Tert-Butanesulfinylthioether ligands: Synthesis and application in palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tetasy.2011.02.031

A class of novel chiral SO-S-type bidentate ligands based on the tert-butylsulfinyl moiety as the sole chiral source were designed and synthesized through a simple and efficient pathway. These ligands are effective catalyst precursors for the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate and moderate to good stereoselectivities (up to 84% ee) were obtained.

Full text of DOI:10.1016/j.tetasy.2011.02.031

Tetrahedron: Asymmetry 22 (2011) 575–579
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
tert-Butanesulfinylthioether ligands: synthesis and application
in palladium-catalyzed asymmetric allylic alkylation
⇑
Jibing Liu, Guihua Chen, Junwei Xing, Jian Liao
Key Laboratory of Asymmetric Synthesis and Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, PR China
Natural Products Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China
Graduate School of Chinese Academy of Sciences, Beijing 100049, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A class of novel chiral SO–S-type bidentate ligands based on the tert-butylsulfinyl moiety as the sole chi-
ral source were designed and synthesized through a simple and efficient pathway. These ligands are
effective catalyst precursors for the palladium-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl
acetate and moderate to good stereoselectivities (up to 84% ee) were obtained.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 2 February 2011
Accepted 28 February 2011
Available online 12 April 2011
1. Introduction
ligands.8 tert-Butanesulfinylphosphine ligands (P–SO ligands)
(R)-3 (Fig. 1) demonstrated encouraging results in Pd-catalyzed
Asymmetric catalysis with transition metal complexes is a rap-
idly developing field in modern synthetic chemistry. The develop-
ment of new and rationally designed chiral ligands is very
important for this area.1 Among the diverse chiral ligands reported
to date, sulfur-containing ligands are one of the most versatile and
widely used classes.2 Chiral sulfur ligands bearing a sulfoxide moi-
ety have been frequently employed as effective catalyst precursors
in various enantioselective transformations.3–8 However, only a
few S,S-type ligands containing a monosulfoxide have been re-
asymmetric allylic substitutions.8b
t-Bu
PhS
S
O
N
Bn
S
S
p-Tol
PhS
PPh2
p-Tol
O
O
R
R = H, OMe, OMOM
ported, for example, Skarzewski et al.9 reported a chiral sulfoxide-
_
(S)-2
(R)-3
(S,S)-1
thioether ligand (SO–S ligand) based on a rigid cyclopentane
backbone (S,S)-1, and high enantioselectivity in asymmetric allylic
alkylation reaction was achieved. The authors, however, suggested
that it behaved more like an N,S-donating ligand than an
S,S-donating ligand. In 1995, Shibasaki et al.10 reported another
chiral p-tolylsulfinylthioether ligand (S)-2, which involved a chiral
sulfoxide as the sole chiral source. Preliminary results in Pd-
catalyzed allylic alkylations led to moderate asymmetric induction
(Fig. 1). This early work suggested that the different coordinating
properties of the sulfoxide group and the sulfur atom could be effi-
cient tools for desymmetrization of the terminal allylic carbons of
substrates in the asymmetric allylic alkylation reaction.
Chiral tert-butanesulfinyl compounds have several advantages:
practical and concise synthesis;3,4,7,8 ortho-lithiation properties;11
high stereogenic stabilities;12 effective coordination capability
with transition metals and excellent asymmetric inductions.5,7,8
Recently, we focused our attention on transition-metal-catalyzed
asymmetric reactions using chiral sulfoxide (tert-butanesulfinyl)
Figure 1. Sulfinylthioether ligands and sulfinylphosphine ligands.
Due to no satisfactory results being achieved using SO–S ligands
in previous reports and encouraged by the results of P–SO ligands,
we herein report a novel class of chiral SO–S type ligands contain-
ing a tert-butylsulfoxide (Fig. 2) and evaluate these ligands in Pd-
catalyzed allylic alkylations.
4a: R1 = H, R2 = H, R3 = Ph
4b: R1 = H, R2 = H, R3 = CH3
4c: R1 = H, R2 = H, R3 = t-Bu
t-Bu
R1
4d: R1 = H, R2 = H, R3 = Bn
S
4e: R1 = H, R2 = H, R3 = naphthalen-1-ylmethyl
4f: R1 = H, R2 = H, R3 = mesitylmethyl
4g: R1 = OCH3, R2 = H, R3 = Bn
4h: R1 = H, R2 = OCH3, R3 = Bn
4i: R1 = H, R2 = Oi-Pr, R3 = Bn
O
SR3
R2
4j: R1 = H, R2 = OMOM, R3 = Bn
4k: R1 = OCH3, R2 = OCH3, R3 = Bn
⇑
Corresponding author.
E-mail address: jliao@cib.ac.cn (J. Liao).
Figure 2. tert-Butylsulfinylthioether ligands.
0957-4166/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2011.02.031

576
J. Liu et al. / Tetrahedron: Asymmetry 22 (2011) 575–579
Table 1
2. Results and discussion
2.1. Preparation of ligands
Optimization of the allylic alkylation of rac-(E)-1,3-diphenyl propenyl acetate with
dimethylmalonate using [Pd(g
3-C3H5) Cl]2/(R)-4aa
OAc
CH(CO2Me)2
[Pd(η3-C3H5)Cl]2 / (R)-4a
∗
Ligands 4a–c were readily prepared in a single step from
2-bromophenylthioether 5. As shown in Scheme 1, an optically
active sulfinyl group was introduced using (R)-tert-butyl tert-
butanethiosulfinate 6 to give (R)-4a–c via bromo-lithium exchange
at low temperature.
CH2(CO2Me)2 / BSA, additive
Ph
Ph
Ph
Ph
Entry
Additive
Solvent
Yieldc (%)
Eed (%)
1b
2
3
4
5
6
7
8
LiOAc
NaOAc
KOAc
LiOAc
LiOAc
LiOAc
LiOAc
LiOAc
CH3CN
CH3CN
CH3CN
CH2Cl2
Toluene
THF
98
41
53
43
52
Trace
36
55
40
43
41
6
ND
14
2
t-Bu
Br
S
EtOAc
Et2O
1) n-BuLi, THF, -78oC
O
31
O
S
2)
t-Bu
SR
, rt
a
SR
Reaction conditions: 0.2 mmol of substrate, 1.0 mg of additive, 0.6 mmol
of dimethylmalonate, 0.6 mmol of N,O-bis(trimethylsilyl)acetamide (BSA),
0.004 mmol of [Pd(
3-C3H5)Cl]2 (2 mol %), 0.01 mmol of (R)-4a (5 mol %). Reactions
t-Bu
S
4a: R = Ph
4b: R = CH3
4c: R = t-Bu
5a: R = Ph
5b: R = CH3
5c: R = t-Bu
g
6
were carried out under argon at room temperature for 48 h.
b
Yield: 36% - 55%
Reaction time was 29 h.
Isolated yield based on substrate.
Determined by chiral HPLC analysis using a chiral stationary column (Chiralpak
c
d
t-Bu
t-Bu
R1
R1
AD-H, hexane/i-PrOH = 95:5).
1) n-BuLi or LDA, THF, -78oC
S
S
O
O
2) S8, rt
3) NH4Cl (aq)
SH
was poor (27% ee). Ligand 4c gave moderate yield and better
enantioselectivity (Table 2, entry 3). The size of the alkyl thiol
group had a great impact on the enantioselectivity: the smaller
group (–SCH3 in 4b) gave a higher yield (98%) and lower ee (27%)
than bigger groups (–St-Bu in 4c) (Table 2, entries 2 and 3). Ligands
4d, 4e, and 4f afforded similar activities, and the asymmetric
inductions were slightly enhanced with increased steric
hindrance of the substituents on the sulfur atom (Table 2, entries
4–6). When a methoxy group was introduced at either the 3- or
6-position of principal phenyl ring, higher enantioselectivities
but different activities were obtained (Table 2, entries 7 and 8).
R2
8
R2
7
t-Bu
R1
S
R3Br
O
NaOH, EtOH, rt
SR3
R2
Yield:18% - 52% (two steps)
4d-k
Scheme 1. Preparation of SO–S ligands.
Another efficient method to prepare this type of ligand is the
deprotonation of 7 with n-BuLi or LDA in THF at ꢀ78 °C, followed
by the addition of elemental sulfur (S8) powder to generate
intermediate 8. Compound 8 can then be treated with NaOH and
bromo-methylarene to give the target ligands 4d–k.
Table 2
Asymmetric allylic alkylation of rac-(E)-1,3-diphenylpropenyl acetate with dimeth-
ylmalonate using [Pd(g
3-C3H5)Cl]2/ligands 4a–ka
Entry
Ligand
T (°C)
Time (h)
Yieldb (%)
eec (%) (config)d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
(R)-4a
(R)-4b
(R)-4c
(R)-4d
(R)-4e
(R)-4f
(R)-4g
(R)-4h
(R)-4i
(R)-4i
(R)-4i
(R)-4j
(R)-4j
(R)-4j
(R)-4k
25
25
25
25
25
25
25
25
25
0
29
15
24
17
11
17
33
11
17
48
48
17
48
48
30
98
98
69
97
91
96
94
96
98
98
34
98
98
37
98
55 (S)
27 (S)
59 (S)
64 (S)
70 (S)
68 (S)
73 (S)
73 (S)
80 (S)
79 (S)
84 (S)
80 (S)
84 (S)
84 (S)
77 (S)
2.2. Palladium-catalyzed allylic alkylation
With chiral ligands 4a–k in hand, we examined their effective-
ness in the asymmetric allylic alkylation reaction. In order to deter-
mine the optimal reaction conditions, ligand (R)-4a was used in the
allylic alkylation of racemic 1,3-diphenylprop-1-en-3-ylacetate
with dimethylmalonate. The reaction was performed in the
ꢀ20
25
0
presence of [Pd(g
3-C3H5)Cl]2 (2.0 mol %), ligand 4a (5.0 mol %),
N,O-bis(trimethylsilyl)acetamide (BSA, 3.0 equiv), dimethylmalo-
nate (3.0 equiv) at room temperature. The reaction proceeded
smoothly to give excellent yield (98%) and moderate enantiomeric
excess (55%ee) using LiOAc as an additive and acetonitrile as the
solvent (Table 1, entry 1). As shown in Table 1, both the activity
and enantioselectivity decreased when NaOAc or KOAc was used
instead of LiOAc as an additive (Table 1, entries 2 and 3). Acetoni-
trile was also necessary in this reaction, otherwise, poor results
were achieved (Table 1, entries 4–8).
Under the optimized reaction conditions (CH3CN as solvent,
LiOAc as additive), the influence of the substituents on the thioe-
ther, the steric properties of the aryl ring, and the temperature
on the catalytic activity and enantioselectivity were examined;
the results are shown in Table 2. The reaction time in the presence
of 4b was shorter than that of 4a at 25 °C, which could be com-
pleted in 15 h (Table 2, entry 2), although the enantioselectivity
ꢀ20
25
a
Reaction conditions: 0.2 mmol of substrate, 1.0 mg LiOAc, 0.6 mmol of dim-
ethylmalonate, 0.6 mmol of N,O-bis(trimethylsilyl)acetamide (BSA), 0.004 mmol of
[Pd(
g
3-C3H5)Cl]2 (2.0 mol %), 0.01 mmol of ligand (5.0 mol %) in 1 mL of CH3CN.
b
Isolated yield based on substrate.
c
Determined by chiral HPLC analysis using a chiral stationary column (Chiralpak
AD-H, hexane/i-PrOH = 95:5).
d
The absolute configuration was determined to be (S) by comparing the specific
rotation or retention time with the literature data.14
Ligand 4i (6-Oi-Pr) and 4j (6-OMOM) provided excellent yield
(98%) and good enantiomeric excess (80%) (Table 2, entries 9 and
12). When the temperature was lowered to 0 °C, ligand 4i acted
the same as it had at 25 °C except a longer reaction time was

J. Liu et al. / Tetrahedron: Asymmetry 22 (2011) 575–579
577
required (Table 2, entry 10). With ligand 4j, in contrast, the enan-
tiomeric excess was increased to 84% (Table 2, entry 13). Decreas-
ing the temperature further to ꢀ20 °C meant that the results of
ligand 4i and 4j were similar: decreased yield and an improvement
of enantioselectivity were observed (Table 2, entries 11 and 14).
Compared with ligand 4g or 4h, the asymmetric induction of the
double methoxy substituted ligand 4k improved slightly (Table 2,
entry 15). It was found that modifications either at the 3- or 6-
position of the principal phenyl ring and the sulfur atom could
affect the asymmetric induction of this class of ligand, and with
an increase in the steric hindrance of the substituents, higher enan-
tiomeric excess could be generated.
The results of the allylic alkylation with other nucleophiles using
the ligand 4j are listed in Table 3. Prolonged reaction times were re-
quired when diethyl malonate was used as the nucleophile while the
yield and enantioselectivity were maintained (Table 3, entry 2).
When dibenzyl malonate was used, the enantiomeric excess of the
alkylation product was slightly decreased to 74% and the reaction
proceeded slowly (Table 3, entry 3). Although only a moderate yield
was obtained, the diastereoselectivity in the alkylation using ethyl
2-cyanoacetate was excellent (Table 3, entry 4).
(75 MHz) spectra were recorded on a Brucker-300 spectrometer.
Optical rotation data were recorded on a Perkin–Elmer Polarime-
ter-341. Enantiomeric excess was determined by HPLC analysis
on chiral stationary columns in comparison with the authentic
racemates. Column chromatography was performed using silica
gel (200–300 mesh) eluting with ethyl acetate and petroleum
ether.
4.1. Synthesis of ligands 4a–c
4.1.1. (R)-(2-(tert-Butylsulfinyl) phenyl) (phenyl) sulfane 4a
To a mixture of 2-bromoaniline (4.3 g, 25 mmol), concentrated
hydrochloric acid (4.2 mL) and ice (5.0 g), the solution of sodium
nitrite (1.76 g, 25.5 mmol) and water (4.3 mL) was added drop-
wise, and the mixture was stirred vigorously for 30 min. To another
round bottomed flask were added thiophenol (3.3 g, 30 mmol),
KOH (5.6 g, 0.1 mol), and water (10 mL), and stirred for 10 min.
The previous solution was added dropwise at 0 °C, and the mixture
was stirred overnight. The reaction mixture was extracted with
CH2Cl2 (15 mL ꢁ 3). The combined organic layers were washed
with brine and dried over anhydrous Na2SO4, filtered, and evapo-
rated under reduced pressure. The crude product was purified by
column chromatography with petroleum ether to afford compound
5a; yellow oil, yield: 57%.
Table 3
To a solution of 5a (0.53 g, 2.0 mmol) in THF (5 mL) was added
dropwise n-BuLi (1.0 mL, 2.5 mmol, 2.5 M solution in hexane) at
ꢀ78 °C, and the mixture was stirred for 30 min under an argon
atmosphere. The solution of (R)-tert-butyl tert-butanethiosulfinate
6 (0.388 g, 2.0 mmol) in THF (2 mL) was then added dropwise to
the reaction mixture at ꢀ78 °C, the temperature was allowed to
slowly warm to room temperature. The reaction mixture was
stirred overnight at room temperature, and then evaporated under
reduced pressure. The residue was purified by column chromatog-
raphy with petroleum ether/EtOAc (4:1, V/V) to afford 4a; yellow
Scope of Pd-catalyzed asymmetric allylic alkylation with ligand (R)-4ja
OAc
Ph
Nu-H
Nu
[Pd(η3-C3H5)Cl]2 / (R)-4j
∗
Nu-H
+
BSA-LiOAc, CH3CN, rt
Ph
Ph
Ph
Entry
Time (h)
Yieldb (%)
eec (%)
1
2
3
4
CH2(CO2Me)2
CH2(CO2Et)2
CH2(CO2Bn)2
NCCH2CO2Et
17
35
70
46
98
96
96
52
80 (S)d
81 (S)e
74 (S)e
79 (dr >50:1)f
oil, yield: 37%; ½a D20
ꢂ
¼ þ244:6 (c 0.8, CH2Cl2); 1H NMR (CDCl3,
a
Reaction conditions: 0.2 mmol of substrate, 1.0 mg LiOAc, 0.6 mmol of NuH,
g
3-C3H5)
300 MHz): d = 7.89 (d, J = 6.3 Hz, 1H), 7.43–7.19 (m, 8H), 1.28 (s,
9H); 13C NMR (CDCl3, 75 MHz): d = 141.7, 136.8, 133.4, 132.0,
131.3, 129.4, 127.7, 127.4, 127.3, 126.5, 58.4, 23.2; HRMS (ESI):
[M+Na]+, calcd for C16H18NaOS2: 313.0691, found: 313.0694.
0.6 mmol of N,O-bis (trimethylsilyl)acetamide (BSA), 0.004 mmol of [Pd(
Cl]2 (2.0 mol %), 0.01 mmol of (R)-4j (5.0 mol %) in 1 mL of CH3CN.
b
Isolated yield based on substrate.
Determined by chiral HPLC analysis using a chiral stationary column.
The absolute configuration was determined by comparing the specific rotation
c
d
with the literature value.14
e
The absolute configuration was determined by comparing the specific rotation
4.1.2. (R)-(2-(tert-Butylsulfinyl) phenyl) (methyl) sulfane 4b
Under an argon atmosphere, to a solution of NaOH (0.32 g,
7.9 mmol) in EtOH (3.0 mL) was added dropwise 2-bromobenze-
nethiol (1.0 g, 5.29 mmol), and the mixture was stirred for
30 min, after which CH3I (0.5 mL, 7.9 mmol) was added. The reac-
tion mixture was stirred for 3 h at room temperature. Next, ice
water (4.0 mL) was added, and the reaction mixture was extracted
with CH2Cl2 (10 mL ꢁ 3). The combined organic layers were
washed with brine and dried over anhydrous Na2SO4, filtered,
and evaporated under reduced pressure. The crude product was
purified by flash column chromatography with petroleum ether
to afford compound 5b; colorless oil, and yield: 98%. The procedure
of the synthesis of 4b from 5b is similar to that of 4a; white solid,
with the literature value.15
dr was determined by 1H NMR analysis of the crude mixture.
f
3. Conclusion
In conclusion, we have successfully prepared a class of novel
chiral SO, S-type bidentate ligands based on a chiral tert-butylsul-
finyl moiety as the sole chiral source. Owing to the useful
ortho-lithiation properties of tert-butylsulfinylbenzene, a simple
and efficient method to access these ligands has been developed.
These ligands were effective catalyst precursors for the palladium-
catalyzed allylic alkylation of racemic 1,3-diphenyl-2-propeny-
lacetate and provide moderate to good stereoselectivity. The
introduction of sterically hindered groups onto the principal
phenyl ring and sulfur atom enhanced the enantioselectivity of
the alkylation reaction.
yield: 55%;
½
a 2D0
ꢂ
¼ þ286:3 (c 1.0, CH2Cl2); 1H NMR (CDCl3,
300 MHz): d = 7.82–7.79 (m, 1H), 7.43–7.31 (m, 3H), 2.48 (s, 3H),
1.24 (s, 9H); 13C NMR (CDCl3, 75 MHz): d = 140.4, 139.3, 131.4,
127.7, 127.2, 125.8, 58.3, 23.2, 17.4. HRMS (ESI): [M+Na]+, calcd
for C11H16NaOS2: 251.0535, found: 251.0537.
4. Experimental
4.1.3. (R)-tert-Butyl (2-(tert-butylsulfinyl) phenyl) sulfane 4c
At 0 °C, to a solution of t-BuOH (0.74 mL) and H2O (3.8 mL) was
added dropwise concentrated sulfuric acid (5 mL). Next, 2-bromo-
benzenethiol (1.0 g, 5.29 mmol) was added dropwise, and stirred
for 20 h. The reaction mixture was extracted with ethyl ether
(10 mL ꢁ 3). The combined organic layers were washed with
All experiments were carried out under an argon atmosphere.
Commercial reagents were used as received without purification.
Commercial grade solvents were dried and purified by standard
literature procedures. The 1H NMR (300 MHz) and 13C NMR

578
J. Liu et al. / Tetrahedron: Asymmetry 22 (2011) 575–579
saturated NaHCO3 and brine and dried over anhydrous Na2SO4, fil-
tered, and evaporated under reduced pressure. The crude product
was purified by flash column chromatography with petroleum
ether to afford compound 5c; colorless oil, yield: 96%. The synthe-
sis of 4c from 5c is similar to that of 4a; colorless oil, yield: 36%;
4.2.3. (R)-(2-(tert-Butylsulfinyl) phenyl) (2,4,6–trimethylbenz-
yl) sulfane 4f
White solid, yield: 33% (from 7); ½a D20
¼ þ206:6 (c 1.0, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz) d = 7.87–7.84 (m, 1H), 7.48–7.42 (m,
3H), 6.86 (s, 2H), 4.13 (q, J = 10.7 Hz, 2H), 2.37 (s, 6H), 2.26 (s,
3H), 1.22 (s, 9H). 13C NMR (CDCl3, 75 MHz): d = 142.4, 137.6,
137.4, 137.3, 131.5, 131.2, 129.1, 128.9, 127.4, 127.0, 58.4, 35.3,
23.2, 20.9, 19.5. HRMS (ESI): [M+Na]+, calcd for C20H26NaOS2:
369.1317, found: 369.1324.
½
a 2D0
ꢂ
¼ þ191:4 (c 1.1, CH2Cl2); 1H NMR (CDCl3, 300 MHz):
d = 7.90–7.87 (m, 1H), 7.56–7.51 (m, 2H), 7.44–7.38 (m, 1H), 1.28
(s, 9H), 1.17 (s, 9H). 13C NMR (CDCl3, 75 MHz): d = 147.0, 138.3,
132.7, 130.2, 128.9, 127.3, 58.5, 48.7, 30.9, 23.4. HRMS (ESI):
[M+Na]+, calcd for C14H22NaOS2: 293.1004, found: 293.1006.
4.2.4. (R)-Benzyl (2-(tert-butylsulfinyl)-3-methoxyphenyl)
4.2. Typical procedure for synthesis of ligands 4d–k
sulfane 4g
Colorless oil, yield: 25% (from 7); ½a D20
¼ þ70:2 (c 1.5, CH2Cl2);
ꢂ
Under an argon atmosphere, to a solution of substituted bromo-
benzene (2.2 mmol) in THF (10 mL) was added dropwise n-BuLi
(1.0 mL, 2.5 mmol) at ꢀ78 °C and the mixture was stirred for
30 min. A solution of (R)-tert-butyl tert-butanethiosulfinate 6
(0.39 g, 2.0 mmol) in THF (2 mL) was then added dropwise to the
reaction mixture at ꢀ78 °C. The temperature was allowed to slowly
warm to room temperature. The reaction mixture was stirred
overnight at room temperature, and then evaporated under
reduced pressure. Saturated NH4Cl (10 mL) was added, and
extracted with CH2Cl2 (10 mL ꢁ 3). The combined organic layers
were washed with brine and dried over anhydrous Na2SO4, filtered,
and evaporated under reduced pressure. The residue was purified
by column chromatography with petroleum ether/EtOAc (4:1,
V/V) to afford 7.13
Under an argon atmosphere, to a solution of 7 (1.0 mmol) in
THF (5 mL) was added dropwise either n-BuLi (0.5 mL, 1.25 mmol,
2.5 M solution in hexane) or LDA (1.1 mmol) at ꢀ78 °C, and the
mixture was stirred for 1 h at ꢀ50 °C. Under an argon flow, ele-
mental sulfur (S8) (64 mg, 2.0 mmol) was added to the reaction
mixture at ꢀ78 °C, and the temperature was allowed to slowly
warm to room temperature. The reaction mixture was stirred over-
night at room temperature, and then evaporated under reduced
pressure. Saturated NH4Cl (10 mL) was added, and extracted with
CH2Cl2 (10 mL ꢁ 3). The combined organic layers were washed
with brine and dried over anhydrous Na2SO4, filtered, and evapo-
rated under reduced pressure to give crude 8. The residue was used
without any further purification. Crude 8 was added to a solution
of NaOH (100 mg, 2.5 mmol) in EtOH (5 mL), stirred for 20 min,
after which ArCH2Br (1.0 mmol) was added, and stirred overnight
at room temperature. The reaction mixture was evaporated under
reduced pressure. The residue was purified by column chromatog-
raphy with petroleum ether/EtOAc (4:1, V/V) to afford the desired
ligand.
1H NMR (CDCl3, 300 MHz): d = 7.37–7.35 (m, 2H), 7.32–7.22 (m,
4H), 6.91 (d, J = 8.03 Hz, 1H), 6.74 (d, J = 8.28 Hz, 1H), 4.13 (s,
2H), 3.82 (s, 3H), 1.36 (s, 9H). 13C NMR (CDCl3, 75 MHz):
d = 159.9, 136.3, 131.9, 129.0, 128.5, 127.3, 125.5, 120.6, 109.4,
60.1, 55.7, 38.6, 31.6, 24.7. HRMS (ESI): [M+Na]+, calcd for
C18H22NaO2S2: 357.0953, found: 357.0952.
4.2.5. (R)-Benzyl (2-(tert-butylsulfinyl)-6-methoxyphenyl)
sulfane 4h
White solid, yield: 28% (from 7); ½a D20
ꢂ
¼ ꢀ35:4 (c 0.8, CH2Cl2); 1H
NMR (CDCl3, 300 MHz): d = 7.49–7.39 (m, 2H), 7.23–7.18 (m, 5H),
6.97–6.94 (m, 1H), 4.00 (s, 2H), 3.90 (s, 3H), 1.18 (s, 9H). 13C NMR
(CDCl3, 75 MHz): d = 159.8, 147.0, 137.1, 129.6, 128.9, 128.3,
127.3, 122.5, 119.3, 112.8, 58.6, 56.1, 39.7, 23.6. HRMS (ESI):
[M+Na]+, calcd for C18H22NaO2S2: 357.0953, found: 357.0962.
4.2.6. (R)-Benzyl (2-(tert-butylsulfinyl)-6-isopropoxyphenyl)
sulfane 4i
Colorless oil, yield: 18% (from 7); ½a D20
¼ ꢀ66:1 (c 0.7, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 7.46–7.35 (m, 2H), 7.28–7.18 (m,
5H), 6.99–6.97(m, 1H), 4.73–4.65 (m, 1H), 4.09–4.00 (m, 2H),
1.48–1.44 (m, 6H), 1.18 (s, 9H). 13C NMR (CDCl3, 75 MHz):
d = 158.0, 146.7, 137.0, 129.2, 128.9, 128.3, 127.1, 123.4, 118.9,
115.0, 58.3, 48.5, 39.3, 29.6, 23.4. HRMS (ESI): [M+Na]+, calcd for
C20H26NaO2S2: 385.1266, found: 385.1266.
4.2.7. (R)-Benzyl (2-(tert-butylsulfinyl)-6-(methoxymethoxy)
phenyl) sulfane 4j
Colorless oil, yield: 52% (from 7); ½a D20
¼ ꢀ17:1 (c 0.7, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 7.48–7.42 (m, 2H), 7.25–7.16 (m,
6H), 5.22 (s, 2H), 4.02 (s, 2H), 3.54 (s, 3H), 1.19 (s, 9H). 13C NMR
(CDCl3, 75 MHz): d = 158.1, 147.0, 137.0, 129.7, 128.9, 128.4,
127.3, 123.5, 120.7, 116.9, 95.4, 58.6, 56.5, 39.9, 23.5. HRMS (ESI):
[M+Na]+, calcd for C19H24NaO3S2: 387.1059, found: 387.1068.
4.2.1. (R)-Benzyl (2-(tert-butylsulfinyl) phenyl) sulfane 4d
White solid, yield: 34% (from 7); ½a D20
¼ þ207:3 (c 0.5, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 7.83–7.80 (m, 1H), 7.41–7.32 (m,
3H), 7.27–7.23 (m, 5H), 4.10 (s, 2H), 1.22 (s, 9H). 13C NMR (CDCl3,
75 MHz): d = 142.1, 136.5, 136.2, 131.4, 131.1, 128.9, 128.5, 127.4,
127.3, 127.1, 58.4, 40.2, 23.2. HRMS (ESI): [M+Na]+, calcd for
4.2.8. (R)-Benzyl (2-(tert-butylsulfinyl)-3,6-dimethoxyphenyl)
sulfane 4k
Colorless oil, yield: 21% (from 7); ½a D20
¼ ꢀ15:3 (c 0.7, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 7.27–7.19 (m, 5H), 6.92 (s, 2H),
4.05 (q, J = 13.7, 2H), 3.83 (s, 3H), 3.80 (s, 3H), 1.32 (s, 9H). 13C
NMR (CDCl3, 75 MHz): d = 154.3, 154.1, 137.1, 132.5, 129.1,
128.3, 127.2, 125.9, 115.6, 114.3, 113.9, 59.7, 56.4, 39.9, 25.2.
HRMS (ESI): [M+Na]+, calcd for C19H24NaO3S2: 387.1059, found:
387.1066.
C17H20NaOS2: 327.0848, found: 327.0853.
4.2.2. (R)-(2-(tert-Butylsulfinyl) phenyl) (naphthalene-1-ylmet-
hyl) sulfane 4e
White solid, yield: 29% (from 7); ½a D20
¼ þ269:3 (c 1.0, CH2Cl2);
ꢂ
1H NMR (CDCl3, 300 MHz): d = 8.14 (d, J = 8.3 Hz, 1H), 7.87 (d,
J = 1.3 Hz, 2H), 7.85 (d, J = 1.9 Hz, 1H), 7.57–7.34 (m, 3H), 7.34–
7.30 (m, 4H), 4.56 (q, J = 12.3 Hz, 2H), 1.21 (s, 9H). 13C NMR (CDCl3,
75 MHz): d = 142.7, 136.6, 133.8, 132.2, 131.7, 131.4, 131.1, 128.7,
128.5, 127.7, 127.5, 127.4, 126.3, 125.8, 125.2, 123.7, 58.4, 38.4,
23.3. HRMS (ESI): [M+Na]+, calcd for C21H22NaOS2: 377.1004,
found: 377.1007.
4.3. Typical procedure for the palladium-catalyzed asymmetric
allylic alkylation
Under an argon atmosphere, to a dried Schlenk flask, ligand 4a
(2.9 mg, 5.0 mol %) and [Pd(g
3-C3H5)Cl]2 (1.4 mg, 2.0 mol %) were

J. Liu et al. / Tetrahedron: Asymmetry 22 (2011) 575–579
579
added, followed by the addition of CH3CN (1.0 mL). The mixture
was stirred at room temperature for 30 min, and then rac-1,3-di-
phenyl-2-propenyl acetate (50 mg, 0.2 mmol) was added to the
column, n-hexane/i-PrOH = 90:10 (V/V), 0.5 mL/min, 254 nm,
tR = 15.2 min, 17.1 min.
reaction system via
a
syringe. Dimethyl malonate (0.69 mL,
Acknowledgments
0.6 mmol) was added to the mixture followed by N,O-bis(trimeth-
ylsilyl)acetamide (BSA, 0.15 mL, 0.6 mmol) and lithium acetate
(1.0 mg). Conversion was monitored by TLC. The reaction was
diluted with Et2O, washed with saturated NH4Cl (aq), saturated
NaHCO3 (aq), and brine. The combined aqueous solutions were
extracted with CH2Cl2. The combined organic phase was dried over
MgSO4, filtered, concentrated in vacuo, and purified by flash
chromatography (petroleum ether/ethyl acetate = 10:1, V/V).
We are grateful for the support from the NSFC (20872139 and
21072186), the West Light Foundation of CAS, the National Basic
Research Program of China (973 Program, 2010CB833300) and
Chengdu Institute of Biology, CAS (Y0B1051100).
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ꢂ
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ꢂ
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n-hexane/i-PrOH = 80:20 (V/V), 1.0 mL/min, 254 nm, tR = 15.8 min
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_
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