Novel α-amino acid-derived phase-transfer catalyst application to a highly enantio- and diastereoselective nitro-Mannich reaction

Article abstract of DOI:10.1039/c7ob02501g

New quaternary ammonium types of bifunctional asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors derived from α-amino acids were readily prepared and found to be highly efficient in the asymmetric nitro-Mannich reactions of amidosulfones. Very broad substrate generality was observed, and the products were achieved in high enantio-/diastereoselectivities (90->99.9% ee, 90:10 to 92:8 dr). Compared with previous reports, the enantioselectivity of aliphatic amidosulfones has been improved to a high level (91-93% ee).

Full text of DOI:10.1039/c7ob02501g

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Y. liu, Z. Wei, Y.
Liu, J. Cao, D. Liang, Y. Lin and H. duan, Org. Biomol. Chem., 2017, DOI: 10.1039/C7OB02501G.
This is an Accepted Manuscript, which has been through the
Volume 14 Number
1 7 January 2016 Pages 1–372
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 9
View Article Online
DOI: 10.1039/C7OB02501G
Journal Name
ARTICLE
Novel α-Amino Acid-derived Phase-Transfer Catalysts Application
to Highly Enantio-and diastereoselective Nitro-Mannich Reaction
Yuxin Liua, Zhonglin Wei, Yu Liu, Jungang Cao, Dapeng Liang, and Yingjie Lin*a, Haifeng Duan*a
Received 00th January 20xx,
Accepted 00th January 20xx
The new quaternary ammonium type of bifunctional asymmetric phase-transfer catalysts bearing multiple hydrogen-
bonding donors derived from α-amino acids were readily prepared and found to be highly efficient in asymmetric nitro-
Mannich reactions of amidosulfones. Very broad substrate generality was observed, and the products were achieved in
high enantio-/diasteroselectivities (90−>99.9% ee, 90:10 to 92:8 dr). Compared with previous reports, the
enantioselectivity of aliphatic amidosulfones have been improved to a high level (91-93% ee).
DOI: 10.1039/x0xx00000x
www.rsc.org/
satisfying results, however, aliphatic aldehyde-derived
amidosulfones were less investigated and the results were
unsatisfactory. Compared with cinchona alkaloids, α-amino
Introduction
The multiple hydrogen-bonding strategy used in the synthesis
of organic catalysts has attracted increasing attention in recent
years, compared with single and double hydrogen-bonding
donors catalysts, the multiple H-bonding donors catalysts
acids, an inexpensive and accessible chiral source, have been
designed as chiral catalysts and successfully applied to a series
of asymmetric reactions.46-48. In this context, developing
accessible and efficient amino acid-derived phase transfer
catalysts with multiple hydrogen bonding donors are feasible
and desirable.
generally
displayed
higher
activity
and
better
enantioselectivity in epoxidation reaction1, 2, Henry reaction3,
Michael reaction4-9, Mannich reaction10, aldol reaction11-17 and
others. Based on this strategy, a number of asymmetric
organocatalysts have been designed, such as ureas18,
thioureas1-8 and squaramides9, 10. However, these catalysts,
which usually contained an organic tertiary amine unit, are
usually used in some weak base-catalyzed or weak acid-
catalyzed reactions. Chiral catalysts bearing multiple hydrogen-
bonding donors and suitable for strong base catalysis, such as
bifunctional phase-transfer catalysts, are rarely synthesized
In previous works, we have developed a series of bifuctional
chiral phase transfer catalysts derived from cinchona alkaloids
and amino alcohols, and successfully applied to asymmetric
nitro-Mannich reactions of amidosulfones.18, 21 In spite of this,
this kind of bifunctional chiral phase transfer catalysts are still
limited, and the skeleton of catalysts mainly focus on superior
cinchona alkaloids. It is well known that amino acids are one of
inexpensive and accessible chiral resources49. Theoretically,
using amino acid derivatives as chiral skeletons and hydrogen
bonding donors, we can construct a variety of structurally
and applied18-21
.
The asymmetric nitro-Mannich reaction22-24 is one of the most
powerful C−C bond formaꢀon methodologies. The addition
products of this reaction can easily be transformed into vicinal
variable
chiral quaternary ammonium salts containing
multiple hydrogen-bonding donors. In terms of their
applicability, these novel quaternary ammonium salts may be
diamines25-30 and α-amino acids31. In previous reported works
23, 29, 32-45
a kind of effective phase transfer catalysts for some
on asymmetric nitro-Mannich
, most of successful
conventional and challenging asymmetric reactions by
structural screening and optimization. Based on this design
strategy, we have synthesized a series of chiral phase transfer
catalysts derived from amino acids. In the nitro-Mannich
reaction of amidosulfones, these bifunctional chiral phase-
transfer catalysts with multiple hydrogen bonding donors
exhibited better asymmetric catalytic activity. It is noteworthy
that aliphatic aldehyde-derived amidosulfones, which usually
dose not match with previously reported amino acid-derived
catalysts, are aslo accomodated with these phase transfer
catalysts. Herein, we would like to report our results.
catalysts for this reaction are based on the skeleton of
cinchona alkaloids29, 33, 35, 42, but chiral α-amino acids as chiral
source is rare. To the best of our knowledge, only amino acid-
derived bifunctional thiourea-ammonium46 and thiourea-
phosphonium47 catalysts have been reported by Zhao’s group,
and applied to asymmetric nitro-Mannich reaction. In this
methodology, aromatic aldehyde-derived amidosulfones gave
a.Address here.
b.Address here.
c. Address here.
Starting from known (S)-N,N,3,3-tetramethylbutane-1,2-
diamine, the catalysts can be easily prepared through the
three steps reaction as outlined in Scheme 1. (S)-N,N,3,3-
† Footnotes relaꢀng to the ꢀtle and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 9
View Article Online
DOI: 10.1039/C7OB02501G
ARTICLE
Journal Name
tetramethylbutane-1,2-diamine was synthesized from L-tert-
leucine in four steps as reported.50 Firstly, (S)-N,N,3,3-
tetramethylbutane-1,2-diamine was transformed with N,N′-
carbonyldiimidazole to the corresponding carbamoylimidazole
Table 1. Optimization of reaction conditions
1; then treatment of
1 with various β-aminoalcohols gave rise
to ureas 2 bearing multiple H-bonding donors under basic
[b]
entry [a]
cat.
x (%)
solvent
yield
(%)
ee[c]
(%)
conditions. Subsequently, the crude product directly
quaternized with various benzyl bromides to afford catalysts
3a−3f
.
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3f
5
5
5
5
5
5
5
5
5
toluene
toluene
toluene
toluene
toluene
toluene
CHCl3
92
95
96
93
93
94
96
96
92
11
Scheme 1. Synthesis of the Catalysts
91
94
88
93
94
95
93
94
3c
3c
3c
CH2Cl2
m-xylene
10
3c
3c
3c
3c
5
MTBE
CHCl3
CHCl3
CHCl3
90
80
97
75
75
94
95
96
11
2.5
5
12[d]
13[e]
5
[a] Reactions were conducted at 0.15 mmol scale in
1.5 mL of solvent. [b] Yield of isolated product. [c]
Determined by HPLC using a chiral stationary phase.
[d] the reactions was performed with 3 equiv KOH. [e]
the reactions was performed with 1.5 equiv KOH.
Table 2. Optimization of catalysts using 3-
phenylpropanal-derived amidosulfone as substrate
With catalysts 3a−3f in hand, we investigated the reaction of
amidosulfone 4a with nitromethane 5a in the presence of 5
equivalent of KOH at −20 °C in toluene (Table 1). Initially,
screening of catalysts 3a-3d was performed, and it was found
that catalyst 3c with L-phenylalaninol gave the best result
(entry 2, 94% ee), catalysts 3b were also efficient and gave
similar results with 3c (entries 1−4). By comparison, L-
phenylalaninol and L-phenylglycinol used as multiple hydrogen
bonding donors were better than D-phenylglycinol and
diphenylglcinol, which indicated that matching the chirality is
very important (entries 1−4). Subsequently, chosing L-
phenylalaninol as multiple hydrogen-bonding donors and
replacing the benzyl moiety with 3,5-di-tert-butylbenzyl and 4-
bromobenzyl respectively, we synthesized catalysts 3e and 3f.
Although catalysts 3e and 3f exhibited high catalytic activity,
the yield and enantioselectivity of product have no further
improvement (entries 5−6). In the sceening of solvents, CHCl3
have a good effect on reaction results, and the ee value of
product was increased up to 95%. Similarly, dichlormethane
and m-xylene also gave the high enantioselectivity (entries
7−10). When the catalyst loading was reduced to 2.5
equivalent, high enantioselectivity was still achieved but the
yield of product dropped to 80% (94% ee, entry 11 ). In the
presence of only 3 equivalent of KOH, high enantioselectivity
and yield was still achieved (95% ee, 97% yield, entries 12).
When
[b]
entry [a]
cat.
x (%)
solvent
yield
(%)
90
ee[c]
(%)
81
80
81
91
1
2
3
4
3c
3e
3f
5
5
5
5
CHCl3
CHCl3
CHCl3
CHCl3
89
87
3b
95
[a] Reactions were conducted at 0.15 mmol scale in
1.5mL of solvent. [b] Yield of isolated product. [c]
Determined by HPLC using a chiral stationary phase.
further reduced the equivalent of
KOH to 1.5, high
enantioselectivity was still achieved but the yield of product
dropped to 75% (96% ee, entry 11 ). Compare with aromatic
amidosulfones, aliphatic amidosulfones used as substrates
were poorly studied and gave unsatisfactory results under the
catalysis of amino-derived catalysts reported in earlier works.
To our delight, when 3-phenylpropanal-drived amidosulfone
was used as substrate, catalysts 3b with L-phenylglycinol gave
a higher level of enantiocontrol after the screening of
catalysts (Table 2, entries 1−3, 91% ee, entry 4).
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 3 of 9
View Article Online
DOI: 10.1039/C7OB02501G
Journal Name
ARTICLE
Table 3. Substrate Scope of asymmetric nitro-Mannich Reaction
cat. 5 mol %
KOH (5 equiv)
Boc
R1
Boc
NH
NH
R2
NO2
R2
CHCl3 (0.1 M)
-20 °C, 12 h
R1
SO2Ph
(5 equiv)
NO2
4
5
6
dr [d]
ee[c] (%)
entry [a]
cat.
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3c
3b
3b
3b
3b
3c
3c
4
R1
5
R2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
Et
6
yield [b] (%)
96
1
4a
4b
4c
4d
4e
4f
Ph
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5a
5b
5c
6a
6b
6c
6d
6e
6f
95
2
p-MeC6H4
99
>99.9
>99.9
95
3
p-MeOC6H4
p-ClC6H4
95
4
96
5
p-BrC6H4
93
95
6
p-CF3C6H4
o-FC6H4
99
95
7
4g
4h
4i
6g
6h
6i
99
90
8
o-MeOC6H4
m-ClC6H4
m-OMeC6H4
β-naphthyl
2-furyl
98
95
9
97
98
10
11
12 e)
13
14
15
16
17
18
4j
6j
95
>99.9
97
4k
4l
6k
6l
93
99
92
4m
4n
4o
4p
4a
4a
phenyl ethyl
isobutyl
ethyl
6m
6n
6o
6p
6q
6r
95
91
97
93
98
91
propyl
Ph
99
92
99
90:10
92:8
95
Ph
99
95
[a] Unless otherwise noted, all reactions were conducted at 0.15 mmol scale in 1.5 mL of CHCl3. [b]Yield of isolated
product. [c] Determined by HPLC using a chiral stationary phase. [d] Determined by chiral HPLC analysis. [e]The reaction
conducted at -30°C.
After above optimization of reaction conditions, the scope of substrates show excellent reactivity and gave the
reaction substrates was further explored under optimal corresponding products in high enantioseclectivity. Finally,
conditions. A series of amidosulfones and nitroalkanes were other nitroalkanes were also investigated under the identical
investigated and corresponding results were listed in Table 3. conditions. Nitroethane 5b and nitropropane 5c showed the
In all cases, excellent yields (93−99%) and excellent ee values same reactivity, and excellent yields (99%) and high enantio-
(90−>99.9% ee) were obtained. The aromaꢀc amidosulfones /diasteroselectivities (95% ee, 90:10 dr; 95% ee, 92:8 dr) were
with either electron-rich or -poor groups were well performed obtained. We have tried aliphatic amidosulfones with ester,
(entries 1−10), and the posiꢀon of the subsꢀtuent on the amide, protected alcohol, unfortunately, we did not get good
aromatic ring had little effect on the reaction (entry 4 vs 9, 3 results. The relevant data can be found in the supporting
vs 8 and 10). Poly- and heteroaromatic substrates were also information.
well tolerated (entries 11 −12). In the development of aliphaꢀc To investigate the role of the quaternary ammonium center
aldehyde-drived amidosulfones, it is gratifying that these and multiple H-bonding donors in this kind of bifunctional
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 9
View Article Online
DOI: 10.1039/C7OB02501G
ARTICLE
Journal Name
catalysts, and gain insight into the catalytic mechanism of the excellent enantioselectivities. Especially, aliphatic aldehyde-
catalysts, two control experiments were performed using derived amidosulfones were also tolerated and the yield and
compounds 3g and 2a as catalysts respectively (Scheme 2). enantioselectivity of proudcts were impoved in a high level.
Compared with catalyst 3b, catalyst 3g, in which the hydroxyl Preliminary mechanism study shows that both the quaternary
group was protected by methylation, have lower ammonium center and the hydroxyl on amino alcohols moiety
stereocontrol ability and gave product 6a in 90% yield with are crucial for the bifunctional phase transfer catalysts to
lower 44% ee. Similarly, catalyst 2a, in absence of a quaternary possess high catalytic activity and enantiocontrol. Detail
ammonium center, exhibited a significant decrease in catalytic mechanism study on this reaction, and further application of
amino acid-derived bifunctional phase transfer catalysts
Scheme 2. Control Experiment for Mechanistic Study
bearing multiple hydrogen bonding donors are underway in
our laboratory.
Experimental
General Information
Unless otherwise stated, all reagents were purchased from
commercial suppliers and used without purification. All
solvents were obtained from commercial sources and were
purified according to standard procedures. For thin-layer
chromatography (TLC), silica gel plates (HSGF 254) were used
and compounds were visualized by irradiation with UV light.
Purification of reaction products was carried out by flash
column chromatography using silica gel (200-300 mesh). 1H
and 13C NMR spectra were recorded on a Varian Mercury-
activity and enantiocontrol ability, and gave a nearly racemic
product in 71% yield. These results supported synergistic
catalysis of bifunctional catalysts and indicated that both the
hydroxy on the phenylglycinol moiety and the quaternary
ammonium center were crucial to achieve excellent catalytic
activity and stereoselectivity in this asymmetric nitro-Mannich
reaction.
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 relative to the
resonance of the deuterated solvent as the internal standard
(CDCl3, δ 7.26 ppm for proton NMR, δ 77.16 ppm for carbon
NMR; CD3OD-d4, δ 3.31 ppm for proton NMR, δ 49.00 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 coupling 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 AD-H column, Chiracel OD-H column,
Chiracel AS-H column and Chiracel IA-3 column. Optical
rotations were measured on a Shanghai ShenGuang SGW-2
Polarimeter at λ = 589 nm. Optical rotations are reported as
follows: [α] D25 (c = g/100 mL, solvent).
Scheme 3. Derivatization of 6a To the Corresponding
acetylated product 8 and 1,2-Diamine 9
The addition products of this nitro-Mannich reaction are
valuable intermediates, they can easily be transformed into
vicinal diamines. To indicate this, two transformations
experiments were performed using optically pure 6a. First, via
Starting materials
(S)-N1,N1,3,3-tetramethylbutane-1,2-diamine was prepared
according to reported procedure.50 Known amidosulfones
were prepared using reported procedures from corresponding
aldehydes.51-53 All aminoalcohols was purchased from
commercial suppliers and used directly.
a nickelboride mediated reduction of nitro-group to get
Followed, acetylate of to give the compound . Or the
removal of Boc of in the presence of trifluoroacetic acid to
7.
7
8
7
get 1,2-Diamine 9.
Preparation and characterization of the chiral Catalysts with
multiple Hydrogen-Bonding Donors.
Conclusions
General Procedure
In summary, we have developed a novel kind of bifunctional
phase-transfer catalysts bearing multiple H-bonding donors
derived from α-amino acids, and successfully applied them to
the nitro-Mannich reactions of amidosulfones. A variety of
amidosulfones and nitroalkanes were investigated and
corresponding products were obtained in excellent yields with
N, N’-carbonyldiimidazole (185 mg, 1.14 mmol, 1.1 equiv) was
dissolved in anhydrous THF (6 mL), a solution of (S)-N1,N1,3,3-
tetramethylbutane-1,2-diamine (150 mg, 1.04 mmol, 1equiv)
in THF (6 mL) was added dropwise in 1 h, the reaction mixture
was stirred for another 1 h. Then aminoalcohol (1.1 equiv) and
triethylamine (160 uL, 1.1 equiv) were added in one portion
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 5 of 9
View Article Online
DOI: 10.1039/C7OB02501G
Journal Name
ARTICLE
respectively, the resulting mixture was stirred until TLC HRMS (ESI): calculated for C24H36N3O2 [M-Br]+: 398.2802,
showed that the reaction was completed. The mixture was found 398.2802.
diluted with 40 ml ethylacetate, then washed with water (S)-N-benzyl-2-(3-((S)-1-hydroxy-3-phenylpropan-2-yl)ureido)-
(10×15 mL), the organic phase was dried over Na2SO4. The N,N,3,3-tetramethylbutan-1-aminium bromide (3c)
solvent was removed under reduced pressure. The crude catalysts 3c derived from L-Phenylalaninoll and benzyl bromide
product was purified by flash chromatography (CH2Cl2/MeOH = Obtained according to the general procedure
10:1) to get urea
the next step. Under N2 protection, The crude product (150mg, (c = 0.5, CHCl3).
2. The crude product was also directly used in White solid, 165mg, 72% yield, mp = 106-107 ℃
, [a]D25 = -60.8
1 equiv) was dissolved in THF (0.1 M), then the corresponding 1H NMR (300 MHz, CD3OD) δ 7.63 – 7.40 (m, 5H), 7.32 – 6.98
benzyl bromide (1.1 equiv) was added, the mixture was heated (m, 5H), 4.56 – 4.46 (m, 1H), 4.46 – 4.38 (m, 1H), 4.14 – 3.95
to reflux, after 12 h the mixture was concentrated and purified (m, 2H), 3.66 – 3.48 (m, 3H), 3.30 – 3.25 (m, 1H), 2.95 (dd, J =
by flash chromatography (CH2Cl2/MeOH=30:1).
1-((S)-1-(dimethylamino)-3,3-dimethylbutan-2-yl)-3-((S)-2-
hydroxy-1-phenylethyl)urea (2b)
13.7, 4.9 Hz, 1H), 2.90 (s, 3H), 2.74 (s, 3H), 2.58 (dd, J = 13.7,
10.1 Hz, 1H), 0.95 (s, 9H).
13C NMR (126 MHz, MeOD) δ 158.18, 138.94, 133.08, 130.60,
129.14, 129.08, 129.02, 128.94, 128.38, 127.89, 127.42, 125.81,
Urea 2b derived from L-phenylglycinol
White solid, 281mg, 83% yield, mp = 34-35
0.5, CHCl3).
℃
, [a]D25 = -5.2 (c = 68.56, 66.36, 64.37, 53.01, 52.84, 52.34, 48.95, 37.73, 35.84,
25.10.
1H NMR (300 MHz, CDCl3) δ 7.43 – 7.20 (m, 5H), 5.63 (brs, 2H), HRMS (ESI): calculated for C25H38N3O2 [M-Br]+: 412.2959,
4.99 – 4.63 (m, 1H), 3.93 – 3.74 (m, 2H), 3.65 (br, 1H), 2.75 (t, J found 412.2958.
= 11.5 Hz, 1H), 2.45 (dd, J = 12.6, 3.6 Hz, 1H), 2.30 (s, 6H), 1.81 (S)-N-benzyl-2-(3-((1R,2S)-2-hydroxy-1,2-diphenylethyl)
(s, 1H), 0.86 (s, 9H).
13C NMR (126 MHz, CDCl3) δ 159.46, 140.77, 128.68, 128.66, catalysts
127.50, 127.46, 126.87, 67.57, 67.38, 57.54, 44.26, 34.68, diphenylethanol and benzyl bromide
29.77, 26.41, 23.76. White solid, 130mg, 60% yield, mp = 137-138
HRMS (ESI): calculated for C17H30N3O2 [M+H]+: 308.2333, found (c = 0.5, CHCl3)
ureido)-N,N,3,3-tetramethylbutan-1-aminium bromide (3d)
3d derived from (1S, 2R)-2-Amino-1,2-
℃
, [a]D25 = -36.4
308.2333.
1H NMR (300 MHz, CD3OD) δ 7.64 – 7.50 (m, 5H), 7.34 – 7.02
(m, 10H), 5.05 (d, J = 7.2 Hz, 1H), 4.83 (d, J = 6.6 Hz, 1H), 4.57
(d, J = 12.9 Hz, 1H), 4.49 (d, J = 12.5 Hz, 1H), 3.98 (d, J = 9.3 Hz,
(S)-N-benzyl-2-(3-((R)-2-hydroxy-1-phenylethyl)ureido)-
N,N,3,3-tetramethylbutan-1-aminium bromide (3a)
catalysts 3a derived from D-phenylglycinol and benzyl bromide 1H), 3.60 (d, J = 13.7 Hz, 1H), 3.41 – 3.31 (m, 1H), 2.94 (s, 3H),
Obtained according to the general procedure
White solid, 178mg, 76% yield, mp = 117-118
(c = 0.5, CHCl3).
2.83 (s, 3H), 0.89 (s, 9H).
, [a]D25 = -25.2 13C NMR (126 MHz, MeOD) δ 158.98, 143.29, 141.80, 134.40,
131.96, 128.99, 128.90, 128.77, 128.49, 128.35, 128.14, 77.78,
℃
1H NMR (300 MHz, CD3OD) δ 7.67 – 7.49 (m, 5H), 7.39 – 7.19 70.00, 67.72, 60.53, 53.74, 50.37, 36.97, 26.32.
(m, 5H), 4.85 – 4.77 (m, 1H), 4.69 (d, J = 12.7 Hz, 1H), 4.61 (d, J HRMS (ESI): calculated for C30H40N3O2 [M-Br]+: 474.3115,
= 12.7 Hz, 1H), 4.16 – 4.05 (m, 1H), 3.78 – 3.65 (m, 2H), 3.60 found 474.3116.
(dd, J = 11.1, 7.4 Hz, 1H), 3.48 (dd, J = 13.8, 9.5 Hz, 1H), 3.09 (s, (S)-N-(3,5-di-tert-butylbenzyl)-2-(3-((S)-1-hydroxy-3-
3H), 3.07 (s, 3H), 0.97 (s, 9H).
phenylpropan-2-yl)ureido)-N,N,3,3-tetramethylbutan-1-
13C NMR (126 MHz, MeOD) δ 159.95, 142.08, 134.38, 131.94, aminium bromide (3e)
130.31, 129.42, 128.80, 128.24, 127.69, 70.14, 68.06, 66.87, catalysts 3e derived from L-Phenylalaninoll and 3,5-di-tert-
61.50, 57.56, 53.90, 50.46, 37.09, 26.41.
butylbenzyl bromide
HRMS (ESI): calculated for C24H36N3O2 [M-Br]+: 398.2802, White solid, 174mg, 61% yield, mp = 232-233
℃
, [a]D25 = -46.8
found 398.2803.
(c = 0.5, CHCl3)
1H NMR (300 MHz, CD3OD) δ 7.65 (t, J = 1.7 Hz, 1H), 7.39 (d, J =
(S)-N-benzyl-2-(3-((S)-2-hydroxy-1-phenylethyl)ureido)-
N,N,3,3-tetramethylbutan-1-aminium bromide (3b)
1.7 Hz, 2H), 7.22 – 7.09 (m, 4H), 7.06 – 6.96 (m, 1H), 4.52 (d, J =
catalysts 3b derived from L-phenylglycinol and benzyl bromide 12.5 Hz, 1H), 4.45 (d, J = 12.5 Hz, 1H), 4.10 – 3.93 (m, 2H), 3.62
Obtained according to the general procedure
White solid, 182mg, 78% yield, mp = 120-122
(c = 0.5, CHCl3).
– 3.48 (m, 3H), 3.30 – 3.22 (m, 1H), 2.99 – 2.93 (m, 1H), 2.92 (s,
, [a]D25 = -39.3 3H), 2.73 (s, 3H), 2.59 (dd, J = 13.8, 10.2 Hz, 1H), 1.38 (s, 18H),
0.94 (s, 9H).
℃
1H NMR (300 MHz, CD3OD) δ 7.65 – 7.39 (m, 5H), 7.36 – 6.93 13C NMR (126 MHz, MeOD) δ 159.52, 153.19, 140.26, 130.40,
(m, 5H), 4.82 – 4.74 (m, 1H), 4.61 (d, J = 12.7 Hz, 1H), 4.46 (d, J 129.14, 128.75, 128.09, 127.02, 125.70, 71.24, 67.54, 65.63,
= 12.7 Hz, 1H), 4.19 – 4.03 (m, 1H), 3.75 (dd, J = 11.1, 5.0 Hz, 54.23, 53.56, 50.18, 50.09, 39.02, 37.21, 35.85, 31.80, 26.36.
1H), 3.71 – 3.63 (m, 2H), 3.51 (dd, J = 13.5, 9.6 Hz, 1H), 2.97 (s, HRMS (ESI): calculated for C33H54N3O2 [M-Br]+: 524.4211,
3H), 2.93 (s, 3H), 1.00 (s, 9H).
found 524.4210.
13C NMR (126 MHz, MeOD) δ 159.91, 142.66, 134.30, 131.88, (S)-N-(4-bromobenzyl)-2-(3-((S)-1-hydroxy-3-phenylpropan-2-
130.26, 129.37, 128.66, 128.21, 127.74, 69.59, 68.36, 66.61, yl)ureido)-N,N,3,3-tetramethylbutan-1-aminium bromide (3f)
57.87, 53.86, 50.53, 50.27, 37.10, 26.41.
catalysts 3f derived from L-Phenylalaninoll and 4-bromobenzyl
bromide
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 9
View Article Online
DOI: 10.1039/C7OB02501G
ARTICLE
Journal Name
White solid, 165mg, 62% yield, mp = 118-120
℃
, [a]D25 = -58.8 hexane/i-PrOH = 97:3, 214 nm, 0.8mL/min, tmajor = 46.12 min,
tminor = 48.78 min).
(c = 0.5, CHCl3)
1H NMR (300 MHz, CD3OD) δ 7.73 (d, J = 8.3 Hz, 2H), 7.42 (d, J 1H NMR (300 MHz, CDCl3) δ 7.18 (s, 4H), 5.39 – 5.28 (m, 1H),
= 8.4 Hz, 2H), 7.24 – 7.11 (m, 4H), 7.10 – 7.00 (m, 1H), 4.50 (d, J 5.20 (br, 1H), 4.92 – 4.77 (m, 1H), 4.68 (dd, J = 12.6, 5.7 Hz, 1H),
= 12.7 Hz, 1H), 4.41 (d, J = 12.8 Hz, 1H), 4.10 – 3.94 (m, 2H), 2.34 (s, 3H), 1.44 (s, 9H).
3.63 – 3.50 (m, 3H), 3.30 – 3.23 (m, 1H), 2.95 (dd, J = 13.8, 4.6 Analytical and spectral data were in agreement with the
Hz, 1H), 2.89 (s, 3H), 2.74 (s, 3H), 2.58 (dd, J = 13.8, 10.3 Hz, literature data.35
1H), 0.95 (s, 9H).
Tert-butyl [(1S)-1-(4-methoxylphenyl)-2-nitroethyl]carbamate
13C NMR (126 MHz, MeOD) δ 159.54, 140.27, 136.15, 133.53, (6c)
130.44, 129.21, 127.90, 127.14, 126.47, 68.89, 67.88, 65.64, White solid, 42mg, 95% yield, mp = 104-106
℃
, [a]D25 = 26 (c =
54.31, 53.71, 50.50, 50.26, 39.04, 37.16, 26.36.
0.5, CHCl3), the ee value was >99.9% (Chiralpak OD-H,
HRMS (ESI): calculated for C25H37BrN3O2 [M-Br]+: 490.2064, hexane/i-PrOH = 90:10, 214 nm, 0.7 mL/min, tmajor = 45.82 min,
found 490.2062.
tminor = 41.98 min).
(S)-N-benzyl-2-(3-((S)-2-methoxy-1-phenylethyl)ureido)-
N,N,3,3-tetramethylbutan-1-aminium bromide (3g)
catalysts 3g derived from L-phenylglycinol and benzyl bromide
Obtained according to the general procedure
1H NMR (300 MHz, CDCl3) δ 7.34 – 7.27 (m, 1H), 6.93 – 6.78 (m,
3H), 5.43 – 5.29 (m, 1H), 5.26 (br, 1H), 4.91 – 4.74 (m, 1H), 4.69
(dd, J = 12.7, 5.5 Hz, 1H), 3.81 (s, 3H), 1.44 (s, 9H).
Analytical and spectral data were in agreement with the
White solid, 125mg, 54% yield, mp = 117-118
(c = 0.5, CHCl3).
1H NMR (300 MHz, CD3OD) δ 7.63 – 7.38 (m, 5H), 7.37 – 7.07 White solid, 44 mg, 96% yield, m.p. = 95-96
℃
, [a]D25 = -18.4 literature data.35
Tert-butyl (1S)-[1-4-chlorophenyl)-2-nitroethyl]carbamate (6d)
25
, [a]D = 26.4 (c
℃
(m, 5H), 4.98 – 4.90 (m, 1H), 4.60 (d, J = 12.6 Hz, 1H), 4.46 (d, J = 0.5, CHCl3),The ee value was 95% (Chiralpak AD-H, hexane/i-
= 12.6 Hz, 1H), 4.11 (d, J = 9.5 Hz, 1H), 3.67 (d, J = 13.8 Hz, 1H), PrOH = 90:10, 214 nm, 0.7 mL/min, tmajor = 18.55 min, tminor
=
3.63 – 3.43 (m, 3H), 3.34 (s, 3H), 2.96 (s, 3H), 2.93 (s, 3H), 1.00 23.83 min).
(s, 9H).
1H NMR (400 MHz, CDCl3) δ 7.40 – 7.29 (m, 2H), 7.26 – 7.09 (m,
13C NMR (126 MHz, MeOD) δ 158.42, 143.83, 141.18, 139.37, 2H), 5.33 (br, 2H), 4.83 (br, 1H), 4.69 (dd, J = 12.8, 4.7 Hz, 1H),
132.91, 130.52, 128.90, 127.95, 127.29, 126.85, 126.30, 75.43, 1.44 (s, 9H).
68.20, 67.00, 57.78, 54.04, 52.46, 49.13, 48.85, 35.73, 24.99.
Analytical and spectral data were in agreement with the
HRMS (ESI): calculated for C25H38BrN3O2 [M-Br]+: 412.2959, literature data.47
found 412.2961.
Tert-butyl (1S)-[1-(4-bromophenyl)-2-nitroethyl]carbamate
General procedure for enantio- and diastereoselective nitro- (6e)
Mannich reaction
Without protection of inert gases, catalyst 3c or 3b (5mol%) = 0.5, CHCl3), the ee value was 95% (Chiralpak AD-H, hexane/i-
White solid, 48 mg, 93% yield, mp = 130-131 ℃
, [a]D25 = 14.0 (c
and amidosulfones (0.15 mmol) were dissolved in dry PrOH = 90:10, 214 nm, 0.7 mL/min, tmajor = 20.84 min, tminor
chloroform (1.5ml ), nitoalkane (0.75 mmol, 5 eq.) was added, 27.09 min).
=
the mixture was cooled to –20 °C, freshly grounded KOH (42.1 1H NMR (300 MHz, CDCl3) δ 7.55 – 7.44 (m, 2H), 7.22 – 7.05 (m,
mg, 5 eq.) was added in one portion, the resulting suspention 2H), 5.33 (br, 2H), 4.81 (br, 1H), 4.74 – 4.60 (m, 1H), 1.44 (s,
was vigorously stirred at –20 °C. After 12 h, 2 ml sat. aq. 9H).
NaHCO3 was added and the solution was allowed to warm to Analytical and spectral data were in agreement with the
room temperature, the aqueous was extracted with literature data.47
ethylacetate (3×5ml), then the organic layer was dried over Tert-butyl
Na2SO4, filtered and concentrated under reduced pressure. carbamate (6f)
(1S)-[1-(4-trifluoromethylphenyl)-2-nitroethyl]
The crude product was purified by flash chromatography White solid, 49.6 mg, 99% yield, mp = 163-164
℃
, [a]D25 = 13.6
(PE/EA).
(c = 0.5, CHCl3), the ee value was 95% (Chiralpak AD-H,
hexane/i-PrOH = 90:10, 214 nm, 0.7 mL/min, tmajor = 14.98 min,
Tert-butyl [(1S)-2-nitro-1-phenylethyl]carbamate (6a)
White solid, 38.3 mg, 96% yield, mp = 103-104
(c = 0.5, CHCl3), the ee value was 95% (Chiralpak AD-H, 1H NMR (300 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 2H), 7.45 (d, J =
℃
, [a]D25 = 24.4 tminor = 23.14 min).
hexane/i-PrOH = 95:5, 214 nm, 0.8mL/min, tmajor = 33.61min, 8.1 Hz, 2H), 5.42 (br, 2H), 4.85 (br, 1H), 4.80 – 4.67 (m, 1H),
tminor = 35.50 min).
1.44 (s, 9H).
1H NMR (300 MHz, CDCl3) δ 7.42 – 7.27 (m, 5H), 5.45 – 5.32 (m, Analytical and spectral data were in agreement with the
1H), 5.26 (br, 1H), 4.93 – 4.78 (m, 1H), 4.71 (dd, J = 12.6, 5.6 Hz, literature data.47
1H), 1.44 (s, 9H).
Tert-butyl
(1S)-[1-(2-fluorophenyl)-2-nitroethyl]carbamate
Analytical and spectral data were in agreement with the (6g)
literature data.35
White solid, 42mg, 99% yield, mp = 102-103
0.5, CHCl3), the ee value was 90% (Chiralpak AD-H, hexane/i-
PrOH = 90:10, 214 nm, 0.7 mL/min, tmajor = 19.36 min, tminor
℃
, [a]D25 = 36.4 (c 16.40 min).
℃
, [a]D25 = 28 (c =
Tert-butyl [(1S)-1-(4-methylphenyl)-2-nitroethyl]carbamate
(6b)
=
White solid, 42 mg, 99% yield, mp = 114-116
= 0.5, CHCl3), the ee value was >99.9% (Chiralpak AD-H,
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 7 of 9
View Article Online
DOI: 10.1039/C7OB02501G
Journal Name
ARTICLE
1H NMR (400 MHz, CDCl3) δ 7.42 – 7.28 (m, 2H), 7.20 – 7.03 (m, 1H NMR (300 MHz, CDCl3) δ 7.40 – 7.34 (m, 1H), 6.37 – 6.28 (m,
2H), 5.83 – 5.29 (m, 2H), 4.95 – 4.79 (m, 1H), 4.72 (dd, J = 12.6, 2H), 5.64 – 5.38 (m, 2H), 5.25 (br, 1H), 4.98 – 4.79 (m, 1H), 4.73
5.4 Hz, 1H), 1.44 (s, 9H).
Analytical and spectral data were in agreement with the Analytical and spectral data were in agreement with the
literature data.47 literature data.47
Tert-butyl [(1S)-1-(2-methoxylphenyl)-2-nitroethyl]carbamate (S)-Tert-butyl (1-nitro-4-phenylbutan-2-yl)carbamate (6m)
(dd, J = 12.9, 5.8 Hz, 1H), 1.46 (s, 9H).
(6h)
White solid, 41.9 mg, 95% yield, mp = 104-105
℃
, [a]D25 = 58.8 (c = 0.5, CHCl3), the ee value was 91% (Chiralpak AD-H,
℃
, [a]D25 = -40
White solid, 43.5 mg, 98% yield, mp = 130-132
(c = 0.5, CHCl3), the ee value was 95% (Chiralpak AD-H, hexane/i-PrOH = 90:10, 214 nm, 0.8 mL/min, tmajor = 12.93 min,
hexane/i-PrOH = 90:10, 214 nm, 0.7 mL/min, tmajor = 23.76 min, tminor = 12.13 min).
tminor = 25.47 min).
1H NMR (300 MHz, CDCl3) δ 7.36 – 7.26 (m, 2H), 7.26 – 7.10 (m,
1H NMR (400 MHz, CDCl3) δ 7.35 – 7.27 (m, 1H), 7.26 – 7.20 (m, 3H), 4.85 (br, 1H), 4.54 (br, 2H), 4.18 – 4.02 (m, 1H), 2.87 –
1H), 6.99 – 6.89 (m, 2H), 5.70 (br, 1H), 5.58 (br 1H), 4.87 – 4.76 2.62 (m, 2H), 2.00 – 1.80 (m, 2H), 1.46 (s, 9H).
(m, 1H), 4.75 – 4.58 (m, 1H), 3.90 (s, 3H), 1.44 (s, 9H).
Analytical and spectral data were in agreement with the
Analytical and spectral data were in agreement with the literature data.42
literature data.54
(S)-Tert-butyl (4-methyl-1-nitropentan-2-yl)carbamate (6n)
Tert-butyl [(1S)-1-(2-chlorophenyl)-2-nitroethyl]carbamate (6i) White solid, 34.5 mg, 93% yield, mp = 68-69
25
White solid, 44.9 mg, 97% yield, mp = 83-84℃, [a]D = 39.6 (c = 0.5, CHCl3), the ee value was 93% (Chiralpak AD-H, hexane/i-
℃
, [a]D25 = -59.2 (c
= 0.5, CHCl3), the ee value was 98% (Chiralpak AD-H, hexane/i- PrOH = 90:10, 214 nm, 0.8 mL/min, tmajor = 8.57 min, tminor
=
PrOH = 90:10, 214 nm, 0.7 mL/min, tmajor = 14.860 min, tminor
18.755 min).
=
7.43min).
1H NMR (300 MHz, CDCl3) δ 4.75 (br, 1H), 4.52 (br, 2H), 4.26 –
1H NMR (300 MHz, CDCl3) δ 7.39 – 7.27 (m, 3H), 7.23 – 7.14 (m, 4.09 (m, 1H), 1.81 – 1.61 (m, 1H), 1.44 (s, 9H), 1.39 – 1.27 (m,
1H), 5.35 (br, 2H), 4.94 – 4.76 (m, 1H), 4.75 – 4.60 (m, 1H), 1.44 1H), 0.95 (d, J = 1.5 Hz, 3H), 0.93 (d, J = 1.4 Hz, 3H).
(s, 9H).
Analytical and spectral data were in agreement with the
Analytical and spectral data were in agreement with the literature data.42
literature data.47
(S)-Tert-butyl (1-nitrobutan-2-yl)carbamate (6o)
Tert-butyl [(1S)-1-(3-methoxyphenyl)-2-nitroethyl]carbamate White solid, 32.5 mg, 99% yield, mp = 58-59
℃
, [a]D25 = -35.2 (c
(6j)
= 0.5, CHCl3), the ee value was 93% (Chiralpak AD-H, hexane/i-
, [a]D25 = 40.8 (c PrOH = 95:5, 214 nm, 1mL/min, tmajor = 11.92 min, tminor = 10.23
White solid, 43 mg, 98% yield, mp = 153-154
℃
= 0.5, CHCl3), the ee value was >99.9% (Chiralpak AD-H, min).
hexane/i-PrOH = 90:10, 214 nm, 0.8 mL/min, tmajor = 24.72 min, 1H NMR (300 MHz, CDCl3) δ 7.36 – 7.26 (m, 2H), 7.26 – 7.10 (m,
tminor = 26.37 min).
3H), 4.86 (br, 1H), 4.54 (br, 2H), 4.18 – 4.02 (m, 1H), 2.87 –
1H NMR (300 MHz, CDCl3) δ 7.25 – 7.19 (m, 2H), 6.94 – 6.85 (m, 2.62 (m, 2H), 2.00 – 1.80 (m, 2H), 1.46 (s, 9H).
2H), 5.39 – 5.25 (m, 1H), 5.19 (br, 1H), 4.83 (br, 1H), 4.66 (dd, J Analytical and spectral data were in agreement with the
= 12.5, 5.9 Hz, 1H), 3.80 (s, 3H), 1.44 (s, 9H).
Analytical and spectral data were in agreement with the (S)-Tert-butyl (1-nitropentan-2-yl)carbamate (6p)
literature data.54 , [a]D25 = -36.4 (c
White solid, 34.6 mg, 99% yield, mp = 74-75
Tert-butyl [(1S)-1-(naphthalen-1-yl)-2-nitroethyl]carbamate = 0.5, CHCl3), the ee value was 93% (Chiralpak AD-H, hexane/i-
literature data.42
℃
(6k)
PrOH = 90:10, 214 nm, 1mL/min, tmajor = 9.15 min, tminor = 8.22
℃, [a]D = 66.8(c min).
25
White solid, 46mg, 98% yield, mp = 152-153
= 0.5, CHCl3), the ee value was 97% (Chiralpak AD-H, hexane/i- 1H NMR (300 MHz, CDCl3) δ 4.80 (br, 1H), 4.52 (br, 2H), 4.18 –
PrOH = 90:10, 214 nm, 0.8 mL/min, tmajor = 25.79 min, tminor
31.78 min).
=
4.04 (m, 1H), 1.59 – 1.50 (m, 2H), 1.44 (s, 9H), 1.41 – 1.22 (m,
2H), 0.94 (t, J = 7.2 Hz, 3H).
1H NMR (300 MHz, CDCl3) δ 7.90 – 7.79 (m, 3H), 7.77 (s, 1H), Analytical and spectral data were in agreement with the
7.57 – 7.48 (m, 2H), 7.40 (dd, J = 8.6, 1.7 Hz, 1H), 5.65 – 5.47 literature data.42
(m, 1H), 5.39 (br, 1H), 4.93 (br, 1H), 4.80 (dd, J = 12.8, 5.6 Hz, Tert-butyl [(1S, 2R)-2-nitro-1-phenylpropyl]carbamate (6q)
1H), 1.45 (s, 9H).
White solid, 41.6 mg, 99% yield, a mixture of diastereomers (dr
Analytical and spectral data were in agreement with the = 90:10, determined by HPLC analysis of the purified product),
literature data.47
25
mp = 137-138 ℃, [a]D = 24.4 (c = 0.5, CHCl3), the ee value
Tert-butyl [(1S)-1-( furan-2-yl)-2-nitroethyl]carbamate (6l) (at was 95% [Chiralpak AD-H, hexane/i-PrOH = 90:10, 214 nm,
-30
℃
)
0.8mL/min, major-anti-(tmajor = 13.77 min, tminor = 14.98 min),
, [a]D25 = -32.4 (c minor-syn-(tmajor = 21.49 min, tminor = 17.57 min)].
White solid, 25.4 mg, 99% yield, mp = 92-93
= 0.5, CHCl3), the ee value was 92% (Chiralpak AD-H, hexane/i- 1H NMR (300 MHz, CDCl3) δ 7.41 – 7.27 (m, 3H), 7.25 – 7.18 (m,
℃
PrOH = 90:10, 214 nm, 0.7 mL/min, tmajor = 13.21 min, tminor
14.03 min).
=
2H), 5.31 (br, 1H), 5.19 (dd, J = 8.8, 5.7 Hz, 1H), 4.91 (br, 1H),
1.53 (d, J = 6.8 Hz, 3H), 1.43 (s, 9H).
Analytical and spectral data were in agreement with the
literature data.47
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 8 of 9
View Article Online
DOI: 10.1039/C7OB02501G
ARTICLE
Journal Name
Tert-butyl [(1S, 2R)-2-nitro-1-phenylbutyl]carbamate (6r)
basified with with 1M NaOH and extracted with CH2Cl2 (3 × 5
White solid, 43.6 mg, 99% yield, a mixture of diastereomers (dr mL). The combined organic layers were washed with brine,
= 92:8, determined by HPLC analysis of the purified product), dried over MgSO4. After evaporation under reduced pressure,
25
mp = 181-183 ℃, [a]D = 34.8 (c = 0.5, CHCl3), the ee value the residue was purified by silica gel flash column
was 95% [Chiralpak AS-H, hexane/i-PrOH = 90:10, 214 nm, 0.5 chromatography (CH2Cl2/MeOH = 3/1) to give 1,2-diamine 9.
mL/min, major-anti-(tmajor = 15.42 min, tminor = 17.90 min), (S)-1-phenylethane-1,2-diamine (9)
minor-syn-(tmajor =13.82 min, tminor = 19.72 min)].
1H NMR (300 MHz, CDCl3) δ 7.41 – 7.28 (m, 3H), 7.26 – 7.17 (m, 0.5, CHCl3), To a solution of 1,2-diamine
2H), 5.13 (br, 2H), 4.73 (br, 1H), 2.14 – 2.00 (m, 1H), 1.95 – CH2Cl2 (1 mL), 10μL m-toluoyl chloride were added at room
1.81 (m, 1H), 1.43 (s, 9H), 0.98 (t, J = 7.4 Hz, 3H). temperature. After stirring for 20 min at room temperature,
Analytical and spectral data were in agreement with the evaporation under reduced pressure, the residue was directly
literature data.47
used for HPLC. The ee value was 95% (Chiralpak IA-3, hexane/i-
White solid, 21 mg, 91% yield, mp = 81-82
℃
, [a]D25 = 78.8 (c =
(5mg, 0.36 mmol) in
9
To a solution of 6a (64 mg, 1 equiv) in MeOH (2.0 mL), PrOH = 90:10, 214 nm, 1 mL/min, tmajor = 9.652 min, tminor
=
NiCl2·6H2O (56 mg, 1 equiv) and NaBH4 (45 mg, 5 equiv) was 26.343 min).
added at 0 °C. After stirring for 1 h at 0 °C, the reaction mixture 1H NMR (500 MHz, CDCl3) δ 7.37 – 7.22 (m, 5H), 4.00 – 3.90 (m,
was quenched with sat. aq. NH4Cl and extracted with CH2Cl2 (4 1H), 2.94 (dd, J = 12.6, 4.7 Hz, 1H), 2.85 (dd, J = 12.6, 7.5 Hz,
× 10 mL). The combined organic layers were washed with brine, 1H), 2.70 (s, 4H).
dried over MgSO4. After evaporation under reduced pressure, 13C NMR (126 MHz, CDCl3) δ 139.24, 128.63, 127.41, 126.49,
the residue was purified by silica gel flash column 57.67, 49.24.
chromatography (CH2Cl2/MeOH = 6/1) to give 1,2-diamine
Tert-butyl (S)-(2-amino-1-phenylethyl)carbamate 7)
White solid, 48 mg, 85% yield, mp = 68-69
, [a]D25 = 74.8 (c =
0.5, CHCl3), the ee value was 95% (Chiralpak 0D-H, hexane/i-
7
.
HRMS (ESI): calculated for C8H13N2 [M+H]+: 137.1073, found
(
137.1073.
℃
Conflicts of interest
PrOH = 80:20, 214 nm, 1mL/min, tmajor = 5.068 min, tminor
4.365 min).
1H NMR (500 MHz, CDCl3) δ 7.41 – 7.30 (m, 2H), 7.30 – 7.23 (m,
3H), 5.42 (br, 1H), 4.68 (br, 1H), 3.15 – 2.87 (m, 2H), 1.86 (s,
2H), 1.43 (s, 9H).
13C NMR (126 MHz, CDCl3) δ 155.70, 140.80, 128.67, 127.41,
126.44, 79.58, 56.42, 47.15, 28.37.
HRMS (ESI): calculated for C13H21N2O2 [M+H]+: 237.1598, found
237.1600.
=
There are no conflicts to declare.
Acknowledgements
We thank the financial support from the National Natural
Science Foundation of China (No. 51373067)
To a solution of 1,2-diamine
mL), Ac2O (30μL, 2 equiv) and Et3N (39μL, 1 equiv) were added
at room temperature. After stirring for at room
7 (32.1mg, 1 equiv) in CH2Cl2 (4
Notes and references
‡Footnotes relating to the main text should appear here. These
might include comments relevant to but not central to the
matter under discussion, limited experimental and spectral data,
and crystallographic data.
§
§§
etc.
1
h
temperature, the reaction mixture was quenched with sat. aq.
NH4Cl and extracted with ethylacetate (4 × 5 mL). The
combined organic layers were washed with brine and dried
over MgSO4. After evaporation under reduced pressure, the
residue was purified by silica gel flash column chromatography
1
Citations should appear here in the format A. Name, B.
Name and C. Name, Journal Title, 2000, 35, 3523; A. Name,
B. Name and C. Name, Journal Title, 2000, 35, 3523.
…
(CH2Cl2/MeOH = 20/1) to give acetylated product
colorless powder.
8 as a
2
Tert-butyl (S)-(2-amino-1-phenylethyl)carbamate (8)
3
White solid, 35.8 mg, 95% yield, mp = 68-69
= 0.5, CHCl3), the ee value was 95% (Chiralpak AD-H, hexane/i-
℃
, [a]D25 = 74.8 (c
1.
S. Meninno, A. Vidal-Albalat and A. Lattanzi, Org. Lett,
2015, 17, 4348-4351.
PrOH = 95:5, 214 nm, 0.6 mL/min, tmajor = 21.949 min, tminor
24.096 min).
=
2.
3.
4.
5.
6.
7.
N. Ji, J. Yuan, S. Xue, J. Zhang and W. He, Tetrahedron,
2016, 72, 512-517.
H. Li, X. Zhang, X. Shi, N. Ji, W. He, S. Zhang and B. Zhang,
Adv. Synth. Catal., 2012, 354, 2264-2274.
M. S. Manna, V. Kumar and S. Mukherjee, Chem.
Commun., 2012, 48, 5193-5195.
O. Bassas, J. Huuskonen, K. Rissanen and A. M. P.
Koskinen, Eur. J. Org. Chem. , 2009, 2009, 1340-1351.
M.-X. Zhao, W.-H. Tang, M.-X. Chen, D.-K. Wei, T.-L. Dai
and M. Shi, Eur. J. Org. Chem. , 2011, 2011, 6078-6084.
X. Shi, W. He, H. Li, X. Zhang and S. Zhang, Tetrahedron
Lett., 2011, 52, 3204-3207.
1H NMR (500 MHz, CDCl3) δ 7.38 – 7.24 (m, 5H), 6.23 (br, 1H),
5.51 (br, 1H), 4.78 (br, 1H), 3.83 – 3.23 (m, 2H), 1.96 (s, 3H),
1.42 (s, 9H).
13C NMR (126 MHz, CDCl3) δ 171.17, 156.18, 139.75, 128.82,
127.82, 126.38, 79.83, 55.35, 45.52, 28.33, 23.16.
HRMS (ESI): calculated for C15H22N2NaO3[M+Na]+: 301.1523,
found 301.1522.
To a solution of 1,2-diamine
7 (40mg,) in CH2Cl2 (0.6 mL),
CF3COOH (0.6 mL) were added at room temperature. After
stirring over night at room temperature, the reaction mixture
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 9 of 9
View Article Online
DOI: 10.1039/C7OB02501G
Journal Name
ARTICLE
8.
Y. Liu, X. Wang, X. Wang and W. He, Org. Biomol. Chem., 39.
2014, 12, 3163-3166.
Z. Dong, G. Qiu, H.-B. Zhou and C. Dong, Tetrahedron: 40.
Asymmetry, 2012, 23, 1550-1556.
M.-X. Zhao, H.-L. Bi, R.-H. Jiang, X.-W. Xu and M. Shi, Org. 41.
Lett, 2014, 16, 4566-4569.
C. Palomo, M. Oiarbide, R. Halder, A. Laso and R. López,
Angew. Chem. Int. Ed. , 2006, 45, 117-120.
R. Pedrosa, J. M. Andrés, D. P. Ávila, M. Ceballos and R.
Pindado, Green Chem., 2015, 17, 2217-2225.
M. T. Robak, M. Trincado and J. A. Ellman, J. Am. Chem.
Soc., 2007, 129, 15110-15111.
9.
10.
11.
Z. Tang, F. Jiang, L.-T. Yu, X. Cui, L.-Z. Gong, A.-Q. Mi, Y.-Z. 42.
Jiang and Y.-D. Wu, J. Am. Chem. Soc., 2003, 125, 5262-
Y. Wei, W. He, Y. Liu, P. Liu and S. Zhang, Org. Lett, 2012,
14, 704-707.
5263.
43.
44.
45.
X. Xu, T. Furukawa, T. Okino, H. Miyabe and Y. Takemoto,
Chem. Eur. J., 2006, 12, 466-476.
K. i. Yamada, S. J. Harwood, H. Gröger and M. Shibasaki,
Angew. Chem. Int. Ed. , 1999, 38, 3504-3506.
T. P. Yoon and E. N. Jacobsen, Angew. Chem., 2005, 117,
470-472.
12.
13.
S. Gandhi and V. K. Singh, J. Org. Chem., 2008, 73, 9411-
9416.
B. Wang, G.-h. Chen, L.-y. Liu, W.-x. Chang and J. Li, Adv.
Synth. Catal., 2009, 351, 2441-2448.
C. G. Kokotos, J. Org. Chem., 2012, 77, 1131-1135.
14.
15.
S. Fotaras, C. G. Kokotos and G. Kokotos, Org. Biomol. 46.
Chem., 2012, 10, 5613-5619.
H.-Y. Wang, Z. Chai and G. Zhao, Tetrahedron, 2013, 69,
5104-5111.
16.
17.
18.
19.
P. Revelou, C. G. Kokotos and P. Moutevelis-Minakakis, 47.
Tetrahedron, 2012, 68, 8732-8738.
I. Triandafillidi, A. Bisticha, E. Voutyritsa, G. Galiatsatou
D. Cao, Z. Chai, J. Zhang, Z. Ye, H. Xiao, H. Wang, J. Chen,
X. Wu and G. Zhao, Chem. Commun., 2013, 49, 5972-
5974.
Q.-W. Jin, Z. Chai, Y.-M. Huang, G. Zou and G. Zhao,
Beilstein J. Org. Chem., 2016, 12, 725-731.
J. M. Andrés, R. Manzano and R. Pedrosa, Chem. Eur. J.,
2008, 14, 5116-5119.
J. M. Andres, R. Manzano and R. Pedrosa, Chem. Eur. J.,
2008, 14, 5116-5119.
L. Huang and W. D. Wulff, J. Am. Chem. Soc., 2011, 133,
8892-8895.
and C. G. Kokotos, Tetrahedron, 2015, 71, 932-940.
B. Wang, Y. Liu, C. Sun, Z. Wei, J. Cao, D. Liang, Y. Lin and
H. Duan, Org. Lett, 2014, 16, 6432-6435.
Y. Sohtome, Y. Hashimoto and K. Nagasawa, Adv. Synth.
Catal., 2005, 347, 1643-1648.
48.
49.
50.
20.
21.
K. Manabe, Tetrahedron Lett., 1998, 39, 5807-5810.
N. Lu, R. Li, Z. Wei, J. Cao, D. Liang, Y. Lin and H. Duan, J. 51.
Org. Chem., 2017, 82, 4668-4676.
22.
23.
24.
25.
26.
27.
28.
29.
30.
B. Westermann, Angew. Chem. Int. Ed. , 2003, 42, 151- 52.
153.
T. Mecozzi and M. Petrini, J. Org. Chem., 1999, 64, 8970-
8972.
A. G. Wenzel and E. N. Jacobsen, J. Am. Chem. Soc., 2002,
124, 12964-12965.
X. Jiang, Y. Zhang, L. Wu, G. Zhang, X. Liu, H. Zhang, D. Fu
and R. Wang, Adv. Synth. Catal., 2009, 351, 2096-2100.
53.
E. Marqués‐López, P. Merino, T. Tejero and R. P.
Herrera, Eur. J. Org. Chem. , 2009, 2009, 2401-2420.
A. Noble and J. C. Anderson,Chem. Rev. , 2013, 113, 2887-
2939.
54.
D. H. Lloyd and D. E. Nichols, J. Org. Chem., 1986, 51,
4294-4295.
4
A. G. Barrett and C. D. Spilling, Tetrahedron Lett., 1988,
29, 5733-5734.
A. K. Beck and D. Seebach, Chem. Ber., 1991, 124, 2897-
2911.
M.-A. Poupart, G. Fazal, S. Goulet and L. T. Mar, J. Org.
Chem., 1999, 64, 1356-1361.
C. Palomo, M. Oiarbide, A. Laso and R. López, J. Am.
Chem. Soc., 2005, 127, 17622-17623.
E. Gomez-Bengoa, A. Linden, R. López, I. Múgica-
Mendiola, M. Oiarbide and C. Palomo, J. Am. Chem. Soc.,
2008, 130, 7955-7966.
31.
32.
H. W. Pinnick, Organic reactions, 1990.
T. A. Davis, J. C. Wilt and J. N. Johnston, J. Am. Chem. Soc.,
2010, 132, 2880-2882.
33.
34.
35.
F. Fini, V. Sgarzani, D. Pettersen, R. P. Herrera, L. Bernardi
and A. Ricci, Angew. Chem., 2005, 117, 8189-8192.
S. Handa, V. Gnanadesikan, S. Matsunaga and M.
Shibasaki, J. Am. Chem. Soc., 2007, 129, 4900-4901.
K. M. Johnson, M. S. Rattley, F. Sladojevich, D. M. Barber,
M. G. Nunez, A. M. Goldys and D. J. Dixon, Org. Lett, 2012,
14, 2492-2495.
36.
37.
38.
K. R. Knudsen, T. Risgaard, N. Nishiwaki, K. V. Gothelf and
K. A. Jørgensen, J. Am. Chem. Soc., 2001, 123, 5843-5844.
B. M. Nugent, R. A. Yoder and J. N. Johnston, J. Am. Chem.
Soc., 2004, 126, 3418-3419.
T. Okino, S. Nakamura, T. Furukawa and Y. Takemoto, Org.
Lett, 2004, 6, 625-627.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
Please do not adjust margins