A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric reduction of ketones by borane

Article abstract of DOI:10.1016/j.tetasy.2011.09.020

A novel C₃-symmetric prolinol-squaramide has been developed for the asymmetric reduction of ketones by borane. By using only 5 mol % catalyst 1a for the reaction, high yields and excellent enantioselectivities (up to 95% yield, 93% ee) were obtained. Moreover, 1a can be easily recovered by simple precipitation and re-used for four cycles without losing the selectivity. Copyright

Full text of DOI:10.1016/j.tetasy.2011.09.020

Tetrahedron: Asymmetry 22 (2011) 1640–1643
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
A novel C3-symmetric prolinol-squaramide catalyst for the asymmetric
reduction of ketones by borane
⇑
Xiang-Fei Wu, Chang Min, Enkhtsetseg Nyamzundui, Hai-Bing Zhou, Chune Dong
State Key Laboratory of Virology, School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 July 2011
Revised 21 September 2011
Accepted 22 September 2011
Available online 1 November 2011
A novel C3-symmetric prolinol-squaramide has been developed for the asymmetric reduction of ketones
by borane. By using only 5 mol % catalyst 1a for the reaction, high yields and excellent enantioselectivi-
ties (up to 95% yield, 93% ee) were obtained. Moreover, 1a can be easily recovered by simple precipitation
and re-used for four cycles without losing the selectivity.
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
synthesis of novel catalysts. As part of our continuous efforts to de-
sign and synthesize novel C3-symmetric chiral squaramides and
The reduction of ketones to enantiomerically enriched alcohols
is a pivotal transformation in synthetic organic chemistry.1 Over
the past decades, many asymmetric catalyst systems, pioneered
by CBS catalysts2 such as hydroxyl-amides,3 sulfonamides,4 and
phosphinamides5 have been developed as efficient catalysts for
the asymmetric reduction of ketones. Meanwhile, chiral squara-
mides were first used in the reduction of ketones in 2001 and re-
cently were used as organocatalysts for asymmetric reactions.6,7
Despite important progress in this area, there is still room for
improvement regarding this type of asymmetric reduction reac-
tion, for example, the cultivation of catalytic enantioselective vari-
ants of this reaction is still in high demand. Furthermore, due to
the difficulty in catalyst recycling, the application of these catalytic
systems in pharmaceutical production has been limited. Therefore,
new strategies to design efficient, recyclable chiral catalysts for
asymmetric reduction reactions are highly desirable.
their applications in asymmetric transformations,13 we decided
to explore the application of C3-symmetric squaramides in enan-
tioselective borane reduction. To the best of our knowledge, there
has been no report on C3-symmetric chiral squaramides for the
asymmetric borane reduction of a ketone. Chiral C3-squaramide
organocatalyst pioneered by our group have been demonstrated
to be a new family of efficient and versatile recyclable organocata-
lysts for the asymmetric additions of 1,3-dicarbonyl compounds to
nitrostyrenes with high enantioselectivity.13a We envisioned that
the combination of a prolinol framework and a squaric acid skele-
ton would enhance the enantioselectivity. Moreover, the poor sol-
ubility of the C3-squaramide in organic solvents enabled its easy
recovery by a simple precipitation method, allowing its recycling.
Herein we report the first C3-symmetric prolinol-squaramide as a
new robust, highly efficient, recyclable catalyst for the enantiose-
lective reduction of ketones by borane.
Recently, C3-symmetric chiral molecules have gained much
attention in the area of supramolecular coordination chemistry8
and molecular recognition.9 In particular, much progress has been
made with C3-symmetric catalysts for asymmetric transforma-
tions.10 For example, Du reported the C3-symmetric phosphora-
mide promoted borane reduction of ketones.11 Liang et al.
developed the C3-symmetric sulfonamide for the asymmetric
reduction of prochiral ketones.12 Meanwhile, due to its diverse
structural features, well-defined coordination geometry and un-
ique chiral environments, C3-symmetric chiral molecules have
great potential in asymmetric catalysis. We anticipated that the
synthesis of C3-symmetric catalysts with a squaric acid moiety,
would not only provide a unique chiral environment in asymmetric
transformations, but also open a new way for the design and
Based on the above consideration, C3-symmetrical catalysts 1a–
e were synthesized, in which the three chiral subunits were con-
nected with each other via a triamine core. As illustrated in
Scheme 1, squaramides 1a–c can be readily prepared in two steps
from commercial available squaric acid and proline in 86% yield
under mild conditions. In addition, C3-symmetrical catalysts 1d
and 1e, possessing the indanol or 2-amino-1,2-diphenylethanol
moiety, and the monosquaramide (C1) 1f were also prepared for
comparison.
2. Results and discussion
With these C3-symmetric squaramides in hand, their efficiency
and activity were examined in detail with a-bromo-acetophenone
as a substrate (Table 1). Initially the reaction was conducted in the
presence of 5 mol % 1a in toluene at 0 °C and afforded the (S)-prod-
uct in 83% ee (entry 1).11 When other solvents such as THF and
⇑
Corresponding author. Tel.: +86 27 68759586; fax: +86 27 68759850.
E-mail address: cdong@whu.edu.cn (C. Dong).
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.09.020

X.-F. Wu et al. / Tetrahedron: Asymmetry 22 (2011) 1640–1643
1641
O
O
O
O
EtOH, rt
Ph
Ph
HO
Ph
Ph
+
N
H
12h, 74%
EtO
N
EtO
OEt
HO
2
3
R
R
H2N
NH2
R'HN
NHR'
R'HN
NHR'
N
R
R
R
R
NH2
3
NHR'
NHR'
4a R = H; 4b R = Me
1c
1a
1b
R=Me
R=H;
CH2Cl2, rt
76-86%
H2N
N
NH2
R''HN
NHR''
1d-e
NH2
4c
NHR''
Ph
OH
Ph
O
O
HO
O
O
O
O
N
O
O
N
N
H
Ph
Ph
OH
Ph
Ph
R'' =
NH
1e
NH
1d
R'' =
R' =
monosquaramide (C1)
OH
1f
Scheme 1. Preparation of C3-symmetric squaramides 1a–f.
Table 1
(entry 9). The C3-symmetric catalyst based on chiral indanol 1d
or 2-amino-1, 2-diphenylethanol 1e gave worse enantioselecitvity
(entries 10 and 11). It can be inferred that the existence of two N–H
groups in the squaramide moiety would disorder the desired tran-
sition states. Under the same reaction conditions, in comparison
with 1a, monosquaramide 1f gave moderate enantioselectivity
(entries 12 and 13). When compound 3 was used, the reaction of
5a with borane formed the desired product in 58% yield and 86%
ee (entry 14).
With the optimized conditions in hand, we next investigated the
scope of the reduction with respect to the ketone. As summarized in
Table 2, a variety of ketones were smoothly reduced to alcohols
with good yields and enantioselectivities. Importantly, the presence
Optimization and catalyst screening for the borane reduction of ketone 5aa
OH
O
Br
Br
BH3-SMe2 / ligand
solvent
5a
6a
Entrya
Catalyst (mol %)
Solvent
Temp (°C)
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a (5.0)
1a (5.0)
1a (5.0)
1a (5.0)
1a (1.0)
1a (10)
1a (5.0)
1b (5.0)
1c (5.0)
1d (5.0)
1e (5.0)
1f (5.0)
1f (15.0)
3 (15.0)
Toluene
THF
DCM
0
0
0
89
90
83
93
84
96
94
86
89
91
84
86
67
58
83
67
78
87
56
82
93
75
84
7
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
50
50
50
30
30
30
30
30
30
30
30
of substituents on the phenyl ring of
a-bromo-acetophenone
substrate had no obvious effect on the enantioselectivity (entries
1–11). For example, ketones 5c and 5g were reduced to their corre-
sponding alcohols in 90% ee (entries 3 and 7), while, p-methyl func-
tionalized a-bromo-acetophenone 5e gave 85% ee (entry 5). Phenyl
alkyl ketones 5j and 5k, as well as cyclic 1-tetralone 5l furnished
corresponding alcohols in modest ee values (entries 10–12). Com-
pared with the CBS catalyst, the slight decrease of ee and relatively
lower efficiency of our C3-catalyst might be attributed to the poorer
solubility of the C3-catalyst in the solvent.
The poor solubility of the C3-squaramide in organic solvents en-
abled its easy recovery by a simple precipitation method, allowing
it to be recycled. We decided to test the recyclability of our re-
agents. To determine the recycling ability of the catalyst, 1a was
recovered after the catalytic process by precipitation from the
reaction mixture with the addition of ethyl ether, and after simple
filtration through a silica pad, reused in the reduction of 5a by bor-
ane under the optimized reaction (Table 3). We were pleased to ob-
serve that the recovered catalyst retained its high activity and
enantioselectivity and can be reused four times without a loss of
reactivity or enantioselectivity.
8
78
80
86
a
Reaction was carried out on a 1.0 mmol scale in 2 mL of solvent, molar of
PhCOCH2Br, BH3–SMe2 = 1.0:1.1.
b
(S)-product was isolated by column chromatography.
Determined by HPLC analysis using a Daicel Chiralcel column.
An (S)-configuration was assigned on the basis of the sign of the specific rota-
c
d
tion with that reported in the literature.
dichloromethane were used, the ee decreased (entries 2 and 3).
Varying the catalyst loading had an obvious effect on the ee values
(entries 5 and 6). Increasing the reaction temperature to 50 °C, re-
sulted in better yield and ee. We were encouraged to observe that
93% ee was obtained in the presence of 5 mol % 1a at 30 °C (entry
7), as Xu reported the catalytic reduction became faster at 30 °C,
then the enantioselectivity improved.3d,e The enantioselectivity de-
creased significantly when changing catalyst 1a to 1b (entry 8),
which may be due to the existence of the methyl group reducing
the steric differentiation between Si- and Re-face of the transition
states. As expected, the more flexible 1c gave inferior ee to 1a
3. Conclusions
New C3-symmetric prolinol-squaramides have been success-
fully prepared in two steps from commercially available squaric
acid and proline with excellent yields. We have demonstrated that

1642
X.-F. Wu et al. / Tetrahedron: Asymmetry 22 (2011) 1640–1643
Table 2
determined by IonSpec 4.7 Tesla FTMS instrument. Enantiomeric
excesses (ee value) were determined by HPLC analysis
Reaction scope for the reduction of ketones by borane
O
4.2. Representative procedure for the synthesis of C3-symmetric
squaramides 1a–e
OH
1a
BH3-SMe2, 5mol%
toluene, 30oC
R2
R2
R1
R1
5
6
To a solution of 2 (382 mg, 1.01 mmol) in CH2Cl2 (10 mL) was
added a solution of amine 3 (53.8 mg, 0.33 mmol) in MeOH (2 mL)
under a N2 atmosphere. After 48 h, the reaction was completed
(monitored by TLC) and the reaction mixture was concentrated
and purified by column chromatography to give product 1a as a yel-
Entrya
R1
Phenyl 5a
R2
Br
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
94
93
95
91
90
81
95
91
92
92
92
83
93 (S)
90 (ꢁ)d
90 (ꢁ)d
88 (S)
85 (S)
50 (S)
90 (S)
84 (S)
68 (R)
68 (R)
70 (R)
70 (R)
3-Bromophenyl 5b
4-Fluorophenyl 5c
4-Bromophenyl 5d
4-Methylphenyl 5e
4-Nitrophenyl 5f
4-Fluorophenyl 5g
4-Bromophenyl 5h
Phenyl 5i
Br
Br
Br
Br
Br
Cl
Cl
H
lowish solid 328 mg (86% yield). Mp 228–230 °C, ½a D23
¼ þ78:6 (c 3,
ꢀ
DMSO), 1H NMR (400 MHz, CDCl3) d 7.79 (s, 3H), 7.35 (br, 30H), 4.93
(s, 3H), 4.77 (s, 3H), 4.37 (s, 3H), 3.88 (br, 6H), 2.62 (s, 3H), 2.20 (s,
3H), 2.14–1.62 (m, 6H), 1.45 (s, 3H), 0.91–0.42 (m, 3H). 13C NMR
(100 MHz, CDCl3) d 182.64, 182.10, 168.28, 167.34, 137.77, 135.74,
127.57, 127.42, 127.14, 127.12, 126.98, 126.61, 78.23, 66.86,
48.84, 45.27, 28.76, 21.53. HRMS (ESI) calcd for C72H66N6O9Na
[M+Na]+ 1181.4751; found 1181.4783.
10
11
12
Phenyl 5j
Phenyl 5k
1-Tetral 5l
Me
Et
H
Compound 1b: Mp 234–238 °C; ½a D23
ꢀ
¼ þ82:7 (c 3, DMSO), 1H
a
Reaction was carried out on a 0.5 mmol scale in 1 mL toluene, the molarity of
PhCOCH2Br, BH3–SMe2 = 1.0:1.1.
NMR (400 MHz, DMSO-d6) d 7.79–7.63 (m, 3H), 7.49 (d, J = 7.6 Hz,
6H), 7.37 (t, J = 7.6 Hz, 6H), 7.26 (dd, 15H), 4.99 (s, 3H), 4.03 (dd,
J = 14.2, 7.1 Hz, 3H), 3.74 (s, 6H), 3.70–3.33 (m, 6H), 2.35 (d, 6H),
2.11–2.00 (m, 3H), 1.86 (s, 3H), 1.74 (s, 6H). 13C NMR (100 MHz,
b
Isolated yield by column chromatography.
Determined by HPLC analysis using a Daicel Chiralcel column, the absolute
c
configuration of the product was assigned by the sign of the specific rotation with
that reported in the literature.3e,14–16
d
DMSO-d6)
d 182.61, 182.56, 170.34, 167.26, 144.84, 137.48,
Not determined.
136.95, 132.69, 132.32, 129.59, 128.56, 127.75, 127.38, 127.34,
127.23, 127.10, 126.95, 126.81, 80.88, 59.75, 49.90, 45.39, 30.80,
27.10, 23.17. HRMS (ESI) calcd for
1223.5238; found 1223.5253.
C
75H72N6O9Na [M+Na]+
Compound 1c: Mp: 208–212 °C; ½a D23
ꢀ
¼ þ33:6 (c 3, DMSO), 1H
Table 3
Recycling experiments of 1a in the reduction of 5a
NMR (400 MHz, DMSO-d6) d 7.54 (s, 6H), 7.37 (t, J = 7.5 Hz, 6H),
7.29 (d, J = 3.4 Hz, 9H), 7.17 (d, J = 7.5 Hz, 9H), 5.49–4.84 (m, 3H),
4.06–3.87 (m, 3H), 3.73 (s, 9H), 3.42–3.27 (m, 9H), 2.11 (t,
O
OH
J = 12.5 Hz, 3H), 1.91 (d, J = 6.3 Hz, 3H), 1.79 (t, J = 13.9 Hz, 6H). 13
C
Br
Br
1a
BH3-SMe2 / 5mol%
toluene
NMR (100 MHz, DMSO-d6) d 182.51, 182.03, 170.35, 167.31,
144.80, 127.73, 127.34, 127.14, 126.92, 126.82, 59.75, 53.34, 49.90,
45.46, 27.23, 23.05. HRMS (ESI) calcd for C69H69N7O9Na [M+Na]+
1162.5060; found 1162.5049.
5a
6a
Cyclea
1
2
3
4
Compound 1d: Mp: 235–240 °C; ½a D23
ꢀ
¼ ꢁ25:3 (c 3, DMSO), 1H
Recovery (%)
Yieldb (%)
eec (%)
88
90
92
85
92
90
86
90
90
85
91
89
NMR (400 MHz, DMSO-d6) d 8.40–7.73 (m, 6H), 7.27 (s, 33H), 5.90
(s, 3H), 5.36 (s, 3H), 5.12 (s, 3H), 4.81 (d, 6H). 13C NMR (100 MHz,
DMSO-d6)
d 182.55, 182.40, 167.27, 166.95, 142.00, 139.75,
a
Reaction was carried out on a 1.0 mmol scale in 2 mL toluene, molar of PhC-
OCH2Br, BH3–SMe2 = 1.0:1.1.
138.75, 138.68, 128.02, 127.68, 127.60, 127.14, 127.05, 126.56,
126.51, 126.21, 84.81, 75.21, 62.62, 46.79, 46.50. HRMS (ESI) calcd
for for C63H54N6O9Na [M+Na]+ 1061.3877; found 1061.3844.
b
Isolated yield by column chromatography.
Determined by HPLC analysis using a Daicel Chiralcel column.
c
Compound 1e: Mp: 233–238 °C; ½a D23
ꢀ
¼ þ14:1 (c 1.7, DMSO), 1H
NMR (400 MHz, DMSO-d6) d 8.16 (s, 3H), 7.89 (d, J = 8.6 Hz, 3H), 7.38
7.24 (m, 15H), 5.51 (s, 6H), 4.84 (d, J = 5.9 Hz, 6H), 4.58 (s, 3H), 3.14
(dd, J = 16.1, 4.5 Hz, 3H), 2.89 (d, J = 16.2 Hz, 3H); 13C NMR
(100 MHz, DMSO-d6) d 182.67, 182.60, 167.73, 167.41, 141.77,
140.46, 139.87, 127.84, 126.64, 126.11, 125.05, 124.22, 72.37,
60.79, 56.03, 46.70. HRMS (ESI) calcd C48H42N6O9Na [M+Na]+
869.2941; found 869.2905.
catalyst 1a is a readily available, efficient, and recoverable reagent
for the asymmetric reduction of ketones by borane. Further appli-
cations of the newly constructed C3-symmetric squaramides to
other asymmetric transformations are underway.
4. Experimental
4.3. Standard procedure for the asymmetric reduction of
ketones
4.1. Materials and methods
Unless otherwise noted, reagents and materials were obtained
from commercial suppliers and used without further purification.
All solvents were purified according to the reported procedures.
Reactions were monitored by thin layer chromatography (TLC)
and column chromatography purifications were performed using
230–400 mesh silica gel. Melting points were uncorrected and mea-
sured on an SGW X-4 apparatus. 1H and 13C NMR spectra were ob-
tained on a Bruker DPX400 apparatus in CDCl3 or DMSO-d6 with
TMS as an internal standard. High resolution MS data were
Under an argon atmosphere, BH3ꢂSMe2 (1.1 mmol) was added to
a suspension of C3-catalyst 1a (0.05 mmol) in toluene (2 mL) at 0 °C.
The mixture was stirred for 3 h at room temperature and heated at
30 °C for 1 h. Then the ketone (1.0 mmol) was added over a period
of 1.5 h and the mixture was stirred for another 1 h. The reaction
mixture was quenchedby the addition of water(2 mL) and extracted
with CH2Cl2 three times. The combined organic extracts were
washed with brine and dried over MgSO4. After evaporating the
solvent under reduced pressure, the product was isolated by flash

X.-F. Wu et al. / Tetrahedron: Asymmetry 22 (2011) 1640–1643
1643
column chromatography on silica gel. The ee value was determined
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Compound 6a: Chiralcel OD column (250 mm ꢃ 4.6 mm), 2%
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Compound 6d: Chiralcel OJ-H column (250 mm ꢃ 4.6 mm), 2%
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½
a 2D3
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¼ þ41:8 (c 1,
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Pansare, S. V.; Paul, E. K. Chem. Commun. 2011, 47, 1027–1029; (h) Wang, Y. F.;
Zhang, W.; Luo, S. P.; Zhang, G. C.; Xia, A. B.; Xu, X. S.; Xu, D. Q. Eur. J. Org. Chem.
2010, 4981–4985; (i) Dai, L.; Wang, S. X.; Chen, F. E. Adv. Synth. Catal. 2010, 352,
2137–2141.
nor = 25.225 min. ½a D20
ꢀ
¼ þ34:5 (c 0.27, CHCl3), Lit.16
½
a 2D3
ꢀ
¼ þ60:8
(c 0.4, CHCl3).
Compound 6g: Chiralcel OJ-H column (250 mm ꢃ 4.6 mm), 2%
iPrOH/hexane, 1 mL/min, 220 nm. Rtmajor = 43.297 min; Rtminor
=
41.187 min. ½a 2D0
ꢀ
¼ þ47:0 (c 0.21, CHCl3), Lit.16
½
a 2D3
ꢀ
¼ þ51:1 (c 1,
CHCl3).
Compound 6h: Chiralcel OJ-H column (250 mm ꢃ 4.6 mm), 2%
iPrOH/hexane, 1 mL/min, 220 nm. Rtmajor = 41.832 min; Rtminor
=
8. (a) Moberg, C. Angew. Chem., Int. Ed. 2006, 45, 4721–4723; (b) Gibson, S. E.;
Castaldi, M. P. Angew. Chem., Int. Ed. 2006, 45, 4718–4720.
36.842 min. ½a 2D0
ꢀ
¼ þ27:5 (c 0.2, CHCl3), Lit.15
½
a 2D3
ꢀ
¼ þ35:9 (c 1.1,
CHCl3).
9. (a) Kim, J.; Kim, S. G.; Seong, H. R.; Ahn, K. H. J. Org. Chem. 2005, 70, 7227–7231;
(b) Kim, S. G.; Kim, K. H.; Jung, J.; Shin, S. K.; Ahn, K. H. J. Am. Chem. Soc. 2002,
124, 591–596; (c) Gade, L. H.; Bellemin-Laponnaz, S. Chem. Eur. J. 2008, 14,
4142–4152; (d) Sambasivan, S.; Kim, S. G.; Choi, S. M.; Rhee, Y. M.; Ahn, K. H.
Org. Lett. 2010, 12, 4228–4231.
10. (a) Murai, K.; Matsushita, T.; Nakamura, A.; Fukushima, S.; Shimura, M.;
Fujioka, H. Angew. Chem., Int. Ed. 2010, 49, 9174–9177; (b) Murai, K.;
Fukushima, S.; Hayashi, S.; Takahara, Y.; Fujioka, H. Org. Lett. 2010, 12, 964–
966; (c) Moorthy, J. N.; Saha, S. Eur. J. Org. Chem. 2010, 6359–6365; (d) Han, J.;
Wu, H.; Teng, M. Y.; Li, Z. Y.; Wang, Y. N.; Wang, L. Y.; Pan, Y. Synlett 2009, 933–
936; (e) Neal, S. R.; Ellern, A.; Sadow, A. D. J. Org. Chem. 2011, 696, 228–234; (f)
Liu, H.; Du, D. M. Eur. J. Org. Chem. 2010, 2121–2131; (g) Gonzalez, A. Z.; Toste,
F. D. Org. Lett. 2010, 12, 200–203; (h) Reetz, M. T.; Guo, H. C.; Ma, J. A.; Goddard,
R.; Mynott, R. J. J. Am. Chem. Soc. 2009, 131, 4136–4142.
11. Du, D. M.; Fang, T.; Xu, J. X.; Zhang, S. W. Org. Lett. 2006, 8, 1327–1330.
12. Li, G. Q.; Yan, Z. Y.; Niu, Y. N.; Wu, L. Y.; Wei, H. L.; Liang, Y. M. Tetrahedron:
Asymmetry 2008, 19, 816–821.
13. (a) Min, C.; Han, X.; Wu, X. F.; Zhou, H.-B.; Dong, C. Adv. Synth. Catal., in press.
doi:10.1002/adsc.201100066.; (b) Dong, Z.; Jin, X.-Q.; Wang, P.-C.; Min, C.;
Dong, C. ARKIVOC 2011, xi, 367–380.
Compound 6i: Chiralcel OD column (250 mm ꢃ 4.6 mm), 2%
iPrOH/hexane, 1.0 mL/min, 220 nm. Rtmajor = 15.988 min; Rtminor
20.677 min. Lit.16
=
½
a 2D3
ꢀ
¼ þ51:2 (c 1.1, CHCl3).
Compound 6j: Chiralcel OD column (250 mm ꢃ 4.6 mm), 2%
iPrOH/hexane, 1.0 mL/min, 220 nm. Rtminor = 17.722 min; Rtma-
jor = 19.183 min. Lit.16
½
a 2D3
ꢀ
¼ þ37:1 (c 0.9, CHCl3).
Compound 6k: Chiralcel OD column (250 mm ꢃ 4.6 mm), 2%
iPrOH/hexane, 1.0 mL/min, 220 nm. Rtminor = 16.367 min; Rtmajor
=
17.645 min. ½a 2D0
ꢀ
¼ þ30:5 (c 0.2, CHCl3), Lit.15
½
a 2D3
ꢀ
¼ þ47:6 (c 0.5,
CHCl3).
Compound 6l: Chiralcel OD column (250 mm ꢃ 4.6 mm), 2%
iPrOH/hexane, 1.0 mL/min, 220 nm. Rtmajor = 23.035 min; Rtminor
=
18.758 min. ½a 2D0
ꢀ
¼ ꢁ20:8 (c 0.25, CHCl3), Lit.16
½
a 2D3
ꢀ
¼ ꢁ32:5 (c
1.0, CHCl3).
14. Li, D. R.; He, A.; Falck, J. R. Org. Lett. 2010, 12, 1756–1759.
Acknowledgments
15. Wang, F.; Liu, H.; Cun, L.; Zhu, J.; Deng, J.; Jiang, Y. J. Org. Chem. 2005, 70, 9424–
9429.
16. Lin, H.; Chen, Y.-Z.; Xu, X.-Y.; Xia, S.-W.; Wang, L.-X. J. Mol. Catal. B: Enzym.
2009, 57, 1–5.
We are grateful to the NSFC (Nos. 20972121, 91017005 and
81172935), the Program for New Century Excellent Talents in Uni-
versity (NCET-10-0625), the National Mega Project on Major Drug
Development (2009ZX09301-014-1).