Construction of chiral quaternary carbon center via catalytic asymmetric aza-Henry reaction with α-substituted nitroacetates

Article abstract of DOI:10.1039/c4ra01390e

The catalytic enantioselective aza-Henry reaction of N-Boc aldimines 2 and 2-nitropropionic acid ethyl ester 3 in the mixed solvents of toluene-saturated brine (10:1) was catalyzed by cinchona quaternary ammonium salts to form a new quaternary carbon center. High yields (up to 90%), and excellent enantioselectivities (up to 99% ee) and diastereoselectivity ratio (up to 22:1) were successfully obtained with mild conditions. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c4ra01390e

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Construction of chiral quaternary carbon center via
catalytic asymmetric aza-Henry reaction with a-
substituted nitroacetates†
Cite this: RSC Adv., 2014, 4, 20346
a
a
a
a
b
*
*
Minghua Li, Nan Ji, Ting Lan, Wei He and Rui Liu
The catalytic enantioselective aza-Henry reaction of N-Boc aldimines 2 and 2-nitropropionic acid ethyl
ester 3 in the mixed solvents of toluene–saturated brine (10 : 1) was catalyzed by cinchona quaternary
ammonium salts to form a new quaternary carbon center. High yields (up to 90%), and excellent
enantioselectivities (up to 99% ee) and diastereoselectivity ratio (up to 22 : 1) were successfully obtained
with mild conditions.
Received 18th February 2014
Accepted 16th April 2014
DOI: 10.1039/c4ra01390e
www.rsc.org/advances
Puglisi and Benaglia7 used thiourea catalysts derived from N,N-
dimethyl amino for this transformation to get the correspond-
Introduction
ing products with yields range from 48–81%, the ee value 27–
81%, but the diastereoselectivities have not been reported.
Huang and Dong,8 applied thiourea–guanidine to this trans-
formation, resulting in moderate yield (up to 80%), dr (up to
7.6 : 1) and ee value (up to 88%). Meanwhile, some other groups
tried different substrates to build the chiral quaternary carbon
center via a similar procedure.9 However, the majority of
these reports focused on thiourea catalysts, some synthetic
steps of the catalysts were complicated, and the substrate scope
needed to be further broadened. In addition, only few high
diastereoselectivities ratios and ee values were observed.
Therefore, it's still an important issue to build up a practical
high enantioselective and diastereoselective method in this
challenging area.
In organic chemistry, the efficient construction of a quaternary
carbon center has always been a very important task for
researchers.1 In this area, the construction of a chiral quater-
nary carbon center is even more appealing, and it oen involves
not only enantioselectivity but also diastereoselectivity in some
transformations,2 which makes it one of the most challenging
topics in modern organic chemistry.
Enantioselective catalytic aza-Henry reaction (or nitro-Man-
nich reaction) is a useful C–C bond-forming process, the nitro
group of the product b-nitramine can easily be converted to the
corresponding amino functional group, to further obtain bio-
logically active compounds or chiral synthetic blocks.3 As a
result, considerable efforts have been directed towards the
asymmetric aza-Henry reaction over the past several years. Both
metal catalysis and organocatalysis have achieved some inter-
esting results in this eld.4 However, the nitro-substrates of the
aza-Henry reaction mostly focused on the straight-chain,
unsubstituted nitroalkanes and simple products were repor-
ted.5 In fact, a-substituted nitroacetates are very good nucleo-
philes to imines, in which adjacent quaternary and tertiary
chiral centers could be constructed concurrently. This trans-
formation is more challenging in organic synthesis, and good
results were relatively less reported in the literature. In 2008, Li
and Chen6 demonstrated the aza-Henry reaction between a-
substituted nitroacetates and N-Boc imines, which were cata-
lyzed by bifunctional thiourea–secondary-amine with naphtha-
lene, and 96% ee, 17 : 1 dr were obtained. Inspired by this,
aDepartment of Chemistry, School of Pharmacy, Fourth Military Medical University,
Xi'an 710032, Shaanxi, China. E-mail: weihechem@fmmu.edu.cn
bTangdu Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, China.
E-mail: liurui2@fmmu.edu.cn
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra01390e
Fig. 1 Structure of the quaternary ammonium salts.
20346 | RSC Adv., 2014, 4, 20346–20350
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
Recently, we have developed a series of novel quaternary
RSC Advances
Table 2 Screening of additives in the aza-Henry reaction of N-Boc
benzaldimine 2a and 2-nitropropionic acid ethyl ester 3a
ammonium salts 1a–1h (Fig. 1), which have showed excellent
chiral induction in the enantioselective alkylations of N-
(diphenylmethylene) glycine tert-butyl ester and the aza-Henry
reaction between simple nitroalkane and a-amido sulfones.10
Considering the benets of the quaternary ammonium salts in
organic catalysis, such as low cost, mild conditions, environ-
mental benign and high enantioselectivities, we attempt to use
these chiral quaternary ammonium salts to catalyze the aza-
Henry reaction between a-substituted nitroacetates and N-Boc
imines in this work, and expect to investigate the versatility of
these organocatalysts.
Entry
Additives (1eq)
Yieldb
drc
eed
1
2
3
4
5
6
7
8
Et3N
40/39
35/33
38/36
33/34
35/30
36/38
45/30
40/39
42/40
40/39
39/40
40/30
47/40
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1.5 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
37
47
45
3
39
3
50
45
40
41
31
47
43
Et2NH
Pyridine
2,2-Bipyridine
DIADe
DBUf
K2CO3
Na2CO3
NaOH
NaOAC
KOH
K2CO3
K2CO3
Results and discussion
The reaction between N-Boc benzaldimine 2a and 2-nitro-
propionic acid ethyl ester 3 was selected as the model reaction
to screen the catalysts 1a–1h (Fig. 1). The results were shown in
Table 1. Our initial studies with the diversely structured cata-
lysts 1a–1h for the analogous reaction failed to give signicant
chiral induction (Table 1, entries 1–8). Nevertheless, a relatively
high ee value was obtained by 1h (entry 8). Hence 1h has been
chosen to further screen the additives.
Then the additives and reaction temperature were screened.
It was observed that a basic additive is needed to promote the
reaction when it was carried out at a low temperature. As it was
shown in Table 2, both organic bases and inorganic bases can
improve the ee value of limited. All of which, K2CO3 was
observed to induce moderate ee value (entry 7). The reaction
temperature was then screened, because in several asymmetric
reactions, a lower temperature is benecial to improve the ee
value. Strangely, when the temperature was decreased to
ꢀ10 ꢁC, the ee value did not improve (entry 12 vs. 7). The
9
10
11
12g
13h
a
All the reactions were carried out with 0.15 mmol of 2-nitropropionic
acid ethyl ester 3 and 0.2 mmol of N-Boc benzaldimine 2a in DCM (1 mL)
in the presence of 10 mol% 1h at ꢀ5 ꢁC for 24 h. b Isolated yield of pure
c
d
4a and 5a. Calculated from the isomers 4a and 5a. ee of 4a was
determined by chiral HPLC analysis using Chiralpak AD-H column;
low ee (<10%) was observed for 5a in the tested reactions.
e
f
g
Diisopropyl azodiformate. 1,8-Diazabicyclo[5,4,0] undec-7-ene. At
ꢀ10 ꢁC. h At 0 ꢁC.
temperature was also increased to 0 ꢁC, the ee value maintained
at the same level (entry 13 vs. 7). So, ꢀ5 ꢁC was chosen to further
screen the conditions.
It was found that solvents have a great effect on the asym-
metric reactions. So, different solvents were screened in the
presence of 1h (Table 3). High yields and low ee values could be
obtained in non-polar solvents (entry 1 and 2). Good yields and
moderate ee value were observed in ether (entry 3). Ethyl
acetate, isopropanol, and acetone were found to show a poor
chiral induction (entries 4–6). Comparing entry 8 to entry 7, it
could be concluded that dried dichloromethane was inferior to
the untreated dichloromethane, which indicated that a bit of
water was benet for this reaction (entry 8 vs. 7). When toluene
was used as the solvent, the ee value could be improved
dramatically (entry 10). Not surprisingly, the best result (90%
isolated yield, >99% ee of 4a, 22 : 1 dr) was obtained using the
mixed solvent toluene–saturated brine (10 : 1) (entry 11).
However, when the ratio of saturated brine in mixed solvent was
increased, both the ee value and dr ratio decreased signicantly
(entry 12).
Table 1 Screening of organocatalysts in the aza-Henry reaction of N-
Boc benzaldimine 2a and 2-nitropropionic acid ethyl ester 3a
Entry
Catalyst
Yieldb
drc
eed
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
45/37
38/41
42/39
39/41
40/38
38/36
33/35
45/40
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
21
18
8
21
23
15
18
33
To summarize, the optimal condition was: 10 mol% of 1h as
ꢁ
the catalyst, 1 equivalent of K2CO3, at ꢀ5 C in the mixture of
1g
1h
toluene–saturated brine (10 : 1). Then, the reaction scope for N-
Boc imine was investigated, and the products were summarized
in Fig. 2.
a
All the reactions were carried out with 0.15 mmol of 2-nitropropionic
acid ethyl ester 3 and 0.2 mmol of N-Boc benzaldimine 2a in DCM (1 mL)
in the presence of 10 mol% of catalyst at ambient temperature for 24 h.
The N-Boc aldimines were derived from different kinds of
substituted aldehyde. From Fig. 2, we can see that the optimal
condition has good substrates applicability. Both the electron-
b
Isolated yield of pure 4a and 5a. c Calculated from the isomers 4a and
5a. d ee of 4a was determined by chiral HPLC analysis using Chiralpak
AD-H column; low ee (<10%) was observed for 5a in the tested reactions.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 20346–20350 | 20347

View Article Online
RSC Advances
Paper
Table 3 Screening of solvents in the aza-Henry reaction of N-Boc
benzaldimine 2a and 2-nitropropionic acid ethyl ester 3a
withdraw group, the ee value was higher than electron-donating
group. Moderate results were obtained for thiophene-substituted
imine. The aliphatic substrates were also tested, but the result
was not satisfactory.11 It should be emphasized that the optical
rotation of the enantiomer products 4 obtained by this method-
ology were just opposite to the literature,6 and to the best of our
knowledge, they were not reported by others so far.
Based on the previous mechanism studies7,9a of the aza-
Henry reaction and the experiment results, a potential transi-
tion state to reveal the possible mechanism of this asymmetric
catalytic aza-Henry reaction was proposed. As shown in Fig. 3,
the hydrogen-bound may be formed between the carbonyl
group of N-Boc benzaldehyde imine and 9-hydroxy group of
cinchonine. Meanwhile, an ion pair may be formed between the
carbon anion generated from 2-nitropropionic acid ethyl ester
with the help of base and ammonium cation of 1h. Subse-
quently, the Si-face attack of the imine affords the desired
adducts 4a with (R, R) conguration. The scaffold of the
bifunctional catalyst plays a signicant role in stereocontrolling
of the aza-Henry reaction. The hydrogen bonding and ion pair
interactions between the catalyst and the two reactants may be
synergistically responsible for the excellent stereoselectivity.
Nevertheless, the real transition state model still needs further
investigation.
Entry
Solvent
Yieldb
drc
eed
1
2
3
4
5
6
7
8
Hexane
Pentane
Ether
Ethyl acetate
Isopropanol
47/34
41/40
78/9
44/40
40/36
43/40
45/40
45/30
78/5
2 : 1
1 : 1
8 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1.5 : 1
16 : 1
17 : 1
22 : 1
20 : 1
21
11
40
20
7
Acetone
3
Dried dichloromethane
Dichloromethane
m-Xylene
Toluene
Toluene–saturated brine
Toluene–saturated brine
17
50
61
82
>99
77
9
10
11e
12f
82/5
86/4
80/4
a
All the reactions were carried out with 0.15 mmol of 2-nitropropionic
acid ethyl ester 3 and 0.2 mmol of N-Boc benzaldimine 2a in solvents (1
mL) in the presence of 10 mol% of 1h and 0.15 mmol K2CO3 at ꢀ5 ꢁC for
15 h. b Isolated yield of pure 4a and 5a. c Calculated from the isomers 4a
d
and 5a. ee of 4a was determined by chiral HPLC analysis using
Chiralpak AD-H column; low ee (<10%) was observed for 5a in the
tested reactions. Reaction for 12 h, 1.1 mL toluene–saturated brine
(10 : 1). Reaction for 12 h, 1 mL toluene–saturated brine (1 : 1).
e
Moreover, four new compounds were prepared with high
yields, dr ratio and excellent ee value. Our work is a good
complement to the previous report.
f
Experimental
General
All the starting materials and reagents were purchased from
commercial suppliers and used without further purication.
Solvents were puried by standard procedures. NMR spectra
were recorded on a Bruker AV-400 spectrometer with CDCl3 as
solvent. High-Resolution Mass Spectroscopy (HRMS) was
carried out on a BRUKER APEX-II. High performance liquid
chromatography (HPLC) was performed by an Agilent 1260
interfaced to an HP 71 series computer workstation with Daicel
Chiralpak AD-H chiral column. The yields are of materials iso-
lated by column chromatography gel plates.
Fig. 2 Scope of stereoselective aza-Henry reaction of N-Boc aldi-
mines 2 and 2-nitropropionic acid ethyl ester 3.
withdraw group and the electron-donating group that con-
nected to the benzene ring can give good yields, and the
majority of corresponding products can be obtained with
excellent ee values and diastereoselectivities. The o,m,p-
substituted substrates gave different results. Where ortho, para-
substituted chlorine, bromine gave excellent results, para-
substituted uorine and triuoromethyl can give high yield and
ee value. When methyl is connected to the benzene ring, meta-
substituted can get better result than para-substituted. In
general, when substituting the aldehyde with the electron-
Fig. 3 Proposed transition state for the reaction.
20348 | RSC Adv., 2014, 4, 20346–20350
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
nm, tmajor ¼ 11.95 min, tminor ¼ 8.89 min. [a]2D0 ꢀ12.3 (in EtOH);
1H NMR (400 MHz, CDCl3): d ¼ 7.63 (d, J ¼ 8.4, 2H), 7.52 (d, J ¼
8, 2H), 6.46–6.43 (m, 1H), 5.59–5.56 (m, 1H), 4.34–4.27 (m, 2H),
1.77 (s, 3H), 1.41 (s, 9H), 1.29 (t, J ¼ 7.2 Hz, 3H) ppm; 13C NMR d
¼ 165.5, 154.6, 140.0, 131.1, 130.7, 129.1, 125.6, 125.5, 94.3,
80.7, 63.4, 59.5, 28.2, 22.3, 13.6 ppm; HRMS: calcd for
Procedure for the synthesis of organocatalysts
The quaternary ammonium salts 1a–1h were synthesized by
condensation of four natural cinchona alkaloids with 2-chlor-
omethyl benzimidazole or 1-chloromethyl benzotriazole
respectively, following our previously reported procedure.10
C
18H23F3N2O6 + Na 443.1400, found 443.1406.
(2R,3R)-Ethyl 3-(tert-butoxycarbonylamino)-2-methyl-2-
Procedure for the synthesis of N-Boc benzaldimine 2a
nitro-3-m-tolylpropanoate 4h. Enantiomeric excess was deter-
mined to be 93% by HPLC on Chiralpak AD-H column (10% 2-
propanol–n-hexane, 1 mL minꢀ1), UV 220 nm, tmajor ¼ 9.10 min,
tminor ¼ 5.89 min. [a]D20 ꢀ9.6 (in EtOH); 1H NMR (400 MHz,
CDCl3): d ¼ 7.25–7.21 (m, 1H), 7.15–7.13 (m, 3H), 6.41 (d, J ¼
8.8, 1H), 5.49 (d, J ¼ 9.6, 1H), 4.33–4.28 (m, 2H), 2.36 (s, 3H),
1.74 (s, 3H), 1.41 (s, 9H), 1.29 (t, J ¼ 7.2 Hz, 3H) ppm; 13C NMR d
¼ 165.7, 154.7, 138.3, 135.7, 129.4, 129.3, 128.5, 125.5, 94.7,
80.2, 65.8, 63.1, 59.8, 28.2, 22.5, 21.5, 15.2, 13.6 ppm; HRMS:
calcd for C18H25N2O6 + Na 389.1683, found 389.1683.
N-Boc benzaldimine 2a was prepared with high yields, following
the reported procedure with minor improvements.12
Representative procedure for the organocatalytic asymmetric
aza-Henry reaction
Conclusions
In summary, a series of readily available cinchona quaternary
ammonium salts were successfully applied in the asymmetric
aza-Henry reaction between esters of a-substituted nitro-acetic
Into a solution of 0.2 mmol of N-Boc benzaldimine 2a in 1.1 mL and N-Boc aldimines with excellent enantioselectivities, yields
toluene–saturated brine (10 : 1), 10 mol% of catalyst 1h, 0.15 and diastereoselectivities. Series of new high enantioselective
mmol of 2-nitropanoinate 3, 0.15 mmol K2CO3 was added, and nitro–amino esters containing chiral quaternary carbon centers
the mixture was stirred for 12 h at ꢀ5 ꢁC. The reaction mixture were successfully synthesized. Cheap catalysts, mild reaction
was then concentrated and puried by ash chromatography on conditions and good results make this methodology very prac-
silica gel (hexane–EtAc, 50/1). Among all the aza–Henry reaction tical. Use of this protocol to synthesize biologically active
adducts, 4d, 4e, 4g, 4h are new compounds.
molecules is ongoing in our laboratory.
(2R,3R)-Ethyl 3-(2-bromophenyl)-3-(tert-butoxycarbonyl
amino)-2-methyl-2-nitropropanoate 4d. Enantiomeric excess
was determined to be 99% by HPLC on Chiralpak AD-H column
Acknowledgements
(10% 2-propanol–n-hexane, 1 mL minꢀ1), UV 220 nm, tmajor
¼
We thank the National Natural Science Foundation of China
9.40 min, tminor ¼ 7.03 min. [a]2D0 +11.3 (in EtOH); 1H NMR (400 (21272272) for nancial support. We also would like to express
MHz, CDCl3): d ¼ 7.61 (d, J ¼ 8.0, 1H), 7.31 (t, 1H), 7.2 (t, 2H), our great thanks to Mr Adam Teslik for language revision.
6.58 (d, J ¼ 9.6, 1H), 6.23 (d, J ¼ 9.2, 1H), 4.43–4.31 (m, 2H), 1.80
(s, 3H), 1.42 (s, 9H), 1.37 (t, J ¼ 7.2 Hz, 3H) ppm; 13C NMR d ¼
Notes and references
166.4, 154.4, 135.6, 133.4, 130.2, 128.6, 128.4, 125.5, 96.8, 80.4,
63.6, 56.3, 28.2, 20.7, 13.9 ppm; HRMS: calcd for C17H23BrN2O6
+ Na 453.0632, found 453.0635.
1 (a) K. Fuji, Chem. Rev., 1993, 93, 2037–2066; (b) D. Seebach,
Angew. Chem., Int. Ed., 2011, 50, 96–101.
(2R,3R)-Ethyl 3-(4-bromophenyl)-3-(tert-butoxycarbonyl
amino)-2-methyl-2-nitropropanoate 4e. Enantiomeric excess
was determined to be 99% by HPLC on Chiralpak AD-H column
2 (a) I. Denissova and L. Barriault, Tetrahedron, 2003, 59,
10105–10146; (b) B. Wang and Y. Q. Tu, Acc. Chem. Res.,
2011, 44, 1207–1222; (c) O. Riant and J. Hannedouche, Org.
Biomol. Chem., 2007, 5, 873–888; (d) J. Christoffers and
A. Baro, Adv. Synth. Catal., 2005, 347, 1473–1482; (e)
J. Christoffers and A. Mann, Angew. Chem., Int. Ed., 2001,
40, 4591–4597.
3 (a) A. Noble and J. C. Anderson, Chem. Rev., 2013, 113, 2887–
2939; (b) A. Ting and S. E. Schaus, Eur. J. Org. Chem., 2007, 35,
5797–5815.
(10% 2-propanol–n-hexane, 1 mL minꢀ1), UV 220 nm, tmajor
¼
1
16.06 min, tminor ¼ 7.94 min. [a]2D0 ꢀ24.5 (in EtOH); H NMR
(400 MHz, CDCl3): d¼ 7.49 (d, J ¼ 8.4, 2H), 7.25 (d, J ¼ 8.4, 2H),
6.41–6.39 (m, 1H), 5.48–5.46 (m, 1H), 4.36–4.24 (m, 2H), 1.75 (s,
3H), 1.40 (s, 9H), 1.30 (t, J ¼ 7.2 Hz, 3H) ppm; 13C NMR d ¼
165.5, 154.6, 135.0, 131.8, 131.5, 130.3, 127.9, 122.9, 94.4, 80.6,
63.3, 59.4, 28.2, 22.4, 13.6 ppm; HRMS: calcd for C17H23BrN2O6
+ Na 453.0632, found 453.0634.
4 For recent examples of the aza-Henry reaction using metal
catalysis and organocatalysis (a) K. I. Yamada,
(2R,3R)-Ethyl 3-(tert-butoxycarbonylamino)-2-methyl-2-
nitro-3-(4-(triuoromethyl)phenyl)propanoate 4g. Enantio-
meric excess was determined to be 96% by HPLC on Chiralpak
AD-H column (10% 2-propanol–n-hexane, 1 mL minꢀ1), UV 220
¨
S. J. Harwood, H. Groger and M. Shibasaki, Angew. Chem.,
Int. Ed., 1999, 38, 3504–3506; (b) T. Okino, S. Nakamura,
T. Furukawa and Y. Takemoto, Org. Lett., 2004, 6, 625–627;
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 20346–20350 | 20349

View Article Online
RSC Advances
Paper
(c) F. Fini, V. Sgarzani, D. Pettersen, R. P. Herrera, L. Bernardi
and A. Ricci, Angew. Chem., Int. Ed., 2005, 44, 7975–7978; (d)
6 B. Han, Q. P. Liu, R. Li, X. Tian, X. F. Xiong, J. G. Deng and
Y. C. Chen, Chem.–Eur. J., 2008, 14, 8094–8097.
´
C. Palomo, M. Oiarbide, A. Laso and R. Lopez, J. Am. Chem.
7 A. Puglisi, L. Raimondi, M. Benaglia, M. Bonsignore and
S. Rossi, Tetrahedron Lett., 2009, 50, 4340–4342.
8 B. Han, W. Huang, Z. R. Xu and X. P. Dong, Chin. Chem. Lett.,
2011, 22, 923–926.
9 For recent examples of the aza-Henry reaction using
different nitro-substrates (a) W. Fan, S. Kong, Y. Cai,
G. Wu and Z. W. Miao, Org. Biomol. Chem., 2013, 11, 3223–
3229; (b) C. B. Ji, Y. L. Liu, X. L. Zhao, Y. L. Guo,
H. Y. Wang and J. Zhou, Org. Biomol. Chem., 2012, 10,
1158–1161; (c) D. Uracuchi, K. Koshimoto, C. Sanada and
T. Ooi, Tetrahedron: Asymmetry, 2010, 21, 1189–1190.
Soc., 2005, 127, 17622–17623; (e) D. Uraguchi,
K. Koshimoto and T. Ooi, J. Am. Chem. Soc., 2008, 130,
10878–10879; (f) B. M. Nugent, R. A. Yoder and
J. N. Johnston, J. Am. Chem. Soc., 2004, 126, 3418–3419; (g)
A. Singh and J. N. Johnston, J. Am. Chem. Soc., 2008, 130,
5866–5867; (h) Z. Chen, H. Morimoto, S. Matsunage and
M. Shibasaki, J. Am. Chem. Soc., 2008, 130, 2170–2171; (i)
H. X. He, W. Yang and D. M. Du, Adv. Synth. Catal., 2013,
355, 1137–1148.
5 For recent examples of the aza-Henry reaction using straight-
chain of the nitro-substrates (a) T. P. Yoon and 10 (a) Y. Wei, W. He, Y. L. Liu, P. Liu and S. Y. Zhang, Org. Lett.,
E. N. Jacobsen, Angew. Chem., Int. Ed., 2005, 44, 466–468;
(b) L. Bernardi, F. Fini, R. P. Herrera, A. Ricci and
V. Sgarzani, Tetrahedron, 2006, 62, 375–380; (c) C. M. Bode,
2012, 14, 704–707; (b) W. He, Q. J. Wang, Q. F. Wang,
B. L. Zhang, X. L. Sun and S. Y. Zhang, Synlett, 2009, 8,
1311–1314.
A. Ting and S. E. Schaus, Tetrahedron, 2006, 62, 11499– 11 Naphthalene–formaldehyde derived imine, methoxy
11505; (d) M. T. Robak, M. Trincado and J. A. Ellman, J.
Am. Chem. Soc., 2007, 129, 15110–15111; (e) Y. W. Chang,
J. J. Yang, J. N. Dang and Y. X. Xue, Synlett, 2007, 14, 2283–
2285; (f) C. Rampalakos and W. D. Wulff, Adv. Synth.
Catal., 2008, 350, 1785–1790; (g) C. Wang, Z. Zhou and
C. Tang, Org. Lett., 2008, 10, 1707–1710.
benzaldehyde imine and cyclohexyl aldimine were also
examined. Unfortunately, cyclohexyl aldimine did not even
react, the other two gave high yields but low ee value. The
product of naphthalene–formaldehyde derived imine was
racemic, and only 15% ee value was obtained by methoxy
benzaldehyde derived imine.
12 J. W. Yang, S. C. Pan and B. List, Org. Synth., 2009, 86, 11–17.
20350 | RSC Adv., 2014, 4, 20346–20350
This journal is © The Royal Society of Chemistry 2014