Copper-catalyzed asymmetric 1,4-conjugate addition of dialkylzinc to enones

Article abstract of DOI:10.1002/aoc.1651

Asymmetric 1,4-conjugation addition of dialkylzinc (diethylzinc and dimethylzinc) to cyclic enones, chalcone and nitroalkenes was achieved by a 25 mol% (R)-6,6'-Br₂-BINOL(1f), 25 mol% CuSPh and 100 mol% dicyclohexylmethylamin(Cy₂NMe) catalyst system. The Cu(I) catalyst system enables the cyclic enone, chalcone and nitroalkene generality with high enantioselectivity (up to84%ee) and isolated yield (up to 94%) under mild reaction conditions.

Full text of DOI:10.1002/aoc.1651

Full Paper
Received: 15 February 2010
Revised: 25 February 2010
Accepted: 26 February 2010
Published online in Wiley Interscience: 13 April 2010
(
www.interscience.com) DOI 10.1002/aoc.1651
Copper-catalyzed asymmetric 1,4-conjugate
addition of dialkylzinc to enones
a∗
a,b
b
a
a
Shaohua Gou , Zhongbin Ye , Leiting Shi , Dayong Qing , Wen Zhang
c
and Yuliang Wang
Asymmetric 1,4-conjugation addition of dialkylzinc (diethylzinc and dimethylzinc) to cyclic enones, chalcone and nitroalkenes
ꢀ
was achieved by a 25 mol% (R)-6,6 -Br2-BINOL(1f), 25 mol% CuSPh and 100 mol% dicyclohexylmethylamin(Cy2NMe) catalyst
system. The Cu(I) catalyst system enables the cyclic enone, chalcone and nitroalkene generality with high enantioselectivity (up
to 84% ee) and isolated yield (up to 94%) under mild reaction conditions. Copyright ꢀc 2010 John Wiley & Sons, Ltd.
Keywords: addition reaction; conjugation; copper; enones; zinc
Introduction
and its derivatives (see Fig. 1) combined with copper salt and a
tertiary amine catalytic system.
Catalytic asymmetric carbon–carbon bond formation using
organometallic reagents is a very important transformation
in the field of organic chemistry. Among these reactions,
copper-catalyzed conjugate addition of dialkylzinc to α, β-
unsaturated compounds has attracted much attention because
of its simplicity and utility for the preparation of biological
[
1]
Catalyst System Screening
Initially, we investigated the 1,4-conjugate addition reaction of
diethyl zinc (Et Zn) to 2-cyclohexen-1-one (2a) in the presence of
2
[
1,2]
active or natural compounds.
Ever since the discovery
15 mol% (R)-BINOL (1a) combined with 15 mol% copper salts (1 : 1
Ž
in the early1990s by Alexakis and co-workers of the Cu-
catalyzed asymmetric conjugated addition of dialkylzinc reagents
approach, considerable effort has been put into this area
ratio) in dry toluene at 0 C under nitrogen atmosphere (Table 1).
The results in Table 1 showed that these copper complexes
could promote the reactions with good to excellent yields
except for the Cu(acac)2 complex (Table 1, entry 9). However,
the enantioselective excess (ee) values were very low, all copper
complexes affording racemic products (Table 1, entries 1–11).
We then thought of introducing another activator (tertiary
amine) to eliminate or decrease the ‘mono-activity’ and form
a Lewis acid–Lewis base catalyst system (dual-activity) for
[
2,3a]
during the past decades by many research groups.
As a
consequence, diorganozinc reagents have taken a prominent
position in this field, and they have been successfully applied
to many α, β-unsaturated compounds, such as cyclic and
acyclic enones, nitro olefins, amides, lactones, lactones and
malonates.[
1,2]
The design of chiral ligands is perhaps the key
[
15]
to attaining high asymmetric induction in the Cu-catalyzed
asymmetric conjugated addition. The most explored chiral ligands
the 1,4-conjugate addition based on Shibasaki’s method.
Therefore, we introduced serial tertiary amines into the (R)-
1a–CuSPh catalyst system (Table 2). A significant improvement
in the ee to 67% and in the yield to 68% was achieved when
15 mol% dicyclohexylmethylamine (Cy2NMe) was employed in
the conjugate addition of diethylzinc to 2-cyclohexen-1-one
(Table 2, entry 1). The use of NEt3, DMAP, cinchonine, cinchon-
[
3]
types were phosphorus-based ligands including phosphites,
diphosphites,[ phosphoramidites, P,O- and P,N-ligands.
4]
[5]
[6]
[7]
Other classes of ligands explored, without a phosphorus atom,
[
8]
[9]
[10]
includedchiralsulfonamides, diaminocarbenes, oxazolines,
S,O-,[ N,N- andN,S- ligands.Ontheotherhand,binaphthol-
based ligands are some of the most widely studied in 1,4-
conjugate addition. Many modifications on the binaphthol
backbone have been developed by many research groups.[
These ligands have provided excellent enantioselectivities with
a wide range of substrates for cyclic, linear, nitro- olefin and
alkylidenemalonate substrates. However, these bear a chiral
phosphite or phosphoramidite in the asymmetric conjugated
addition. To the best of our knowledge, there has been only
one example of the enantioselective 1,4-conjugate addition
11]
[12]
[13]
0
dine, spartein, AD-Mix-Alpha, i-Pr2NEt, [2,2 ]bipyridinyl, 3,4,7,8-
tetramethyl-5,6-dihydro-[1,10]phenanthroline and pyridine gave
lower ee (Table 2, entries 3–12 vs entry 1). Surprisingly, the
2a,14]
Ł
Correspondence to: Shaohua Gou, Southwest Petroleum University, School of
Chemistry and Chemical Engineering, Chengdu 610500, People’s Republic of
China. E-mail: shaohuagou@swpu.edu.cn
a School of Chemistry and Chemical Engineering, Southwest Petroleum
University, Chengdu 610500, People’s Republic of China
of dialkylzinc to enones using chiral BINOL-ligands without a
phosphorus atom.[
types of catalytic system for conjugate addition, especially based
on the chiral BINOL without a phosphorus atom. We report here
the enantioselective conjugate addition of diorganozinc (ZnEt2 or
ZnMe2) to cyclic enones, chalcone and nitroalkenes using BINOL
11b,c]
Thus, it is still necessary to develop new
b State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation,
Southwest Petroleum University, Chengdu 610500, People’s Republic of China
c College of Chemistry, Sichuan University, Chengdu 610064, People’s Republic
of China
Appl. Organometal. Chem. 2010, 24, 517–522
Copyright ꢀc 2010 John Wiley & Sons, Ltd.

S. Gou et al.
R1
R
Table 2. Screening of different tertiary amine for the conjugation
addition of diethylzinc to 2-cyclohexen-1-one
OH
OH
Entrya
Yield (%)b
Ee(%)c
Tertiary amine
R1
R
1
2d
3
Cy NMe
2
68
66
67
40
41
67
11
15
58
10
15
67(S)
65(R)
58(S)
30(S)
32(S)
17(S)
10(S)
7(S)
(
R)-1a-g
Cy2NMe
1
1
1
1
a: R = R1 = H
NEt3
1
1
b: R = Br, R = H
1e: R = P(O)Ph , R = H
1f: R = H, R = Br
2
4
DMAP
1
1
c: R = I, R = H
1
1
5
Cinchonine
Cinchondine
Spartin
d: R = SiPh , R = H 1g: R = H, R = I
3
6
Figure 1. Screening chiral ligands structures.
7
8
AD-Mix-Alpha
i-Pr2NEt
9
62(S)
16(R)
18(R)
0
10
[2,2 ]Bipyridinyl
Table 1. Screening of different metal salts for the conjugation
addition of diethylzinc to 2-cyclohexen-1-one
11
3,4,7,8-Tetramethyl-5,6-
dihydro-[1,10]phenanthroline
O
O
12
Pyridine
35
24(S)
1
1
5 mol% (R)-1a
5 mol% CuX
a
Conditions: concentration of 2a, 0.2 M in PhCH3; CuSPh, 15 mol%;
tertiary amine, 15 mol%; (R)-1a, 15 mol%; Et2Zn, 1.8 equiv. in hexane
+
ZnEt2
Toluene, 0 °C, 5h
*
Ž
solution; reaction performed for 5 h at 0 C.
2a
3a
b
Isolated yield.
The ee was determined by chiral GC G-TA column.
c
[3j,16]
Entrya
CuX
Yield (%)b
Ee(%)c
d
(
S)-1a was used under same conditions as entry 1.
1
2
3
4
5
6
7
8
9
CuI
26
88
2
3
Cu(TfO)2
CuBr
25
2
Table 3. Screening of different salts and solvent for the conjugate
addition using (R)-1a and Cy2NMe
CuCl
75
3
CuCN
96
1
CuCl
80
4
Entrya
Yield (%)b
Ee(%)c
CuX
CuSPh
Solvent
Cu(AcO)2.H2O
CuSO4.5H2O
Cu(acac)2
CuBrPh3P
CuSPh
42
3
63
2
1
2
3
4
5
6
7
8
9
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
68
90
25
85
99
80
58
94
10
91
92
15
49
80
58
67
5
trace
91
1
Cu(TfO)2
CuBr
1
0
1
3
24
14
0
1
65
8(S)
CuCl
CuCN
a
Conditions: concentration of 2a, 0.2 M in PhCH3; Et2Zn, 1.8 equiv. in
hexane solution; reaction performed for 5 h at 0 C.
Isolated yield.
The ee was determined by chiral GC G-TA column.
Ž
CuCl2
47
11
57
38
3
b
Cu(AcO)2žH2O
CuSO4ž5H2O
Cu(acac)2
CuBrPh3P
CuI
c
[3j,16]
1
0
1
1
44
59
25
38
43
configuration of the products were converted from S to R
when employing [2,2 ]bipyridinyl and 3,4,7,8-tetramethyl-5,6-
dihydro-[1,10]phenanthroline(Table 2,entries10and11).Notably,
similar results were obtained when the (S)-1a was employed in the
same conjugate addition (Table 2, entry 2).
0
12
CuSPh
13
14
15
CuSPh
Et2O
CuSPh
CH2Cl2
Hexene
CuSPh
a
Conditions: concentration of 2a, 0.2 M in PhCH3; CuSPh, 15 mol%;
tertiary amine, 15 mol%; (R)-1a, 15 mol%; Et2Zn, 1.8 equiv. in hexane
Ž
solution; reaction performed for 5 h at 0 C.
Catalyst System Optimization
b
Isolated yield.
c
The ee was determined by chiral GC G-TA column, and the
Having realized the potential of activators in the asymmet-
ric copper-catalyzed 1,4-conjugate addition of diethylzinc to
[3j,16]
configuration was S.
2
-cyclohexen-1-one (2a), the effects of several reaction parame-
ters, such as copper sources, BINOL derivatives 1b–g and reaction
solvent were studied with the aim of optimizing the reaction
conditions and developing more efficient catalytic system.
Cu(OAc)2.H2O and Ph3PCuS gave very bad results (Table 3, entries
2, 4, 5, 7, 10).
Initially, the effects of various copper sources such as CuI,
Cu(TfO)2, CuBr, CuCl, CuCN, CuCl2, CuSO4ž5H2O, Cu(acac)2 and
Cu(OAc)2.H2O were investigated using (R)-1a combined with the
most promising activator (Cy2NMe; Table 3). In all cases, except
in entry 5, a combination of CuI, CuCl2, CuSO4ž5H2O, Cu(acac)2
and CuBr gave moderate ee values (Table 2, entries 3, 6, 8, 9,
Next, we investigated the effect of different solvents (toluene,
CH2Cl2, THF, Et2O and hexane) using the complex of (R)-1a
with CuSPh combined with Cy2NMe (Table 3, entries 12–15). It
was found that THF gave very low yield with 59% ee, and the
configuration of product was converted (Table 3, entry 12). Et2O
gave moderate yield and ee (Table 3, entry 13). CH2Cl2 and hexane
gave moderate ee values with moderate to good yield (Table 3,
1
1 vs 1). Other copper complexes, such as CuCl, Cu(TfO)2, CuCN,
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Copyright ꢀc 2010 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 517–522

Copper-catalyzed asymmetric 1,4-conjugate addition
Lewis base or play an additive role in the asymmetric conjugate
addition.[ Better enantioselectivity could be obtained when
lowering the concentration of 2a from 0.2 to 0.1 M, although
it led to a slightly drop in reactivity (Table 5, entry 10). In
contrast, a further increase of the concentration of 2a led to less
satisfactory enantioselectivity (Table 5, entry 11). Changing the
reaction temperature could not improve the enantioselectivity
Table 4. Screening of the ligands 1a–g for the conjugation addition
of diethylzinc to 2-cyclohexen-1-one
16]
Entrya
ligand (15 mol%)
Time (h)
Yield (%)b
Ee(%)c
1
1a
1b
1c
1d
1e
1f
5
10
10
5
68
30
45
72
91
77
73
75
76
67
16
18
8
2
3
(
Table 5, entries 12 and 13).
4
5
5
5
6
5
70
66
28
72
Substrate Generality
7
1g
1f
5
8d
9e
5
Encouraged by the results obtained from 2a under the optimized
conditions(Table 5,entry10),severalα,β-unsaturatedcompounds
were evaluated using Et2Zn or Me2Zn (Table 6). It was found that
these reactions gave the corresponding product with up to 84% ee
1f
5
a
Conditions: concentration of 2a, 0.2 M in PhCH3; Et2Zn, 1.8 equiv.
Ž
in hexene solution, Cy2NMe 15 mol%; reaction performed at 0 C,
PhSCu:1f D 1 : 1 (mol%).
and 94% yield (Table 6, entries 1 and 8). Introducing Me Zn to the
2
b
Isolated yield.
1
,4-conjugate addition of 2a, similar results were obtained after
longer reaction times (3b, Table 6, entry 2 vs entry 1). Cyclopent-2-
enone (2b) led to similar results reacting with Et Zn and Me Zn (3c
c
The ee was determined by chiral GC G-TA column, and the
[3j,16]
configuration was S.
d
e
(
S)-1f was used.
2
2
Et2Zn: 1.8 equiv. in toluene solution.
and 3d, Table 6, entries 3 and 4 vs 1). When 4,4-dimethyl-cyclohex-
-enone (2c) with Et2Zn was employed in the 1,4-conjugate
2
addition, moderate ee and yield with converse configuration
were afforded under same conditions (Table 6, entry 5). ee Values
of 67 and 63% were obtained when the cyclohept-2-enone (2d)
and Et2Zn or Me2Zn were employed in the 1,4-conjugate addition,
respectively (Table 6, entries 6 and 7). 1,3-Diphenyl-propenone
entries 14 and 15). The highest ee of 67% was obtained in toluene
(Table 3, entry 1).
BINOL derivatives (R)-1b-g combined with Cy2NMe and CuSPh
were also determined under the same conditions with (R)-1a and
(2e) and (2-nitro-vinyl)-benzene (2f) gave very low ee, although
Cy2NMe catalyst systems (Table 4, entries 2–8 vs entry 1). The
excellent yields were obtained (Table 6, entries 8 and 9). These
above results revealed that the copper(I) complex of (R)-1f and
Cy2NMe catalyst was effective for the addition of dialkylzinc to
various enones.
0
data indicated that the catalytic system of (R)-1f (6,6 -Br2-BINOL)
was the best one (Table 4, entry 6). Other catalytic systems could
catalyze the 1,4-conjugate addition with moderate to excellent
yields in 5–66% ee (Table 4, entries 2–5 and 7). Better results
could be obtained when the Et2Zn in toluene solution was used in
the catalytic system (Table 4, entry 9).
The optimum loadings of (R)-1f and Cy2NMe were investigated
under the best conditions (Table 5). It was found that the best
loading was 25 mol% (R)-1f and 100 mol% Cy2NMe, respectively
Catalytic Cycle Considerations
Based on previous works in the field of the 1,4-conjugate addition
dialkylzinc to enones,[
2,12]
the copper(I) complex might play a
(
(
Table 5, entry 7); higher or lower loadings afforded inferior results
Table 5, entries 1–4, 6–9). The excess Cy2NMe may act as a
multifunctional role in this reaction. As shown in Fig. 2, the
expected active species I could be generated in addition to Et2Zn
Table 5. Optimization of the catalytic system for the conjugation addition of diethylzinc to 2-cyclohexen-1-one
Concentration
(R)-1f
(mol%)
Cy2NMe
(mol%)
Temperature
Time
(h)
Yield
(%)
Entrya
of 2a
( C)
Ž
b
Ee(%)c
1
2
3
4
5
6
7
8
9
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.1
0.4
0.1
0.1
15
10
10
15
15
25
25
45
45
25
25
25
25
15
10
0
0
5
5
76
35
74
71
75
69
77
74
68
67
86
61
36
72
38
73
76
79
77
80
78
69
84
65
59
46
100
50
0
5
0
5
100
25
0
5
0
5
100
100
150
100
100
100
100
0
5
0
5
0
5
1
1
1
1
0
1
2
3
0
10
10
3
0
20
ꢁ20
15
a
b
c
Ž
Conditions: solvent, PhCH3; Et2Zn, 1.8 equiv. in toluene solution; reaction performed for 5 h at 0 C, PhSCu:1f D 1 : 1 (mol%).
Isolated yield.
The ee was determined by chiral GC G-TA column, and the configuration was S.[3j,15]
Appl. Organometal. Chem. 2010, 24, 517–522
Copyright ꢀc 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/aoc

S. Gou et al.
Br
Br
Et
Table 6. Extension the substrates for the conjugate addition of
dialkylzinc to enones
Zn
O
O
S Ph
Cu
2
5 mol% (R)-1f
O
25 mol% CuSPh
O
Zn Et
1
00 mol% Cy NMe
2
N
Cy
+
ZnR2
Cy
O
Toluene, 0 °C
*
ZnEt2
CH3
R
I
2a-f
3a-i
Time Yield
Ee
(%)
O
2
a
Entrya
Enones
R
Product
(h)
(%)
b
c
H+
Br
Br
Et
1
2
2a Et
2a Me
3a
3b
5
67
63
84(S)
O
Zn
S
Cu
10
80(S)
Ph
(
S)-3a
O
O
3
4
2b Et
2b Me
3c
5
63
78
81(S)
78(S)
Zn
O
O
3d
10
O
N
Cy
CH3
Cy
II
5
2c Et
3e
5
44
76(R)
Figure 2. The proposed catalytic cycle.
6
7
2d Et
2d Me
3f
5
90
88
67(S)
63(S)
O
Experimental Section
3g
10
General Remarks
Enantiomeric ratios of the products were determined using chiral
GC or HPLC techniques. Analytical thin-layer chromatography
8
2e Et
3h
3i
5
5
94
86
9(R)
7(R)
O
(
TLC) was carried out on commercial plates coated with 0.25 mm
Ph
Ph
Ph
NO2
ofsilicagel.Preparativeflashsilicachromatographywasperformed
using silica gel 200–400 mesh. All reactions were carried out under
an atmosphere of nitrogen in flame- or oven-dried glassware with
magnetic stirring unless otherwise indicated.
9
2f
Et
a
Conditions: concentration of 2, 0.1 M in PhCH3; Et2Zn or Me2Zn, 1.8
Ž
equiv. in PhCH3 solution, 0 C.
b
Isolated yield.
c
The ee was determined by chiral GC G-TA, γ -DEX, β-DEX, HPLC-AD
Materials
or OD-H column, the absolute configuration of the major product
compared with the reported value of optical rotation.[3j,16]
(
R)-1a, (S)-1a, diethylzinc (Et2Zn), dimethylzinc (Me2Zn), all tertiary
amine such as DMAP, Et3N, dicyclohexylmethylamine (Cy2NMe),
-cyclohexen-1-one (2a), cyclopent-2-enone (2b), 4,4-dimethyl-
2
cyclohex-2-enone (2c), cyclohept-2- enone (2d), 1,3-diphenyl-
propenone (2e) and (2-nitro-vinyl)-benzene (2f), and all copper
salts such as CuSPh, CuI, Cu(TfO)2, CuBr, CuCl, CuCN, CuCl2,
or Me2Zn from the mixture of CuSPh and (R)-1f, and the centre
metal (Zn) might coordinate weakly to the S atom of PhSCu. Part of
the Cy2NMe might form a salt of PhSCu–Zn(Me)Et2, and another
part might be coordinated to the metal Zn and act as a Lewis base.
When the cyclic enones (2) were added to the mixture, the metal
moiety (Cu and Zn) of complex I might have acted as a Lewis acid
to activate the cyclic enones 2 and engender species II. Then the
product 3a was obtained by work-up with aqueous acid (HCl) and
one catalytic cycle accomplished.
ž
CuSO4.5H2O, Cu(acac)2 and Cu(OAc)2 H2O were commercially
available, and used without further purification. Anhydrous
solvents such as THF, CH2Cl2, toluene, hexene and Et2O were
treated by typical methods. Chiral ligands 1b–g were synthesized
[17]
according to the literature procedures.
General Procedure for Copper-catalyzed Asymmetric
1,4-Conjugate Addition
A mixture of CuSPh (10.75 mg, 0.0625 mmol), (R)-1f (27.6 mg,
Conclusion
0
.0625 mmol) and Cy2NMe (0.25 mmol, 54 µl) in dried toluene
Ž
(
1.30 ml) was stirred under nitrogen atmosphere at 22 C for
In summary, we have developed a new class of catalyst system
for the enantioselective copper-catalyzed 1,4-conjugate addition
of dialkylzinc to various enones. The catalyst system could form
a Lewis acid–Lewis base centre in the 1,4-conjugate addition
reactionofdialkylzinctoenones,basedonthebifuntionalconcept.
The work presented here paves the way for the development of a
new catalytic system for asymmetric reactions. Further studies of
other asymmetry reaction applications of the catalyst system are
in progress.
10 min, and then Et Zn (0.45 mmol, 450 µl, 1.0 M in hexane)
2
was injected into the mixture and stirred for 1.0 h at same
temperature. Cyclic enone 2 (0.25 mmol) was added after 10 min
at the indicated temperature and the resulting mixture was stirred
for indicated time before being quenched by aqueous HCl (2 ml,
1.0 M). The mixture was extracted with EtOAc (3 ð 20 ml); the
organic phases were combined, dried over Na SO , filtered and
2
4
evaporated to dryness. The crude product was purified by silica
gel column chromatography on silica gel (ethyl acetate–hexane)
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Copyright ꢀc 2010 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 517–522

Copper-catalyzed asymmetric 1,4-conjugate addition
to give the desired products 3a–i; these known compounds were
(R)- (1-Nitromethyl-propyl)-benzene (3i)
1
13
characterized by comparing their H, C NMR spectra with those
[
5c,16]
7% ee by chiralcel OD-H (DAICEL) analysis (eluent, hexane–2-
propanol, 95 : 5, 0.7 ml/min). Retention times, t1 D 33.2 (minor),
t2 D 21.1 min (major). The absolute configuration was assigned
published in the literature.
-(S)-Ethyl-cyclohexan-1-one (3a)[3j,16b]
[11e]
3
by analogy.
Ž
8
2
(
4% ee by GC analysis (Chiracel G-TA column, 110 C, and flow,
.0 ml/min). Retention times, t1 D 5.4 (minor), t2 D 5.6 min
Acknowledgment
2
5
[3j]
28
major). [a] D D ꢁ11.2 (c D 1.0, CH2Cl2). fLit. [a] D D ꢁ15.6
c D 1.0, CHCl3) for S enantiomer in 99% eeg.
The authors gratefully acknowledge the Open Fund (no. PLN0908)
ofKeyLaboratoryofOilandGasReservoirGeologyandExploitation
(
(
Southwest Petroleum University) for financial support.
3
-(S)-Methyl-cyclohexan-1-one (3b)[3j,16b]
0% ee by GC analysis (Chiracel γ -DEX column, 70 C, 30 min,
Ž
8
1
Ž
Ž
References
0 C/min, final temperature 150 C). Retention times, t1 D 36.8
2
5
(
major), t2 D 38.2 min (minor). [a] D D ꢁ9.7 (c D 1.0, CH2Cl2).
[
1] a) K. Tomioka, in Comprehensive Asymmetric Catalysis (Eds.:
E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer: Berlin, 2004,
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[3j] 28
fLit. [a] D D ꢁ13.4 (c D 0.6, CHCl3) for S enantiomer in 99%
eeg.
3
-(S)-Ethyl-cyclopentan-1-one (3c)[3j]
Ž
8
5
1% ee by GC analysis (Chiracel γ -DEX column, 70 C, 25 min,
Ž
Ž
C/min, final temperature 120 C). Retention times, t1 D 30.2
a¨ ckvall, N. Krause, O. Pa’mies,
2
5
[2] For reviews, see: a) A. Alexakis, J. E. B
(
major), t2 D 32.0 min (minor). [a] D D ꢁ71.4 (c D 1.0, CH2Cl2).
M. Die’guez, Chem. Rev. 2008, 108, 2796; b) S. R. Harutyunyan,
T. Den. Hartog, K. Geurts, A. J. Minnaard, B. L. Feringa, Chem. Rev.,
2008, 108, 2824; c) N. Krause, A. Hoffmann-R o¨ der, Synthesis
[3j] 29
fLit. [a] D D ꢁ81.2 (c D 0.5, CHCl3) for S enantiomer in 93%
eeg.
2
2
001, 171; b) A. Alexakis, C. Benhaim, Eur. J. Org. Chem.
002, 3221; d) B. L. Feringa, Acc. Chem. Res. 2000, 33, 346;
3
-(S)-Methyl-cyclopentan-1-one (3d)[3j]
e) M. P. Sibi, S. Manyem, Tetrahedron 2000, 56, 8033; f) B. E. Rossiter,
N. M. Swingle, Chem. Rev., 1992, 92, 771.
Ž
7
5
8% ee by GC analysis (Chiracel γ -DEX column, 60 C, 20 min,
[3] a) A. Alexakis, J. C. Frutos, P. Mangeney, Tetrahedron: Asymmetry
1993, 4, 2427; b) A. Alexakis, J. Vastra, J. Burton, P. Mangeney,
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P. Mangeney, Tetrahedron Lett. 1997, 44, 7745; d) A. Alexakis,
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Ž
Ž
C/min, final temperature 120 C). Retention times, t1 D 24.3
2
5
(
major), t2 D 24.8 min (minor). [a] D D ꢁ10.8 (c D 0.5, CH2Cl2).
[3j] 29
fLit. [a] D D ꢁ14.1 (c D 0.2, CHCl3) for S enantiomer in 92%
eeg.
1
998, 39, 7869; e) O. Pamies, G. Net, A. Ruiz, C. Claver, Tetrahedron:
Asymmetry 1999, 10, 2007; f) A. Alexakis, J. Burton, J. Vastra,
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3
-(R)-Ethyl-4,4-dimethyl-cyclohexanone (3e)[16b,c]
2
2
000, 56, 2879; h) T.-L. L. Terry, A. Yeung, A. S. C. Chan, Org. Lett.,
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7
1
6% ee by GC analysis (Chiracel G-TA column, 100 C, and flow,
.0 ml/min). Retention times, t1 D 33.3 (minor), t2 D 34.2 min
2006, 25, 2284; j) K. Kawamura, H. Fukuzawa, M. Hayashi, Org. Lett.
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2
5
[16c]
29
(
major). [a] D D ꢁ16.6 (c D 0.5, CH2Cl2). fLit.
c D 1.38, CHCl3) for R enantiomer in 75% eeg.
[a] D D ꢁ17.2
(
[
[
4] a) M. Yan, L. W. Yang, K. Y. Wong, A. S. C. Chan, Chem. Commun.
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3
Ž
6
1
7% ee by GC analysis (Chiracel G-TA column, 100 C, and flow,
.0 ml/min). Retention times, t1 D 26.7(major), t2 D 27.2 min
2
5
[3j]
30
(
(
minor). [a] D D ꢁ35.8 (c D 0.5, CH2Cl2). fLit. [a] D D ꢁ43.9
c D 0.75, CHCl3) for S enantiomer in 79% eeg.
1
104; c) L. A. Arnold, R. Imbos, A. Mandoli, A. H. M. Vries, R. Naasz,
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-(S)-Methyl-cycloheptan-1-one (3g)[3j]
2004, 69, 5660; f) F. Boeda, D. Rix, H. Clavier, C. Crevisy, M. Mauduit,
Tetrahedron: Asymmetry 2006, 17, 2726.
Ž
6
5
3% ee by GC analysis (Chiracel β-DEX column, 80 C, 30 min,
[
6] N. Fuchs, M. d’ Augustin, M. Humam, A. Alexis, R. Taras, S. Gladiali,
Ž
Ž
C/min, final temperature 120 C). Retention times, t1 D 35.3
Tatrahedron: Asymmetry 2005, 16, 3143.
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2
5
(
major), t2 D 37.1 min(minor). [a] D D ꢁ4.0 (c D 0.5, CH2Cl2).
[3j] 26
fLit. [a] D D ꢁ6.2 (c D 1.0, CHCl3) for S enantiomer in 88% eeg.
1
2
999, 38, 3518; c) I. H. Escher, A. Pfaltz, Tetrahedron 2000, 56,
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1
[
8] a) I. Chataigner,C. Gennari,S. Ongeri,U. Piarulli,S. Ceccarelli,Chem.-
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9
propanol, 99 : 1, 1.0 ml/min). Retention times, t1 D 8.3 (minor),
t2 D 11.0 min (major). The absolute configuration was assigned
by analogy.[
3j]
Appl. Organometal. Chem. 2010, 24, 517–522
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Copyright ꢀc 2010 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 517–522