Copper-catalyzed asymmetric propargylic amination of propargylic acetates with amines using BICMAP

Article abstract of DOI:10.1016/j.tetasy.2013.10.007

The copper-catalyzed asymmetric propargylic amination of propargylic acetates 1 with amines 2 using BICMAP as a chiral ligand gave the desired products 3 in good yields and with moderate to high enantioselectivities (up to 90% ee).

Full text of DOI:10.1016/j.tetasy.2013.10.007

Tetrahedron: Asymmetry 24 (2013) 1520–1523
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Copper-catalyzed asymmetric propargylic amination of propargylic
acetates with amines using BICMAP
⇑
Takashi Mino , Hiroyuki Taguchi, Masatoshi Hashimoto, Masami Sakamoto
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The copper-catalyzed asymmetric propargylic amination of propargylic acetates 1 with amines 2 using
BICMAP as a chiral ligand gave the desired products 3 in good yields and with moderate to high
enantioselectivities (up to 90% ee).
Received 6 September 2013
Accepted 2 October 2013
Available online 5 November 2013
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
Herein we report the copper-catalyzed propargylic amination of
propargylic acetates 1 with amines 2 using (R)-BICMAP as a chiral
Optically active propargylic amines, known as synthetic inter-
mediates to biologically active compounds and polyfunctional
amino derivatives, have attracted considerable attention from
medicinal chemists.1 In 1994, Murahashi et al. described the syn-
thesis of propargylic amines via the copper-catalyzed propargylic
aminations of propargylic esters.2 There have been only a few
reports of an asymmetric version of this reaction with propargylic
acetates. A few years ago, van Maarseveen et al.1g,3 and Nishibay-
ashi et al.4 independently developed the copper-catalyzed
propargylic asymmetric amination of propargylic acetates using a
pybox–CuI catalyst system and a Cl–MeO–BIPHEP–CuOTf catalyst
system, respectively. Recently, Hu et al. reported on this reaction
using chiral tridentate P,N,N-type ligands.5 On the other hand,
we recently reported the synthesis of an atropisomeric diphos-
phine ligand (BICMAP)6 (Fig. 1) bearing a dihydrobenzofuran
(coumaran) core. The dihedral angle of the biaryl atropisomeric
backbone is greatly different from BICMAP (110.2°) between the
palladium complex of BICMAP (62.5°). We also reported on the
rhodium-catalyzed asymmetric 1,4-addition of aryl- and
alkenylboronic acids to cyclic enones using BICMAP as a ligand.7
ligand.
2. Results and discussion
2.1. Optimization of the reaction conditions
The reaction of 1-phenylpropargylic acetate 1a with N-methy-
laniline 2a was performed in the presence of 5 mol % of
CuOTfꢀ0.5C6H6 and 10 mol % of (R)-BICMAP as a model reaction
(Table 1). The reaction using 1.2 equiv of diisopropylethylamine
Table 1
Optimization of the copper-catalyzed asymmetric propargylic amination of
1-phenylpropargylic acetate 1a with N-methylaniline 2a using (R)-BICMAP
5 mol% CuOTf·0.5C6H6
Ph
Ph
Me
10 mol% (R)-BICMAP
OAc
N
Ph
Me
1.2 equiv base
N
H
+
Ph
MeOH (0.2 M)
temp., 18 hr, Ar
1a
2a
3a
1.5 equiv
Entry
Base
Temp (°C)
Yielda (%)
59
eeb
1c
2
iPr2NEt
iPr2NEt
iPr2NEt
iPr2NEt
Et3N
0
0
83
83
87
79
86
—
84
68
57
66
Trace
N.R.
O
O
PPh2
PPh2
3
ꢁ10
ꢁ10
ꢁ10
ꢁ10
ꢁ10
4d
5
6
7
PhNMe2
PhNHMe
—
Figure 1. (R)-BICMAP ligand.
a
Isolated yield.
b
Determined by HPLC analysis using a chiral column. The absolute configuration
was assigned by the comparison of the specific rotation with the reported data.4c
c
⇑
This reaction was carried out using 0.1 M of MeOH as a solvent.
5.5 mol % of (R)-BICMAP was added.
Corresponding author. Tel.: +81 43 290 3385; fax: +81 43 290 3401.
E-mail address: tmino@faculty.chiba-u.jp (T. Mino).
d
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.10.007

T. Mino et al. / Tetrahedron: Asymmetry 24 (2013) 1520–1523
1521
as a base in MeOH (0.1 M) at 0 °C for 18 h produced the corre-
sponding product 3a in 59% yield with 83% ee (entry 1). When
the reaction was carried out in 0.2 M of MeOH, the yield of product
3a increased to 84% with 83% ee (entry 2). Next, the effect of the
reaction temperature was investigated. The reaction at ꢁ10 °C gave
3a with good enantioselectivity (87% ee) and with 68% yield (entry
3). When the reaction was carried out using 5.5 mol % of
(R)-BICMAP, the enantioselectivity decreased to 79% ee with mod-
erate yield (entry 4). We also investigated the effect of a base. In
the case of using triethylamine as a base, the enantioselectivity
and yield were slightly decreased (entry 5). The reaction using
N,N-dimethylaniline and N-methylaniline did not result in the cor-
responding product 3a (entries 6 and 7). Nishibayashi et al. already
reported4c that the reaction using similar axial chiral bisphosphine
ligands such as SEGPHOS and Cl–MeO–BIPHEP gave the corre-
sponding product 3a with 59% ee and 86% ee, respectively. The
enantioselectivity of product 3a using BICMAP (entry 3) was better
than that of SEGPHOS and a similar level of Cl–MeO–BIPHEP.
did not proceed (entry 9). Using N-ethyl-4-chloroaniline 2f led to
product 3j in good yield and with high enantioselectivity (88%
ee) (entry 11). The reactions with N-ethylaniline 2g and aniline
2h gave the corresponding products with 82% ee and 44% ee,
respectively (entries 12 and 13). Finally, we tested the reaction of
indoline 2i as an amine. The reaction produced the corresponding
product 3m with 70% ee (entry 14). The absolute configurations of
products 3 were assigned by comparison of the specific rotation
with reported data4a,c or were tentatively assigned by analogy.
Based on the model of the transition state for the asymmetric
propargylic amination of propargylic acetate with BIPHEP type li-
gand by Nishibayashi,4c the crystal structure of the PdCl2–BICMAP
complex,6and the observed absolute configuration of the major
enantiomer using (R)-BICMAP, we proposed a model for the
enantioinduction (Scheme 1). The attack of N-methylaniline occurs
at the cationic c-carbon atom of the ligand in the copper acetylide
complex. As a result, the (S)-product was obtained in this reaction
using (R)-BICMAP.
2.2. Substrate scope and limitation
Under the optimized reaction conditions (Table 1, entry 3), we
investigated a copper-catalyzed asymmetric propargylic amination
of propargylic acetate 1 with amine 2 using (R)-BICMAP (Table 2).
The reactions with 1-(4-methylphenyl)propargylic acetate 1b and
1-(4-chlorophenyl)propargylic acetate 1c with N-methylaniline
2a gave the corresponding products in good enantioselectivites
O
P
P
+
Cu
Ph
Ph
Me
O
N
H
(entries
2 and 3). On the other hand, the reaction using
(S)
1-(4-methoxyphenyl)propargylic acetate 1d led to low enantiose-
lectivity (37% ee) (entry 4). When we used 1-(2-methyl-
phenyl)propargylic acetate 1e and 1-(2-naphthyl)propargylic
acetate 1f, the reactions generated corresponding products with
good enantioselectivities (entries 5 and 6). We also investigated
the reactions of 1-phenylpropargylic acetate 1a with various
N-methylaniline derivatives 2. The reactions with N-methyl-4-
methylaniline 2b, N-methyl-4-methoxyaniline 2c, and N-methyl-
4-chloroaniline 2e resulted in the corresponding products with
83% ee, 79% ee, and 90% ee, respectively (entries 7, 8 and 10).
However, the reaction with N-methyl-4-trifluoromethylaniline 2d
Ph
Me
N
H
H
Scheme 1. Proposed model for the enantioinduction.
3. Conclusions
In conclusion, we have found that the copper-catalyzed asym-
metric propargylic amination of propargylic acetates with
1
amines 2 using BICMAP as the chiral ligand and diisopropylethyl-
amine as the base generated the desired products 3 with good
yields and with moderate to high enantioselectivities (up to 90%
ee) at ꢁ10 °C in MeOH.
Table 2
The scope and limitations of the copper-catalyzed asymmetric propargylic amination
of propargylic acetate 1 with amine 2 using (R)-BICMAP
5 mol% CuOTf·0.5C6H6
Ar2
Ar1
R
4. Experimental
4.1. General
10 mol% (R)-BICMAP
N
OAc
Ar2
R
1.2 equiv iPr2NEt
N
H
+
Ar1
MeOH (0.2 M)
-10 °C, 18 hr, Ar
3
Melting points were measured on a AS ONE micromelting point
apparatus and are uncorrected. The 1H and 13C NMR spectra were
recorded in CDCl3 on a Bruker DPX-300 spectrometer or JEOL
ESA500 spectrometer. The chemical shifts of the 1H NMR spectra
are reported relative to TMS (d 0.00) and 13C NMR spectra are re-
ported relative to CDCl3 (d 77.0), as an internal standard. Mass
spectra were determined on a Shimadzu GCMS-QP5050A using
EI, and presented as m/z (% rel intensity). HRMS were recorded
on a Thermo Fisher Scientific Exactive using ESI. Analytical high-
perfomance liquid chromatography (HPLC) was done with a JASCO
GULLIVER 900 or 2000 system coupled with a UV detector using a
chiral column. Optical rotations were measured on JASCO P-2100.
1
2
1.5 equiv
Ar2
Entry
Ar1
R
Yielda (%)
eeb
1
2
3
4
5
6
7
8
Ph 1a
Ph
Ph
Ph
Ph
Ph
Ph
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
Me 2a
68 3a
85 3b
68 3c
85 3d
68 3e
52 3f
63 3g
80 3h
N.R.
70 3i
67 3j
54 3k
83 3l
77 3m
87
77
87
37
81
72
83
79
—
90
88
82
44
70
4-MeC6H4 1b
4-ClC6H4 1c
4-MeOC6H4 1d
2-MeC6H4 1e
2-Naphth 1f
Ph 1a
Ph 1a
Ph 1a
Ph 1a
Ph 1a
4-MeC6H4
4-MeOC6H4
4-CF3C6H4
4-ClC6H4
4-ClC6H4
Ph
Me 2b
Me 2c
Me 2d
Me 2e
Et 2f
9
10
11
12
13
14
4.2. General procedure for the copper-catalyzed asymmetric
propargylic amination of aropargylic acetate 1 with amine 2
Ph 1a
Ph 1a
Ph 1a
Et 2g
Ph
H 2h
Indoline 2i
a
Under an argon atmosphere, CuOTfꢀ0.5C6H6 (2.5 mg, 10
lmol)
Isolated yield.
Determined by HPLC analysis using a chiral column.
b
was added to (R)-BICMAP (12.7 mg, 20 mol) in MeOH (1 mL).
l

1522
T. Mino et al. / Tetrahedron: Asymmetry 24 (2013) 1520–1523
The mixture was stirred for 1 h at 60 °C and concentrated under re-
duced pressure. Propargylic acetate 1 (0.20 mmol) in MeOH (1 mL),
114.8, 118.7, 125.7, 128.1, 128.8, 129.2, 130.7, 135.4, 137.3,
149.8; EI-MS m/z (rel intensity) 235 (M+, 23); HPLC (Daicel CHIR-
ALPAKÒ AD-H, 0.46 / ꢃ 25 cm, UV 254 nm, hexane/2-propa-
nol = 97:3, 1.0 mL/min) tR = 5.0 min (minor) and 5.5 min (major).
amine
2
(0.30 mmol), and diisopropylethylamine (42.0 lL,
0.24 mmol) were added to the copper complex. A mixture was stir-
red at ꢁ10 °C under an argon atmosphere. After 18 h, the mixture
was concentrated under reduced pressure. The residue was puri-
fied by silica gel chromatography (hexane or hexane/
EtOAc = 250–100/1).
4.2.6. (S)-(ꢁ)-N-Methyl-N-[1-(naphthalen-2-yl)-2-propynyl]ani-
line 3f4a (Table 2, entry 6)
51% Yield (27.6 mg), 72% ee; ½a D20
¼ ꢁ7:1 (c 0.81, CHCl3); pale
ꢂ
yellow solid; mp 78–79 °C; 1H NMR (CDCl3, 300 MHz) d 2.56 (d,
J = 2.3 Hz, 1H), 2.63 (s, 3H), 6.36 (s, 1H), 6.90 (t, J = 7.3 Hz, 1H),
7.10 (d, J = 8.0 Hz, 2H), 7.34–7.53 (m, 5H), 7.84–7.94 (m, 3H),
8.04 (d, J = 7.1 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 33.1, 53.3,
75.1, 80.0, 114.7, 118.7, 123.6, 125.0, 125.9, 126.6, 127.0, 128.7,
129.2, 129.3, 131.2, 132.7, 133.9, 149.4; EI-MS m/z (rel intensity)
271 (M+, 19); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / ꢃ 25 cm,
UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.6 min
(minor) and 7.8 min (major).
4.2.1. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)aniline 3a4c
(Table 2, entry 1)
68% Yield (30.3 mg), 87% ee; ½a D20
¼ þ6:2 (c 0.27, CHCl3) {lit.
ꢂ
½
a 2D2
ꢂ
¼ þ10:7 (c 1.42, CHCl3) as 86% ee}; yellow oil; 1H NMR (CDCl3,
300 MHz) d 2.53 (d, J = 2.4 Hz, 1H), 2.70 (s, 3H), 5.81 (s, 1H), 6.86 (t,
J = 7.3 Hz, 1H), 7.00 (d, J = 8.1 Hz, 2H), 7.26–7.41 (m, 5H), 7.59 (d,
J = 7.2 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 33.6, 56.3, 74.8, 79.9,
115.2, 118.9, 127.5, 127.8, 128.4, 129.2, 137.8, 150.1; EI-MS m/z
(rel intensity) 221 (M+, 24); HPLC (Daicel CHIRALPAKÒ AD-H,
0.46 / ꢃ 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1,0 mL/
min) tR = 5.6 min (minor) and 7.2 min (major).
4.2.7. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-methylan-
iline 3g4a (Table 2, entry 7)
63% Yield (29.5 mg), 83% ee; ½a D20
¼ þ16:8 (c 0.25, CHCl3); pale
ꢂ
4.2.2. (S)-(ꢁ)-N-Methyl-N-[1-(4-methylphenyl)-2-propynyl]ani-
yellow oil; 1H NMR (CDCl3, 300 MHz) d 2.29 (s, 3H), 2.51 (d,
J = 2.3 Hz, 1H), 2.65 (s, 3H), 5.73 (s, 1H), 6.92 (d, J = 8.6 Hz, 2H),
7.10 (d, J = 8.6 Hz, 2H), 7.31–7.39 (m, 3H), 7.59 (d, J = 7.5 Hz, 2H);
13C NMR (CDCl3, 75 MHz) d 20.4, 33.7, 57.0, 74.9, 79.8, 115.9,
127.6, 127.7, 128.4, 128.5, 129.7, 137.9, 148.0; EI-MS m/z (rel
intensity) 235 (M+, 48); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 /
ꢃ 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min)
tR = 5.1 min (minor) and 6.7 min (major).
line 3b4a (Table 2, entry 2)
85% Yield (39.8 mg), 77% ee; ½a D20
¼ ꢁ1:4 (c 0.50, CHCl3); pale
ꢂ
yellow solid; mp 56–57 °C; 1H NMR (CDCl3, 300 MHz) d 2.36 (s,
3H), 2.51 (d, J = 2.7 Hz, 1H), 2.69 (s, 3H), 5.78 (s, 1H), 6.85 (t,
J = 7.3 Hz, 1H), 6.99 (d, J = 8.1 Hz, 2H), 7.18 (d, J = 8.0 Hz, 2H),
7.25–7.32 (m, 2H), 7.46 (d, J = 8.0 Hz, 2H); 13C NMR (CDCl3,
75 MHz) d 21.1, 33.5, 56.0, 74.6, 80.1, 115.2, 118.8, 127.4, 129.1,
129.1, 134.8, 137.5, 150.1; EI-MS m/z (rel intensity) 235 (M+, 19);
HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / ꢃ 25 cm, UV 254 nm, hex-
ane/2-propanol = 97:3, 1.0 mL/min) tR = 5.6 min (minor) and
7.8 min (major).
4.2.8. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-methoxyan-
iline 3h4c (Table 2, entry 8)
80% Yield (40.2 mg), 79% ee; ½a D20
¼ þ12:7 (c 0.52, CHCl3) {lit.
ꢂ
½
a 2D5
ꢂ
¼ þ13 (c 1.38, CHCl3) as 80% ee}; brown oil; 1H NMR (CDCl3,
4.2.3. (S)-(ꢁ)-N-Methyl-N-[1-(4-chlorophenyl)-2-propynyl]ani-
300 MHz) d 2.53 (d, J = 1.8 Hz, 1H), 2.61 (s, 3H), 3.78 (s, 3H), 5.59
(s, 1H), 6.87 (d, J = 9.1 Hz, 2H), 7.00 (d, J = 9.1 Hz, 2H), 7.31–7.40
(m, 3H), 7.61 (d, J = 7.1 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 34.2,
55.6, 58.6, 75.3, 79.7, 114.4, 118.5, 127.7, 127.8, 128.3, 128.7,
137.9, 144.6, 153.6; EI-MS m/z (rel intensity) 251 (M+, 21); HPLC
(Daicel CHIRALPAKÒ AD-H, 0.46 / ꢃ 25 cm, UV 254 nm, hexane/
2-propanol = 97:3, 1.0 mL/min) tR = 7.3 min (minor) and 17.8 min
(major).
line 3c4a (Table 2, entry 3)
68% Yield (34.8 mg), 87% ee; ½a D20
¼ ꢁ12:1 (c 0.49, CHCl3); pale
ꢂ
yellow solid; mp 70–71 °C; 1H NMR (CDCl3, 300 MHz) d 2.54 (d,
J = 2.3 Hz, 1H), 2.68 (s, 3H), 5.74 (s, 1H), 6.87 (t, J = 7.3 Hz, 1H),
6.98 (d, J = 8.2 Hz, 2H), 7.25–7.36 (m, 4H), 7.52 (d, J = 8.5 Hz, 2H);
13C NMR (CDCl3, 75 MHz) d 33.7, 56.0, 75.2, 79.4, 115.5, 119.2,
128.6, 128.9, 129.2, 133.7, 136.4, 149.9; EI-MS m/z (rel intensity)
255 (M+, 24); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / ꢃ 25 cm,
UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 6.3 min
(minor) and 7.4 min (major).
4.2.9. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)-p-chloroaniline
3i4a (Table 2, entry 10)
70% Yield (36.8 mg), 90% ee; ½a D20
¼ þ3:3 (c 0.28, CHCl3); pale
ꢂ
4.2.4. (S)-(ꢁ)-N-Methyl-N-[1-(4-methoxyphenyl)-2-propynyl]ani-
yellow oil; 1H NMR (CDCl3, 300 MHz) d 2.53 (d, J = 2.3 Hz, 1H),
2.68 (s, 3H), 5.72 (s, 1H), 6.89 (d, J = 9.0 Hz, 2H), 7.22 (d,
J = 8.9 Hz, 2H), 7.32–7.40 (m, 3H), 7.54–7.56 (d, J = 7.3 Hz, 2H);
13C NMR (CDCl3, 75 MHz) d 33.9, 56.6, 75.0, 79.5, 116.5, 123.8,
127.4, 127.9, 128.5, 129.0, 137.3, 148.6; EI-MS m/z (rel intensity)
255 (M+, 17); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / ꢃ 25 cm,
UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/min) tR = 6.3 min
(minor) and 8.2 min (major).
line 3d4a (Table 2, entry 4)
85% Yield (42.7 mg), 37% ee; ½a D20
¼ ꢁ8:0 (c 0.25, CHCl3); pale
ꢂ
yellow solid; mp 47–48 °C; 1H NMR (CDCl3, 500 MHz) d 2.50 (d,
J = 2.4 Hz, 1H), 2.68 (s, 3H), 3.82 (s, 3H), 5.75 (d, J = 2.0 Hz, 1H),
6.84–6.92 (m, 3H), 6.99 (d, J = 8.0 Hz, 2H), 7.25–7.31 (m, 2H),
7.47–7.50 (m, 2H); 13C NMR (CDCl3, 75 MHz) d 33.4, 55.3, 55.7,
74.6, 80.2, 113.7, 115.3, 118.9, 128.7, 129.1, 129.8, 150.1, 159.2;
EI-MS m/z (rel intensity) 251 (M+, 8); HPLC (Daicel CHIRALPAKÒ
AD-H, 0.46 / ꢃ 25 cm, UV 254 nm, hexane/2-propanol = 97:3,
1.0 mL/min) tR = 8.3 min (minor) and 10.6 min (major).
4.2.10. (S)-(ꢁ)-N-Ethyl-N-(1-phenyl-2-propynyl)-p-chloroaniline
3j (Table 2, entry 11)
67% Yield (36.2 mg), 88% ee; ½a D20
¼ ꢁ27:1 (c 0.22, CHCl3);
ꢂ
4.2.5. (S)-(+)-N-Methyl-N-[1-(2-methylphenyl)-2-propynyl]ani-
yellow oil; 1H NMR (CDCl3, 300 MHz) d 1.07 (t, J = 7.0 Hz, 3H),
2.53 (d, J = 2.4 Hz, 1H), 3.22–3.34 (m, 2H), 5.61 (s, 1H), 6.84
(d, J = 8.9 Hz, 2H), 7.18 (d, J = 8.7 Hz, 2H), 7.30–7.39 (m, 3H),
7.55 (d, J = 7.3 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 13.2, 42.8,
56.2, 74.7, 80.8, 117.2, 123.5, 127.4, 127.8, 128.5, 128.8, 137.7,
146.5; EI-MS m/z (rel intensity) 269 (M+, 14); HRMS (ESI-orbi-
trap) m/z calcd for C17H16NCl+H 270.1038, found: 270.1044;
HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / ꢃ 25 cm, UV 254 nm,
line 3e4c (Table 2, entry 5)
68% Yield (32.2 mg), 81% ee; ½a D20
¼ þ41:2 (c 0.25, CHCl3) {lit.
ꢂ
½
a 2D5
ꢂ
¼ þ51 (c 1.41, CHCl3) as 82% ee}; pale yellow solid; mp 80–
81 °C; 1H NMR (CDCl3, 300 MHz) d 2.28 (s, 3H), 2.49 (d, J = 2.3 Hz,
1H), 2.63 (s, 3H), 5.78 (s, 1H), 6.85 (t, J = 7.2 Hz, 1H), 7.01 (d,
J = 8.3 Hz, 2H), 7.17–7.20 (m, 1H), 7.24–7.34 (m, 4H), 7.78–7.81
(m, 1H); 13C NMR (CDCl3, 75 MHz) d 19.1, 33.0, 53.7, 74.7, 80.1,

T. Mino et al. / Tetrahedron: Asymmetry 24 (2013) 1520–1523
1523
hexane/2-propanol = 97:3, 1.0 mL/min) tR = 5.5 min (minor) and
6.0 min (major).
J = 7.7 Hz, 2H), 7.32–7.41 (m, 3H), 7.66 (d, J = 7.2 Hz, 2H); 13C
NMR (CDCl3, 75 MHz) d 28.2, 49.0, 52.8, 74.5, 79.4, 108.5, 118.9,
124.6, 127.1, 127.8, 127.9, 128.4, 130.8, 137.1, 150.6; EI-MS m/z
(rel intensity) 233 (M+, 46); HPLC (Daicel CHIRALPAKÒ AD-H,
4.2.11. (S)-(ꢁ)-N-Ethyl-N-(1-phenyl-2-propynyl)aniline 3k4a
(Table 2, entry 12)
0.46
/ ꢃ 25 cm,
UV
254 nm,
hexane/2-propanol = 97:3,
54% Yield (25.2 mg), 82% ee; ½a D20
ꢂ
¼ ꢁ13:8 (c 0.31, CHCl3);
1.0 mL/min) tR = 5.4 min (minor) and 8.4 min (major).
yellow oil; 1H NMR (CDCl3, 300 MHz) d 1.07 (t, J = 7.1 Hz, 3H),
2.52 (d, J = 2.3 Hz, 1H), 3.24–3.35 (m, 2H), 5.69 (s, 1H), 6.82 (t,
J = 7.3 Hz, 1H), 6.94 (d, J = 8.1 Hz, 2H), 7.23–7.38 (m, 5H), 7.59 (d,
J = 7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz) d 13.4, 42.3, 56.0, 74.4,
81.1, 115.8, 118.5, 127.5, 127.7, 128.4, 129.0, 138.2, 148.0; EI-MS
m/z (rel intensity) 235 (M+, 29); HPLC (Daicel CHIRALPAKÒ AD-H,
0.46 / ꢃ 25 cm, UV 254 nm, hexane/2-propanol = 97:3, 1.0 mL/
min) tR = 4.5 min (minor) and 4.9 min (major).
Acknowledgments
This work was supported by a Grant-in-Aid for Young Scientists
(WAKATE B-22750082) from the Ministry of Education, Culture,
Sports, Science and Technology, Japan and the COE Start-up
Program in the Chiba University.
References
4.2.12. (S)-(+)-N-(1-phenyl-2-propynyl)aniline 3l3 (Table 2, entry
13)
1. (a) Porco, J. A., Jr.; Schoenen, F. J.; Stout, T. J.; Clardy, J.; Schreiber, S. L. J. Am.
Chem. Soc. 1990, 112, 7410–7411; (b) Nicolaou, K. C.; Hwang, C.-K.; Smith, A. L.;
Wendeborn, S. V. J. Am. Chem. Soc. 1990, 112, 7416–7418; (c) Yu, P. H.; Davis, B.
A.; Boulton, A. A. J. Med. Chem. 1992, 35, 3705–3713; (d) Jiang, B.; Xu, M. Angew.
Chem., Int. Ed. 2004, 43, 2543–2546; (e) Yamamoto, Y.; Hayashi, H.; Saigoku, T.;
Nishiyama, H. J. Am. Chem. Soc. 2005, 127, 10804–10805; (f) Fleming, J. J.; Du
Bois, J. J. Am. Chem. Soc. 2006, 128, 3926–3927; (g) Detz, R. J.; Abiri, Z.; le Griel,
R.; Hiemstra, H.; van Maarseveen, J. H. Chem. Eur. J. 2011, 17, 5921–5930.
2. Imada, Y.; Yuasa, M.; Nakamura, S.; Murahashi, S.-I. J. Org. Chem. 1994, 59, 2282–
2284.
83% Yield (34.4 mg), 44% ee; ½a D20
¼ þ33:3 (c 0.27, CHCl3)
ꢂ
{lit. ½a 2D0
¼ þ103 (c 1.0, CHCl3) as 87% ee}; pale yellow solid; mp
ꢂ
84–85 °C; 1H NMR (CDCl3, 300 MHz) d 2.48 (d, J = 2.3 Hz, 1H),
4.05 (d, J = 6.4 Hz, 1H), 5.29 (d, J = 5.1 Hz, 1H), 6.73–6.82 (m, 3H),
7.19–7.25 (m, 2H), 7.31–7.43 (m, 3H), 7.61 (t, J = 6.9 Hz, 2H); 13C
NMR (CDCl3, 75 MHz) d 49.8, 73.1, 83.0, 114.0, 118.8, 127.2,
128.2, 128.8, 129.2, 139.0, 146.3; EI-MS m/z (rel intensity) 207
(M+, 30); HPLC (Daicel CHIRALPAKÒ AD-H, 0.46 / ꢃ 25 cm, UV
254 nm, hexane/2-propanol = 98:2, 1.0 mL/min) tR = 26.7 min
(major) and 34.8 min (minor).
3. Detz, R. J.; Delville, M. M. E.; Hiemstra, H.; van Maarseveen, J. H. Angew. Chem.,
Int. Ed. 2008, 47, 3777–3780.
4. (a) Hattori, G.; Matsuzawa, H.; Miyake, Y.; Nishibayashi, Y. Angew. Chem., Int. Ed.
2008, 47, 3781–3783; (b) Matsuzawa, H.; Tanage, Y.; Miyake, Y.; Nishibayashi, Y.
Organometallics 2008, 27, 4021–4024; (c) Hattori, G.; Sakata, K.; Matsuzawa, H.;
Tanabe, Y.; Miyake, Y.; Nishibayashi, Y. J. Am. Chem. Soc. 2010, 132, 10592–
10608.
4.2.13. (S)-(+)-N-Methyl-N-(1-phenyl-2-propynyl)indoline 3m4a
5. Zhang, C.; Wnag, Y.-H.; Hu, X.-H.; Zheng, Z.; Xu, J.; Hu, X.-P. Adv. Synth. Catal.
2012, 354, 2854–2858.
6. Mino, T.; Naruse, Y.; Kobayashi, S.; Oishi, S.; Sakamoto, M.; Fujita, T. Tetrahedron
Lett. 2009, 50, 2239–2241.
7. Mino, T.; Hashimoto, M.; Uehara, K.; Naruse, Y.; Kobayashi, S.; Sakamoto, M.;
Fujita, T. Tetrahedron Lett. 2012, 53, 4562.
(Table 2, entry 14)
77% Yield (36.1 mg), 70% ee; ½a D20
¼ þ54:3 (c 0.23, CHCl3);
ꢂ
brown oil; 1H NMR (CDCl3, 300 MHz) d 2.39 (d, J = 2.2 Hz, 1H),
2.95 (t, J = 9.0 Hz, 2H), 3.08–3.15 (m, 1H), 3.29–3.38 (m, 2H), 5.61
(s, 1H), 6.64 (d, J = 7.8 Hz, 1H), 6.74 (t, J = 7.5 Hz, 1H), 7.11 (t,