
13C NMR (75.5 MHz, CDCl3): δ = 14.1, 22.6, 27.2, 29.2, 29.4, 29.5 (2 C),
31.8, 32.2, 51.8, 117.3, 128.4 (2 C), 128.5 (2 C), 132.9, 136.8, 137.2,
201.2.
According to GP C, 2a (385 mg, 1.60 mmol) was isomerized to 4a with
PtCl2 (6.7 mg, 0.025 mmol) and AgSbF6 (17.2 mg, 0.050 mmol) in DCE
(3 mL). When MeCN or MeCN–DCE (2:1) was used as solvent for the
second step, the mixture was concentrated. H2NCO2Me (90.0 mg, 1.20
mmol), MeCN (3 mL), and aldehyde 5 (1.0 mmol) were added to the
crude product. The mixture was stirred and treated with neat
BF3·OEt2 (0.185 mL, 1.50 mmol) or a solution of BF3·OEt2 (1.0 M in
DCE, 1.5 mL, 1.5 mmol) at the temperature given in Table 9. When
DCE was used as solvent for the second step, H2NCO2Me, DCE (1 mL),
and 5 were added to the mixture without concentration. The mixture
was stirred and treated with a solution of BF3·OEt2 (1.0 M in DCE, 1.0
mL, 1.0 mmol). After reaction for 24 or 48 h, the product was isolated
by GP C.
.
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Synthesis
HRMS (EI+): m/z [M]+ calcd for C19H28O: 272.2140; found: 272.2129.
3-(Methoxymethyl)dodec-1-ene (11f)
Following GP I using 10f (80.4 mg) and 2a (341 mg) (Table 11, entry
14) gave 11f as a colorless liquid; yield: 156 mg (74%).
3-Nonylnon-1-en-4-one (9d)
IR (neat): 2924, 2854, 1462, 1119, 913 cm–1
.
Following GP I using 8d (216 mg) and 2a (339 mg) with BF3·OEt2 (1.0
M in DCE, 0.20 mL) (Table 10, entry 10) gave 9d as a colorless liquid;
yield: 227 mg (84%); ratio 9d/9d′ 97:3.
1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.18–1.48 (m,
16 H), 2.23–2.34 (m, 1 H), 3.30 (d, J = 6.4 Hz, 2 H), 3.33 (s, 3 H), 5.02–
5.09 (m, 2 H), 5.59–5.68 (m, 1 H).
IR (neat): 2926, 2855, 1714, 1466, 1377, 917 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.86–0.92 (m, 6 H), 1.15–1.79 (m, 22
H), 2.40 (ddd, J = 17.0, 7.5, 7.0 Hz, 1 H), 2.47 (ddd, J = 17.0, 8.0, 7.0 Hz,
1 H), 3.05–3.10 (m, 1 H), 5.11–5.15 (m, 2 H), 5.66–5.73 (m, 1 H). The
following signals of (E)-9c′ were detected: δ = 1.85 (d, J = 7.0 Hz, 3 H),
2.60 (t, J = 7.5 Hz, 2 H), 6.68 (q, J = 7.0 Hz, 1 H).
13C NMR (125.8 MHz, CDCl3): δ = 14.1, 22.7, 27.0, 29.3, 29.58, 29.59,
29.7, 31.2, 31.9, 44.1, 58.8, 76.5, 115.4, 140.4.
HRMS (EI+): m/z [M]+ calcd for C14H28O: 212.2140; found: 212.2137.
13C NMR (75.5 MHz, CDCl3): δ = 13.9, 14.1, 22.4, 22.6, 23.2, 27.1, 29.3,
29.43, 29.45, 29.5, 30.9, 31.4, 31.8, 41.4, 57.8, 117.5, 136.8, 211.6.
Supporting Information
HRMS (EI+): m/z [M]+ calcd for C18H34O: 266.2610; found: 266.2597.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560380.
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3-Nonylhepta-1,5-dien-4-one (9e)
Following GP I using 8e (156 mg) and 2a (339 mg) (Table 10, entry
11); gave 9e as a colorless liquid; yield: 143 mg (60%).
References
IR (neat): 2925, 2854, 1697, 1672, 1631, 969 cm–1
.
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1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.8 Hz, 3 H), 1.15–1.79 (m,
16 H), 1.89 (dd, J = 6.8, 1.6 Hz, 3 H), 3.23–3.29 (m, 1 H), 5.10–5.15 (m,
2 H), 5.70–5.80 (m, 1 H), 6.20 (dq, J = 15.6, 1.6 Hz, 1 H), 6.90 (dq,
J = 15.6, 6.8 Hz, 1 H).
13C NMR (75.5 MHz, CDCl3): δ = 14.0, 18.2, 22.6, 27.1, 29.2, 29.4,
29.48, 29.50, 31.1, 31.8, 55.3, 117.4, 130.4, 136.8, 142.7, 200.2.
HRMS (EI+): m/z [M]+ calcd for C16H28O: 236.2140; found: 236.2138.
3-(Diphenylmethyl)dodec-1-ene (11a)
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Following GP I using 10b (229 mg) and 2a (340 mg) (Table 11, entry 6)
gave 11a as a colorless liquid; yield: 320 mg (94%).
IR (neat): 2925, 2854, 1495, 1452, 910, 744, 702 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 0.87 (t, J = 7.0 Hz, 3 H), 1.21–1.39 (m,
16 H), 2.81–2.92 (m, 1 H), 3.72 (d, J = 10.5 Hz, 1 H), 4.86–4.92 (m, 2 H),
5.44 (ddd, J = 17.0, 10.5, 9.0 Hz, 1 H), 7.09–7.31 (m, 10 H).
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13C NMR (125.8 MHz, CDCl3): δ = 14.1, 22.7, 27.0, 29.3, 29.5, 29.6 (2
C), 31.9, 32.8, 47.9, 57.3, 116.0, 125.9, 126.0, 128.1 (4 C), 128.4 (2 C),
128.5 (2 C), 141.2, 144.1 (2 C).
Anal. Calcd for C25H34: C, 89.76; H, 10.24. Found: C, 89.57; H, 10.22.
3-(4-Methoxybenzyl)dodec-1-ene (11c)
Following GP I using 10e (157 mg) and 2a (340 mg) (Table 11, entry
12) gave 11c as a colorless liquid; yield: 206 mg (71%).
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IR (neat): 2924, 2853, 1513, 1465, 1247, 1040 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 7.0 Hz, 3 H), 1.18–1.45 (m,
16 H), 2.18–2.28 (m, 1 H), 2.53 (dd, J = 13.6, 7.6 Hz, 1 H), 2.59 (dd,
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4.92 (dd, J = 10.4, 2.0 Hz, 1 H), 5.59 (ddd, J = 17.2, 10.4, 8.6 Hz, 1 H),
6.79–6.82 (m, 2 H), 7.03–7.06 (m, 2 H).
13C NMR (125.8 MHz, CDCl3): δ = 14.1, 22.7, 27.2, 29.3, 29.62, 29.63,
29.7, 31.9, 34.1, 40.9, 45.8, 55.1, 113.4 (2 C), 114.3, 130.1 (2 C), 132.7,
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HRMS (EI+): m/z [M]+ calcd for C20H32O: 288.2453; found: 288.2457.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 520–534