Application of ferrocenyl substituted aziridinylmethanols (FAM) as chiral ligands in enantioselective conjugate addition of diethylzinc to enones

Article abstract of DOI:10.1016/j.tetasy.2007.02.015

Easily available ferrocenyl substituted aziridinylmethanol FAM-4a complexes with nickel and catalyzes the enantioselective diethylzinc addition to various enones with enantiomeric excesses reaching 80%. The ligand can be recovered and used without losing its activity. The sense of induction was found to be dependent on the configuration of the aziridine ring.

Full text of DOI:10.1016/j.tetasy.2007.02.015

Tetrahedron: Asymmetry 18 (2007) 679–684
Application of ferrocenyl substituted aziridinylmethanols
(FAM) as chiral ligands in enantioselective conjugate addition
of diethylzinc to enones
*
¨
Alper Isleyen and Ozdemir Dogan
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
Received 12 February 2007; accepted 14 February 2007
Available online 19 March 2007
Abstract—Easily available ferrocenyl substituted aziridinylmethanol FAM-4a complexes with nickel and catalyzes the enantioselective
diethylzinc addition to various enones with enantiomeric excesses reaching 80%. The ligand can be recovered and used without losing
its activity. The sense of induction was found to be dependent on the configuration of the aziridine ring.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
selective diethylzinc addition reactions to enones. Herein,
we report the full details of this study.
Development of a new chiral catalyst for enantioselective
C–C bond formation is one of the most studied fields in
organic chemistry. Among the C–C bond forming reactions,
diethylzinc addition to aldehydes has been studied exten-
sively and considered as a test reaction for understanding
the catalytic potential of new chiral catalysts.1 Another
useful C–C bond formation reaction is the diethylzinc addi-
tion to enones which has not been studied as extensively as
the previous reaction.2 Diethylzinc addition to enones
requires a metal catalyst such as Cu(I)3 or Ni(II)4 generally.
Aziridine based ligands have recently gained increasing
importance and have been used as catalysts in diethylzinc
addition reactions to aldehydes.5 In a recent study by
Nayak et al., N-tritiyl aziridinyl methanol was used as
the chiral catalyst for the enantioselective diethylzinc addi-
tion reaction to chalcones to give the products in good
yields and up to 90% ee’s.6 We recently synthesized novel
ferrocenyl substituted aziridinyl methanols and used them
as chiral catalysts for 1,3-dipolar cycloaddition reactions
of azomethine ylides to obtain pyrrolidines with ee’s up
to 95%.7 The use of these ligands in diethylzinc addition
reactions to aldehydes gave the secondary alcohols with
ee’s up to 96%.8 These results prompted us to use these
ligands with Ni(acac)2 as a chiral catalyst for the enantio-
2. Results and discussion
Chiral ligands 4a–d were prepared in high yields and enan-
tiomeric excess from acryloylferrocene following the litera-
ture procedure7 (Scheme 1). First the efficiency of the
ligands in the enantioselective diethylzinc addition to chal-
cone was tested by adapting the literature procedure.4a The
reaction of chalcone with diethylzinc (1.5 equiv) in the
presence of 25 mol % of ligand 4a and 1 mol % Ni(acac)2
gave the expected product in 82% yield and 80% ee (Table
1, entry 1) at ꢀ35 ꢁC. Under the same reaction conditions,
the other ligands 4b–d were less efficient (Table 1, entries 2–
4). Previous studies carried out with aminoalcohols as
ligands on the enantioselective diethylzinc addition to
chalcones showed that the test solvent is acetonitrile and
Co, Cu, and Zn salts are less efficient than Ni(acac)2. We
found similar results, when using toluene as the solvent
and Cu(OTf)2 instead of Ni(acac)2 to give the product in
low yield and ee.
After determining that ligand 4a catalyzed the reaction
with the highest yield and ee, the effect of ligand and Ni-
(acac)2 concentrations on the yield and enantioselectivity of
the reaction was explored. When the ligand concentration
was lowered to 15 mol % or 5 mol %, both the yield and
the ee of the product were low (Table 1, entries 5 and 6).
On the other hand, increasing the ligand concentration
*
Corresponding author. Tel.: +90 312 210 51 34; fax: +90 312 210 32
00; e-mail: dogano@metu.edu.tr
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.02.015

¨
680
A. Isleyen, O. Dogan / Tetrahedron: Asymmetry 18 (2007) 679–684
H
Me
H
S
N
Me
O
Ph
Ph
O
O
S
O
Br2
N
Et3N
H
S
NH2
Br
+
Fe
Fe
S
Br
>95%
Me
R
Fe
H
Fe
H
Ph
54%
42%
1
2
3a
3b
THF
-78 oC
THF
NaBH4
ZnCl2
THF
MeOH
-78 oC
LiAlH4
ZnCl2
L-selectride
Me
L-selectride
-78 oC
-78 oC
H
H
S
H
S
N
H
S
Me
H
Me
OH
Me
HO
Ph
Ph
Ph
Ph
S
OH
H
HO
H
H
N
N
N
R
H
S
H
S
R
H
R
R
S
S
Fe
Fe
Fe
Fe
H
90% yield
>99% de
89% yield
>99% de
85% yield
selectivity 2.5:1
93% yield
4a
4b
4c
4d
selectivity 3:1
Scheme 1.
Table 1. Diethylzinc addition to chalcone under different conditions
O
O
chiral ligand 4
∗
+
Ph
Et2Zn
Ph
Ph
Ph
Ni(acac)2
CH3CN, -35 oC
Entry
Ligand
Ligand mol %
Ni(acac)2 mol %
Yielda (%)
eeb (%)
Config.c
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4a
4a
4a
4a
4a
4a
25
25
25
25
15
5
35
25
15
5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.5
0.2
82
61
72
65
61
40
78
71
78
84
80
42
3
34
69
47
82
76
70
44
R
R
S
S
R
R
R
R
R
R
10
a Isolated yield.
b Determined by HPLC using a Chiracel AD column.
c Determined by comparing the reported specific rotation data.
from 25 mol % to 35 mol % did not show a significant effect
on the yield and ee (Table 1, entry 7). By keeping the ligand
concentration at 25 mol % and reducing the Ni(acac)2 con-
centration from 1 mol % to 0.5 mol % the product was
formed in a slightly lower yield and ee (Table 1, entry 8).
Interestingly, at a concentration of 5 mol % ligand and
0.2 mol % Ni, the product was formed in 84% yield and
44% ee (Table 1, entry 10). These results are very similar
to the findings of previous studies where Bolm et al.4a
and Feringa et al.4d reported that the ligand to nickel ratio
is crucial for obtaining high enantioselectivity. They also
reported that the asymmetric induction depends upon the
equilibrium between the chiral nickel complex and catalyt-
ically active nickel species which lead to the racemic
product.
(25 mol % ligand, 1 mol % Ni-salt, acetonitrile, and
ꢀ35 ꢁC). The results of these reactions are summarized in
Table 2.
As can be seen from Table 2, the enantioselective diethyl-
zinc addition to enonones, where R1 and R2 are aromatic
took place smoothly to give the b-ethylated ketones in
good chemical yields and ee’s in the range of 42–80%.
Enantioselective diethylzinc addition to an enone with R2
being methyl formed the product in acceptable yield but
low ee (Table 2, entry 13). In the study of Bolm et al.,4a
the same substrate gave the product in 76% yield as a race-
mic mixture. Enones with methyl or cyclohexyl groups at
the b-position gave the products in reasonable yields and
ee’s (Table 2, entries 14 and 15). However, when a sterically
hindered tert-butyl group is introduced at either R1
(R2 = Ph) or R2 (R1 = Ph) position of the enone, most of
the starting materials were recovered, no b-ethylated
ketone was observed. A similar result was also seen when
In order to show the catalytic effect of ligand 4a, enantio-
selective diethylzinc addition reaction to various enones
were carried out under the optimized conditions

¨
A. Isleyen, O. Dogan / Tetrahedron: Asymmetry 18 (2007) 679–684
681
Table 2. Diethylzinc addition to various enonesa
O
O
25 (or 15) mol % 4a
∗
R1
R2
R1
R2
+ Et2Zn
1 (or 0.5) mol % Ni(acac)2
5a-n
6a-n
CH3CN, -35 oC, 5 h
Entry
R1
R2
Substrate
Yieldb (%)
eec (%)
Config.d,e
1f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
5a
5b
5c
5d
5e
5f
85
80
R
ꢀ
+
R
R
ꢀ
R
+
+
+
+
+
R
R
S
2g
3g
4
p-MeC6H4
p-CF3C6H4
p-ClC6H4
p-MeOC6H4
m-MeOC6H4
o-MeOC6H4
o-ClC6H4
o-FC6H4
o-FC6H4
2-Naphthyl
Fc
90(95)
80(86)
77(94)
75(96)
85(71)
60(85)
55(88)
77(94)
82
57(63)
71(63)
49(66)
57(60)
45(55)
72(62)
70(52)
70(60)
76(60)
80(74)
66(54)
50(40)
76(70)
76
78(72)
42(40)
22(16)
60(53)
70(57)
5
6
7
8
5g
5h
5i
9
10f
11g
12g,h,i
13h
14
15
5i
5j
5k
5l
Ph
Me
c-C6H11
Me
Ph
Ph
5m
5n
a An amount of 1 mol % Ni(acac)2 with 25 mol % of 4a or 0.5 mol % Ni(acac)2 with 15 mol % of 4a (data in parenthesis) were used.
b Isolated yield.
c Determined by chiral HPLC.
d Absolute configuration was assigned by comparing the reported specific rotation data.
e The + or ꢀ signs refer to the optical rotation.
f The recovered ligand was used.
g Enone was dissolved in CH2Cl2 because of solubility problems in CH3CN.
h Reaction was conducted at 0 ꢁC.
i Yield was 13% and ee was 56% at ꢀ35 ꢁC.
R2 (R1 = Ph) was a ferrocenyl group.9 The numbers in
parenthesis in Table 2 obtained by using 15 mol % ligand
and 0.5 mol % Ni(acac)2 indicate that at low ligand concen-
tration, products are formed in high yield but low ee. Once
again these results support the hypothesis that at low
ligand concentration less chiral nickel-complex which leads
to the enantiomerically enriched product is formed.
Interms of substituent effect, stereoselectivity did not signif-
icantly change with the electronic nature of the substituents
at the para-position of the b-phenyl group of the enones
(entries 2–5), which is contrary to the findings of the liter-
ature where considerably lower stereoselectivities were
reported for the p-CF3 substituent.3b,g These results show
that our catalyst is active enough to react with enones hav-
ing electron donating and withdrawing para-substituents.
For the ortho-substituted enones (entries 7–9), it seemed
that the size of the substituent was more important than
its electronic nature because electronegative fluoride on
the substrate gives the product in high yield and ee as
compared to the less electronegative chloride. Steric effects
can also be seen by the results of the p-, m-, and o-methoxy
substituted enones (entries 5–7), where the first two gave
the product in about the same yield and ee but the last
one gave the product in lower yield and ee.
and vice versa (Table 1, entries 3 and 4). b-Cyclohexyl-
enone (Table 2, entry 15) is an exception to this observation.
3. Conclusion
It has been shown that the aziridine based chiral ligand
FAM-4a can be used as a catalyst for the enantioselective
diethylzinc addition reaction to enones to give b-ethylated
ketones in up to 80% ee. The advantage of this ligand is
that it can easily be prepared on a gram scale in enantio-
merically pure form in three easy steps. It can be recovered
in >90% yield and used without losing its activity. Another
advantage of this ligand is that its antipode can be easily
prepared starting from (R)-methylbenzylamine. Thus one
can synthesize b-alkylated ketones with the desired config-
uration by choosing the appropriate ligand. The catalytic
effect of these ligands for other asymmetric reactions is
currently under investigation in our laboratory and will
be reported in due course.
4. Experimental
The 1H and 13C NMR spectra were recorded in CCl4/
CDCl3 (2/3, v/v) solvent system on a Bruker Spectrospin
Avance DPX 400 spectrometer. 1H NMR spectra were
reported in parts per million using TMS as an internal stan-
dard (TMS at 0.00 ppm). 13C NMR spectra were reported
in parts per million using solvent as an internal standard
Based on the assigned configurations, the configuration of
ligand 4 at the aziridine center is important in determining
the configuration of the product. Thus ligands with (S)-
configuration at the aziridine center gave the product with
(R)-configuration (Table 2, entries 1, 4, 5, 7, 13, and 14)

¨
A. Isleyen, O. Dogan / Tetrahedron: Asymmetry 18 (2007) 679–684
682
(CDCl3 at 76.9 ppm). Infrared spectra were recorded on a
Perkin Elmer 16 PC FT-IR spectrometer using CHCl3 as
the solvent. GC–MS spectra were obtained with a Thermo-
Quest (TSP) TraceGC-2000 Series instrument equipped
with a Phenomenex Zebron ZB-5 capillary column (5%
phenylmethylsiloxane, 30 m, 250 lm), MS: Thermo Quest
Finnigan multi Mass (EI, 70 eV). Optical rotations were
measured in a 1 dm cell using a Rudolph Autopol III
polarimeter at 25 ꢁC. HPLC measurements were performed
with Dionex System instrument. Separations were carried
out on Chiralcel AD, OD-H or OD analytical columns
(250 · 4.60 mm) with hexane/2-propyl alcohol as eluent.
Flash column chromatography was performed on silica
gel (60 mesh, Merck). Analytical thin layer chromato-
graphy (TLC) was performed on precoated silica gel (60
F254, Merck). Solvents CH3CN and CH2Cl2 were distilled
from CaH2 before use. All other reagents were commer-
cially available and used without further purification.
Melting points were obtained using an electrothermal
digital melting point apparatus (Gallenkamp) and were
uncorrected.
4.4. General procedure for the asymmetric addition of
diethylzinc to enones
Chiral ligands 4a–d and Ni(acac)2 were benzene azeotroped
and used from a stock solution in acetonitrile. Method A:
Chiral ligand (0.88 mL, 0.079 M, 25 mol %, freshly pre-
pared) and Ni(acac)2 (30 lL, 0.093 M, 1 mol %) or Method
B: Chiral ligand (0.53 mL, 0.079 M, 15 mol % freshly pre-
pared) and Ni(acac)2 (60 lL, 0.023 M, 0.5 mol %) were
mixed and refluxed under an argon atmosphere for 1 h.
At the end of this period, the reaction mixture was cooled
to room temperature and enone (0.280 mmol) in CH3CN
(0.2 mL) was added. Diethylzinc (0.42 mL, 0.42 mmol,
1 M in hexane) was then added slowly over a period of
10 min to the reaction mixture cooled to ꢀ35 ꢁC. The color
of the reaction mixture was changed from orange to dark
brown. After stirring for 5 h at this temperature, the mix-
ture was quenched with sat. NH4Cl solution followed by
extraction with ether (2 · 10 mL). The combined organic
layers were dried over Na2SO4, concentrated, and purified
by flash column chromatography (EtOAc/hexanes 1:20) to
obtain the pure product.
4.1. Synthesis of aziridino ketones 3a and 3b
4.4.1. 1,3-Diphenyl-1-pentanone 6a. Using method A, 6a
was obtained as a white solid (54.7 mg, 82% yield), mp:
25
Applying the literature procedure7 aziridino ketone 3a was
55–56 ꢁC; ½aꢁD = ꢀ4.3 (c 1.35, EtOH) for 80% ee; HPLC:
25
obtained in 54% yield, ½aꢁD = ꢀ90.0 (c 1.0, CHCl3) and 3b
Chiralcel AD column, UV detection at 240 nm, eluent: hex-
ane/2-propanol = 95:5 flow 1.0 mL minꢀ1, 20 ꢁC, tR (+)-
6a: 7.3 min; for (S), tR (ꢀ)-6a: 8.9 min for (R). All spectro-
scopic data are in good agreement with those reported in
the literature.3b,i,13a,b
25
was obtained in 42% yield, ½aꢁD = ꢀ220.0 (c 1.0, CHCl3)
as an orange solid from L-(ꢀ)-a-methylbenzylamine. All
spectroscopic data of the ketones were identical to those
synthesized from D-(+)-a-methylbenzylamine.
4.4.2. 1-Phenyl-3-p-tolylpentan-1-one 6b. Using method
4.2. Synthesis of chiral ligands FAM-4a–d
A, 6b was obtained as a pale yellow oil (63.6 mg, 90%
25
yield), ½aꢁD = ꢀ9.4 (c 2.22, EtOH) for 72% ee; HPLC: Chi-
Using the literature procedure7 FAM-4a was obtained as a
ralcel AD column, UV detection at 240 nm, eluent: hexane/
2-propanol = 95:5 flow 1.0 mL minꢀ1, 20 ꢁC, tR (+)-6b:
6.7 min, tR (ꢀ)-6b: 9.2. All other spectroscopic data are
in good agreement with those reported in the literature.13a
yellow oil in 89% yield as the only diastereomer,
25
½aꢁD = ꢀ45.2 (c 1.00, CHCl3); for FAM-4b: 90% yield
25
(obtained as the only diastereomer), ½aꢁD = ꢀ46.3 (c 1.00,
25
CHCl3); for FAM-4c: 70% yield, ½aꢁD = ꢀ3.0 (c
25
1.0, CHCl3), for FAM-4d 68% yield, ½aꢁD = ꢀ20.9
4.4.3. 3-(4-(Trifluoromethyl)phenyl)-1-phenylpentan-1-one
6c. Using method A, 6c was obtained as a yellow waxy
(c 1.00, CHCl3); all spectroscopic data are in good agree-
25
ment with those previously reported for the enantiomers.
oil (68.6 mg, 80% yield), ½aꢁD = +4.2 (c 1.92, EtOH) for
70% ee; HPLC: Chiralcel AD column, UV detection at
240 nm, eluent: hexane/2-propanol = 95:5 flow 1.0
mL minꢀ1, 20 ꢁC, tR (ꢀ)-6c: 6.5 min, tR (+)-6c: 8.6 min.
All other spectroscopic data are in good agreement with
those reported in the literature.3b
4.3. General procedure for the synthesis of enones10
The aldehyde (43.2 mmol) was added gradually to a solu-
tion of NaOH (2.2 g) in H2O (20.0 mL) and ketone
(43.3 mmol) in ethanol (12 mL) at 0 ꢁC. The mixture was
then allowed to warm to room temperature and stirred
for 4 h. At the end of this period, sat. NH4Cl solution
was added to the flask, followed by extraction with ether.
The combined organic layers were dried over Na2SO4
and concentrated to give a solid which was washed succes-
sively with hexane to get pure enones 5a–l. Enone 5n was
obtained as an oil and purified by flash column chromato-
graphy using EtOAc–hexanes (1:30). Enone 5m was
synthesized from trans-crotonyl chloride and benzene
according to the literature procedure.11 All spectroscopic
data of the enones were identical to those reported in the
literature.12
4.4.4. 3-(4-Chlorophenyl)-1-phenylpentan-1-one 6d. Using
method A, 6d was obtained as a colorless oil (58.8 mg,
25
77% yield), ½aꢁD = ꢀ1.8 (c 1.97, EtOH) for 70% ee; HPLC:
Chiralcel AD column, UV detection at 240 nm, eluent:
hexane/2-propanol = 95:5 flow 1.0 mL minꢀ1, 20 ꢁC, tR
(+)-6d: 7.8 min for (S), tR (ꢀ)-6d: 11.1 min for (R). All
other spectroscopic data are in good agreement with those
reported in the literature.3i,13a
4.4.5.
3-(4-Methoxyphenyl)-1-phenylpentan-1-one
6e.
Using method A, 6e was obtained as a pale yellow solid
25
(56.4 mg, 75% yield), mp: 49–50 ꢁC; ½aꢁD = ꢀ12.4 (c 1.49,
EtOH) for 76% ee; HPLC: Chiralcel AD column, UV

¨
A. Isleyen, O. Dogan / Tetrahedron: Asymmetry 18 (2007) 679–684
683
detection at 240 nm, eluent: hexane/2-propanol = 95:5 flow
1.0 mL minꢀ1, 20 ꢁC, tR (+)-6e: 9.2 min for (S), tR (ꢀ)-6e:
13.7 min for (R). All other spectroscopic data are in good
agreement with those reported in the literature.3i,13a
m/z (%): 256 (22) [M+], 227 (94), 137 (7), 135 (39), 120
(59), 105 (100), 76 (65), 50 (41).
4.4.10. 3-(Naphthalen-2-yl)-1-phenylpentan-1-one 6j. Using
method A, 6j was obtained as a pale yellow solid (46.03 mg,
57% yield), Rf = 0.42, 1:10 EtOAc–hexanes; mp: 51–52 ꢁC;
½aꢁ2D5 = +1.1 (c 1.99, EtOH) for 78% ee; HPLC: Chiralcel
AD column, UV detection at 240 nm, eluent: hexane/2-pro-
panol = 95:5 flow 1.0 mL minꢀ1, 20 ꢁC, tR (ꢀ)-6j: 8.8 min,
tR (+)-6j: 11.1 min; IR (CHCl3): m = 3061, 3004, 2970,
2929, 2868, 1677, 1602, 1582, 1507, 1446, 1385, 1354,
4.4.6.
3-(3-Methoxyphenyl)-1-phenylpentan-1-one
6f.
Using method A, 6f was obtained as a pale yellow waxy
oil (63.9 mg, 85% yield), Rf = 0.35, 1:10 EtOAc–hexanes,
25
½aꢁD = ꢀ3.4 (c 2.06, EtOH) for 80% ee; HPLC: Chiralcel
AD column, UV detection at 240 nm, eluent: hexane/2-
propanol = 95:5 flow 1.0 mL minꢀ1, 20 ꢁC, tR (+)-6f:
8.3 min, tR (ꢀ)-6f: 9.8 min; IR (CHCl3): m = 3039, 3008,
2964, 2930, 2878, 2835, 1687, 1604, 1486, 1452, 1363,
1286, 1235, 1198, 1174, 1099, 1021, 983, 925 cmꢀ1 1H
;
NMR (CDCl3–CCl4): d 0.83 (t, J = 7.3 Hz, 3H), 1.54–1.77
(m, 1H), 1.79–1.91 (m, 1H), 3.21–3.32 (m, 2H), 3.35–3.44
(m, 1H), 7.35–7.42 (m, 4H), 7.47 (t, J = 7.3 Hz, 1H), 7.62
(s, 1H), 7.74 (d, J = 8.2 Hz, 3H), 7.88 (d, J = 7.5 Hz, 2H);
13C NMR (CDCl3–CCl4): d 12.23, 29.13, 43.06, 45.63,
125.22, 125.84 (2C), 126.24, 127.57, 127.63, 128.06,
128.13, 128.44, 132.42, 132.71, 133.62, 137.38, 142.03,
198.20; MS (EI) m/z (%): 288 (15) [M+], 259 (15), 241 (5),
182 (21), 168 (61), 152 (22), 140 (35), 127 (14), 114 (10),
104 (91), 76 (100), 54 (10), 50 (27).
1316, 1261, 1155, 1047, 1013, 976, 923 cmꢀ1 1H NMR
;
(CDCl3–CCl4): d 0.82 (t, J = 7.3 Hz, 3H), 1.57–1.67 (m,
1H), 1.72–1.82 (m, 1H), 3.17–3.27 (m, 3H), 3.77 (s, 3H),
6.68 (d, J = 8.0 Hz, 1H), 6.73 (s, 1H), 6.79 (d, J = 7.6 Hz,
1H), 7.16 (t, J = 7.9 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H),
7.50 (t, J = 7.3 Hz, 1H), 7.88 (d, J = 7.5 Hz, 2H); 13C
NMR (CDCl3–CCl4): d 12.13, 29.10, 43.04, 45.58, 54.93,
111.32, 113.67, 119.94, 128.05, 128.42, 129.29, 132.69,
137.40, 146.32, 159.68, 198.44; MS (EI) m/z (%): 268 (18)
[M+], 239 (25), 185 (20), 163 (75), 148 (95), 134 (8), 121
(40), 105 (83), 91 (36), 77 (100), 65 (13), 55 (17), 50 (24).
4.4.11. 3-Ferrocenyl-1-phenylpentan-1-one 6k. Using
4.4.7. 3-(2-Methoxyphenyl)-1-phenylpentan-1-one 6g. Using
method A, 6k was obtained as a yellow oil (12.6 mg, 13%
25
method A, 6g was obtained as a pale yellow oil (45.1 mg,
yield), ½aꢁD = +42.9 (c 0.84, EtOH) for 56% ee; HPLC:
25
60% yield), ½aꢁD = ꢀ5.7 (c 1.80, EtOH) for 66% ee; HPLC:
Chiralcel AD column, UV detection at 240 nm, eluent: hex-
ane/2-propanol = 95:5 flow 1.0 mL minꢀ1, 20 ꢁC, tR (+)-
6k: 9.4 min, tR (ꢀ)-6k: 16.8 min. All other spectroscopic
data are in good agreement with those reported in the
literature.3i
Chiralcel AD column, UV detection at 240 nm, eluent: hex-
ane/2-propanol = 95:5 flow 1.0 mL minꢀ1, 20 ꢁC, tR (+)-6g:
7.7 min for (S), tR (ꢀ)-6g: 9.4 min for (R). All other spectro-
scopic data are in good agreement with those reported in the
literature.3a,6
4.4.12. 4-Phenylhexan-2-one 6l. Using method A, 6l was
4.4.8. 3-(2-Chlorophenyl)-1-phenylpentan-1-one 6h. Using
25
obtained as a yellow oil (24.2 mg, 49% yield), ½aꢁD = ꢀ3.5
method A, 6h was obtained as a pale yellow solid
25
(c 1.61, EtOH) for 22% ee; HPLC: Chiralcel OD-H col-
umn, UV detection at 220 nm, eluent: hexane/2-propa-
nol = 99:1 flow 1.0 mL minꢀ1, 20 ꢁC, tR (+)-6h: 9.8 min
for (S), tR (ꢀ)-6h: 10.8 min for (R). All other spectroscopic
data are in good agreement with those reported in the
literature.3i,13b,c
(42.0 mg, 55% yield), mp: 61–62 ꢁC; ½aꢁD = +16.4 (c 1.30,
EtOH) for 50% ee; HPLC: Chiralcel AD column, UV
detection at 240 nm, eluent: hexane/2-propanol = 95:5 flow
1.0 mL minꢀ1, 20 ꢁC, tR (ꢀ)-6h: 7.2 min, tR (+)-6h:
8.7 min. All other spectroscopic data are in good agree-
ment with those reported in the literature.3a
4.4.9. 3-(2-Fluorophenyl)-1-phenylpentan-1-one 6i. Using
method A, 6i was obtained as a pale yellow solid
4.4.13. 3-Methyl-1-phenylpentan-1-one 6m. Using method
A, 6m was obtained as a colorless oil (28.1 mg, 57% yield),
25
(55.2 mg, 77% yield), Rf = 0.48, 1:10 EtOAc–hexanes;
½aꢁD = ꢀ10.4 (c 1.87, Et2O) for 60% ee; HPLC: Chiralcel
25
mp: 38–39 ꢁC; ½aꢁD = +10.0 (c 2.19, EtOH) for 76% ee;
OD column, UV detection at 240 nm, eluent: hexane/2-
propanol = 99.8:0.2 flow 0.5 mL minꢀ1, 20 ꢁC, tR (ꢀ)-6m:
24.3 min for (R), tR (+)-6m: 25.8 min for (S). All other
spectroscopic data are in good agreement with those
reported in the literature.13b,d
HPLC: Chiralcel AD column, UV detection at 240 nm, elu-
ent: hexane/2-propanol = 95:5 flow 1.0 mL minꢀ1, 20 ꢁC,
tR (ꢀ)-6i: 7.3 min, tR (+)-6i: 8.4 min; IR (CHCl3):
m = 3072, 3039, 2967, 2934, 2874, 1685, 1599, 1586, 1490,
1448, 1365, 1289, 1243, 1180, 1117, 1022, 985, 929 cmꢀ1
;
1H NMR (CDCl3–CCl4): d 0.83 (t, J = 7.4 Hz, 3H), 1.65–
1.85 (m, 2H), 3.23–3.36 (m, 2H), 3.46–3.54 (m, 1H),
6.95–7.05 (m, 2H), 7.11–7.16 (m, 1H), 7.21 (td, J = 7.4,
1.6 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H),7.50 (t, J = 7.3 Hz,
1H), 7.90 (d, J = 7.3 Hz, 2H); 13C NMR (CDCl3–CCl4):
d 12.16, 27.82, 37.53, 43.90, 115.60 (d, J = 22.9 Hz),
123.94 (d, J = 3.7 Hz), 127.66 (d, J = 8.9 Hz), 128.04,
128.43, 129.55 (d, J = 5.5 Hz), 131.13 (d, J = 13.6 Hz),
132.72, 137.23, 161.22 (d, J = 243.8 Hz), 198.00; MS (EI)
4.4.14. 3-Cyclohexyl-1-phenylpentan-1-one 6n. Using
method A, 6n was obtained as a white waxy oil (30.8 mg,
25
45% yield), ½aꢁD = +0.7 (c 1.54, EtOH) for 70% ee; HPLC:
Chiralcel AD column, UV detection at 240 nm, eluent: hex-
ane/2-propanol = 99.9:0.1 flow 1.0 mL minꢀ1, 20 ꢁC, tR
(ꢀ)-6n: 22.4 min for (R), tR (+)-6n: 25.4 min for (S). All
other spectroscopic data are in good agreement with those
reported in the literature.3i

¨
684
A. Isleyen, O. Dogan / Tetrahedron: Asymmetry 18 (2007) 679–684
Su, W.; Xiao, Y.-N.; Liu, D.-X.; Wang, R. Chin. J. Chem.
Acknowledgements
2003, 21, 1105; (j) Unaleroglu, C.; Aydin, A. E.; Demir, A. S.
Tetrahedron: Asymmetry 2006, 17, 742; (k) Yamashita, M.;
Yamada, K.; Tomioka, K. Org. Lett. 2005, 7, 2369; (l) Cobb,
A. J. A.; Marson, C. M. Tetrahedron 2005, 61, 1269.
We thank the Scientific and Technical Research Council of
Turkey (TUBITAK, Grant No. TBAG-106T071) and the
Middle East Technical University Research Foundation
for the financial support. We are also grateful to Professor
Ayhan S. Demir’s (METU) group for providing us with the
mass spectra of the new compounds. Undergraduate stu-
dent Azize Aydın is thanked for her help in synthesizing
the ligands and the enones.
5. (a) Tanner, D.; Korno, H. T.; Gujarro, D.; Andersson, P. G.
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