Direct asymmetric michael additions of ketones to nitroolefins and chalcones catalyzed by a Chiral C2-symmetric pyrrolidine-based tetraamine

Article abstract of DOI:10.1002/cjoc.201200214

C₂-Symmetric pyrrolidine-based tetraamine, available from commercially starting materials, showed good catalytic activity for asymmetric Michael additions of ketones to nitroalkenes especially to chalcones. The reactions proceeded to give the corresponding products in good yields and in a highly selective manner.

Full text of DOI:10.1002/cjoc.201200214

FULL PAPER
DOI: 10.1002/cjoc.201200214
Direct Asymmetric Michael Additions of Ketones to Nitroole-
fins and Chalcones Catalyzed by a Chiral C2-Symmetric
Pyrrolidine-based Tetraamine
Ma, Shijun(马世俊)
Wu, Lulu(吴璐璐)
Liu, Ming(刘明)
Wang, Yongmei*(王永梅)
Department of Chemistry, The Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071,
China
C2-Symmetric pyrrolidine-based tetraamine, available from commercially starting materials, showed good cata-
lytic activity for asymmetric Michael additions of ketones to nitroalkenes especially to chalcones. The reactions
proceeded to give the corresponding products in good yields and in a highly selective manner.
Keywords asymmetric catalysis, Michael addition, tetraamine, chalcones, enantioselectivity
Introduction
not without their drawbacks, such as long reaction time,
high catalyst loding and low chemical yields, and these
will limit their further application.
The Michael addition reaction is widely recognized
as powerful tools for the generation of carbon-carbon
bonds in organic synthesis.[1] During the past few years,
there have witnessed a tremendous growth in the num-
ber of organocatalyzed highly stereoselective Michael
addition reactions. Among the variants of asymmetric
conjugation additions, Michael reactions of ketones to
nitroolefins have received much attention. Stimulated
by the seminal works of Barbas[2] and List,[3] a wide
variety of highly effective organocatalysts have been
developed for this reaction. Among all of the catalysts,
proline[4] and its derivatives,[5] imidazolidinones devel-
oped by MacMillan[6] and chiral thioureas-based cata-
lysts[7] dominated the field.
On the other hand, enantioselective catalytic Michael
addition of ketones to chalcones has remained signifi-
cantly less developed probably due to the low reactivity
and high steric hindrance of substrates. As far as we
know, only few papers have been published on the
asymmetric Michael addition of ketones to chalcones.
Wang et al. accomplished the addition of ketones to
chalcones for the first time with high enantioselectivity
using a chiral pyrrolidinylmethylsulfonamide catalyst.[8]
Li et al. reported the asymmetric Michael addition of
cyclopentanone to chalcones directly catalyzed by sim-
ple chiral 1,2-diaminocyclohexane-hexanedioic acid
with good yields and excellent enantioselectivity.[9] We
reported an amino acid ionic liquid[10] and a pyr-
rolidine-pyridine base catalyst[11] serving for this type
Michael addition reaction. Although these catalysts
were effective on this type Michael addition, they are
Herein, in an effort to search for new and high effec-
tive catalysts serving for these reactions, in the present
work, we presented a C2-symmetric pyrrolidine-based
tetraamine and the evaluation of the catalyst in asym-
metric Michael addition of ketones to nitroolefins and
chalcones. The reactions provided Michael adducts in
good to excellent yields, diastereoselectivities and ena-
tioselectivities.
Results and Discussion
Using the Michael addition of cyclohexanone (3a)
and nitrostyrene (4a) as a model reaction, our investiga-
tion began with screening the organocatalysts 1 and 2
for their catalytic abilities. The initial reactions were
performed by using 10 mol% of the catalysts at room
temperature under neat condition. As can be seen from
the results summarized in Table 1, catalyst 1 is not an
effective catalyst for this process (Entry 1), while cata-
lyst 2 exhibited good catalytic activity affording the
corresponding products in excellent chemical yields
with good diastereoselectivity and enatioselectivity
(99% yield, 96∶4 dr, 66% ee, Entry 2), and this cata-
lyst was selected for further studies. Therefore, the
screening of different solvents with catalyst 2 was car-
ried out (Entries 3—9). The results therein show that
good yields were achieved in 24 h in solvents such as
CHCl3, THF, CH2Cl2 and CH3CN, whereas ionic liquid
[Bmim][PF6], toluene and i-PrOH only gave moderate
yields. The reaction performed in CH3CN gave high
*
E-mail: ymw@nankai.edu.cn; Tel.: 0086-022-23503281; Fax: 0086-022-23502654
Received March 3, 2012; accepted April 22, 2012; published online XXXX, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200214 or from the author.
Chin. J. Chem. 2012, XX, 1—7
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1

Ma et al.
FULL PAPER
diastereoselectivity and enantioselectivity (95∶5 dr,
74% ee, Entry 9), whereas the enantioseectivity de-
creased in CHCl3, THF, [Bmim][PF6], toluene and
i-PrOH (Entries 3—6 and 8), and CH2Cl2 gave the same
ee value with neat condition (Entry 7).
Table 2 The effect of different acid additives on asymmetric
Michael additions of cyclohexanone and nitrostyrenea
O
O
Ph
cat. 2 (10 mol%)
additive (15 mol%)
NO2
NO2
+
Ph
CH3CN, r.t.
4a
3a
5a
Table 1 The effect of different chiral catalysts and solvents on
asymmetric Michael additions of cyclohexanone and nitrostyre-
nea
Entry Additive
t/h Yieldb/% drc[syn/anti] eed/%
1
TFA
48
—
—
—
75
61
68
85
82
78
91
O
O
Ph
2
PhCOOH
AcOH
20 97
20 95
20 73
96∶4
94∶6
99∶1
94∶6
97∶3
95∶5
97∶3
cat. (10 m ol%)
solvent, r.t.
NO2
NO2
+
Ph
3
4
2-napthanol
phenol
3a
4a
5a
5
8
98
6e
7f
8
phenol
12 96
15 91
NH HN
NH HN
phenol
3,5-dimethylphenol
8
98
NH
HN
NH
HN
a All reactions were carried out in CH3CN (0.5 mL) by using 3a
(10 equiv., 2.0 mmol) and 4a (0.2 mmol) in the presence of cata-
lysts 2 (0.02 mmol, 10 mol%) and acid additive (0.03 mmol, 15
mol%) at room temperature. b Isolated yield after silica gel col-
1
2
Entry Cat.Solvent
t/h Yieldb/% dr c[syn/anti] eed/%
1e
2e
3
1
2
2
2
2
2
2
2
2
neat
72 <10
24 99
24 93
24 92
n.d.
n.d.
66
58
59
43
56
66
64
74
umn chromatography. c Determined by H NMR spectroscopy.
1
neat
96∶4
91∶9
92∶8
94∶6
95∶5
94∶6
95∶5
95∶5
d Determined by HPLC analysis. Phenol (10 mol%) was used.
e
CHCl3
THF
f Phenol (20 mol%) was used.
4
5
[Bmim][PF6] 24 74
Having established the optimal reaction conditions,
the scope and the limitation of this Michael reactions
with different nitroolefins were examined. As shown in
Table 3 (Entries 1—8), excellent yields were achieved
in only 8—12 h for all the reactions, regardless of the
electronic nature of the aromatic substituents. In most
cases, we obtained the syn products in high diastereose-
lectivities (up to 99∶1) and enantioselectivities (up to
91% ee). To further study the scope of the reaction,
other ketones were also examined as the donor (Entries
9, 10), reactions proceeded smoothly to give the Mi-
chael adducts in good yields with good diastereoselec-
tivities and moderate enantioselectivities.
6
toluene
CH2Cl2
i-PrOH
CH3CN
24 64
24 93
24 76
24 97
7
8
9
a All reactions were carried out in solvent (0.5 mL) by using 3a
(10 equiv., 2.0 mmol) and 4a (0.2 mmol) in the presence of the
catalysts (0.02 mmol, 10 mol%) at room temperature. b Isolated
yield after silica gel column chromatography. c Determined by 1H
d
NMR spectroscopy. Determined by HPLC analysis. e 3a (20
equiv., 4.0 mmol) was used.
Having identified CH3CN to be the best solvent for
the Michael reaction of cyclohexanone (3a) and ni-
trostyrene (4a), the effect of different acid additives
were investigated, the results are summarized in Table 2.
It has been observed that the presence of additive has a
significant influence on the reaction. Initially, when we
studied TFA as additive, no reaction was observed (En-
try 1). This may be due to the poisoning of catalyst
through salt formation. Then we utilized mild acids such
as PhCOOH, AcOH, 2-napthanol, phenol and 3,5-di-
methylphenol to promote the reaction (Entries 2—8).
Among the employed acids, phenol and 3,5-dimeth-
ylphenol gave better results than PhCOOH, AcOH and
2-napthanol. Then we screened the amount of the addi-
tives using phenol as additive, we found that 15 mol%
of additives gave the best result (Entries 5—7). Finally,
we chose 3,5-dimethylphenol for the best additive in
combination with catalyst 2 (98% yield, 97∶3 dr, 91%
ee, Entry 8).
After the above success, we sought to extend the
catalytic activity of the C2-symmetric pyrrolidine-based
tetraamine in other Michael addition of cyclohexanone
and chalcones. Then, the solvents and acid additives
screenings were carried out using catalyst 2. The initial
reactions were performed by using 20 mol% of the
catalysts at room temperature in different solvents. The
results were shown in Table 4, CH3CN also offered the
best results than other solvents including neat condition,
THF and i-PrOH (Entry 2). The acid additives were
proved to have a significant influence on the reaction,
phenol and its derivatives (Entries 5—7, 11, 12) gave
better results than PhCOOH and its derivatives no mat-
ter with electron-donating or electron-withdrawing sub-
stituents (Entries 8—10). Finally, we found 4-nitro-
phenol was the best additive and 30 mol% of it gave the
best result in only 24 h (67% yield, 97∶3 dr, 92% ee,
Entry 7), and it was selected for further studies.
2
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Chin. J. Chem. 2012, XX, 1—7

Direct Asymmetric Michael Additions of Ketones to Nitroolefins and Chalcones
Table 3 Michael reaction of ketones to nitroolefinsa
Table 4 The effect of different solvents and acid additives on
asymmetric Michael additions of cyclohexanone and chalconea
O
cat. 2 (10 mol%)
3,5-dimethylphenol (15 mol%)
O
O
Ph
O
+
NO2
cat. 2 (20 mol%)
additive (30 mol%)
O
Ar
CH3CN, r.t.
X
Ph
+
Ph
Ph
3
4
solvent, r.t.
O
X
Ar
7a
3a
6a
NO2
Yieldb/ dr c
%
Entry Solvent Additive
t/h
eed/%
[syn/anti]
5
1e
2
neat
CH3CN —
THF
—
36 50
36 63
72 31
36 41
24 54
97∶3
74
79
74
70
81
Yieldb/ drc
eed/
%
Entry X
Ar
Ph
Product t/h
96∶4
96∶4
98∶2
96∶4
%
[syn/anti]
97∶3
3
—
1
2
3
4
5
6
7
8
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
C[O-
5a
5b
5c
8
8
8
98
93
86
91
84
85
81
85
77
75
85
4
i-PrOH —
4-FC6H4
94∶6
5
CH3CN phenol
4-ClC6H4
3-ClC6H4
4-MeC6H4
82∶18
89∶11
90∶10
90∶10
95∶5
3,5-dimethyl-
phenol
5d 10 86
5e 12 93
6
CH3CN
24 58
96∶4
81
7
8
CH3CN 4-nitrophenol 24 67
97∶3
95∶5
92
80
4-OMeC6H4
5f
8 96
CH3CN PhCOOH
48 49
2,4-Cl2C6H3 5g 12 89
4-methoxy-
CH3CN
1-naphthyl
5h
5i
8
8
99
84
95∶5
9
48 40
94∶6
95∶5
79
76
benzoic acid
4-bromoben-
CH3CN
9
Ph
85∶15
63
10
48 41
(CH2)2O]
zoic acid
10
O
Ph
5j 10 94
95∶5
66
11f
12g
CH3CN 4-nitrophenol 48 60
95∶5
97∶3
91
92
a All reactions were carried out in CH3CN (0.5 mL) by using 3
(10 equiv., 2.0 mmol) and 4 (0.2 mmol) in the precence of cata-
lyst 2 (0.02 mmol, 10 mol%) and 3,5-dimethylphenol (0.03 mmol,
15 mol%) at room temperature. b Isolated yield after silica gel
column chromatography. c Determined by H NMR spectroscopy.
d Determined by HPLC analysis.
CH3CN 4-nitrophenol 48 63
a All reactions were carried out in solvents (0.5 mL) using 3a (10
equiv., 2.0 mmol) and 6a (0.2 mmol) in the presence of catalysts
2 (0.04 mmol, 20 mol %) and acid additive (0.06 mmol, 30 mol%)
1
b
at room temperature. Isolated yield after silica gel column
chromatography. c Determined by H NMR spectroscopy. d De-
1
termined by HPLC analysis. e 3a (20 equiv., 4.0 mmol) was used.
f 4-Nitrophenol (20 mol%) was used. g 4-Nitrophenol (40 mol%)
was used.
With the optimal conditions in hand, we then ex-
plored the generality of this reaction with a variety of
chalcones, the results are summarized in Table 5. The
present catalytic system is tolerant to a broad range of
chalcones with aromatic systems (Ar1) possessing elec-
tron-withdrawing or electron-donating substituents
(84%—93% ee, Entries 2—9). Excellent levels of enan-
tioselectivities (90%—92% ee) and diastereoselectivi-
ties (≥95∶5) were obtained for reactions of chalcones
containing different aromatic substituents (Ar2) (Entries
10—12). To further study the scope of catalyst 2 in Mi-
chael additions, other cyclic ketones were also exam-
ined as the donor (Entries 10—12), reactions with
N-methyl-4-piperidone and tetrahydro-4H-pyran-4-one
gave the Michael adducts in good yields (71%—84%)
with excellent enantioselectivities (88% ee). Reaction of
cyclopentanone occurred in high yield (91%), but the
diastereoselectivity was low (81∶19), and the major
isomer had a comparably lower ee (60%) (Entry 12).
The stereochemistries of the major products were
determined by comparision of their HPLC spectra with
other previous studies.[5c,7b,7i,8-11,13,14] To account for the
stereochemical outcome of the Michael reaction, plausi-
ble transition states to rationalize the high levels of en-
antio- and diastereoselectivity of Michael addition reac-
tions of ketones with nitroolefins and chalcones
are shown in Figure 1 (States A and B). One of the sec-
ondary amine of the pyrrolidine ring activates the ke-
tones through the formation of an enamine intermediate,
the NH protons can provide transition state stabilization
through hydrogen bonding interaction with nitroolefins
nitryl group (State A) or chalcone carbonyl group (State
B), then, the enamine intermediate adds to the Si-face of
nitroolefins and chalcones, the Michael adducts are ob-
tained in a highly selective manner after hydrolysis.
Conclusions
In conclusion, we have developed C2-symmetric
pyrrolidine-based tetraamine as a highly effective or-
ganocatalyst. The tetraamine catalyst, easily prepared
from commercially available L-proline, is capable of
catalyzing highly enantioselective and diastereoselective
Michael additions of ketones to nitroolefins especially
ketones to chalcones. It is one of few universal catalysts
that can be employed in both of these two kinds of Mi-
chael additions to give high yields and good to excellent
diastereoselectivities and enantioselectivities. Based on
Chin. J. Chem. 2012, XX, 1—7
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3

Ma et al.
FULL PAPER
Table 5 Asymmetric Michael reaction of ketones and chalconesa
O
cat. 2 (20 mol%)
4-nitrophenol (30 mol%)
O
X
Ar1
O
O
+
Ar2
Ar2
Ar1
CH3CN, r.t.
X
3
6
7
Entry
X
Ar1
Ph
Ar2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Product
7a
t/h
24
48
48
48
48
24
24
24
Yieldb/%
67
drc [syn/anti] eed/%
1
2
3
4
5
6
7
8
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
97∶3
>99∶1
76∶24
94∶6
91∶9
96∶4
98∶2
99∶1
92
4-F-C6H4
2-Cl-C6H4
3-Cl-C6H4
4-Cl-C6H4
4-Br-C6H4
4-Me-C6H4
Ph
7b
70
93
87
90
84
84
92
90
7c
77
7d
73
7e
78
7f
71
7g
70
4-ClC6H4
4-OMe-
C6H4
7h
88
9
CH2
2-Cl-C6H4
7i
72
61
99∶1
92
10
11
12
N(CH3)
O
Ph
Ph
Ph
Ph
7j
7k
7l
48
48
24
84
71
91
83∶17
97∶3
88
88
60
Ph
Ph
none
81∶19
a All reactions were carried out in CH3CN (0.5 mL) by using 3 (10 equiv., 2.0 mmol) and 6 (0.2 mmol) in the presence of catalysts 2 (0.04
mmol, 20 mol%) and 4-nitrophenol (0.06 mmol, 30 mol%) at room temperature. b Isolated yield after silica gel column chromatography.
c Determined by 1H NMR spectroscopy. d Determined by HPLC analysis.
by using a Chiralpak AD-H, OD-H or AS-H column
purchased from Daicel Chemical Industries. The chemi-
cals were purchased from commercial suppliers (Aldrich,
USA and Shanghai Chemical Company, China), and
were used without purification prior to use. All reactions
unless otherwise noted were carried out directly under
air.
N
H
N
H
N
H
N
H
HN
HN
N
X
N
X
O
O
O
Ar2
N
A
Ar1
Ar
Si-face approach
Synthesis of organocatalysts
B
Catalysts 1 and 2 are prepared according to previ-
ously reported method[12] from commercially available
Boc-L-proline, (1R,2R)-1,2-diaminocyclohexane and
o-phenylenediamine. The catalyst 1 was obtained in
67% yield as a dark oil, 2 in 62% yield as a colorless oil.
Figure 1 Proposed transition states for 2-catalyzed Michael
reaction.
the experimental results, plausible transition states and
the mode of activity of the organocatalyst with the sub-
strate were deduced. Further investigation into the use
of this organocatalyst in asymmetric catalysis is still in
progress.
Typical procedure for asymmetric Michael reaction
of ketones with nitroolefins
3,5-Dimethylphenol (0.03 mmol, 15 mol%) was
added to a mixture of catalyst 2 (0.02 mmol, 10 mol%)
and ketones 3 (10 equiv., 2.0 mmol) in CH3CN (0.5 mL)
at room temperature under air. The reaction mixture was
stirred for 10 min, and then nitroolefins 4 (0.2 mmol)
were added. The homogeneous reaction mixture was
stirred at room temperature for 8—12 h. The reaction
mixture was directly loaded onto a silica gel column
eluting with various mixtures of petroleum ether :
EtOAc to afford the Michael adducts 5a—5j.
Experimental
General information
All the solvents were purified according to standard
1
procedures. The H NMR spectra were recorded at 400
MHz, 13C NMR spectra were recorded at 100 MHz. H
1
and 13C NMR chemical shifts were calibrated to tetra-
methylsilane as an external reference. Coupling con-
stants (J) are given in Hz. The following abbreviations
are used to indicate the multiplicity: s, singlet; d, double;
t, triplet; m, multiplet. HR-MS were recorded on an
IonSpec FT-ICR mass spectrometer with ESI resource.
HPLC analysis was performed on Shimadzu CTO-10AS
(S)-2-((R)-2-Nitro-1-phenylethyl)-cyclohexanone
1
(5a)[5c,7b,13] Yield 98%; syn/anti＝97∶3; H NMR
(400 MHz, CDCl3) δ: 1.52—1.19 (m, 1H), 1.79—1.52
(m, 4H), 2.10—2.04 (m, 1H), 2.49—2.33 (m, 2H), 2.68
4
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Direct Asymmetric Michael Additions of Ketones to Nitroolefins and Chalcones
(ddd, J＝8.1, 8.4, 11.7 Hz, 1H), 3.76 (dt, J＝4.5, 9.9 Hz,
1H), 4.63 (dd, J＝9.9, 12.3 Hz, 1H), 4.95 (dd, J＝4.5,
12.6 Hz, 1H), 7.16 (d, J＝6.9 Hz, 2H), 7.34—7.23 (m,
3H); HPLC analysis: Chiralpak AD-H column, i-PrOH/
hexane 10∶90, flow rate 1.0 mL/min, λ＝254 nm, re-
tention time: 9.91 min (minor) and 12.04 min (major),
91% ee.
umn, i-PrOH/hexane 10∶90, flow rate 1.0 mL/min, λ＝
254 nm, retention time: 12.72 min (minor) and 15.67
min (major), 77% ee.
(S)-2-((R)-1-(2,4-Dichlorophenyl)-2-nitroethyl)-
cyclohexanone (5g)[7i] Yield 89%; syn/anti＝95∶5;
1H NMR (400 MHz, CDCl3) δ: 1.29—1.38 (m, 1H),
1.57—1.83 (m, 4H), 2.08—2.13 (m, 1H), 2.32—2.48 (m,
2H), 2.82—2.89 (m, 1H), 4.23—4.29 (m, 1H), 4.82—
4.93 (m, 2H), 7.18—7.25 (m, 2H), 7.40 (t, J＝1.6 Hz,
1H); HPLC analysis: Chiralpak AS-H column, i-PrOH/
hexane 10∶90, flow rate 0.7 mL/min, λ＝210 nm, re-
tention time: 15.29 min (minor) and 26.38 min (major),
75% ee.
(S)-2-((R)-1-(Naphthalen-1-yl)-2-nitroethyl)-cyclo-
hexanone (5h)[5c,7i,13] Yield 99%; syn/anti＝95∶5; 1H
NMR (400 MHz, CDCl3) δ: 1.30—1.19 (m, 1H), 1.69—
1.47 (m, 4H), 2.10—2.04 (m, 1H), 2.52—2.39 (m, 2H),
2.85 (br s, 1H), 4.76 (br s, 1H), 4.86—4.96 (m, 1H),
5.07 (dd, J＝4.2, 12.6 Hz, 1H), 7.58—7.36 (m, 4H),
7.80 (d, J＝8.1 Hz, 1H), 7.85 (d, J＝8.1 Hz, 1H), 8.15 (s,
1H); HPLC analysis: Chiralpak AS-H column, i-PrOH/
hexane 20∶80, flow rate 1.0 mL/min, λ＝210 nm, re-
tention time: 12.38 min (minor) and 17.18 min (major),
85% ee.
(S)-7-[(R)-2-Nitro-1-phenylethyl]-1,4-dioxaspiro-
[4.5]decan-8-one(5i)[7i] Yield 84%; syn/anti＝85∶15;
1H NMR (400 MHz, CDCl3) δ: 1.57 (t, J＝13.4 Hz, 1H),
1.70 (ddd, J＝13.0, 5.5, 3.5 Hz, 1H), 1.97 (td, J＝13.0,
5.1 Hz, 1H), 2.06 (ddt, J＝13.0, 6.6, 3.5 Hz, 1H), 2.48
(dd, J＝13.8, 5.1, 3.5 Hz, 1H), 2.76—2.68 (m, 1H), 3.08
(ddd, J＝13.0, 10.1, 5.5 Hz, 1H), 4.01—3.82 (m, 5H),
4.63 (dd, J＝12.5, 9.8 Hz, 1H), 4.96 (dd, J＝12.5, 4.7
Hz, 1H), 7.19—7.17 (m, 2H), 7.36—7.26 (m, 3H);
HPLC analysis: Chiralpak AS-H column, i-PrOH/
hexane 20∶80, flow rate 1.0 mL/min, λ＝210 nm, re-
tention time: 13.88 min (minor) and 21.40 min (major),
63% ee.
(S)-2-[(R)-1-(4-Fluorophenyl)-2-nitroethyl]-cyclo-
1
hexanone (5b)[7i] Yield 93%; syn/anti＝94∶6; H
NMR (400 MHz, CDCl3) δ: 1.29—1.17 (m, 1H), 1.84—
1.52 (m, 4H), 2.14—2.06 (m, 1H), 2.44—2.34 (m, 1H),
2.51—2.45 (m, 1H), 2.70—2.63 (m, 1H), 3.78 (td, J＝
10.1, 4.5 Hz, 1H), 4.61 (dd, J＝12.5, 10.1 Hz, 1H), 4.95
(dd, J＝12.5, 4.5 Hz, 1H), 7.02 (t, J＝8.6 Hz, 2H), 7.18
—7.15 (m, 2H); HPLC analysis: Chiralpak AD-H col-
umn, i-PrOH/hexane 25∶75, flow rate 0.7 mL/min, λ＝
254 nm, retention time: 8.93 min (minor) and 10.81 min
(major), 84% ee.
(S)-2-((R)-1-(4-Chlorophenyl)-2-nitroethyl)-cyclo-
1
hexanone (5c)[7i,13] Yield 86%; syn/anti＝82∶18; H
NMR (400 MHz, CDCl3) δ: 1.17—1.28 (m, 1H), 1.51—
1.82 (m, 4H), 2.06—2.13 (m, 1H), 2.33—2.50 (m, 2H),
2.61—2.68 (m, 1H), 3.76 (dt, J＝10, 4.4 Hz, 1H), 4.59
(dd, J＝10.4, 12.8 Hz, 1H), 4.94 (dd, J＝4.4, 12.4 Hz,
1H), 7.03—7.18 (m, 2H), 7.28—7.31 (m, 2H); HPLC
analysis: Chiralpak AD-H column, i-PrOH/hexane 10∶
90, flow rate 1.0 mL/min, λ＝254 nm, retention time:
10.78 min (minor) and 16.07 min (major), 85% ee.
(S)-2-((R)-1-(3-Chlorophenyl)-2-nitroethyl)-cyclo-
hexanone (5d)[13,14] Yield 86%; syn/anti＝89∶11; 1H
NMR (400 MHz, CDCl3) δ: 1.23—1.29 (m, 1H), 1.53—
1.83 (m, 4H), 2.07—2.14 (m, 1H), 2.34—2.51 (m, 2H),
2.62—2.69 (m, 1H), 3.76 (dt, J＝10, 4.4 Hz, 1H), 4.61
(dd, J＝10, 12.8 Hz, 1H), 4.95 (dd, J＝4.4, 12.8 Hz,
1H), 7.05—7.10 (m, 1H), 7.17 (s, 1H), 7.25—7.27 (m,
2H); HPLC analysis: Chiralpak AS-H column, i-PrOH/
hexane 10∶90, flow rate 1.0 mL/min, λ＝210 nm, re-
tention time: 15.97 min (minor) and 28.15 min (major),
81% ee.
(R)-Tetrahydro-3-((R)-2-nitro-1-phenylethyl)-
1
pyran-4-one (5j)[14] Yield 94%; syn/anti＝95∶5; H
(S)-2-((R)-2-Nitro-1-p-tolylethyl)-cyclohexanone
(5e)[7i,13] Yield 93%; syn/anti＝90∶10; 1H NMR (400
MHz, CDCl3) δ: 1.17—1.28 (m, 1H), 1.51—1.80 (m,
4H), 2.03—2.11 (m, 1H), 2.31 (s, 3H), 2.34—2.41 (m,
1H), 2.44—2.50 (m, 1H), 2.63—2.69 (m, 1H), 3.72 (dt,
J＝10, 4.4 Hz, 1H), 4.60 (dd, J＝10, 12.4 Hz, 1H), 4.92
(dd, J＝4.8, 12.4 Hz, 1H), 7.04 (d, J＝8.0 Hz, 2H), 7.12
(d, J＝7.6 Hz, 2H); HPLC analysis: Chiralpak AD-H
column, i-PrOH/hexane 10∶90, flow rate 1.0 mL/min,
λ＝254 nm, retention time: 7.84 min (minor) and 9.83
min (major), 85% ee.
NMR (400 MHz, CDCl3) δ: 2.52—2.72 (m, 2H), 2.84—
2.92 (m, 1H), 3.27 (dd, J＝9.0, 11.7 Hz, 1H), 3.66—
3.87 (m, 3H), 4.10—4.18 (m, 1H), 4.64 (dd, J＝9.9,
12.6 Hz, 1H), 4.93 (dd, J＝4.5, 12.9 Hz, 1H), 7.17—
7.41 (m, 5H); HPLC analysis: Chiralpak AD-H column,
i-PrOH/hexane 20∶80, flow rate 1.0 mL/min, λ＝254
nm, retention time: 10.33 min (minor) and 18.45 min
(major), 66% ee.
Typical procedure for asymmetric Michael reaction
of ketones with chalcones
(S)-2-((R)-1-(4-Methoxyphenyl)-2-nitroethyl)-
cyclohexanone (5f)[5c,7i] Yield 96%; syn/anti＝90∶10;
1H NMR (400 MHz, CDCl3) δ: 1.30—1.16 (m, 1H),
1.83—1.51 (m, 4H), 2.13—2.03 (m, 1H), 2.52—2.32 (m,
2H), 2.69—2.60 (m, 1H), 3.71 (dt, J＝4.5, 9.9 Hz, 1H),
3.78 (s, 3H), 4.58 (dd, J＝9.9, 12.0 Hz, 1H), 4.91 (dd,
J＝4.5, 12.3 Hz, 1H), 6.85 (d, J＝8.7 Hz, 2H), 7.08 (d,
J＝8.7 Hz, 2H); HPLC analysis: Chiralpak AD-H col-
Catalyst 2 (0.04 mmol, 20 mol%) and 4-nitrophenol
(0.06 mmol, 30 mol%) were added to a mixture of ke-
tones 3 (10 equiv., 2.0 mmol) and chalcones 6 (0.2
mmol) in CH3CN (0.5 mL) at room temperature. The
mixture was stirred vigorously and monitored by TLC.
When the reaction was finished, the mixture was puri-
fied by flash silica gel chromatography eluting with
various mixtures of petroleum ether : EtOAc to afford
Chin. J. Chem. 2012, XX, 1—7
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
5

Ma et al.
FULL PAPER
the desired products 7a—7m.
2H), 7.40—7.44 (m, 2H), 7.51—7.54 (m, 1H), 7.90 (d,
J＝6.8 Hz, 2H); HPLC analysis: Chiralpak AD-H col-
umn, i-PrOH/hexane 10∶90, flow rate 1.0 mL/min, λ＝
254 nm, retention time: 14.25 min (minor) and 18.30
min (major), 84% ee.
(S)-2-((R)-3-Oxo-1,3-diphenylpropyl)-cyclohe-
xanone (7a)[8] Yield 67%; syn/anti＝97∶3; H NMR
1
(400 MHz, CDCl3) δ: 1.23—1.30 (m, 1H), 1.59—1.81
(m, 4H), 1.95—2.03 (m, 1H), 2.36—2.49 (m, 1H), 2.52
—2.58 (m, 1H), 2.75 (dt, J＝10.2, 4.8 Hz, 1H), 3.25 (dd,
J＝9.9, 16.5 Hz, 1H), 3.51 (dd, J＝4.2, 16.5 Hz, 1H),
3.75 (dt, J＝9.6, 3.9 Hz, 1H), 7.12—7.16 (m, 3H), 7.22
—7.32 (m, 2H), 7.40—7.49 (m, 2H), 7.50—7.57 (m,
1H), 7.89 (d, J＝7.2 Hz, 2H); HPLC analysis: Chiralpak
AS-H column, i-PrOH/hexane 40∶60, flow rate 0.5
mL/min, λ＝254 nm, retention time: 13.64 min (minor)
and 20.91 min (major), 92% ee.
(S)-2-((R)-1-(4-Bromophenyl)-3-oxo-3-phenyl-
propyl)-cyclohexanone (7f)[10] Yield 71%; syn/anti＝
1
96∶4; HNMR (400 MHz, CDCl3) δ: 1.26—1.29 (m,
1H), 1.62—1.81 (m, 4H), 1.97—2.03 (m, 1H), 2.35—
2.55 (m, 2H), 2.71 (dt, J＝10.0, 4.8 Hz, 1H), 3.20 (dd,
J＝16.37, 9.79 Hz, 1H), 3.51 (dd, J＝16.4, 3.9 Hz, 1H),
3.70 (dt, J＝9.8, 3.9 Hz, 1H), 7.09 (d, J＝8.4 Hz, 2H),
7.39 (d, J＝8.4 Hz, 2H), 7.45 (d, J＝7.8 Hz, 2H), 7.56 (t,
J＝7.3 Hz, 1H), 7.92 (d, J＝7.2 Hz, 2H); HPLC analysis:
Chiralpak AD-H column, i-PrOH/hexane 10∶90, flow
rate 0.9 mL/min, λ＝254 nm, retention time: 16.80 min
(minor) and 20.86 min (major), 84% ee.
(S)-2-((R)-1-(4-Fluorophenyl)-3-oxo-3-phenylpro-
pyl)-cyclohexanone (7b)[8] Yield 70%; syn/anti ＞
1
99∶1; H NMR (400 MHz, CDCl3) δ: 1.21—1.28 (m,
1H), 1.53—1.81 (m, 4H), 1.97—2.05 (m, 1H), 2.37—
2.47 (m, 1H), 2.50—2.56 (m, 1H), 2.72 (dt, J＝10.0, 4.8
Hz, 1H), 3.20 (dd, J＝10.0, 16.0 Hz, 1H), 3.51 (dd, J＝
4.0, 16.0 Hz, 1H), 3.74 (dt, J＝10.0, 4.0 Hz, 1H), 6.96
(t, J＝8.8 Hz, 2H), 7.14—7.18 (m, 2H), 7.44 (t, J＝7.6
Hz, 2H), 7.54 (t, J＝7.2 Hz, 1H) 7.93 (d, J＝7.5 Hz,
2H); HPLC analysis: Chiralpak OD-H column, i-PrOH/
hexane 10∶90, flow rate 1.0 mL/min, λ＝254 nm, re-
tention time: 7.85 min (minor) and 8.42 min (major),
93% ee.
(S)-2-((R)-1-(2-Chlorophenyl)-3-oxo-3-phenyl-
propyl)-cyclohexanone (7c)[8] Yield 77%; syn/anti＝
76∶24; 1H NMR (400 MHz, CDCl3) δ: 1.20—1.39 (m,
1H), 1.57—1.83 (m, 4H), 2.00—2.09 (m, 1H), 2.36—
2.43 (m, 1H), 2.56—2.58 (m, 1H), 2.89 (dt, J＝10.0, 4.8
Hz, 1H), 3.38 (dd, J＝10.0, 15.6 Hz, 1H), 3.57 (dd, J＝
4.0, 16.0 Hz, 1H), 4.22 (dt, J＝10.0, 4.0 Hz, 1H), 7.09 (t,
J＝7.2 Hz, 1H), 7.17 (t, J＝7.2 Hz, 1H), 7.26—7.31 (m,
2H), 7.41 (t, J＝7.2 Hz, 2H), 7.51 (t, J＝7.2 Hz, 1H),
7.93 (d, J＝7.2 Hz, 2H); HPLC analysis: Chiralpak
AS-H column, i-PrOH/hexane 40∶60, flow rate 0.5
mL/min, λ＝254 nm, retention time: 12.24 min (minor)
and 20.18 min (major), 87% ee.
(S)-2-((R)-1-(3-Chlorophenyl)-3-oxo-3-phenyl-
propyl)-cyclohexanone (7d)[11] Yield 73%; syn/anti
＝94∶6; 1H NMR (400 MHz, CDCl3) δ: 1.21—1.29 (m,
1H), 1.53—1.81 (m, 4H), 1.99—2.04 (m, 1H), 2.34—
2.42 (m, 1H), 2.46—2.52 (m, 1H), 2.70 (dt, J＝10.0, 4.8
Hz, 1H), 3.22 (dd, J＝9.6, 16.4 Hz, 1H), 3.49 (dd, J＝
3.6, 16.4 Hz, 1H), 3.71 (dt, J＝9.6, 3.6 Hz, 1H), 7.08—
7.20 (m, 4H), 7.42 (t, J＝7.6 Hz, 2H), 7.52 (t, J＝7.2 Hz,
1H), 7.90 (d, J＝7.6 Hz, 2H); HPLC analysis: Chiralpak
AD-H column, i-PrOH/hexane 10∶90, flow rate 1.0
mL/min, λ＝254 nm, retention time: 10.62 min (minor)
and 20.17 min (major), 90% ee.
(S)-2-((R)-3-Oxo-3-phenyl-1-p-tolylpropyl)-cyclo-
1
hexanone (7g)[11] Yield 70%; syn/anti＝98∶2; H
NMR (400 MHz, CDCl3) δ: 1.21—1.40 (m, 1H), 1.56—
1.87 (m, 4H), 1.96—2.06 (m, 1H), 2.30 (s, 3H), 2.30—
2.43 (m, 1H), 2.49—2.57 (m, 1H), 2.69 (dt, J＝10.0, 4.8
Hz, 1H), 3.19 (dd, J＝9.2, 15.6 Hz, 1H), 3.47 (dd, J＝
2.8, 16.0 Hz, 1H), 3.67 (dt, J＝10.0, 4.0 Hz, 1H), 7.07
(d, J＝7.2 Hz, 4H), 7.43 (t, J＝6.8 Hz, 2H), 7.52 (t, J＝
6.0 Hz, 1H), 7.93 (d, J＝7.2 Hz, 2H); HPLC analysis:
Chiralpak AD-H column, i-PrOH/hexane 10∶90, flow
rate 1.0 mL/min, λ＝254 nm, retention time: 11.33 min
(minor) and 16.45 min (major), 92% ee.
(S)-2-((R)-1-(4-Phenyl)-3-oxo-3-(4'-Chlorophenyl)-
propyl)-cyclohexanone (7h)[8] Yield 88%; syn/anti＝
1
99∶1; H NMR (400 MHz, CDCl3) δ: 1.22—1.27 (m,
1H), 1.62—1.80 (m, 4H), 1.97—2.05 (m, 1H), 2.35—
2.55 (m, 2H), 2.73 (dt, J＝10.2, 10.0, 4.9 Hz, 1H), 3.15
(dd, J＝15.9, 9.6 Hz, 1H), 3.50 (dd, J＝15.9, 4.0 Hz,
1H), 3.70 (dt, J＝9.9, 4.0 Hz, 1H), 7.11—7.20 (m, 3H),
7.26 (d, J＝7.5 Hz, 2H), 7.39 (d, J＝8.6 Hz, 2H), 7.86
(d, J＝8.6 Hz, 2H); HPLC analysis: Chiralpak AS-H
column, i-PrOH/hexane 40∶60, flow rate 0.5 mL/min,
λ＝254 nm, retention time: 12.82 min (minor) and 17.88
min (major), 90% ee.
(S)-2-((R)-1-(2-Chlorophenyl)-3-(4-methoxyphe-
nyl)-3-oxopropyl)-cyclohexanone (7i)[11] Yield 61%;
syn/anti＝99∶1; 1H NMR (400 MHz, CDCl3) δ: 1.29—
1.39 (m, 1H), 1.57—1.85 (m, 4H), 2.01—2.06 (m, 1H),
2.36—2.44 (m, 1H), 2.48—2.54 (m, 1H), 2.89 (dt, J＝
10.0, 4.8 Hz, 1H), 3.32 (dd, J＝10.0, 16.0 Hz, 1H), 3.84
(s, 3H), 3.54 (dd, J＝4.0, 16.4 Hz, 1H), 4.24 (dt, J＝9.6,
3.6 Hz, 1H), 6.90 (d, J＝8.8 Hz, 2H), 7.09 (t, J＝6.8 Hz,
1H), 7.18 (t, J＝7.2 Hz, 1H), 7.27—7.32 (m, 2H), 7.95
(d, J＝8.8 Hz, 2H); HPLC analysis: Chiralpak OD-H
column, i-PrOH/hexane 30∶70, flow rate 1.0 mL/min,
λ＝254 nm, retention time: 6.16 min (minor) and 8.07
min (major), 92% ee.
(S)-2-((R)-1-(4-Chlorophenyl)-3-oxo-3-phenyl-
propyl)-cyclohexanone (7e)[11] Yield 78%; syn/anti＝
1
91∶9; H NMR (400 MHz, CDCl3) δ: 1.20—1.29 (m,
1H), 1.62—1.81 (m, 4H), 1.95—2.05 (m, 1H), 2.31—
2.53 (m, 2H), 2.65—2.72 (m, 1H), 3.19 (dd, J＝9.9,
16.5 Hz, 1H), 3.50 (dd, J＝4.2, 16.5 Hz, 1H), 3.71 (dt,
J＝9.6, 3.9 Hz, 1H), 7.10—7.13 (m, 2H), 7.20—7.23 (m,
(R)-3-((R)-3-Oxo-1,3-diphenylpropyl)-1-methyl-
piperidin-4-one (7j)[11] Yield 84%; syn/anti＝83∶17
1
1
(by H NMR); H NMR (400 MHz, CDCl3) δ: 2.04—
2.14 (m, 1H), 2.20 (s, 3H), 2.34 (s, 1H), 2.37—2.47 (m,
6
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—7

Direct Asymmetric Michael Additions of Ketones to Nitroolefins and Chalcones
4253; (d) Mossé, S.; Alexakis, A. Org. Lett. 2005, 7, 4361; (e)
1H), 2.58 (d, J＝14.2 Hz, 2H), 2.71—2.88 (m, 2H), 3.28
(dd, J＝16.5, 9.3 Hz, 2H), 3.48 (d, J＝14.3 Hz, 1H),
3.90 (s, 1H), 7.23 (dd, J＝14.4, 7.3 Hz, 3H), 7.40 (d,
J＝7.4 Hz, 2H), 7.88 (d, J＝7.3 Hz, 2H); HPLC analysis:
Chiralpak AD-H column, i-PrOH/hexane 20∶80, flow
rate 0.6 mL/min, λ＝254 nm, retention time: 17.15 min
(minor) and 21.32 min (major), 88% ee.
Mitchell, C. E. T.; Cobb, A. J. A.; Ley, S. V. Synlett 2005, 611; (f)
Planas, L.; Perand-Viret, J.; Royer, J. Tetrahedron: Asymmetry 2004,
15, 2399.
[5] For representative examples of proline-derived organocatalysts, see:
(a) Alexakis, A.; Andrey, O. Org. Lett. 2002, 4, 3611; (b) Mase, N.;
Thayumanavan, R.; Tanaka, F.; Barbas III, C. F. Org. Lett. 2004, 6,
2527; (c) Ishii, T.; Fujioka, S.; Sekiguchi, Y.; Kotsuki, H. J. Am.
Chem. Soc. 2004, 126, 9558; (d) Cobb, A. J. A.; Longbottom, D. A.;
Shaw, D. M.; Ley, S. V. Chem. Commun. 2004, 1808; (e) Wang, W.;
Wang, J.; Li, H. Angew. Chem., Int. Ed. 2005, 44, 1369; (f) Cobb, A.
J. A.; Shaw, D. M.; Longbottom, D. A.; Gold, J. B.; Ley, S. V. Org.
Biomol. Chem. 2005, 3, 84; (g) Mase, N.; Watanabe, K.; Yoda, H.;
Takabe, K.; Tanaka, F.; Barbas III, C. F. J. Am. Chem. Soc. 2006,
128, 4966; (h) Vishnumaya; Singh, V. K. Org. Lett. 2007, 9, 1117; (i)
Ni, B.; Zhang, Q.; Headley, A. D. Tetrahedron: Asymmetry 2007, 18,
1443; (j) Xu, D.; Wang, L.; Luo, S.; Wang, Y.; Zhang, S.; Xu, Z.
Eur. J. Org. Chem. 2008, 1049; (k) Li, P.; Wang, L.; Zhang, Y.;
Wang, G. Tetrahedron 2008, 64, 7633; (l) Chen, G.; Wang, Z.; Ding,
K. Chin. J. Chem. 2009, 27, 163; (m) Saha, S.; Seth, S.; Moorthy, J.
N. Tetrahedron Lett. 2010, 51, 5281; (n) Cao, X.; Zheng, J.; Lia, Y.;
Shua, Z.; Sun, X.; Wang, B.; Tang, Y. Tetrahedron 2010, 66, 9703;
(o) Lu, D.; Gong, Y.; Wang, W. Adv. Synth. Catal. 2010, 352, 644;
(p) Lu, A.; Wu, R.; Wang, Y.; Zhou, Z.; Wu, G.; Fang, J.; Tang, C.
Eur. J. Org. Chem. 2010, 2057; (q) Chen, J.; Fu, L.; Zou, Y.; Chang,
N.; Rong, J.; Xiao, W. Org. Biomol. Chem. 2011, 9, 5280; (r) Agar-
wal, J.; Peddinti, R. K. Tetrahedron Lett. 2011, 52, 117; (s) Liu, Y.;
Wu, Y.; Lu, A.; Wang, Y.; Wu, G.; Zhou, Z.; Tang, C. Tetrahedron:
Asymmetry 2011, 22, 476.
(R)-3-((R)-3-Oxo-1,3-diphenylpropyl)-tetrahydro-
pyran-4-one (7k)[11] Yield 71%; syn/anti＝97∶3 (by
1
1H NMR); H NMR (400 MHz, CDCl3) δ: 2.45—2.59
(m, 1H), 2.69—2.85 (m, 2H), 3.28—3.50 (m, 3H), 3.54
—3.66 (m, 1H), 3.82—4.03 (m, 3H), 7.10—7.35 (m,
4H), 7.38—7.49 (m, 2H), 7.48—7.54 (m, 1H), 7.87 (d,
J＝6.4 Hz, 2H); HPLC analysis: Chiralpak AD-H col-
umn, i-PrOH/hexane 15∶85, flow rate 0.7 mL/min, λ＝
254 nm, retention time: 24.58 min (minor) and 27.30
min (major), 88% ee.
(R)-2-((S)-3-Oxo-1,3-diphenylpropyl)-cyclopen-
tanone (7l)[9] Yield 91%; syn/anti＝81∶19; 1H NMR
(400 MHz, CDCl3) δ: 1.51—1.60 (m, 1H), 1.65—1.75
(m, 1H), 1.87—1.90 (m, 2H), 2.06 (dd, J＝9.0, 18.6 Hz,
1H), 2.21—2.27 (m, 1H), 2.46 (dd, J＝8.7, 17.1 Hz, 1H),
3.36 (dd, J＝7.5, 16.8 Hz, 1H), 3.70 (dd, J＝7.5, 14.4
Hz, 1H), 3.87 (dd, J＝6.3, 16.5 Hz, 1H), 7.17—7.29 (m,
5H), 7.42 (t, J＝7.5 Hz, 2H), 7.53 (t, J＝7.2 Hz, 1H),
7.91 (d, J＝7.2 Hz, 2H); HPLC analysis: Chiralpak
AD-H column, i-PrOH/hexane 50∶50, flow rate 1.0
mL/min, λ＝254 nm, retention time: 7.56 min (major)
and 10.76 min (minor), 60% ee.
[6] Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2000, 122, 4243.
[7] For representative examples of chiral thioureas-based organocata-
lysts, see: (a) Sigman, M. S.; Jacobsen, E. N. J. Am. Chem. Soc.
1998, 120, 4901; (b) Tsogeva, S. B.; Wei, S. Chem. Commun. 2006,
1451; (c) Wei, S.; Yalalov, D. A.; Tsogoeva, S. B.; Schmata, S.
Catal. Today 2007, 121, 151; (d) Huang, H.; Jacobsen, E. N. J. Am.
Chem. Soc. 2006, 128, 7170; (e) Inokuma, T.; Hoashi, Y.; Takemoto,
Y. J. Am. Chem. Soc. 2006, 128, 9413; (f) Li, P.; Wang, Y.; Liang,
X.; Ye, J. Chem. Commun. 2008, 3302; (g) Kokotos, C. G.; Kokotos,
G. Adv. Synth. Catal. 2009, 351, 1355; (h) Jiang, X.; Zhang, B.;
Zhang, Y.; Lin, L.; Yan, W.; Wang, R. Chirality 2010, 22, 625; (i)
Chuan, Y.; Yin, L.; Zhang, Y.; Peng, Y. Eur. J. Org. Chem. 2011,
578.
Acknowledgement
This work was financially supported by the Ph.D.
Programs Foundation of Ministry of Education of China
(No. 20090031110019) and National Basic Research
Program of China (973 Program) (No. 2010CB833300).
We also thank the Nankai University State Key Labora-
tory of Elemento-Organic Chemistry for support.
[8] Wang, J.; Li, H.; Zu, L.; Wang, W. Adv. Synth. Catal. 2006, 348,
425.
[9] Wang, J.; Wang, X.; Ge, Z.; Cheng, T.; Li, R. Chem. Commun. 2010,
46, 1751.
[10] Qian, Y.; Xiao, S.; Liu, L.; Wang, Y. Tetrahedron: Asymmetry 2008,
19, 1515.
[11] Xu, D.; Shi, S.; Wang, Y. Tetrahedron 2009, 65, 9344.
[12] (a) Alcón, M. J.; Iglesias, M.; Sánchez, F.; Viani, I. J. Organomet.
Chem. 2001, 634, 25; (b) Kitagawa, S.; Murakami, T.; Hatano, M.
Inorg. Chem. 1975, 14, 2347.
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