The practical synthesis of double axial chiral guanidines

Article abstract of DOI:10.2174/157017809787893028

Two novel double axial chiral guanidines were designed according to the concept of double axial chirality. The practical synthetic procedures from (S)-1, 1'-binaphthol have been developed. The title compounds were fully characterized by NMR, MS, IR and el

Full text of DOI:10.2174/157017809787893028

Letters in Organic Chemistry, 2009, 6, 197-202
197
The Practical Synthesis of Double Axial Chiral Guanidines
Qun-Sheng Guoa and Da-Ming Du*a,b
aBeijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecu-
lar Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China
bSchool of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, P. R. China
Received September 20, 2008: Revised December 29, 2008: Accepted December 31, 2008
Abstract: Two novel double axial chiral guanidines were designed according to the concept of double axial chirality. The
practical synthetic procedures from (S)-1,1’-binaphthol have been developed. The title compounds were fully character-
ized by NMR, MS, IR and elemental analysis or HRMS. The two chiral guanidines can be interesting catalysts for asym-
metric catalysis and preliminary asymmetric catalytic activity was investigated in Henry reaction and conjugate addition.
Keywords: Guanidine, chiral catalyst, organic base, synthesis.
As strong organic base catalysts, chiral guanidines have
been used for many enantioselective transformations such as
epoxidation [1], Michael addition reaction [2], silylation of
secondary alcohols [3], Strecker reaction [4], Henry reaction
[5] and Diels-Alder reaction [6]. Recently, highly efficient
axial chiral guanidine catalysts were reported by Terada and
co-workers [7]. The development of new chiral guanidines
with novel backbones and the expansion of their application
lysis. We assumed that if the substitutents at 3,3’-positions
of BINOL possess a stable double axial chirality, better per-
formance in organocatalysis may be achieved [8]. The target
guanidines (S,S)-1 and (S,S)-2 have a larger chiral pocket
than the former developed chiral guanidine catalysts [7].
The practical synthetic routes to chiral guanidines (S,S)-1
and (S,S)-2 were outlined in Scheme 1 and Scheme 2, re-
spectively. (S,S)-2,2’’’-dicyclohexyloxy-1,1’:3’,3’’:1’’,1’’’-
O
O
H
N
CH3
NH
N
N
NH2
N
H
O
O
(S,S)-1
(S,S)-2
Fig. (1). New double axially chiral guanidines.
to other useful asymmetric organic transformations are still a
great challenge for chemists. In this paper, the design, and
synthesis of novel double axially chiral guanidines (S,S)-1
and (S,S)-2 (Fig. 1) were reported.
quaternaphthalene-2’,2’’-diol (S,S)-3, prepared from (S)-
BINOL according to our previous procedure [8], reacted
with Tf2O in CH2Cl2 to afford its ditriflate, which was not
purified and directly reacted with MeMgBr in Et2O by the
catalysis of (Et3P)2NiCl2 to provide (S,S)-2,2’’’-dicyclo-
hexyloxy-2’,2’’-dimethyl-1,1’:3’,3’’:1’’,1’’’-quaternaphtha-
lene (S,S)-4 in 87% yield for two steps. We also attempted
NiCl2(dppp) or NiCl2(PPh3)2 as catalyst in this reaction, but
none of the desired coupled product was obtained. (S,S)-
The rationale for our design of novel chiral guanidine
catalysts originated from the observation that the substi-
tutents at 3,3’-positions of BINOL are very important in con-
trolling the enantioselectivity in asymmetric organocata-
2’,2’’-dibromomethyl-2,2’’’-
dicyclohexyloxy-1,1’:3’,3’’:
*Address correspondence to this author at the School of Chemical Engineer-
ing and Environment, Beijing Institute of Technology, Beijing 100081, P. R.
China; Fax: 86-10-68914985; E-mail: dudm@bit.edu.cn
1’’,1’’’-quaternaphthalene (S,S)-5 was then prepared in 78%
yield by bromination of (S,S)-4 with N-bromosuccinimide
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

198 Letters in Organic Chemistry, 2009, Vol. 6, No. 3
Guo and Du
O
O
O
0.1 eq (Et3P)2NiCl2
4 eq MeMgBr
2.2 eq Tf2O,
4.4 eq pyridine
CH3
CH3
OTf
OTf
OH
OH
ether, 0 ˚C-rt
87%
CH2Cl2, 0 ˚C-rt
O
O
O
(S,S)-4
(S,S)-3
O
O
2.3 eq NBS
4 eq guanidine
0.1 eq AIBN
NH
NH2
Br
Br
N
THF-EtOH(1:1), reflux
85%
benzene,reflux
78%
O
O
(S,S)-1
(S,S)-5
Scheme 1. The synthesis of double axial chiral guanidine (S,S)-1.
(NBS) in benzene. Finally, the compound (S,S)-5 reacted
with free guanidine in THF-EtOH to afford the new double
axially chiral guanidine catalyst (S,S)-1 in 85% yield.
But the enantioselectivity is low, only 7% ee was obtained
with guanidine 2 as catalyst. No improvement in results was
obtained during the optimization of reaction conditions such
as with lower temperature and change solvents.
Compound (S,S)-5 reacted with NaN3 in DMF to afford
(S,S)-2’,2’’-diazidomethyl-2,2’’’-dicyclohexyloxy-1,1’:3’,3’’:
1’’,1’’’-quaternaphthalene, which was treated with LiAlH4 in
THF to produce (S,S)-2’,2’’-diaminomethyl-2,2’’’-dicyclo-
hexyloxy-1,1’:3’,3’’:1’’,1’’’-quaternaphthalene (S,S)-6 in
70% yield for two steps. (S,S)-6 reacted with CSCl2 in the
presence of diisopropylethylamine in CH2Cl2 to afford (S,S)-
2,2’’’-dicyclohexyloxy-2’,2’’-diisothiocyanatomethyl- 1,1’:
3’,3’’:1’’,1’’’-quaternaphthalene, which was treated with
H2O in pyridine at 80 °C to give the thiourea (S,S)-7 in 81%
yield [7a]. A CuI-catalyzed cross-coupling reaction of (S,S)-
7 with MeNH3Cl in the presence of K2CO3 provided chiral
guanidine (S,S)-2 in 75% yield.
The asymmetric conjugate addition of naphthoquinone to
nitroalkenes is another important reaction because it pro-
duces chiral nitroalkylated compounds, which are precursors
of a variety of other functionalized bioactive compounds
[10]. We then investigated the addition reaction of 2-
hydroxynaphthoquinone to nitrostyrene catalyzed by 10 mol
% of new guanidines 1 or 2 in toluene at room temperature.
The guanidines can catalyze the conjugate addition reaction
efficiently and the corresponding product was obtained in
98% and 97% yield, respectively. But the enantioselectivity
is low, only 10% ee was obtained with guanidine 2 as
catalyst under optimized conditions. Currently, we do not
know why the results obtained with each of the two catalysts
so different.
With these new guanidines in hand, the asymmetric cata-
lytic activity in a series of organic reactions was investi-
gated. We initially studied the Henry reaction [9] of p-
bromobenzaldehyde with nitromethane by the catalysis of 10
mol % of new guanidines 1 or 2 in toluene at room
temperature. These guanidines can catalyze the Henry
reaction efficiently and the corresponding Henry reaction
product was obtained in 100% and 97% yield, respectively.
In summary, a practical method for the preparation of
sterically hindered double axially chiral guanidines (S,S)-1
and (S,S)-2 has been developed. In the first step,
(Et3P)2NiCl2 was first used by us to catalyze the cross-
coupling reaction between the ditriflate of (S,S)-3 and
MeMgBr. Guanidines (S,S)-1 and (S,S)-2 have a larger chiral

Double Axial Chiral Guanidines
Letters in Organic Chemistry, 2009, Vol. 6, No. 3
199
O
N3
N3
O
O
3 eq NaN3
NH2
NH2
O
Br
Br
O
3 eq LiAlH4
DMF, 80 ˚C
THF, 0 ˚C-rt
70%
O
(S,S)-6
(S,S)-5
(i) 5 eq DIPEA,
2.1 eq CSCl2,
O
O
O
O
(i) 3 eq MeI
acetone, rt
CH2Cl2, -78 ˚C-rt
H
N
H
CH3
N
S
N
N
H
N
H
(ii) 1 eq CuI
(ii) pyridine, H2O, 80 ˚C
81%
15 eq K2CO3
10 eq MeNH3Cl
THF, reflux
75%
(S,S)-7
(S,S)-2
Scheme 2. The synthesis of double axial chiral guanidine (S,S)-2.
OH
ꢀ
CHO
NO2
10 mol% cat.
toluene
CH3NO2
+
Br
Br
cat. 1: >99% yield, 0% ee
2: 97% yield, 7% ee
Scheme 3. Asymmetric Henry reaction.
O
O
O
O
*
NO2
NO2
10 mol% cat.
toluene
+
OH
OH
cat. 1: 98% yield, 0% ee
2: 97% yield, 10% ee
Scheme 4. Asymmetric conjugate addition.

200 Letters in Organic Chemistry, 2009, Vol. 6, No. 3
Guo and Du
1591, 1508, 1466, 1328, 1264, 1235, 1146, 809, 747 cm-1. 1H
NMR (200 MHz, CDCl3): ꢁ = 0.82-1.65 (m, 20H), 1.92 (s,
6H), 4.08-4.25 (m, 2H), 7.13-7.43 (m, 14H), 7.81-7.95 (m,
8H). 13C NMR (50 MHz, CDCl3): ꢁ 17.7, 22.8, 23.0, 25.2,
31.6, 32.0, 75.9, 117.2, 123.7, 124.3, 125.0, 125.39, 125.45,
126.2, 126.4, 127.6, 127.7, 127.9, 128.9, 129.2, 132.0, 132.7,
133.3, 134.0, 134.6, 141.3, 153.0. HRMS (ESI): m/z calcd
for C54H51O2 ([M+H]+) 731.3889. Found 731.3884. Anal.
calcd for C54H50O2: C, 88.73; H, 6.89; found: C, 88.63; H,
7.44.
pocket than the formerly developed chiral guanidine cata-
lysts, and have potential as good organocatalysts. The pre-
liminary results in asymmetric reaction demonstrate their
high catalytic reactivity as strong brønsted base although
with low enantioselectivity. We are currently seeking to in-
vestigate the application of the two chiral guanidines in other
asymmetric catalysis in our group.
EXPERIMENTAL
All air- and moisture-sensitive manipulations were car-
ried out with standard Schlenk techniques under nitrogen or
under argon. Unless otherwise indicated, all commercially
available compounds were used without further purification.
THF was either distilled over benzophenone ketyl under ni-
trogen or purified by passing through a neutral alumina col-
umn under nitrogen. Et2O was purified by passing through a
neutral alumina column under nitrogen. CH2Cl2 was distilled
over CaH2 under nitrogen. DMF was distilled over CaH2
under vacuum. Melting points were measured on an XT-4
melting point apparatus and uncorrected. The 1H NMR spec-
tra were recorded on Varian Mercury Plus (200 MHz). 13C
NMR spectra were recorded on Varian Mercury Plus spec-
trometer (50 MHz). Infrared spectra were obtained on a
Nicolet AVATAR 330 FT-IR spectrometer. Mass spectra
were obtained on a VGZAB-HS mass spectrometer, a
Thermo Finnigan LCQ Decaxp PLUS LC/MS spectrometer
(ESI) and a Bruker Apex IV FTMS spectrometer. Elemental
analyses were carried out on an Elementar VARIO EL in-
strument. Optical rotations were measured on a Perkin-Elmer
341 LC spectrometer.
Synthesis of (S,S)- 2’,2’’-dibromomethyl-2,2’’’-dicyclohe-
xyloxy-1,1’:3’,3’’:1’’,1’’’- quaternaphthalene [(S,S)-5]
To a solution of (S,S)-2’,2’’-dimethyl-2,2’’’-dicyclohexy-
loxy-1,1’:3’,3’’:1’’,1’’’- quaternaphthalene (2.19 g, 3.0
mmol) in benzene (20 mL) was added N-bromosuccinimide
(NBS) (1.26 g, 7.0 mmol) and 2,2’-azobis(isobutyronitrile)
(AIBN) (0.05 g, 0.3 mmol). The mixture was heated and
refluxed for 8 h. After being cooled to room temperature, the
mixture was washed with water (20 mL) and dried over
Na2SO4 and concentrated. The residue was purified by col-
umn chromatography with PE(60-90 °C)-AcOEt-DCM
(10:1:2) as eluent to give the product (S,S)-5 (2.1 g, 78%
25
yield) as colorless solid. m.p. 135 °C (decomp.). [ꢀ]D = -
123.1 (c 1.0, CHCl3). IR (FT-IR, film): 3056, 2933, 2856,
1621, 1590, 1507, 1465, 1330, 1264, 1236, 1146, 810, 736
cm-1. 1H NMR (200 MHz, CDCl3): ꢁ 0.80-1.79 (m, 20H),
4.20 (d, J = 6.4 Hz, 2H), 4.21 (br, 2H), 4.37 (d, J = 6.4 Hz,
2H), 7.05-7.50 (m, 14H), 7.86 -8.03 (m, 6H), 8.18 (s, 2H).
13C NMR (50 MHz, CDCl3): ꢁ 23.1, 23.5, 25.2, 31.3, 31.6,
32.3, 76.4, 116.4, 122.0, 123.8, 126.1, 126.2, 126.5, 126.8,
127.6, 128.1, 129.0, 129.8, 130.3, 132.8, 133.0, 133.3, 134.1,
135.7, 137.7, 152.6. HRMS (ESI): m/z calcd for C54H48Br2O2
([M]+) 886.2021. found 886.2016. Anal. calcd for
C54H48Br2O2: C, 72.98; H, 5.44; found: C, 72.57; H, 6.08.
Synthesis of (S,S)-2,2’’’-Dicyclohexyloxy-2’,2’’-dimethyl-
1,1’:3’,3’’:1’’,1’’’- quaternaphthalene [(S,S)-4]
To a solution of (S,S)-2,2’’’-dicyclohexyloxy-1,1’:3’,3’’:
1’’,1’’’- quarternaphthalene-2’,2’’-diol (10.29 g, 14 mmol)
and pyridine (5.0 mL, 62 mmol) in CH2Cl2 (100 mL) was
added Tf2O (5.87 mL, 31.3 mmol) dropwise at 0 °C. The
solution was allowed to warm to room temperature and
stirred overnight. Evaporation of the solvents and the residue
was redissolved in AcOEt (150 mL) and washed with 1 N
HCl (50 mL), saturated NaHCO3 solution (50 mL) and satu-
rated brine (30 mL). The organic phase were dried over
Na2SO4 and concentrated to give the crude bis-
trifluoromethanesulfonic acid ester, which was directly used
for the following reaction without any further purification.
Synthesis of Chiral Guanidine [(S,S)-1]
To
a solution of (S,S)-2’,2’’-dibromomethyl-2,2’’’-
dicyclohexyloxy-1,1’:3’,3’’:1’’,1’’’- quaternaphthalene (600
mg, 0.67 mmol) in THF-EtOH(1:1) (20 mL) was added free
guanidine (159 mg, 2.7 mmol). The mixture was refluxed for
10 h and cooled to room temperature. The reaction was
quenched by 1 N HCl (30 mL) and extracted with CH2Cl2
(50 mL), The extracts were washed with 2N KOH solution
(30 mL), saturated brine (20 mL) and dried over anhydrous
Na2SO4. Evaporation of solvents gave the chiral guanidine
product (S,S)-1 (450 mg, 85% yield) as pale yellow solid.
To a solution of the crude bis-trifluoromethanesulfonic
acid ester and (Et3P)2NiCl2 (0.512 g, 1.4 mmol) in Et2O (200
mL) was slowly added MeMgBr (3.0 M in Et2O, 19 mL, 57
mmol) at 0 °C. The solution was allowed to warm to room
temperature and stirred for 100 h. The reaction was
quenched by 2 N HCl (30 mL), the whole mixture was fil-
tered to remove the catalyst. The filtrate was extracted with
AcOEt (2 ꢀ 100 mL). The organic extracts were washed with
saturated brine (100 mL) and dried over Na2SO4. Evapora-
tion of solvents and purification of the residue by column
chromatography on silica gel with PE(60-90 °C)-AcOEt-
DCM (50:1:4) as eluent to afford the product (S,S)-4 (8.9 g,
87% yield) as colorless solid. m.p.123-126 °C. [ꢀ]D25 = -85.9
(c 1.0, CHCl3). IR (FT-IR, film): 3055, 2932, 2857, 1620,
25
m.p. 231-235 °C (decomp.). [ꢀ]D = -79.6 (c 1.0, CHCl3).
IR (FT-IR, film): 3056, 2931, 2855, 2357, 1621, 1591, 1466,
1446, 1330, 1264, 1236, 810, 735 cm-1. 1H NMR (200 MHz,
DMSO): ꢁ 0.87-1.73 (m, 20H), 3.58-3.85 (m, 2H), 4.22 (br,
2H), 4.36 (br, 2H), 6.12 (br, 2H), 6.76-7.69 (m, 14H), 7.96-
8.33 (m, 6H), 8.50 (s, 2H). 13C NMR (50 MHz, DMSO): ꢁ
28.8, 30.7, 31.1, 32.6, 33.7, 34.5, 74.7, 111.4, 114.3, 116.2,
120.6, 126.2, 127.0, 127.8, 128.7, 129.3, 129.9, 130.9, 131.6,
133.0, 135.5, 138.2, 142.1, 143.4, 144.8, 151.1, 155.7.
HRMS (ESI): m/z calcd for C55H52N3O2 ([M+H]+) 786.4060;
found 786.4054.

Double Axial Chiral Guanidines
Letters in Organic Chemistry, 2009, Vol. 6, No. 3
201
Synthesis of (S,S)-2’,2’’-diaminomethyl-2,2’’’-dicyclohe-
xyloxy-1,1’:3’,3’’:1’’,1’’’- quaternaphthalene [(S,S)-6]
126.6, 127.2, 127.9, 128.4, 128.8, 129.6, 130.6, 132.8, 133.0,
133.3, 134.0, 136.0, 138.6, 154.2. HRMS (ESI): m/z calcd
for C55H51N2O2S ([M+H]+) 803.3671; found 803.3666. Anal.
calcd for C55H50N2O2S ꢃH2O: C, 80.46; H, 6.38; N, 3.41;
found: C, 80.84; H, 6.46; N, 3.43.
A
mixture
of
(S,S)-2’,2’’-dibromomethyl-2,2’’’-
dicyclohexyloxy-1,1’:3’,3’’:1’’,1’’’- quaternaphthalene (620
mg, 0.7 mmol) and NaN3 (135 mg, 2.1 mmol) in DMF (15
mL) was stirred at 80 °C for 10 h. The reaction mixture was
cooled to room temperature and diluted with water (30 mL)
and extracted with AcOEt (60 mL). The organic extracts
were dried over anhydrous Na2SO4 and concentrated. The
crude diazide obtained was used for subsequent reaction
without further purification.
Synthesis of Chiral Guanidine [(S,S)-2]
To a solution of thiourea (241 mg, 0.3 mmol) in acetone
(10 mL) was added MeI (38 ꢀL, 0.9 mmol) and the solution
was stirred for 2 h at room temperature. After removal of
solvents, crude isothiourea was obtained. To a solution of
crude isothiourea in THF (15 mL) was added CuI (58 mg,
0.3 mmol), K2CO3 (620 mg, 4.5 mmol) and MeNH3Cl (203
mg, 3 mmol). The reaction mixture was refluxed for 20 h.
After cooling to room temperature, the reaction was
quenched by 1N HCl (30 mL) and extracted with AcOEt (2
ꢁ 20 mL). The extracts were dried over anhydrous Na2SO4
and concentrated. The residue was purified by column chro-
matography with PE(60-90 °C) -AcOEt (4:1) as eluent to
give guanidinium salt. The obtained guanidinium salt was
redissolved in CH2Cl2 (30 mL) and neutralized by 2N KOH
(20 mL). The organic phase was separated and dried over
anhydrous Na2SO4. Evaporation of solvents gave guanidine
(S,S)-2 (180 mg, 75% yield) as colorless solid. m.p.212 °C
(decomp.). [ꢁ]D25 = -135.5 (c 1.0, CHCl3).
1H NMR (200 MHz, CDCl3): ꢂ 0.87-1.76 (m, 20H), 2.35
(s, 3H), 3.62-3.87 (m, 4H), 4.03-4.51 (m, 4H), 7.11-7.61 (m,
14H), 7.85-8.14 (m, 8H). 13C NMR (50 MHz, CDCl3): ꢂ
22.8, 23.2, 25.3, 25.9, 31.6, 32.2, 76.4, 115.3, 119.5, 120.5,
126.1, 126.7, 128.0, 129.2, 130.1, 130.5, 132.4, 133.2, 134.2,
134.8, 136.0, 139.1, 139.9, 141.1, 146.5, 149.8, 155.6. IR
(FT-IR, film): 2933, 2857, 1641, 1591, 1507, 1466, 1332,
1264, 1235, 1147, 809, 735 cm-1. MS (EI): m/z = 799 (M+,
3), 768 (5), 728 (6), 562 (20). HRMS (ESI): m/z calcd for
C56H54N3O2 ([M+H]+) 800.4216; found 800.4211.
To a suspension of LiAlH4 (80 mg, 2.1 mmol) in THF (20
mL) was added the solution of the above crude diazide in
THF (20 mL) at 0 °C. The reaction mixture was gradually
warmed to room temperature and stirred for 14 h. The reac-
tion was quenched with water (2 mL) and Na2SO4 (10 g) was
added. The mixture was filtered through a pad of Celite and
the filtrate was concentrated. Evaporation of solvents gave
the diamine product (S,S)- 2’,2’’-diaminomethyl-2,2’’’-
dicyclohexyloxy-1,1’:3’,3’’:1’’,1’’’-quaternaphthalene (S,S)-
25
6 (370 mg, 70% yield) as yellow oil. [ꢁ]D = ꢀ132.6 (c 1.0,
CHCl3). IR (FT-IR, film): 3058, 2932, 2856, 1620, 1591,
1508, 1465, 1330, 1264, 1235, 1146, 809, 749 cm-1. 1H
NMR (200 MHz, CDCl3): ꢂ 0.78–1.78 (m, 20H), 2.79 (s,
1H), 2.84 (s, 1H), 3.27–3.59 (m, 4H), 4.12-4.29 (m, 2H),
6.97–7.40 (m, 14H), 7.72–7.94 (m, 8H). 13C NMR (50 MHz,
CDCl3): ꢂ 23.1, 23.4, 25.1, 29.6, 31.5, 32.3, 76.4, 122.9,
123.9, 125.2, 125.9, 126.7, 126.9, 127.8, 128.1, 129.2, 129.5,
132.3, 132.4, 132.9, 133.1, 133.5, 134.5, 139.0, 139.1, 139.7,
153.0. HRMS (ESI): m/z calcd for C54H53N2O2 ([M+H]+)
761.4107; found 761.4102. Anal. Calcd for C54H52N2O2
ꢃ1.5H2O: C, 82.31; H, 7.03; N, 3.55; found: C, 82.10; H,
7.05; N, 3.46.
Synthesis of Chiral Thiourea [(S,S)-7]
To
a solution of (S,S)-2’,2’’-diaminemethyl-2,2’’’-
dicyclohexyloxy-1,1’:3’,3’’:1’’,1’’’- quaternaphthalene (457
mg, 0.6 mmol) and diisopropylethylamine (522 ꢀL, 3 mmol)
in CH2Cl2 (20 mL) was added thiophosgene (CSCl2) (87 ꢀL,
1.25 mmol) in CH2Cl2 (10 mL) at -78 °C. The mixture was
allowed to warm to room temperature and stirred for 8 h.
The reaction was quenched by 1N NaHSO4 solution (30 mL)
and extracted with CH2Cl2 (2 ꢁ 20 mL). The organic layer
was dried over anhydrous Na2SO4 and concentrated. The
crude diisothiocyanate obtained was used for subsequent
reaction without further purification.
General Procedure for the Henry Reaction
To a glass vial with magnetic stir bar was added p-
bromobenzaldehyde (18.5 mg), chiral gunidine 2 (8 mg, 10
mol%), and THF (3 mL). To this solution was added MeNO2
(61 mg) and the reaction mixture was stirred for 72 h at room
temperature. The solvent was evaporated in vacuo, and the
residue was purified by silica gel column chromatography
with petroleum ether-ethyl acetate (5:1) as eluent to provide
77 mg product (97% yield). The enantiomeric excess was
analyzed by chiral HPLC.
To a solution of the crude diisothiocyanate in pyridine
(20 mL) was added water (3 mL) and stirred for 20 h at
80 °C. After removel of solvents, the residue was purified by
column chromatorgraphy with PE (60-90 °C)-AcOEt (4:1) as
eluent to afford the thiourea product (390 mg, 81% yield) as
General Procedure for the Conjugate Addition to Ni-
trostyrene
To a glass vial with magnetic stir bar was added 2-
hydroxy-1,4-naphthoquinone (17.4 mg, 0.1 mmol), nitro-
styrene (14.9 mg, 0.1 mmol), guanidine 2 (8 mg, 10 mol%),
and toluene (3 mL). After being stirred at room temperature
for 48 h, the solvent was evaporated in vacuo, and the resi-
due was purified by silica gel column chromatography with
petroleum ether-ethyl acetate (2:1) as eluent. The nitroalky-
lated naphthoquinone was afforded, and the enantiomeric
excess was analyzed by chiral HPLC.
25
pale yellow solid. m.p. 159-163 °C. [ꢁ]D = -96.5 (c 1.0,
CHCl3). IR (FT-IR, film): 3051, 2933, 2856, 1620, 1590,
1523, 1508, 1339, 1247, 1237, 1146, 827, 734 cm-1. 1H
NMR (200 MHz, CDCl3): ꢂ 0.79-1.71 (m, 20H), 3.82 (dd, J
= 15.6, 7.8 Hz, 2H), 4.33-4.45 (m, 4H), 5.49 (t, J = 7.2 Hz,
2H), 6.98 (d, J = 8.2 Hz, 2H), 7.19-7.55 (m, 12H), 7.88 (d, J
= 7.8 Hz, 2H), 8.00 (d, J = 8.2 Hz, 4H), 8.17 (s, 2H). 13C
NMR (50 MHz, CDCl3): ꢂ 22.9, 23.1, 25.2, 31.5, 32.3, 47.3,
74.9, 114.3, 116.0, 120.2, 123.62, 123.64, 126.2, 126.3,

202 Letters in Organic Chemistry, 2009, Vol. 6, No. 3
Guo and Du
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ACKNOWLEDGEMENT
This project was partially supported by National Natural
Science Foundation of China (Grant Nos: 20572003,
20772006), the Program for New Century Excellent Talents
in University (NCET-07-0011).
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