The effect of coordination on the reaction of N-tosyl imines with diethylzinc

Article abstract of DOI:10.1016/j.tet.2005.09.111

The effect of coordination on the reaction of N-tosyl imines and diethylzinc was studied in detail. It showed that there was strong coordination between N-tosyl imine and diethylzinc. Due to this coordination, N-tosyl imines could be reduced directly thro

Full text of DOI:10.1016/j.tet.2005.09.111

Tetrahedron 61 (2005) 12238–12243
The effect of coordination on the reaction of N-tosyl imines
with diethylzinc
*
Feifeng Gao, Minzhi Deng and Changtao Qian
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, China
Received 26 August 2005; revised 20 September 2005; accepted 23 September 2005
Available online 21 October 2005
Abstract—The effect of coordination on the reaction of N-tosyl imines and diethylzinc was studied in detail. It showed that there was strong
coordination between N-tosyl imine and diethylzinc. Due to this coordination, N-tosyl imines could be reduced directly through the b-H
transferring mechanism by diethylzinc in nonpolar solvents to afford the corresponding secondary amines in excellent yields at mild
conditions. The coordination of diethylzinc and N-tosyl imine was hindered by reacting in polar solvents or adding TMEDA to the reaction, it
afforded ethylating product partially or exclusively.
q 2005 Elsevier Ltd. All rights reserved.
Table 1. Reduction of imines by diethylzinc in toluene
1. Introduction
The reduction of imines to amines is an important
transformation in organic chemistry. Most of the methods
involve borohydride reagents or transition metal hydro-
Entry
Ar
R
Time (h)
Yielda of 2
(%)
genation catalysts;1 Few general methods employing main
group Lewis acid catalysts have appeared.2 Imines also
could be reduced by Grignard reagents bearing b-H. Thies
et al. have observed that N-benzylidene-N-butylimine could
be partially reduced to amines by i-PrMgI during the
addition reaction.3 Davis et al. have also found that
N-sulfinylimine could be slightly reduced to amines by
n-BuMgCl during the addition reaction.4 Crowe et al. have
even reported that, in the presence of a catalytic amount of
Cp2TiCl2, n-BuMgCl could be used as the reductive reagent
in the reduction of imine.5
1
2
3
4
5
6
7
8
9
10
1a, Ph
Ts
1
1
1
2
1
5
1
24
24
24
2a, 98
2b, 96
2c, quant.
2d, 71
2e, 98
2f, 70
2g, 86
—
1b, 4-MeOC6H4
1c, 2-MeOC6H4
1d, 4-MeC6H4
1e, 4-ClC6H4
1f, 1-C10H7
1g, Ph
1h, Ph
1i, Ph
1j, Ph
Ms
P(O)Ph2
Ph
2-MeOC6H4
—
—
a Isolated yield.
Diethylzinc has been widely applied in organic synthesis,
such as addition to aldehydes,6 ketones7 and imines,1a
radical addition as chain-transfer agent2b,8 and catalytic
enantioselective reduction of ketones as the precatalyst.9
Various imines were allowed to react with diethylzinc in
toluene at rt, the results were summarized in Table 1. All
N-tosyl imines afforded the corresponding reduction
products with good to excellent yields exclusively (entry
1–7, Table 1) while there was no reductive or addition
reaction product under the same conditions in the case of
N-aryl aldimines and N-phosphinylimine (entry 8–10,
Table 1). For N-phosphinylimine had the similar structure
to N-tosyl imine, it was possible due to the bond length
differences between N-tosyl-imine and N-phosphinylimine.
Though diethylzinc could reduce benzaldehyde to afford
benzyl alcohol as the byproduct in the addition reaction to
benzaldehyde,10 there are also a few reports about the
reduction of imines by diethylzinc during the enantioselec-
tive addition to the imines.11
Keywords: N-Tosyl imines; Diethylzinc; Reduction; Ethylation; Solvent
effect; Coordination.
The effect of solvents on the reaction of N-tosyl imine and
diethylzinc was studied. The results were shown in Table 2.
It turned out that solvents had strong effect on the reaction.
*
Corresponding author. Tel.: C86 21 54925030; fax: C86 21 64166148;
e-mail: qianct@mail.sioc.ac.cn
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.111

F. Gao et al. / Tetrahedron 61 (2005) 12238–12243
Table 3. Nitro-Mannich reaction in CH3NO2
12239
Table 2. Effect of the solvents
Entry
Solvent
Time (h)
2aa (%)
3aa(%)
Entry
Ar
Amount of
Et2Zn (equiv)
Time (h) Yielda of 4
(%)
1
2
3
4
5
6
Hexane
Toluene
THF
Et2O
CH3CN
CH2Cl2
3
1
6
6
6
6
92
98
27
65
51
85
—
—
40
14
18
14
1
2
3
4
5
6
7
9
1a, Ph
1.2
0.5
0.2
1.2
6
18
24
6
4a, 73
4a, 62
4a, 25
4b, 86
4c, 59
4d, 79
4e, 75
4f, 50b
1b, 4-MeOC6H4
1c, 2-MeOC6H4
1d, 4-MeC6H4
1e, 4-ClC6H4
1f, 1-C10H7
6
6
a Isolated yield.
6
12
It was found that N-tosyl imine 1a could be readily reduced
by diethylzinc at very mild conditions in nonpolar solvents
(entry 1–2, Table 2). Though the N-tosyl imine 1a and the
corresponding reduction product 2a were almost insoluble
in hexane, the reduction reaction still proceeded smoothly
(entry 1, Table 2). The reaction phenomenon in toluene was
especially interesting. Those N-tosyl imines could not be
dissolved in toluene completely under the reaction
conditions (entry 1–7, Table 1). After diethylzinc was
added into the mixture, the turbid mixture became clear.
About 30 min later, white precipitates came out in company
with a releasing gas which was trapped by liquid N2 and
proved to be ethylene by GC–MS.
a Isolated yield.
b 47% Reduction product 2f was isolated.
The coordination between N-tosyl imine and diethylzinc
was shown more obviously in nitro-Mannich reaction when
CH3NO2 was used as the reaction solvent (Table 3). In those
reaction, it was found that dialkylzinc could only promote
but not catalyze the nitro-Mannich reaction either in
CH3NO2 (entry 1–3, Table 3) or in other solvents such as
toluene, hexane, CH2Cl2, Et2O and THF, while even Et3N
(20 mol%) could catalyze the nitro-Mannich reaction of
N-tosyl imine with a yield of 74%.12
Interestingly, when imine 1f and diethylzinc were reacted in
CH3NO2, the product ratio between 4f (nitro-Mannich
adduct) and 2f (reduction product) was almost 1:1 (entry 9,
Table 3). We thought it might be caused by the steric effect,
which suppressed the nitro-Mannich reaction. If a stronger
coordination ligand was added to break the coordination
between imine 1f and diethylzinc, it would reduce the
amount of reduction product. Indeed, when this reaction was
taken place in THF, no reduction product was detected other
than 51% nitro-Mannich addition product 4f (Scheme 2).
These were all in accordance with the b-H transferring
mechanism also.
But in polar solvents, ethylating product was also found in
the reaction along with reduction product (entry 3–6,
Table 2).
According to the reaction phenomenon and results, we
proposed the reaction of N-tosyl imines and diethylzinc in
different solvents may proceed as Scheme 1.
Scheme 1.
In nonpolar solvent diethylzinc and the N-tosyl imine
brought out a zinc specie with the presumed structure A,
then the b-hydrogen atom of the ethyl group was transferred
to the C]N double bond with release of ethylene, therefore
the reduction product 2 was formed. The product 2 was
obtained exclusively in toluene and hexane.
Scheme 2.
This could be confirmed by the results of another steric
hindered imine 1k (Scheme 3). Similar to the imine 1f, it
took much longer time, 12 h, for imine 1k to be reduced in
toluene than other imines 1a–1e and the reduction product
2k was also isolated with 15% yield when imine 1k and
diethylzinc was reacted in CH3NO2. Unlike imine 1a, the
reduction product 2k was the major one when it was reacted
in THF.
On the contrary, the polar solvent such as THF, which could
coordinate predominately with diethylzinc and activate
diethylzinc in some extent, led to the addition reaction. As a
result, the addition product 3 became the main product
(entry 3, Table 2). When weaker coordination solvent such
as Et2O was used, it was still predominated by the reduction
reaction was still the (entry 4, Table 2).
The coordination effects could be proven by following
experiments more clearly. Diethylzinc with an equiv of

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F. Gao et al. / Tetrahedron 61 (2005) 12238–12243
Scheme 3.
TMEDA (tetramethyl ethylene diamine) or (S)-1,20-methyl-
enedipyrrolidine, which could prevent the coordination of
diethylzinc with N-tosyl imine, were stirred for 30 min at rt,
and then 1 equiv of N-tosyl imine was added to the reaction
mixture. It was found all gave ethylating product in good
yield without detection of the reduction product in NMR
whether in THF or toluene. In the case of the chiral ligand
(S)-1,20-methylenedipyrrolidine, it gave 98% yield with
77% ee in toluene (Scheme 4).
on BRUCKER AMX-300 for proton. IR spectra were
obtained on a Shimadzu IR-440 infrared spectrophotometer.
Mass spectra were determined on a Finnigan 8230 mass
spectrometer. Elemental analyses were performed on a
Foss-Heraeus Vario EL instrument.
2.1.1. General procedure (for reduction of Imine 1a–1k
by diethylzinc). Under N2 atmosphere, imine 1a (260 mg,
1 mmol) was dissolved in 5 mL toluene at rt. Diethylzinc
(1.2 mL, 1 M in hexane) was syringed into the solution. The
turbid mixture soon became clear in 5 min. After about
30 min, white precipitates came out while bubbling. When
no gas was released, the reaction was treated with 1 M HCl,
15 mL ethyl acetate was added, washed with water and
brine, dried over Na2SO4, evaporated in vacuum to give a
white solid 2a, N-Benzyl-4-methylbenzenesulfonamide
(254 mg, 98% yield), no need for further purification. Mp
1
111.1 8C; H NMR (300 MHz, CDCl3, 25 8C, TMS): dZ
7.69 (d, JZ8.25 Hz, 2H), 7.26–7.12 (m, 7H), 4.64 (t, JZ
6.1 Hz, 1H), 4.05 (d, JZ6.1 Hz, 2H), 2.37 (s, 3H); IR (KBr):
nZ3271, 1599, 1381, 1163 cmK1; MS (m/z) 262, 135. Anal.
Calcld for C14H15NO2S: C: 64.34, H: 5.79, N: 5.38, S:
12.27. Found: C: 64.62, H: 5.78, N: 5.23, S: 12.42.
2.1.2. N-(4-Methoxybenzyl)-4-methylbenzenesulfona-
mide 2b. The product was obtained according to the
general procedure, isolated as a white solid in quantitative
Scheme 4.
1
yield. Mp 116.6 8C; H NMR (300 MHz, CDCl3, 25 8C,
TMS): dZ7.76 (d, JZ7.63 Hz, 2H), 7.31 (d, JZ7.73 Hz,
2H), 7.10 (d, JZ7.91 Hz, 2H), 6.80 (d, JZ7.86 Hz, 2H),
4.63 (br s, 1H), 4.05 (d, JZ3.34 Hz, 2H), 3.77 (s, 3H), 2.44
(s, 3H); IR (KBr): nZ3253, 1612, 1381, 1160 cmK1; MS
(m/z) 291, 135. Anal. Calcld for C15H17NO3S: C: 61.83, H:
5.88, N: 4.81, S: 11.01. Found: C: 61.57, H: 5.76, N: 4.81, S:
11.29.
In conclusion, we studied the effect of solvents on the
reaction of N-tosyl imines and diethylzinc in detail and
found there was strong coordination between N-tosyl imine
and diethylzinc. The N-tosyl imines were reduced directly
by diethylzinc in nonpolar solvents to give corresponding
secondary amines in good to excellent yields through the
b-H transferring mechanism. The coordination of diethyl-
zinc and N-tosyl imine was hindered by using the polar
solvents or addition of TMEDA or (S)-1,20-methylene-
dipyrrolidine to the reaction, it afforded ethylating product
partially or exclusively. This coordination could be used in
the further study.
2.1.3. N-(2-Methoxybenzyl)-4-methylbenzenesulfona-
mide 2c. The product was obtained according to the general
procedure, purified by silica gel chromatography (petroleum
ether/acetate ethylZ5:1) and isolated as a pale oil in 96%
yield; 1H NMR (300 MHz,CDCl3, 25 8C, TMS): dZ7.58 (d,
JZ8.20 Hz, 2H), 7.12–7.09 (m, 3H), 6.98 (t, JZ7.4 Hz,
1H), 6.72 (t, JZ7.4 Hz, 1H), 6.64 (d, JZ8.2 Hz, 1H), 5.13
(t, JZ6.4 Hz, 1H), 4.05 (d, JZ6.4 Hz, 2H), 3.64 (s, 3H),
2. Experimental
2.1. General
2.37 (s, 3H); IR (KBr): nZ3362, 1599, 1381, 1162 cmK1
;
MS (m/z) 291, 136; HRMS: Calcld for C15H17NO3S:
291.0929, found: 291.0956.
All reactions were performed under a nitrogen atmosphere
using oven-dried glassware. Unless otherwise stated, all
reagents were employed as received. Solvents were distilled
on CaH2 or Na/benzophenon. NMR spectrums were made
2.1.4. 4-Methyl-N-(4-methylbenzyl)benzenesulfonamide
2d. The product was obtained according to the general

F. Gao et al. / Tetrahedron 61 (2005) 12238–12243
12241
procedure, purified by silica gel chromatography (petroleum
ether/acetate ethylZ5:1) and isolated as a white solid in
71% yield. Mp 86.7 8C; 1H NMR (300 MHz, CDCl3, 25 8C,
TMS): dZ7.76 (d, JZ8.23 Hz, 2H), 7.30 (d, JZ8.10 Hz,
2H), 7.08 (s, 4H), 4.69 (t, JZ5.93 Hz, 1H), 4.07 (d, JZ
5.93 Hz, 2H), 2.44 (s, 3H), 2.33 (s, 3H); IR (KBr): nZ3250,
1598, 1378, 1167 cmK1; MS (m/z) 274, 120. Anal. Calcld
for C15H17NO2S: C: 65.45, H: 6.18, N: 5.09, S: 11.64.
Found: C: 65.27, H: 6.17, N: 5.22, S: 11.38.
8.33 Hz, 2H), 7.32–6.99 (m,7H), 5.09 (d, JZ7.29 Hz, 1H),
4.22–4.15 (m, 1H), 2.35 (s, 3H), 1.86–1.64 (m, 2H), 0.78
(t, JZ7.39 Hz, 3H); IR (KBr): nZ3059, 1598, 1368,
1130 cmK1; MS (m/z) 289, 260, 91. Anal. Calcld for
C16H19NO2S: C: 66.40, H: 6.62, N: 4.84, S: 11.08. Found:
C: 66.46, H: 6.64, N: 4.68, S: 11.26.
2.2.2. N-(1-(2-Bromophenyl)propyl)-4-methylbenzene-
sulfonamide 3k. According to the general procedure,
purified by silica gel chromatography(petroleum ether/
acetate ethylZ5:1) and isolated a mixture of 3k in 16%
yield and 2k in 80% yield which were hard to separate. The
pure 3k was obtained by following: Diethylzinc (1.2 mL,
1 M in hexane) and TMEDA were stirred in THF at rt for
1 h. Imine 1k(1 mmol) was added into the reaction mixture.
After 10 h, the reaction was treated with 1 M HCl, 30 mL
ethyl acetate was added, washed with water and brine, dried
over Na2SO4, evaporated in vacuum and purified by silica
gel chromatography(petroleum ether/acetoneZ6:1) to a
white solid 3k in 89% yield. Mp 131.5 8C; 1H NMR
(300 MHz, CDCl3, 25 8C, TMS): dZ7.63–7.61 (m, 2H),
7.36–7.32 (m, 1H), 7.18–6.93 (m, 5H), 5.93 (d, JZ7.8 Hz,
1H), 4.70 (d, JZ7.2 Hz, 1H), 2.32 (s, 3H), 1.76–1.66 (m,
2H), 0.84 (t, JZ7.5 Hz, 3H); IR (KBr): nZ3273, 1438,
1335, 1159 cmK1; MS (m/z) 370, 368, 155. Anal. Calcld
for C16H18BrNO2S: C: 52.18, H: 4.93, N: 3.80. Found: C:
52.29, H: 5.11, N: 3.76.
2.1.5. N-(4-Chlorobenzyl)-4-methylbenzenesulfonamide
2e. The product was obtained according to the general
procedure, purified by silica gel chromatography (petroleum
ether/acetate ethylZ5:1) and isolated as a white solid in
70% yield. Mp 101.6 8C; 1H NMR (300 MHz, CDCl3,
25 8C, TMS): dZ7.71 (d, JZ8.3 Hz, 2H), 7.27 (d, JZ
8.10 Hz, 2H), 7.21 (d, JZ8.5 Hz, 2H), 7.12 (d, JZ8.4 Hz,
2H), 5.17 (t, JZ6.2 Hz, 1H), 4.07 (d, JZ6.4 Hz, 2H),2.43
(s, 3H); IR (KBr): nZ3330, 1597, 1392, 1157 cmK1; MS
(m/z) 296, 140. Anal. Calcld for C14H14ClNO2S: C: 56.85,
H: 4.47, N: 4.74, S: 10.84. Found: C: 56.95, H: 4.61, N:
4.61, S: 11.12.
2.1.6. 4-Methyl-N-(naphthalen-1-ylmethyl)benzenesul-
fonamide 2f. The product was obtained according to the
general procedure, isolated as a white solid in 98% yield.
1
Mp 151.9 8C; H NMR (300 MHz, CDCl3, 25 8C, TMS):
dZ7.81–7.61 (m, 5H), 7.40–7.39 (m, 2H), 7.24–7.17 (m,
4H), 4.61 (t, JZ5.7 Hz, 1H), 4.46 (d, JZ5.7 Hz, 2H), 2.35
(s, 3H); IR (KBr): nZ3330, 1597, 1392, 1157 cmK1; MS
(m/z) 311, 154. Anal. Calcld for C18H17NO2S: C: 69.43, H:
5.50, N: 4.50, S: 10.30. Found: C: 69.38, H: 5.50, N: 4.37, S:
10.35.
2.3. General procedure (for Nitro-Mannich reaction of
Imine 1a–1k in CH3NO2)
Under N2 atmosphere, imine 1 (1 mmol) was dissolved in
5 mL CH3NO2 at rt. Diethylzinc (1.2 mL, 1 M in hexane)
was syringed into the mixture solution. After about 24 h, the
reaction was treated with 1 M HCl, 20 mL ethyl acetate was
added, washed with water and brine, dried over Na2SO4,
evaporated in vacuum and purified by silica gel
chromatography.
2.1.7. N-(2-Bromobenzyl)-4-methylbenzenesulfonamide
2k. The product was obtained according to the general
procedure, purified by silica gel chromatography (petroleum
ether/acetate ethylZ5:1) and isolated as a white solid in
70% yield. Mp 73.5 8C; 1H NMR (300 MHz, CDCl3, 25 8C,
TMS): dZ7.71 (d, JZ8.1 Hz, 2H), 7.46 (d, JZ7.8 Hz, 1H),
7.32–7.08 (m, 6H), 4.97 (t, JZ6.3 Hz, 1H), 4.23 (d, JZ
6.3 Hz, 2H), 2.41 (s, 3H); IR (KBr): nZ3258, 1597,
1438,1392, 1155 cmK1; MS (m/z) 342, 340, 260, 184.
Anal. Calcld for C14H14BrNO2S: C: 49.42, H: 4.15, N: 4.12.
Found: C: 49.32, H: 4.07, N: 3.96.
2.3.1. 4-Methyl-N-(2-nitro-1-phenylethyl)benzenesul-
fonamide 4a. The product was obtained according to the
general procedure, purified by silica gel chromatography
(petroleum ether/acetoneZ4:1) and isolated as a white solid
in 70% yield. Mp 155–157 8C; 1H NMR (300 MHz, CDCl3,
25 8C, TMS): dZ7.65 (d, JZ8.3 Hz, 2H), 7.27–7.24 (m,
5H), 7.10 (d, JZ8.3 Hz, 2H), 5.50 (d, JZ7.57 Hz, 1H),
5.03–4.96 (m, 1H), 4.84 (d-d, JZ13.08, 6.64 Hz, 1H), 4.66
(d-d, JZ13.07, 6.34 Hz, 1H), 2.40 (s, 3H); IR (KBr): nZ
3426, 1550, 1380, 1167 cmK1; MS (m/z) 274, 260, 91. Anal.
Calcld for C15H16N2O4S: C: 56.24, H: 5.03, N: 8.74, S:
10.00. Found: C: 56.50, H: 4.95, N: 8.82, S: 10.15.
2.2. General procedure (for reaction between diethylzinc
and N-tosyl imine 1a and 1k in THF)
Under N2 atmosphere, imine 1a (1 mmol) was dissolved in
5 mL THF at rt. Diethylzinc (1.2 mL, 1 M in hexane) was
syringed into the mixture. After about 6 h, the reaction was
treated with 1 M HCl, 30 mL ethyl acetate was added,
washed with water and brine, dried over Na2SO4,
evaporated in vacuum and purified by silica gel
chromatography.
2.3.2. N-(1-(4-Methoxyphenyl)-2-nitroethyl)-4-methyl-
benzenesulfonamide 4b. The product was obtained
according to the general procedure, purified by silica gel
chromatography (petroleum ether/acetoneZ4:1) and iso-
lated as a white solid in 86% yield. Mp 142.4 8C; 1H NMR
(300 MHz, CDCl3, 25 8C, TMS): dZ7.64 (d, JZ8.2 Hz,
2H), 7.24 (d, JZ8.0 Hz, 2H), 7.00 (d, JZ8.62 Hz, 2H), 6.76
(d, JZ8.62 Hz, 2H), 5.43 (d, JZ6.92 Hz, 1H), 4.93–4.89
(m, 1H), 4.83 (d-d, JZ12.83, 6.67 Hz, 1H), 4.64 (d-d, JZ
12.71, 6.57 Hz, 1H), 3.76 (s, 3H), 2.41 (s, 3H); IR (KBr):
nZ3255, 1615, 1380, 1163 cmK1; MS (m/z) 350, 91. Anal.
2.2.1. 4-Methyl-N-(1-phenylpropyl)benzenesulfonamide
3a. The product was obtained according to the general
procedure, purified by silica gel chromatography(petroleum
ether/acetate ethylZ5:1) and isolated as a white solid 3a
in 40% yield along with 2a in 27% yield. Mp 109–110 8C;
1H NMR (300 MHz, CDCl3, 25 8C, TMS): dZ7.54 (d, JZ

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F. Gao et al. / Tetrahedron 61 (2005) 12238–12243
Calcld for C16H18N2O5S: C: 54.85, H: 5.18, N: 7.99, S:
9.15. Found: C: 54.88, H: 5.31, N: 7.89, S: 9.29.
7.61 (d, JZ7.8 Hz, 2H), 7.44 (d, JZ7.8 Hz, 1H), 7.26–7.06
(m, 5H), 6.21 (d, JZ8.7 Hz, 1H), 5.52–5.45 (m, 1H),
4.78–4.64 (m, 2H), 2.35 (s, 3H); IR (KBr): nZ3244, 1554,
1341, 1158 cmK1; MS (m/z) 340, 338, 319, 91. Anal. Calcld
for C15H15BrN2O4S: C: 45.12 H: 3.79, N: 7.02. Found: C:
45.01, H: 3.95, N: 7.04.
2.3.3. N-(1-(2-Methoxyphenyl)-2-nitroethyl)-4-methyl-
benzenesulfonamide 4c. The product was obtained
according to the general procedure, purified by silica gel
chromatography (petroleum ether/acetoneZ4:1) and iso-
lated as a white solid in 59% yield. Mp 142.4 8C; 1H NMR
(400 MHz, CDCl3, 25 8C, TMS): dZ7.56 (d, JZ8.3 Hz,
2H), 7.21–7.16 (m, 1H), 7.10 (d, JZ8.0 Hz, 2H), 6.95–6.93
(m, 1H), 6.78–6.72 (m, 2H), 6.00 (br s, 1H), 5.1 (br s, 1H),
4.81 (d-d, JZ12.60, 7.5 Hz, 1H), 4.64 (d-d, JZ12.60,
6.70 Hz, 1H), 3.80 (s, 3H), 2.33 (s, 3H); IR (KBr): nZ3289,
1601, 1368, 1159 cmK1; MS (m/z) 354, 91. Anal. Calcld for
C16H18N2O5S: C: 54.85, H: 5.18, N: 7.99, S: 9.15. Found:
C: 54.99, H: 5.02, N: 8.12, S: 9.44.
2.4. General procedure (for nitro-Mannich reaction of
Imine 1f in THF)
Under N2 atmosphere, imine 1a (1 mmol) was dissolved in
5 mL THF and 5 equiv CH3NO2 at rt for 10 min.
Diethylzinc (1.2 mL, 1 M in hexane) was syringed into the
solution. After about 12 h, the reaction mixture was treated
with 1 M HCl, 30 mL of ethyl acetate was added, washed
with water and brine, dried over Na2SO4, evaporated in
vacuum and purified by silica gel chromatography
(petroleum ether/acetoneZ4:1) and 4f was isolated as a
white solid 4f in 51% yield.
2.3.4. 4-Methyl-N-(2-nitro-1-p-tolylethyl)benzenesulfo-
namide 4d. The product was obtained according to the
general procedure, purified by silica gel chromatography
(petroleum ether/acetoneZ4:1) and isolated as a white solid
Procedure (for the ethylating reaction of imine 1a with
TMEDA (Scheme 4)). Diethylzinc (1.2 mL, 1 M in hexane)
and TMEDA were stirred in THF at rt for 1 h. Imine 1a
(1 mmol) was added. After 10 h, the reaction was treated
with 1 M HCl, 30 mL of ethyl acetate was added, washed
with water and brine, dried over Na2SO4, evaporated in
vacuum and purified by silica gel chromatography(petro-
leum ether/acetate ethylZ5:1) to give 3a as a white solid in
69% yield.
1
in 79% yield. Mp 192.5 8C; H NMR (300 MHz, CDCl3,
25 8C, TMS): dZ7.67 (d, JZ8.2 Hz, 2H), 7.26 (d, JZ
8.0 Hz, 2H), 7.01 (d, JZ7.9 Hz, 2H), 6.98 (d, JZ6.9 Hz,
2H), 5.24 (d, JZ7.1 Hz, 1H), 4.92 (q, JZ6.7 Hz, 1H), 4.84
(d-d, JZ13.0, 6.4 Hz, 1H), 4.67 (d-d, JZ12.9, 6.7 Hz, 1H),
2.41 (s, 3H), 2.39 (s, 3H); IR (KBr): nZ3248, 1552, 1378,
1167 cmK1; MS (m/z) 335, 91. Anal. Calcld for
C16H18N2O4S: C: 57.47, H: 5.43, N: 8.38, S: 9.59. Found:
C: 57.49, H: 5.50, N: 8.33, S: 9.36.
Procedure (for the ethylating reaction of Imine 1a with (S)-
1,20-methylenedipyrrolidine (Scheme 4)). Diethylzinc
(1.2 mL, 1 M in hexane) and (S)-1,20-methylenedipyrroli-
dine were stirred in toluene at K78 8C for 1 h. Imine 1a
(1 mmol) was added. After 10 h, the reaction was treated
with 1 M HCl, 30 mL of ethyl acetate was added, washed
with water and brine, dried over Na2SO4, evaporated in
vacuum and purified by silica gel chromatography
(petroleum ether/acetate ethylZ5:1) to afford an optical
3a in 98% yield and 77% ee (determined by HPLC analysis
2.3.5. N-(1-(4-Chlorophenyl)-2-nitroethyl)-4-methyl-
benzenesulfonamide 4e. The product was obtained
according to the general procedure, purified by silica gel
chromatography (petroleum ether/acetoneZ4:1) and iso-
lated as a white solid in 75% yield. Mp 193.8 8C; 1H NMR
(400 MHz, CDCl3, 25 8C, TMS): dZ7.41 (d, JZ8.1 Hz,
2H), 7.16–7.08 (m, 6H), 5.04–4.99 (m, 1H), 4.68 (d, JZ
7.5 Hz, 2H), 2.34 (s, 3H); IR (KBr): nZ3242, 1599, 1380,
1168 cmK1; MS (m/z) 355, 91. Anal. Calcld for C15H15-
ClN2O4S: C: 50.85, H: 4.26, N: 7.90, S: 9.04. Found: C:
51.04, H: 4.12, N: 7.97, S: 9.33.
i
on a chiralcel OD column with PrOH/hexaneZ20/80 as
the eluent).
2.3.6. 4-Methyl-N-(1-(naphthalen-1-yl)-2-nitroethyl)ben-
zenesulfonamide 4f. The product was obtained according
to the general procedure, purified by silica gel chromato-
graphy (petroleum ether/acetoneZ4:1) and isolated as a
white solid in 50% yield along with 2f in 47% yield. Mp
Acknowledgements
Financial supports from the National Natural Sciences
Foundation of China and the State Key Project of Basic
Research (Project 973, No. G2000048007) are gratefully
acknowledged.
1
164.6 8C; H NMR (300 MHz, CDCl3, 25 8C, TMS): dZ
7.84–7.74 (m, 3H), 7.57–7.26 (m, 6H), 7.08 (d, JZ7.99 Hz,
2H), 5.88–5.86 (m, 1H), 5.74 (d, JZ7.28 Hz, 1H), 4.99 (d-d,
JZ13.14, 7.35 Hz, 1H), 4.64 (d-d, JZ13.14, 5.94 Hz, 1H),
2.33 (s, 3H); IR (KBr): nZ3359, 1597, 1402, 1157 cmK1
;
MS (m/z) 350, 154. Anal. Calcld for C19H18N2O4S: C: 61.61
H: 4.90, N: 7.56, S: 8.65. Found: C: 61.62, H: 4.92, N: 7.47,
S: 8.75.
References and notes
1. For recent reviews on imine reductions, see (a) Kobayashi, S.;
Ishtani, H. Chem. Rev. 1999, 99, 1069–1094. (b) Hutchins, R. O.;
Hutchins, M. K. In Trost, B. M., Fleming, I., Eds.;
Comprehensive Organic Synthesis; Pergamon Press: New
York, 1991; Vol. 8, pp 251–254.
2.3.7. N-(1-(2-Bromophenyl)-2-nitroethyl)-4-methylben-
zenesulfonamide 4k. The product was obtained according
to the general procedure, purified by silica gel chromato-
graphy (petroleum ether/acetoneZ4:1) and isolated as a
white solid in 58% yield along with 2k in 15% yield. Mp
2. (a) Blackwell, J. M.; Sonmor, E. R.; Scoccitti, T.; Piers, W. E.
Org. Lett.2000, 2, 3921–3923. (b)Aida,T.;Kuboki,N.;Kato, K.;
1
137.7 8C; H NMR (300 MHz, CDCl3, 25 8C, TMS): dZ

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