Highly efficient asymmetric-axle-supported N-O amides in enantioselective hydrosilylation of ketimines with trichlorosilane

Article abstract of DOI:10.1016/j.tet.2013.06.081

A novel asymmetric-axle-supported chiral N-O amide was synthesized and used in catalytic enantioselective hydrosilylation of N-aryl ketimines with HSiCl₃ at room temperature instead of the typical -20°C. High conversion yield and high enantiose

Full text of DOI:10.1016/j.tet.2013.06.081

Tetrahedron 69 (2013) 7253e7257
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Highly efficient asymmetric-axle-supported NeO amides in
enantioselective hydrosilylation of ketimines with trichlorosilaneq
,
,
,
,b,
Wei Pan a c, Yu Deng a c, Jiang-Bo He a c, Bing Bai a, Hua-Jie Zhu a
*
a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academic of Sciences (CAS), Kunming
650204, PR China
b Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, and School of Life Science of Hebei University, Baoding
071002, PR China
c Graduate University of CAS, Beijing, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 May 2013
Received in revised form 15 June 2013
Accepted 24 June 2013
Available online 29 June 2013
A novel asymmetric-axle-supported chiral NeO amide was synthesized and used in catalytic enantio-
selective hydrosilylation of N-aryl ketimines with HSiCl3 at room temperature instead of the typical
ꢀ20 ꢁC. High conversion yield and high enantioselectivity up to 96% were observed.
Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric-axle-supported
Hydrosilylation
Ketimines
Trichlorosilane
1. Introduction
application to hydrosilylation of ketimines with trichlorosilane at
room temperature. Catalyst 8 is different from ligand 6, in which
Enantioselective hydrosilylation of C]N with HSiCl3 has been
proven to be a powerful method for producing chiral amines.1
Three major families of organocatalysts have been developed
(Fig. 1): N-formyl derivative (1),1b,2 picolinamide analog (2),3 and
pyridyl-oxazoline (3).1c,4 When classified by catalyst structural
characteristics, an axial ligand, such as a BINAM derivative (4),5
a polymer-supported ligand (5),6 a C2-asymmetric ligand (6),7
and others8 were also found to have good enantioselectivities. All
reactions reported were performed at low temperatures (e.g.,
ꢀ20 ꢁC). Until now, the catalysts with NeO structure have rarely
reported in the enantioselective hydrosilylation of C]N with
HSiCl3. In our recent study, a biscarboline ester with NeO structure
(7)9 was synthesized and used in asymmetric additions of tri-
chlorosilanes to aldehydes to give up corresponding products with
up to 99% ee. For the polymer-supported and axial catalyst struc-
tures, we have designed and synthesized a series of asymmetric-
axle-supported ligands, such as 8, and investigated their
two chiral active moieties are connected via a flexible linear linkage
such that no axial conformer can form in solution. While the CeC
bond connections in 8 forms an axial asymmetric space, it was
anticipated only one chiral molecular residue (e.g., the moiety
highlighted in the blue box) catalyzes the reactions.
2. Results and discussion
The synthetic route to 8 is illustrated in Scheme 1. Compound 9
was synthesized as described in our previous study.9 After hydro-
lysis of 9, the intermediate 10, which was obtained in a yield of 93%
was condensed with (1S,2R)-(þ)-2-amino-1,2-diphenylethanol to
form 11 in a yield of 95%, which is oxidized to 8 using 8 equiv of
peroxide-urea and TFA at room temperature for 2 days. One major
epimer product was obtained with a single step yield of 48% after
column chromatography. Bis-NeO products were obtained in a low
yield (less than 10%).
Stereochemistry of the major structure was determined using
a widely accepted quantum theory.10 Conformational searches
were performed by first using a MMFF94S force field. All stable
conformations were then optimized at the B3LYP/6-31G(d) level.
Single point energy (SPE) was computed for the low energy con-
formers (0e2.5 kcal/mol) at the B3LYP/6-311G(d) level. The catalyst
q
This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution, and
reproduction in any medium, provided the original author and source are credited.
* Corresponding author. Fax: þ86 312 5994812; e-mail addresses: hjzhu@mail.-
kib.ac.cn, zhuhuajie@hotmail.com (H.-J. Zhu).
0040-4020/$ e see front matter Ó 2013 The Authors. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.081

7254
W. Pan et al. / Tetrahedron 69 (2013) 7253e7257
Fig. 1. Effective catalysts designed by us that have been previously reported.
was found to consist of 87% of the major geometry 8a and 13% of the
other epimer (ep-8a).
axle-supported moiety and indol were absent as in 12, only
26% ee was achieved. The results showed that the active moiety
(NeO-containing residue) is crucial in efficiently catalyzing the
enantioselective hydrosilylation.
Our initial attempt with 10 mol % of catalyst 8a gave a 74% ee in
enantioselective hydrosilylations of ketimine 13 (R1¼Ph, R2¼Ph,
R3¼Me) with HSiCl3 at 0 ꢁC in CH2Cl2. We then investigated the
effects of temperature (from ꢀ20e40 ꢁC) and solvent (CH2Cl2,
CHCl3 or toluene) on the enantioselectivity. The optimized reaction
condition was found to be 20 mol % of 8 in CHCl3 at room tem-
perature for 4 h (Table 1, entry 1). Finally, we examined a series of
ketimines and the results are summarized in Table 1. All substrates
were converted to the corresponding amines in high yields (ꢂ94%)
and good ee% values (up to 96%). The N-(1-phenylethyl)aniline has
an OR of ꢀ13.5ꢁ in CH3OH.
Ph
Ph
H
N
N
O
HO
O
12
3. Conclusion
The effect of different moiety of the catalyst on the hydro-
silylation was investigated. The loss of the free eOH (e.g., ligand 8b)
led to a decrease in ee% from 93% to 30%. Once the eO on N was
removed, as in 11a, the ee% decreased to 7%. If the asymmetric-
In conclusion, we prepared a novel asymmetric-axle-supported
chiral NeO amide 8a as highly efficient Lewis basic organocatalyst
Scheme 1. Synthesis of catalyst 8.

W. Pan et al. / Tetrahedron 69 (2013) 7253e7257
7255
Table 1
110.8, 117.4, 120.7, 120.8, 122.3, 129.2, 129.8, 136.3, 136.7, 139.6, 142.6,
166.8.
Asymmetric hydrosilylation of various ketimines catalyzed by 8a
R2
R2
HSiCl3
8a (20mol%)
4.2.2. N,N0-Bis(1R,2S-2-hydroxy-1,2-diphenylethyl)
9,90-dimethyl-
HN
9H,90H-1,10-bipyrido[3,4-b]indole-3,30-dicarboxamide (11a). To a so-
lution of 10 and 1-hydroxybenzotriazole (HOBT, 2.2 equiv) in DMF
kept under nitrogen at 0 ꢁC, DMF solution of 1-[3-(dimethylamino)
propyl]-3-ethylcarbodiimine hydrochloride (EDC, 2.2 equiv) was
added, stirred for 0.5 h, then (1S,2R)-(þ)-2-amino-1,2-diphen
ylethanol was added. The mixture solution was warmed to room
temperature and stirred overnight. After quenched with ice water,
the precipitate was filtered, washed with water, and then dried in
N
, r,t
CHCl3
R3
R1
R1
R3
14
13
Entrya
R1, R2, R3
Yield %b
ee (%)c
OR
1(a)
2(b)
3(c)
4(d)
5(e)
6(f)
7(g)
8(h)
9(i)
10(j)
11(k)
12(l)
13(m)
14(n)
Ph, Ph, Me
95
98
97
96
95
95
98
94
97
95
95
95
98
95
93
95
94
93
84
78
76
77
96
94
93
89
75
94
ꢀ13.5
ꢀ17.1
ꢀ12.1
ꢀ17.1
ꢀ40.0
þ16.5
þ11.7
ꢀ13.9
ꢀ2.0d
ꢀ18.2
þ5.7
oven. Light yellow powder 11a was obtained. [
a
]
11 þ189.47 (c 0.38,
4-FePh, Ph, Me
D
CHCl3), MS-ESI, m/z 863 [MþNa]þ. HRMS-EI m/z, calcd for
4-ClePh, Ph, Me
4-BrePh, Ph, Me
4-F3CePh, Ph, Me
4-NO2ePh, Ph, Me
4-BrePh, PMP, Me
4-MeOePh, Ph, Me
Ph, PMP, Me
Ph, 4-EtOePh, Me
Ph, 4-MeePh, Me
Ph, 4-EtePh, Me
Ph, 4-BrePh, Me
Ph, Ph, Et
C
54H44N6O4 [M]þ 840.3432, found 840.3438. 1H NMR (600 MHz,
CDCl3)
d
9.02 (s, 1H, NH), 8.95 (s, 1H, NH), 8.66 (d, J¼7.5 Hz,1H), 8.32
(d, J¼7.9 Hz, 1H), 8.18 (d, J¼7.9 Hz, 1H), 7.70 (t, J¼7.6 Hz, 1H), 7.64 (t,
J¼7.6 Hz,1H), 7.49e7.38 (m, 2H), 7.30 (t, J¼7.5 Hz,1H), 7.18e7.06 (m,
8H), 7.03e6.95 (m, 6H), 6.86 (dt, J¼15.3, 9.3 Hz, 6H), 6.73 (d,
J¼6.9 Hz, 2H), 5.56 (dd, J¼7.6, 5.0 Hz, 1H, PhCHOH), 5.48e5.37 (m,
1H, PhCHOH), 5.06 (d, J¼4.9 Hz, 1H, PhCHN), 4.96 (s, 1H, PhCHN),
3.28 (s, 3H, NCH3), 3.26 (s, 3H, NCH3)/13C NMR (150 MHz, CDCl3)
ꢀ1.74
þ26.6
þ40
d
165.28, 164.67, 143.11, 143.08, 139.88, 139.48, 138.23, 138.06,
137.81, 137.49, 137.29, 137.20, 131.29, 129.56, 129.44, 128.33, 128.12,
127.83, 127.79, 127.70, 127.58, 127.29, 127.25, 126.88, 126.21, 122.23,
122.21, 121.33, 121.29, 121.15, 121.02, 115.09, 114.88, 110.06, 110.03,
79.50, 77.51, 77.32, 77.11, 76.89, 75.71, 59.91, 59.65, 32.85, 32.57.
Unless specified, reactions were carried out with 2 equiv of HSiCl3 and 20% of 8a in
2 mL of CHCl3 at room temperature for 4 h.
a
The bold letter in bracket represents the number for compound 14, e.g., a means
14a.
b
Isolated yield.
Determined using HPLC.
The sign of OR was not very stable during measurement due to resolution
c
4.2.3. N,N0-Bis(1R,2S-2-acetoxyl-1,2-diphenylethyl)
9,90-dimethyl-
d
9H,90H-1,10-bipyrido[3,4-b]indole-3,30-dicarboxamide (11b). To a so-
lution of 11a in DCM, 1.2 equiv acetic anhydride and 5 mol % DMAP
were added then stirred at room temperature for 3 h, after wash with
limitation of the polarimeter.
to promote hydrosilylation of N-aryl ketimines with HSiCl3. N-oxide
pyridine compounds has been used in this model reaction for the first
time. Instead of typical low temperature, this reaction can be carried
out at room temperature within only 4 h in good excellent yields and
ee values.
water, and purification through silicon gel, it can gives 11b. [
a
]
11 þ167.1
D
(c 0.07, CHCl3). MS-ESI, m/z 947 [MþNa]þ. HRMS-EI m/z calcd for
C
58H48N6O6 [M]þ 924.3635, found 924.3652.1H NMR (400 MHz, CDCl3)
d
9.12 (s, 1H, NH), 9.09 (s, 1H, NH), 8.76 (d, J¼9.2 Hz, 1H), 8.60 (d,
J¼9.1 Hz, 1H), 8.37 (t, J¼7.7 Hz, 2H), 7.74 (t, J¼7.7 Hz, 2H), 7.55 (d,
J¼8.4 Hz,1H), 7.45 (dt, J¼23.4, 8.1 Hz, 3H), 7.28 (d, J¼1.8 Hz, 2H), 7.20 (s,
6H), 7.15e7.11 (m, 2H), 7.01e6.91 (m, 6H), 6.80 (t, J¼7.7 Hz, 2H), 6.67 (t,
J¼7.6 Hz, 1H), 6.56 (t, J¼7.4 Hz, 1H), 6.15 (dd, J¼11.2, 5.0 Hz, 1Hꢃ2,
PhCHOH), 5.76 (dt, J¼8.9, 6.4 Hz,1Hꢃ2, PhCHN), 3.35 (s, 3H, NCH3), 3.30
(s, 3H, NCH3), 1.91 (s, 3H, COCH3), 1.79 (s, 3H, COCH3). 13C NMR
4. Experimental section
4.1. General method
Thin layerchromatography was performed onTLC plates (GF254).
Flash column chromatography was performed with silica gel
(300e400 mesh). Enantiomeric excess was determined using a Wa-
ters HPLC with a 2695 pump and a 2996 diode array detector. Optical
rotations were performed on an Optical Activity AA-55 polarimeter
using a 10 cm cell with a Na 589 nm filter. IR spectra were obtained
with an FTIR spectrometer (Bruker Tensor 27). 1H NMR and 13C NMR
were recorded on a Bruker AV-400 or Bruker DRX-600 spectrometer.
The mass spectrawere measured onan API QSTAR Pulsar. Allsolvents
for the reactions were of reagent grade and were dried and distilled
before use.
(101 MHz, CDCl3)d169.92,169.55,164.33,164.23,143.13,143.03,138.27,
138.24, 138.16, 138.10, 137.79, 137.14, 137.12, 135.91, 134.82, 131.55,
131.23, 129.53, 129.36, 128.32, 128.24, 128.19, 128.05, 127.97, 127.61,
127.19, 126.98, 122.13, 122.06, 121.45, 121.31, 121.14, 114.91, 114.61,
110.07, 110.02, 77.62, 77.21, 56.48, 56.45, 32.72, 32.61, 20.93, 20.68.
4.2.4. 3,30-Bis[(1R,2S-2-hydroxy-1,2-diphenylethyl)aminocarbonyl]-
9,90-dimethyl-9H,90H-1,10-bipyrido[3,4-b]indole-2-oxide
(8a). Peroxide-urea (8 equiv) and TFA (8 equiv) were added to the
solution of 11a, and stirred at room temperature for 48 h. After
purified by silicon column and Chiralpak IC column, yellow powder
11
8a was obtained. [
a
]
D
ꢀ211.05 (c 0.16, CHCl3). MS-ESI, m/z 879
4.2. General procedure for preparation of catalysts
[MþNa]þ. HRMS-EI m/z calcd for C54H44N6O5 [M]þ, 856.3373, found
856.3401. 1H NMR (600 MHz, CDCl3)
d 9.08 (s, 1H, NH), 8.91 (s, 1H,
4.2.1. 9,90-Dimethyl-9H,90H-1,10-bipyrido[3,4-b]indole-3,30-di-
carboxylic acid (10). To a solution of 9 (5 mmol in CH3OH (40 mL))
NaOH (4 mL, 5 mol/L) was added at 0 ꢁC, the mixture was heated to
60 ꢁC, and refluxed for 12 h, then HCl solution (1 M) was added to
adjust its pH to 3e4. The precipitate was filtered, and washed with
water, then dried in vacuum oven. Light yellow powder 10 was ob-
tained. MS-ESI, m/z 473 [MþNa]þ. HRMS m/z calcd for C26H18N4O4Na
NH), 8.35 (d, J¼7.6 Hz, 1H), 7.86 (d, J¼7.3 Hz, 1H), 7.70 (dt, J¼14.4,
7.4 Hz, 2H), 7.53 (d, J¼8.3 Hz, 1H), 7.50e7.43 (m, 2H), 7.15 (dt,
J¼22.9, 7.3 Hz, 8H), 7.04 (d, J¼7.3 Hz, 2H), 6.98 (d, J¼6.9 Hz, 6H),
6.92 (d, J¼6.6 Hz, 4H), 6.68 (d, J¼3.3 Hz, 2H), 6.37 (d, J¼55.1 Hz, 1H),
5.47 (s, 1H, PhCHOH), 5.37 (d, J¼6.4 Hz, 1H, PhCHOH), 5.18 (d,
J¼6.4 Hz, 1H, PhCHN), 4.49 (s, 1H, PhCHN), 3.64 (s, 3H, NCH3), 3.08
(s, 3H, NCH3). 13C NMR (151 MHz, CDCl3)
d 164.48, 160.56, 144.23,
[MþNa]þ 473.1225, found 473.1230. 1H NMR (400 MHz, DMSO)
d
3.47
142.95, 140.35, 140.27, 139.11, 138.78, 138.16, 138.14, 136.00, 132.77,
131.69, 131.04, 130.46, 129.79, 129.51, 128.68, 128.39, 127.87, 127.71,
127.62, 127.38, 127.20, 127.06, 126.40, 126.18, 123.12, 122.84, 122.37,
(3Hꢃ2, s, NCH3), 7.42 (1Hꢃ2, t, J¼7.4 Hz), 7.66e7.78 (2Hꢃ2, m), 8.58
(1Hꢃ2, d, J¼7.9 Hz), 9.16 (1Hꢃ2, s).13C NMR (100 MHz, DMSO)
d 32.6,

7256
W. Pan et al. / Tetrahedron 69 (2013) 7253e7257
122.13, 121.51, 121.46, 120.96, 120.16, 116.31, 110.31, 109.95, 74.97,
74.56, 60.67, 60.45, 32.03, 29.86.
in anhydrous CHCl3 at 27 ꢁC. The mixture was allowed to stir at the
same temperature for 4 h. The reaction was quenched with satu-
rated aqueous solution of NaHCO3 and was extracted with CH2Cl2.
The combined organic layers were washed with brine and dried
over anhydrous MgSO4 and the solvents were evaporated. Purifi-
cation by column chromatography (silica gel, hexane/EtOAc)
afforded pure amine 14. The ee% values were determined using
established HPLC techniques with chiral stationary phases.
4.2.5. 3,30-Bis[(1R,2S-2-acetoxyl-1,2-diphenylethyl)aminocarbonyl]-
9,90-dimethyl-9H,90H-1,10-bipyrido[3,4-b]indole-2-oxide
(8b). Following procedure to give 8a, starting from 11b, light yellow
powder 8b was obtained. MS-ESI, m/z 963 [MþNa]þ. HRMS-EI m/z
calcd for C58H48N6O7 [M]þ 940.3584, found 940.3519. [
a]
11 þ405.56
D
(c 0.36, CHCl3). 1H NMR (600 MHz, CDCl3)
d
9.30 (s, 1H, NH), 9.08 (s,
1H, NH), 8.44 (d, J¼9.1 Hz, 1H), 8.32 (d, J¼7.9 Hz, 1H), 8.26 (d,
J¼7.9 Hz, 1H), 7.74 (t, J¼7.7 Hz, 1H), 7.68 (t, J¼7.7 Hz, 1H), 7.55 (t,
J¼7.1 Hz, 1H), 7.45 (qd, J¼12.6, 8.7 Hz, 4H), 7.24e7.15 (m, 16H), 6.97
(d, J¼7.4 Hz, 3H), 6.92 (t, J¼7.4 Hz, 1H), 6.75 (t, J¼7.7 Hz, 2H), 6.22 (t,
J¼7.0 Hz, 1H, PhCHOH), 6.11 (d, J¼6.1 Hz, 1H, PhCHOH), 5.72 (td,
J¼9.3, 6.5 Hz, 2H, PhCHN), 3.53 (s, 3H, NCH3), 2.95 (s, 3H, NCH3), 1.88
(s, 3H, COCH3), 1.78 (s, 3H, COCH3). 13C NMR (151 MHz, CDCl3)
4.4.1. N-Phenyl-N-(1-phenylethyl)amine (14a). 1H NMR (400 MHz,
CDCl3)
d
7.45e7.28 (m, 17H), 7.22 (dd, J¼29.8, 22.9 Hz, 7H), 7.10 (d,
J¼7.4 Hz, 6H), 6.68 (t, J¼7.3 Hz, 4H), 6.55 (d, J¼7.8 Hz, 8H), 4.50 (q,
J¼6.7 Hz, 5H), 1.54 (d, J¼6.7 Hz, 13H). Enantiomeric excess was
determined by HPLC with a chiralcel OD-H column (hexane/2-
propanol¼98/2, 1 mL/min), tminor¼10.7 min; tmajor¼12.9 min, 93%
14
ee. [
a]
ꢀ13.5 (c 0.85, CH3OH).
D
d
169.87, 169.59, 163.92, 160.19, 144.01, 142.83, 138.68, 138.62, 137.84,
137.74, 137.32, 137.05, 136.09, 132.19, 131.81, 130.81, 130.08, 129.74,
129.29, 128.25, 128.19, 128.14, 127.98, 127.72, 127.33, 127.05, 122.91,
122.33, 122.24, 121.74, 121.29, 121.27, 121.15, 120.18, 116.26, 109.99,
109.83, 77.07, 76.85, 57.79, 56.55, 31.88, 29.75, 20.95, 20.79.
4.4.2. N-Phenyl-N-[1-(4-fluorophenyl)ethyl]amine (14b). 1H NMR
(400 MHz, CDCl3) 7.45e7.26 (m, 2H), 7.15e6.90 (m, 4H), 6.71 (t,
d
J¼7.3 Hz,1H), 6.55 (d, J¼7.8 Hz, 2H), 4.47 (dd, J¼13.4, 6.6 Hz, 1H), 1.53
(d, J¼6.7 Hz, 3H). Enantiomeric excess was determined by HPLC with
a chiralcel OD-H column (hexane/2-propanol¼98/2, 0.5 mL/min),
4.2.6. 2-[(1R,2S-2-Hydroxy-1,2-diphenylethyl)aminocarbonyl]pyridine
oxide(12). To a solution of picolinic acid and 1-hydroxybenzotriazole
(HOBT 1.1 equiv) in DMF kept under nitrogen at 0 ꢁC, DMF solution of
tminor¼19.9 min; tmajor¼22.7min, 95% ee. [
a
]
14 ꢀ17.1 (c 0.002, CH3OH).
D
4.4.3. N-Phenyl-N-[1-(4-chlorophenyl)ethyl]amine (14c). 1H NMR
(400 MHz, CDCl3)
1-[3-(dimethylamino)propyl]-3-ethylcarbodiimine
hydrochloride
d
7.45e7.28 (m,17H), 7.22 (dd, J¼29.8, 22.9 Hz, 7H),
(EDC$HCl, 1.1 equiv) was added, stirred for 0.5 h, then (1S,2R)-(þ)-2-
amino-1,2-diphenylethanol was added. The mixture was warmed to
room temperature and overnight, then quenched with ice water. The
precipitate was filtered, and washed with water. Dried in vacuum
oven. Light yellow powder can be obtained. The powder was dis-
solved in DCM, 8 equiv peroxide-urea, and 8 equiv TFA were added
7.10 (d, J¼7.4 Hz, 6H), 6.68 (t, J¼7.3 Hz, 4H), 6.55 (d, J¼7.8 Hz, 8H), 4.50
(q, J¼6.7 Hz, 5H), 1.54 (d, J¼6.7 Hz, 13H). Enantiomeric excess was
determined by HPLC with a chiralcel OD-H column (hexane/2-
propanol¼98/2, 0.5 mL/min), tminor¼26.3 min; tmajor¼29.6 min, 94%
ee. [
a
]
14 ꢀ12.1 (c 0.03, CH3OH).
D
and stirred at room temperature for 48 h. After silicon column
4.4.4. N-Phenyl-N-[1-(4-bromophenyl)ethyl)amine] (14d). 1H NMR
(400 MHz, CDCl3)
11
chromatography, 12 was obtained. [
a
]
þ52.63 (c 0.19, CHCl3) MS-
d
7.34 (d, J¼8.4 Hz, 2H), 7.16 (d, J¼8.2 Hz, 2H), 7.01
D
ESI, m/z 357 [MþNa]þ. HRMS-EI m/z calcd for C20H18N2O3 [M]þ
334.1317, found 334.1312. 1H NMR (600 MHz, CDCl3), 8.35e8.36 (d,
J¼2.1 Hz, 1H), 8.23e8.20 (m, 1H), 7.45e7.40 (m, 1H), 7.38e7.34 (m,
1H), 7.26e7.20 (m, 7H), 7.17e7.14 (m, 2H), 7.14e7.10 (m, 2H), 5.48 (dd,
J¼8.1, 4.9 Hz, 1H), 5.14 (d, J¼4.8 Hz, 1H). 13C NMR (151 MHz, CDCl3)
(t, J¼7.9 Hz, 2H), 6.59 (t, J¼7.3 Hz, 1H), 6.40 (d, J¼7.7 Hz, 2H), 4.34
(dd, J¼13.4, 6.7 Hz, 1H), 1.41 (d, J¼6.7 Hz, 3H). Enantiomeric excess
was determined by HPLC with a chiralcel OD-H column (hexane/2-
propanol¼95/5, 1 mL/min), tminor¼10.7 min; tmajor¼12.1 min, 90%
14
ee. [
a]
ꢀ17.1 (c 0.02, CH3OH).
D
d
159.56,140.73,140.64, 140.04, 137.27, 129.19,128.42,128.28,128.23,
128.10, 127.92, 127.73, 127.61, 126.94, 77.18, 60.57.
4.4.5. N-Phenyl-N-[1-(4-trifluoromethylphenyl)ethyl]amine
(14e). 1H NMR (400 MHz, CDCl3)
d
7.58 (s, 6H), 7.53 (dd, J¼29.2,
4.3. General procedure for preparation of imines
A mixture of NaHCO3 (50 mmol), and the corresponding amine
8.1 Hz, 29H), 7.28 (s, 2H), 7.15 (dd, J¼37.7, 29.8 Hz, 26H), 6.72 (t,
J¼7.3 Hz, 9H), 6.54 (d, J¼7.6 Hz, 16H), 4.53 (dd, J¼13.4, 6.7 Hz, 12H),
1.56 (d, J¼6.7 Hz, 35H). Enantiomeric excess was determined by HPLC
with a chiralcel OD-Hcolumn (hexane/2-propanol¼90/10,1 mL/min),
ꢀ
(10 mmol) and ketone (10 mmol) plus activated molecular 4 A sieves
(8.0g)inanhydrous toluene(10 mL)washeatedat80ꢁCfor12hunder
an argon atmosphere. The mixture was filtered through Celite. The
filtrate was then evaporated in vacuum and the product was crystal-
lized from appropriate solvents or purified by distillation to give pure
imine. Only the 1H NMR data of two new imines were listed here.
tminor¼8.7 min; tmajor¼9.8 min, 84% ee. [
a
]
14 ꢀ40 (c 0.015, CH3OH).
D
4.4.6. N-Phenyl-N-[1-(4-nitrophenyl)ethyl)amine] (14f). 1H NMR
(400 MHz, CDCl3)
d
8.18 (d, J¼8.7 Hz, 4H), 7.56 (d, J¼8.6 Hz, 4H), 7.11
(dd, J¼8.5, 7.4Hz, 4H), 6.71 (t, J¼7.3Hz, 2H), 6.48 (d, J¼7.7Hz, 4H), 4.57
(dd, J¼13.5, 6.8 Hz, 3H), 1.56 (d, J¼6.8 Hz, 6H). Enantiomeric excess
was determined by HPLC with a chiralcel OD-H column (hexane/2-
propanol¼98/2, 0.5 mL/min), tminor¼20.4 min; tmajor¼22.1 min, 78%
4.3.1. Compound 13j. MS-ESI, m/z 240 [MþH]þ 1H NMR (400 MHz,
CDCl3)
d
8.02e7.94 (m, 2H), 7.45 (dd, J¼5.2, 1.9 Hz, 3H), 6.96e6.89
(m, 2H), 6.76 (dd, J¼6.6, 2.2 Hz, 2H), 4.04 (q, J¼7.0 Hz, 2H), 2.26 (s,
ee. [
a
]
14 þ16.5 (c 0.03, CH3OH).
D
3H), 1.44 (t, J¼7.0 Hz, 3H).
4.4.7. N-Methoxyphenyl-N-[1-(4-bromophenyl)ethyl]amine
(14g). 1H NMR (400 MHz, CDCl3)
4.3.2. Compound 13l. MS-ESI, m/z 224 [MþH]þ 1H NMR (400 MHz,
d
7.42 (d, J¼8.4 Hz, 2H), 7.25 (d,
CDCl3)
d
8.02 (m, 2H), 7.51 (dd, J¼8.0, 2.3 Hz, 3H), 7.05 (d, J¼8.1 Hz,
J¼9.2 Hz, 2H), 6.74e6.66 (m, 2H), 6.50 (d, J¼8.7 Hz, 2H), 4.36 (dd,
J¼13.2, 6.6 Hz, 1H), 3.69 (d, J¼6.0 Hz, 3H), 1.51 (d, J¼6.7 Hz, 3H).
Enantiomeric excess was determined by HPLC with a chiralcel OD-
H column (hexane/2-propanol¼98/2, 1 mL/min), tmajor¼19.8 min;
2H), 6.67 (d, J¼8.2 Hz, 2H), 2.63 (m, 2H), 2.29 (s, 3H), 1.26 (t,
J¼7.6 Hz, 3H).
4.4. General procedure for the hydrosilylation of ketimines
tminor¼26.2 min, 80% ee. [
a
]
14 þ11.69 (c 0.03, CH3OH).
D
Under an argon atmosphere, 2 equiv trichlorosilane was added
dropwise to a stirred solution of imine 13 and catalyst 8a (20 mol %)
4.4.8. N-Phenyl-N-[1-(4-methoxyphenyl)ethyl]amine (14h). 1H NMR
(400 MHz, CDCl3)
7.30 (t, J¼12.4 Hz, 2H), 7.17e6.99 (m, 2H), 6.99e6.79
d

W. Pan et al. / Tetrahedron 69 (2013) 7253e7257
7257
14
(m, 2H), 6.73e6.46 (m, 3H), 4.47 (q, J¼6.7 Hz, 1H), 3.79 (s, 3H), 1.52 (d,
1 mL/min), tminor¼13.0 min; tmajor¼15.2 min, 94% ee. [
a
]
þ40 (c
D
J¼6.7 Hz, 3H). Enantiomeric excess was determined by HPLC with
a chiralcel OD-H column (hexane/2-propanol¼98/2, 1 mL/min), tmi-
0.01, CH3OH).
¼13.2 min; tmajor¼14.1 min, 79% ee. [
a
]
14 ꢀ13.93 (c 0.01, CH3OH).
Acknowledgements
nor
D
4.4.9. N-Methoxyphenyl-N-[(1-phenyl)ethyl]amine (14i). 1H NMR
(400 MHz, CDCl3) 7.57e7.28 (m, 4H), 7.31e7.14 (m, 1H), 6.82e6.66
H.J.Z. thanks the 973 Program (2009CB 522300) and Hebei
University for their support of this research. We also acknowledged
the Super-Computer-Center in CAS for their help in this study.
d
(m, 2H), 6.51(d,J¼8.9Hz, 2H), 4.44(dd, J¼13.3, 6.6 Hz,1H), 3.72 (s, 3H),
1.53 (d, J¼6.7 Hz, 3H). Enantiomeric excess was determined by HPLC
with a chiralcel AD-H column (hexane/2-propanol¼98/2, 1 mL/min),
References and notes
tmajor¼10.7 min; tminor¼12.3 min, 96% ee. [
a
]
14 ꢀ2.03 (c 0.013, CH3OH).
D
1. (a) Guizzetti, S.; Benaglia, M. Eur. J. Org. Chem. 2010, 2010, 5529e5541; (b)
Iwasaki, F.; Onomura, O.; Mishima, K.; Maki, T.; Matsumura, Y. Tetrahedron Lett.
1999, 40, 7507e7511; (c) Malkov, A. V.; Stewart-Liddon, A. J. P.; McGeoch, G. D.;
Ramirez-Lopez, P.; Kocovsky, P. Org. Biomol. Chem. 2012, 10, 4864e4877; (d)
Carpentier, J.-F.; Bette, V. Curr. Org. Chem. 2002, 6, 913e916.
4.4.10. N-Ethoxyl-N-[(1-phenyl)ethyl]amine (14j). MS-ESI, m/z 242
[MþH]þ. 1H NMR (400 MHz, CDCl3)
d 7.56e7.10 (m, 5H), 6.92e6.58
(m, 2H), 6.51 (d, J¼8.6 Hz, 2H), 4.42 (dd, J¼13.2, 6.6 Hz, 1H), 3.91
(dd, J¼13.9, 7.0 Hz, 2H), 1.53 (d, J¼6.7 Hz, 3H), 1.34 (t, J¼7.0 Hz, 3H).
Enantiomeric excess was determined by HPLC with a chiralcel AD-
H column (hexane/2-propanol¼98/2, 1 mL/min), tmajor¼9.9 min;
2. (a) Iwasaki, F.; Onomura, O.; Mishima, K.; Kanematsu, T.; Maki, T.; Matsumura,
Y. Tetrahedron Lett. 2001, 42, 2525e2527; (b) Malkov, A. V.; Mariani, A.; Mac-
ꢁ
ꢂ
Dougall, K. N.; Kocovsky, P. Org. Lett. 2004, 6, 2253e2256; (c) Malkov, A. V.;
ꢁ
ꢁ
ꢂ
Stoncius, S.; Kocovsky, P. Angew. Chem., Int. Ed. 2007, 46, 3722e3724; (d) Mal-
kov, A. V.; Vrankova, K.; Cerny, M.; Kocovsky, P. J. Org. Chem. 2009, 74,
8425e8427; (e) Malkov, A. V.; Vrankova, K.; Sigerson, R. C.; Stoncius, S.;
Kocovsky, P. Tetrahedron 2009, 65, 9481e9486; (f) Wang, Z.; Ye, X.; Wei, S.; Wu,
P.; Zhang, A.; Sun, J. Org. Lett. 2006, 8, 999e1001; (g) Zhou, L.; Wang, Z.; Wei, S.;
Sun, J. Chem. Commun. 2007, 2977e2979.
ꢁ
14 ꢀ18.2 (c 0.015, CH3OH).
ꢂ
ꢂ
ꢁ
ꢂ
tminor¼11.5 min, 92% ee. [
a]
D
ꢂ
ꢁ
ꢁ
ꢂ
4.4.11. N-Methylphenyl-N-[(1-lphenyl)ethyl]amine (14k). 1H NMR
(400 MHz, CDCl3)
d
7.46e7.30 (m, 4H), 7.25 (s, 1H), 6.93 (d, J¼8.1 Hz,
3. (a) Guizzetti, S.; Benaglia, M.; Cozzi, F.; Annunziata, R. Tetrahedron 2009, 65,
6354e6363; (b) Guizzetti, S.; Benaglia, M.; Rossi, S. Org. Lett. 2009, 11,
2928e2931; (c) Zheng, H.; Deng, J.; Lin, W.; Zhang, X. Tetrahedron Lett. 2007, 48,
7934e7937; (d) Jiang, Y.; Chen, X.; Zheng, Y.; Xue, Z.; Shu, C.; Yuan, W.; Zhang,
X. Angew. Chem., Int. Ed. 2011, 50, 7304e7307.
2H), 6.48 (d, J¼8.4 Hz, 2H), 4.48 (q, J¼6.7 Hz,1H), 2.22 (s, 3H),1.54 (d,
J¼6.7 Hz, 3H). Enantiomeric excess was determined by HPLC with
a chiralcel OD-H column (hexane/2-propanol¼99/1, 1 mL/min), tma-
jor¼11.3 min; tminor¼13.1 min, 93% ee. [
a]
D
14 þ3.6 (c 0.025, CH3OH).
ꢂ
ꢂ
4. Malkov, A. V.; Liddon, A. J. P. S.; Ramírez-Lopez, P.; Bendova, L.; Haigh, D.;
ꢁ
ꢂ
Kocovsky, P. Angew. Chem., Int. Ed. 2006, 45, 1432e1435.
5. (a) Sugiura, M.; Sato, N.; Kotani, S.; Nakajima, M. Chem. Commun. 2008,
4309e4311; (b) Guizzetti, S.; Benaglia, M.; Cozzi, F.; Rossi, S.; Celentano, G.
Chirality 2009, 21, 233e238.
6. Malkov, A. V.; Figlus, M.; Kocovsky, P. J. Org. Chem. 2008, 73, 3985e3995.
7. (a) Wang, Z.; Wei, S.; Wang, C.; Sun, J. Tetrahedron: Asymmetry 2007, 18, 705e709;
(b) Pei, D.; Zhang, Y.;Wei, S.; Wang, M.; Sun, J. Adv. Synth. Catal.2008, 350, 619e623.
8. (a) Pei, D.; Wang, Z.; Wei, S.; Zhang, Y.; Sun, J. Org. Lett. 2006, 8, 5913e5915;
(b) Wang, C.; Wu, X.; Zhou, L.; Sun, J. Chem.dEur. J. 2008, 14, 8789e8792.
9. (a) Bai, B.; Shen, L.; Ren, J.; Zhu, H. J. Adv. Synth. Catal. 2012, 354, 354e358;
(b) Bai, B.; Zhu, H.-J.; Pan, W. Tetrahedron 2012, 68, 6829e6836.
4.4.12. N-Ethylphenyl-N-[(1-phenyl)ethyl]amine (l4l). MS-ESI, m/z
226 [MþH]þ. 1H NMR (400 MHz, CDCl3)
d 7.60e7.09 (m, 5H), 6.95
(d, J¼8.0 Hz, 2H), 6.51 (d, J¼8.0 Hz, 2H), 4.47 (dd, J¼12.9, 6.3 Hz,1H),
2.51 (dd, J¼14.9, 7.4 Hz, 2H), 1.54 (d, J¼6.6 Hz, 3H), 1.16 (t, J¼7.5 Hz,
3H). Enantiomeric excess was determined by HPLC with a chiralcel
OD-H column (hexane/2-propanol¼97/3þ0.1% Et3N, 1 mL/min),
ꢁ
ꢂ
tmajor¼8.2 min; tminor¼8.8 min, 93% ee. [
a
]
14 ꢀ1.74 (c 0.025, CH3OH).
D
10. (a) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratemann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.;
Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuk, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J.
V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-
Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03 User’s
Reference; Gaussian: Carnegie, PA 15106, USA, 2003; (b) Zhu, H. J.; Jiang, J. X.;
Saobo, S.; Pittman, C. U. J. Org. Chem. 2005, 70, 261e267.
4.4.13. N-4-Bromophenyl-N-[(1-phenyl)ethyl]amine (14m). 1H NMR
(400 MHz, CDCl3) 7.41e7.29 (m, 4H), 7.29e7.22 (m, 1H), 7.16 (d,
d
J¼8.8 Hz, 2H), 6.40 (d, J¼8.8 Hz, 2H), 4.44 (q, J¼6.7 Hz, 1H), 1.53 (d,
J¼6.7 Hz, 3H). Enantiomeric excess was determined by HPLC with
a chiralcel OD-H column (hexane/2-propanol¼99/1, 1 mL/min), tma-
jor¼15.3 min; tminor¼20.5 min, 76% ee. [
a]
14 26.6 (c 0.008, CH3OH).
D
4.4.14. N-phenyl-N-(1-lphenylpropyl)amine (14n). 1H NMR (400 MH
z, CDCl3)
d
7.54e7.17 (m, 5H), 7.09 (t, J¼7.3 Hz, 2H), 6.64 (dd, J¼41.1,
6.7 Hz, 3H), 4.22 (t, J¼6.4 Hz, 1H), 1.88 (dd, J¼13.1, 6.5 Hz, 2H), 0.92
(dd, J¼19.6, 12.4 Hz, 3H). Enantiomeric excess was determined by
HPLC with a chiralcel AD-H column (hexane/2-propanol¼98/2,