Bronsted acid catalyzed enantio- and diastereoselective one-pot three component Mannich reaction

Article abstract of DOI:10.1016/j.tetasy.2015.09.006

A chiral derivative of 1,2-benzenedisulfonimide, (-)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide is herein proven to be an efficient chiral catalyst in a one pot three-component Mannich protocol. Reaction conditions are mild and green, while th

Full text of DOI:10.1016/j.tetasy.2015.09.006

Tetrahedron: Asymmetry 26 (2015) 1180–1188
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Brønsted acid catalyzed enantio- and diastereoselective one-pot
three component Mannich reaction
⇑
Margherita Barbero, Silvano Cadamuro, Stefano Dughera
Dipartimento di Chimica, Università di Torino, iC.so Massimo d’Azeglio 48, 10125 Torino, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
A chiral derivative of 1,2-benzenedisulfonimide, (ꢀ)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfon-
imide is herein proven to be an efficient chiral catalyst in a one pot three-component Mannich protocol.
Reaction conditions are mild and green, while the enantio- and diastereoselectivity are excellent.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 17 August 2015
Accepted 16 September 2015
Available online 8 October 2015
1. Introduction
It should be stressed that axially chiral Brønsted acids have also
found their place as efficient catalysts, providing very good dia-
Mannich reactions1 are among the most important carbon–
carbon bond forming reactions in synthetic organic chemistry
and are a standard method for the synthesis of b-amino carbonyl
compounds, which are key intermediates in the production of sev-
eral nitrogen containing natural products and pharmaceuticals.2
The reaction can be conducted either via a two or three-component
protocol.2
Three-component reactions have proven themselves to be a
most useful synthetic approach, as the combination of three-
components to generate new products in a single step provides
simple, mild and economically valid procedures, which synthesize
complex products along with the added advantages of atom
efficiency and waste reduction.3
For these reasons, a three-component approach to the Mannich
reaction which is carried out in the presence of various catalysts
and which sees imines formed in situ, has gained considerable
importance. A variety of catalysts have been used for this reaction
including Brønsted4 and Lewis acids5 (organic or mineral), Lewis
bases,6 ionic liquids,7 and many others.2 Catalysts that allow the
reaction to be carried out under mild and green conditions are
obviously favoured.
stereo- and enantioselectivity.8 Nevertheless, the majority of chiral
Brønsted acid catalyzed Mannich reactions are still run with imine
catalysis.10 In fact the literature only contains a few examples of
chiral Brønsted acid catalyzed one-pot three component Mannich
reactions.
The most significant are as follows: in 2007 Gong et al.11a
reported that an axially chiral phosphoric acid promoted an
anti-selective direct asymmetric Mannich reaction between
cyclohexanone and other heterocyclic ketones, aniline and
various aldehydes (18 examples) with good diastereo- (average
anti/syn ratio 87:13) and enantioselectivity (enantiomeric excess
over 75%; average 85%) while acyclic ketones (6 examples) gave
reasonably good enantioselectivity (enantiomeric excess over
70%; average 78%); it should be noted that to the best of our
knowledge, this is the only significant example of a one-pot
three component Brønsted acid catalyzed asymmetric Mannich
reaction carried out in the presence of acyclic and aromatic
ketones as Mannich donors.
In 2012 Zhang et al.11b demonstrated that a double axially chiral
bisphosphorylimide was a very efficient catalyst in furnishing
syn-b-aminoketones by reacting cyclohexanone, aniline and
various aldehydes (13 examples) with excellent diastereo-
(average syn/anti ratio over 99:1) and enantioselectivity
(enantiomeric excess over 90%; average 97%). Furthermore, in
2012 Enders et al.11c synthesized a new planar chiral Brønsted
acid, which was derived from [2.2]paracyclophane and tested it
in a direct asymmetric Mannich reaction between cyclohexanone,
4-nitrobenzaldehyde and aniline giving poor enantiomeric excess
(38%).
Chiral catalyst promoted stereoselective Mannich reactions
have also attracted considerable attention as they are a powerful
protocol for the enantioselective preparation of b-amino carbonyl
compounds.8 In particular, the literature shows that -proline8
L
(first introduced by List9a in his seminal work), several of its
derivatives,8 other chiral amines,8 thioureas8,9b and other chiral
organocatalytic systems are all excellent catalysts.8,9c,d
We have recently reported the use of o-benzenedisulfonimide 1
(Fig. 1) in catalytic amounts as a safe, non-volatile and non-corro-
sive Brønsted acid in several acid-catalyzed organic reactions, and
⇑
Corresponding author. Tel.: +39 0116707645; fax: +39 0116707642.
E-mail address: stefano.dughera@unito.it (S. Dughera).
http://dx.doi.org/10.1016/j.tetasy.2015.09.006
0957-4166/Ó 2015 Elsevier Ltd. All rights reserved.

M. Barbero et al. / Tetrahedron: Asymmetry 26 (2015) 1180–1188
1181
at rt and in the presence of 5% mol of 2, which gave b-aminoketone
6a in excellent yields and with excellent enantioselectivity (over
90%; entry 9).
Catalyst 2 was easily recovered and was reused in other two
consecutive reactions. The results are listed in Table 2 where it
can be seen that the yields and the enantioselectivity of 6a were
consistently good over the various runs.
O2
S
NH
O2
S
NH
S
S
O2
O2
1
(-)-2
Table 2
Consecutive runs with recovered (ꢀ)-2
Figure 1. o-Benzenedisulfonimide
benzenedisulfonimide 2.
1
and (ꢀ)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-
Entry
Time (h)
Yield (%) of 6aa,b
Recovery (%)
Ee (%) in 6a
of (ꢀ)-2
1
2
3
24
24
24
100
94
85
100, 11 mgc
91, 10 mgd
85, 8.5 mg
90.2
90.7
90.3
Ar'
O
O
NH
2
(-)-
ArCHO
Ar'NH2
+
+ R
R
Ar
a
Yields refer to the pure and isolated product.
b
The reaction was performed at rt with 0.5 mmol of 3a, 4a, 5a and 5 mol % of (ꢀ)
3
4
5
6: average ee over 90%
2 (11 mg, 0.025 mmol).
c
Recovered 2 was used as a catalyst in entry 2.
Recovered 2 was used as a catalyst in entry 3.
Scheme 1. Three-component Mannich reaction catalyzed by (ꢀ)-2.
d
obtained excellent results.12a The results and advantages of using
of o-benzenedisulfonimide 1 are very promising if one considers
its applications in the field of asymmetric catalysis. Therefore, a
chiral derivative of 1,2-benzenedisulfonimide, 4,5-dimethyl-3,6-
Encouraged by these excellent results and with the optimized
conditions in hand, a number of other aldehydes 3, aromatic ami-
nes 4 and ketones 5 with electron withdrawing or electron donat-
ing groups were reacted. Target adducts 6 were always obtained in
good yields and with excellent enantioselectivities (22 examples,
average yield 86%; average enantiomeric excess 94%) regardless
of the electronic effects of the substituents (Table 3), whereas their
position was crucial: the reaction did not occur in the presence of a
substituent at the ortho-position of 4 and 5 (Table 3; entries 10, 13
and 18), most likely due to the steric hindrance of these groups.
To further expand upon the scope of our work, we decided to
test cyclohexanone 5g as a carbonyl partner (Scheme 2).
bis(o-tolyl)-1,2-benzenedisulfonimide
2
(Fig. 1) has been
synthesized and its (ꢀ)-atropisomer has been demonstrated to
be an efficient chiral catalyst in Strecker reactions.12b
In light of this research and in order to further enhance the new
chiral catalyst (ꢀ)-2, we herein report our studies into a stereose-
lective three-component Mannich reaction between aromatic alde-
hydes 3, aromatic amines 4 and aromatic or aliphatic acyclic
ketones 5 carried out in the presence of chiral catalyst (ꢀ)-2
(Scheme 1).
2. Results and discussion
At first, 1 was used as a catalyst and little diastereoselectivity
was found when reacting 5g with 3a and 4a (Table 4, entry 2),
3b and 4a (Table 4, entry 4), 3a and 4c (Table 4, entry 8). However,
total diastereoselectivity was found when using (ꢀ)-2. In fact
the syn-diastereomer was formed exclusively (Table 4). The syn-
configuration was determined by comparing the chemical shift
The model reaction between benzaldehyde 3a, aniline 4a and
acetophenone 5a was initially studied in the presence of a catalytic
amount of (ꢀ)-2 and under various conditions. As reported in
Table 1, the best results were obtained in neat, green conditions,
Table 1
Trial reactions
Ph
O
O
NH
(-)-2
PhCHO + PhNH2
+
Ph
Ph
Ph
5a
6a
3a
4a
Entry
Solvent
2; mol %
Time (h)
Temperature (°C)
Yield (%) of 6aa,b
Eec (%)
d
1
2
3
4
5
6
7
8
Neat
—
5
5
5
5
5
5
10
5
5
24
24
24
24
24
24
8
50
Reflux
50
—
—
—
—
—
—
—
53.5
51.8
90.2
91.8
6.7
CH2Cl2
MeCN
THF
Toluene
H2O
Neat
Neat
Neat
48b,d
62b,d
25b,d
51b,d
12b,d
97e
50
50
50
50
50
rt
6
94e
9
10
11
24
24
24
96e
Neat
ꢀ20
45b
Neatf
5
rt
99e
a
b
c
Reactants 3a, 4a and 5a were present in equimolar amounts (0.5 mmol).
Yields refer to pure 6a.
Ee was determined by chiral analysis on GC connected to a column with a chiral stationary phase.
d
e
GC–MS analyses showed the presence of starting products 3a, 4a and 5a.
Pure 6a (GC, GC–MS, 1H NMR) was obtained after filtering on a Büchner funnel and washing with a small amount of H2O and
petroleum ether the crude residues.
f
The reaction was performed in the presence of 5% mol of 1 as a catalyst.

1182
M. Barbero et al. / Tetrahedron: Asymmetry 26 (2015) 1180–1188
Table 3
Three-component Mannich reaction between 3, 4, 5 catalyzed by (ꢀ)-2
Ar'
O
O
NH
(-)-2
ArCH2O + Ar'NH2
+
R
R
Ar
3
4
5
6
Entry
Ar in 3
Ar0 in 4
R in 5
Products 6
Time (h)
Yielda (%)
Ee (%) in 6b
1
2
3
4
5
6
7
8
Ph; 3a
Ph; 4a
Ph; 4a
Ph; 4a
Ph; 4a
Ph; 4a
Ph; 4a
Ph; 4a
Ph; 4a
4-MeC6H4; 4b
2-MeC6H4; 4c
3-MeC6H4; 4d
4-NO2C6H4; 4e
2-NO2C6H4; 4f
3-NO2C6H4; 4g
4-ClC6H4; 4h
Ph; 4a
Ph; 4a
Ph; 4a
Ph; 4a
Ph: 4a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
Ph; 5a
4-MeC6H4; 5b
4-ClC6H4; 5c
2-MeC6H4; 5d
3-MeC6H4; 5e
Ph; 5a
nPr; 5f
nPr; 5f
nPr; 5f
4-ClC6H4; 5c
3-MeC6H4; 5e
6a
6b
6c
6d
6e
6f
6g
6h
6i
—
6j
6k
—
6l
6m
6n
6o
—
6p
6q
6r
6s
6t
24
36
48
32
48
48
36
24
24
48
32
28
48
32
24
36
24
48
48
36
32
48
36
32
48
96c
75c
72c
77c
88c
74c
90c
89c
92c
90.2
92.8
92.2
93.6
96.8
96.4
97.8
97.8
90.2
—
96.2
96.3
—
92.0
95.0
92.2
95.4
—
4-MeC6H4; 3b
2-MeC6H4; 3c
3-MeC6H4; 3d
4-NO2C6H4; 3e
2-NO2C6H4; 3f
3-NO2C6H4; 3g
4-ClC6H4; 3h
Ph; 3a
Ph; 3a
Ph; 3a
Ph; 3a
Ph; 3a
Ph; 3a
Ph; 3a
Ph; 3a
Ph; 3a
Ph; 3a
Ph; 3a
2-Thienyl; 3i
Ph; 3a
4-MeC6H4; 3b
Ph; 3a
9
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
—
77c
100c
d
—
95c
97c
78c
92c
d
—
81c
92c
87c
71c
92c
87c
85c
95.0
90.6
94.2
92.4
90.2
91.8
91.2
Ph; 4a
Ph; 4a
4-NO2C6H4; 4c
4-MeC6H4; 4b
3-NO2C6H4; 4g
4-NO2C6H4; 3e
3-ClC6H4; 3j
6u
6v
a
b
c
The reactants 3, 4 and 5 were in equimolar amounts (0.5 mmol). The reactions were performed at rt in the presence of 5 mol % of (ꢀ)-2.
Ee was determined by chiral analyses on GC connected to a column with a chiral stationary phase.
Yields refer to the pure adducts 6 obtained after filtering on a Hirsch funnel and washing with a small amount of H2O and petroleum ether. They were then purified in a
short chromatography column (EP–EtOAc, 9:1).
d
The reaction did not take place. The sole detected product on GC–MS analyses was the imine.
O
O
NH Ar'
Ar
3. Conclusion
(-)-2
ArCHO
+
Ar'NH2
+
Herein we have reported on an asymmetric one pot three-com-
ponent Mannich reaction catalyzed by (ꢀ)-4,5-dimethyl-3,6-bis(o-
tolyl)-1,2-benzenedisulfonimide 2. The target products b-amino
ketones 6 and 7 were obtained via an efficient, mild, green and
simple procedure. Enantio- (over 90%) and diastereoselectivity
(dr 100:0) were always excellent and significantly better compared
with those reported in the literature11a regarding asymmetric
Mannich reactions involving acyclic and aromatic ketones.
5g
4
7: dr (syn/anti) 100/0;
3
average ee over 92%
Scheme 2. Three-component Mannich reaction between 3, 4 and cyclohexanone 5g
catalyzed by (ꢀ)-2.
and J values of 1H NMR peaks in adducts 7a–d, 7f with those of the
literature data.13 Indeed, the J value of CH(NH) in the anti-diastere-
omer was approximately 6–7 Hz, while the same value in the syn-
diastereomer is about 4 Hz. Moreover, the CH(NH) anti-proton was
more shielded than the CH(NH) syn-proton. Interestingly, the
enantioselectivity was excellent: the enantiomeric excess was over
90% (Table 4; average enantiomeric excess 92%) in the presence of
an electron-donating group (Table 4; entry 2). In light of these
results, it can be stated that (ꢀ)-2 is a powerful chiral catalyst
for the asymmetric one-pot three component Mannich reaction.
From a mechanistic point of view, it would appear obvious that
(ꢀ)-2 promotes imine 8 formation first. Then, as demonstrated by
Akiyama,10h 2 protonates 8 to form iminium salt 9, which bears the
chiral counteranion of 2. The formation of this ion pair 9 is
fundamental to inducing enantioselectivity and thus creating the
chiral environment needed to direct the nucleophile’s attack
towards the iminium salt (Scheme 3). This chiral Brønsted acid
catalyzed reaction could be classified as asymmetric counterion
directed catalysis (ACDC) for these reasons.14
4. Experimental
4.1. General
Analytical grade reagents and solvents were used and reactions
were monitored by GC, GC–MS. Column chromatography and TLC
were performed on Merck silica gel 60 (70–230 mesh ASTM) and
GF 254, respectively. Petroleum ether (PE) refers to the fraction
boiling in the range 40–70 °C. Mass spectra were recorded on an
HP5989B mass selective detector connected to an HP 5890 GC with
a cross-linked methyl silicone capillary column. Chiral analyses
were performed on a Perkin–Elmer Autosystem GC connected to
a J&W Scientific Cyclosil-B column; stationary phase: 30% heptakis
(2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-
1701. 1H NMR and 13C NMR spectra were recorded on a Bruker
Avance 200 spectrometer at 200 and 50 MHz respectively. IR spec-
tra were recorded on a IR Perkin–Elmer UATR-two spectrometer.
For the determination of the optical rotations, a Jasco P-2000

M. Barbero et al. / Tetrahedron: Asymmetry 26 (2015) 1180–1188
1183
Table 4
Three-component Mannich reaction between 3, 4 and cyclohexanone 5g catalyzed by 1 or (ꢀ)-2
Ar'
O
O
NH
(-)-2
ArCHO
+
Ar'NH2 +
Ar
3
4
5g
7
Entry
Ar in 3
Ar0 in 4
Products 7
Time (h)
Yield (%)a,b
drc in (syn/anti) 7
eec (%) in syn 7
1
2
3
4
5
6
7
8
7
Ph; 3a
Ph; 3a
Ph; 4a
Ph; 3a
Ph; 4a
Ph; 4a
Ph; 4a
Ph; 4a
4-NO2C6H4; 4c
4-NO2C6H4; 4c
4-ClC6H4; 4h
7a
7a
7b
7b
7c
7d
7e
7e
7f
42
40
54
48
36
36
42
40
42
87
100:0
83:17
100:0
85:15
100:0
100:0
100:0
57:44
100:0
92.0
3.3
94.1
6.0
93.8
92.6
90.0
3.9
85d
71
4-MeC6H4; 3b
4-MeC6H4; 3b
4-NO2C6H4; 3c
4-ClC6H4; 3d
Ph; 3a
68d
89
91
87
Ph; 3a
Ph; 3a
87d
84
91.4
a
b
c
The reactants 3, 4 and 5g were in equimolar amounts (0.5 mmol). The reactions were performed at rt.
Yields refer to the pure and isolated syn adducts 7 obtained after filtering on a Büchner funnel and washing with a small amount of H2O and petroleum ether.
Dr and ee were determined by chiral analysis on GC connected to a column with chiral stationary phase.
The reactions were carried out in the presence of 1 as a catalyst.
d
4.2. Chiral sulfonimide (ꢀ)-2 as a catalyst in a Mannich reaction.
H2O
OH
General procedure
+
ZH
ArCHO
Ar
C
Z
+ Ar'NH2
H
2
3
4
Chiral
catalyst
(ꢀ)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-ben-
zenedisulfonimide 2 (5 mol %, 11 mg, 0.025 mmol) was added to
a stirred mixture of aldehydes 3 (0.5 mmol), aromatic amines 4
(0.5 mmol) and ketones 5 (0.5 mmol). The mixture was stirred at
rt for the times listed in Tables 2 and 4, until the GC and GC–MS
analyses showed the complete disappearance of starting com-
pounds and the complete formation of b-aminoketones 6. Cold
H2O (2 ml) was added to the reaction mixture, under vigorous stir-
ring. The resulting solids were filtered on a Hirsch funnel and
washed with additional cold H2O (2 ꢁ 1 ml) and a small amount
of petroleum ether (1 ml). Virtually pure (TLC, GC, GC–MS, 1H
NMR, 13C NMR) b-aminoketones 6 were obtained.
After the above work-up, the ee was measured. However, in
order to verify the accuracy of these measurements, the crude resi-
due of 6a, instead of being filtered, was chromatographed in a short
column (EP–EtOAc, 9:1), after which ee was determined. The ee
values were identical (90.2%).
Ar'
O
NH
ZH
Z
Ar
C
Ar
H
N
+
ZH
C
N
R
Ar
Ar'
Ar'
H
H
8
9
2
6
+
ee over 90%
O
HO
R
H
R
H
5
O2
S
N
Z =
S
O2
Scheme 3. Mechanism of enantioselective Mannich reaction catalyzed by (ꢀ)-2.
The aqueous washing was collected and evaporated under
reduced pressure. Virtually pure (1H NMR) (ꢀ)-2a was recovered
(11 mg, 100% yield) and reused in another two consecutive runs
as reported in Table 4. The same protocol was employed in the
presence of o-benzenedisulfonimide (1) as a catalysts.
polarimeter was used. o-Benzenedisulfonimide 112a,15 and chiral
catalyst
(ꢀ)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfon-
imide 212b were synthesized as previously reported by us. All
reagents and solvent were purchased from Sigma–Aldrich or
Alfa-Aesar. The structures and purities of all products obtained
were confirmed by their spectroscopic (NMR, MS, IR) data,
similar to those reported in the literature. The yields and ee of
the pure (GC, GC–MS and NMR) isolated b-aminoketones 6 and 7
are reported in Tables 2 and 4. Compounds 6f, 6p 7e are known
in the literature but no spectroscopic data were reported.
Satisfactory microanalyses were obtained for new compounds 6c,
6d, 6s, 6u 6v. The absolute configurations of the optically active
compounds 6b, 6n, 6o10d and 7a–7d, 7f10b,11b were determined
on the basis of the measured specific rotations compared with
literature values. All other absolute configurations were assigned
by analogy.
4.2.1. (R)-1,3-Diphenyl-3-(N-phenylamino)propan-1-one 6a
White solid (144 mg, 96% yield); mp 170–172 °C (EtOH; lit16
169–171 °C). Rf = 0.61. 90.2% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
tR = 6.253 min (major), tR = 6.362 min (minor); [
a
]
21 = ꢀ14.4 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.82 (d, J = 7.4 Hz,
2H), 7.41–7.16 (m, 10H), 7.07 (t, J = 7.4 Hz, 1H), 6.78–6.65 (m,
2H), 4.98–4.92 (m, 1H), 3.62–3.58 (m, 2H); 13C NMR (50 MHz,
CDCl3): d = 198.2, 146.8, 142.9, 136.8, 133.6, 129.3, 129.0, 128.9,
128.4, 127.6, 126.6, 118.3, 114.3, 55.2, 46.4. MS (m/z, EI): 208
[M+ꢀ93] (90), 207 (100), 181 (95), 180 (100). IR (neat)
m
(cmꢀ1):
3335 (NH), 1684 (CO).

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M. Barbero et al. / Tetrahedron: Asymmetry 26 (2015) 1180–1188
4.2.2. (R)-1-Phenyl-3-(N-phenylamino)-3-(4-tolyl)propan-1-one
6b
4.2.6. (R)-3-(2-Nitrophenyl)-1-phenyl-3-(N-phenylamino)pro-
pan-1-one 6f
White solid (116 mg, 75% yield); mp 127–128 °C (EtOH; lit16
129–130 °C). Rf = 0.65. 92.8% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
Yellow solid (128 mg, 74% yield). Mp 160–161 °C (EtOH; lit17
158–162 °C). Rf = 0.42. 96.4% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
tR = 7.289 min (major), tR = 7.431 min (minor); [
a
]
21 = ꢀ18.4 (c
tR = 7.560 min (major), tR = 7.756 min (minor); [
a
]
21 = ꢀ19.9 (c
D
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.84 (d, J = 7.0 Hz,
2H), 7.54–7.20 (m, 6H), 7.08–7.00 (m, 4H), 6.67–6.53 (m, 2H),
4.95–4.89 (m, 1H), 3.52–3.41 (m, 2H), 2.24 (s, 3H); 13C NMR
(50 MHz, CDCl3): d = 198.4, 147.1, 140.0, 137.2, 136.9, 133.6,
129.7, 129.3, 128.9, 128.4, 126.5, 118.0, 114.1, 54.8, 46.9, 21.3.
MS (m/z, EI): 222 [M+ꢀ93] (45), 221 (50), 207 (100), 195 (55),
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.91–7.87 (m, 3H),
7.50–7.31 (m, 6H), 7.05–6.97 (m, 2H), 6.61 (t, J = 7.2 Hz, 1H), 6.41
(d, J = 7.6 Hz, 2H), 5.52 (dd, J1 = 8.2 Hz, J2 = 4.0 Hz, 1H), 4.85 (br s,
1H), 5.52 (dd, J1 = 8.0 Hz, J2 = 4.0 Hz, 1H), 3.72 (dd, J1 = 16.0 Hz,
J2 = 4.0 Hz, 1H), 3.34 (dd, J1 = 16.0 Hz, J2 = 8.0 Hz, 1H); 13C NMR
(50 MHz, CDCl3): d = 198.2, 149.0, 146.4, 140.4, 138.6, 136.6,
134.0, 133.9, 129.5, 129.2, 129.0, 128.6, 125.1, 118.4, 113.8, 50.9,
45.1. MS (m/z, EI): 226 [M+ꢀ120] (45), 209 (100), 207 (40), 179
194 (60). IR (neat)
m
(cmꢀ1): 3348 (NH), 1681 (CO).
4.2.3. (R)-1-Phenyl-3-(N-phenylamino)-3-(2-tolyl)propan-1-one
6c
(80), 152 (70), 105 (100), 77 (75). IR (neat)
1676 (CO).
m
(cmꢀ1): 3333 (NH),
Grey solid (114 mg, 72% yield); mp 114–115 °C (EtOH). Calcd
for C22H21NO: C, 83.78; H, 6.71; N, 4.48; found: C, 83.74; H,
6.76; N, 4.47. Rf = 0.67. 92.2% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
4.2.7. (R)-3-(3-Nitrophenyl)-1-phenyl-3-(N-phenylamino)pro-
pan-1-one 6g
Yellow solid (155 mg, 90% yield). Mp 141–142 °C (EtOH; lit16
140–141 °C). Rf = 0.43. 97.8% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
tR = 7.196 min (major), tR = 7.304 min (minor); [
a
]
D
21 = ꢀ12.8 (c
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.90 (d, J = 8.0 Hz,
2H), 7.58–7.39 (m, 4H), 7.17–7.05 (m, 5H), 6.70–6.50 (m, 3H),
5.26–5.20 (m, 1H), 4.92 (br s, 1H), 3.43–3.37 (m, 2H), 2.50 (s,
3H); 13C NMR (50 MHz, CDCl3): d = 198.5, 147.5, 141.1, 137.1,
135.3, 133.7, 131.2, 129.6, 129.0, 128.5, 127.5, 127.0, 125.8,
118.0, 113.9, 51.2, 44.9, 19.6. MS (m/z, EI): 222 [M+ꢀ93] (5),
tR = 7.560 min (major), tR = 7.756 min (minor); [
a
]
21 = ꢀ13.7 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 8.28 (s, 1H), 7.85 (d,
J = 7.0 Hz, 2H), 7.77 (d, J = 7.8 Hz, 1H), 7.56–7.36 (m, 4H), 7.09–
7.02 (m, 2H), 6.65 (t, J = 7.2 Hz, 1H), 6.50 (d, J = 8.4 Hz, 2H), 5.11–
5.04 (m, 1H), 4.21 (br s, 1H), 3.49–3.46 (m, 2H); 13C NMR
(50 MHz, CDCl3): d = 197.4, 148.9, 146.6, 145.8, 136.6, 133.9,
133.3, 129.9, 129.5, 129.0, 128.4, 122.7, 121.8, 118.6, 114.4, 54.2,
46.1. MS (m/z, EI): 253 [M+ꢀ93] (100), 236 (40), 226 (100), 206
221 (10), 207 (100), 195 (100), 194 (100). IR (neat)
3354 (NH), 1678 (CO).
m
(cmꢀ1):
(35), 178 (45), 105 (100), 77 (50). IR (neat)
1682 (CO).
m
(cmꢀ1): 3345 (NH),
4.2.4. (R)-1-Phenyl-3-(N-phenylamino)-3-(3-tolyl)propan-1-one
6d
Pale green solid (121 mg, 77% yield). Mp 107–108 °C (EtOH).
Calcd for C22H21NO: C, 83.78; H, 6.71; N, 4.44; found C, 83.82;
H, 6.68; N, 4.48. Rf = 0.68. 93.6% ee (GC connected to a J&W
Scientific Cyclosil-B column; stationary phase: 30% heptakis
4.2.8. (R)-3-(4-Chlorophenyl)-1-phenyl-3-(N-phenylamino)pro-
pan-1-one 6h
Pale brown solid (150 mg, 89% yield). Mp 115–116 °C (EtOH;
lit16 114–115 °C). Rf = 0.74. 97.8% ee (GC connected to a J&W
Scientific Cyclosil-B column; stationary phase: 30% heptakis
(2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin
in
DB-1701), tR = 7.099 min (major), tR = 7.243 min (minor);
[
a
]
21 = ꢀ14.7 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.83
D
(2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin
in
(d, J = 8.2 Hz, 2H), 7.50–7.34 (m, 3H), 7.20–6.97 (m, 6H), 6.71–
6.58 (m, 3H), 4.93–4.87 (m, 1H), 3.51–3.47 (m, 2H), 2.25 (s,
3H); 13C NMR (50 MHz, CDCl3): d = 198.5, 147.2, 143.1, 141.7,
138.7, 136.7, 133.6, 131.7, 129.3, 128.9, 128.4, 127.3, 123.6,
118.0, 114.1, 54.8, 46.5, 21.7. MS (m/z, EI): 222 [M+ꢀ93] (45),
DB-1701), tR = 7.494 min (major), tR = 7.683 min (minor);
[a]
21 = ꢀ15.2 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.83
D
(d, J = 7.8 Hz, 2H), 7.55–7.31 (m, 6H), 7.25–7.21 (m, 2H), 7.08–
7.01 (m, 2H), 6.67–6.41 (m, 1H), 6.50 (d, J = 8.4 Hz, 2H), 4.96–
4.90 (m, 1H), 4.53 (br s, 1H), 3.42–3.38 (m, 2H); 13C NMR
(50 MHz, CDCl3): d = 198.2, 146.6, 141.5, 136.7, 133.8, 133.2,
129.4, 129.1, 128.4, 128.1, 127.9, 118.4, 114.2, 54.5, 46.2. MS (m/
z, EI): 242 [M+ꢀ93] (100), 211 (90), 210 (100), 207 (65), 179 (50),
221 (50), 207 (100), 195 (80), 194 (100). IR (neat)
3340 (NH), 1685 (CO).
m
(cmꢀ1):
4.2.5. (R)-3-(4-Nitrophenyl)-1-phenyl-3-(N-phenylamino)pro-
pan-1-one 6e
165 (60). IR (neat)
m
(cmꢀ1): 3402 (NH), 1678 (CO).
Yellow solid (153 mg, 88% yield). Mp 170–171 °C (EtOH; lit16
168–169 °C). Rf = 0.44. 96.8% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
4.2.9. (R)-1,3-Diphenyl-3-[N-(4-tolyl)amino]propan-1-one 6i
Grey solid (144 mg, 92% yield). Mp 111–112 °C (EtOH; lit18
107–110 °C). Rf = 0.64. 90.28% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
tR = 7.702 min (major), tR = 7.910 min (minor); [
a
]
21 = ꢀ19.5 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 8.09 (d, J = 8.6 Hz,
2H), 7.85 (d, J = 8.6 Hz, 2H), 7.60–7.36 (m, 5H), 7.09–7.01 (m,
2H), 6.69–6.62 (m, 1H), 6.61–6.47 (m, 2H), 5.10–5.04 (m, 1H),
4.41 (br s, 1H), 3.49–3.46 (m, 2H); 13C NMR (50 MHz, CDCl3):
d = 197.4, 150.9, 147.4, 146.4, 136.5, 134.0, 129.5, 129.0, 128.3,
127.7, 124.3, 118.7, 114.1, 54.4, 45.9. MS (m/z, EI): 253 [M+ꢀ93]
tR = 6.987 min (major), tR = 7.110 min (minor); [
a
]
21 = ꢀ11.7 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 8.09 (d, J = 8.6 Hz,
2H), 7.85 (d, J = 8.6 Hz, 2H), 7.60–7.36 (m, 5H), 7.09–7.01 (m,
2H), 6.69–6.62 (m, 1H), 6.61–6.47 (m, 2H), 5.10–5.04 (m, 1H),
4.41 (br s, 1H), 3.49–3.46 (m, 2H); 13C NMR (50 MHz, CDCl3):
d = 198.5, 143.7, 142.4, 136.8, 133.6, 129.9, 129.1, 128.9, 128.6,
128.4, 127.7, 126.9, 115.0, 56.1, 46.1, 20.6. MS (m/z, EI): 208
(35), 236 (20), 226 (100), 225 (50), 179 (50). IR (neat)
3398 (NH), 1683 (CO).
m
(cmꢀ1):

M. Barbero et al. / Tetrahedron: Asymmetry 26 (2015) 1180–1188
1185
[M+ꢀ107] (85), 207 (100), 195 (100), 194 (100). IR (neat)
m
(cmꢀ1):
4.2.14. (R)-3-Phenyl-3-(N-phenylamino)-1-(4-tolyl)propan-1-
one 6n
3418 (NH), 1675 (CO).
White solid (123 mg, 78% yield). Mp 135–136 °C (EtOH; lit21
136–137 °C). Rf = 0.58. 92.2% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
4.2.10. (R)-1,3-Diphenyl-3-[N-(3-tolyl)amino]propan-1-one 6j
White solid (122 mg, 77% yield). Mp 136–137 °C (EtOH; lit19
138–140 °C). Rf = 0.65. 96.2% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
tR = 6.730 min (major), tR = 6.847 min (minor); [
a
]
21 = ꢀ15.8 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.73 (d, J = 8.0 Hz,
2H), 7.41–7.38 (m, 2H), 7.28–7.14 (m, 5H), 7.08–7.00 (m, 2H),
6.70–6.57 (m, 3H), 4.96–4.89 (m, 1H), 3.49–3.47 (m, 2H); 13C
NMR (50 MHz, CDCl3): d = 198.9, 147.2, 144.5, 143.2, 134.4,
129.6, 129.3, 128.9, 128.6, 127.5, 126.7, 117.9, 114.1, 55.1, 46.3.
MS (m/z, EI): 222 [M+ꢀ93] (55), 221 (60), 181 (90), 180 (100). IR
tR = 6.998 min (major), tR = 7.126 min (minor);
[
a
]
21 = ꢀ5.4 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.85 (d, J = 8.2 Hz,
2H), 7.53–7.46 (m, 1H), 7.41–7.30 (m, 4H), 7.26–7.18 (m, 3H),
6.97–6.89 (m, 1H), 6.53–6.37 (m, 3H), 4.98–4.92 (m, 1H), 4.61
(br s, 1H), 3.52–3.49 (m, 2H), 2.15 (s, 3H); 13C NMR (50 MHz,
CDCl3): d = 198.5, 146.5, 142.8, 139.2, 136.8, 133.7, 129.3, 129.1,
128.9, 128.5, 127.8, 126.9, 119.2, 115.6, 111.8, 55.6, 46.2, 21.9.
MS (m/z, EI): 222 [M+ꢀ93] (35), 207 (100), 195 (100), 194
(neat)
m
(cmꢀ1): 3400 (NH), 1679 (CO).
4.2.15. (R)-3-Phenyl-3-(N-phenylamino)-1-(4-chlorophenyl)pro-
pan-1-one 6o
Pale green solid (155 mg, 92% yield). Mp 123–124 °C (EtOH;
lit19 122–124 °C). Rf = 0.58. 95.4% ee (GC connected to a J&W Scien-
tific Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
(100), 178 (60), 105 (75), 77 (80). IR (neat)
(NH), 1684 (CO).
m
(cmꢀ1): 3400
4.2.11. (R)-1,3-Diphenyl-3-[N-(4-nitrophenyl)amino]propan-1-
one 6k
Yellow solid (173 mg, 100% yield using (ꢀ) 2 as catalyst).
Mp 186–187 °C (EtOH; lit20 185–186 °C). Rf = 0.39. 96.3% ee
(GC connected to a J&W Scientific Cyclosil-B column; stationary
phase: 30% heptakis (2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-
b-cyclodextrin in DB-1701), tR = 7.724 min (major), tR = 7.934
tR = 7.439 min (major), tR = 7.512 min (minor); [
a
]
21 = ꢀ13.2 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.75 (d, J = 8.6 Hz,
2H), 7.35–7.18 (m, 7H), 7.10–7.02 (m, 2H), 6.77–6.62 (m, 3H),
4.97–4.91 (m, 1H), 3.56–3.41 (m, 2H); 13C NMR (50 MHz, CDCl3):
d = 197.4, 146.6, 142.6, 140.1, 135.1, 129.8, 129.4, 129.2, 129.1,
127.7, 126.6, 117.9, 114.4, 55.2, 46.2. MS (m/z, EI): 242 [M+ꢀ93]
min (minor); [
a
]
21 = ꢀ13.8 (c 0.1, CH2Cl2). 1H NMR (200 MHz,
D
CDCl3): d = 7.88 (d, J = 9.2 Hz, 2H), 7.56–7.20 (m, 10H), 6.47
(d, J = 9.2 Hz, 2H), 5.07–5.01 (m, 1H), 4.69 (br s, 1H), 3.49–
3.46 (m, 2H); 13C NMR (50 MHz, CDCl3): d = 198.2, 141.8,
141.3, 136.6, 133.9, 129.3, 129.1, 128.9, 128.4, 128.1, 126.3,
120.5, 112.5, 54.7, 45.6. MS (m/z, EI): 226 [M+ꢀ120] (100),
(40), 241 (60), 181 (90), 180 (100). IR (neat)
1683 (CO).
m
(cmꢀ1): 3377 (NH),
4.2.16. (R)-3-Phenyl-3-(N-phenylamino)-1-(3-tolyl)propan-1-
one 6p
225 (80), 207 (100), 206 (90). IR (neat)
1677 (CO).
m
(cmꢀ1): 3392 (NH),
Grey solid (128 mg, 81% yield). Mp 172–173 °C (EtOH; lit22
172 °C). Rf = 0.69. 95.0% ee (GC connected to a J&W Scientific Cyclo-
sil-B column; stationary phase: 30% heptakis (2,3-di-O-methyl-6-
O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701), tR = 6.727 min
4.2.12. (R)-1,3-Diphenyl-3-[N-(3-nitrophenyl)amino]propan-1-
one 6l
(major), tR = 6.820 min (minor); [
a
]
21 = ꢀ13.2 (c 0.1, CH2Cl2). 1H
D
Yellow solid (165 mg, 95%). Mp 144–145 °C (EtOH; lit21 146–
147 °C). Rf = 0.41. 92.0% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
NMR (200 MHz, CDCl3): d = 7.65 (s, 2H), 7.41–7.14 (m, 7H), 7.08–
7.01 (m, 2H), 6.69–6.54 (m, 3H), 4.98–4.91 (m, 1H), 3.47–3.44
(m, 2H), 2.33 (s, 3H); 13C NMR (50 MHz, CDCl3): d = 198.6, 146.7,
142.7, 138.7, 136.9, 134.4, 129.3, 129.0, 128.8, 127.7, 126.7,
125.6, 121.4, 118.4, 114.5, 55.4, 46.3, 21.5. MS (m/z, EI): 222
tR = 7.814 min (major), tR = 8.014 min (minor); [
a
]
21 = ꢀ12.2 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.84 (d, J = 7.4 Hz,
2H), 7.55–7.08 (m, 11H), 6.82–6.78 (m, 1H), 5.01–4.95 (m, 1H),
3.47–3.44 (m, 2H); 13C NMR (50 MHz, CDCl3): d = 198.3, 149.2,
147.8, 141.9, 136.6, 133.9, 129.8, 129.2, 129.0, 128.4, 127.9,
126.5, 119.8, 112.5, 108.1, 54.9, 46.2. MS (m/z, EI): 226 [M+ꢀ120]
[M+ꢀ93] (85), 221 (100), 181 (90), 180 (100). IR (neat)
m
(cmꢀ1):
3365 (NH), 1684 (CO).
4.2.17. (R)-1-Phenyl-3-(N-phenylamino)-3-(2-thienyl)propan-1-
one 6q
Pale brown solid (141 mg, 92% yield). Mp 114–115 °C (EtOH;
lit18 116–117 °C). Rf = 0.57. 90.6% ee (GC connected to a J&W
Scientific Cyclosil-B column; stationary phase: 30% heptakis
(2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-
(50), 225 (40), 207 (100), 179 (25), 131 (25), 77 (50). IR (neat)
(cmꢀ1): 3412 (NH), 1684 (CO).
m
4.2.13. (R)-1,3-Diphenyl-3-[N-(4-chlorophenyl)amino]propan-
1-one 6m
1701),
tR = 6.289 min
(major),
tR = 6.338 min
(minor);
White solid (163 mg, 97% yield). Mp 170–171 °C (EtOH; lit16
168–169 °C). Rf = 0.58. 95.0% ee (GC connected to a J&W Scientific
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
[a
]
D
21 = ꢀ10.4 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3):
d = 7.87 (d, J = 8.0 Hz, 2H), 7.51–7.32 (m, 5H), 7.13–7.04 (m,
3H), 6.96–6.94 (m, 1H), 6.69–6.62 (m, 2H), 5.35–5.29 (m, 1H),
3.56–3.53 (m, 2H); 13C NMR (50 MHz, CDCl3): d = 198.0, 147.8,
146.8, 136.9, 133.7, 129.5, 128.9, 128.4, 127.1, 124.4, 124.2,
118.6, 114.3, 50.9, 46.1. MS (m/z, EI): 214 [M+ꢀ93] (100), 187
tR = 7.419 min (major), tR = 7.579 min (minor); [
a
]
21 = ꢀ14.1 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.83 (d, J = 7.2 Hz,
2H), 7.51–7.18 (m, 8H), 6.87 (d, J = 8.6 Hz, 2H), 6.48 (d, J = 8.6 Hz,
2H), 4.92–4.87 (m, 1H), 3.47–3.44 (m, 2H); 13C NMR (50 MHz,
CDCl3): d = 198.2, 145.1, 141.8, 136.6, 133.8, 129.4, 129.2, 128.9,
128.8, 127.9, 126.8, 121.4, 116.2, 56.1, 45.9. MS (m/z, EI): 215
(90), 186 (100), 185 (40), 137 (40). IR (neat)
(NH), 1677 (CO).
m
(cmꢀ1): 3375
4.2.18. (R)-1-Phenyl-1-(N-phenylamino)hexan-3-one 6r
Pale yellow solid (116 mg, 87% yield). Mp 89–90 °C (EtOH; lit23
87–88 °C). Rf = 0.72. 94.2% ee (GC connected to a J&W Scientific
[M+ꢀ120] (100), 214 (100), 207 (100), 206 (40). IR (neat)
m
(cmꢀ1): 3415 (NH), 1680 (CO).

1186
M. Barbero et al. / Tetrahedron: Asymmetry 26 (2015) 1180–1188
Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
heptakis (2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodex-
trin in DB-1701), tR = 7.925 min (major), tR = 8.123 min (minor);
tR = 6.596 min (major), tR = 6.701 min (minor); [
a
]
D
21 = ꢀ9.4 (c 0.1,
[a]
21 = ꢀ16.9 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.65
D
CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.29–7.20 (m, 5H), 7.08–
7.00 (m, 2H), 6.65–6.48 (m, 3H), 4.81–4.74 (m, 1H), 2.87–2.84
(m, 2H), 2.25 (t, J = 7.4 Hz, 2H), 1.55–1.37 (m, 2H), 0.77 (t,
J = 7.4 Hz, 3H); 13C NMR (50 MHz, CDCl3): d = 209.9, 147.1, 142.9,
129.4, 129.0, 127.6, 126.6, 118.0, 114.0, 54.7, 50.5, 45.8, 17.1,
(s, 2H), 7.49–7.10 (m, 9H), 6.78–6.74 (m, 1H), 4.97–4.91 (m, 1H),
3.42–3.39 (m, 2H), 2.33 (s, 3H); 13C NMR (50 MHz, CDCl3):
d = 198.0, 149.3, 147.7, 144.3, 138.9, 136.5, 135.1, 134.8, 130.6,
130.1, 129.9, 128.9, 128.2, 126.5, 125.6, 124.8, 119.6, 112.9,
108.1, 54.4, 46.1, 21.5. MS (m/z, EI): 257 [M+ꢀ137] (25), 256
13.9. MS (m/z, EI): 267 [M+] (25), 182 (100), 180 (55). IR (neat)
m
(100), 221 (75), 138 (100). IR (neat)
(CO).
m
(cmꢀ1): 3341 (NH), 1682
(cmꢀ1): 3375 (NH), 1677 (CO).
4.2.19. (R)-1-(N-phenylamino)-1-(4-tolyl)hexan-3-one 6s
4.2.23. syn/anti-2-[Phenyl(N-phenylamino)methyl]cyclohexan-
one 7a
Pale brown solid (100 mg, 71% yield). Mp 100–101 °C (EtOH).
Calcd for C19H23NO: C, 81.10; H, 8.24; N, 4.98; found: C, 81.03;
H, 8.27; N, 5.04. Rf = 0.75. 92.4% ee (GC connected to a J&W Scien-
tific Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-O-
methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
White solid (0.48 g, 85% yield, using 1 as a catalyst). 1H NMR
(200 MHz, CDCl3): d = 7.36–6.98 (m, 7H), 6.72–6.49 (m, 3H), 4.77
(d, Jsyn = 4.6 Hz) and 4.60 (d, Janti = 7.0 Hz; 1H in total; ratio syn/anti
72:28), 3.95 (br s, 1H), 2.81–2.67 (m, 1H), 2.43–2.21 (m, 2H), 1.84–
1.54 (m, 6H). Ratio between syn and anti diastereomers, deter-
mined by chiral analysis, is 83.3:16.7. Four peaks are detected:
tR = 5.536 min (syn), tR = 5.742 min (syn), tR = 6.343 min (anti),
tR = 6.406 min (anti).
tR = 6.805 min (major), tR = 6.929 min (minor); [
a
]
21 = ꢀ10.7 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.20–6.92 (m, 6H),
6.69–6.47 (m, 3H), 4.78–4.91 (m, 1H), 2.84–2.80 (m, 2H), 2.32–
2.21 (m, 5H), 1.52–1.38 (m, 2H), 0.78 (t, J = 7.4 Hz, 3H); 13C NMR
(50 MHz, CDCl3): d = 209.8, 147.1, 142.6, 129.9, 129.7, 129.3,
126.4, 117.9, 113.9, 54.4, 50.5, 45.7, 21.3, 17.6, 13.8. MS (m/z, EI):
4.2.24. (R)-2-[(R)-Phenyl(N-phenylamino)methyl]cyclohexan-
one 7a
281 [M+] (15), 196 (80), 195 (80), 194 (100), 145 (50). IR (neat)
(cmꢀ1): 3400 (NH), 1681 (CO).
m
White solid (121 mg, 87% yield, using (ꢀ) 2 as a catalyst).
Mp 140–141 °C (EtOH; lit25 138–140 °C). Rf = 0.68. 92.0% ee
(GC connected to a J&W Scientific Cyclosil-B column; stationary
phase: 30% heptakis (2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-
b-cyclodextrin in DB-1701), tR = 5.419 min (major), tR = 5.652 -
4.2.20. (R)-1-[N-(4-nitrophenyl)amino]-1-phenylhexan-3-one 6t
Yellow solid (144 mg, 92% yield). Mp 103–104 °C (EtOH; lit24
104–106 °C). Rf = 0.51. 90.1% ee (GC connected to a J&W Scien-
tific Cyclosil-B column; stationary phase: 30% heptakis (2,3-di-
O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-1701),
min (minor); [a]
21 = +35.9 (c 0.1, CH2Cl2). 1H NMR (200 MHz,
D
CDCl3): d = 7.34–6.98 (m, 7H), 6.62–6.48 (m, 3H), 4.77 (d,
Jsyn = 4.6 Hz, 1H), 4.30 (br s, 1H), 2.82–2.67 (m, 1H), 2.42–2.24
(m, 2H), 1.87–1.53 (m, 6H); 13C NMR (50 MHz, CDCl3):
d = 213.1, 146.7, 142.0, 130.7, 129.3, 128.7, 127.5, 127.4, 113.9,
58.2, 57.7, 40.6, 31.5, 28.7, 24.1. MS (m/z, EI): 186 [M+ꢀ93]
tR = 6.884 min (major), tR = 6.991 min (minor); [
a
]
21 = ꢀ10.0 (c
D
0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.91 (d, J = 9.2 Hz,
2H), 7.24–7.15 (m, 5H), 6.42 (d, J = 9.2 Hz, 2H), 5.28 (br s, 1H),
4.89–4.83 (m, 1H), 2.93–2.87 (m, 2H), 2.23 (t, J = 7.4 Hz, 2H),
1.49–1.34 (m, 2H), 0.74 (t, J = 7.4 Hz, 3H); 13C NMR (50 MHz,
CDCl3): d = 209.5, 152.6, 141.1, 138.3, 129.2, 128.0, 126.4,
126.3, 112.3, 54.1, 49.4, 46.1, 16.9, 13.7. MS (m/z, EI): 312 [M+]
(75), 185 (100), 181 (75), 180 (100). IR (neat)
(NH), 1692 (CO).
m
(cmꢀ1): 3376
(25), 227 (100), 131 (75). IR (neat)
(CO).
m
(cmꢀ1): 3398 (NH), 1684
4.2.25. syn/anti-2-[4-Tolyl(N-phenylamino)methyl]cyclohexan-
one 7b
Pale green solid (0.40 g, 68% yield, using 1 as a catalyst). 1H
NMR (200 MHz, CDCl3): d = 7.33–7.15 (m, 2H), 7.12–6.98 (m, 4H),
6.75–6.47 (m, 3H), 4.72 (d, Jsyn = 4.6 Hz) and 4.56 (d, Janti = 7.2 Hz;
1H in total; ratio syn/anti 72:28), 4.03 (br s, 1H), 2.76–2.64 (m,
1H), 2.38–2.18 (m, 2H), 2.26 (s, 3H), 1.84–1.53 (m, 6H). Ratio
between syn and anti diastereomers, determined by chiral analysis,
is 84.6:16.4. Four peaks are detected: tR = 6.592 min (syn),
tR = 6.816 min (syn), tR = 7.445 min (anti), tR = 7.517 min (anti).
4.2.21. (R)-1-(4-Chlorophenyl)-3-(4-nitrophenyl)-3-[N-(4-tolyl)-
amino]propan-1-one 6u
Pale brown solid (171 mg, 87% yield). Mp 143–144 °C (EtOH).
Calcd for C22H19ClN2O3: C, 66.92; H, 4.85; Cl, 8.98; N, 7.09; found:
C, 66.83; H, 4.88; Cl, 8.91; N, 7.12. Rf = 0.48. 91.8% ee (GC connected
to a J&W Scientific Cyclosil-B column; stationary phase: 30% hep-
takis (2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin
in DB-1701), tR = 7.909 min (major), tR = 8.118 min (minor);
[a
]
D
21 = ꢀ18.3 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 8.09
4.2.26. (R) 2-[(R)-4-Tolyl(N-phenylamino)methyl]cyclohexan-
one 7b
(d J = 8.6 Hz, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.6 Hz, 2H),
7.35 (d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.2 Hz, 2H), 6.40 (d, J = 8.2 Hz,
2H), 5.05–4.99 (m, 1H), 4.12 (br s, 1H), 3.44–3.40 (m, 2H), 2.13
(s, 3H); 13C NMR (50 MHz, CDCl3): d = 196.3, 151.1, 147.3, 144.1,
140.4, 134.9, 130.2, 130.0, 129.8, 129.3, 127.8, 124.2, 114.3, 54.5,
45.9, 20.6. MS (m/z, EI): 287 [M+ꢀ107] (25), 270 (30), 252 (100),
Pale green solid (104 mg, 71% yield, using 2 as a catalyst). Mp
120–121 °C (EtOH; lit26 118–119 °C). Rf = 0.74. 94.1% ee (GC con-
nected to a J&W Scientific Cyclosil-B column; stationary phase:
30% heptakis (2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cy-
clodextrin in DB-1701), tR = 6.406 min (major), tR = 6.649 min
240 (100), 193 (45), 176 (30), 139 (65). IR (neat)
(NH), 1688 (CO).
m
(cmꢀ1): 3325
(minor); [a]
21 = +24.2 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3):
D
d = 7.23–7.15 (m, 2H), 7.11–6.98 (m, 4H), 6.66–6.47 (m, 3H), 4.72
(d, Jsyn = 4.6 Hz, 1H), 2.77–2.64 (m, 1H), 2.38–2.29 (m, 2H), 2.26
(s, 3H), 1.91–1.75 (m, 3H), 1.69–1.53 (m, 3H); 13C NMR (50 MHz,
CDCl3): d = 212.5, 147.6, 139.0, 136.1, 130.0, 129.7, 129.3, 118.8,
115.4, 58.3, 57.7, 40.5, 31.4, 29.2, 23.5, 21.6. MS (m/z, EI): 200
[M+ꢀ93] (15), 199 (20), 195 (85), 194 (100), 185 (100). IR (neat)
4.2.22. (R)-3-(3-Chlorophenyl)-3-[N-(3-nitrophenyl)amino]-1-
(3-tolyl)propan-1-one 6v
Brown solid (168 mg, 85% yield). Mp 136–137 °C (EtOH). Calcd
for C22H19ClN2O3: C, 66.92; H, 4.85; Cl, 8.98; N, 7.09; found: C,
66.85; H, 4.90; Cl, 9.05; N, 7.00. Rf = 0.44. 91.2% ee (GC connected
to a J&W Scientific Cyclosil-B column; stationary phase: 30%
m
(cmꢀ1): 3385 (NH), 1695 (CO).

M. Barbero et al. / Tetrahedron: Asymmetry 26 (2015) 1180–1188
1187
21
4.2.27. (R)-2-[(R)-4-Nitrophenyl(N-phenylamino)methyl]cyclo-
hexanone 7c
DB-1701), tR = 6.122 min (major), tR = 6.321 min (minor); [
a]
D
=
+32.3 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.36–7.18
(m, 4H), 7.03–6.94 (m, 3H), 6.52–6.42 (m, 2H), 4.87 (d, Jsyn = 3.4 Hz),
2.93–2.81 (m, 1H), 2.49–2.23 (m, 2H), 1.88–1.55 (m, 6H); 13C NMR
(50 MHz, CDCl3): d = 213.5, 146.5, 142.3, 130.6, 129.3, 128.8,
128.6, 124.9, 116.5, 58.9, 58.5, 40.9, 32.2, 28.7, 23.2. MS (m/z, EI):
216 [M+ꢀ98] (100), 215 (100), 186 (80), 185 (100). IR (neat)
Yellow solid (144 mg, 89% yield, using 2 as a catalyst). Mp 122–
123 °C (EtOH; lit27 123–125 °C). Rf = 0.49. 93.8% ee (GC connected
to a J&W Scientific Cyclosil-B column; stationary phase: 30% hep-
takis (2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin
in DB-1701), tR = 6.875 min (major), tR = 7.128 min (minor);
[
a]
D
21 = +27.7 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 8.04
m
(cmꢀ1): 3346 (NH), 1695 (CO).
(d, J = 8.8 Hz, 2H), 7.53–7.49 (m, 2H), 7.07–6.96 (m, 2H), 6.65–
6.54 (m, 1H), 6.44 (d, J = 8.8 Hz, 2H), 4.76 (d, Jsyn = 4.6 Hz, 1H),
4.04 (br s, 1H), 2.92–2.72 (m, 1H), 2.34–2.23 (m, 2H), 1.98–1.86
(m, 3H), 1.77–1.56 (m, 3H); 13C NMR (50 MHz, CDCl3): d = 212.0,
150.2, 147.0, 146.8, 130.9, 129.4, 123.8, 118.9, 113.7, 57.7, 57.1,
40.6, 32.1, 29.2, 23.9. MS (m/z, EI): 231 [M+ꢀ93] (15), 230 (20),
226 (100), 214 (100), 179 (35), 184 (45), 128 (40), 116 (45). IR
Acknowledgments
This work was supported by Ministero dell’Università e della
Ricerca and by University of Torino.
References
(neat)
m
(cmꢀ1): 3394 (NH), 1698 (CO).
1. Mannich, C.; Krösche, W. Arch. Pharm. 1912, 250, 647–667.
2. (a) For reviews see: Akiyama, T., 2nd ed. In Comprehensive Organic Synthesis;
Knochel, P., Molander, G. A., Eds.; Elsevier: Amsterdam, 2014; Vol. 2, pp 629–
681. part 2; (b) Cordova, A. Acc. Chem. Res. 2004, 37, 102–112; (c) Arend, M.
Angew. Chem., Int. Ed. 1999, 38, 2873–2874; (d) Kobayashi, S.; Ishitani, H. Chem.
Rev. 1999, 99, 1069–1094.
3. For recent literature see: (a) Lu, H.; Wu, R.; Cheng, H.; Nie, S.; Tang, Y.; Gao, Y.;
Luo, Z. Synthesis 2015, 1447–1454; (b) Rajesh, U. C.; Kholiya, R.; Pavan, V. S.;
Rawat, D. S. Tetrahedron Lett. 2014, 55, 2977–2978; (c) Fiorot, R. J.; Allochio
Filho, J. F.; Pereira, T. M. C.; Lacerda, V., Jr.; dos Santos, R. B.; Romão, W.; Greco,
S. J. Tetrahedron Lett. 2014, 55, 4373–4377.
4. (a) Zareyee, D.; Alizadeh, H. RSC Adv. 2014, 5, 37941–37946; (b) She, Y.; Liu, X.;
Yang, Z. Adv. Mater. Res. 2014, 989–994; (c) Chen, C.; Zhu, X.; Wu, Y.; Sun, H.;
Zhang, G.; Zhang, W.; Gao, Z. J. Mol. Catal. A: Chem. 2014, 395, 124–127; (d)
Chang, T.; He, L.; Bian, L.; Han, H.; Yuan, M.; Gao, X. RSC Adv. 2014, 4, 727–731.
5. (a) Zhang, Y.; Han, J.; Liu, Z.-J. RSC Adv. 2015, 5, 25485–25488; (b) Wu, Y.; Chen,
C.; Jia, G.; Zhu, X.; Sun, H.; Zhang, G.; Zhang, W.; Gao, Z. Chem. Eur. J. 2014, 20,
8530–8535; (c) Ramalingam, S.; Kumar, P. Catal. Commun. 2008, 9, 2445–2448.
6. (a) Demirkol, O.; Akbasßlar, D.; Giray, S.; Barısß Anıl, B. Synth. Commun. 2014, 44,
1279–1285; (b) Hao, W.; Jiang, B.; Tu, S.; Cao, X. Org. Biomol. Chem. 2009, 7,
1410–1414; (c) Fujisawa, H.; Takahashi, E.; Mukaiyama, T. Chem. Eur. J. 2006,
12, 5082–5093.
4.2.28. (R)-[(R)-4-Chlorophenyl(N-phenylamino)methyl]cyclo-
hexanone 7d
Grey solid (142 mg, 91% yield, using 2 as a catalyst). Mp 132–
133 °C (EtOH; lit28 134–135 °C). 92.6% ee (GC connected to a J&W
Scientific Cyclosil-B column; stationary phase: 30% heptakis
(2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in DB-
21
1701), tR = 6.121 min (major), tR = 6.334 min (minor);
[
a]
=
D
+29.8 (c 0.1, CH2Cl2). 1H NMR (200 MHz, CDCl3): d = 7.27–7.22
(m, 4H), 7.15–6.99 (m, 2H), 6.65–6.60 (m, 1H), 6.49–6.44 (m,
2H), 4.69 (d, Jsyn = 4.6 Hz, 1H), 2.77–2.64 (m, 1H), 2.36–2.29 (m,
2H), 1.87–1.82 (m, 3H), 1.67–1.54 (m, 3H). 13C NMR (50 MHz,
CDCl3): d = 212.7, 146.6, 140.3, 129.4, 129.2, 128.8, 118.7, 115.3,
113.9, 57.7, 57.5, 42.2, 31.7, 27.2, 23.5. MS (m/z, EI): 220
[M+ꢀ93] (75), 219 (80), 215 (90), 214 (100), 185 (70), 129 (100),
115 (75). IR (neat)
m
(cmꢀ1): 3399 (NH), 1705 (CO).
7. (a) Cheng, C.; Jing, H. RSC Adv. 2014, 4, 34325–34331; (b) Kumar, V.; Sharma,
U.; Verma, P. K.; Kumar, N.; Singh, B. Chem. Pharm. Bull. 2011, 59, 639–645.
8. For reviews see: (a) Cai, X.; Xie, B. Arkivoc 2013, 264–293; (b) Karimi, B.;
Enders, D.; Jafari, E. Synthesis 2013, 2769–2812; (c) Akiyama, T. In
Comprehensive Chirality; Carreira, E. M., Yamamoto, H., Eds.; Elsevier:
Amsterdam, 2012; vol. 6, pp 69–93.
4.2.29. syn/anti-2-{Phenyl[N-(4-nitrophenylamino)]methyl}cyclo-
hexanone 7e
Yellow solid (0.57 g, 87% yield, using 1 as a catalyst). 1H NMR
(200 MHz, CDCl3): d = 7.97 (d, J = 9.2 Hz, 2H), 7.89 (d, J = 9.2 Hz,
2H), 7.27–7.25 (m, 5H), 6.53 (d, J = 9.2 Hz, 2H), 6.43 (d, J = 9.2 Hz,
2H), 4.82 (d, Jcis = 4.4 Hz) and 4.60 (d, Janti = 6.2 Hz; 1H in total; ratio
syn/anti 52:48), 2.84–2.77 (m, 1H), 2.46–2.24 (m, 2H), 1.97–1.83
(m, 3H), 1.65–1.45 (m, 3H). Ratio between syn and anti diastere-
omers, determined by chiral analysis, is 56.5:43.5. Four peaks are
detected: tR = 6.447 min (syn), tR = 6.658 min (syn), tR = 7.242 min
(anti), tR = 7.295 min (anti).
9. (a) List, B. J. Am. Chem. Soc. 2000, 122, 9336–9337; (b) Rachwalski, M.; Leenders,
T.; Kaczmarczyk, S.; Kiełbasin´ ski, P.; Les´niakb, S.; Rutjesa, F. P. J. T. Org. Biomol.
Chem. 2013, 11, 4207–4213; (c) Ji, S.; Alkhalil, A. E.; Su, Y.; Xia, X.; Chong, S.;
Wang, K.-H.; Huang, D.; Fu, Y.; Hu, Y. Synlett 2015, 26, 1725–1731; (d) Zhang,
S.; Li, L.; Hu, Y.; Zha, Z.; Wang, Z.; Loh, T.-P. Org. Lett. 2015, 17, 1050–1053.
10. (a) Yao, Y.; Shu, H.; Tang, B.; Chen, S.; Lu, Z.; Xue, W. Chin. J. Chem. 2015, 33,
601–609; (b) Yanagisawa, A.; Lin, Y.; Miyake, R.; Yoshida, K. Org. Lett. 2014, 16,
86–89; (c) Zhang, H.; Wen, X.; Gan, L.; Peng, Y. Org. Lett. 2012, 14, 2126–2129;
(d) Scettri, A.; Massa, A.; Palombi, L.; Villano, R.; Acocella, M. R. Tetrahedron:
Asymmetry 2008, 19, 2149–2152; (e) Yamanaka, M.; Itoh, J.; Fuchibe, K.;
Akiyama, T. J. Am. Chem. Soc. 2007, 129, 6756–6764; (f) Rueping, M.; Sugiono,
E.; Schoepke, F. R. Synlett 2007, 1441–1445; (g) Tillman, A. L.; Dixon, D. J. Org.
Biomol. Chem. 2007, 5, 606–609; (h) Akiyama, T.; Saitoh, Y.; Morita, H.; Fuchibe,
K. Adv. Synth. Catal. 2005, 347, 1523–1526; (i) Uraguchi, D.; Terada, M. J. Am.
Chem. Soc. 2004, 126, 5356–5357.
4.2.30. (R)-2-{(R)-Phenyl[N-(4-nitrophenylamino)]methyl}cyclo-
hexanone 7e
Yellow solid (142 mg, 87% yield). Mp 123–124 °C (EtOH; lit29
121–123 °C). 90.0% ee (GC connected to a J&W Scientific Cyclosil-
B column; stationary phase: 30% heptakis (2,3-di-O-methyl-6-O-
t-butyldimethylsilyl)-b-cyclodextrin in DB-1701), tR = 6.437 min
11. (a) Guo, Q.-X.; Liu, H.; Guo, C.; Luo, S.-W.; Gu, Y.; Gong, L.-Z. J. Am. Chem. Soc.
2007, 129, 3790–3791; (b) Chen, Y.-Y.; Jiang, Y.-J.; Fan, Y.-S.; Sha, D.; Wang, Q.;
Zhang, G.; Zheng, L.; Zhang, S. Tetrahedron: Asymmetry 2012, 23, 904–909; (c)
Enders, D.; Ludwig, M.; Raabe, G. Chirality 2012, 24, 215–222.
(major), tR = 6.683 min (minor); [a]
21 = +25.1 (c 0.1, CH2Cl2). 1H
D
NMR (200 MHz, CDCl3): d = 7.89 (d, J = 9.2 Hz, 2H), 7.27–7.25 (m,
5H), 6.43 (d, J = 9.2 Hz, 2H), 4.82 (d, Jsyn = 4.4 Hz, 1H), 2.92–2.78
(m, 1H), 2.46–2.24 (m, 2H), 2.00–1.75 (m, 3H), 1.65–1.51 (m,
3H); 13C NMR (50 MHz, CDCl3): d = 212.5, 153.9, 153.4, 140.4,
130.5, 128.9, 126.5, 126.3, 113.4, 57.6, 56.8, 42.1, 32.3, 27.2, 25.0.
MS (m/z, EI): 226 [M+ꢀ98] (100), 225 (35), 186 (50), 185 (100).
12. (a) Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S. Curr. Org. Chem. 2011, 15,
576–599. and references cited therein; (b) Barbero, M.; Cadamuro, S.; Dughera,
S.; Torregrossa, R. Org. Biomol. Chem. 2014, 12, 3902–3911.
13. (a) For 7a see Goswani, P.; Das, B. Tetrahedron Lett. 2009, 50, 2384–2388; (b) for
7b see Xu, F.; Li, P.-B.; Tian, Y.-P.; Li, H.-L.; Li, Q. J. Chem. Res. 2010, 1, 15–18; (c)
for 7c and 7d see Ref. 11a; (d) for 7f see Eftekhari-Sis, B.; Abdollahifar, A.;
Hashemi, M. M.; Zirak, M. Eur. J. Org. Chem. 2006, 5152–5157.
14. Mahlau, M.; List, B. Angew. Chem., Int. Ed. 2013, 52, 518–533.
15. Barbero, M.; Bazzi, S.; Cadamuro, S.; Dughera, S. Eur. J. Org. Chem. 2009, 430–
436.
IR (neat)
m
(cmꢀ1): 3390 (NH), 1702 (CO).
16. Li, N.; Wang, J.; Zhang, X.; Qiu, R.; Wang, X.; Chen, J.; Yin, S.-F.; Xu, X. Dalton
Trans. 2014, 43, 11696–11708.
17. Kulkarni, P.; Totawar, B.; Zubaidha, P. K. Monatsh. Chem. 2012, 143, 625–629.
18. Akiyama, T.; Takaya, J.; Kagoshima, H. Adv. Synth. Catal. 2002, 344, 338–347.
19. Yang, H.-M.; Li, L.; Li, F.; Jiang, K.-Z.; Shang, J.-Y.; Lai, G.-Q.; Xu, L.-W. Org. Lett.
2011, 13, 6508–6511.
4.2.31. (R) 2-{(R)-Phenyl[N-(4-chlorophenylamino)]methyl}cyclo-
hexanone 7f
Brown solid (132 mg, 84% yield, using 2 as a catalyst). Mp 135–
136 °C (EtOH; lit20 137–138 °C). 91.4% ee (GC connected to
a J&W Scientific Cyclosil-B column; stationary phase: 30% heptakis
(2,3-di-O-methyl-6-O-t-butyldimethylsilyl)-b-cyclodextrin in
20. Kidwai, M.; Mishra, N. K.; Bansal, V.; Kumar, A.; Mozumdar, S. Tetrahedron Lett.
2009, 50, 1355–1358.

1188
M. Barbero et al. / Tetrahedron: Asymmetry 26 (2015) 1180–1188
21. Jafari, A. A.; Moradgholi, F.; Tamaddon, F. Eur. J. Org. Chem. 2009, 1249–
1255.
26. Eshghi, H.; Rahimizadeh, M.; Hosseini, M.; Javadian-Saraf, A. Monatsh. Chem.
2013, 144, 197–203.
22. Mayer, C. Bull. Soc. Chim. Fr. 1905, 33, 397.
27. Nemati, F.; Fakhaei, A. S.; Amoozadeh, A.; Hayeniaz, Y. S. Synth. Commun. 2011,
41, 3695–3702.
28. Fang, D.; Gong, K.; Zhang, D.-Z.; Liu, Z.-L. Monatsh. Chem. 2009, 140, 1325–
1329.
23. Yi, W.-B.; Chai, C. J. Fluorine Chem. 2006, 127, 1515–1521.
24. Kamble, S.; Kumbhar, A.; Rashinkar, G.; Barge, M.; Salunkhe, R. Ultrason.
Sonochem. 2012, 19, 812–815.
25. Sukumari, S.; Azath, I. A.; Pitchumani, K. Synlett 2012, 2328–2332.
29. MaGee, D. I.; Dabiri, M.; Salehi, P.; Torkian, L. Arkivoc 2011, xi, 156–164.