Enantio- and Diastereoselective Nitro-Mannich Reaction of α-Aryl Nitromethanes with Amidosulfones Catalyzed by Phase-Transfer Catalysts

Article abstract of DOI:10.1021/acs.joc.7b00306

A high-yield, highly diastereo- and enantioselective nitro-Mannich reaction of α-aryl nitromethanes with amidosulfones catalyzed by a novel chiral phase-transfer catalyst, bearing multiple H-bonding donors, derived from quinine was developed. A variety of α-aryl nitromethanes and amidosulfones were investigated; and the corresponding products were obtained in excellent yields with excellent diastereo- and enantioselectivities (up to 99% yield, > 99:1 dr and >99% ee). As a demonstration of synthetic utility, the resulting β-nitroamines could be converted to corresponding meso-symmetric and optically pure unsymmetric anti-1,2-diarylethylenediamines.

Full text of DOI:10.1021/acs.joc.7b00306

Subscriber access provided by ORTA DOGU TEKNIK UNIVERSITESI KUTUPHANESI
Article
Enantio- and diastereoselective Nitro-Mannich Reaction of #-Aryl
Nitromethanes with Amidosulfones catalyzed by phase-transfer catalysts
Ning Lu, Ruxu Li, Zhonglin Wei, Jungang Cao, Dapeng Liang, Yingjie Lin, and Haifeng Duan
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 18 Apr 2017
Downloaded from http://pubs.acs.org on April 19, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 10
The Journal of Organic Chemistry
1
2
3
4
5
6
Enantio- and diastereoselective Nitro-Mannich Reaction of α-Aryl
Nitromethanes with Amidosulfones catalyzed by phase-transfer cata-
lysts
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
*
*
Ning Lu, Ruxu Li, Zhonglin Wei, Jungang Cao, Dapeng Liang, Yingjie Lin , and Haifeng Duan
Department of Organic Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China
Supporting Information Placeholder
ABSTRACT: A high-yield, highly diastereo- and enantioselective nitro-Mannich reaction of α-aryl nitromethanes with amidosulfones
catalyzed by a novel chiral phase-transfer catalyst, bearing multiple H-bonding donors, derived from quinine was developed. A vari-
ety of α-aryl nitromethanes and amidosulfones were investigated; and the corresponding products were obtained in excellent yields
with excellent diastereo- and enantioselectivities (up to 99% yield, >99:1 dr and >99% ee). As a demonstration of synthetic utility,
the resulting β-nitroamines could be converted to corresponding meso-symmetric and optically pure unsymmetric anti-1,2-
diarylethylenediamines.
INTRODUCTION
Vicinal diamines are one of most important core structures
of many drugs. Moreover, they are also used as chiral ligands
Scheme 1. Previously reported asymmetric nitro-Mannich reaction
of N-Boc imines with α-aryl nitromethanes, and a new method with
respect to this reaction.
1
and have been widely used in asymmetric catalysis. As a result,
chiral vicinal diamines have been the subject of research, and a
number of highly stereoselective synthetic methodologies have
2
been developed. Among structurally diverse vicinal diamines,
optically active 1,2-diarylethylenediamines have been widely
used to prepare chiral ligands, organocatalysts and biologically
3
active molecules. Despite their utility, effective methods for
the preparation of optically pure 1,2-diarylethylenediamines
1
b
are still limited. Among these existing synthetic methodolo-
gies, cumbersome asymmetric synthesis started from chiral
starting materials, and chiral resolution of a racemic multi-
steps reaction product using an appropriate chiral reagent are
2b-c, 4
two traditional strategies.
However, expensive prices of
chiral materials and a limited range of substrates limited the
application of these two strategies. Recently, an attractive
strategy which can generate
a wide scope of 1,2-
diarylethylenediamines, catalytic asymmetric nitro-Mannich
found to be efficient in the asymmetric addition of α-aryl ni-
tromethanes to N-Boc aldimines, and aza-Henry adducts were
obtained in good yields with good to high diastereo- and enan-
tioselectivities (2:1->20:1 dr and 76-93% ee) (Scheme 1a). In
another work reported by Ooi’s group, chiral ammonium beta-
ines were successfully used to catalyze the highly diastereo-
and enantioselective nitro-Mannich reaction of α-aryl nitrome-
thanes with N-Boc imines. However, the reaction should be
reaction of aromatic aldimines with α-aryl nitromethanes fol-
5
lowed by the reduction of nitro group, has been developed.
Although a series of asymmetric nitro-Mannich reaction of
nitromethane and its alkyl congeners have been successfully
6
reported, to the best of our knowledge, the successful asym-
metric nitro-Mannich reactions using α-aryl nitromethanes as
substrates are rare. There are two research efforts that are im-
pressive. One of them was reported by Johnston and co-
8
carried out under stringent anhydrous conditions (Scheme
7
workers in 2011. In this work, chiral bisamidine-quinoline
1b). Although these elegant works have
catalysts were
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 10
a
Table 1. Optimization of Reaction Conditions
reaction (Table 1), and investigated the catalytic activity of
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
catalyst 2a. Gratifyingly, in the presence of KOH and toluene
at -30 ℃, catalyst 2a showed a good asymmetric catalytic activ-
ity, and the desired adduct 6aa (1S, 2R) was isolated in 67%
yield with 96:4 dr and 71% ee (entry 1), The product configu-
7
ration is in agreement with the data reported in the literature.
In further screening of bases, K
parent improvement in the yield and ee value of the product
entries 2-3). Surprisingly, when LiOH was employed in the
2
CO
3
and Cs
2
CO have no ap-
3
(
reaction, the yield of 6aa increased from 67% to 93%, and the
dr and ee values were also improved slightly (entry 4). In-
spired by these good results, we turned our attention on the
modification of catalyst on the basis of catalyst 2a. To this end,
catalyst 2b was synthesized using sterically hindered 3,5-di-
tert-butyl benzyl in place of benzyl on the nitrogen atom of
quinine according to the procedure described in our previous
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
entry cat. solvent base
temp yieldb d.r.c
(℃) (%)
eed
1
2
3
4
5
6
7
8
9
1
1
1
1
2a
2a
2a
2a
2b
3
2b
2b
2b
2b
2b
2b
2b
toluene KOH
toluene CO
toluene Cs
toluene LiOH
toluene LiOH
toluene LiOH
-30
-30
-30
-30
-30
-30
-30
-30
-40
-40
-40
-40
-40
67
43
56
93
98
84
85
99
99
85
95
99
92
96:4 71
94:6 70
98:2 68
98:2 74
98:2 87
97:3 72
99:1 98
99:1 95
99:1 99
98:2 91
99:1 98
99:1 99
99:1 99
K
2
3
11
work. Remarkably, catalyst 2b exhibited an improved asym-
metric catalytic activity and stereoselectivity in the presence of
LiOH and using toluene as the reaction solvent (entry 5). In
addition, well-behaved catalyst 3, which was developed by
Dixon group and exhibited excellent asymmetric activity in the
nitro-Mannich reaction of nitromethane, was also evaluated
under the identical reaction conditions. Compared with cata-
lyst 2b, it did not have a positive impact on the yield and enan-
tioselectivity (entry 6), and the relative and absolute configu-
rations of the product is consistent. In subsequent screening of
solvents and reaction temperatures, dichloromethane used as
the solvent have a beneficial effect on the enantioselectivity of
adduct 6aa, and the ee value increased from 87% to 98% at -
30 ℃. However, the yield decreased to 85% (entry 7). On the
contrary, chloroform led to a high yield but ee value decreased
slightly at -30 ℃ (entry 8). Lowering the reaction temperature
to -40 ℃ further improved the reaction results. In this case,
catalyst 2b exhibited excellent catalytic activity and diastereo-
and enantiocontrolling ability (entry 9, 99% yield, 99:1 dr, 99%
ee). In the final optimization of loadings of catalyst 2b and
substrate 4a, lowering catalyst 2b loadings led to a decrease in
the yield (entries 10 and 11). Satisfyingly, reducing the
amounts of substrate 4a from 5 to 1.5 equiv., we can still get
the best result (entry 12). However, performing this reaction
with 1.1 equiv. of 4a led to a slight decline in the yield (entry
2
CO
3
CH
2
Cl
2
LiOH
LiOH
LiOH
LiOH
LiOH
LiOH
LiOH
CHCl
CHCl
CHCl
CHCl
CHCl
CHCl
3
3
3
3
3
3
e
f
0
1
2
3
g
h
aUnless otherwise noted, Reactions were carried out with 0.1
mmol of 4a, 0.5 mmol of 5a, and 5 mol% of catalyst in 1.0 mL of
b
c
solvent. Yield of isolated product. Diastereomeric ratios deter-
1
d
mined by H NMR. Determined by HPLC using a chiral station-
e
f
ary phase. 1 mol% catalyst was used. 2.5 mol% catalyst was used.
g
h
0
.15 mmol of 5a was used. 0.11 mmol of 5a was used.
been reported, in terms of α-aryl nitromethanes and the corre-
sponding adducts containing acidic hydrogen atoms at benzyl
position, developing an efficient base-catalyzed highly dia-
stereo- and enantioselective catalytic system is still challenging
8
, 9
and desirable.
Amidosulfones due to their broad range and good stability
compared with the N-Boc imines have been used in several
asymmetric catalytic reactions.
amidosulfones successfully reacted with nitroalkanes in the
6
c,6d,10
In our previous work,
13). After a series of screenings and optimizations, eventually,
the optimal reaction conditions were identified as follows: 1.5
1
1a
presence of the bifunctional phase transfer catalyst 2a. En-
lightened by this work and as a continuation of our studies on
developing bifunctional chiral phase transfer catalysts bearing
multiple H-bond donors, we anticipated that a similar protocol
could be applied to the asymmetric nitro-Mannich reaction of
α-aryl nitromethanes, albeit controlling diastereo- and enanti-
oselectivity that would be significantly more challenging.
Herein, we would like to report an efficient and highly dia-
stereo- and enantioselective nitro-Mannich reaction of N-Boc
amidosulfones with α-aryl nitromethanes catalyzed by a novel
phase transfer catalyst bearing multiple H-bonding donors.
equiv. of 4a, 5 mol% of catalyst 2b, 5 equiv. of LiOH, CHCl
used as solvent, the reaction temperature of -40 ℃ and 12 h.
3
With the optimal conditions in hand, the scope of the reac-
tion with respect to amidosulfones and α-aryl nitromethanes
were investigated, and corresponding results were summarized
in Table 2. For all cases, excellent yields (90-99%), excellent
diastereo- and enantioselectivities (93:7-99:1 dr, 91-99% ee)
were obtained across the series. In these cases, a variety of
amidosulfones derived from aromatic aldehydes proved effec-
tive, with an electron-donating or electron-withdrawing group
in ortho-, meta- as well as para-position all being well-tolerated
with excellent reactivity and stereoseclectivities observed (en-
tries 1-12). In spite of this, in terms of methoxyl-substituted
amidosulfones, the position of methoxy have a slight effect on
the diastereoselectivity. For example, compared with sub-
strates 4c and 4j, meta-methoxy-substituted amidosulfone 4d
afforded adduct 6da with a slightly decreased dr (93:7) (entry
(
Scheme 1c).
RESULTS AND DISCUSSION
In order to evaluate the catalytic potential of chiral phase
transfer phase catalysts in the asymmetric nitro-Mannich reac-
tion of α-aryl nitromethanes, we initially chose the reaction of
amidosulfone 4a with α-phenyl nitromethane 5a as a model
ACS Paragon Plus Environment

Page 3 of 10
The Journal of Organic Chemistry
a
Table 2. Substrate Scope of Nitro-Mannich Reaction Using Catalyst 2b
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
2
b
c
d
entry
1
2
3
4
5
6
7
8
4
Ar
o-FC
o-MeOC
m-MeOC
m-ClC
p-FC
5
Ar
6
yield (%)
d.r.
ee (%)
e
4b
4c
4d
4e
4f
6
H
4
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5b
5c
5d
5e
5f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
o-FC
m-MeOC
p-BrC
p-MeC
p-MeOC
2-naphthyl
o-FC
p-BrC
p-BrC
Ph
6ba
6ca
6da
6ea
6fa
6ga
6ha
6ia
99
99
99
99
99
99
97
99
99
99
93
97
90
99
99
94
99
99
99
99
99
98
96
99
99
>99:1
99:1
93:7
>99:1
98:2
>99:1
>99:1
>99:1
99:1
>99:1
94:6
98:2
>99:1
98:2
97:3
93:7
99:1
98:2
>99:1
99:1
98:2
99:1
97:3
97:3
99
6
H
4
98
98
e
6
H
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
6
H
4
98
98
f
6
H
4
H
H
f
4g
4h
4i
p-ClC
p-BrC
p-MeC
6
4
99
99
e
6
4
f
6
H
4
96
98
98
f
9
10
11
4j
p-MeOC
p-CF
p-NO
p-CNC
2-naphthyl
2-furyl
2-thienyl
Ph
Ph
Ph
Ph
Ph
6
H
4
6ja
f
4k
4l
C
3 6
H
4
6ka
6la
2
C
4
H
6
99
95
12
13
14
15
16
17
18
19
20
4m
4n
4o
4p
4a
4a
4a
4a
4a
4a
4j
4
H
6
6ma
6na
6oa
6pa
6ab
6ac
6ad
6ae
6af
f
97
e
99
92
e
6
H
4
99
e
6
H
4
98
e
6
H
4
99
e
6
H
4
99
e,f
6
H
4
91
e,f
21
22
23
Ph
p-MeOC
p-MeOC
p-BrC
5g
5b
5d
5d
5a
6ag
6jb
6jd
6hd
6aa
96
e
6
6
H
H
4
4
6
H
4
98
e
4j
6
H
4
4
96
2
2
4
5
4h
4a
6
H
4
6
H
99
99
g
e
Ph
99:1
a
. bYield of
Unless otherwise noted, Reactions were carried out with 0.1 mmol of 4,0.15 mmol of 5, and 5 mol% of 2b in 1.0 mL of CHCl
isolated product. Diastereomeric ratios determined by HPLC. Determined by HPLC using a chiral stationary phase. Absolute and rela-
tive configurations of anti-isomers were determined by comparison to literature data. The reaction was performed with 3.0 mmol of 4a,
4.50 mmol of 5a, and 5 mol% of 2b in 30 mL of CHCl
,9 vs 3). Unfortunately, the desired product was not detected
3
c
d
e,f
7,8
g
3
.
2
after column chromatography (1.03 g, 99% yield, 99:1 dr and
99% ee, entry 25).
when the aminosulfone derived from 4-dimethylamino benzal-
dehyde was used as the substrate. Moreover, polycyclic aro-
matic and heteroaromatic substrates were also proved effective
(entries 13-15). Next, we set out to investigate the generality
of the reaction with other α-aryl nitromethanes. Pleasingly, the
present catalytic system was applicable to a range of α-aryl ni-
tromethanes with an electron-withdrawing or electron-
donating group, and corresponding products were yielded in
high yields (94-99%) with excellent dr and ee values (93:7-
9:1 dr, 91-99% ee, entries 16-19). In addition, 1-(2-naphthyl)
nitromethane 5g used as the substrate also proved effective
entry 21, 98:2 dr and 96% ee). Similarly, arbitrary combina-
tions of amidosulfones and α-aryl nitromethanes were well
accommodated (entries 22 and 23), and products containing
underlying symmetric 1,2-diarylethylenediamines scaffold
could be obtained in high yields (entry 24). Subsequently, we
have successfully conducted a gram scale reaction of 4a with 5a
under standard conditions, and optically pure 6aa was obtained
To investigate the role of the quaternary ammonium center
and multiple H-bonding donors in this kind of bifunctional
catalysts, and to test their synergistic catalysis, two control
experiments were performed using compounds 2c and 1 as
catalysts respectively (Scheme 2). Compared with catalyst 2b,
catalyst 2c, in which the hydroxyl group was protected by
methylation, has lower catalytic activity and stereocontrol abil-
ity. Similarly, catalyst 1, in absence of a quaternary ammonium
center, exhibited a significant decrease in catalytic activity and
diastereo- and enantiocontrol ability, and configurations of the
product is consistent. These results supported synergistic ca-
talysis of bifunctional catalysts and indicated that both the
hydroxy on the phenylglycinol moiety and the quaternary am-
monium center were crucial to achieve excellent catalytic activ-
ity and stereoselectivity in this asymmetric nitro-Mannich reac-
tion.
9
(
To explain the stereoselectivity of the reaction, a possible
transition-state model was proposed (Figure 1). The ammoni-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 10
um motif pairs with the nitro compounds by electrostatic in- of α-aryl nitromethanes and amidosulfones were investigated,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
teraction and the urea motif captures the N-Boc imines by hy-
drogen bond (HB) interaction. Therefore, a highly ordered
transition state is formed and the nitro compounds can attack
the N-Boc imines from the Re face.
and corresponding products were obtained in excellent yields
with excellent diastereo- and enantioselectivities. Using this
asymmetric catalytic protocol, optically pure unsymmetric and
meso-symmetric 1,2-diarylethylenediamines could be synthe-
sized. Detail mechanism study on this reaction, and further
application of this kind of bifunctional phase transfer catalysts
bearing multiple H-donors are underway in our laboratory.
Scheme 2. Control Experiment for Mechanistic Study.
EXPERIMENTAL SECTION
General Information
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Unless otherwise stated, all reagents were purchased from
commercial suppliers and used without purification. All sol-
vents were obtained from commercial sources and were puri-
fied according to standard procedures. For thin-layer chroma-
tography (TLC), silica gel plates (HSGF 254) were used and
compounds were visualized by irradiation with UV light. Puri-
fication of reaction products was carried out by flash column
The universality of the present system was further demon-
strated by the application to aliphatic amidosulfone, excellent
levels of diastereo- and enantioselectivity were also obtained
with amidosulfone 4q as a substrate (Scheme 3a). Finally, the
applicability of this protocol was demonstrated by the derivati-
zation of optically pure 6aa and 6ea. As shown in scheme 3b,
1
13
chromatography using silica gel (200-300 mesh). H and
NMR, F NMR spectra were recorded on a Varian Mercury-
C
19
300BB (300 MHz); a Bruker NMR Spectrometer (400 MHz)
or a Bruker NMR Spectrometer (500 MHz). All chemical
shifts (δ) were given in ppm. Chemical shifts ( δ ppm) are rela-
tive to the resonance of the deuterated solvent as the internal
6aa could be readily derivatized into meso-symmetric 1,2-
diarylethylenediamine 8aa, and 6aa could be coverted to un-
symmetric anti-1,2-diarylethylenediamine 8ea via a nickel-
boride mediated reduction of nitro-group followed by the
removal of Boc in the presence of trifluoroacetic acid.
standard (CDCl
carbon NMR; CD
ppm for carbon NMR; DMSO-d
3
, δ 7.26 ppm for proton NMR, δ 77.2 ppm for
OD-d , δ 3.31 ppm for proton NMR, δ 49.0
, δ 2.50 ppm for proton NMR,
3
4
6
δ 39.5 ppm for carbon NMR). Data are presented as follows:
chemical shift, integration, multiplicity (br = broad, s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet) and cou-
pling constant in Hertz (Hz). Mass spectra were recorded on
the Bruker Agilent1290 MicrOTOF Q II. Melting points were
measured on a melting point apparatus and were uncorrected.
The ee values determination was carried out using chiral
HPLC (Waters) with Chiracel IA-3 column, Chiracel IC-3
column and Chiracel AD-H column. Optical rotations were
Figure 1. Proposed transition state model leading to anti-adducts.
measured on a Shanghai ShenGuang SGW-2 Polarimeter at λ =
20
5
(
89 nm. Optical rotations are reported as follows: [α]
c=g/100 mL, solvent).
Starting materials
9-amino(9-deoxy)epicinchona alkaloids of quinine were pre-
D
Scheme 3. Reaction of aliphatic amidosulfone with α-phenyl nitro-
methane, and derivatization of 6aa and 6ea to the corresponding
12
1,2-diarylethylenediamine 8aa and 8ea.
pared according to reported procedure. All amidosulfones
were prepared using reported procedures from corresponding
aldehydes. Nitro compounds were prepared by following the
literature. All aminoalcohols was purchased from commercial
suppliers and used directly.
1
3
1
4
Preparation and characterization of the chiral ureas with multiple
Hydrogen-Bonding Donors.
General Procedure:
N, N’-carbonyldiimidazole (165 mg, 1.02 mmol, 1.1 equiv) was
dissolved in anhydrous THF, a solution of 9-amino(9-
deoxy)epiquine (300 mg, 0.93 mmol, 1equiv) in THF (5 ml)
was added dropwise in 1 h, the reaction mixture was stirred for
another 1 h. Then aminoalcohol (1.1 equiv) and triethylamine
CONCLUSIONS
(
142ul, 1.1 equiv) were added in one portion respectively, the
In summary, we have developed an efficient and highly dia-
stereo- and enatioselective nitro-Mannich reaction of α-aryl
nitromethanes with stable amidosulfones in place of N-Boc
imines, which was catalyzed by a novel bifunctional phase-
transfer catalyst bearing multiple H-bonding donors. A variety
resulting mixture was stirred until TLC showed that the reac-
tion was completed. The mixture was diluted with 36 ml
ethylacetate, then washed with water (10×15ml), the organic
phase was dried over Na
2
SO . The solvent was removed under
4
ACS Paragon Plus Environment

Page 5 of 10
The Journal of Organic Chemistry
3.88 (m, 4H), 3.81 – 3.37 (m, 5H), 2.84 – 2.56 (m, 1H), 2.25 –
reduced pressure and the crude product was purified by flash
1
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
chromatography (ethylacetate/MeOH=10:1).
1.72 (m, 5H), 1.22 – 1.07 (m, 1H). C NMR (101 MHz,
CD OD) δ 160.6, 158.7, 148.6, 148.3, 145.6, 145.4, 142.2,
3
Urea 1 derived from quinine and L-phenylglycinol / [(S)-(+)-2-
Phenylglycinol]
137.5, 134.7, 131.9, 131.5, 130.4, 129.4, 128.8, 128.4, 128.2,
128.0, 127.4, 124.2, 124.0, 120.6, 118.2, 102.6, 69.4, 67.3, 66.4,
Light yellow solid, 334 mg, 74% yield, m.p.
61.6, 58.1, 56.6, 51.5, 50.4, 38.6, 28.7, 28.1, 25.5. HRMS (ESI):
25
=
CHCl
109-111 ℃ , [a]
D
= -21 (c = 0.33,
+
41
calculated for C36H N
4
O
3
[M-Br] : 577.3173, found 577.3167.
1
3
). H NMR (300 MHz, CDCl ) δ
3
Catalyst 2b
8
1
9
.64 (d, J = 4.6 Hz, 1H), 7.99 (d, J = 9.2 Hz,
H), 7.64 (d, J = 2.3 Hz, 1H), 7.35 (dd, J =
.1, 2.6 Hz, 1H), 7.30 – 7.25 (m, 3H), 7.21
Obtained according to the general procedure, the crude prod-
uct
(Et
was
purified
by
flash
chromatography
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
–
7.11 (m, 3H), 6.25 (br. s, 1H), 5.87 (br. s, 1H), 5.79 – 5.53
2
O/MeOH=10:1).
(
m, 1H), 5.22 (br. s, 1H), 5.09 – 4.86 (m, 2H), 4.64 (d, J = 5.2
Light yellow solid, 115 mg, 48 % yield,
Hz, 1H), 3.92 (s, 3H), 3.73 (d, J = 4.8 Hz, 2H), 3.16 (br. s,
2H), 3.03 – 2.85 (m, 1H), 2.75 – 2.36 (m, 2H), 2.24 (br. s,
1H), 1.72 – 1.30 (m, 4H), 1.01 – 0.77 (m, 1H). C NMR (101
MHz, CDCl ) δ 158.2, 157.9, 147.5, 144.7, 141.2, 140.9, 140.5,
131.6, 128.9, 128.6, 128.4, 127.4, 126.7, 121.8, 114.9, 102.0,
66.9, 60.5, 57.2, 55.7, 55.5, 40.7, 39.2, 34.4, 27.5, 27.3, 26.0.
HRMS (ESI): calculated for C29
found 487.2695.
25
m.p. =147-148 ℃ (decomp.), [a]
0.8 (c = 0.5, CHCl ).
H NMR (500 MHz, CD
J = 45.6 Hz, 1H), 8.00 (d, J = 9.1 Hz,
H), 7.81 – 7.59 (m, 3H), 7.55 – 7.43
m, 1H), 7.30 (s, 2H), 7.13 (s, 2H), 7.02
6.58 (m, 3H), 6.32 (d, J = 10.0 Hz,
D
= -
9
3
1
3
1
3
OD) δ 8.72 (d,
3
1
(
–
+:
H
35
N
4
O [M+H] 487.2704,
3
1
4
1
H), 6.06 – 5.81 (m, 1H), 5.21 (dd, J = 19.5, 14.3 Hz, 2H),
.91 (d, J = 11.8 Hz, 3H), 4.80 (br, J = 34.7 Hz, 1H), 4.34 (s,
H), 4.19 (s, 1H), 4.06 (s, 3H), 3.70 – 3.34 (m, 5H), 2.70 (br,
Urea derived from quinine and (1S)-2-Methoxy-1-
phenylethanamine
Light yellow solid, 306 mg, 66% yield, m.p. =
1H), 2.25 – 1.72 (m, 4H), 1.39 (s, 2H), 1.34 (s, 18H), 1.14 (d,
25
1
13
9
0-91 ℃, [a]
D
= -25.2 (c = 0.5, CHCl
3
). H
J = 13.3 Hz, 1H). C NMR (126 MHz, CD OD) δ 160.6,
3
NMR (300 MHz, CDCl
3
) δ 8.69 (d, J = 4.6
Hz, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.66 (d, J
= 2.6 Hz, 1H), 7.37 (dd, J = 9.2, 2.7 Hz, 1H),
7.28 (d, J = 1.4 Hz, 1H), 7.25 – 7.17 (m, 5H),
6.34 (br.s, 1H), 5.78 – 5.59 (m, 1H), 5.51 (d,
158.7, 153.2, 148.6, 146.0, 145.5, 141.9, 138.0, 131.9, 129.3,
129.0, 128.7, 128.2, 128.1, 127.2, 125.8, 124.3, 120.8, 118.2,
102.4, 70.2, 68.0, 66.6, 61.2, 57.7, 56.6, 51.0, 50.2, 38.6, 35.8,
31.8, 29.1, 28.1, 25.6. HRMS (ESI): calculated for C44
H
57
N
4
O
3
+
[M-Br] : 689.4425, found 689.4425.
J = 6.7 Hz, 1H), 5.25 (br.s, 1H), 5.07 – 4.91 (m, 2H), 4.83 (dd,
J = 11.4, 6.2 Hz, 1H), 3.95 (s, 3H), 3.57 – 3.40 (m, 2H), 3.37 –
Catalyst 2c.
Obtained according to the general procedure, the crude prod-
uct was purified by flash chromatography (EA /MeOH=10:1).
3.14 (m, 6H), 2.90 – 2.64 (m, 2H), 2.45 – 2.25 (m, 1H), 1.77 –
1
3
1
.59 (m, 3H), 1.53 – 1.37 (m, 1H), 1.06 – 0.94 (m, 1H).
) δ 157.7, 147.4, 145.7, 144.6, 141.1,
40.6, 131.5, 129.8, 128.4, 128.2, 127.4, 127.1, 126.5, 121.5,
14.5, 102.0, 75.6, 71.7, 60.0, 58.6, 55.7, 55.5, 53.9, 40.7, 39.3,
7.6, 27.3, 25.9. HRMS (ESI): calculated for C30
C
Light yellow solid, 146 mg, 62 % yield,
NMR (101 MHz, CDCl
3
2
5
m.p. =167-168 ℃, [a]
D
= -25.5 (c =
). H NMR (300 MHz,
OD) δ 8.77 (d, J = 4.7 Hz, 1H), 8.01
(d, J = 9.2 Hz, 1H), 7.65 (d, J = 15.0 Hz,
1
1
2
1
0
.33, CHCl
3
CD
3
H
37
N
4
O
3
+
[M+H] : 501.2860, found 501.2844.
3
7
H), 7.55 – 7.43 (m, 1H), 7.29 (s, 2H),
.14 (d, J = 6.9 Hz, 2H), 6.94 (d, J = 7.4
Preparation and characterization of the chiral PTC with multiple
Hydrogen-Bongding donors
Hz, 3H), 6.31 (d, J = 10.6 Hz, 1H), 5.99
– 5.87 (m, 1H), 5.28 – 5.13 (m, 2H), 5.03 – 4.92 (m, 2H), 4.88
– 4.78 (m, 1H), 4.40 (br, 1H), 4.19 (br, 1H), 4.07 (s, 3H),
3.77 – 3.53 (m, 2H), 3.48 (dd, J = 10.0, 4.4 Hz, 2H), 3.42 –
3.32 (m, 2H), 3.13 (s, 3H), 2.71 (d, J = 6.2 Hz, 1H), 2.26 –
General Procedure:
Under N protection, 9-amino(9-deoxy)epiquine-derived urea
2
1 (150 mg, 1 eq.)was dissolved in THF (0.1 M), then benzyl
bromide (1.1 eq.) was added, the mixture was heated to reflux,
after 12 h the mixture was concentrated and purified by flash
chromatography.
1
3
1.93 (m, 4H), 1.88 (br, 2H), 1.33 (s, 18H). C NMR (75
MHz, CD OD) δ 160.8, 158.8, 153.4, 148.7, 146.0, 145.8,
41.9, 138.0, 132.1, 129.4, 129.1, 128.8, 128.3, 127.9, 127.3,
3
1
1
5
Catalyst 2a
25.9, 124.3, 120.8, 118.3, 102.7, 77.0, 70.2, 68.2, 61.5, 59.2,
Obtained according to the general procedure, the crude prod-
6.7, 55.5, 51.4, 50.4, 38.7, 36.0, 31.9, 29.2, 28.3, 25.8. HRMS
uct
Et
was
purified
by
flash
chromatography
+
(
ESI): calculated for C45
59
H N
4
O
3
[M-Br] : 703.4582, found
(
2
O/MeOH=10:1).
703.4569.
Light yellow solid, 87 mg, 43 % yield,
m.p. =178-179 ℃ (decomp.), [a]
General procedure for enantio- and diastereoselective nitro-
Mannich reaction
25
D
= -
1
4
4.4 (c = 0.5, CHCl
MHz, CD OD) δ 8.77 (d, J = 4.1 Hz, 1H),
.01 (d, J = 9.2 Hz, 1H), 7.81 – 7.63 (m,
3
). H NMR (300
Without protection of inert gases, catalyst 2b (5 mol%) and
amidosulfones (0.10 mmol) were dissolved in dry chloroform
1.0 mL), α-Aryl nitromethane (0.15 mmol, 1.5 eq.) was added,
the mixture was cooled to –40 °C, freshly grounded LiOH
12.0 mg, 5 eq.) was added in one portion, the resulting sus-
pention was vigorously stirred at –40 °C. After 12 h, 5 ml sat.
3
8
2
2
(
H), 7.60 – 7.32 (m, 7H), 7.28 – 7.14 (m,
H), 7.13 – 6.95 (m, 2H), 6.32 (d, J =
(
10.6 Hz, 1H), 5.98 – 5.71 (m, 1H), 5.34 –
5.05 (m, 3H), 5.03 – 4.96 (m, 1H), 4.44 – 4.24 (m, 1H), 4.20 –
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 10
aq. NH
room temperature, the aqueous was extracted with ethylacetate
(3×5ml), then the organic layer was dried over Na SO , fil-
tered and concentrated under reduced pressure. The crude
product was purified by flash chromatography (PE/EA=10:1).
4
Cl was added and the solution was allowed to warm to
7.22 (m, 2H), 6.95 – 6.82 (m, 2H), 5.75 (d, J = 9.9 Hz, 1H),
5.61 (t, J = 9.4 Hz, 1H), 4.72 (d, J = 9.4 Hz, 1H), 3.80 (s, 3H),
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
2
4
1.25 (s, 9H). Analytical and spectral data were in agreement
8
with the literature data.
Tert-butyl
[(1S,2R)-1-(3-chlorophenyl)-2-nitro-2-
Synthesis of racemates:
phenylethyl]carbamate (6ea)
Without protection of inert gases, amidosulfones (0.10 mmol)
were dissolved in dry chloroform (1.0 mL), α-Aryl nitrome-
thane (0.15 mmol, 1.5 eq.) was added, the mixture was stirred
at room temperature, DBU(20 mol%) was added. After 12 h, 5
White solid, 37.3 mg, 99% yield, dr=99:1, m.p. =192-194 ℃,
20
[a]D = 33.6 (c = 0.5, CHCl ), The ee value was 98% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =12.34 min., tminor =13.47 min), Minor-syn-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
mL sat. aq. NH
ethylacetate (3×5 mL), then the organic layer was dried over
Na SO , filtered and concentrated under reduced pressure.
4
Cl was added, the aqueous was extracted with
(tmajor =16.28 min., tminor =9.81 min)]. H NMR (300 MHz,
CDCl ) δ 7.60 – 7.49 (m, 2H), 7.47 – 7.39 (m, 3H), 7.37 –
3
2
4
7.28 (m, 3H), 7.25 – 7.21 (m, 1H), 5.71 (dd, J = 18.0 Hz, 2H),
1
3
The crude product was purified by flash chromatography
(PE/EA=10:1).
4.85 (br, 1H), 1.26 (s, 9H). C NMR (101 MHz, CDCl ) δ
3
154.19, 139.60, 134.87, 131.18, 130.39, 130.27, 128.97, 128.65,
127.44, 125.51, 93.93, 80.71, 56.33, 28.05. HRMS (ESI): cal-
Tert-butyl [(1S,2R)-2-nitro-1,2-diphenylethyl]carbamate (6aa)
+
+
culated for C19H21ClN
2
NaO
4
([M+Na] ) 399.1082. Found
White solid, 34 mg, 99% yield, dr=99:1, m.p. =198-200 ℃,
399.1080. Absolute and relative configurations were assigned
on the analogy of 6aa.
2
0
[a]
D
= 49.2 (c = 0.5, CHCl ), The ee value was 99% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
Tert-butyl
[(1S,2R)-1-(4-fluorophenyl)-2-nitro-2-
Major-anti-(tmajor =17.74 min., tminor =16.11min), Minor-syn-
1
phenylethyl]carbamate (6fa)
(
t
major =25.23 min., tminor =12.24 min)]. H NMR (300 MHz,
CDCl
3
) δ 7.62 – 7.52 (m, 3H), 7.49 – 7.39 (m, 3H), 7.38 –
White solid, 36 mg, 99% yield, dr=98:2, m.p. =191-193 ℃,
20
7.24 (m, 4H), 5.74 (br, 1H), 5.63 (br, 1H), 4.84 (s, 1H), 1.26
[a]D = 82.8 (c = 0.5, CHCl ), The ee value was 98% [Chi-
3
(s, 9H). Analytical and spectral data were in agreement with
ralpak IA-3, hexane/EtOH = 95:5, 230 nm, 1.0 mL/min, Ma-
8
the literature data.
jor-anti-(tmajor =13.39 min., tminor =12.74 min), Minor-syn-(t
=15.60 min., tminor =25.46 min)]. H NMR (300 MHz, CDCl
major
1
3
)
Tert-butyl
[(1S,2R)-1-(2-fluorophenyl)-2-nitro-2-
δ 7.63 – 7.50 (m, 2H), 7.49 – 7.38 (m, 3H), 7.34 (dd, J = 8.6,
5.2 Hz, 2H), 7.14 – 6.98 (m, 2H), 5.76 (d, J = 10.1 Hz, 1H),
5.65 (d, J = 9.1 Hz, 1H), 4.79 (d, J = 8.8 Hz, 1H), 1.26 (s, 9H).
phenylethyl]carbamate (6ba)
White solid, 35.8 mg, 99% yield, dr=99:1, m.p. =181-183 ℃,
2
0
[a]
D
= 56.8 (c = 0.5, CHCl3), The ee value was 99% [Chi-
1
9
F NMR (376 MHz, CDCl
3
) δ -112.7. Analytical and spectral
ralpak IC-3, hexane/EtOH = 16:1, 210 nm, 0.5 mL/min, Ma-
7
data were in agreement with the literature data.
jor-anti-(tmajor =12.12 min., tminor =13.27 min), Minor-syn-(tmajor
1
Tert-butyl
[(1S,2R)-1-(4-chlorophenyl)-2-nitro-2-
=
18.67 min., tminor =15.16 min)]. H NMR (300 MHz, CDCl
3
)
phenylethyl]carbamate (6ga)
δ7.63 (dd, J = 6.5, 3.1 Hz, 2H), 7.53 – 7.29 (m, 5H), 7.21 –
7
.02 (m, 2H), 5.87 (d, J = 3.6 Hz, 2H), 5.07 (br, 1H), 1.22 (s,
White solid, 37.4 mg, 99% yield, dr=99:1, m.p.=196-197 ℃,
1
9
20
9H). F NMR (376 MHz, CDCl
3
) δ -117.2 Analytical and
[a]D = 24.8 (c = 0.5, CHCl ), The ee value was 99% [Chi-
3
8
spectral data were in agreement with the literature data.
ralpak AD-H, hexane/i-PrOH = 90:10, 214 nm, 1.0 mL/min,
Major-anti-(tmajor =21.14 min., tminor =35.13 min), Minor-syn-
Tert-butyl [(1S,2R)-1-(2-methoxyphenyl)-2-nitro-2-
phenylethyl]carbamate (6ca)
1
(tmajor =32.27 min., tminor =22.89 min)]. H NMR (300 MHz,
CDCl ) δ 7.59 – 7.49 (m, 2H), 7.48 – 7.38 (m, 3H), 7.38 –
3
White solid, 37 mg, 99% yield, dr=99:1, m.p. =185-187 ℃,
7.26 (m, 4H), 5.76 (d, J = 9.8 Hz, 1H), 5.62 (d, J = 9.2 Hz,
1H), 4.76 (d, J = 9.0 Hz, 1H), 1.26 (s, 9H). Analytical and
2
0
[a]
D
= 59.2 (c = 0.5, CHCl ), The ee value was 98% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
7
spectral data were in agreement with the literature data.
Major-anti-(tmajor =8.73min., tminor =27.67 min), Minor-syn-
1
Tert-butyl
[(1S,2R)-1-(4-boranylphenyl)-2-nitro-2-
(
t
major =10.06 min., tminor =17.63 min)]. H NMR (300 MHz,
phenylethyl]carbamate (6ha)
CDCl ) δ 7.64 (s, 2H), 7.40 (s, 3H), 7.35 – 7.22 (m, 2H), 7.02
3
–
6.83 (m, 2H), 5.99 (d, J = 7.2 Hz, 1H), 5.81 (t, J = 10.4 Hz,
White solid, 40.8 mg, 97% yield, dr=99:1, m.p.=189-190 ℃,
13
20
1H), 5.51 (d, J = 10.4 Hz, 1H), 3.98 (s, 3H), 1.20 (s, 9H). C
[a]D = 38 (c = 0.3, CHCl ), The ee value was 99% [Chi-
3
NMR (101 MHz, CDCl
3
) δ 157.2, 154.4, 132.0, 131.5, 130.1,
ralpak AD-H, hexane/i-PrOH = 95:5, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =41.54 min., tminor =29.64 min), Minor-syn-
129.9, 128.96, 128.5, 124.4, 121.3, 111.2, 93.2, 79.7, 55.9, 55.6,
+
+
1
28.1. HRMS (ESI): calculated for C20
H
24
N
2
O
5
Na ([M+Na] )
(tmajor =55.38 min., tminor =34.92 min)]. H NMR (300 MHz,
395.1577. Found 395.1577. Absolute and relative configura-
tions were assigned on the analogy of 6aa.
CDCl ) δ 7.59 – 7.46 (m, 4H), 7.46 – 7.38 (m, 3H), 7.30 –
3
7.18 (m, 2H), 5.75 (d, J = 9.3 Hz, 1H), 5.61 (br, 1H), 4.81 (br,
1H), 1.26 (s, 9H). Analytical and spectral data were in agree-
Tert-butyl
[(1S,2R)-1-(3-methoxyphenyl)-2-nitro-2-
8
ment with the literature data.
phenylethyl]carbamate (6da)
Tert-butyl [(1S,2R)-2-nitro-2-phenyl-1-(p-tolyl)ethyl]carbamate
(6ia)
White solid, 37.1 mg, 99% yield, dr=93:7, m.p. =177-178 ℃,
20
[a]
D
= 43 (c = 0.4, CHCl ), The ee value was 98% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
White solid, 35.4 mg, 99% yield, dr=99:1, m.p.=190-192 ℃,
20
Major-anti-(tmajor =21.75 min., tminor =31.58 min), Minor-syn-
[a]D = 31.2 (c = 0.5, CHCl ), The ee value was 96% [Chi-
3
1
(
t
major =18.77 min., tminor =16.02 min)]. H NMR (300 MHz,
ralpak AD-H, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =15.66 min., tminor =14.40 min), Minor-syn-
CDCl ) δ 7.64 – 7.51 (m, 2H), 7.47 – 7.35 (m, 3H), 7.32 –
3
ACS Paragon Plus Environment

Page 7 of 10
The Journal of Organic Chemistry
1
(
t
major =24.43 min., tminor =11.97 min)]. H NMR (300 MHz,
Tert-butyl
[(1S,2R)-1-(naphthalen-2-yl)-2-nitro-2-
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
CDCl
) δ 7.61 – 7.52 (m, 2H), 7.49 – 7.35 (m, 3H), 7.28 –
phenylethyl]carbamate (6na)
3
7.20 (m, 2H), 7.17 (d, J = 8.2 Hz, 1H), 5.75 (d, J = 10.1 Hz,
1H), 5.64 (br, 1H), 4.76 (d, J = 9.4 Hz, 1H), 2.34 (s, 3H),
1.24 (s, 9H). Analytical and spectral data were in agreement
White solid, 35.3 mg, 90% yield, dr=99:1, m.p. =190-191 ℃,
20
[a]
D
= 23.5 (c = 0.4, CHCl ), The ee value was 97% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =23.21 min., tminor =17.95 min), Minor-syn-
(tmajor =28.97 min., tminor =14.68 min)]. H NMR (300 MHz,
8
with the literature data.
1
Tert-butyl
phenylethyl]carbamate (6ja)
[(1S,2R)-1-(4-methoxyphenyl)-2-nitro-2-
CDCl3) δ 7.93 – 7.74 (m, 4H), 7.68 – 7.56 (m, 2H), 7.55 –
7.36 (m, 6H), 5.89 (s, 2H), 4.89 (d, J = 8.1 Hz, 1H), 1.25 (s,
9H). Analytical and spectral data were in agreement with the
White solid, 37.1 mg, 99% yield, dr=99:1, m.p. =191-193 ℃,
20
[a]
D
= 49.6 (c = 0.5, CHCl ), The ee value was 98% [Chi-
3
8
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
literature data.
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =18.74 min., tminor =60.96 min), Minor-syn-
Tert-butyl
phenylethyl]carbamate (6oa)
[(1R,2R)-1-(furan-2-yl)-2-nitro-2-
1
(
tmajor =33.19 min., tminor =20.76 min)]. H NMR (300 MHz,
CDCl ) δ 7.65 – 7.52 (m, 2H), 7.42 (dd, J = 5.1, 2.0 Hz, 3H),
3
White solid, 33 mg, 99% yield, dr=98:2, m.p. =163-165 ℃,
7.34 – 7.25 (m, 1H), 6.93 (d, J = 7.8 Hz, 1H), 6.90 – 6.82 (m,
2H), 5.76 (d, J = 9.9 Hz, 1H), 5.68 (d, J = 9.0 Hz, 1H), 4.75 (d,
J = 9.0 Hz, 1H), 3.80 (s, 3H), 1.25 (s, 9H). Analytical and
20
[a]
D
= 44.8 (c = 0.5, CHCl ), The ee value was 99% [Chi-
3
ralpak IC-3, hexane/i-PrOH = 98:2, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =22.69 min., tminor =35.67 min), Minor-syn-
8
spectral data were in agreement with the literature data.
1
(
tmajor =47.19 min., tminor =40.83 min)]. H NMR (300 MHz,
Tert-butyl
[(1S,2R)-2-nitro-2-phenyl-1-(4-
CDCl ) δ 7.60 – 7.49 (m, 2H), 7.46 – 7.33 (m, 4H), 6.34 (d, J
3
(trifluoromethyl)phenyl)ethyl]carbamate (6ka)
= 1.3 Hz, 2H), 5.83 (s, 2H), 4.88 (br, 1H), 1.26 (s, 9H). Ana-
lytical and spectral data were in agreement with the literature
White solid, 41.0 mg, 99% yield, dr=99:1, m.p. =191-193 ℃,
8
20
data.
[a]
D
= 54.8 (c = 0.5, CHCl ), The ee value was 98% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 95:5, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =37.53 min., tminor =23.85 min), Minor-syn-
Tert-butyl
[(1R,2R)-2-nitro-2-phenyl-1-(thiophen-2-
yl)ethyl]carbamate (6pa)
1
(
tmajor =47.90 min., tminor =33.23 min)]. H NMR (300 MHz,
White solid, 34.7 mg, 99% yield, dr=97:3, m.p. =166-167 ℃,
CDCl
3
) δ 7.63 (d, J = 8.2 Hz, 2H), 7.58 – 7.52 (m, 2H), 7.52 –
20
[a]
D
=38.4 (c = 0.5, CHCl ), The ee value was 92% [Chi-
3
7.38 (m, 5H), 5.79 (s, 1H), 5.73 (d, J = 8.6 Hz, 1H), 4.82 (d, J
= 8.9 Hz, 1H), 1.26 (s, 9H). F NMR (376 MHz, CDCl ) δ -
62.7. Analytical and spectral data were in agreement with the
literature data.
ralpak IC-3, hexane/EtOH = 16:1, 210 nm, 0.5 mL/min, Ma-
jor-anti-(tmajor =13.77 min., tminor =15.11 min), Minor-syn-(tmajor
19
3
1
=
19.71 min., tminor =17.53 min)]. H NMR (300 MHz, CDCl
3
)
7
δ 7.61 – 7.48 (m, 2H), 7.47 – 7.35 (m, 3H), 7.33 – 7.21 (m,
1H), 7.06 (d, J = 3.4 Hz, 1H), 6.97 (dd, J = 5.1, 3.6 Hz, 1H),
5.95 (d, J = 9.4 Hz, 1H), 5.86 (d, J = 9.6 Hz, 1H), 4.79 (br,
Tert-butyl
phenylethyl]carbamate (6la)
[(1S,2R)-2-nitro-1-(4-nitrophenyl)-2-
1
3
1H), 1.28 (s, 9H). C NMR (101 MHz, CDCl
3
) δ 154.1, 140.4,
White solid, 36.0 mg, 93% yield, dr=94:6, m.p. =187-188 ℃,
20
131.5, 130.2, 128.9, 128.6, 127.1, 126.4, 125.8, 94.5, 80.6, 52.6,
28.1. HRMS (ESI): calculated for C17
371.1036. Found 371.1034. Absolute and relative configura-
tions were assigned on the analogy of 6aa.
[a]
D
= 22 (c = 0.4, CHCl ), The ee value was 99% [Chi-
3
+
+
H
20
N
2
NaO S ([M+Na] )
4
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =24.73 min., tminor =20.13 min), Minor-syn-
(tmajor =36.53 min., tminor =27.63 min)]. H NMR (400 MHz,
1
CDCl
3
) δ 8.28 – 8.19 (m, 2H), 7.60 – 7.51 (m, 4H), 7.50 –
Tert-butyl
[(1S,2R)-2-(2-fluorophenyl)-2-nitro-1-
7.41 (m, 3H), 5.83 (br, 1H), 5.72 (t, J = 8.9 Hz, 1H), 4.88 (d,
J = 8.5 Hz, 1H), 1.27 (s, 9H). C NMR (101 MHz, CDCl
154.2, 148.0, 144.7, 130.8, 130.7, 129.2, 128.5, 128.4, 124.1,
phenylethyl]carbamate (6ab)
1
3
3
) δ
White solid, 33.8 mg, 94% yield, dr=93:7, m.p. =175-176 ℃,
20
[a]
D
=25.6 (c = 0.5, CHCl ), The ee value was 99% [Chi-
3
93.5, 81.1, 56.3, 28.1. HRMS (ESI): calculated for
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 0.5 mL/min,
Major-anti-(tmajor =33.81 min., tminor =17.89 min), Minor-syn-
(tmajor =27.08 min., tminor =19.56 min)]. H NMR (300 MHz,
+
+
C
19
H
21
N
3
NaO ([M+Na] ) 410.1323. Found 410.1330. Abso-
6
lute and relative configurations were assigned on the analogy of
aa.
1
6
CDCl
3
) δ 7.80 (t, J = 7.0 Hz, 1H), 7.37 (s, 6H), 7.27 – 7.18 (m,
Tert-butyl
phenylethyl]carbamate (6ma)
[(1S,2R)-1-(4-cyanophenyl)-2-nitro-2-
1H), 7.12 (t, J = 9.3 Hz, 1H), 6.21 (d, J = 10.4 Hz, 1H), 5.72
1
9
(br, 1H), 4.90 (d, J = 9.2 Hz, 1H), 1.23 (s, 9H). F NMR (376
MHz, CDCl ) δ -117.9. Analytical and spectral data were in
agreement with the literature data.
3
White solid, 35.7 mg, 97% yield, dr=98:2, m.p. =176-177 ℃,
8
2
0
[a]
D
= 37 (c = 0.5, CHCl ), The ee value was 95% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =21.34 min., tminor =19.77 min), Minor-syn-
(tmajor =32.67 min., tminor =27.95 min)]. H NMR (400 MHz,
Tert-butyl
[(1S,2R)-2-(3-methoxyphenyl)-2-nitro-1-
phenylethyl]carbamate (6ac)
1
White solid, 37.1 mg, 90% yield, dr=99:1, m.p. =179-181 ℃,
CDCl
3
) δ 7.67 (d, J = 8.1 Hz, 2H), 7.60 – 7.39 (m, 7H), 5.79
20
[a]
D
= 22 (c = 0.5, CHCl ), The ee value was 98% [Chi-
3
(
br, 1H), 5.68 (d, J = 8.1 Hz, 1H), 4.90 (br, 1H), 1.27 (s, 9H).
C NMR (101 MHz, CDCl
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, Major-anti-
1
3
3
) δ 154.2, 142.8, 132.7, 130.8,
(
t
major =40.56 min., tminor =20.92 min), Minor-syn-(tmajor =22.33
130.6, 129.2, 128.5, 128.2, 118.2, 112.8, 93.5, 81.0, 52.1, 28.0.
1
min., tminor =16.54 min)]. H NMR (300 MHz, CDCl
3
) δ 7.43 –
+
+
HRMS (ESI): calculated for C20
H
21
N
3
NaO
4
([M+Na] )
7.27 (m, 6H), 7.17 – 7.08 (m, 2H), 7.01 – 6.92 (m, 1H), 5.73
(t, J = 13.6 Hz, 2H), 4.77 (br, 1H), 3.83 (s, 3H), 1.27 (s, 9H).
390.1424. Found 390.1425. Absolute and relative configura-
tions were assigned on the analogy of 6aa.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 10
Analytical and spectral data were in agreement with the litera- 117.8. Analytical and spectral data were in agreement with the
8
8
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
ture data.
literature data.
Tert-butyl
phenylethyl)carbamate (6ad)
[(1S,2R)-2-(4-bromophenyl)-2-nitro-1-
Tert-butyl [(1S,2R)-2-(4-bromophenyl)-1-(4-methoxyphenyl)-2-
nitroethyl]carbamate (6jd)
White solid, 42.1 mg, 99% yield, dr=98:2, m.p. =169-171 ℃,
White solid, 45.1 mg, 99% yield, dr=97:3, m.p. =181-182 ℃,
2
0
20
[a]
D
= 29.6 (c = 0.5, CHCl
3
), The ee value was 99% [Chi-
[a]
D
= 37 (c = 0.6, CHCl ), The ee value was 96% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
ralpak IA-3, hexane/i-PrOH = 80:20, 254 nm, 1.0 mL/min,
Major-anti-(tmajor =9.68 min., tminor =36.58 min),Minor-syn-
(tmajor =26.66 min., tminor =10.57 min)]. H NMR (400 MHz,
Major-anti-(tmajor =16.20 min., tminor =20.86 min), Minor-syn-
1
1
(
t
major =43.19 min., tminor =12.67 min)]. H NMR (300 MHz,
CDCl
7
1
3
) δ 7.55 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 7.9 Hz, 2H),
.41 – 7.22 (m, 5H), 5.74 (br, 1H), 5.63 (br, 1H), 4.85 (br,
H), 1.27 (s, 9H). Analytical and spectral data were in agree-
CDCl ) δ 7.55 (d, J = 8.3 Hz, 2H), 7.46 (d, J = 8.3 Hz, 2H),
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
7.30 (d, J = 7.8 Hz, 1H), 6.89 (dd, J = 12.5, 7.8 Hz, 3H), 5.74
(d, J = 9.6 Hz, 1H), 5.61 (br, 1H), 4.76 (d, J = 9.4 Hz, 1H),
3.80 (s, 3H), 1.27 (s, 9H). Analytical and spectral data were in
8
ment with the literature data.
8
agreement with the literature data.
Tert-butyl [(1S,2R)-2-nitro-1-phenyl-2-(p-tolyl)ethyl]carbamate
(
6ae)
Tert-butyl
[(1S,2R)-1,2-bis(4-bromophenyl)-2-
nitroethyl]carbamate (6hd)
White solid, 35.5 mg, 99% yield, dr=99:1, m.p. =184-186 ℃,
2
0
[a]
D
= 91.6 (c = 0.5, CHCl
3
), The ee value was 99% [Chi-
White solid, 50 mg, 99% yield, dr=97:3, m.p. =183-185 ℃,
2
0
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
[a]
D
= -13.2 (c = 0.5, CHCl ), The ee value was 99% [Chi-
3
Major-anti-(tmajor =16.32 min., tminor =15.14 min), Minor-syn-
ralpak IA-3, hexane/EtOH = 90:5, 230 nm, 1.0 mL/min, Ma-
jor-anti-( tmajor =23.64 min., tminor =15.92 min), Minor-syn-
(tmajor =69.55 min., tminor =29.89 min)]. H NMR (300 MHz,
1
(
tmajor =25.18 min., tminor =11.36 min)]. H NMR (300 MHz,
1
CDCl
3
) δ 7.44 (d, J = 8.2 Hz, 2H), 7.40 – 7.30 (m, 5H), 7.21
(
d, J = 7.9 Hz, 2H), 5.73 (d, J = 9.9 Hz, 1H), 5.66 (d, J = 8.4
CDCl ) δ 7.63 – 7.53 (m, 2H), 7.53 – 7.47 (m, 2H), 7.43 (d, J
3
Hz, 1H), 4.76 (br, 1H), 2.37 (s, 3H), 1.26 (s, 9H). Analytical
and spectral data were in agreement with the literature data.
= 8.6 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 5.74 (d, J = 9.5 Hz,
1H), 5.56 (t, J = 9.6 Hz, 1H), 4.82 (br, 1H), 1.28 (s, 9H).
Analytical and spectral data were in agreement with the litera-
8
Tert-butyl
[(1S,2R)-2-(4-methoxyphenyl)-2-nitro-1-
7
ture data.
phenylethyl]carbamate (6af)
Tert-butyl
(6oa)
[(1R,2S)-1-nitro-1,4-diphenylbutan-2-yl]carbamate
White solid, 37.1 mg, 99% yield, dr=99:1, m.p. =181-182 ℃,
2
0
[a]
D
= 38.8 (c = 0.5, CHCl ), The ee value was 91% [Chi-
3
ralpak IA-3, hexane/i-PrOH = 90:10, 210nm, 1.0 mL/min,
White solid, 34 mg, 91% yield, dr=94:6, m.p. =133-134 ℃,
2
0
Major-anti-(tmajor =22.83 min., tminor =19.13 min), Minor-syn-
[a]
D
= 10.4 (c = 0.5, CHCl ), The ee value was 97% [Chi-
3
1
(
t
major =37.92 min., tminor = 15.12 min)]. H NMR (300 MHz,
ralpak AD-H, hexane/i-PrOH = 95:5, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =26.57 min., tminor =38.17 min), Minor-syn-
CDCl
3
) δ 7.58 – 7.48 (m, 2H), 7.43 – 7.32 (m, 5H), 7.00 –
.89 (m, 2H), 5.72 (t, J = 13.3 Hz, 2H), 4.79 (br, 1H), 3.85 (s,
H), 1.30 (s, 9H). Analytical and spectral data were in agree-
1
6
3
(tmajor =33.70 min., tminor =42.41 min)]. H NMR (300 MHz,
CDCl
(d, J = 6.9 Hz, 1H), 7.14 (d, J = 6.8 Hz, 2H), 5.65 (s, 1H),
.55 – 4.27 (m, 2H), 2.89 – 2.74 (m, 1H), 2.72 – 2.56 (m, 1H),
3
) δ 7.46 – 7.34 (m, 5H), 7.30 (d, J = 6.8 Hz, 1H), 7.21
8
ment with the literature data.
4
Tert-butyl
[(1S,2R)-2-(naphthalen-2-yl)-2-nitro-1-
1
3
1.94 (br, 2H), 1.33 (s, 9H). C NMR (75 MHz, CDCl ) δ
3
phenylethyl]carbamate (6ag)
155.0, 140.7, 132.2, 129.9, 128.9, 128.7, 128.5, 128.4, 126.3,
93.7, 80.1, 53.3, 32.8, 32.3, 28.3. HRMS (ESI): calculated for
White solid, 39.1 mg, 99% yield, dr=98:2, m.p. =183-186 ℃,
2
0
[a]
D
= 45.6 (c = 0.5, CHCl
3
), The ee value was 96% [Chi-
+
+
C
21
H
26
N
2
O
4
Na ([M+Na] ) 393.1785. Found 393.1777. Abso-
lute and relative configurations were assigned on the analogy of
aa.
ralpak IA-3, hexane/i-PrOH = 90:10, 210 nm, 1.0 mL/min,
Major-anti-(tmajor =30.77 min., tminor =25.86 min),Minor-syn-
6
1
(
t
major =35.52 min., tminor =14.65 min)]. H NMR (300 MHz,
Derivatization of 6aa and 6ea
CDCl
Hz, 1H), 7.59 – 7.48 (m, 2H), 7.44 – 7.33 (m, 5H), 5.97 (d, J
9.9 Hz, 1H), 5.78 (br, 1H), 4.80 (d, J = 8.5 Hz, 1H), 1.16 (s,
H). Analytical and spectral data were in agreement with the
3
) δ 8.03 (s, 1H), 7.93 – 7.81 (m, 3H), 7.69 (d, J = 8.5
To a solution of 6aa (34.2 mg, 0.10 mmol) in anhydrous
=
MeOH (0.5 mL) was added NiCl
at room temperature. The mixture solution was cooled to 0 ℃
before NaBH (56.7 mg, 1.50 mmol) was added in portions.
The reaction mixture was then stirred for 2 h and poured into a
saturated aqueous solution of NH Cl. The aqueous phase was
extracted with ethyl acetate (5 mL) twice. The combined or-
ganic phases were washed with brine and dried over Na SO
2
·6H O (23.8 mg, 0.10 mmol)
2
9
8
literature data.
4
Tert-butyl [(1S,2R)-2-(2-fluorophenyl)-1-(4-methoxyphenyl)-2-
nitroethyl]carbamate (6jb)
4
White solid, 38.5 mg, 98% yield, dr=99:1, m.p. =145-146 ℃,
2
4
2
0
[a]
D
= 72 (c = 0.35, CHCl ), The ee value was 98% [Chi-
3
and filtered. After concentration, the resulting residue was
purified by column chromatography on silica gel (PE/EA=2:1
as eluent) to give 7aa.
ralpak IA-3, hexane/i-PrOH = 10:1, 210 nm, 1.0 mL/min,
1
Major-anti-(tmajor =18.52 min., tminor =16.50 min)]. H NMR
(
400 MHz, CDCl
3
) δ 7.79 (t, J = 7.3 Hz, 1H), 7.46 – 7.36 (m,
To a solution of 7aa (31.2 mg, 0.10 mmol) in anhydrous
1
7
2
3
H), 7.30 (t, J = 7.9 Hz, 1H), 7.23 (d, J = 7.7 Hz, 1H), 7.16 –
.09 (m, 1H), 6.95 (d, J = 7.6 Hz, 1H), 6.88 (d, J = 8.3 Hz,
CH
2
2
Cl (0.15 mL) was added trifluoroacetic acid (0.15 mL) at
0 ℃. The reaction mixture was then stirred for 2 h and poured
into an ice-cooled 1 N aqueous solution of NaOH. The aque-
H), 6.19 (d, J = 10.3 Hz, 1H), 5.70 (br, 1H), 4.82 (br, 1H),
19
.81 (s, 3H), 1.23 (s, 9H). F NMR (376 MHz, CDCl
3
) δ -
ous phase was extracted with CH
2
2
Cl (5 mL) twice. The com-
ACS Paragon Plus Environment

Page 9 of 10
The Journal of Organic Chemistry
bined organic phases were washed with brine and dried over
MgSO and filtered. After concentration, the resulting residue
was purified by column chromatography on silica gel
Corresponding Author
E-mail: linyj@jlu.edu.cn.
*E-mail: duanhf@jlu.edu.cn.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
4
*
(PE/EA=1:2 as eluent) to give 8aa.
Notes
The authors declare no competing financial interest.
Determination of the ee value of 8ea
To a solution of 8ea (5 mg，1 equiv) in anhydrous CH
mL) was added Et N (6 μL，2 equiv) and m-toluoylchloride
3 μL，1.1 equiv) at rt. The reaction mixture was then stirred
for 20 min and poured into a saturated aqueous solution of
NH Cl. Take the organic phase 100 μL. After concentration,
2
2
Cl (1
ACKNOWLEDGMENT
3
We thank the financial support from the National Natural Science
Foundation of China (No. 51373067), and Science and Technol-
ogy Development Project of Jilin Province (No. 20140520085JH).
(
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
dissolved in 1 mL of isopropanol, determination by HPLC.
REFERENCES
Tert-butyl [(1S,2R)-2-amino-1,2-diphenylethyl]carbamate (7aa)
(1) (a) Kizirian, J.-C., Chem. Rev. 2008, 108, 140-205; (b) Lucet, D.; Le
Gall, T.; Mioskowski, C., Angew. Chem. Int. Ed. 1998, 37, 2580-2627; (c)
Ghosh, U.; Ganessunker, D.; Sattigeri, V. J.; Carlson, K. E.; Mortensen, D.
J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A., Biorg. Med. Chem.
2003, 11, 629-657; (d) Saibabu Kotti, S. R. S.; Timmons, C.; Li, G., Chem.
Biol. Drug Des. 2006, 67, 101-114.
20
White solid, 25.6 mg, 82% yield, dr=99:1, [a]
D
= 67 (c = 0.35,
CHCl ), The ee value was 99% [Chiralpak AD-H, hexane/i-
3
PrOH = 97:3, 210 nm, 1.0 mL/min, Major-anti-(tmajor =10.44
min., tminor = 11.58 min).
(2) (a) Kim, H.; Nguyen, Y.; Yen, C. P.-H.; Chagal, L.; Lough, A. J.; Kim,
1
H NMR (300 MHz, DMSO-d
6
) δ 7.46 – 7.06 (m, 12H), 4.54
B. M.; Chin, J., J. Am. Chem. Soc. 2008, 130, 12184-12191; (b) Kise, N.;
Ueda, N., Tetrahedron Lett. 2001, 42, 2365-2368; (c) Zhong, Y.-W.; Izumi,
K.; Xu, M.-H.; Lin, G.-Q., Org. Lett. 2004, 6, 4747-4750; (d) Tamura, K.;
Kumagai, N.; Shibasaki, M., Eur. J. Org. Chem. 2015, 2015, 3026-3031; (e)
Roskamp, E. J.; Pedersen, S. F., J. Am. Chem. Soc. 1987, 109, 3152-3154;
(3) (a) Cardona, F.; Goti, A., Nat Chem 2009, 1, 269-275; (b) Funk, T. W.;
Berlin, J. M.; Grubbs, R. H., J. Am. Chem. Soc. 2006, 128, 1840-1846; (c)
Surry, D. S.; Buchwald, S. L., Chem. Sci. 2010, 1, 13-31; (d) Miyazaki, M.;
Uoto, K.; Sugimoto, Y.; Naito, H.; Yoshida, K.; Okayama, T.; Kawato, H.;
Miyazaki, M.; Kitagawa, M.; Seki, T.; Fukutake, S.; Aonuma, M.; Soga, T.,
Biorg. Med. Chem. 2015, 23, 2360-2367.
(4) (a) Proskurnina, M. V.; Lozinskaya, N. A.; Tkachenko, S. E.; Zefirov,
N. S., Russ. J. Org. Chem. 2002, 38, 1149-1153; (b) Hatano, B.; Ogawa, A.;
Hirao, T., J. Org. Chem. 1998, 63, 9421-9424; (c) De, C. K.; Seidel, D., J.
Am. Chem. Soc. 2011, 133, 14538-14541.
(5) (a) Davis, T. A.; Vilgelm, A. E.; Richmond, A.; Johnston, J. N., J. Org.
Chem. 2013, 78, 10605-10616; (b) Vara, B. A.; Mayasundari, A.; Tellis, J.
C.; Danneman, M. W.; Arredondo, V.; Davis, T. A.; Min, J.; Finch, K.;
Guy, R. K.; Johnston, J. N., J. Org. Chem. 2014, 79, 6913-6938; (c)
Walvoord, R. R.; Kozlowski, M. C., Tetrahedron Lett. 2015, 56, 3070-3074;
(d) Westermann, B., Angew. Chem. Int. Ed. 2003, 42, 151-153
(
t, J = 8.8 Hz, 1H), 3.97 (d, J = 8.4 Hz, 1H), 1.60 (br, 2H),
.18 (s, 9H). C NMR (101 MHz, DMSO-d6) δ 154.5, 143.9,
1
3
1
1
2
3
41.4, 127.8, 127.6, 127.5, 126.8, 126.5, 99.5, 77.5, 60.8, 59.6,
+
8.1. HRMS (ESI): calculated for C19
13.1911, found 313.1903.
H
25
N
2
O
2
[M+H] :
Tert-butyl
[(1S,2R)-2-amino-1-(3-chlorophenyl)-2
phe-
nylethyl]carbamate (7ea)
20
White solid, 26 mg, 75% yield, dr=98:2, [a]
D
= -17 (c = 0.2,
CHCl
3
), The ee value was 98% [Chiralpak IA-3, hexane/i-
PrOH = 90:10, 210 nm, 0.5 mL/min, Major-anti-(tmajor =20.39
1
min., tminor = 22.88 min). H NMR (300 MHz, CD
3
OD) δ 7.43
–
7.19 (m, 9H), 4.85 (br, 1H), 4.79 (d, J = 7.8 Hz, 1H), 4.11
13
(
d, J = 8.7 Hz, 1H), 1.27 (s, 9H). C NMR (75 MHz, CD
δ 157.1, 144.0, 142.3, 135.4, 131.0, 129.4, 129.1, 128.9, 128.8,
28.7, 127.2, 80.4, 61.5, 61.0, 28.6. HRMS (ESI): calculated
3
OD)
1
+
for C19
H24ClN
2
O
2
[M+H] : 347.1521, found 347.1521.
(
1R,2S)-1,2-diphenylethane-1,2-diamine (8aa)
(6) (a) Marqués-López, E.; Merino, P.; Tejero, T.; Herrera, R. P., Eur. J.
Org. Chem. 2009, 2009, 2401-2420. (b) Noble, A.; Anderson, J. C., Chem.
Rev. 2013, 113, 2887-2939; (c) Fini, F.; Sgarzani, V.; Pettersen, D.;
Herrera, R. P.; Bernardi, L.; Ricci, A., Angew. Chem. Int. Ed. 2005, 44,
7975-7978; (d) Johnson, K. M.; Rattley, M. S.; Sladojevich, F.; Barber, D.
M.; Nuñez, M. G.; Goldys, A. M.; Dixon, D. J., Org. Lett. 2012, 14, 2492-
2495; (e) Wang, H.-Y.; Zhang, K.; Zheng, C.-W.; Chai, Z.; Cao, D.-D.;
Zhang, J.-X.; Zhao, G., Angew. Chem. Int. Ed. 2015, 54, 1775-1779;
1
White solid, 19.3 mg, 97% yield, H NMR (300 MHz, CDCl3)
1
3
δ 7.34 – 7.16 (m, 10H), 4.10 (s, 2H), 1.55 (s, 4H). C NMR
(
(
2
101 MHz, CDCl3) δ 143.5, 128.2, 127.0, 126.9, 61.9. HRMS
+
ESI): calculated for C14
13.1380.
(1S,2R)-1-(3-chlorophenyl)-2-phenylethane-1,2-diamine (8ea)
H
17
2
N [M+H] : 213.1386, found
(7) Davis, T. A.; Johnston, J. N., Chem. Sci. 2011, 2, 1076-1079.
20
White solid, 22.9 mg, 94% yield, [a]
D
= 89 (c = 0.5, CHCl
3
),
(8) Uraguchi, D.; Oyaizu, K.; Noguchi, H.; Ooi, T., Chem. Asian J. 2015,
10, 334-337.
The ee value was 98% [Chiralpak IC-3, hexane/i-PrOH/EtOH
= 80:14:6, 254 nm, 0.5 mL/min, Major-anti-(tmajor =12.21 min.,
(9) For unfavourable effect of external bases on the diastereo- and
enantioselectivity of asymmetric reaction, see: (a) Liu, Y.; Wang, X.; Wang,
X.; He, W., Org. Biomol. Chem. 2014, 12, 3163-3166; (b) Ma, C.-H.; Kang,
T.-R.; He, L.; Liu, Q.-Z., Eur. J. Org. Chem. 2014, 2014, 3981-3985.
(10) (a) Cao, D.; Chai, Z.; Zhang, J.; Ye, Z.; Xiao, H.; Wang, H.; Chen, J.;
Wu, X.; Zhao, G., Chem. Commun. 2013, 49, 5972-5974; (b) Jiang, X.;
Zhang, Y.; Wu, L.; Zhang, G.; Liu, X.; Zhang, H.; Fu, D.; Wang, R., Adv.
Synth. Catal. 2009, 351, 2096-2100; (c) Palomo, C.; Oiarbide, M.; Laso, A.;
López, R., J. Am. Chem. Soc. 2005, 127, 17622-17623; (d) Wang, H.-Y.;
Chai, Z.; Zhao, G., Tetrahedron 2013, 69, 5104-5111; (e) Wang, H.-Y.;
Zhang, J.-X.; Cao, D.-D.; Zhao, G., ACS Catal. 2013, 3, 2218-2221.
1
t
minor = 12.76 min). H NMR (300 MHz, CDCl
3
) δ = 7.57 – 7.00
13
(m, 9H), 4.12 – 3.89 (m, 2H), 1.51 (br, 4H). C NMR (75
MHz, CDCl ) δ 145.3, 142.6, 134.5, 129.7, 128.6, 127.9, 127.6,
127.7, 127.65, 126.1, 62.8, 62.5. HRMS (ESI): calculated for
3
+
C
14
H
16ClN [M+H] : 247.0997, found 247.1002.
2
ASSOCIATED CONTENT
(11) (a) Wang, B.; Liu, Y.; Sun, C.; Wei, Z.; Cao, J.; Liang, D.; Lin, Y.;
Supporting Information
Duan, H., Org. Lett. 2014, 16, 6432-6435; (b) Wang, B.; He, Y.; Fu, X.;
Wei, Z.; Lin, Y.; Duan, H., Synlett 2015, 26, 2588-2592.
(12) Cassani, C.; Martin-Rapun, R.; Arceo, E.; Bravo, F.; Melchiorre, P.,
Nat. Protoc. 2013, 8, 325-344.
Detailed experimental procedures including complete characteri-
1
13
zations ( H NMR and C NMR spectra, spectral data, and
HRMS).This material is available free of charge via the Internet at
http://pubs.acs.org.
(
1
13) (a) Wenzel, A. G.; Jacobsen, E. N., J. Am. Chem. Soc. 2002, 124,
2964-12965. (b) Huang, L.; Wulff, W. D., J. Am. Chem. Soc. 2011, 133,
8892-8895. (c) Mecozzi, T.; Petrini, M., J. Org. Chem. 1999, 64, 8970-8972.
AUTHOR INFORMATION
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 10
(14) Walvoord, R. R.; Berritt, S.; Kozlowski, M. C., Org. Lett. 2012, 14,
4
086-4089.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
ACS Paragon Plus Environment