Chiral Zn-catalyzed aerobic oxidative kinetic resolution of α-hydroxy ketones

Article abstract of DOI:10.1016/j.tetasy.2011.02.025

The aerobic oxidative kinetic resolution of racemic α-hydroxy ketones was accomplished using a chiral Zn-quinine complex as the catalyst in the presence of molecular oxygen. The resulting optimized reaction conditions were applied to resolute different types of racemic α-hydroxy ketones and a maximum of 9.2 selectivity (s) was obtained with 88% ee for the recovered α-hydroxy ketone.

Full text of DOI:10.1016/j.tetasy.2011.02.025

Tetrahedron: Asymmetry 22 (2011) 512–517
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Chiral Zn-catalyzed aerobic oxidative kinetic resolution of a-hydroxy ketones
⇑
Pandi Muthupandi, Govindasamy Sekar
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, Tamil Nadu, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The aerobic oxidative kinetic resolution of racemic a-hydroxy ketones was accomplished using a chiral
Received 20 December 2010
Accepted 28 February 2011
Available online 31 March 2011
Zn–quinine complex as the catalyst in the presence of molecular oxygen. The resulting optimized reac-
tion conditions were applied to resolute different types of racemic -hydroxy ketones and a maximum
of 9.2 selectivity (s) was obtained with 88% ee for the recovered -hydroxy ketone.
Ó 2011 Elsevier Ltd. All rights reserved.
a
a
1. Introduction
active a-hydroxy ketones, which serve as precursors for the syn-
thesis of chiral ligands and are also found in antidepressants, anti-
Enantiopure alcohols are very important structural units for the
synthesis of a wide range of natural products, chiral ligands and
biologically active compounds.1 Over the past few years, the tran-
sition metal-catalyzed aerobic oxidative kinetic resolution of race-
mic alcohols has received much attention as a synthetic method for
the preparation of optically active alcohols. Recently, a few
research groups have reported the oxidative kinetic resolution of
racemic alcohols using transition metal catalysts such as Pd,2
Ru,3 V,4 Ir,5 and Mn,6 which have considerably widened the scope
of this field. Since most of these catalysts are made of precious
metals, there is still a need for new catalysts that are economical
and readily available.
Over the course of our investigations into finding inexpensive
and easily accessible catalysts for oxidative kinetic resolution of
racemic alcohols,7 we discovered that zinc could catalyze the enan-
tioselective oxidation reaction. Despite the use of catalytic quanti-
ties of zinc salts in a diverse range of reactions, their use in the
oxidation of alcohols is surprisingly very rare. Herein, we report
the chiral zinc complex-catalyzed aerobic oxidative kinetic resolu-
tumor agents, and antibiotics.8
2. Results and discussion
In our initial studies, we chose ( )-benzoin 1 (2-hydroxy-1,2-
diphenylethanone) as model substrate, which was subjected to
oxidative kinetic resolution with 5 mol % of ZnSO4ꢀ7H2O and
5 mol % of enantiopure (R)-BINAM L1 along with 5 mol % of TEMPO
in toluene at 90 °C in the presence of molecular oxygen. The reac-
tion took 9 days to give 54% conversion9 and yielded 38% of recov-
ered benzoin with 8% ee while the selectivity10 was 1.3 (Table 1,
entry 1). This result encouraged us to screen various ligands
(Fig. 1) searching for better selectivity. Replacing BINAM L1 with
BINAM derived imine L2 did not alter the selectivity (entry 2).
When L1 was replaced with L3, the reaction proceeded slightly fas-
ter with an increased selectivity of 2.4 and furnished 43% ee for
recovered benzoin (entry 3). However, the selectivity and reactiv-
ity with these types of ligands were not well improved.
Considering the common structural feature of zinc enzymes in
biological systems whereby zinc can effectively coordinate to
nitrogen atoms present in amides, imidazoles and aliphatic
amines,11 we turned our attention toward the search for similarly
functionalized ligands to improve selectivity and reactivity. The
substitution of BINAM derived imine L3 with BINAM derived pro-
linamide L4 and BINAM derived imidazole L5 provided poor selec-
tivity or the reaction occurred without any selectivity (entry 4 and
5).
Quinine ligand L6 increased both the reactivity and selectivity
even at lower temperature (60 °C). The reaction took just 20 h for
60% conversion and the recovered benzoin was obtained with
55% ee and s = 3.6 (entry 7). Although the reaction provided better
selectivity with the quinine ligand at 60 °C compared to 90 °C (en-
try 7 vs 6), the reaction failed to give any selectivity at room tem-
perature (entry 8).
tion of ( )-
a
-hydroxy ketones (Scheme 1) to synthesize optically
oxidative kinetic
resolution
O
O
O
Chiral Zn catalyst
Ar
Ar
Ar
+
Ar
*
Ar
Ar
O2
~ 50%
OH
O
OH
( )
enantiomerically
enriched benzoin
Scheme 1. Zn-catalyzed oxidative kinetic resolution of racemic a-hydroxy ketones.
⇑
Corresponding author. Tel.: +91 44 2257 4229.
E-mail address: gsekar@iitm.ac.in (G. Sekar).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.02.025

P. Muthupandi, G. Sekar / Tetrahedron: Asymmetry 22 (2011) 512–517
513
Table 1
Effect of ligands on the oxidative kinetic resolution of ( )-benzoin
Ligand
O
O
O
ZnSO4·7H2O (5 mol %)
Ph
Ph
Ph
Ph
∗
Ph
Ph
(S)-1
TEMPO (5 mol %)
PhMe, O2 (balloon)
OH
( )-1
O
2
OH
Entry
Ligand
T (°C)
Time
Conversiona (C %)
ee of benzoinb (%)
s
1
2
3
4
5
6
7
8
9
L1 (5 mol %)
L2 (5 mol %)
L3 (5 mol %)
L4 (10 mol %)
L5 (10 mol %)
L6 (10 mol %)
L6 (10 mol %)
L6 (10 mol %)
L7 (10 mol %)
L8 (5 mol %)
L9 (10 mol %)
L10 (5 mol %)
90
90
90
90
90
90
60
rt
60
60
60
60
9 d
6 d
6 d
7 d
8 d
54
67
64
61
59
68
60
20
65
67
69
63
8
12
43
18
0
46
55
0
6
0
28
4
1.3
1.2
2.4
1.5
—
2.3
3.6
—
1.1
—
1.6
1.1
8 h
20 h
10 d
21 h
29 h
11 h
5 d
10
11
12
a
Conversion was determined by 1H NMR analysis of crude reaction mixture.
% ee was determined by HPLC using Daicel chiralPAK AS-H column.
b
O
N
H
N
N
N
N
N
OH
OH
NH
NH
OH
NH2
NH2
N
N
OH
N
H
N
O
L5
L4
L3
L1
L2
OH
N
O
O
OH
N
H
HO
H2N
O
N
N
N
N
O
N
N
Meo
MeO
MeO
MeO
MeO
N
N
N
N
L6
N
L10
L9
L7
L8
Figure 1. Ligands screened for the oxidative kinetic resolution of racemic
a-hydroxy ketones.
Table 2
Effect of zinc salts and solvents on the oxidative kinetic resolution of ( )-benzoin
O
O
Quinine L6 (10 mol %)
O
Zn salt (5 mol %)
Ph
Ph
Ph
∗
Ph
Ph
( )-1
Ph
(S)-1
TEMPO (5 mol %)
Solvent, O2, 60 o
C
2
O
OH
OH
Entry
Zn salt
Solvent
Time
Conversiona (C %)
ee of benzoinb (%)
s
1
2
3
4
5
6
7
8
9
Zn(OAc)2ꢀ7H2O
ZnO
ZnCI2
PhMe
PhMe
PhMe
PhMe
PhMe
Benzene
CHCI3
CH3CN
DMF
8 h
14 h
47 h
3 d
20 h
34 h
6 d
3 d
2 d
4 d
3 d
66
61
63
65
60
67
63
57
60
56
60
61
26
28
0
1.6
1.8
—
Zn(NO3)2ꢀ6H2O
ZnSO4ꢀ7H2O
ZnSO4ꢀ7H2O
ZnSO4ꢀ7H2O
ZnSO4ꢀ7H2O
ZnSO4ꢀ7H2O
ZnSO4ꢀ7H2O
ZnSO4ꢀ7H2O
ZnSO4ꢀ7H2O
0
—
55
42
10
0
0
8
3.6
2.2
1.2
—
—
10
11
12
EtOH
THF
Acetone
1.2
1.7
1.4
23
14
9 d
a
Conversion was determined by 1H NMR analysis of crude reaction mixture.
% ee was determined by HPLC using Daicel chiralPAK AS-H column.
b

514
P. Muthupandi, G. Sekar / Tetrahedron: Asymmetry 22 (2011) 512–517
Table 3
The oxidative kinetic resolution of racemic
a-hydroxy ketones using Zn–quinine complex
Quinine L6 (10 mol %)
O
O
O
ZnSO4.7H2O (5 mol %)
Ar
Ar
Ar
∗
Ar
Ar
Ar
TEMPO (5 mol %)
PhMe, O2, 60 o
C
( )
O
OH
OH
Entry
1
Recovered
a
-hydroxy ketones
Time (h)
Ca (%)
60
Yieldb (%)
eec (%)
55
s
O
20
46
36(93)
3.6
OH
O
2
3
67
71
30(95)
27(96)
50
52
2.6
2.4
OH
Et
Br
O
O
47
OH
OH
Et
4
5
60
28
62
70
30(87)
27(89)
88
29
9.2
1.6
Br
Cl
O
OH
O
6
7
8
9
36
40
36
35
74
71
64
60
23(92)
27(91)
32(93)
37(94)
36
30
41
22
1.7
1.6
2.3
2.6
OH
O
MeO
OMe
OH
O
OH
O
OH
Conversion was determined by 1H NMR analysis of crude reaction mixture.
a
b
Isolated yield of enantiomerically enriched benzoins after silica gel column chromatography. Numbers in parentheses is the total combined yield of the benzoin and
benzil.
c
% ee was determined by HPLC using Daicel chiralPAK AS-H column.
Since, quinine L6 was found to be a better ligand in terms of
reactivity and selectivity, different types of quinine based ligands
L7–L10 were synthesized and used for the oxidative kinetic
resolution of ( )-benzoin. However, all of these ligands gave less
selectivity than the commercially available quinine ligand (entries
7 vs 9–12).
combinations screened, a 5:10 ratio of zinc salt and ligand was
found to be the best. The reactions without a zinc salt or TEMPO
or molecular oxygen decreased the reactivity and selectivity. Sim-
ilarly, the reaction with only TEMPO did not occur, which indicates
that there is no background reaction because of the TEMPO.
To study the scope of the chiral zinc catalyst, different types of
The oxidative kinetic resolution reaction was further optimized
using a number of zinc salts and solvents with quinine as the ligand
and the results are summarized in Table 2. Zinc acetate and zinc
oxide increased the reaction rate but decreased the selectivity (en-
tries 1 and 2). On the other hand, zinc chloride and zinc nitrate fur-
nished racemic benzoin (entries 3 and 4). In the solvent screening,
the reaction worked better in non-polar solvents compared to other
solvents (entries 5, 6 vs 7–12). The ZnSO4ꢀ7H2O–quinine L6 complex
remained the catalyst of choice for the oxidative kinetic resolution
of ( )-benzoin with toluene being the solvent of choice (entry 5).
To study the effect of the ratio of the zinc salt and ligand, the
reaction was performed with different ratios. From the various
racemic
reaction conditions and the results are summarized in Table 3.
The asymmetric oxidation proceeded smoothly with -hydroxy
ketones bearing electron-releasing as well as electron-withdraw-
ing groups. In the same way, substitutions at the para-, meta-.
a-hydroxy ketones were oxidized under the optimized
a
and ortho-positions of the a-hydroxy ketones were tolerated under
optimized conditions. It is noteworthy that, ortho-methylbenzoin,
a sterically hindered substrate, was also resolved and 41% ee was
obtained for the recovered ortho-methylbenzoin with 2.3 selectiv-
ity (entry 8). All of the racemic benzoins were oxidized with mod-
erate to good ee (up to 88%) and selectivity (up to 9.2). Unreacted
para-bromobenzoin was recovered with a maximum of 88% ee and

P. Muthupandi, G. Sekar / Tetrahedron: Asymmetry 22 (2011) 512–517
515
9.2 selectivity (entry 4). In all of the examples, the (R)-enantiomer
of the racemate benzoins were oxidized to the corresponding
benzils while the slow reacting (S)-enantiomers12 were recovered
in enantiomerically enriched form.
excess (% ee) was determined to be 55% in HPLC using a Daicel
ChiralPAK AS-H column (20% i-PrOH/hexanes, 1 mL/min,
254 nm): tR (major, 7.953 min), tR (minor, 11.906 min).
4.2.2. Spectroscopic data for product: 1,2-diphenylethane-1,2-
dione (Table 3, entry 1)
3. Conclusion
Rf 0.43; (hexanes/ethyl acetate, 90:10 v/v): 1H NMR (400 MHz,
CDCl3): d 7.51 (t, J = 8.0 Hz, 4H), 7.66 (t, J = 7.2 Hz, 2H), 7.95–8.01
(m, 4H); 13C NMR (100 MHz, CDCl3): d 129.1, 130.0, 133.1, 135.0,
194.7; IR (Neat) 1656, 3064 cmꢁ1; HRMS (m/z): [MNa]+ calcd for
In conclusion, we have shown that a chiral zinc complex can be
used as a catalyst for the oxidative kinetic resolution of racemic a-
hydroxy ketones in the presence of molecular oxygen as a stoichi-
ometric oxidant. Due to the advantages of being an inexpensive
and readily available catalytic system (zinc sulfate, quinine, and
molecular oxygen) with milder reaction conditions and substrate
generality, with moderate to good selectivity, this zinc catalyst
could be considered as a new entry in the field of aerobic oxidative
kinetic resolution of racemic alcohols.
C14H10O2Na1, 233.0578; found, 233.0585.
4.2.3. (S)-2-Hydroxy-1,2-di-p-tolylethanone (Table 3, entry 2)
Rf 0.19; (hexanes/ethyl acetate, 90:10 v/v): ½a D25
¼ þ79:2 (c 1,
ꢃ
MeOH); 1H NMR (400 MHz, CDCl3): d 2.28 (s, 3H), 2.35 (s, 3H),
4.56 (d, J = 6.0 Hz, 1H), 5.90 (d, J = 6.0 Hz, 1H), 7.12 (d, J = 8.0 Hz,
2H), 7.16–7.24 (m, 4H), 7.79–7.84 (m, 2H); 13C NMR (100 MHz,
CDCl3): d 21.3, 21.9, 75.9, 127.8, 129.4, 129.5, 129.9, 131.1, 136.5,
138.5, 145.1, 198.7; IR (Neat) 1674, 2917, 3473 cmꢁ1; HRMS
(m/z): [MNa]+ calcd for C16H16O2Na1, 263.1048; found, 263.1045.
The enantiomeric excess (% ee) was determined to be 50% by HPLC
using a Daicel ChiralPAK AS-H column (30% i-PrOH/hexanes,
1 mL/min, 220 nm): tR (major, 6.169 min), tR (minor, 8.437 min).
4. Experimental
4.1. General information
Zinc(II)sulfate heptahydrate was purchased from SD Fine chem-
icals, India while quinine was purchased from Alfa Aesar chemical
company and used as such received. Thin-layer chromatography
(TLC) was performed using Merck silica gel 60 F254 precoated
plates (0.25 mm) and visualized by UV fluorescence quenching. Sil-
ica gel for column chromatography (particle size 100–200 mesh)
purchased from SRL India. 1H and 13C NMR spectra were recorded
by a Bruker 400 MHz instrument. 1H NMR spectra were reported
relative to Me4Si (d 0.0 ppm) or residual CDCl3 (d 7.26 ppm). 13C
NMR were reported relative to CDCl3 (d 77.16 ppm). FTIR spectra
were recorded on a Nicolet 6700 spectrometer and are reported
in frequency of absorption (cmꢁ1). High resolution mass spectra
(HRMS) were recorded on Q-Tof Micro mass spectrometer. Optical
rotations were measured with Autopol IV—Rudolph Research Ana-
lytical Polarimeter. The enantiomeric excess (% ee) was determined
by SHIMADZU HPLC using a Daicel ChiralPAK AS-H (0.46 cm
4.2.4. 1,2-Di-p-tolylethane-1,2-dione (Table 3, entry 2)
Rf 0.40; (hexanes/ethyl acetate, 90:10 v/v): 1H NMR (400 MHz,
CDCl3): d 2.33 (s, 6H), 7.20 (d, J = 8.0 Hz, 4H), 7.77 (d, J = 8.0 Hz,
4H); 13C NMR (100 MHz, CDCl3): d 22.0, 129.8, 130.1, 130.8,
146.2, 194.6; IR (Neat) 1659, 2918 cmꢁ1; HRMS (m/z): [MNa]+
calcd for C16H14O2Na1, 261.0891; found, 261.0892.
4.2.5. (S)-1,2-Bis(4-ethylphenyl)-2-hydroxyethanone (Table 3,
entry 3)
Rf 0.17; (hexanes/ethyl acetate, 90:10 v/v): ½a D25
¼ þ41:3 (c 1,
ꢃ
MeOH); 1H NMR (400 MHz, CDCl3): d 1.02–1.20 (m, 6H), 2.42–
2.60 (m, 4H), 4.49 (d, J = 5.6 Hz, 1H), 5.83 (d, J = 5.6 Hz, 1H), 7.07
(d, J = 8.4 Hz, 2H), 7.10–7.20 (m, 4H), 7.78 (d, J = 8.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3): d 15.0, 15.4, 28.6, 29.1, 75.9, 127.8,
128.3, 128.7, 129.5, 131.2, 136.7, 144.7, 151.1, 198.6; IR(Neat)
973, 1041, 1252, 1672, 2873, 2965, 3462 cmꢁ1; HRMS (m/z):
[MNa]+ calcd for C18H20O2Na1, 291.1361; found, 291.1364. The
enantiomeric excess (% ee) was determined to be 52% by HPLC
using a Daicel ChiralPAK AS-H column (30% i-PrOH/hexanes,
1 mL/min, 220 nm): tR (major, 5.336 min), tR (minor, 6.818 min).
u
ꢂ 25 cm) column. 1H and 13C NMR and HRMS spectral data have
been included for all compounds.
4.2. General experimental procedure for the aerobic oxidative
kinetic resolution of a-hydroxy ketones
A mixture of L6 (8.1 mg, 0.025 mmol) and zinc(II)sulfate hepta-
hydrate (3.6 mg, 0.0125 mmol) in 5 mL of toluene was stirred at
room temperature for 10 min, after which TEMPO (2 mg,
0.0125 mmol) was added to the reaction mixture. After stirring
for 5 min, benzoin (53 mg, 0.25 mmol) was added and the reaction
then stirred under an O2 atmosphere (using O2 balloon). The reac-
tion was followed by TLC. The conversion was measured by record-
ing the 1H NMR of the crude reaction mixture. The reaction
mixture was concentrated after 60% conversion and the resulting
residue was purified by silica gel column chromatography (elu-
ents: hexanes/ethyl acetate, 85:15 v/v) to give benzil (57%) and
unreacted benzoin (36%).
4.2.6. 1,2-Bis(4-ethylphenyl)ethane-1,2-dione (Table 3, entry 3)
Rf 0.47; (hexanes/ethyl acetate, 90:10 v/v): 1H NMR (400 MHz,
CDCl3): d 1.15 (t, J = 7.6 Hz, 6H), 2.62 (q, J = 7.6 Hz, 4H), 7.23 (d,
J = 8.0 Hz, 4H), 7.80 (d, J = 8.0 Hz, 4H); 13C NMR (100 MHz, CDCl3):
d 15.2, 29.3, 128.6, 130.2, 130.9, 152.3, 194.7; IR (Neat) 1668, 2875,
2933, 2968 cmꢁ1
267.1385; found, 267.1388.
;
HRMS (m/z): [MꢁH]+ calcd for C18H19O2,
4.2.7. (S)-1,2-Bis(4-bromophenyl)-2-hydroxyethanone (Table 3,
entry 4)
Rf 0.17; (hexanes/ethyl acetate, 90:10 v/v): ½a D25
¼ þ9:1 (c 1,
ꢃ
4.2.1. Spectroscopic data for recovered alcohol: (S)-2-hydroxy-
MeOH); 1H NMR (400 MHz, CDCl3): d 4.49 (s, 1H), 5.86 (s, 1H),
7.18 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.8 Hz,
2H), 7.74 (d, J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): d 75.7,
123.1, 129.5, 129.7, 130.6, 132.0, 132.3, 132.6, 137.7, 197.8; IR
(Neat) 1673, 1688, 3398, 3441 cmꢁ1; The enantiomeric excess (%
ee) was determined to be 88% by HPLC using a Daicel ChiralPAK
AS-H column (30% i-PrOH/hexanes, 1 mL/min, 220 nm): tR (major,
6.158 min), tR (minor, 7.427 min).
1,2-diphenylethanone (Table 3, entry 1)
Rf 0.26 (hexanes/ethyl acetate, 90:10 v/v); ½a D25
¼ þ44:2 (c 1,
ꢃ
acetone); 1H NMR (400 MHz, CDCl3): d 4.61 (d, J = 6.4 Hz, 1H), 6.0
(d, J = 6.4 Hz, 1H), 7.28–7.41 (m, 5H), 7.41–7.47 (m, 2H), 7.56 (t,
J = 8.0 Hz, 1H), 7.96 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 76.4, 127.9, 128.7, 128.8, 129.3, 133.6, 134.0, 139.1, 199.1; IR
(Neat) 1068, 1261, 1679, 3418 cmꢁ1; HRMS (m/z): [MNa]+ calcd
for C14H12O2Na1, 235.0735; found, 235.0727; The enantiomeric

516
P. Muthupandi, G. Sekar / Tetrahedron: Asymmetry 22 (2011) 512–517
4.2.8. 1,2-Bis(4-bromophenyl)ethane-1,2-dione (Table 3,
entry 4)
4.2.14. 1,2-Bis(3-methoxyphenyl)ethane-1,2-dione (Table 3,
entry 7)
Rf 0.47; (hexanes/ethyl acetate, 90:10 v/v): 1H NMR (400 MHz,
CDCl3): d 7.67 (d, J = 8.5 Hz, 4H), 7.83 (d, J = 8.5 Hz, 4H); 13C NMR
(100 MHz, CDCl3): d 130.9, 131.4, 131.7, 132.7, 192.7; IR (Neat)
Rf 0.61; (hexanes/ethyl acetate, 70:30 v/v): 1H NMR (400 MHz,
CDCl3): d 3.85 (s, 6H), 7.16–7.23 (m, 2H), 7.38 (t, J = 8.0 Hz, 2H),
7.44–7.49 (m, 2H), 7.51–7.56 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 55.6, 113.0, 122.0, 123.3, 130.1, 134.3, 160.2, 194.5; IR (Neat)
1581, 1662, 2923 cmꢁ1
.
1016, 1256, 2966 cmꢁ1
;
HRMS (m/z): [MNa]+ calcd for
C16H14O4Na1, 293.0790; found, 293.0785.
4.2.9. (S)-2-(4-Chlorophenyl)-2-hydroxy-1-phenylethanone
(Table 3, entry 5)
Rf 0.19; (hexanes/ethyl acetate, 90:10 v/v): ½a D25
ꢃ
¼ þ24:8 (c 1,
4.2.15. (S)-2-Hydroxy-1,2-di-o-tolylethanone (Table 3, entry 8)
Rf 0.21; (hexanes/ethyl acetate, 90:10 v/v): ½a D25
¼ þ47:5 (c 0.5,
ꢃ
MeOH); 1H NMR (400 MHz, CDCl3): d 4.44 (d, J = 5.6 Hz, 1H), 5.84
(d, J = 5.6 Hz, 1H), 7.19–7.38 (m, 7H), 7.79 (d, J = 8.8 Hz, 2H); 13C
NMR (100 MHz, CDCl3): d 76.4, 127.9, 128.9, 129.2, 129.4, 130.6,
131.9, 138.8, 140.6, 197.9; IR (Neat) 1678, 3063, 3461 cmꢁ1; HRMS
(m/z): [M]+ calcd for C14H11ClO2Na1, 269.0345; found, 269.0347.
The enantiomeric excess (% ee) was determined to be 29% by HPLC
using a Daicel ChiralPAK AS-H column (30% i-PrOH/hexanes, 1 mL/
min, 220 nm): tR (major, 6.302 min), tR (minor, 8.315 min).
MeOH); 1H NMR (400 MHz, CDCl3): d 2.39 (s, 3H), 2.42 (s, 3H), 4.25
(s, 1H), 6.08 (s, 1H), 7.11–7.26 (m, 6H), 7.35 (t, J = 6.4 Hz, 1H), 7.43
(d, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 19.4, 20.7, 74.9,
125.5, 126.5, 127.8. 128.3, 128.4, 128.5, 131.2, 131.9, 134.8,
136.3, 136.4, 138.7, 203.0; IR (Neat) 1682, 2928, 2961, 3022,
3462 cmꢁ1
;
HRMS (m/z): [MNa]+ calcd for C16H16O2Na1,
263.1048; found, 263.1053. The enantiomeric excess (% ee) was
determined to be 41% by HPLC using a Daicel ChiralPAK AS-H col-
umn (30% i-PrOH/hexanes, 1 mL/min, 220 nm): tR (major,
5.276 min), tR (minor, 7.193 min).
4.2.10. 1-(4-Chlorophenyl)-2-phenylethane-1,2-dione (Table 3,
entry 5)
Rf 0.53; (hexanes/ethyl acetate, 90:10 v/v): 1H NMR (400 MHz,
CDCl3): d 7.46–7.56 (m, 4H), 7.67 (t, J = 7.2 Hz, 1H), 7.92 (d,
J = 8.4 Hz, 2H), 7.96 (d, J = 7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 129.2, 129.6, 130.1, 131.4, 131.5, 132.9, 135.2, 141.7, 193.2,
194.0; IR (Neat) 712, 1210, 1666 cmꢁ1; HRMS (m/z): [M]+ calcd
for C14H9ClO2Na1, 265.0189; found, 265.0187.
4.2.16. 1,2-Di-o-tolylethane-1,2-dione (Table 3, entry 8)
Rf 0.44; (hexanes/ethyl acetate, 90:10 v/v): 1H NMR
(400 MHz, CDCl3): d 2.61 (s, 6H), 7.17 (t, J = 7.6 Hz, 2H), 7.24 (d,
J = 7.6 Hz, 2H), 7.38 (td, J = 7.6, 0.8 Hz, 2H), 7.57 (dd, J = 8, 0.8 Hz,
2H); 13C NMR (100 MHz, CDCl3): d 22.0, 126.1, 131.9, 132.7,
133.1, 133.7, 141.6, 197.0; IR (Neat) 752, 1673, 2968 cmꢁ1
;
HRMS (m/z): [MNa]+ calcd for C16H14O2Na1, 261.0891; found,
4.2.11. (S)-2-Hydroxy-1,2-di-m-tolylethanone (Table 3, entry 6)
Rf 0.45; (hexanes/ethyl acetate, 80:20 v/v): ½a D25
¼ þ49:4 (c 1,
ꢃ
261.0890.
MeOH); 1H NMR (400 MHz, CDCl3): d 2.20 (m, 3H), 2.25 (m,
3H), 3.95 (s, 1H), 5.82 (s, 1H), 6.98 (d, J = 7.2 Hz, 1H), 7.02–7.20
(m, 4H), 7.22 (d, J = 7.2 Hz, 1H), 7.60 (d, J = 7.2 Hz, 1H), 7.67 (s,
1H); 13C NMR (100 MHz, CDCl3): d 21.4, 21.5, 76.3, 125.0, 126.5,
128.3, 128.6, 129.0, 129.4, 129.7, 133.7, 134.8, 138.6, 138.9,
139.1, 199.3; IR (Neat) 1276, 1676, 2920, 3452 cmꢁ1; HRMS
(m/z): [MNa]+ calcd for C16H16O2Na1, 263.1048; found,
263.1043. The enantiomeric excess (% ee) was determined to be
4.2.17. (S)-2-Hydroxy-1,2-di(naphthalen-2-yl)ethanone (Table 3,
entry 9)
Rf 0.37; (hexanes/ethyl acetate, 80:20 v/v): ½a D25
¼ þ10:4 (c 1,
ꢃ
MeOH); 1H NMR (400 MHz, CDCl3): d 4.80 (s, 1H), 6.34 (s, 1H),
7.41–7.57 (m, 5H), 7.73–7.88 (m, 6H), 7.98 (s, 1H), 8.03 (dd,
J = 8.6, 1.2 Hz, 1H), 8.53 (s, 1H); 13C NMR (100 MHz, CDCl3): d
76.4, 124.3, 124.9, 126.4, 126.5, 127.0, 127.5, 127.7, 128.1, 128.6,
129.0, 129.2, 129.7, 130.8, 131.4, 132.2, 133.2, 133.4, 135.8,
136.6, 198.9; IR (Neat) 1678, 3055, 3445 cmꢁ1; HRMS (m/z):
[M+H]+ calcd for C22H17O2, 313.1229; found, 313.1228. The enan-
tiomeric excess (% ee) was determined to be 22% by HPLC using
a Daicel ChiralPAK AD-H column (25% i-PrOH/hexanes, 1 mL/min,
220 nm): tR (major, 28.664 min), tR (minor, 18.328 min).
36% by HPLC using
a Daicel ChiralPAK AD-H column (15%
i-PrOH/hexanes, 1 mL/min, 220 nm): tR (major, 12.402 min), tR
(minor, 9.190 min).
4.2.12. 1,2-Di-m-tolylethane-1,2-dione (Table 3, entry 6)
Rf 0.50; (hexanes/ethyl acetate, 90:10 v/v): 1H NMR (400 MHz,
CDCl3): d 2.40 (s, 6H), 7.39 (t, J = 7.6 Hz, 2H), 7.46 (d, J = 7.6 Hz,
2H), 7.72–7.82 (m, 4H); 13C NMR (100 MHz, CDCl3): d 21.4, 127.3,
129.0, 130.3, 133.1, 135.8, 139.1, 195.1; IR (Neat) 729, 1667,
2922 cmꢁ1; HRMS (m/z): [M+H]+ calcd for C16H15O2, 239.1072;
found, 239.1070.
4.2.18. 1,2-Di(naphthalen-2-yl)ethane-1,2-dione (Table 3, entry
9)
Rf 0.45; (hexanes/ethyl acetate, 90:10 v/v): 1H NMR (400 MHz,
CDCl3): d 7.50–7.58 (m, 2H), 7.63 (td, J = 6.8, 1.2 Hz, 2H), 7.86–
7.94 (m, 4H), 7.97 (d, J = 8.8 Hz, 2H), 8.17 (dd, J = 8.8, 1.6 Hz, 2H),
8.49 (s, 2H); 13C NMR (100 MHz, CDCl3): d 194.8, 136.5, 133.7,
132.5, 130.6, 130.0, 129.6, 129.3, 128.0, 127.3, 123.9; IR (Neat)
1629, 1665, 3006 cmꢁ1; HRMS (m/z): [M+H]+ calcd for C22H15O2,
311.1072; found, 311.1072.
4.2.13. (S)-2-Hydroxy-1,2-bis(3-methoxyphenyl) ethanone
(Table 3, entry 7)
Rf 0.30; (hexanes/ethyl acetate, 70:30 v/v): ½a D25
¼ þ17:8 (c 1,
ꢃ
MeOH); 1H NMR (400 MHz, CDCl3): d 3.79 (s, 3H), 3.83 (s, 3H),
4.58 (s, 1H), 5.94 (s, 1H), 6.85 (d, J = 8.4 Hz, 1H), 6.90 (s, 1H), 6.97
(d, J = 8.8 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 7.24–7.37 (m, 2H),
7.47–7.56 (m, 2H); 13C NMR (100 MHz, CDCl3): d 55.4, 55.5, 76.3,
113.3, 113.5, 114.3, 120.3, 120.6, 121.9, 129.8, 130.3, 134.9,
140.6, 159.9, 160.2, 198.8; IR (Neat) 1039, 1263, 1680, 2943,
Acknowledgments
We thank DST (Project No.: SR/S1/OC-06/2008), New Delhi for
the financial support. P.M. thanks UGC, New Delhi, for a senior re-
search fellowship. We thank DST, New Delhi, for the funding to-
ward the 400 MHz NMR instrument to the Department of
Chemistry, IIT-Madras under the IRPHA scheme and ESI-MS facility
under the FIST program.
3441 cmꢁ1
;
HRMS (m/z): [MNa]+ calcd for C16H16O4Na1,
295.0946; found, 295.0940. The enantiomeric excess (% ee) was
determined to be 30% by HPLC using a ChiralPAK AS-H column
(30% i-PrOH/hexanes, 1 mL/min, 220 nm): tR (major, 11.857 min),
tR (minor, 19.031 min).

P. Muthupandi, G. Sekar / Tetrahedron: Asymmetry 22 (2011) 512–517
517
5424–5427; (c) Muthupandi, P.; Alamsetti, S. K.; Sekar, G. Chem. Commun. 2009,
3288–3290.
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