382
Published on the web March 13, 2010
Efficient and Enantioselective Kinetic Resolution of Cyclic ¢-Hydroxy Sulfides
by Chiral 1,2-Diamine Catalyzed Asymmetric Acylation
Yoshiyuki Kawamata and Takeshi Oriyama*
Department of Chemistry, Faculty of Science, Ibaraki University, 2-1-1 Bunkyo, Mito 310-8512
(Received January 25, 2010; CL-100074; E-mail: tor@mx.ibaraki.ac.jp)
Kinetic resolution of cyclic ¢-hydroxy sulfides has been
Table 1. Catalytic asymmetric acylation of racemic trans-2-
phenylsulfanyl-1-cyclohexanol
achieved by reaction with benzoyl chloride in the presence of a
catalytic amount (0.1 mol %) of a chiral 1,2-diamine combined
with triethylamine. This reaction affords the corresponding
benzoates and unreacted alcohols with excellent enantioselec-
tivities.
Bn
N
N
N
N
1
2
0.75 equiv
BzCl
OBz
SPh
OH
OH
Catalyst (1 or 2) (x mol%)
+
+
NEt3 (0.5 equiv), MS 4A (40 mg)
SPh
SPh
CH2Cl2 (2 mL), − 78 °C
Optically active ¢-hydroxy sulfides are known to be
versatile synthetic intermediates in organic synthesis.1 For
example, they can be converted to useful ligands for asymmetric
synthesis.2 They can generally be obtained by asymmetric ring-
opening of meso-epoxides with thiols3 or asymmetric reduction
of ¢-keto sulfides.4 Only a few reports describe the preparation
of cyclic ¢-hydroxy sulfides with high enantioselectivities. In
1997, Shibasaki and co-workers developed a gallium-lithium-
bis(binaphthoxide) complex, which is presently the most
enantioselective catalyst (up to 98% ee) available for the
asymmetric ring-opening reaction of cyclic meso-epoxides with
thiols.5 However, the nucleophile is limited to t-BuSH.
-
0.3 mmol
3a
4a
3a
4a
Catalyst Time
(x/mol %) /h
Run
se
Yield
/%a
ee
/%b
Yield
/%a /%c,d
ee
1
2
3
4f
5g
6h
1 (0.3)
2 (0.3)
1 (0.1)
1 (0.1)
1 (0.1)
1 (0.1)
5
24
12
12
12
24
49
19
49
50
44
15
97
96
98
97
98
99
47
78
47
49
51
82
99
22
97
96
85
16
220
60
360
300
290
170
Kinetic resolution of ¢-hydroxy sulfides by asymmetric
acylation is another prominent protocol for obtaining optically
active ¢-hydroxy sulfide derivatives. However, only enzymatic
methods for this purpose have been demonstrated.6 We have
developed highly enantioselective non-enzymatic methods for
the organocatalytic asymmetric acylation of a variety of racemic
alcohols7 and meso-diols.8 The reaction of alcohols with benzoyl
chloride as an achiral acylating agent in the presence of a
catalytic amount (0.3-0.5 mol %) of a chiral 1,2-diamine derived
from (S)-proline produced excellent enantioselectivities. Over-
all, chiral 1,2-diamines having an isoindoline (1) or a benzyl-
methylamino group (2) were the most promising organocatalysts
for the asymmetric acylation of various alcohols.
Herein, we report a kinetic resolution of cyclic ¢-hydroxy
sulfides by highly efficient organocatalytic asymmetric acylation.
First, we attempted the reaction of racemic trans-2-phenyl-
sulfanyl-1-cyclohexanol (0.3 mmol) as a model substrate with
0.75 equiv of benzoyl chloride in the presence of 0.3 mol % of
chiral diamine 1 combined with 0.5 equiv of triethylamine and
40 mg of molecular sieves (MS) 4A9 in dichloromethane at
¹78 °C. After stirring for 5 h, the reaction catalyzed by chiral
diamine 1 afforded the corresponding benzoate, (+)-trans-1-
benzoyloxy-2-phenylsulfanylcyclohexane (3a), in 49% yield
with 97% ee and unreacted alcohol, (¹)-trans-2-phenylsulfanyl-
1-cyclohexanol (4a), in 47% yield with 99% ee (Table 1,
Run 1). Chiral diamine 2 also catalyzed the acylation with
excellent enantioselectivities. However the acylation proceeded
slowly to give benzoate 3a in lower yield in 24 h (Table 1,
Run 2). When the chiral diamine 1 content was decreased to
0.1 mol % from 0.3 mol %, asymmetric acylation gave the
benzoate 3a in 49% yield with 98% ee (s = 360) in 12 h
aIsolated yields. bDetermined by HPLC analysis using a Daicel
Chiralpak AD-H column. cDetermined by HPLC analysis
using a Daicel Chiralcel OD column. Absolute configuration
was determined by the comparison of optical rotation of 4a
(Ref. 3a). eCalculated from the conversion (isolated yield) and
ee of the acylated product (Ref. 10). 30 mg of MS 4A were
d
f
g
h
used. 20 mg of MS 4A were used. Without MS 4A.
(Table 1, Run 3). Decreasing MS 4A from 40 mg to 30 mg also
resulted in a similar yield of the benzoate 3a with similar
enantioselectivity (s = 300) (Table 1, Run 4). As a result, the
optimal reaction conditions involved ¢-hydroxy sulfides
(0.3 mmol) with benzoyl chloride (0.75 equiv) in the presence
of chiral diamine 1 (0.1 mol %) combined with triethylamine
(0.5 equiv) and MS 4A (30 mg) in dichloromethane (2 mL) at
¹78 °C.
Table 2 summarizes the successful results of the substrate
scope of this reaction.11 The asymmetric acylation of six-
membered cyclic ¢-hydroxy sulfides afforded the corresponding
benzoates 3 and unreacted alcohols 4 with high to excellent
enantioselectivities except for the unreacted alcohol of Run 6
(Runs 1-6, 10, and 11). The five-membered cyclic ¢-hydroxy
sulfide was acylated with moderate enantioselectivity (Run 7).
The asymmetric synthesis of seven- and eight-membered cyclic
¢-hydroxy sulfides with excellent enantioselectivities is diffi-
cult; however, the asymmetric acylation of seven- and eight-
membered cyclic ¢-hydroxy sulfides proceeded smoothly with
excellent enantioselectivities (Runs 8 and 9).
In conclusion, we have succeeded in developing the first
non-enzymatic method for the asymmetric acylation of ¢-
Chem. Lett. 2010, 39, 382-384
© 2010 The Chemical Society of Japan
Kawamata, Yoshiyuki
