A general, highly enantioselective Michael addition of nitroalkanes to α,β-unsaturated enones catalyzed by 9-amino(9-deoxy)-epi-quinine: a remarkable additive effect

Article abstract of DOI:10.1016/j.tet.2016.07.008

A particularly general protocol for the organocatalytic asymmetric Michael addition of nitroalkanes to α,β-unsaturated enones is reported. The Michael reaction proceeded smoothly and provided the desired adducts in moderate to excellent yields (55–99%) an

Full text of DOI:10.1016/j.tet.2016.07.008

Tetrahedron 72 (2016) 5115e5120
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A general, highly enantioselective Michael addition of nitroalkanes
to a,b-unsaturated enones catalyzed by 9-amino(9-deoxy)-epi-
quinine: a remarkable additive effect
Siyang Liu a, Qingqing Wang a, Ling Ye b, Zhichuan Shi a, Zhigang Zhao a, Xuejun Yang a,
,
Keyi Ding a, Xuefeng Li a
*
a College of Chemistry and Environment Protection Engineering, Southwest University for Nationalities, Chengdu 610041, China
b Faculty of Geosciences and Environmental Engineering, Southwest Jiaotong University, Chengdu 610031, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 May 2016
Received in revised form 29 June 2016
Accepted 2 July 2016
Available online 4 July 2016
A particularly general protocol for the organocatalytic asymmetric Michael addition of nitroalkanes to
a,b-unsaturated enones is reported. The Michael reaction proceeded smoothly and provided the desired
adducts in moderate to excellent yields (55e99%) and good to excellent enantioselectivities (65e99% ee).
The addition of readily available achiral base significantly enhanced the reactivity without compromising
the enantioselectivity.
Ó 2016 Elsevier Ltd. All rights reserved.
Keywords:
Michael addition
Nitroalkane
a,b-Unsaturated enone
Additive
9-Amino(9-deoxy)-epi-quinine
1. Introduction
utility and easy scale-up of this transformation were therefore
limited to a certain extent.
Chiral primary amines are effective covalent-based activators of
sterically hindered carbonyl compounds,1 and overcome the in-
trinsic limitations of chiral secondary amine catalysis,2 which is
restricted to the functionalization of unhindered aldehyde com-
pounds. They enrich the aminocatalytic activation modes and
provide new opportunities for developing challenging and non-
conventional transformations in carbonyl compound chemistry.
Among all reported primary aminocatalysts, cinchona-derived
primary amines1e,f constantly infer high levels of stereocontrol in
the case of various iminium ion,3 vinylogous iminium ion,4 en-
amine,5 dienamine,6 and trienamine7 activation modes, thus pro-
viding a reliable catalytic platform for functionalization of hindered
The development of efficient chiral catalyst is crucial to a suc-
cessful catalytic asymmetric course. However, not every chemist is
fortunate enough to always obtain satisfactory catalyst from rou-
tine design and synthesis. Furthermore, even the superior catalyst
is presumably obtained after long-term optimization and design in
most cases. On the other hand, it is indicated that the addition of
suitable achiral additive will lead to impressive improvement of
reactivity and even enantioselectivity in some cases,10 when com-
paring with the use of organocatalyst alone.11 This economical
approach is beneficial in avoiding tedious chemical synthesis and
will allow highly efficient construction of libraries of catalyst sys-
tem via simply changing the additives of choice. Considering the
outstanding catalytic performance of cinchona-derived primary
amines, the combination of easily accessible additive with them is
clearly worthy exploring.3a The positive influence exerted by ad-
ditive will efficiently avoid large screening of catalysts during the
course of optimization of reaction conditions, therefore researchers
can concentrate on exploring novel reactivity patterns and
expanding the synthetic potential of aminocatalysis.
carbonyl compounds at their a 5 b 3 g6 and even d4 positions. Al-
, ,
though cinchona-based primary amines have been successfully
applied to a range of highly enantioselective conjugate addi-
tions,3a,b,8 quite poor reactivity was observed in the case of Michael
addition of nitroalkane to a,b
-unsaturated enone.9 Although good
conversion was later achieved under high-pressure condition, the
Based on our continuous interest in asymmetric conjugate ad-
dition reactions,12 herein we present a highly enantioselective
Michael reaction of nitroalkanes to a,b
-unsaturated enones9,13 in
* Corresponding author. Tel.: þ86 28 85928015; e-mail address: lixuefeng@swun.
edu.cn (X. Li).
http://dx.doi.org/10.1016/j.tet.2016.07.008
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

5116
S. Liu et al. / Tetrahedron 72 (2016) 5115e5120
the presence of 9-amino(9-deoxy)-epi-quinine. Remarkably, the
addition of appropriate additives greatly enhanced the reactivity of
this asymmetric process. As a result, this asymmetric Michael re-
action proceeded smoothly under ambient pressure with high
levels of enantioselectivity.
model reaction was remarkably accelerated by a range of tertiary
amines with minimal loss of enantioselectivity (entries 2e5).
Triethylamine (TEA) and N-methylmorpholine (NMM) significantly
improved the isolated yields from early 48% to later 91% and 96%,
respectively (entries 2 and 3). However, relatively lower rate was
observed in the presence of Hunig’s base (DIPEA, N,N-diisopropy-
lethylamine) and 1,4-diazabicyclo[2.2.2]octane (DABCO) (entries 4
and 5). Especially for DABCO, prolonged reaction time (144 h) was
required to achieve acceptable yield. Encouraged by the reactivity
enhancement afforded by these tertiary amines, we successively
evaluated the effect of easily accessible secondary amines. Piperi-
dine and the hindered base, 2,2,6,6-tetramethylpiperidine (TMP),
both enabled the model transformation to complete within due
time and afforded the desired adducts with 95% ee (entries 6 and 7).
On the other hand, tetrahydropyrrole led to a significant activity
improvement (24 h, 92% yield) at the cost of pronounced enan-
tioselectivity erosion, presumably owing to the intensive back-
ground reaction (entry 8). Apparently, the observed catalytic
reactivity was closely correlated with the basicity of additive. In
accordance with DABCO, the strongly basic additives, 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) and tetramethylguanidine
(TMG), both generated adduct 3aa in somewhat poorer yields
2. Result and discussion
Considering the poor reactivity of Michael addition of nitro-
methane to cyclic a,b-unsaturated enones exhibited in the previous
report,9 we initially performed the model reaction in neat nitro-
methane. In agreement with the early study,9 the Michael addition
of nitromethane to cinnamone afforded sluggish conversion again
(Table 1, entry 1). Less than half of desired adduct 3a was obtained
even after 96 h, albeit with excellent enantioselectivity. It was
documented that a twofold excess of acid with respect to the
aminocatalyst was generally essential for the iminium ion-
promoted transformations of unsaturated carbonyl compounds,
because condensation with carbonyl group could be considerably
accelerated under acidic conditions.1f As a consequence, the more
basic tertiary amine of the quinuclidine core was preferentially
protonated, thereby losing ability to deprotonate nitromethane.
Having realized that the low conversion might be caused by pro-
tonation of the basic bridge-head nitrogen atom, we assumed that
introducing extra base might improve reactivity.3a Indeed, the
(entries 5,
9
and 10). Meanwhile, proton-sponge (1,8-
bis(dimethylamino)naphthalene) could also efficiently accelerate
this asymmetric process and generated the adduct 3aa almost
Table 1
Additive evaluation in the Michael addition of nitromethane 2a to cinnamone 1aa
Entry
Additive
Yield (%)b
ee (%)c
1
2
3
/
48
91
96
86
78
97
93
92
80
68
96
87
58
67
63
NR
97
94
96
96
96
95
95
49
90
94
97
95
96
96
94
/
TEA
NMM
DIPEA
4
5d
6
DABCO
Piperidine
TMP
Tetrahydropyrrole
DBU
TMG
Proton-sponge
K2CO3
KHCO3
KOAc
Na2CO3
NaOH
7
8e
9
10
11
12
13
14
15
16
a
Unless otherwise noted, the reaction was performed with 0.1 mmol of 1a, 20 mol % 4, 40 mol % benzoic acid and 20 mol % additive in 1 mL of nitromethane at 30 ꢀC for 96 h.
NR¼no reaction.
b
Isolated yield after flash chromatography on silica gel.
Determined by HPLC on chiral AS-H column.
The reaction time was 144 h.
The transformation completed after 24 h.
c
d
e

S. Liu et al. / Tetrahedron 72 (2016) 5115e5120
5117
without compromise of enantiopurity (entry 11 vs entry 1). In ad-
dition to the organic base, the inorganic base could also serve as
effective additive, albeit relatively less reactivity improvement was
detected (entries 12e15). Notably, the involvement of NaOH totally
suppressed this transformation (entry 16).
substituents on the aromatic rings worked properly and furnished
the desired adducts 3abeah in high yields with excellent enan-
tioselectivities (Table 3, entries 2e8). This asymmetric process was
independent of the electronic character of substituted group. Both
electron-deficient cinnamones 1bee and electron-rich analogues
1feh undertook complete transformations and displayed high
degree of enantioselectivities (entries 2e5 vs entries 6e8). At the
same time, the steric hindrance imposed by the substituents lo-
cated on the aromatic rings exerted limited influence on the re-
activity and stereocontrol. The ortho-substituted electrophiles 1e
and 1g were fully converted into target products within 48 h (en-
tries 5 and 7). Compounds 1i and 1j, both possessing a bulky
naphthyl group on the terminal site of double bond, were also
suitable acceptors and afforded the desired adducts with 93% and
99% ee, respectively (entries 9 and 10). The heteroaromatic accep-
tors 1k and 1l were all well tolerated, however, prolonged reaction
time was required probably owing to the electron-rich property of
furanyl and thiophenyl groups (entries 11 and 12). In addition, al-
iphatic enones 1m and 1n were competent acceptors and afforded
the corresponding adducts 3am and 3an with high optical purities
(entries 13 and 14). In line with previous research,13iek these sub-
strates exhibited relatively poorer reactivity and 144 h was neces-
sary for their complete conversions. After a careful investigation of
substituted groups at the end of double bond, we next evaluated
Once indentifying proton-sponge as the optimal additive, we
turned our attention to investigate the effect of acid cocatalyst. A
variety of substituted aromatic acids proved to be efficient co-
catalysts (Table 2, entries 2e5). The model reaction proceeded
smoothly in the presence of these substituted acids and afforded
the desired adduct in 82e93% yields, however, slightly poorer en-
antiomeric excesses were afforded in contrast with benzoic acid
(entries 2e5 vs entry 1). Further study revealed that aliphatic acid
displayed diminished catalytic activity in comparison with aro-
matic acids (entry 6 vs entries 1e5). Notably, the model reaction
almost didn’t occur in the presence of commonly-used strong acids,
including trifluoroacetic acid (TFA), p-toluenesulfonic acid (TsOH)
and trifluoromethanesulfonic acid (TfOH) (entries 7e9). The re-
activity and enantioselectivity slightly decreased when benzoic
acid and 4 was combined in a 1:1 ratio (entry 10). Moreover, the
reactivity was also relatively sensitive to the loading of additive.
Diminished catalytic efficiency was observed when 10 mol % of
proton-sponge was utilized, however, only negligible reactivity
improvement was achieved in the presence of 40 mol % of proton-
sponge (entries 11 and 12). Furthermore, the yield of 3aa decreased
to 80% when the amount of aminocatalyst 4 was reduced to 10 mol
% (entry 13). To our delight, elevating reaction temperature exerted
beneficial effect on catalytic activity. Nearly quantitative desired
adduct was formed almost without loss of enantioselectivity at
40 ꢀC after 48 h (entry 14). After careful investigation, the optimal
reaction conditions were therefore found to be a combination of
the effect of substituent at the a
0-site of enones (entries 15e16). In
general, relatively poorer reactivity was observed for these com-
pounds in comparison with cinnamones bearing a methyl group
adjacent to the carbonyl group (entries 15 and 16 vs entry 1).13j,k
Even after 168 h, less than 80% isolated yields were attained in
the case of ethyl-substituted 1o and isopropyl-substituted 1p (en-
tries 15 and 16). The bulky alkyl group beside the carbonyl group
might retard formation of iminium ion with primary aminocatalyst
4, thereby leading to poor reactivity. To our delight, cyclic enones,
such as 2-cyclohexene-1-one and 2-cyclopenten-1-one, were all
highly active acceptors (entries 17 and 18). Reactions of 1q and 1r
went to completion within 24 h and provided the desired adducts
with good levels of enantioselectivity (96% ee for 1aq, 81% ee for
1ar). Gratifyingly, trace double Michael addition products were
detected for these two cyclic acceptors and the desired mono-
addition adducts were isolated in 98% and 92% yields, re-
spectively. As mentioned by previous approach, double addition
was found to be prone to occur in the case of cyclic enones.13l Be-
sides nitromethane, nitroethane and 2-nitropropane were favor-
ably applicable to this asymmetric process (entries 19 and 20).
When nitroethane reacted with cinnamone 1a, excellent enantio-
selectivities were obtained for both diastereoisomers, but the di-
astereomeric ratio was close to 1:1, presumably due to facile
epimerization of the adduct in the presence of proton-sponge.
More importantly, this Michael addition also occurred efficiently
when the amount of donor was reduced. The model reaction
completed within 96 h in the case of nine equivalent of nitro-
methane and afforded the desired adduct 3aa in satisfactory yield
and excellent enantiomeric excess (entry 21).
To our delight, our organocatalytic protocol was also effective
with chalcones, a class of challenging substrates for iminium ion
activation.3b,12a As demonstrated in Table 4, the Michael reactions
of chalcone 5a and its analogues 5bei proceeded smoothly, gen-
erating the desired adducts 6aei with good to excellent enantio-
selectivities (65e97% ee) (Table 4, entries 1e9). Owning to the
steric hindrance imposed by the aromatic ring adjacent to the
carbonyl group, chalcone and its analogues displayed relatively
lower reactivity in comparison with cinnamones. Nevertheless,
good conversions could be achieved when reaction time was pro-
longed to 168 h. Gratifyingly, both electron-neutral 5a, electron-
rich 5bec, 5f and electron-poor chalcones 5d, 5g delivered the
corresponding adducts in good yields and with satisfactory
cinchona-derived primary amine
4 (20 mol %), benzoic acid
(40 mol %) and proton-sponge (20 mol %) as additive at 40 ꢀC.
Table 2
Optimization of reaction conditions for Michael addition of nitromethane 2a to
cinnamone 1aa
Entry
Additive
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
BA
96
91
82
86
93
70
NR
NR
NR
93
80
98
80
99
97
96
96
94
97
95
/
PNBA
ONBA
SA
OFBA
HOAc
TFA
TsOH
TfOH
BA
BA
BA
BA
BA
/
/
9
10d
11e
12f
13g
14h
96
96
96
96
96
a
Unless otherwise noted, the reaction was performed with 0.1 mmol of 1a,
20 mol % 4, 40 mol % benzoic acid and 20 mol % proton-sponge in 1 mL of nitro-
methane at 30 ꢀC for 96 h. BA¼benzoic acid, PNBA¼p-nitrobenzoic acid, ONBA¼o-
nitrobenzoic acid, SA¼salicylic acid, OFBA¼o-fluorobenzoic acid.
b
Isolated yield after flash chromatography on silica gel.
Determined by HPLC on chiral AS-H column.
With 20 mol % benzoic acid.
With 10 mol % proton-sponge.
With 40 mol % proton-sponge.
The reaction was performed with 10 mol % 4, 20 mol % benzoic acid and 20 mol %
c
d
e
f
g
proton-sponge.
h
The reaction was conducted at 40 ꢀC for 48 h.
With the optimal reaction conditions in hand, we subsequently
examined a range of a,b-unsaturated enones and nitroalkanes to
explore the generality of this novel catalytic system. As illustrated
in Table 3, cinnamone derivatives 1beh possessing various

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S. Liu et al. / Tetrahedron 72 (2016) 5115e5120
Table 3
Substrate scope of Michael addition of nitroalkanes to cinnamones and its analoguesa
Entry
R1
R2
1
3
Time (h)
Yield (%)b
ee (%)c
1
2
3
4
5
6
7
8
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
1a
1b
1c
1d
1e
1f
1g
1h
1i
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
48
48
48
48
48
48
48
48
48
48
96
96
144
144
168
168
24
8
99
92
93
98
96
95
98
91
97
99
75
78
99
95
75
61
96
95
98
98
95
97
95
98
93
99
96
95
92
95
97
95
96
81
98(96)
95
97
p-FC6H4
p-ClC6H4
m-ClC6H4
o-ClC6H4
p-MeC6H4
o-MeC6H4
p-MeOC6H4
1-Naphthyl
2-Naphthyl
2-Furanyl
2-Thiophenyl
Me
n-Bu
Ph
Ph
eC3H6e
eC2H4e
Ph
Ph
Ph
9
10
11
12
13
14
15
16d
17
18
19e
20g
21h
1j
1k
1l
3aj
3ak
3al
1m
1n
1o
1p
1q
1r
1a
1a
1a
3am
3an
3ao
3ap
3aq
3ar
3ba
3ca
3aa
i-Pr
98
92
Me
Me
Me
36
24
96
93f(47þ46)
99
92
a
Unless otherwise noted, the reaction was performed with 0.1 mmol of 1, 20 mol % 4, 40 mol % benzoic acid and 20 mol % proton-sponge in 1 mL of nitromethane at 40 ꢀC.
Isolated yield after flash chromatography on silica gel.
Determined by HPLC on chiral column.
With 40 mol % proton-sponge.
With 1 mL of nitroethane as the donor.
Total yield for both diastereoisomers. The diastereomeric ratio (syn/anti) was 1:1, and the ee value of the anti-diastereoisomer was shown in parentheses.
With 1 mL of 2-nitropropane as the donor.
b
c
d
e
f
g
h
The reaction was performed with 0.2 mmol of 1, 1.8 mmol of nitromethane, 20 mol % 4, 40 mol % benzoic acid and 20 mol % proton-sponge in 0.5 mL of tetrahydrofuran at
40 ꢀC.
enantiomeric excesses (entries 1e4, 6 and 7). Notably, 6g was the
crucial intermediate of the therapeutically useful GABA (g-amino-
Fortunately, the heteroaromatic chalcones 5e and 5hei, which
had been rarely reported before, underwent clean reactions and
gave rise to the desired products in moderate to good yields and
good to excellent enantioselectivities (entries 5, 8 and 9).
butyric acid) receptor agonist, baclofen, and our approach allowed
its synthesis with significantly high enantioselectivity (entry 7).14
Table 4
Substrate scope of Michael addition of nitromethane to chalconesa
Entry
Ar1
Ar2
5
6
Yield (%)b
ee (%)c
1
2
3
Ph
Ph
Ph
Ph
Ph
p-MeC6H4
p-MeOC6H4
p-FC6H4
5a
5b
5c
5d
5e
5f
5g
5h
5i
6a
6b
6c
6d
6e
6f
6g
6h
6i
87
85
82
85
60
78
82
76
67
95
97
97
92
65
92
92
95
93
4
5d
6
Ph
2-Thiophenyl
p-MeOC6H4
p-ClC6H4
2-thiophenyl
2-furanyl
Ph
Ph
Ph
Ph
7
8
9d
a
Unless otherwise noted, the reaction was performed with 0.1 mmol of 5, 20 mol % 4, 40 mol % benzoic acid and 20 mol % proton-sponge in 1 mL of nitromethane at 40 ꢀC.
Isolated yield after flash chromatography on silica gel.
Determined by HPLC on chiral column.
With 40 mol % proton-sponge.
b
c
d

S. Liu et al. / Tetrahedron 72 (2016) 5115e5120
5119
Scheme 1. Michael addition of nitromethane to b,b-disubstituted enones.
Finally, this catalytic system was also compatible with a variety
of sterically congested -disubstituted enones 7 (Scheme 1). As
disubstituted pyrrolidine 9 was efficiently constructed in overall
73% yield without compromise of enantiopurity. This three-step
synthesis was conveniently conducted in one-pot without iso-
lation of reaction intermediate. Remarkably, the resulting 4-
phenylpyrrolidine was the central structural motif of kainic acid
analogues, which could be employed as dual NK-1 antagonists and
selective serotonin reuptake inhibitors.15
b,b
a result, a range of adducts 8aee containing an all-carbon quater-
nary carbon center were efficiently created in highly enantiose-
lective manner. This approach proceeded with exclusive
regioselectivity in the case of 2,6,6-trimethylcyclohexene-1,4-dione
(see product 8c). This observation revealed that the primary ami-
O2N
1. NiCl2.6H2O,
NaBH4
O
CH3
H3C
N
Ts
ð1Þ
2. TsCl, Et3N
9 73% yield,
3aa 96% ee
3:1 dr,
97% ee / 94% ee
nocatalyst 4 preferred to activate the less sterically hindered car-
bonyl group. Notably, this catalytic conjugate addition allowed the
direct and stereocontrolled creation of adjacent carbon-substituted
quaternary and tertiary stereocenters. For instance, the Michael
addition of nitroethane to 3-methylcyclohex-2-enone generated
highly congested 8d in acceptable yield. Additionally, excellent
enantioselectivities were observed for both diastereoisomers. Fur-
thermore, five-membered cyclic enone was also suitable acceptor
for this conversion (see product 8e).
The optically active adduct obtained via this new methodology
was valuable starting material for the preparation of chiral pyrro-
lidine (Eq. 1). Upon treatment of 3aa with NaBH4/NiCl2$6H2O, re-
duction of nitro group and the following reductive cyclization
proceeded smoothly. After subsequent N-protection, the 2,4-
The absolute configuration of Michael adduct 8 was determined
to be S by comparison of HPLC traces and optical rotation value with
those of literatures reported.13jel The other adducts were similarly
assigned on the basis of the assumed similar reaction pathway.
A plausible transition state model was depicted in Scheme 2.
The primary amine motif of 9-amino(9-deoxy)-epi-quinine 4 was
engaged in iminium formation with the carbonyl group of benza-
lacetone 1a. Subsequently, nitromethane was activated via
hydrogen-bonding interaction with the protonated tertiary amine
moiety of aminocatalyst 4, thereby leading to feasible deprotona-
tion of nitromethane by basic additive. As a result, the corre-
sponding Michael addition proceeded smoothly. In this context, the
relatively poorer reactivity of strongly basic additive (Table 1, en-
tries 5, 9, 10 and 16) might be caused by inefficient iminium

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S. Liu et al. / Tetrahedron 72 (2016) 5115e5120
References and notes
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Melchiorre, P. Angew. Chem., Int. Ed. 2012, 51, 9748; (g) Zhang, L.; Fu, N.; Luo, S.
Acc. Chem. Res. 2015, 48, 986.
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2007, 107, 5416; (d) Mukherjee, S.; Yang, J. W.; Hoffmann, S.; List, B. Chem. Rev.
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Scheme 2. Postulated transition state model for the Michael addition.
formation. As postulated by Melchiorre, the protonated tertiary
amine moiety of aminocatalyst 4 played a crucial role during the
course of iminium formation.1f The strongly basic additives could
competitively combine with acidic cocatalyst, thereby retarding the
iminium formation. On the other hand, the sluggish conversion of
strongly acidic cocatalysts (Table 2, entries 7e9) might result from
the consumption of basic additive. Once the basic additive was
protonated by the strongly acidic cocatalyst, it should lose ability to
deprotonate nitromethane. All these observations suggested that
the combination of aminocatalyst 4 with proper acid and base was
crucial for achieving high reactivity. Nevertheless, the real catalytic
mechanism still awaits further investigation.
ꢀ
Fares, C.; Polyak, I.; Gopakumar, G.; Thiel, W.; List, B. J. Am. Chem. Soc. 2013, 135,
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In conclusion, we have established a highly efficient protocol for
the enantioselective Michael addition of nitroalkanes to
a,b-un-
saturated enones in moderate to high yields (55e99%) with good to
excellent enantiomeric excesses (65e99% ee). The reaction allows
utilization of a quite wide range of enones with a considerable
degree of structural variations, including cinnamones as well as its
analogues, various chalcones, sterically hindered b,b-disubstituted
enones and cyclic enones. Notably, the heteroaromatic chalcones
could also afford the desired adducts with moderate to excellent
enantioselectivity. Remarkably, an appropriate basic additive effi-
ciently improves reactivity of this transformation without com-
promise of enantiocontrol. Compared with Gong’s13i and Ye’s13l
well-designed primary aminocatalysts, the primary amine
employed in our approach can be obtained via a straightforward
one-step conversion from naturally occurring cinchona alkaloid,
thereby avoiding the tedious synthetic procedure. This approach
further expands applicable scope of cinchona-based primary ami-
nocatalyst, providing an efficient optimization fashion for primary
aminocatalysis.
~
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This work is financially supported by the National Natural Sci-
ence Foundation of China (No. 21402163), the Science and Tech-
nology Department of Sichuan Province (No. 2013JY0135). Liu
Siyang gratefully acknowledges the Graduate Innovation Project of
Southwest University for Nationalities (No. CX2016SZ059). We
gratefully thank Professor Ding Keyi and Professor Liu Jun for their
kindly help.
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Supplementary data
̇
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Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2016.07.008.
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