Iridium-catalyzed asymmetric allylation of sodium triisopropylsilanethiolate: A new way to form chiral thiols

Article abstract of DOI:10.1039/c1ob06332d

The iridium phosphoramidite complex-promoted regio- and enantioselective reaction of allylic carbonates with sodium triisopropylsilanethiolate produced allylic sulfides in 40-77% yields with up to 97:3 (branched:linear) and 89% ee, which were readily tran

Full text of DOI:10.1039/c1ob06332d

View Article Online / Journal Homepage / Table of Contents for this issue
Organic &
Biomolecular
Chemistry
Dynamic Article Links
Cite this: Org. Biomol. Chem., 2011, 9, 7897
www.rsc.org/obc
PAPER
Iridium-catalyzed asymmetric allylation of sodium triisopropylsilanethiolate:
A new way to form chiral thiols†
Weiqing Huang,a Shengcai Zheng,a,b Jialiang Tanga and Xiaoming Zhao*a
Received 5th August 2011, Accepted 25th August 2011
DOI: 10.1039/c1ob06332d
The iridium phosphoramidite complex-promoted regio- and enantioselective reaction of allylic
carbonates with sodium triisopropylsilanethiolate produced allylic sulfides in 40–77% yields with up to
97 : 3 (branched : linear) and 89% ee, which were readily transformed into chiral thiol in 68% yield with
87% ee or disulfides with two chiral C–S bond centers in 40–73% yields with up to 90 : 10 dr and 99% ee.
excellent regio- and enantioselectivity, and its applications in the
preparation of thiols and disulfides.
Introduction
Iridium-catalyzed allylation methods for enantioselective forma-
tion of carbon–sulfur bonds1 are less developed than those for con-
Results and discussion
structing carbon–carbon,2 carbon–nitrogen,3 and carbon–oxygen
linkages4 because the sulfur nucleophile may poison transition
metal catalysts.5 More recently, iridium-catalyzed enantioselective
allylic alkylation of sulfur compounds with various allylic sub-
strates has drawn considerable attention due to the importance of
chiral thiols and organosulfur compounds in organic chemistry
and chemical biology.6 Traditionally, an enantio-enriched thiol
could be prepared from the corresponding alcohol; however, this
makes one reliant on the availability of the desired alcohol in
an enantiopure form. To date, few reports regarding the prepa-
ration of thiols have been disclosed.6b,7 In connection with our
research interests on carbon–sulfur bond formation, we have been
searching to expand the scope of sulfur nucleophiles that can be
directly utilized for the synthesis of allylic thiols. In this context, we
note that the use of sulfur–heteroatom compounds (e.g., sodium
triisopropylsilanethiolate, an SH equivalent) as nucleophiles in
iridium-catalyzed enantioselective allylation has not been explored
yet. The reaction of this type mainly forms a branched allylation
product,1d,1e which could undergo useful transformations such as
(1) metathesis to give an unsymmetrical 1,3-disubstituted allylic
sulfide1d,8 that could occur by 1,3-chirality transfer through [2,3]-
sigmatropic rearrangement,9 (2) cleavage of TIPS to provide a
thiol10 or disulfide, and (3) hydrogenation to furnish an ethyl-
substituted sulfide. In particular, chiral disulfides are of great
importance to natural products,11 bioactive molecules,12 versatile
building blocks,13 and ligands.14 Herein, we first report the highly
efficient iridium-catalyzed allylation of sodium triisopropylsilan-
ethiolate with various allylic substrates, which proceeds with both
Initially, the experimental conditions were set identical with those
used for the allylic alkylation with sodium cyclohexanethiolate,1e
that is an iridacycle complex1–4 made from
1
mol% of
[Ir(COD)Cl]2 and
2
mol% of L1,15,16 methyl allyl car-
bonate, and dichloromethane (DCM) at 15 ◦C (Table 1).
Triisopropylsilanethiol17 was first tested as a nucleophile, however,
this reaction failed to proceed. Notably, potassium triethyl-
silanolate, a hard nucleophile, was successfully employed in
the iridium complex-catalyzed enantioselective allylation for the
preparation of allylic alcohols.4b Encouraged by these results,
sodium triisopropylsilanethiolate (3),18 a soft nucleophile, was
examined and 75% yield of the branched product 4a with
93 : 7 regioselectivity and 66% ee19 was achieved. In fact, the
cleavage of 4a with TBAF was carried out and the allylic
disulfides instead of thiol were unexpectedly obtained, these results
attracted our attention to investigate the transformation of 4a
into disulfides. In addition, the hydrogenation of 4a catalyzed
by Pd/C was conducted but it failed to proceed since sulfur
compounds can poison the palladium catalyst. Furthermore, o-
nitrobenzenesulfonylhydrazide (NBSH) is an efficient reagent for
the reduction of terminal olefins.20 As a result, a tandem reduction
of 4a with NBSH, followed by treating with TBAF, was performed
and it readily produced the corresponding disulfide 6a14a,21 in two
steps 47% yield with 72 : 28 dr and 92% ee (entry 1). In order to
further optimize the allylation reaction conditions, cesium fluoride
(CsF) was used as an additive in this reaction, it appeared that 77%
of 4a with 93 : 7 (4a : 5a) and 87% ee19 was attained. Similarly, the
transformation of 4a into 6a occurred in two steps and 46% yield
with 88 : 12 dr and 99% ee (entry 2). These outcomes indicate that
CsF has a considerable effect on efficiency and enantioselectivity
(entry 1 vs. entry 2), which are consistent with those of the iridium-
catalyzed allylation of sodium thiophenoxide as well.1d A further
survey was performed on the chiral phosphoramidite ligands
including L2,15 L3,16 L4,22 L5,23 and PHOX ligand L624 (Fig. 1)
aDepartment of Chemistry, Tongji University, 1239 Siping Road, Shanghai,
200092, P.R. China. E-mail: xmzhao08@mail.tongji.edu.cn
bState Key Laboratory of Fine Chemicals, Dalian University of Technology,
158 Zhongshan Road, Dalian, P.R. China, 116012
† Electronic supplementary information (ESI) available: NMR and HPLC
spectra of the compounds. See DOI: 10.1039/c1ob06332d
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 7897–7903 | 7897
©

View Article Online
Table 1 Reaction conditions optimization of Ir-catalyzed asymmetric allylation of 3a
Entry
L
Sol.
Add.b
T (◦C)
Yield of 4a (%)c
4a : 5ad
ee of 4a (%)e
Yield of 6a (%)f
DL : mesog
ee of 6a (%)g
1
2
3
4
5
6
7
8
L1
L1
L2
L3
L4
L5
L6
L1
L1
L1
L1
L1
L1
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
THF
none
CsF
CsF
CsF
CsF
CsF
CsF
CsCl
LiCl
CsF
CsF
CsF
CsF
15
15
15
15
15
15
15
15
15
0
75
77
55
93 : 7
93 : 7
72 : 28
—
88 : 12
93 : 7
—
96 : 4
90 : 10
97 : 3
99 : 1
—
66
87
—
—
—
57
—
81
72
—
—
—
—
47
46
—
—
—
45
—
52
42
—
—
—
—
72 : 28
88 : 12
—
—
—
69 : 31
—
84 : 16
77 : 23
—
92
99
—
—
—
83
—
97
93
—
—
—
—
Trace
45
80
Trace
74
80
26
23
9
10
11
12
13
-25
15
15
—
—
—
Trace
Toluene
22
85 : 15
a Reaction conditions: 1 mol% of [Ir(COD)Cl]2, 2 mol% of L, 110 mol% of 2a, and 100 mol% of 3 at -25 to 15 ◦C. b 300 mol% of additive was used
in entries 2–13. c Isolated yield based on 3. d Determined by GC-MS of the crude reaction mixture. e The ee value was calculated on the basis of both
DL : meso and ee of 6a as shown in ref. 19. f Isolated yield based on 4a. g Determined by a chiral HPLC analysis of 6a.
Using this optimized procedure, iridium-catalyzed enantioselec-
tive allylation of 3 with a diversity of methyl allylic carbonates was
surveyed (Table 2). The reaction of phenyl- and aromatic allylic
methyl carbonates 2a–2d with an electron-rich group (e.g., p-CH3,
p-CH3O, and m-CH3O) on the phenyl ring occurred in 62–77%
yields with excellent regioselectivity (92 : 8 to 97 : 3) and 74–87%
ee,19 and the transformation of 4a–4d into 6a–6d proceeded in two
steps giving 46–73% yields with 76 : 24 to 88 : 12 dr and 95–99%
ee (entries 1–4). Moreover, the reaction of hetero- and aromatic
allylic carbonates 4e–4g with an electron-deficient group (e.g., p-Cl
and p-Br) on the phenyl ring took place in 41–72% yields and 80–
85% ee,19 although the regioselectivity was slightly lower (89 : 11
to 94 : 6); in the same manner, 6e–6g were generated from 4e–4g in
Fig. 1 Chiral ligands L1–L6.
two steps giving 40–51% yields with 82 : 18 to 87 : 13 dr and 97–99%
ee (entries 5–7). It is noted that a small amount of iridium catalyst
(0.5 mol% of [Ir(COD)Cl]2 and 1 mol% of L1) was required
for an allylation of (E)-methyl 3-(thiophen-2-yl)allyl carbonate.
Otherwise, a mixture of 4g : 5g (52 : 48) was obtained under the
optimized conditions (entry 7). We are currently studying the
reason for this reaction. The reaction also worked well with the
aliphatic allylic carbonate 2h but with poor regioselectivity (57 : 43,
entry 8). This deterioration in regioselectivity may stem from
to identify how the structural variation of the ligands may affect
regio- and enantioselectivity. L1 gave the best results (77% yield,
93 : 7 4a : 5a, and 87% ee) in favor of the branched product 4a (entry
2). Both L2 and L4 led to the formation of the desired product 4a in
only 45–55% yields with a slightly lower regioselectivity (72 : 28 to
88 : 12) (entry 3 vs. entry 5). L5 gave rise to the highest yield (80%)
of 4a but with a somewhat low enantioselectivity (57% ee, entry
6). The iridium complex generated from either L3 or L6 failed
to promote this allylation reaction (entry 4 vs. entry 7). Finally,
the first ligand we tested, L1, appeared to be the best compromise
between high regio- and enantioselectivity. The effect of additive,
solvent, and temperature on this reaction was also investigated.
The utilization of additives including CsF, CsCl, and LiCl had
considerable influences on efficiency, regio- and enantioselectivity
(entries 2, 8 and 9). Adjusting the temperature had a dramatic
effect on the efficiency as well (entries 2, 10 and 11). The survey of
solvents revealed that DCM is the optimal solvent (entry 2). Other
solvents such as THF and toluene were not effective (entries 12
and 13). Thus, the reaction conditions shown in entry 2 of Table 1
were chosen as the optimal conditions for further study.
i
the influence of the bulky group of NaSSiPr3 on this allylation
reaction. A similar result was observed in the iridium complex-
catalyzed allylation using NaOTIPS as a nucleophile because of
the hindered effect of TIPS.4b The higher ee of 6 with two chiral C–
S bond centers made from the corresponding 4 may result from the
preferential kinetic resolution in the oxidative coupling reaction.
Further proving the value of this synthetic method, a chiral
secondary thiol was prepared in this way, demonstrated in eqn
(1). A tandem reduction of 4a with NBSH, followed by reaction
with a solution of HCl in Et2O in the presence of AlCl3 under
argon atmosphere, provided the thiol 7a25 in two steps in 68%
yield and 87% ee,26 and its absolute configuration was determined
as S by means of comparing with those of the known (R)- or
7898 | Org. Biomol. Chem., 2011, 9, 7897–7903
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Table 2 Ir-catalyzed asymmetric allylation of allyl methyl carbonates with 3a
Entry
R
Product
Yield of 4 (%)b
4 : 5c
ee of 4 (%)d
Yield of 6 (%)e
DL : meso (%)f
ee of 6 (%)f
1
2
3
4
5
6
7h
8
C6H5
4a
4b
4c
4d
4e
4f
77
76
72
62
69
72
41
40
93 : 7
92 : 8
97 : 3
93 : 7
87
74
83
82
84
80
85
89
46
44
69
73
51
49
40
55
88 : 12
76 : 24
84 : 16
86 : 14
84 : 16
82 : 18
87 : 13
90 : 10
99
96
97
95
99
97
97
99
3-MeOC6H4
4-MeOC6H4
4-MeC6H4
4-ClC6H4
4-BrC6H4
2-thienyl
94 : 6
90 : 10g
89 : 11
57 : 43
4g
4h
PhCH2CH2
a Reaction conditions: 1 mol% of [Ir(COD)Cl]2, 2 mol% of L1, 300 mol% of CsF, 110 mol% of 2 and 100 mol% of 3 in DCM at 15 ◦C. b Isolated yield
based on 3. c Determined by GC-MS of the crude reaction mixture. d The ee value was calculated on the basis of both DL : meso and ee of 6 as shown in
ref. 19. e Isolated yield based on 4. f Determined by a chiral HPLC analysis of 6. g Determined by 1H NMR of the crude reaction mixture. h 0.5 mol% of
[Ir(COD)Cl]2 and 1 mol% of L1 was used in this case.
(S)-1-phenylpropane-1-thiol.6b,25 To the best of our knowledge, this
is the first report regarding transition metal-catalyzed allylation
method for the synthesis of chiral thiols.
integration). Data for 13C NMR are reported in terms of chemical
shift (d, ppm).
General procedure for the iridium-catalyzed enantioselective allylic
i
alkylation of NaSSiPr3
[Ir(COD)Cl]2 (0.0020 mmol, 1.0 mol%), phosphoramidite
ligand L1 [O,O¢-(S)-(1,1¢-dinaphthyl-2,2¢-diyl)-N,N¢-di-(S,S)-
[phenylethylphosphoramidite] (0.0040 mmol, 2.0 mol%) were
dissolved in THF (0.5 mL) and propylamine (0.2 mL) in a dry
Schlenk tube filled with argon. The reaction mixture was heated
(1)
◦
at 50 C for 30 min and then the volatile solvents were removed
Conclusions
under vacuum to give a yellow solid. After that, allylic carbonate 2
(0.22 mmol, 110 mol%), sodium triisopropylsilanethiolate 3 (0.20
mmol, 100 mol%), cesium fluoride (0.60 mmol, 300 mol%), and
dichloromethylene (2.0 mL) were added. The reaction mixture was
stirred at room temperature until the mixture became clear. Then
the crude reaction mixture was filtered through celite and the
solvent was removed under reduced pressure. The ratio of regioiso-
mers (branched to linear) was determined by 1H NMR or GC-MS
of the crude reaction mixture. The crude residue was purified by
flash column chromatography to give the desired product.
In conclusion, we have developed a practical method for iridium-
catalyzed regio- and enantioselective transformation of allylic
carbonates into branched allylic sulfides which are converted to
bisulfur compounds with two chiral carbon–sulfur bond centers.
Using this method for the preparation of a chiral secondary thiol
is also discussed.
Experimental section
General experimental details
(S)-Triisopropyl(1-phenylallylthio)silane (4a). GC-MS of the
crude mixture showed a ratio of branched : linear in 93 : 7. The
mixture was purified by flash column chromatography (100%
petroleum ether) to give 4a as a colorless liquid in 77% yield.
All manipulations were carried out under an argon atmosphere
using standard Schlenk techniques. All glassware was oven or
flame dried immediately prior to use. All solvents were purified and
dried according to standard methods prior to use, unless stated
otherwise.
1
Calculated ee = 87%. [a]D20 -164.0 (c 0.7, CHCl3). H NMR (300
MHz, CDCl3) d = 7.39–7.20 (m, 5H), 6.13 (ddd, J = 16.8, 9.9, 7.5
Hz, 1H), 5.03 (dd, J = 15.9, 9.3 Hz, 2H), 4.58 (d, J = 7.2 Hz, 1H),
1.25 (tt, J = 7.2, 6.9 Hz, 3H), 1.10 (d, J = 6.9 Hz, 9H), 1.04 (d,
J = 6.9 Hz, 9H). 13C NMR (100 MHz, CDCl3) d = 143.7, 141.9,
128.3, 127.7, 126.8, 113.7, 47.3, 18.6, 18.5, 12.9. MS (EI+, m/z,
rel. intensity): 117 (100), 307 (M+). HRMS (EI+, m/z): calcd. for
C18H30SSi [M]+: 306.1838, found: 306.1845. IR (KBr): nmax (cm-1) =
2941, 2864, 2357, 2338, 1650, 1557, 1455, 990, 880, 699, 668, 647.
All reagents were obtained from commercial sources and used
without further purification. H NMR spectra were obtained at
1
300 MHz or 400 MHz and recorded relative to the tetramethylsi-
lane signal (0 ppm) or residual protio-solvent. 13C NMR spectra
were obtained at 100 MHz, and chemical shifts were recorded
relative to the solvent resonance (CDCl3, 77.0 ppm). Data for 1H
NMR are recorded as follows: chemical shift (d, ppm), multiplicity
(s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet
or unresolved, br = broad singlet, coupling constant(s) in Hz,
(S)-Triisopropyl(1-(3-methoxyphenyl)allylthio)silane
(4b).
GC-MS of the crude mixture showed a ratio of branched : linear in
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 7897–7903 | 7899
©

View Article Online
92 : 8. The mixture was purified by flash column chromatography
(petroleum ether : ethyl acetate = 40 : 1) to give 4b as a colorless
liquid in 76% yield. Calculated ee = 74%. [a]2D0 -193.7 (c 0.7,
(S)-(1-(4-Bromophenyl)allylthio)triisopropylsilane
(4f). 1H
NMR of the crude mixture showed a 90 : 10 branched : linear
ratio. The mixture was purified by flash column chromatography
(100% petroleum ether) to give 4f as a colorless liquid in 72%
yield. Calculated ee = 80%. [a]2D0 -135.7 (c 0.6, CHCl3). 1H NMR
(300 MHz, CDCl3) d = 7.42 (d, J = 8.7 Hz, 2H), 7.26 (d, J = 8.4
Hz, 2H), 6.07 (ddd, J = 17.1, 9.9, 7.5 Hz), 5.02 (dd, J = 15.6, 10.2
Hz, 2H), 4.53 (d, J = 7.5 Hz, 1H), 1.25 (tt, J = 7.5, 7.2 Hz, 3H),
1.09 (d, J = 7.2 Hz, 9H), 1.03 (d, J = 7.2 Hz, 9H). 13C NMR (100
MHz, CDCl3) d = 142.8, 141.4, 131.4, 129.4, 120.6, 114.1, 46.6,
18.6, 18.5, 12.9. MS (EI+, m/z, rel. intensity): 116 (100), 384
(M+). HRMS (EI+, m/z): calcd. for C18H29BrSSi [M]+: 384.0943,
found: 384.0948. IR (KBr): nmax (cm-1) = 2941, 2865, 1631, 1483,
1462, 1397, 1074, 1009, 991, 917, 877, 840, 815, 745, 671.
1
CHCl3). H NMR (400 MHz, CDCl3): d = 7.21 (dd, J = 8.0, 8.4
Hz, 1H), 6.96–6.95 (m, 2H), 6.75 (dd, J = 8.0, 1.6 Hz, 1H), 6.11
(ddd, J = 17.2, 10.0, 7.6 Hz, 1H), 5.07 (d, J = 16.8 Hz, 1H), 5.01
(d, J = 10.0 Hz, 1H), 4.55 (d, J = 7.6 Hz, 1H), 3.80 (s, 3H), 1.25
(tt, J = 7.6, 7.2 Hz, 3H), 1.10 (d, J = 7.2 Hz, 9H) 1.05 (d, J = 7.2
Hz, 9H). 13C NMR (100 MHz, CDCl3) d = 159.6, 145.3, 141.7,
129.3, 120.0, 113.8, 113.7, 113.3, 112.4, 55.2, 47.4, 18.6, 18.5, 12.9.
MS (EI+, m/z, rel. intensity): 147 (100), 337 (M+). HRMS (EI+,
m/z): calcd. for C19H32OSSi [M+]: 336.1943, found: 336.1945. IR
(KBr): nmax (cm-1) = 2943, 2864, 2356, 2339, 1681, 1556, 1259,
915, 751, 669.
(S)-Triisopropyl(1-(4-methoxyphenyl)allylthio)silane
(4c).
(S)-Triisopropyl(1-(thiophen-2-yl)allylthio)silane
(4g). GC-
GC-MS of the crude mixture showed a 97 : 3 branched : linear
ratio. The mixture was purified by flash column chromatography
(petroleum ether : ethyl acetate = 40 : 1) to give 4c as a colorless
liquid in 72% yield. Calculated ee = 83%. [a]2D0 -153.2 (c 0.9,
MS of the crude mixture showed a 89 : 11 branched : linear
ratio. The mixture was purified by flash column chromatography
(petroleum ether : DCM = 20 : 1) to give 4g as a colorless liquid in
41% yield. Calculated ee = 85%. [a]2D0 -192.2 (c 0.1, CHCl3). H
1
1
CHCl3). H NMR (400 MHz, CDCl3) d = 7.29 (d, J = 8.4 Hz,
NMR (400 MHz, CDCl3) d = 7.18 (dd, J = 5.2, 1.2 Hz, 1H), 6.98
(d, J = 3.6 Hz, 1H), 6.91 (dd, J = 5.2, 3.6 Hz, 1H), 6.10 (ddd, J =
17.2, 10.0, 8.0 Hz, 1H), 5.11 (d, J = 17.2 Hz, 1H), 5.05 (d, J = 10.0
Hz, 1H), 4.82 (d, J = 8.0 Hz, 1H), 1.28 (tt, J = 7.6, 7.2 Hz, 3H),
1.12 (d, J = 7.2 Hz, 9H), 1.09 (d, J = 7.0 Hz, 9H). 13C NMR (100
MHz, CDCl3) d = 148.3, 141.4, 126.5, 124.7, 124.6, 113.9, 42.3,
18.6, 12.9. MS (EI+, m/z, rel. intensity): 123 (100), 313 (M+).
HRMS (EI+, m/z): calcd. for C16H28S2Si [M]+: 312.1402, found:
312.1409. IR (KBr): nmax (cm-1) = 2923, 2865, 1742, 1458, 1271,
920, 877, 698.
2H), 6.84 (d, J = 8.4 Hz, 2H), 6.11 (ddd, J = 17.2, 9.6, 7.6 Hz,
1H), 5.02 (d, J = 17.2 Hz, 1H), 4.99 (d, J = 10.0 Hz, 1H), 4.56
(d, J = 7.6 Hz, 1H), 3.79 (s, 1 H), 1.25 (tt, J = 7.6, 7.2 Hz, 3H),
1.10 (d, J = 7.2 Hz, 9 H), 1.04 (d, J = 7.6 Hz, 9H). 13C NMR (100
MHz, CDCl3) d = 158.4, 142.1, 135.9, 128.6, 113.7, 113.4, 55.2,
46.8, 18.6, 18.5, 12.9. MS (EI+, m/z, rel. intensity): 147 (100), 337
(M+). HRMS (EI+, m/z): calcd. for C19H32OSSi [M]+: 336.1943,
found: 336.1946. IR (KBr): nmax (cm-1) = 2944, 2865, 1609, 1508,
1462, 1429, 1175, 1040, 883, 825, 738, 674, 646, 591.
(S)-Triisopropyl(1-p-tolylallylthio)silane (4d). GC-MS of the
crude mixture showed a 93 : 7 branched : linear ratio. The mixture
was purified by flash column chromatography (100% petroleum
ether) to give 4d as a colorless liquid in 62% yield. Calculated ee =
82%. [a]2D0 -229.2 (c 0.5, CHCl3). 1H NMR (400 MHz, CDCl3) d =
7.25 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.12 (ddd, J =
17.2, 9.6, 7.6 Hz, 1H), 5.04 (d, J = 16.8 Hz, 1H), 4.99 (d, J = 10.0
Hz, 1H), 4.55 (d, J = 7.6 Hz, 1H), 2.31 (s, 3H), 1.26 (tt, J = 7.2,
7.2 Hz, 3 H), 1.10 (d, J = 7.2 Hz, 9 H), 1.04 (d, J = 7.2 Hz, 9H).
13C NMR (100 MHz, CDCl3) d = 142.0, 140.8, 136.4, 129.0, 127.4,
113.4, 47.1, 21.0, 18.6, 18.5, 12.9. MS (EI+, m/z, rel. intensity):
131 (100), 320 (M+). HRMS (EI+, m/z): calcd. for C19H32SSi [M]+:
320.1994, found: 320.1998. IR (KBr): nmax (cm-1) = 2944.6, 2865,
1511, 1462, 1382, 988, 920, 877, 815.
(S)-Triisopropyl(5-phenylpent-1-en-3-ylthio)silane (4h). GC-
MS of the crude mixture showed a 57 : 43 branched : linear
ratio. The mixture was purified by flash column chromatography
(petroleum ether : DCM = 20 : 1) to give 4h as a colorless liquid in
1
40% yield. Calculated ee = 89%. [a]2D0 -187.9 (c 0.4, CHCl3). H
NMR (400 MHz, CDCl3) d = 7.27 (t, J = 7.6 Hz, 2H), 7.18 (t,
J = 7.6 Hz, 3H), 5.80 (ddd, J = 17.2, 9.6, 7.6 Hz, 1H), 5.03 (dd,
J = 17.6, 9.6 Hz, 2H), 3.60 (dt, J = 8.4, 8.8 Hz, 1H), 2.73 (m, 1H),
2.63 (m, 1H), 2.00 (m, 2H), 1.19 (tt, J = 7.6, 7.2 Hz, 3H), 1.07 (d,
J = 7.2 Hz, 18H). 13C NMR (100 MHz, CDCl3) d = 142.0, 141.6,
128.5, 128.3, 125.8, 113.7, 42.8, 41.0, 33.4, 18.64, 18.60, 12.9. MS
(EI+, m/z, rel. intensity): 147 (100), 334 (M+). HRMS (EI+, m/z):
calcd. for C20H34SSi [M]+: 334.2150, found: 334.2153. IR (KBr):
nmax (cm-1) = 2945, 2865, 1462, 1071, 991, 914, 880, 745, 698.
(S)-(1-(4-Chlorophenyl)allylthio)triisopropylsilane (4e). GC-
MS of the crude mixture showed a 94 : 6 branched : linear ratio.
The mixture was purified by flash column chromatography (100%
petroleum ether) to give 4e as a colorless liquid in 69% yield.
(E)-Triisopropyl(5-phenylpent-2-enylthio)silane (5h). The mix-
ture was purified by flash column chromatography (petroleum
ether : DCM = 20 : 1) to give 5h as a colorless liquid in 30% yield.
1H NMR (400 MHz, CDCl3) d = 7.28 (t, J = 7.6 Hz, 2H), 7.18 (t,
J = 7.6 Hz, 3H), 5.60 (m, 2H), 3.15 (d, J = 6.4 Hz, 2H), 2.68 (t,
J = 7.6 Hz, 2H), 2.33 (dt, J = 6.8, 6.4 Hz, 2H) 1.26 (tt, J = 7.6, 7.2
Hz, 3H), 1.11 (d, J = 7.2 Hz, 18H). 13C NMR (100 MHz, CDCl3)
d = 141.9, 131.3, 129.2, 128.4, 128.3, 125.8, 35.7, 34.1, 27.9, 18.6,
12.7. MS (EI+, m/z, rel. intensity): 147 (100), 334 (M+). HRMS
(EI+, m/z): calcd. for C20H34SSi [M]+: 334.2150, found: 334.2151.
IR (KBr): nmax (cm-1) = 2944, 2865, 2360, 2338, 1458, 1385, 877,
674.
1
Calculated ee = 84%. [a]D20 -170.6 (c 0.7, CHCl3). H NMR (400
MHz, CDCl3) d = 7.31 (d, J = 8.8 Hz, 2H) 7.26 (d, J = 8.0 Hz,
2H), 6.08 (ddd, J = 17.2, 10.0, 7.2 Hz, 1H), 5.02 (dd, J = 16.8, 10.0
Hz, 2H), 4.55 (d, J = 7.2 Hz, 1H), 1.25 (tt, J = 7.6, 7.2 Hz, 3H),
1.10 (d, J = 7.6 Hz, 9H), 1.04 (d, J = 7.2 Hz, 9H). 13C NMR (100
MHz, CDCl3) d = 142.3, 141.5, 132.5, 129.1, 128.5, 114.1, 46.6,
18.6, 18.5, 12.9. MS (EI+, m/z, rel. intensity): 151 (100), 340 (M+).
HRMS (EI+, m/z): calcd. for C18H29ClSSi [M]+: 340.144, found:
340.1447. IR (KBr): nmax (cm-1) = 2948, 2868, 2360, 2338, 1649,
1563, 1258, 1092, 1012, 914, 880, 751, 668.
7900 | Org. Biomol. Chem., 2011, 9, 7897–7903
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
General procedure for the preparation of disulfides (6)
hexane : 2-propanol = 100 : 1, 0.7 mL min-1, l = 214 nm, t (major) =
8.727 min, t (minor) = 11.477 min, t (meso) = 15.075 min]. [a]D20
-70.5 (c 0.4, CHCl3). H NMR (400 MHz, CDCl3) d = 7.11 (d,
J = 8.0 Hz, 4H), 7.04 (d, J = 8.0 Hz, 4H), 3.17 (dd, J = 9.6, 5.2
Hz, 2H), 2.34 (s, 6H), 2.02 (dq, J = 8.0, 7.2 Hz, 2H), 1.76 (dq,
J = 7.6, 7.2 Hz, 2H), 0.77 (t, J = 7.2 Hz, 6H). 13C NMR (100
MHz, CDCl3) d = 138.1, 137.0, 129.0, 128.2, 56.6, 27.7, 21.1, 12.2.
HRMS (EI+, m/z): calcd. for C20H26S2 [M]+: 330.1476, found:
330.1472. IR (KBr): nmax (cm-1) = 2960, 2923, 2868, 1511, 1458,
1385, 1261, 1185, 1114, 1080, 815, 797, 748.
To a solution of the triisopropylsilicane sulfide 4 (0.20 mmol,
100 mol%) in THF (2 mL) and i-PrOH (2 mL) was added
o-nitrobenzenesulfonylhydrazide (0.40 mmol, 200 mol%) and
triethylamine (0.80 mmol, 400 mol%) at 30 ◦C. The reaction
was carried out overnight. After the addition the mixture was
cooled to 0 ◦C and treated with a solution of TBAF (0.40 mmol,
200 mol%) in THF (2 mL). The mixture was stirred at room
temperature for 2 h, and then partitioned between H2O (5 mL)
and DCM (5 mL), separated and the water layer was re-extracted
with DCM (3 ¥ 5 mL). The combined organic layer was dried with
anhydrous Na2SO4, concentrated and purified by flash column
chromatography to give the desired product.
1
1,2-Bis(1-(4-chlorophenyl)propyl)disulfane (6e). The mixture
was purified by flash column chromatography (100% petroleum
ether) to give 6e as a colorless liquid in 51% yield. ee = 99%,
DL : meso = 84 : 16 [CHIRALCEL OJ-H (0.46 cm ¥ 25 cm),
hexane : 2-propanol = 90 : 10, 1.0 mL min-1, l = 214 nm, t (major) =
4.597 min, t (minor) = 4.997 min, t (meso) = 5.487 min]. [a]2D0 -317.3
(c 0.3, CHCl3). 1H NMR (400 MHz, CDCl3) d = 7.27 (d, J = 8.4
Hz, 4H), 7.08 (d, J = 8.4 Hz, 4H), 3.17 (dd, J = 9.6, 5.6 Hz, 2H),
2.05 (dq, J = 7.6, 5.6 Hz, 2H), 1.78 (dq, J = 9.6, 7.2 Hz, 2H),
0.77 (t, J = 7.2 Hz, 6H). 13C NMR (100 MHz, CDCl3) d = 139.7,
133.2, 129.5, 128.5, 56.4, 27.8, 12.1. HRMS (EI+, m/z): calcd.
for C18H20Cl2S2[M]+: 370.0383, found: 370.0387. IR (KBr): nmax
(cm-1) = 2960, 2929, 2868, 1895, 1489, 1455, 1403, 1375, 1286,
1178, 1092, 1012, 911, 825, 742, 520.
1,2-Bis(1-phenylpropyl)disulfane (6a)27. The mixture was puri-
fied by flash column chromatography (100% petroleum ether) to
give 6a as a colorless liquid in 46% yield, ee = 99%, DL : meso =
88 : 12 [CHIRALCEL OJ-H (0.46 cm ¥ 25 cm), hexane : 2-
propanol = 90 : 10, 1.0 mL min-1, l = 214 nm, t (major) = 5.988
min, t (minor) = 4.702 min, t (meso) = 6.569 min]. 1H NMR (400
MHz, CDCl3) d = 7.33–7.24 (m, 6H), 7.15 (d, J = 8.4 Hz, 4H),
3.16 (dd, J = 9.6, 5.6 Hz, 2H), 2.05 (dq, J = 7.6, 5.6 Hz, 2H), 1.78
(dq, J = 9.6, 7.2 Hz, 2H), 0.77 (t, J = 7.2 Hz, 6H). 13C NMR (100
MHz, CDCl3) d = 141.2, 128.3, 127.4, 56.8, 27.7, 12.2.
1,2-Bis(1-(3-methoxyphenyl)propyl)disulfane (6b). The mix-
ture was purified by flash column chromatography (100%
petroleum ether) to give 6b as a colorless liquid in 44% yield.
ee = 96%, DL : meso = 76 : 24 [CHIRALCEL OJ-H (0.46 cm ¥ 25
cm), hexane : 2-propanol = 90 : 10, 1.0 mL min-1, l = 214 nm, t
(major) = 7.307 min, t (minor) = 7.919 min, t (meso) = 9.852 min].
[a]2D0 -87.0 (c 0.6, CHCl3). 1H NMR (400 MHz, CDCl3) d = 7.23
(dd, J = 8.0, 7.6 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 6.75 (d, J = 7.6
Hz, 2H), 6.70 (s, 2H), 3.80 (s, 6H), 3.14 (dd, J = 9.6, 5.6 Hz, 2H).
2.02 (dq, J = 7.6, 6.4 Hz, 2H), 1.77 (dq, J = 7.6, 6.8 Hz, 2H), 0.78
(t, J = 7.6 Hz, 6H). 13C NMR (100 MHz, CDCl3) d = 159.6, 142.9,
129.3, 120.6, 113.9, 112.8, 56.9, 55.1, 27.7, 12.2. HRMS (EI+,
m/z): calcd. for C20H26O2S2 [M]+: 362.1374, found: 362.1376. IR
(KBr): nmax (cm-1) = 2960, 2360, 2338, 1652, 1560, 1258, 911, 748.
1,2-Bis(1-(4-bromophenyl)propyl)disulfane (6f). The mixture
was purified by flash column chromatography (100% petroleum
ether) to give 6f as a colorless liquid in 49% yield. ee = 97%,
DL : meso = 82 : 18 [CHIRALCEL OJ-H (0.46 cm ¥ 25 cm),
hexane : 2-propanol = 98 : 2, 0.3 mL min-1, l = 214 nm, t (major) =
22.325 min, t (minor) = 26.313 min, t (meso) = 27.774 min]. [a]D20
-504.0 (c 0.2, CHCl3). 1H NMR (400 MHz, CDCl3) d = 7.44 (d,
J = 8.4 Hz, 4H), 7.01 (d, J = 8.4 Hz, 4H), 3.15 (dd, J = 6.0, 5.6
Hz, 2H), 1.99 (dq, J = 7.2, 6.4 Hz, 2H), 1.74 (dq, J = 7.6, 6.8 Hz,
2H), 0.79 (t, J = 7.6 Hz, 6H). 13C NMR (100 MHz, CDCl3) d =
140.2, 131.5, 129.9, 56.5, 27.8, 12.2. HRMS (EI+, m/z): calcd.
for C18H20Br2S2 [M]+: 457.9373, found: 457.9377. IR (KBr): nmax
(cm-1) = 3480, 2963, 1649, 1483, 1452, 1403, 1262, 1077, 1071, 803,
738, 702, 523.
1,2-Bis(1-(4-methoxyphenyl)propyl)disulfane (6c). The mix-
ture was purified by flash column chromatography (100%
petroleum ether) to give 6c as a pale yellow solid (mp: 91–97 ◦C)
in 69% yield. ee = 98%, DL : meso = 84 : 16 [CHIRALCEL OJ-H
(0.46 cm ¥ 25 cm), hexane : 2-propanol = 90 : 10, 1.0 mL min-1, l =
214 nm, t (major) = 9.512 min, t (minor) = 14.193 min, t (meso) =
1,2-Bis(1-(thiophen-2-yl)propyl)disulfane (6g). The mixture
was purified by flash column chromatography (100% petroleum
ether) to give 6g as a colorless liquid in 40% yield. ee = 97%,
DL : meso = 87 : 13 [CHIRALCEL OJ-H (0.46 cm ¥ 25 cm),
hexane : 2-propanol = 90 : 10, 1.0 mL min-1, l = 254 nm, t (major) =
8.195 min, t (minor) = 9.315 min, t (meso) = 10.938 min]. [a]2D0 -252
(c 0.25, CHCl3). 1H NMR (400 MHz, CDCl3) d = 7.25 (d, J = 5.6
Hz, 2H), 6.96 (dd, J = 4.8, 3.6 Hz, 2H), 6.90 (d, J = 3.2 Hz, 2H),
3.49 (dd, J = 5.6, 5.6 Hz, 2H), 2.09 (dq, J = 7.2, 6.4 Hz, 2H),
1.83 (dq, J = 7.2, 6.8 Hz, 2H), 0.89 (t, J = 7.2 Hz, 6H). 13C NMR
(100 MHz, CDCl3) d = 144.9, 126.6, 126.1, 124.9, 52.2, 29.2, 12.2.
HRMS (EI+, m/z): calcd. for C14H18S4 [M]+: 314.0291, found:
314.0277. IR (KBr): nmax (cm-1) = 2960, 2926, 2846, 1723, 1452,
1385, 1252, 1077, 800, 695.
1
17.431 min]. [a]2D0 -173.3 (c 0.6, CHCl3). H NMR (400 MHz,
CDCl3) d = 7.09 (d, J = 8.8 Hz, 4H), 6.84 (d, J = 8.8 Hz, 4H),
3.81 (s, 6H), 3.17 (dd, J = 9.6, 5.2 Hz, 2H), 2.03 (dq, J = 7.2, 5.6
Hz, 2H), 1.75 (dq, J = 7.2, 6.4 Hz, 2H), 0.78 (t, J = 7.6 Hz, 6H).
13C NMR (100 MHz, CDCl3) d = 159.0, 133.1, 129.3, 113.7, 56.2,
55.3, 27.7, 12.2. HRMS (EI+, m/z): calcd. for C20H26O2S2 [M]+:
362.1374, found: 362.1360. IR (KBr): nmax (cm-1) = 2963, 2929,
1726, 1609, 1511, 1458, 1385, 1302, 1246, 1172, 1117, 1034, 828,
797, 763, 732, 698.
1,2-Bis(1-phenylpentan-3-yl)disulfane (6h). The mixture was
purified by flash column chromatography (100% petroleum ether)
to give 6h as a colorless liquid in 55% yield. ee = 99%,
DL : meso = 90 : 10 [CHIRALCEL OJ-H (0.46 cm ¥ 25 cm),
hexane : 2-propanol = 100 : 1, 0.7 mL min-1, l = 214 nm, t
1,2-Bis(1-p-tolylpropyl)disulfane (6d). The mixture was puri-
fied by flash column chromatography (100% petroleum ether)
to give 6d as a white solid (mp: 67–77 ◦C) in 73% yield. ee =
95%, DL : meso = 86 : 14 [CHIRALCEL OJ-H (0.46 cm ¥ 25 cm),
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 7897–7903 | 7901
©

View Article Online
(major) = 28.718 min, t (minor) = 20.552 min, t (meso) = 23.817
Notes and references
1
min]. [a]2D0 -129.7 (c 0.35, CHCl3). H NMR (400 MHz, CDCl3)
1 (a) M. Ueda and J. F. Hartwig, Org. Lett., 2010, 12, 92–94; (b) Q. Xu,
W. Liu, L. Dai and S. You, J. Org. Chem., 2010, 75, 4615–4618; (c) Q.
Xu, L. Dai and S. You, Org. Lett., 2010, 12, 800–803; (d) S. Zheng, N.
Gao, W. Liu, D. Liu, X. Zhao and T. Cohen, Org. Lett., 2010, 12, 4454–
4457; (e) N. Gao, S. Zheng, W. Yang and X. Zhao, Org. Lett., 2011, 13,
1514–1516; (f) S. Zheng, W. Huang, N. Gao, R. Cui, M. Zhang and X.
Zhao, Chem. Commun., 2011, 47, 6969–6971.
2 (a) A. Alexakis and D. Polet, Org. Lett., 2004, 6, 3529–3532; (b) T.
Graening and J. F. Hartwig, J. Am. Chem. Soc., 2005, 127, 17192–
17193; (c) D. J. Weix and J. F. Hartwig, J. Am. Chem. Soc., 2007, 129,
7720–7721; (d) G. Helmchen, A. Dahnz, P. Du¨bon, M. Schelwies and
R. Weihofen, Chem. Commun., 2007, 675–691; (e) H. He, X. Zheng, Y.
Li, L. Dai and S. You, Org. Lett., 2007, 9, 4339–4341; (f) G. Onodera,
K. Watabe, M. Matsubara, K. Oda, S. Kezuka and R. Takeuchi, Adv.
Synth. Catal., 2008, 350, 2725–2732; (g) H. He, W. Liu, L. Dai and
S. You, J. Am. Chem. Soc., 2009, 131, 8346–8347; (h) S. Spiess, J. A.
Raskatov, C. Gnamm, K. Broner and G. Helmchen, Chem.–Eur. J.,
2009, 15, 11087–11090; (i) A. Alexakis, S. Hajjaji, E. D. Polet and X.
Rathgeb, Org. Lett., 2007, 9, 3393–3395; (j) X. Gao, Y. J. Zhang and
M. J. Krische, Angew. Chem., Int. Ed., 2011, 50, 4173–4175.
3 (a) T. Ohmura and J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 15164–
15165; (b) K. Tissot-Croset, D. Polet and A. Alexakis, Angew. Chem.,
Int. Ed., 2004, 43, 2426–2428; (c) C. Welter, A. Dahnz, B. Brunner, S.
Streiff, P. Dubon and G. Helmchen, Org. Lett., 2005, 7, 1239–1242;
(d) M. J. Pouy, A. Leitner, D. J. Weix, S. Ueno and J. F. Hartwig, Org.
Lett., 2007, 9, 3949–3952; (e) H. He, W. Liu, L. Dai and S. You, Angew.
Chem., 2010, 122, 1538–1541, (Angew. Chem. Int. Ed.,, 2010, 49, 1496–
1499); (f) J. Xia, W. Liu, T. Wang and S. You, Chem.–Eur. J., 2010,
16, 6442–6446; (g) M. Roggen and E. M. Carreira, J. Am. Chem. Soc.,
2010, 132, 11917–11919; (h) J. F. Teichert, M. Fan˜ana´s-Mastral and B.
L. Feringa, Angew. Chem., Int. Ed., 2011, 50, 688–691.
4 (a) C. T. Shu and J. F. Hartwig, Angew. Chem., Int. Ed., 2004, 43, 4794–
4797; (b) I. Lyothier, C. Defieber and E. M. Carreira, Angew. Chem.,
Int. Ed., 2006, 45, 6204–6207; (c) S. Ueno and J. F. Hartwig, Angew.
Chem., Int. Ed., 2008, 47, 1928–1931; (d) M. Ga¨rtner, S. Mader, K.
Seehafer and G. Helmchen, J. Am. Chem. Soc., 2011, 133, 2072–2075;
(e) C. Fischer, C. Defieber, T. Suzuki and E. M. Carreira, J. Am. Chem.
Soc., 2004, 126, 1628–1629.
d = 7.27 (dd, J = 7.6, 6.8 Hz, 4H), 7.18 (dd, J = 6.8, 6.4 Hz, 6H),
2.74 (dd, J = 8.0, 7.2 Hz, 4H), 2.59 (tt, J = 6.8, 6.4 Hz, 2H), 1.92 (dt,
J = 7.2, 6.8 Hz), 1.68 (dq, J = 7.2, 6.8 Hz, 4H), 0.97 (t, J = 7.2 Hz,
6H). 13C NMR (100 MHz, CDCl3) d = 141.8, 128.4, 128.4, 125.9,
53.2, 35.3, 33.0, 26.9, 11.1. HRMS (EI+, m/z): calcd for C22H30S2
[M]+: 358.1789, Found: 358.1791. IR (KBr): nmax (cm-1) = 2951,
2363, 2338, 1557, 1523, 1268, 917, 745, 702.
Synthesis of (S)-1-phenylpropane-1-thiol (7a)
To a solution of the triisopropylsilane sulfide 4a (77 mg, 0.25
mmol) in THF (2 mL) and i-PrOH (2 mL) were added o-
nitrobenzenesulfonylhydrazide (109 mg, 0.50 mmol) and triethy-
lamine (101 mg, 1.00 mmol) at 30 ◦C. The reaction was carried
out overnight with TLC-followed. After the addition the mixture
was quenched by sat. NaHCO3 and extracted by hexane (3 ¥ 5
mL). The organic layer was washed by sat. NaCl (aq.), dried
by Na2SO4 and then concentrated. Under Ar atmosphere, the
crude product was dissolved in HCl/Et2O (4.5 M, 5 mL) with
anhydrous AlCl3 (200 mg, 1.5 mmol). The mixture was stirred
overnight, and then partitioned between H2O (5 mL) and Et2O
(5 mL), separated and the water layer was re-extracted with
Et2O (3 ¥ 5 mL). The combined organic layer was dried with
anhydrous Na2SO4, concentrated and purified by flash column
chromatography (petroleum ether) to give 7a (26 mg, 68% yield).
[a]2D0 -86 (c 0.1, CHCl3). 1H NMR (400 MHz, CDCl3) d = 7.32 (d,
J = 4.0 Hz, 4H), 7.23 (t, J = 4.4 Hz, 1H), 3.89 (dt, J = 5.6, 7.2 Hz,
1H), 1.97 (dq, J = 7.2, 7.6 Hz, 2H), 1.91(d, J = 5.2 Hz, 1H), 0.93 (t,
J = 7.6 Hz, 3H). MS (EI+, m/z, rel. intensity): 119 (100), 152 (M+).
5 (a) L. L. Hegedus and R. W. McCabe, Catalyst Poisoning, Marcel
Dekker, New York, 1984; (b) A. T. Hutton, In Comprehensive Coordi-
nation Chemistry; G. Wilkinson, R. D. Gillard and J. A. McCleverty,
ed., Pergamon, Oxford, U.K, 1984, Vol. 5, p 1151.
6 (a) For an excellent review, see: J. Clayden and P. MacLellan, Beilstein
J. Org. Chem., 2011, 7, 582–595; (b) A. Peschiulli, B. Procuranti,
C. J. O’Connor and S. J. Connon, Nat. Chem., 2010, 2, 380–384;
(c) C. Chatgilialoglu and K. D. Asmus, Sulfur-Centered Reactive
Intermediates in Chemistry and Biology, Springer, 1991; (d) A. Thuillier
and P. Metzner, Sulfur Reagents in Organic Synthesis, Academic Press,
1994.
7 (a) P. MacLellan and J. Clayden, Chem. Commun., 2011, 47, 3395–
3397; (b) R. T. Dere, Y. Wang and X. Zhu, Org. Biomol. Chem., 2008,
6, 2061–2063; (c) S. Nakamura, A. Furutani and T. Toru, Eur. J. Org.
Chem., 2002, 10, 1690–1695; (d) J. C. J. de Pomar and J. A. Soderquist,
Tetrahedron Lett., 1998, 39, 4409–4411; (e) E. I. Miranda, M. J. Diaz, I.
Rosado and J. A. Soderquist, Tetrahedron Lett., 1994, 35, 3221–3224;
(f) B. Strijtveen and R. M. Kellogg, J. Org. Chem., 1986, 51, 3664–3671.
8 Y. A. Lin, J. M. Chalker, N. Floyd, G. J. L. Bernardes and B. G. Davis,
J. Am. Chem. Soc., 2008, 130, 9642–9643.
9 (a) For an excellent review, see: M. Reggelin, Top. Curr. Chem., 2007,
275, 1–65; (b) A. Itoh, S. Ozawa, K. Oshima, S. Sasaki, H. Yamamoto,
T. Hiyama and H. Nozaki, Bull. Chem. Soc. Jpn., 1980, 53, 2357–2362;
(c) T. Cohen and Z. J. Kosarych, J. Org. Chem., 1982, 47, 4005–4007.
This example of 1,3-chirality transfer was not included in the Reggelin
review.
Acetylation of (S)-1-phenylpropane-1-thiol (7a)
To a solution of (S)-1-phenylpropane-1-thiol 7a (26 mg, 0.17
mmol) in DCM (3 mL), acetyl chloride (0.1 mL) and triethylamine
(0.1 mL) were added. The mixture was stirred at room temperature
for 1h. After the addition the mixture was quenched by water, and
separated. The water layer was re-extracted by DCM (2 mL ¥
3). The organic layer was combined, washed with saturated NaCl
(aq.) and then dried by anhydrous Na2SO4. Concentrated and the
residue was treated by flash column chromatography (petroleum
ether : DCM = 3 : 1) to give 8a6a,23 (32 mg, 99% yield) with 87% ee
[CHIRALCEL OD-H (0.46 cm ¥ 25 cm), hexane : 2-propanol =
100 : 1, 0.5 mL min-1, l = 214 nm, t (major) = 10.214 min, t
(minor) = 13.580 min]. [a]2D0 -260 (c 0.2, CHCl3). H NMR (400
MHz, CDCl3) d = 7.27–7.31 (m, 4H), 7.25–7.23 (m, 1H), 4.49 (t,
J = 7.6 Hz, 1H), 2.30 (s, 3H), 1.96 (dq, J = 7.6, 7.2 Hz, 2H), 0.91 (t,
J = 7.2 Hz, 3H). MS (EI+, m/z, rel. intensity): 119 (100), 194 (M+).
1
Acknowledgements
10 (a) Y. Gareau, M. Tremblay, D. Gauvreau and H. Juteau, Tetrahedron,
2001, 57, 5739–5750; (b) S. Bjoern and T. Andreas, Org. Biomol. Chem.,
2010, 8, 3552–3562.
11 (a) J. Gong, X. Shen, L. Yao, H. Jiang, K. Krohn and Y. Guo, Org.
Lett., 2007, 9, 1715–1716; (b) T. J. Greshock, D. M. Johns, Y. Noguchi
and R. M. Willians, Org. Lett., 2008, 10, 613–616; (c) N. A. Calandra,
Y. Cheng, K. A. Kocak and J. S. Miller, Org. Lett., 2009, 11, 1971–1974.
12 (a) Y. Chen, C. Gambs, Y. Abe, J. P. Wentworth and K. D. Janda, J.
Org. Chem., 2003, 68, 8902–8905; (b) S. Jiang, P. Li, S. Lee, C. Lin,
We gratefully acknowledge the Pu Jiang Program of Shanghai
(2010–2013), the Innovative Program of Shanghai Education
Committee (09ZZ36), the NSFC (20942003), the Jiao Gai Pro-
gram of the Department of Chemistry in Tongji University
(2009–2011) and the State Key Laboratory of Fine Chemicals,
Dalian University of Technology (KF1006) for generous financial
support.
7902 | Org. Biomol. Chem., 2011, 9, 7897–7903
This journal is
The Royal Society of Chemistry 2011
©

View Article Online
Y. Long, M. D. Johnson, R. B. Dickson and P. P. Roller, Org. Lett.,
2007, 9, 9–12; (c) L. Wang and D. L. J. Clive, Org. Lett., 2011, 13,
1734–1737; (d) S. Choh, D. Cross and C. Wang, Biomacromolecules,
2011, 12, 1126–1136.
SS)/RS = 88/12 (DL/meso of 6a); R = 187.12; S = 12.88; ee% of 4a = (R
- S)/(R + S) = 87%. Other branched products 4b–4h were calculated
according to the same method as well.
20 A. G. Myers, B. Zheng and M. Movassaghi, J. Org. Chem., 1997, 62,
13 T. Waag, C. Gelhaus, J. Rath, A. Stich, M. Leippe and T. Schirmeister,
Bioorg. Med. Chem. Lett., 2010, 20, 5541–5543.
14 (a) Y. Inada, Y. Nishibayashi and S. Uemura, Angew. Chem., Int. Ed.,
2005, 44, 7715–7717; (b) H. Matsuzawa, K. Kanao, Y. Miyake and Y.
Nishibayashi, Org. Lett., 2007, 9, 5561–5564.
15 K. Tissot-Croset, D. Polet, S. Gille, C. Hawner and A. Alexakis,
Synthesis, 2004, 2586–2590.
16 L. A. Arnold, R. Imbos, A. Mandoli, A. H. M. de Vries, R. Naasz and
B. L. Feringa, Tetrahedron, 2000, 56, 2865–2878.
7507–7507.
21 The chiral disulfide derivatives were prepared from the corresponding
chiral alcohols, which was made by Ti-catalyzed enantioselective
addition of ZnEt2 to aldehyde, in four steps with low yields, see: ref. 14.
22 D. J. Cram, R. C. Helgeson, S. C. Peacock, L. J. Kaplan, L. A. Domeier,
P. Moreau, K. Koga, J. M. Mayer, Y. Chao, M. G. Siegel, D. H. Hoffman
and G. D. Y. Sogah, J. Org. Chem., 1978, 43, 1930–1946.
23 A. Alexakis, S. Rosset, J. Allamand, S. March, F. Guillen and C.
Benhaim, Synlett, 2001, 9, 1375–1378.
17 Triisopropylsilanethiol (TIPS-SH) as a nucleophile was successfully
used in the palladium-catalyzed coupling reaction, see: (a) M. Kreis and
S. Bra¨se, Adv. Synth. Catal., 2005, 347, 313–319; (b) M. A. Ferna´ndez-
Rodr´ıguez and J. F. Hartwig, Chem.–Eur. J., 2010, 16, 2355–2359.
18 For the preparation of NaSSiiPr3, see: (a) I. Kova´cs, F. Be´langer-
Garie´py and A. Shaver, Inorg. Chem., 2003, 42, 2988–2991; (b) E. I.
Miranda, M. J. Diaz, I. Rosado and J. A. Soderquist, Tetrahedron
Lett., 1994, 35, 3221–3224.
24 (a) P. V. Matt and A. Pfaltz, Angew. Chem., Int. Ed. Engl., 1993, 32,
566–568; (b) J. Sprinz and G. Helmchen, Tetrahedron Lett., 1995, 34,
1769–1772.
25 The enantio-enriched thiol 7a has been prepared by the kinetic
resolution of the corresponding racemic thiol through chiral thioacetal
in two steps with low yield, see: C. R. Noe, M. Knollmueller, I.
Ziebarth-Schroth and M. Letschnig, Liebigs Annalen, 1996, 6, 1009–
1013.
19 The ee value of 4a can not be directly determined by a chiral HPLC
and was calculated on the basis of both ee and DL/meso of 6a by the
following equations: (RR - SS)/(RR + SS) = 99% ee of 6a; (RR +
26 The ee value of 7a was determined by a chiral HPLC analysis of a
derivative 8a made from 7a, for details, see: Experimental section.
27 F. Asinger and K. Halcour, Monatsh. Chem., 1963, 94, 1047–1053.
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 7897–7903 | 7903
©