Chiral NHC Ligands Bearing a Pyridine Moiety in Copper-Catalyzed 1,2-Addition of Dialkylzinc Reagents to β-Aryl-α,β-unsaturated N-Tosylaldimines

Article abstract of DOI:10.1021/acs.joc.6b00093

Asymmetric 1,2-addition of dialkylzinc reagents to α,β-unsaturated N-tosylaldimines was catalyzed by copper salt in the presence of chiral imidazolium salts having a pyridine ring, which were derived from amino acid, to afford the corresponding chiral allylic amines with up to 91% ee in reasonably high yields. The chiral N-heterocyclic carbene (NHC) ligand played an important role in controlling chemoselectivity.

Full text of DOI:10.1021/acs.joc.6b00093

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Article
Chiral NHC Ligands Bearing a Pyridine Moiety in Copper-
Catalyzed 1,2-Addition of Dialkylzinc Reagents to
beta-Aryl-alpha,beta-unsaturated N-Tosylaldimines
Takahiro Soeta, Tomohiro Ishizaka, and Yutaka Ukaji
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00093 • Publication Date (Web): 11 Mar 2016
Downloaded from http://pubs.acs.org on March 16, 2016
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Chiral NHC Ligands Bearing a Pyridine Moiety in
Copper-Catalyzed 1,2-Addition of Dialkylzinc Reagents to
β-Aryl-α,β-unsaturated N-Tosylaldimines
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Takahiro Soeta*, Tomohiro Ishizaka, Yutaka Ukaji*
Division of Material Chemistry, Graduate School of Natural Science and Technology,
Kanazawa University, Kakuma, Kanazawa 920-1192, Japan.
soeta@se.kanazawa-u.ac.jp; ukaji@staff.kanazawa-u.ac.jp
Abstract
–
Cl
+
N
N
HN
t-Bu
N
O
6
.5 mol%
R1
5
.0 mol% CuCl ·2H O
2
2
Ts
R12Zn
+
Ar
NHTs
Ar
N
toluene-HMPA
1,2-selective
up to 91% ee
Asymmetric 1,2-addition of dialkylzinc reagents to α,β-unsaturated N-tosylaldimines
was catalyzed by copper salt in the presence of chiral imidazolium salts having a
pyridine ring, which were derived from amino acid, to afford the corresponding chiral
allylic amines with up to 91% ee in reasonably high yields. The chiral N-heterocyclic
carbene (NHC) ligand played an important role in controlling chemoselectivity.
Introduction
Allylic amines are common in biologically active compounds, such as the antifungal
1
2
drug naftifine and the calcium channel blocker flunarizine. Chiral allylic amines, in
particular, are synthetically and biologically relevant, not only for their therapeutic
properties but also because they have been proven to be useful intermediates—for
3
example, in the synthesis of conformationally restricted peptide isosteres. Several
methods of obtaining such compounds stereoselectively have recently been developed,
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based either on control of asymmetric induction in the new C-C bond, or functional
group transformation in a suitable precursor. In particular, catalytic asymmetric addition
of organometallic reagents to the C=N double bond of imines constitutes an important
0
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method of obtaining optically active amines with a stereogenic center at the α-position.
Three types of enantioselective 1,2-addition to aldimines have been developed by
various research groups: chiral-ether-mediated addition of organolithium reagents to
5
4
-methoxyphenylimines,
copper(I)-chiral-amidophosphane-catalyzed addition of
6
dialkylzinc
reagents
to
N-sulfonylimines,
and
rhodium-chiral-amidophosphane-catalyzed addition of arylboroxine reagents to
7
N-sulfonylimines. As part of our continuing effort to broaden the scope of
8
copper-chiral-NHC-catalyzed addition of dialkylzinc reagents to imines, we explored
the possibility of controlling 1,4- and 1,2-addition to aldimines of α,β-unsaturated
9
aldehydes to afford the corresponding chiral allylic amines (Scheme 1) . We
2 2
demonstrate herein that a combination of CuCl ·2H O and amino acid-based chiral
imidazolium salts bearing a pyridine ring catalyzes selective 1,2-addition of dialkylzinc
reagents to aldimines of α,β-unsaturated aldehydes to give the corresponding allylic
amines in reasonably high yields with up to 91% ee.
Chiral NHC Ligand 5
R2
R2
R1
CuX2
R22Zn
+
+
Ar
N
R1
NHR1
Ar
Ar
N
1
2
3
4
Chemoselectivity?
Enantioselectivity?
Scheme 1. Chemo- and enantioselective alkylation of α,β-unsaturated aldimines.
10c
After the discovery of the first stable nucleophilic carbene around 1990 by Bertrand,
Arduengo and coworkers, the utilization of N-heterocyclic carbenes (NHCs) has been
1
0
paid attention in organic synthesis. NHCs have become popular ligands, along with
11
phosphine, in organometallic chemistry. Recently, chiral NHCs have been examined
in the area of asymmetric synthesis. During the course of studies, chiral multidendate
1
2
13
14
15
NHC has been developed.
In particular, Katsuki,
Sakaguchi,
Williams,
1
6
17
Hayashi,
and Tomioka
all independently developed chiral multidendate
imidazolium salts as a NHC precursors, whicn were used for copper-catalyzed
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asymmetric reactions. We have also reported the synthesis of a series of chiral
imidazolium salts, derived from commercially available -amino acids and each bearing
L
a pyridine moiety, and the corresponding NHC generated in situ from the salts act as a
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ligand for copper catalytic asymmetric reaction of N-sulfonylimines with dialkylzinc
8
reagents (Figure 1) .
Results and Discussion
Figure 1. Chiral imidazolium salts derived from amino acid bearing a pyridine ring and
phenyl ring.
–
–
–
X
Cl
Cl
+
N
+
N
+
N
N
N
N
HN
t-Bu
HN
t-Bu
HN
t-Bu
N
O
O
O
N
–
X = Cl 5a X = BF4 5c
X = Br 5b X = PF6 5d
7
6
N
9
–
Cl
–
Bn
O
Me
O
Cl
Cl
+
N
+
N
+
N
N
N
HN
t-Bu
N
HN
t-Bu
N
N
N
t-Bu
O
8
10
–
–
–
Cl
Cl
O
Cl
+
N
+
N
+
N
N
N
N
HN
HN
Ph
N
N
N
N
O
O
O
11
12
13
At first, we have examined the reaction of α,β-unsaturated N-sulfonylaldimine 1a with
diethylzinc (2E) in the presence of 5.0 mol% copper(II) triflate and the chiral
imidazolium salt 5a (6.5 mol%) in toluene at 0 °C. Surprisingly, the main product was
19
the 1,2-adduct (R)-3aE, with a yield of 64% and an ee of 85%, while the 1,4-adduct
2
0
(
S)-4E was obtained in 25% yield (Table 1, entry 1). Generally, in the case of
copper-catalyzed addition reactions of organometallic reagents to α,β-unsaturated
carbonyl compounds in the absence of an NHC ligand, the predominant reaction is
1
,4-addition, as shown in Table 1, entry 2. These results indicate that the NHC ligand
generated from the chiral imidazolium salt 5a controls the chemoselectivity of this
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reaction system. In the absence of hexamethylphosphoric triamide (HMPA), although
the desired ethylated products 3aE and 4E were obtained in 22% yield and 52% yield,
respectively, there was no enantioselectivity (Table 1, entry 3). We have found that
HMPA was efficient co-solvent for chemical yield and enantioselectivity (entry 3). The
enantioselectivity increased to 89% ee when the reaction was carried out at –40 °C
0
1
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3
4
5
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9
0
(entry 4). To confirm the influence of the substituent on the imine nitrogen group on the
chemoselectivity of the reaction, we examined various substituents on the N-sulfonyl
group (entries 5–7). For substrates bearing a methyl or 2,4,6-triisopropylphenyl group
on the sulfonyl group (TIPBS), the same levels of chemoselectivity and
enantioselectivity were observed as for the 4-tolyl group (entries 5 and 6). When there
was a 2-nitrophenyl group on the sulfonyl group, the reaction did not proceed at all, and
the starting 1d was recovered (entry 7).
Since it was evident that the reaction was influenced by the solvent,, we examined
different solvents in the ethylation of α,β-unsaturated N-tosylaldimine 1a with
diethylzinc (entries 8–11). When dichloromethane was used as a solvent, the reaction
proceeded smoothly to give the ethylated product 3aE in 55% yield with 69% ee (entry
8
). In addition, diethylether and THF, which are coordinative solvents, were also
effective to this reaction, affording 3aE with good enantioselectivity (entries 9 and 10).
When acetonitrile was used as a solvent, the reaction proceeded slowly, affording an
almost 1:1 mixture of 1,2- and 1,4-adducts with lower enantioselectivity (entry 11).
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Table 1. Asymmetric ethylation of N-α,β-unsaturated N-sulfonylaldimines with
diethylzinc in the presence of Copper salts.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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47
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49
50
51
52
53
54
55
56
57
58
59
60
5
.0 mol%
Cu(OTf)2
6.5 mol%
Et
Et
H
5
a
Y
+
Et Zn
+
2
Ph
N
solv.-HMPA
40 °C, 24 h
Ph
NHY
Ph
O
–
1
1
a Y = Ts
b Y = Ms
2E
3aE Y = Ts
4E
then, HCl aq-THF
3bE Y = Ms
3cE Y = TIPBS
3dE Y = 2-Ns
1c Y = TIPBS
d Y = 2-Ns
1
a
b
Entry
1
Solvent
Yield of
ee of 3/%
Yield of ee of 4/%
4/%
3/%
c
1
1a
1a
1a
1a
1b
1c
1d
1a
1a
1a
1a
toluene
toluene
toluene
toluene
toluene
toluene
toluene
64
21
22
64
63
50
nr
85
-
25
60
52
17
21
28
nr
30
-
c, d
2
e
3
0
2
4
5
6
7
8
9
89
87
89
-
29
22
28
-
CH
Et
THF
MeCN
2
Cl
2
55
52
62
47
69
82
83
47
26
24
27
27
29
26
21
2
O
1
1
0
1
38
a
b
2
.0 equiv of 2E and 10 equiv of HMPA were used unless otherwise noted. The ee was
c
determined by HPLC after conversion to the corresponding alcohol using NaBH
4
. The reaction
d
e
was carried out at 0 °C. In the absence of HMPA and 5a. In the absence of HMPA.
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3
3
3
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4
4
4
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5
5
5
5
5
5
5
6
–
We examined the various kind of chiral imizolium salts 5–13. We found that Cl (as in
5a) was suitable counter anion of the imidazolium salt, however, the reactions using
–
–
–
chiral imidazolium salts with Br (5b), BF
4 6
(5c), and PF (5d) all resulted in slightly
0
1
2
3
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0
lower enantioselectivities, especially in the case of 5c, in which the 1,2- and 1,4-adducts
were obtained in a ratio of almost 1:1 (Table 2, entries 1–4). Next, we carried out
present asymmetric ethylation of the α,β-unsaturated N-tosylaldimine 1a with the
imidazolium salt 6 bearing a phenyl ring. The reaction proceeded slower than that using
5
a, affording the product 3aE in 39% yield with 70% ee (entry 5). This result indicated
clealy that the pyridinyl group is critical in realizing the high chemical yield and
stereoselectivity. Furthermore, introduction of a nitrogen atom onto the C3-position of
the aromatic ring (7) lowered the enantioselectivity (entry 6). Chiral imidazolium salts
prepared from
L
-alanine (8),
L
-phenylalanine (9), and -proline (10) were examined in
L
the present asymmetric reaction (entries 7-9). In all cases, reaction proceeded efficiently,
however, the enantioselectivities of the product was lower. The amidocarbonyl group of
the imidazolium salt played an important role for the enantioselectivity. Thus, the
imidazolium salt 5a bearing pivaloyl group was found to be the best ligand for the
present catalytic asymmetric reaction, affording 3aE with 89% ee, whereas, chiral
imidazolium salts bearing isobutylamide or benzamide groups were not effective to this
reaction (entries 10 and 11). Finally, the hydrogen atom of the amidocarbonyl group
was found to be a critical factor in realizing high enantio- and chemoselectivity. Thus,
when a imidazolium salt 13 bearing phthalimide group was used for asymmetric
copper-catalyzed ethylation of 1a, the significant decreace of enantioselectivity was
observed, and the 1,4-adduct 4E was obtained as the major product with a yield of 60%
and 10% ee (entry 12).
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Table 2. Copper-catalyzed asymmetric ethylation of α,β-unsaturated N-tosylaldimine
using various chiral imidazolium salts.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
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37
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39
40
41
42
43
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46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
.0 mol%
Cu(OTf)2
6.5 mol%
imidazolium salt
Et
Et
H
Ts
+
Et Zn
+
2
Ph
N
toluene-HMPA
40 °C, 24 h
Ph
NHTs
Ph
O
–
1
a
2E
3aE
4E
then, HCl aq-THF
a
Entry
Imidazolium salt Yield of 3/% ee of 3/% Yield of 4/% ee of 4/%
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
6
64
63
48
69
39
17
49
52
45
72
49
26
89
86
88
88
70
66
32
44
–29
75
63
45
17
25
35
23
15
22
38
30
26
19
37
60
29
37
16
38
30
36
13
27
23
24
24
–10
7
8
9
10
11
12
13
1
1
1
0
1
2
a
2
.0 equiv of 2E and 10 equiv of HMPA were used.
The use of other copper salts in the asymmetric alkylation of α,β-unsaturated
N-tosylaldimine was also investigated (Table 3). In the case of CuCl ·2H O in particular,
higher chemoselectivity was observed, and the chiral allylic amine 3aE was obtained in
5% yield with 91% ee (entry 2). Other copper(I) salts were also good candidates in this
2
2
7
reaction, affording the product with excellent enantioselectivity and high yields,
whereas only in the case of CuCN, the 1,4-adduct was obtained as the major product in
64% with 4% ee (entry 11).
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1
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1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 3. The effect of copper salts in the catalytic asymmetric ethylation of
α,β-unsaturated N-tosylaldimine
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
.0 mol%
Cu salt
6.5 mol%
5
a
Et
Et
H
Ts
+
Et Zn
+
2
Ph
N
toluene-HMPA
40 °C, 24 h
Ph
NHTs
Ph
O
–
1
a
2E
3aE
4E
then, HCl aq-THF
a
Entry
Cu salt
Cu(OTf)
CuCl ·2H
CuCl
Yield of 3/% ee of 3/% Yield of 4/% ee of 4/%
1
2
3
4
5
6
7
8
9
2
64
75
68
72
76
70
74
72
70
73
17
89
91
90
90
89
89
90
90
91
89
88
17
11
21
14
12
15
10
9
29
54
53
41
47
41
62
44
34
51
4
2
2
O
2
Cu(acac)
(CuOTf) -PhH
Cu(MeCN) BF
2
2
4
4
b
CuTC
CuCl
CuBr
CuI
15
17
64
1
1
0
1
CuCN
a
b
2.0 equiv of 2E and 10 equiv of HMPA were used.. CuTC = copper(I)
thiophene-2-carboxylate.
Under the optimized reaction conditions, the scope of the catalytic asymmetric
alkylation was demonstrated with various kinds of β-aryl α,β-unsaturated
N-tosylaldimines and dialkylzinc reagents (Table 4). It was gratifying to observe that
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wide range of α,β-unsaturated N-tosylaldimines were applicable to the present catalytic
2 2
system when the reactions were carried out using 5 mol% CuCl ·2H O and 6.5 mol% of
the imidazolium salt 5a. The α,β-unsaturated N-tosylaldimines 1e and 1f, bearing a 1-
or 2-naphthyl group at the β-position, were good substrates, giving the 1,2-adducts 3eE
and 3fE as major products with 82% ee and 86% ee, respectively (entries 2 and 3). Even
the relatively deactivated α,β-unsaturated N-tosylaldimine 1g, derived from
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
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60
4
-methoxycinnamaldehyde, was successfully used in the reaction, affording the product
3
gE in 53% yield with 91% ee (entry 4). Other substituted α,β-unsaturated
N-tosylaldimines bearing an electron-withdrawing group at the para-position of the
phenyl group at the β-position were investigated: the reactions of diethylzinc (2E) with
α,β-unsaturated
4-(trifluoromethyl)cinnamaldehyde and 4-bromocinnamaldehyde, gave the products
hE and 3iE with 85% ee and 88% ee, respectively (entries 5 and 6). The reaction of 1j,
N-tosylaldimines
1h
and
1i,
derived
from
3
derived from 3-(furan-2-yl)acrylaldehyde, gave 3jE in 62% yield with 91% ee (entry 7).
The reactions of 1k, 1l, and 1m, which contain a 2-, 3-, or 4-methylphenyl group at the
β-position, gave 3kE, 3lE, and 3mE with 85% ee, 89% ee, and 88% ee, respectively,
and a significant improvement in chemoselectivity was achieved by introducing a
2
-substituted phenyl group at the β-position (entries 8–10). Since a trimethylsilyl (TMS)
group on a phenyl ring is easily convertible to a proton or halogen, the ethylation
reaction was examined using the 2-TMS-cinnamaldehyde imine 1n. The ratio of the
1
9
,2- to 1,4- product was dramatically improved to 11:1, giving 3nE in 80% yield with
0% ee (entry 11). Furthermore, the α,β-unsaturated N-tosylaldimine 1o, bearing a
bulky 2,4,6-trimethylphenyl group at the β-position, was found to be 1,2-selectively
converted to 3oE, with 88% ee and a yield of 93% (entry 12). Diisopropylzinc (2I) was
also employed in this reaction, and the reaction proceeded with high chemoselectivity to
afford the 1,2-adduct (R)-3nI with 72% ee and 87% yield (entry 13). On the other hand,
the methylation of 1n with 5.0 equiv of dimethylzinc (2M) was sluggish at 0 °C,
generating (R)-3nM with 88% ee and a yield of 59% after 120 h (entry 14). Alkylation
of 1o with diisopropylzinc (2I) and dimethylzinc (2M) selectively afforded the
1,2-adducts 3oI and 3oM with good enantioselectivities (entries 15 and 16).
Furthermore, diphenylzinc (2P) and diallylzinc (2A) were employed in this reaction.
The reactions of 1n and 1o with diphenylzinc (2P) proceeded smoothly to afford the
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6
products 3nP and 3oP with good to high enantioselectivities but chemoselectivities
were lower (entries 17 and 18). In the case of diallylzinc (2A), the 1,2-adducts were
obtained predominantly in excellent yields, however, no enantioselectivities were
observed (entries 19 and 20).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Table 4. Catalytic asymmetric 1,2-addition reactions of α,β-unsaturated
N-tosylaldimines with various dialkylzinc reagents.
5
.0 mol%
CuCl ·2H O
2
2
6
.5 mol%
R
5
a
Ts
+
R Zn
2
Ar
N
toluene-HMPA
40 °C, 24 h
Ar
NHTs
–
1
2
3
then, HCl aq-THF
a
Entry
1
Ar
R
Yield of
ee of 1,2-/1,4-
3/%
3/%
C
6
H
5
(1a)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
Et (2E)
i-Pr (2I)
Me (2M)
i-Pr (2I)
Me (2M)
Ph (2P)
75 (3aE)
60 (3eE)
63 (3fE)
53 (3gE)
71 (3hE)
67 (3iE)
62 (3jE)
60 (3kE)
69 (3lE)
56 (3mE)
80 (3nE)
93 (3oE)
87 (3nI)
59 (3nM)
93 (3oI)
55 (3oM)
60 (3nP)
91
82
86
91
85
88
91
85
89
88
90
88
72
88
73
79
86
7:1
3:1
d
2
1-naphthyl (1e)
2-naphthyl (1f)
d
3
3:1
4
5
6
7
8
4-MeOC
4-CF
4-BrC
6
H
4
(1g)
3:1
3
C
6
H
4
(1h)
(1i)
6:1
6
H
4
5:1
2-furyl (1j)
3:1
f
2-MeC
3-MeC
4-MeC
2-TMSC
2,4,6-Me
6
H
4
(1k)
(1l)
15:1
4:1
e
9
6 4
H
e
10
6
H
4
(1m)
(1n)
(1o)
2:1
d
1
1
6
H
4
11:1
>20:1
15:1
3:1
d,
1
2
3
C
6
H
2
d
13
2-TMSC
2-TMSC
6
6
H
4
(1n)
(1n)
h
14
H
4
d,g
h
15
2,4,6-Me
3
3
C
C
6
6
H
2
2
(1o)
(1o)
>20:1
i
16
2,4,6-Me
H
nd
d i
17
2-TMSC
6
H
4
(1n)
3:1
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d i
d j
d j
1
8
2,4,6-Me
2-TMSC
2,4,6-Me
3
C
6
H
2
(1o)
(1n)
(1o) CH
Ph (2P)
37 (3oP)
99 (3nA)
99 (3oA)
70
0
1:1
19
6
H
4
CH
2
=CH-CH
2
(2A)
(2A)
>20:1
>20:1
2
0
3
C
6
H
2
2
=CH-CH
2
0
10
11
12
13
14
15
16
17
18
19
20
21
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49
50
51
52
53
54
55
56
57
58
59
60
a
b
2
.0 equiv of 2 and 10 equiv of HMPA were used unless otherwise noted. The ratio was
1
c
determined by H-NMR. The absolute configurations of 3, except for 3aE, were determined
d
based on the analogous reactions in Table 1 (also see reference 18). The reaction was carried
e
f
out at 0 °C. The reaction was carried out at –20 °C. The ee was determined by HPLC using
the corresponding amino alcohol, which was prepared from 3kE by treatment of ozonolysis
g
h
i
followed by reduction. Using 3.0 equiv of 2E. Using 5.0 equiv of 2M at 0 °C for 120 h. The
1
i
peaks of the 1,2- and 1,4-adducts overlapped in H-NMR. Diphenylzinc was prepared by
21
j
22
following literature.
Diallylzinc was prepared by following literature .
The 2-TMS group on the phenyl ring of 3nE was easily converted to other functional
groups. Thus, 3nE was protodesilylated with potassium iodide and TMSCl in the
2
3
presence of water to afford (R)-3aE in 74% yield without any racemization (eq. 1).
The chiral allylic amines obtained from these catalytic asymmetric reactions could be
transformed to the corresponding 2-aminoalcohols. We demonstrated ozonolysis of 3aE
with 98% ee, which was obtained by recrystallization, followed by reduction to afford
2
4
the 2-aminoalcohol 14 in 89% yield without any loss of enantioselectivity (eq. 2).
KI (2.0 equiv)
TMSCl (2.0 equiv)
TMS
Et
H
Et
H O ( 1.0 equiv)
Ts
2
Ts
(1)
N
H
N
H
MeCN, rt, 6 h
3nE (83% ee)
3aE
4%, 83% ee
7
Et
Et
O3
Ts
HO
Ts
(2)
N
H
CH Cl , –78 ºC, 2.5 h
N
H
2
2
then, NaBH4
3
aE
14
98% ee
89%, 98% ee
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6
Conclusion
Asymmetric 1,2-addition of dialkylzinc reagents to α,β-unsaturated N-tosylaldimines
was catalyzed by copper salt in the presence of chiral imidazolium salts having a
pyridine ring, which were derived from amino acid, to afford the corresponding chiral
allylic amines with up to 91% ee in reasonably high yields. We have found that the
chiral NHC ligand played an important role in controlling chemo- and enantioselectivity.
In addition, the obtained allylic amine was able to convert the corresponding chiral
amino alcohol without any loss of enantioselectivities.
0
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9
0
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3
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7
8
9
0
Experimental Section
1
13
H NMR and C NMR spectra were recorded using a 400 MHz NMR spectrometer.
Chemical shifts were given in ppm downfield from TMS with chloroform as an internal
standard. Infrared spectra (IR) were recorded as FT-IR spectra are reported in terms of
−
1
frequency of absorption (cm ). HRMS (FAB and DART) were measured with a
quadrupole and TOF mass spectrometers. Unless otherwise noted, all reagents were
reagent grade and used without further purification.
8, 25
The substrates 1 were prepared following the reported literatures.
4-Methyl-N-((1E,2E)-3-phenylallylidene)benzenesulfonamide (1a)
1
White solid of mp = 116–117 °C (recrystallized from hexane/ethyl acetate). H NMR
(
CDCl
7.40–7.56 (m, 6H), 7.86 (d, J = 8.0 Hz, 2H), 8.79 (d, J = 9.6 Hz, 1H). C NMR
CDCl ): 21.6, 124.6, 127.9, 128.6, 129.1, 129.7, 131.6, 134.0, 135.2, 144.4, 153.8,
70.8. IR (KBr): 2980, 1620, 1580, 1490, 1450, 1360, 1310, 1290, 1170, 1150, 1090
3
): 2.44 (s, 3H), 7.00 (dd, J = 9.6, 14.4 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H),
1
3
(
3
1
–
1
+
2
cm . HRMS–DART (m/z): Calcd for C16H16NO S [M+H] : 286.0902. Found:
286.0892.
N-((1E,2E)-3-Phenylallylidene)methanesulfonamide (1b)
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2
3
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5
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7
8
9
1
White solid of mp = 103–104 °C (recrystallized from hexane/ethyl acetate). H NMR
(CDCl
3
): 3.07 (s, 3H), 7.00 (dd, J = 9.6, 16.0 Hz, 1H), 7.34–7.59 (m, 6H), 8.75 (d, J =
13
9
.6 Hz, 1H). C NMR (CDCl ): 40.2, 124.2, 128.4, 128.6, 129.1, 131.7, 133.9, 154.4.
3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
–
1
IR (KBr): 2970, 1620, 1580, 1460, 1360, 1310, 1260, 1160, 1040 1010, 970 cm .
+
HRMS–DART (m/z): Calcd for C10
H
12NO
2
S [M+H] : 210.0589. Found: 210.0596.
2
,4,6-Triisopropyl-N-((1E,2E)-3-phenylallylidene)benzenesulfonamide (1c)
1
White solid of mp = 163–165 °C (recrystallized from hexane/ethyl acetate). H NMR
(CDCl ): 1.19–1.26 (m, 18H), 2.89 (septet, J = 6.8 Hz, 1H), 4.21 (septet, J = 6.8 Hz,
H), 6.98 (dd, J = 9.6, 15.6 Hz, 1H), 7.16 (s, 2H), 7.40–7.55 (m, 6H), 8.72 (d, J = 9.6
3
2
1
3
Hz, 1H). C NMR (CDCl
3
): 23.5, 24.7, 29.7, 34.2, 123.8, 125.0, 128.5, 129.1, 131.0,
131.4, 134.2, 151.0, 152.8, 153.5, 169.3. IR (KBr): 2950, 1620, 1580, 1460, 1360, 1300,
–
1
+
1
260, 1150, 1040 cm . HRMS–DART (m/z): Calcd for C24
H32NO
2
S [M+H] : 398.2154.
Found: 398.2150.
2-Nitro-N-((1E,2E)-3-phenylallylidene)benzenesulfonamide (1d)
1
White solid of mp = 150–152 °C (recrystallized from hexane/ethyl acetate). H NMR
(
CDCl
J = 16.0 Hz, 1H), 7.77–7.89 (m, 3H), 8.34–8.36 (m, 1H), 8.81 (d, J = 9.6 Hz, 1H). C
NMR (CDCl ): 124.2, 124.7, 129.0, 129.2, 131.9, 132.0, 132.1, 132.6, 134.0, 134.5,
43.8, 156.0, 174.5. IR (KBr): 2960, 1610, 1580, 1540, 1460, 1360, 1320, 1260, 1160,
3
): 7.04 (dd, J = 9.6, 16.0 Hz, 1H), 7.43–7.46 (m, 3H), 7.58–7.60 (m, 2H), 7.64 (d,
1
3
3
1
1
–
1
+
13 2 4
120, 1050 cm . HRMS–DART (m/z): Calcd for C15H N O S [M+H] : 317.0596.
Found: 317.0587.
4
-Methyl-N-((1E,2E)-3-(naphthalen-1-yl)allylidene)benzenesulfonamide (1e)
1
White solid of mp = 152–153 °C (recrystallized from hexane/ethyl acetate). H NMR
(CDCl
3
): 2.45 (s, 3H), 7.12 (dd, J = 8.4, 15.6 Hz, 1H), 7.37 (d, J = 8.0 Hz, 2H),
7
1
.51–7.65 (m, 3H), 7.84 (d, J = 8.4 Hz, 1H), 7.89–7.92 (m, 3H), 7.96 (d, J = 8.4 Hz,
1
3
H), 8.15 (d, J = 8.0 Hz, 1H), 8.35 (d, J = 15.6 Hz, 1H), 8.93 (d, J = 9.6 Hz, 1H). C
): 21.6, 122.6, 125.4, 125.8, 126.4, 126.6, 127.4, 127.9, 128.9, 129.8,
30.9, 131.1, 132.0, 133.6, 135.3, 144.5, 150.2, 170.8. IR (KBr): 2960, 1620, 1590,
NMR (CDCl
3
1
1
–
1
2
370, 1320, 1180, 1150, 1090 cm . HRMS–DART (m/z): Calcd for C20H18NO S
+
[
M+H] : 336.1058. Found: 336.1054.
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1
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2
2
2
2
2
2
2
2
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3
3
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3
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4-Methyl-N-((1E,2E)-3-(naphthalen-2-yl)allylidene)benzenesulfonamide (1f)
1
White solid of mp = 166–167 °C (recrystallized from hexane/ethyl acetate). H NMR
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(CDCl
3
): 2.44 (s, 3H), 7.10 (dd, J = 9.6, 15.6 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.56 (m,
2H), 7.65 (d, J = 15.6 Hz, 1H), 7.67–7.68 (m, 1H), 7.83–7.89 (m, 5H), 7.98 (s, 1H),
1
3
8
1
.83 (d, J = 9.6 Hz, 1H). C NMR (CDCl
3
): 21.6, 123.2, 124.8, 127.0, 127.8, 127.9,
28.0, 128.8, 129.1, 129.8, 131.3, 131.7, 133.1, 134.7, 135.4, 144.4, 153.8, 170.8. IR
–
1
(
KBr): 2950, 1610, 1560, 1340, 1310, 1290, 1240, 1160, 1090 cm . HRMS–DART
+
(m/z): Calcd for C20
H18NO
2
S [M+H] : 336.1058. Found: 336.1057.
N-((1E,2E)-3-(4-Methoxyphenyl)allylidene)-4-methylbenzenesulfonamide (1g)
1
White solid of mp = 101–103 °C (recrystallized from hexane/ethyl acetate). H NMR
(CDCl
3
): 2.43 (s, 3H), 3.86 (s, 3H), 6.88 (dd, J = 9.6, 15.6 Hz, 1H), 6.94 (d, J = 8.4 Hz,
2
H), 7.33 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 15.6 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 7.85
1
3
(
d, J = 8.4 Hz, 2H), 8.74 (d, J = 9.6 Hz, 1H). C NMR (CDCl ): 21.6, 55.5, 114.6,
3
122.3, 127.0, 127.8, 129.2, 130.6, 135.6, 144.2, 153.9, 162.6, 171.1. IR (KBr): 2950,
–1
1
630, 1600, 1570, 1360, 1300, 1260, 1150, 1080, 1010 cm . HRMS–DART (m/z):
+
Calcd for C17
H18NO
3
S [M+H] : 316.1007. Found: 316.0998.
4
-Methyl-N-((1E,2E)-3-(4-(trifluoromethyl)phenyl)allylidene)benzenesulfonamide
1h)
White solid of mp = 153–155 °C (recrystallized from hexane/ethyl acetate). H NMR
(CDCl ): 2.45 (s, 3H), 7.04 (d, J = 9.2, 15.6 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.50 (d, J
15.6 Hz, 1H), 7.63–7.68 (m, 4H), 7.86 (d, J = 8.0 Hz, 2H), 8.79 (d, J = 9.2 Hz, 1H).
(
1
3
=
1
3
1
3
C NMR (CDCl ): 21.6, 123.6 ( JC-F = 271.8 Hz), 126.1 ( JC-F = 2.9 Hz), 128.0, 128.6,
3
2
129.9, 132.7 ( JC-F = 32.4 Hz), 134.9, 137.3, 144.8, 151.1, 170.1. IR (KBr): 2960, 1630,
–
1
1
2 3
590, 1460, 1320, 1160, 1090 cm . HRMS–DART (m/z): Calcd for C17H15NO SF
+
[
M+H] : 354.0776. Found: 354.0772.
N-((1E,2E)-3-(4-Bromophenyl)allylidene)-4-methylbenzenesulfonamide (1i)
1
White solid of mp = 193–194 °C (recrystallized from hexane/ethyl acetate). H NMR
(CDCl
3
): 2.44 (s, 3H), 6.96 (dd, J = 9.2, 16.0 Hz, 1H), 7.35 (d, J = 7.8 Hz, 2H),
7
..39–7.44 (m, 3H), 7.57 (d, J = 7.8 Hz, 2H), 7.86 (d, J = 7.8 Hz, 2H), 8.77 (d, J = 9.2
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2
3
4
5
6
7
8
9
1
3
Hz, 1H). C NMR (CDCl
3
): 21.6, 125.2, 126.1, 127.9, 129.6, 129.8, 132.4, 133.0, 135.1,
144.6, 152.0, 170.5. IR (KBr): 2960, 1620, 1570, 1480, 1320, 1160, 1090, 1070, 1000
–1
+
cm . HRMS–DART (m/z): Calcd for C16
2
H15NO SBr [M+H] : 364.0007. Found:
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
3
64.0000.
N-((1E,2E)-3-(Furan-2-yl)allylidene)-4-methylbenzenesulfonamide (1j)
White solid of mp = 110–111 °C (recrystallized from hexane/ethyl acetate). H NMR
CDCl ): 2.43 (s, 3H), 6.54 (dd, J = 1.6, 3.2 Hz, 1H), 6.77 (d, J = 3.2 Hz, 1H), 6.84 (dd,
1
(
3
J = 9.6, 15.2 Hz, 1H), 7.22 (d, J = 15.2 Hz, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.57 (d, J =
13
1
1
.6 Hz, 1H), 7.84 (d, J = 8.0 Hz, 2H), 8.68 (d, J = 9.6 Hz, 1H). C NMR (CDCl ): 21.5,
3
13.1, 117.6, 122.1, 127.8, 129.7, 135.4, 138.5, 144.3, 146.5, 150.8, 170.2. IR (KBr):
–
1
2960, 1630, 1590, 1460, 1390, 1350, 1310, 1290, 1170, 1090 cm . HRMS–DART
+
(
m/z): Calcd for C14
H
14NO
3
S [M+H] : 276.0694. Found: 276.0703.
4
-Methyl-N-((1E,2E)-3-(o-tolyl)allylidene)benzenesulfonamide (1k)
White solid of mp = 122–124 °C (recrystallized from hexane/ethyl acetate). H NMR
CDCl ): 2.44 (s, 3H), 2.46 (s, 3H), 6.94 (dd, J = 9.6. 15.6 Hz, 1H), 7.25–7.26 (m, 2H),
.31–7.35 (m, 3H), 7.58 (d, J = 7.6 Hz, 1H), 7.78 (d, J = 15.6 Hz, 1H), 7.87 (d, J = 7.6
1
(
3
7
1
3
Hz, 2H), 8.81 (d, J = 9.6 Hz, 1H). C NMR (CDCl
3
): 19.7, 21.6, 125.5, 126.7, 126.8,
1
1
27.9, 129.8, 131.1, 131.4, 132.9, 135.4, 138.3, 144.5, 151.4, 171.1. IR (KBr): 2980,
–1
620, 1580, 1350, 1310, 1290, 1170, 1150, 1080 cm . HRMS–DART (m/z): Calcd
+
for C17
H18NO
2
S [M+H] : 300.1058. Found: 300.1064.
4
-Methyl-N-((1E,2E)-3-(m-tolyl)allylidene)benzenesulfonamide (1l)
White solid of mp = 90–91 °C (recrystallized from hexane/ethyl acetate). H NMR
(CDCl ): 2.38 (s, 3H), 2.44 (s, 3H), 6.97 (dd, J = 9.6, 15.6 Hz, 1H), 7.24–7.37 (m, 6H),
.46 (d, J = 15.6 Hz, 1H), 7.85 (d, J = 8.4 Hz, 2H), 8.77 (d, J = 9.6 Hz, 1H). C NMR
CDCl ): 21.2, 21.5, 124.4, 125.7, 127.8, 129.0, 129.2, 129.7, 132.4, 134.0, 135.4, 138.8,
1
3
1
3
7
(
3
–
1
1
44.4, 154.1, 170.9. IR (KBr): 2970, 1620, 1570, 1320, 1290, 1160, 1150, 1090 cm .
+
HRMS–DART (m/z): Calcd for C17
H
18NO
2
S [M+H] : 300.1058. Found: 300.1063.
4
-Methyl-N-((1E,2E)-3-(p-tolyl)allylidene)benzenesulfonamide (1m)
1
White solid of mp = 150–151 °C (recrystallized from hexane/ethyl acetate). H NMR
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(
CDCl
3
): 2.40 (s, 3H), 2.44 (s, 3H), 6.94 (dd, J = 9.6, 15.6 Hz, 1H), 7.23 (d, J = 8.0 Hz,
2H), 7.33 (d, J = 8.0 Hz, 2H), 7.44 (t, J = 8.0 Hz, 2H), 7.46 (d, J = 15.6 Hz, 1H), 7.85 (d,
13
J = 8.0 Hz, 2H), 8.75 (d, J = 9.6 Hz, 1H). C NMR (CDCl ): 21.5, 123.5, 127.8, 128.6,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
29.7, 129.8, 131.4, 135.3, 142.4, 144.3, 154.0, 171.0. IR (KBr): 2960, 1610, 1580,
–
1
1460, 1370, 1320, 1300, 1180, 1160, 1090 cm . HRMS–DART (m/z): Calcd for
+
C
17
H18NO
2
S [M+H] : 300.1058. Found: 300.1056.
4
-Methyl-N-((1E,2E)-3-(2-(trimethylsilyl)phenyl)allylidene)benzenesulfonamide
(1n)
White solid of mp = 124–125 °C (recrystallized from hexane/ethyl acetate). H NMR
CDCl ): 0.39 (s, 9H), 2.45 (s, 3H), 6.93 (dd, J = 9.2, 15.6 Hz, 1H), 7.36 (d, J = 8.4 Hz,
2H), 7.39–7.43 (m, 2H), 7.58–7.60 (m, 1H), 7.67–7.69 (m, 1H), 7.85–7.86 (m, 1H),
1
(
3
1
3
7
1
.88 (d, J = 8.4 Hz, 2H), 8.81 (d, J = 9.2 Hz, 1H). C NMR (CDCl
3
): 0.0, 21.2, 125.0,
26.3, 127.5, 129.3, 129.4, 129.9, 134.7, 135.0, 139.1, 142.0, 144.1, 154.3, 170.3. IR
–
1
(KBr): 2960, 1620, 1580, 1320, 1260, 1160, 1120, 1090, 970 cm . HRMS–DART
+
(m/z): Calcd for C19
H24NO
2
SSi [M+H] : 358.1297. Found: 358.1298.
N-((1E,2E)-3-Mesitylallylidene)-4-methylbenzenesulfonamide (1o)
White solid of mp = 157–158 °C (recrystallized from hexane/ethyl acetate). H NMR
CDCl ): 2.30 (s, 3H), 2.36 (s, 6H), 2.44 (s, 3H), 6.68 (dd, J = 9.2, 15.6 Hz, 1H), 6.92 (s,
H), 7.35 (d, J = 7.6 Hz, 2H), 7.71 (d, J= 15.6 Hz, 1H), 7.87 (d, J = 7.6 Hz, 2H), 8.78 (d,
1
(
3
2
1
3
J = 9.2 Hz, 1H). C NMR (CDCl
3
): 21.3, 21.5, 21.6, 127.9, 129.2, 129.8, 129.9, 130.2,
135.4, 137.8, 140.3, 144.5, 152.9, 171.7. IR (KBr): 2920, 1620, 1580, 1380, 1320, 1290,
–1
+
1
180, 1150, 1090 cm . HRMS–DART (m/z): Calcd for C19
2
H22NO S [M+H] : 328.1371.
Found: 328.1359.
General
procedure
for
the
alkylation
of
β-Aryl-α,β-unsaturated
N-Toluenesulfonylaldimines
with dialkylzinc reagentes catalyzed by
NHC-copper(I) complex
Under Ar atmosphere, the solution of imidazolium salt 4 (11.4 mg, 0.033 mmol) in 0.9
mL of HMPA and 2 mL of toluene was added to CuCl2·2H O (4.2 mg, 0.025 mmol).
2
The mixture was diluted with toluene (10.1 mL) and the whole was cooled to –40 °C.
After 15 min, a hexane solution of dialkyllzinc (1.0 mL, 1.0 mmol) was added dropwise
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over 3 min at –40 °C and stirred for 30 min. A solution of imine 1 (0.5 mmol) in 3.0 mL
of toluene was added dropwise over 4 min at –40 °C. After 24 h, the reaction was
quenched with satd. NH
organic layer was separated and the aqueous layer was extracted with ethyl acetate. The
combined organic layers were washed with satd. NaHCO and brine, and then dried
over Na SO . Concentration gave a pale yellow oil, which was treated with 6 M HCl aq
1 mL) in THF (5 mL) for 0.5 h at room temperature. The reaction mixture was
4
Cl aq and stirred at room temperature for another 0.5 h. The
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60
3
2
4
(
neutralized by satd. NaHCO3. The organic layer was separated and the aqueous layer
was extracted with ethyl acetate. The combined organic layers were washed with brine,
and then dried over Na
chromatography.
2 4
SO . Concentration and purification by silica gel column
In the case of the asymmetric methylation, dimethylzinc (1.0 M in toluene) was used.
Absolute configuration of (R)-3aE was determined by comparison of the specific
18
rotation with the reported value . Those of other 3 were assigned by the reaction
analogy.
(
R,E)-4-Methyl-N-(1-phenylpent-1-en-3-yl)benzenesulfonamide (3aE)
Silica gel column chromatography (hexane/ ethyl acetate = 20/1~3/1) gave 3aE (119
2
5
mg, 75% yield, 0.5 mmol scale) as a white solid of mp = 98–99 °C and [α]
D
+97.5 (c
0
.53, CHCl
3
). The ee was determined to be 91% by HPLC (Daicel Chiralcel IA,
1
hexane/i-PrOH = 20/1, 0.7 mL/min, 254 nm, major 37.9 min and minor 33.9 min). H
NMR (CDCl
3
): 0.89 (t, J = 7.2 Hz, 3H), 1.57–1.64 (m, 2H), 2.31 (s, 3H), 3.84–3.88 (m,
1H), 4.46 (d, J = 8.0 Hz, 1H), 5.71 (dd, J = 7.6, 15.6 Hz, 1H), 6.22 (d, J = 15.6 Hz, 1H),
1
3
7
.12 (d, J = 8.0 Hz, 2H), 7.18–7.27 (m, 5H), 7.72 (d, J = 8.0 Hz, 2H). C NMR
CDCl ): 9.9, 21.3, 38.8, 57.8, 126.2, 127.2, 127.5, 128.3, 128.6, 129.4, 131.4, 136.2,
138.0, 143.1. IR (KBr): 3260, 2960, 1600, 1500, 1460, 1440, 1320, 1160, 1030, 970
(
3
–
1
+
2
cm . HRMS–FAB (m/z): Calcd for C18H22NO S [M+H] : 316.1371. Found: 316.1368.
(
R,E)-N-(1-Phenylpent-1-en-3-yl)methanesulfonamide (3bE)
Silica gel column chromatography (hexane/ ethyl acetate = 20/1~3/1) gave 3bE (75 mg,
2
5
6
D 3
3% yield, 0.5 mmol scale) as a colorless oil and [α] +47.8 (c 0.21, CHCl ). The ee
was determined to be 87% by HPLC (Daicel Chiralcel IB, hexane/i-PrOH = 20/1, 1.5
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1
mL/min, 254 nm, major 22.5 min and minor 17.1 min). H NMR (CDCl
3
): 1.00 (t, J =
7.2 Hz, 3H), 1.66–1.71 (m, 2H), 2.95 (s, 3H), 3.97–4.04 (m, 1H), 4.59 (d, J = 6.4 Hz,
13
1
H), 6.05 (dd, J = 8.4, 15.6 Hz, 1H), 6.61 (d, J = 15.6 Hz, 1H), 7.25–7.39 (m, 5H). C
0
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2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
NMR (CDCl ): 10.2, 29.1, 42.2, 58.0, 126.4, 128.0, 128.6, 129.2, 132.0, 136.0. IR
3
–
1
(KBr): 3280, 2970, 1600, 1490, 1450, 1440, 1320, 1150, 1040, 970 cm . HRMS–FAB
+
(
m/z): Calcd for C12
H18NO
2
S [M+H] : 240.1058. Found: 240.1041.
(
R,E)-2,4,6-Triisopropyl-N-(1-phenylpent-1-en-3-yl)benzenesulfonamide (3cE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3cE (107 mg,
2
5
5
D 3
0% yield, 0.5 mmol scale) as a colorless oil and [α] +63.7 (c 0.27, CHCl ). The ee
was determined to be 89% by HPLC (Daicel Chiralcel IB x2, hexane/i-PrOH = 20/1,
1
0.7 mL/min, 254 nm, major 11.9 min and minor 8.8 min). H NMR (CDCl
3
): 0.92 (t, J
=
7.2 Hz, 3H), 1.18 (d, J = 7.6 Hz, 3H), 1.19 (d, J = 7.6 Hz, 3H), 1.22 (d, J = 7.2 Hz,
6
3
H), 1.26 (d, J = 6.8 Hz, 6H), 1.59–1.67 (m, 2H), 2.82 (septet, J = 7.2 Hz, 1H),
.94–3.97 (m, 1H), 4.13 (septet, J = 6.8 Hz, 2H), 4.45 (d, J = 6.0 Hz, 1H), 5.71 (dd, J =
7.6, 15.6 Hz, 1H), 6.22 (d, J = 15.6 Hz, 1H), 7.02–7.03 (m, 2H), 7.08 (s, 2H), 7.15–7.25
13
(
m, 3H). C NMR (CDCl ): 10.0, 23.5, 24.6, 24.6, 24.9, 29.0, 29.7, 34.0, 57.5, 123.6,
3
1
26.2, 127.6, 128.3, 128.8, 131.6, 134.2, 136.2, 149.6, 152.4. IR (KBr): 3290, 2960,
–
1
1600, 1560, 1490, 1460, 1390, 1320, 1150, 1060, 960 cm . HRMS–FAB (m/z): Calcd
+
for C26
H38NO
2
S [M+H] : 428.2623. Found: 428.2606.
(
R,E)-4-Methyl-N-(1-(naphthalen-1-yl)pent-1-en-3-yl)benzenesulfonamide (3eE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3eE (110 mg,
2
5
6
0
D
0% yield, 0.5 mmol scale) as a yellow solid of mp = 144–146 °C and [α] +63.1 (c
.36, CHCl
3
). The ee was determined to be 82% by HPLC (Daicel Chiralcel IB x2,
1
hexane/i-PrOH = 20/1, 0.8 mL/min, 240 nm, major 88.2 min and minor 82.5 min). H
NMR (CDCl
3
): 0.97 (t, J = 7.2 Hz, 3H), 1.63–1.73 (m, 2H), 2.27 (s, 3H), 3.96–4.04 (m,
1
7
H), 4.70 (brs, 1H), 5.79 (dd, J = 7.6, 15.6 Hz, 1H), 7.01 (d, J = 15.6 Hz, 1H),
1
3
.17–7.21 (m, 3H), 7.34 (t, J = 7.6 Hz, 1H), 7.45–7.49 (m, 2H), 7.72–7.82 (m, 5H). C
): 10.0, 21.4, 29.2, 57.9, 123.6, 123.8, 125.4, 125.8, 126.0, 127.2, 128.0,
28.4, 128.9, 129.6, 130.9, 132.0, 133.4, 134.0, 138.2, 143.2. IR (KBr): 3290, 2960,
NMR (CDCl
3
1
1
–
1
590, 1490, 1430, 1400, 1330, 1160, 1080, 970 cm . HRMS–DART (m/z): Calcd for
+
C
22
H24NO
2
S [M+H] : 366.1528. Found: 366.1517.
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(R,E)-4-Methyl-N-(1-(naphthalen-2-yl)pent-1-en-3-yl)benzenesulfonamide (3fE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3fE (115 mg,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
5
6
D
3% yield, 0.5 mmol scale) as a white solid of mp = 144–146 °C and [α] +86.2 (c
0.36, CHCl
3
). The ee was determined to be 86% by HPLC (Daicel Chiralcel IB,
1
hexane/i-PrOH = 20/1, 1.0 mL/min, 254 nm, major 25.0 min and minor 22.4 min). H
NMR (CDCl
3
): 0.92 (t, J = 7.6 Hz, 3H), 1.57–1.71 (m, 2H), 2.25 (s, 3H), 3.88–3.95 (m,
1
H), 4.63 (d, J = 7.6 Hz, 1H), 5.53 (dd, J = 7.6, 15.6 Hz, 1H), 6.35 (d, J = 15.6 Hz, 1H),
7.17 (d, J = 8.4 Hz, 2H), 7.28 (dd, J = 4.6, 8.8 Hz, 1H), 7.41–7.48 (m, 3H), 7.70–7.78
13
(
m, 5H). C NMR (CDCl ): 10.0, 21.3, 28.9, 57.9, 123.4, 125.9, 126.3, 126.4, 127.2,
3
1
27.3, 127.6, 127.9, 129.1, 129.5, 131.7, 132.9, 133.4, 133.7, 138.2, 143.2. IR (KBr):
–
1
3250, 2930, 1600, 1500, 1420, 1330, 1160, 1080, 1040, 980 cm . HRMS–FAB (m/z):
+
Calcd for C22
H24NO
2
S [M+H] : 366.1528. Found: 366.1529.
(
R,E)-N-(1-(4-Methoxyphenyl)pent-1-en-3-yl)-4-methylbenzenesulfonamide (3gE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3gE (92 mg,
2
5
5
D
3% yield, 0.5 mmol scale) as a white solid of mp = 95–97 °C and [α] +94.3 (c 0.45,
CHCl
3
). The ee was determined to be 91% by HPLC (Daicel Chiralcel IB x 2,
1
hexane/i-PrOH = 20/1, 0.5 mL/min, 254 nm, major 103.6 min and minor 100.4 min). H
NMR (CDCl
3
): 0.80 (t, J = 7.6 Hz, 3H), 1.43–1.59 (m, 2H), 2.26 (s, 3H), 3.74 (s, 3H),
.72–3.79 (m, 1H), 4.40 (brs, 1H), 5.50 (dd, J = 8.0, 15.6 Hz, 1H), 6.08 (d, J = 15.6 Hz,
H), 6.72 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 7.65 (d,
3
1
1
3
J = 8.4 Hz, 2H). C NMR (CDCl
3
): 10.0, 21.4, 29.0, 55.3, 57.8, 113.4, 126.4, 127.3,
1
1
27.5, 129.0, 129.5, 131.1, 138.2, 143.1, 159.2. IR (KBr): 3300, 2960, 1610, 1510,
–
1
3
460, 1420, 1330, 1160, 1030, 970 cm . HRMS–FAB (m/z): Calcd for C19H24NO S
+
[M+H] : 346.1477. Found: 346.1452.
(
R,E)-4-Methyl-N-(1-(4-(trifluoromethyl)phenyl)pent-1-en-3-yl)benzenesulfonamid
e (3hE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3hE (137 mg,
2
5
7
D
1% yield, 0.5 mmol scale) as a white solid of mp = 67–68 °C and [α] +85.4 (c 0.85,
CHCl
3
). The ee was determined to be 85% by HPLC (Daicel Chiralcel IB,
1
hexane/i-PrOH = 20/1, 1.0 mL/min, 254 nm, major 17.3 min and minor 16.2 min). H
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4
4
4
4
4
4
4
4
4
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5
5
5
5
5
5
5
5
6
NMR (CDCl
3
): 0.85 (t, J = 7.2 Hz, 3H), 1.56–1.65 (m, 2H), 2.31 (s, 3H), 3.81–3.92 (m,
1H), 4.66 (d, J = 6.4 Hz, 1H), 5.83 (dd, J = 7.2, 15.6 Hz, 1H), 6.28 (d, J = 15.6 Hz, 1H),
13
7
.18–7.27 (m, 4H), 7.50 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H). C NMR
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
(CDCl
3
): 9.9, 21.3, 28.7, 57.5, 123.5 ( JC-F = 271.8 Hz), 125.3 ( JC-F = 2.9 Hz), 126.5,
2
127.2, 129.3 ( JC-F = 26.7 Hz), 129.5, 130.1, 131.5, 138.1, 139.8, 143.3. IR (KBr): 3270,
–
1
2
960, 1610, 1420, 1320, 1160, 1100, 1080, 970 cm . HRMS–FAB (m/z): Calcd for
+
C
19
H
21
F
3
NO
2
S [M+H] : 384.1245. Found: 384.1263.
(R,E)-N-(1-(4-Bromophenyl)pent-1-en-3-yl)-4-methylbenzenesulfonamide (3iE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3iE (132 mg,
2
5
6
D
7% yield, 0.5 mmol scale) as a white solid of mp = 83–84 °C and [α] +78.1 (c 1.23,
CHCl
3
). The ee was determined to be 88% by HPLC (Daicel Chiralcel IB x 2,
1
hexane/i-PrOH = 20/1, 1.0 mL/min, 254 nm, major 17.3 min and minor 16.2 min). H
NMR (CDCl
3
): 0.87 (t, J = 7.2 Hz, 3H), 1.54–1.63 (m, 2H), 2.30 (s, 3H), 3.81–3.88 (m,
1
H), 4.45 (d, J = 7.6 Hz, 1H), 5.72 (dd, J = 7.2, 15.6 Hz, 1H), 6.17 (d, J = 15.6 Hz, 1H),
6.98 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 7.6 Hz, 2H), 7.38 (d, J = 7.6 Hz, 2H), 7.71 (d, J =
13
8
1
.4 Hz, 2H). C NMR (CDCl ): 9.9, 21.3, 28.7, 57.6, 121.2, 127.2, 127.8, 129.4, 129.6,
3
30.2, 131.3, 135.2, 138.0, 143.1. IR (KBr): 3230, 2960, 1600, 1490, 1460, 1330, 1150,
–
1
+
2
1080, 980 cm . HRMS–FAB(m/z): Calcd for C18H21BrNO S [M+H] : 394.0476.
Found: 394.0457.
(
R,E)-N-(1-(Furan-2-yl)pent-1-en-3-yl)-4-methylbenzenesulfonamide (3jE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3jE (94 mg,
2
5
6
0
D
2% yield, 0.5 mmol scale) as a white solid of mp = 64–66 °C and [α] +124.6 (c
.63, CHCl
3
). The ee was determined to be 91% by HPLC (Daicel Chiralcel IA,
1
hexane/i-PrOH = 20/1, 1.5 mL/min, 254 nm, major 19.5 min and minor 15.2 min). H
NMR (CDCl
3
): 0.86 (t, J = 7.2 Hz, 3H), 1.48–1.59 (m, 2H), 2.35 (s, 3H), 3.77–3.86 (m,
H), 4.60 (brs, 1H), 5.72 (dd, J = 8.8, 15.6 Hz, 1H), 6.07 (d, J = 15.6 Hz, 1H), 6.09 (s,
H), 6.31 (dd, J = 2.0, 3.6 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.26 (s, 1H), 7.73 (d, J =
1
1
8
1
1
1
3
.4 Hz, 2H). C NMR (CDCl
3
): 9.9, 21.4, 28.5, 57.3, 108.2, 111.2, 119.9, 127.2, 127.3,
29.5, 138.0, 141.9, 143.2, 151.8. IR (KBr): 3240, 2970, 1640, 1490, 1440, 1320, 1160,
–
1
+
3
090, 1070, 970 cm . HRMS–FAB(m/z): Calcd for C16H20NO S [M+H] : 306.1164
Found: 306.1157.
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(R,E)-4-Methyl-N-(1-(o-tolyl)pent-1-en-3-yl)benzenesulfonamide (3kE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3kE (123 mg,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2
5
6
0% yield, 0.5 mmol scale) as a white solid of mp = 53–54 °C and [α]
D
+83.8 (c 1.22,
CHCl
3
). The ee was determined to be 85% by HPLC (Daicel Chiralcel IA,
hexane/i-PrOH = 10/1, 1.0 mL/min, 254 nm, major 48.4 min and minor 23.5 min) after
1
conversion to the corresponding amino alcohol 13. H NMR (CDCl
3
): 0.89 (t, J = 7.2
Hz, 3H), 1.51–1.67 (m, 2H), 2.19 (s, 3H), 2.31 (s, 3H), 3.79–3.90 (m, 1H), 5.07 (brs,
1H), 5.62 (dd, J = 7.2, 15.6 Hz, 1H), 6.44 (d, J = 15.6 Hz, 1H), 7.02–7.13 (m, 4H), 7.19
13
(
d, J = 8.0 Hz, 2H), 7.75 (d, J = 8.0 Hz, 2H). C NMR (CDCl ): 9.9, 19.5, 21.3, 29.0,
3
5
7.9, 125.5, 125.7, 127.1, 127.4, 129.2, 129.4, 130.0, 130.1, 135.2, 135.4, 138.1, 143.0.
–
1
IR (KBr): 3280, 2970, 1600, 1490, 1460, 1320, 1160, 1100, 1090, 970 cm .
+
HRMS–FAB(m/z): Calcd for C19
H24NO
2
S [M+H] : 330.1528. Found: 330.1524.
(
R,E)-4-Methyl-N-(1-(m-tolyl)pent-1-en-3-yl)benzenesulfonamide (3lE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3lE (113 mg,
2
5
6
D
9% yield, 0.5 mmol scale) as a white solid of mp = 84–85 °C and [α] +92.8 (c 0.68,
CHCl
3
). The ee was determined to be 89% by HPLC (Daicel Chiralcel IA x 2,
1
hexane/i-PrOH = 20/1, 1.0 mL/min, 254 nm, major 38.3 min and minor 35.1 min). H
NMR (CDCl
3
): 0.81 (t, J = 7.2 Hz, 3H), 1.43–1.56 (m, 2H), 2.22 (s, 3H), 2.25 (s, 3H),
.73–3.80 (m, 1H), 4.63 (brs, 1H), 5.62 (dd, J = 7.2, 15.6 Hz, 1H), 6.11(d, J = 15.6 Hz,
H), 6.84 (d, J = 7.6 Hz, 2H), 6.95 (d, J = 7.6 Hz, 1H), 7.06 (t, J = 7.6 Hz, 1H), 7.12 (d,
3
1
1
3
J = 8.0 Hz, 2H), 7.66 (d, J = 8.0 Hz, 2H). C NMR (CDCl
3
): 9.9, 21.2, 21.3, 28.8, 57.8,
1
23.5, 126.9, 127.2, 128.2, 128.3, 128.4, 129.4, 131.5, 136.2, 137.8, 138.2, 143.0. IR
–
1
(
KBr): 3270, 2930, 1600, 1490, 1430, 1330, 1160, 1090, 970 cm . HRMS–FAB(m/z):
+
Calcd for C19
H24NO
2
S [M+H] : 330.1528. Found: 330.1507.
(
R,E)-4-Methyl-N-(1-(p-tolyl)pent-1-en-3-yl)benzenesulfonamide (3mE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3mE (92 mg,
2
5
56% yield, 0.5 mmol scale) as a white solid of mp = 98–99 °C and [α]
D
+98.8 (c 0.16,
CHCl
3
). The ee was determined to be 88% by HPLC (Daicel Chiralcel IB x2,
1
hexane/i-PrOH = 20/1, 1.0 mL/min, 254 nm, major 32.8 min and minor 39.2 min). H
NMR (CDCl
3
): 0.88 (t, J = 7.2 Hz, 3H), 1.54–1.65 (m, 2H), 2.31 (s, 3H), 2.32 (s, 3H),
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1
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1
1
1
1
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1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
.80–3.88 (m, 1H), 4.41 (d, J = 7.6 Hz, 1H), 5.66 (dd, J = 7.6, 16.0 Hz, 1H), 6.18 (d, J =
16.0 Hz, 1H), 7.01 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H),
13
7
1
.72 (d, J = 8.0 Hz, 2H). C NMR (CDCl ): 9.9, 21.3, 21.4, 28.9, 57.8, 126.2, 127.3,
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
27.6, 129.0, 129.5, 131.5, 133.5, 137.5, 138.1, 143.1. IR (KBr): 3290, 2960, 1600,
–
1
2
1510, 1420, 1310, 1160, 1090, 970 cm . HRMS–FAB(m/z): Calcd for C19H24NO S
+
[
M+H] : 330.1528. Found: 330.1515.
(R,E)-4-Methyl-N-(1-(2-(trimethylsilyl)phenyl)pent-1-en-3-yl)benzenesulfonamide
3nE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3nE (155 mg,
(
2
5
80% yield, 0.5 mmol scale) as a white solid of mp = 82–83 °C and [α]
D
+99.8 (c 0.39,
CHCl
3
). The ee was determined to be 90% by HPLC (Daicel Chiralcel IB x 2,
1
hexane/i-PrOH = 20/1, 0.5 mL/min, 254 nm, major 38.7 min and minor 41.7min). H
3
NMR (CDCl ): 0.21 (s, 9H), 0.80 (t, J = 7.2 Hz, 3H), 1.45–1.63 (m, 2H), 2.23 (s, 3H),
3.77 (m, 1H), 4.85 (d, J = 7.6 Hz, 1H), 5.57 (dd, J = 7.2, 15.2 Hz, 1H), 6.57 (d, J = 15.2
Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 7.09–7.13 (m, 3H), 7.16 (d, J = 7.6 Hz, 1H), 7.37 (d,
1
3
J = 8.0 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H). C NMR (CDCl
3
): 0.1, 10.0, 21.3, 28.9, 57.9,
125.4, 126.7, 127.2, 129.0, 129.5, 129.9, 132.8, 134.2, 138.1, 138.3, 142.2, 143.2. IR
–
1
(KBr): 3250, 2960, 1600, 1490, 1430, 1310, 1250, 1170, 1120, 1090, 970 cm .
+
HRMS–FAB(m/z): Calcd for C21
H30NO
2
SSi [M+H] : 388.1767. Found: 388.1785.
(R,E)-N-(1-Mesitylpent-1-en-3-yl)-4-methylbenzenesulfonamide (3oE)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3oE (166 mg,
2
5
9
D
3% yield, 0.5 mmol scale) as a white solid of mp = 111–113 °C and [α] +82.8 (c
0.93, CHCl
3
). The ee was determined to be 88% by HPLC (Daicel Chiralcel IB x 2,
1
hexane/i-PrOH = 20/1, 0.5 mL/min, 254 nm, major 42.7 min and minor 49.2 min). H
NMR (CDCl
3
): 0.92 (t, J = 7.2 Hz, 3H), 1.58–1.64 (m, 2H), 2.08 (s, 6H), 2.24 (s, 3H),
2
1
.41 (s, 3H), 3.84–3.91 (m, 1H), 4.49 (d, J = 7.2 Hz, 1H), 5.39 (dd, J = 7.2, 16.0 Hz,
H), 6.29 (d, J = 16.0 Hz, 1H), 6.81 (s, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 8.0
13
Hz, 2H). C NMR (CDCl ): 9.9, 20.6, 20.9, 21.4, 29.3, 57.8, 127.0, 128.4, 129.0, 129.6,
3
1
1
33.0, 133.8, 135.7, 136.2, 138.1, 143.2. IR (KBr): 3290, 2920, 1610, 1510, 1430, 1320,
–
1
+
2
160, 1090, 990 cm . HRMS–FAB(m/z): Calcd for C21H28NO S [M+H] : 358.1841.
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Found: 358.1836.
(
R,E)-4-Methyl-N-(4-methyl-1-(2-(trimethylsilyl)phenyl)pent-1-en-3-yl)benzenesulf
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
onamide (3nI)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3nI (175 mg,
2
5
8
D
7% yield, 0.5 mmol scale) as a white solid of mp = 94–96 °C and [α] +83.3 (c 0.51,
CHCl
3
). The ee was determined to be 72% by HPLC (Daicel Chiralcel IA x 2,
1
hexane/i-PrOH = 20/1, 0.8 mL/min, 254 nm, major 21.1 min and minor 22.5 min). H
NMR (CDCl
3
): 0.28 (s, 9H), 0.89 (d, J = 6.8 Hz, 3H), 0.93 (d, J = 6.8 Hz, 3H), 1.85
septet, J = 6.8 Hz, 1H), 2.27 (s, 3H), 3.72–3.78 (m, 1H), 4.55 (d, J = 7.6 Hz, 1H), 5.65
dd, J = 8.0, 15.6 Hz, 1H), 6.60 (d, J = 15.6 Hz, 1H), 7.08 (d, J = 7.2 Hz, 1H),
(
(
1
3
7.16–7.24 (m, 4H), 7.43–7.46 (m, 1H), 7.72 (d, J = 8.4 Hz, 2H). C NMR (CDCl
3
): 0.1,
8.3, 18.7, 21.3, 33.4, 62.1, 125.4, 126.7, 127.2, 128.0, 129.0, 129.5, 133.5, 134.2,
38.1, 138.3, 142.1, 143.1. IR (KBr): 3250, 2960, 1600, 1440, 1320, 1160, 1100, 1040,
1
1
9
–
1
+
2
70 cm . HRMS–FAB(m/z): Calcd for C22H32NO SSi [M+H] : 402.1923. Found:
402.1901.
(
R,E)-4-Methyl-N-(4-(2-(trimethylsilyl)phenyl)but-3-en-2-yl)benzenesulfonamide
(3nM)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3nM (111
25
mg, 59% yield, 0.5 mmol scale) as a white solid of mp = 94–96 °C and [α]
.51, CHCl
hexane/i-PrOH = 20/1, 0.8 mL/min, 254 nm, major 42.9 min and minor 46.1 min). H
NMR (CDCl ): 0.28 (s, 9H), 1.30 (d, J = 6.8 Hz, 3H), 2.38 (s, 3H), 4.06–4.14 (m, 1H),
.40 (d, J = 7.2 Hz, 1H), 5.75 (dd, J = 6.4, 15.6 Hz, 1H), 6.73 (d, J = 15.6 Hz, 1H),
D
+83.9 (c
0
3
). The ee was determined to be 88% by HPLC (Daicel Chiralcel IA x 2,
1
3
4
1
3
7.16–7.28 (m, 5H), 7.44–7.47 (m, 1H), 7.70 (d, J = 8.4 Hz, 2H). C NMR (CDCl
3
): 0.3,
2
1
1.3, 21.6, 51.5, 125.3, 126.6, 127.1, 129.0, 129.5, 131.2, 131.6, 134.1, 137.8, 138.2,
–1
42.1, 143.2. IR (KBr): 3280, 2960, 1590, 1420, 1320, 1150, 1120, 1090, 960 cm .
+
HRMS–FAB(m/z): Calcd for C20
H28NO
2
SSi [M+H] : 374.1610. Found: 374.1619.
(
R,E)-N-(1-Mesityl-4-methylpent-1-en-3-yl)-4-methylbenzenesulfonamide (3oI)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3oI (173 mg,
2
5
9
D
3% yield, 0.5 mmol scale) as a white solid of mp = 97–99 °C and [α] +60.7 (c 1.06,
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2
2
2
2
2
2
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3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
CHCl
3
). The ee was determined to be 73% by HPLC (Daicel Chiralcel IB,
1
hexane/i-PrOH = 20/1, 0.7 mL/min, 254 nm, major 13.1 min and minor 15.1 min). H
NMR (CDCl
s, 3H), 2.37 (s, 3H), 3.77–3.82 (m, 1H), 4.80 (brs, 1H), 5.40 (dd, J = 7.6, 16.8 Hz, 1H),
6.25 (d, J = 16.8 Hz, 1H), 6.80 (s, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 8.0 Hz,
3
): 0.93 (d, J = 6.8 Hz, 6H), 1.86 (septet, J = 6.8 Hz, 1H), 2.05 (s, 6H), 2.24
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
1
3
2
1
1
H). C NMR (CDCl
3
): 18.1, 18.4, 20.7, 20.8, 21.4, 33.4, 61.7, 126.9, 128.4, 129.5,
29.6, 131.9, 133.2, 135.7, 136.1, 138.3, 143.0. IR (KBr): 3280, 2960, 1600, 1440,
–
1
+
2
320, 1160, 1090, 970 cm . HRMS–FAB(m/z): Calcd for C22H30NO S [M+H] :
372.1997. Found: 372.1974.
(
R,E)-N-(4-Mesitylbut-3-en-2-yl)-4-methylbenzenesulfonamide (3oM)
Silica gel column chromatography (hexane/ethyl acetate = 20/1~3/1) gave 3oM (94 mg,
2
5
5
D
5% yield, 0.5 mmol scale) as a white solid of mp = 95–97 °C and [α] +65.2 (c 0.48,
CHCl
3
). The ee was determined to be 79% by HPLC (Daicel Chiralcel IB x 2,
1
hexane/i-PrOH = 20/1, 1.0 mL/min, 254 nm, major 24.7 min and minor 27.8 min). H
NMR (CDCl
3
): 1.31 (d, J = 6.8 Hz, 3H), 2.10 (s, 6H), 2.26 (s, 3H), 2.40 (s, 3H),
4
1
.05–4.13 (m, 1H), 4.51 (brs, 1H), 5.40 (dd, J = 6.4, 16.0 Hz, 1H), 6.32 (d, J = 16.0 Hz,
1
3
H), 6.81 (s, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H). C NMR (CDCl ):
3
20.6, 20.9, 21.5, 22.4, 51.8, 127.0, 128.0, 128.5, 129.6, 132.9, 135.2, 135.7, 136.3,
38.0, 143.3. IR (KBr): 3270, 2920, 1610, 1460, 1430, 1320, 1160, 1100, 1090, 970
1
–1
+
2
cm . HRMS–FAB(m/z): Calcd for C20H26NO S [M+H] : 344.1684. Found: 344.1671.
(S,E)-4-methyl-N-(1-phenyl-3-(2-(trimethylsilyl)phenyl)allyl)benzenesulfonamide
3nP)
Silica gel column chromatography (hexane/ ethyl acetate = 20/1~3/1) gave 3nP (130
(
2
5
mg, 60% yield, 0.5 mmol scale) as a colorless oil of [α]
D 3
+37.5 (c 0.40, CHCl ). The
ee was determined to be 86% by HPLC (Daicel Chiralcel IB, hexane/i-PrOH = 20/1, 1.0
1
mL/min, 254 nm, major 14.2 min and minor 11.7 min). H NMR (CDCl
3
): 0.15 (s, 9H),
2
.34 (s, 3H), 5.00 (d, J = 6.2 Hz, 1H), 5.14 (t, J = 6.2 Hz, 1H), 6.07 (dd, J = 6.2, 15.6
Hz, 1H), 6.58 (d, J = 15.6 Hz, 1H), 7.14–7.30 (m, 10H), 7.41–7.44 (m, 1H), 7.65 (d, J =
13
8
1
2
.2 Hz, 2H). C NMR (CDCl ): –0.13, 21.3, 125.2, 126.8, 127.1, 127.1, 127.6, 128.5,
3
29.1, 129.4, 129.6, 133.8, 134.2, 137.6, 138.6, 139.3, 141.8, 143.1. IR (KBr): 3280,
–
1
960, 1720, 1600, 1490, 1460, 1330, 1160, 840 cm . HRMS–DART (m/z): Calcd for
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+
25 2
C H30NO SSi [M+H] : 436.1767. Found: 436.1775.
(
S,E)-N-(3-mesityl-1-phenylallyl)-4-methylbenzenesulfonamide (3oP)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Silica gel column chromatography (hexane/ ethyl acetate = 20/1~3/1) gave 3oP (75 mg,
2
5
37% yield, 0.5 mmol scale) as a white solid of mp = 139–140 °C and [α]
D
+10.0 (c
0
.33, CHCl
3
). The ee was determined to be 70% by HPLC (Daicel Chiralcel IB,
1
hexane/i-PrOH = 20/1, 1.0 mL/min, 254 nm, major 14.3 min and minor 18.8 min). H
3
NMR (CDCl ): 2.11 (s, 6H), 2.24 (s, 3H), 2.38 (s, 3H), 4.80 (d, J = 6.2 Hz, 1H), 5.12 (t,
J = 6.2 Hz, 1H), 5.71 (dd, J = 6.2, 16.0 Hz, 1H), 6.42 (d, J = 16.0 Hz, 1H), 6.81 (s, 2H),
13
7
1
.20–7.29 (m, 7H), 7.69 (d, J = 8.2 Hz, 2H). C NMR (CDCl ): 20.7, 20.9, 21.4, 59.9,
3
27.0, 127.1, 127.7, 128.5, 128.7, 129.5, 129.9, 132.7, 133.3, 135.8, 136.4, 137.7, 140.0,
–
1
143.3. IR (KBr): 3280, 1450, 1320, 1150, 1090, 1060 cm . HRMS–DART(m/z): Calcd
+
for C25
H28NO
2
S [M+H] : 406.1841. Found: 406.1868.
(
E)-4-methyl-N-(1-(2-(trimethylsilyl)phenyl)hexa-1,5-dien-3-yl)benzenesulfonamid
e (3nA)
Silica gel column chromatography (hexane/ ethyl acetate = 5/1) gave 3nA (198 mg,
9% yield, 0.5 mmol scale) as a white solid of mp = 58–59 °C. The ee was determined
9
to be 0% by HPLC (Daicel Chiralcel IB, hexane/i-PrOH = 20/1, 1.0 mL/min, 254 nm,
1
1
3
5
3.1 min and 14.5 min). H NMR (CDCl
3
): 0.29 (s, 9H), 2.27–2.40 (m, 2H), 2.36 (s,
H), 4.01–4.08 (m, 1H), 4.50 (d, J = 6.8 Hz, 1H), 5.08–5.14 (m, 2H), 5.59–5.69 (m, 1H),
.74 (dd, J = 6.8, 15.6 Hz, 1H), 6.75 (d, J = 15.6 Hz, 1H), 7.14–7.28 (m, 5H), 7.45–7.47
1
3
(m, 1H), 7.74 (d, J = 8.2 Hz, 2H). C NMR (CDCl
3
): 0.05, 21.3, 40.1, 55.5, 119.1,
1
25.4, 126.6, 127.1, 129.0, 129.5, 129.5, 132.6, 132.8, 134.1, 137.9, 138.2, 142.0, 143.1.
–
1
IR (KBr): 3310, 2960, 1440, 1320, 1250, 1160, 1100, 970, 910, 840 cm .
+
HRMS–DART (m/z): Calcd for C22
H
30NO
2
SSi [M+H] : 400.1767. Found: 400.1760.
(
E)-N-(1-mesitylhexa-1,5-dien-3-yl)-4-methylbenzenesulfonamide (3oA)
Silica gel column chromatography (hexane/ ethyl acetate = 5/1) gave 3oA (183 mg,
9% yield, 0.5 mmol scale) as a white solid of mp = 84–86 °C. The ee was determined
9
to be 0% by HPLC (Daicel Chiralcel IB, hexane/i-PrOH = 20/1, 0.7 mL/min, 254 nm,
1
1
2
5.9 min and 17.6 min). H NMR (CDCl
3
): 2.10 (s, 6H), 2.24 (s, 3H), 2.31–2.44 (m,
H), 2.40 (s, 3H), 4.01–4.07 (m, 1H), 4.53–4.57 (m, 1H), 5.07–5.15 (m, 2H), 5.46 (dd, J
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2
2
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2
2
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=
6.4, 16.0 Hz, 1H), 5.62–5.72 (m, 1H), 6.35 (d, J = 16.0 Hz, 1H), 6.82 (s, 2H), 7.28 (d,
1
3
J = 8.2 Hz, 2H), 7.78 (d, J = 8.2 Hz, 2H). C NMR (CDCl
3
): 20.6, 20.8, 21.3, 40.6,
5
5.4, 119.0, 127.0, 128.3, 128.9, 129.5, 132.9, 133.0, 133.3, 135.6, 136.1, 137.9, 143.1.
0
1
2
3
4
5
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7
8
9
0
1
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7
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9
0
1
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
–
1
IR (KBr): 3290, 2920, 1640, 1610, 1430, 1320, 1160, 1090, 1060 cm . HRMS–DART
+
(m/z): Calcd for C22
H28NO
2
S [M+H] : 370.1841. Found: 370.1864.
(
S)-3-Phenylpentan-1-ol (4E’)
The obtained aldehydes 4E was treated with NaBH
4
(0.5 mmol) in methanol (4 mL) for
0.5 h at room temperature. After addition of water and ethyl acetate, the organic layer
was separated and the aqueous layer was extracted with ethyl acetate. The combined
3 2 4
organic layers were washed with satd NaHCO and brine, and then dried over Na SO .
Concentration and purification by silica gel column chromatography (hexane/ethyl
acetate = 20/1~3/1) gave 4E’ as a colorless oil. The ee was determined by HPLC
(Daicel Chiralcel IB, hexane/i-PrOH = 20/1, 0.3 mL/min, 220 nm, major 26.4 min and
1
minor 23.9 min). H NMR (CDCl
3
): 0.78 (t, J = 7.6 Hz, 3H), 1.43 (brs, 1H), 1.59–1.98
1
3
(m, 4H), 2.57 (tt, J = 5.2, 5.2 Hz, 1H), 3.43–3.57 (m, 2H), 7.15–7.31 (m, 5H). C NMR
CDCl ): 12.1, 29.8, 39.2, 44.2, 61.2, 126.1, 127.7, 128.4, 144.9. IR (KBr): 3860, 2930,
600, 1490, 1450, 1020 cm . HRMS–DART (m/z): Calcd for C11
165.1279. Found: 165.1281.
(
3
–
1
+
1
H17O [M+H] :
Protodesilation to (R,E)-4-Methyl-N-(1-phenylpent-1-en-3-yl)benzenesulfonamide
3aE)
To a solution of 3nE (116 mg, 83% ee, 0.3 mmol scale), KI (100 mg, 0.6 mmol), and
O (5.4 µL, 0.3 mmol) in MeCN (4.5 mL), TMSCl (65 mg, 0.6 mmol) was added at
(
H
2
room temperature. After 6 h, water was added to the reaction mixture and the aqueous
layer was extracted with ethyl acetate (5 mL x3). The combined organic layers were
washed with brine and dried over Na
2 4
SO . Silica gel column chromatography (hexane/
ethyl acetate = 5/1~3/1) gave 3aE (116 mg, 74% yield). The ee was determined to be
8
3
3% by HPLC (Daicel Chiralcel IA, hexane/i-PrOH = 20/1, 0.7 mL/min, 254 nm, major
7.9 min and minor 33.9 min.
(
R)-N-(1-Hydroxybutan-2-yl)-4-methylbenzenesulfonamide (14)
2 2
To a solution of 3aE (158 mg, 98% ee, 0.5 mmol scale) in CH Cl (4.0 mL), gentle
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stream of ozone was passed through the solution at –78 °C. After 2.5 hours, NaBH (95
mg, 2.5 mmol) in MeOH (2.0 mL) was added dropwise at –78 °C and the whole was
steered for 15 min, then warmed to room temperature. Water was added and the
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aqueous layer was extracted with CHCl
3
(5 mL x3). The combined organic layers were
SO . Silica gel column chromatography
= 1/1/1) gave 14 (108 mg, 89% yield, 2 steps) as an colorless
D 3
+83.3 (c 0.51, CHCl ). The ee was determined to be 98% by HPLC (Daicel
washed with brine and dried over Na
2
4
(hexane/acetone/CHCl
3
25
oil of [α]
Chiralcel IA, hexane/i-PrOH = 10/1, 1.0 mL/min, 254 nm, major 48.3 min and minor
1
23.5 min). H NMR (CDCl
3
): 0.75 (t, J = 7.2 Hz, 3H), 1.33 –1.44 (m, 1H), 1.45–1.52
(m, 1H), 1.98 (brs, 1H), 2.42 (s, 3H), 3.13–3.20 (m, 1H), 3.47–3.58 (m, 2H), 4.72 (d, J
1
3
=
7.6 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H). C NMR (CDCl
3
):
10.0, 21.4, 24.5, 57.1, 64.2, 126.9, 129.6, 137.6, 143.3. IR (KBr): 3220, 2970, 1600,
–
1
+
1
2
3
460, 1320, 1160, 1040 cm . HRMS–DART (m/z): Calcd for C11H18NO S [M+H] :
44.1007. Found: 244.1006.
Acknowledgments This work was supported by a Grant-in-Aid for Young Scientists
(B) (24750037), a Grant-in-Aid for Scientific Research (B) from the Japan Society for
the Promotion of Science (24350022), Kanazawa University CHOZEN Project, and
Kanazawa University SAKIGAKE Project.
Supporting Information
1
13
Copies of H NMR and C NMR spectra of products. This material is available free of
charge via the Internet at http://pubs.acs.org.
1
(a) Stütz, A. Angew. Chem. Int. Ed. Engl. 1987, 26, 320–328. (b) Ryder, N. S.;
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Dupont, M.-C. Biochem. J. 1985, 230, 765–770. (c) Petranyi, G.; Ryder, N. S.; Stütz, A.
Science 1984, 224, 1239–1241. (d) Berney, D.; Schuh, K. Helv. Chim. Acta. 1978, 61,
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(a) Tomioka, K. Synthesis 1990, 541–549. (b) Noyori, R. Asymmetric Catalysis in
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(a) Hata, S.; Iwasawa, T.; Iguchi, M.; Yamada, K.; Tomioka, K. Synthesis 2004,
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1 For selected recent reviews, see: (a) N-Heterocyclic Carbenes, S. Díez-González,
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3 Uchida, T.; Katsuki, T. Tetrahedron Lett. 2009, 50, 4741–4743.
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