A general and efficient method for the synthesis of silyl-protected arenethiols from aryl halides or triflates

Article abstract of DOI:10.1002/adsc.200404299

An improved palladium-catalyzed synthesis of silyl-protected arenethiols has been developed. This method is particularly useful because of its experimental simplicity, high generality and high level of functional group toleration. The first synthesis of enantiomerically pure [2.2]paracyclophane-4- thiol was realized employing this method.

Full text of DOI:10.1002/adsc.200404299

UPDATES
A General and Efficient Method for the Synthesis of
Silyl-Protected Arenethiols from Aryl Halides or Triflates
Michael Kreis, Stefan Brꢀse*
Institut fꢁr Organische Chemie, Universitꢀt Karlsruhe (TH), Fritz-Haber Weg 6, 76131 Karlsruhe, Germany
Fax: (þ49)-721-608-8581, e-mail: braese@ioc.uka.de
Received: September 29, 2004; Accepted: December 10, 2004
Abstract: An improved palladium-catalyzed syn-
thesis of silyl-protected arenethiols has been devel-
oped. This method is particularly useful because of
its experimental simplicity, high generality and high
level of functional group toleration. The first syn-
thesis of enantiomerically pure [2.2]paracy-
clophane-4-thiol was realized employing this meth-
od.
Results and Discussion
4-Bromoanisole and triisopropylsilanethiol were used
as the prototypical substrate combination for the opti-
mization of the reaction conditions. Various bases
were tested. Separate syntheses of NaSTIPS or KSTIPS
from TIPSSH and sodium or potassium hydride and uti-
lization of these substrate bases in the reaction gave
good yields in some cases. However, these results were
difficult to reproduce because traces of KH or NaH dis-
turbed the reaction up to a total inhibition. Cs2CO3 gave
superior results in yield, reproducibility, and reagent
handling. With limitations, both t-BuOK and t-BuONa
were efficient bases for the reaction. However, we chose
Cs2CO3 because of the milder reaction conditions and
greater range of functional group tolerance. The corre-
Keywords: arenethiols; cross-coupling reaction;
[2.2]paracyclophanes; palladium; protecting groups
Introduction
Arenethiols are important intermediates in chemical sponding alkali metal carbonates gave inferior results
synthesis. While there are numerous reactions to intro- up to a total halt of the reaction employing Li2CO3 as
duce this functionality[1] starting from aryl halides[2] or base. Toluene was the solvent of choice, yielding results
phenols,[3] most of these transformations require drastic superior to DME and THF. Pd(PPh3)4 was used as cata-
reaction conditions and tolerate few if any functionali- lyst in loadings from 0.5 to 15 mol %, resulting in
ties. Despite the fact that in the last few years the effi- 5 mol % as being optimal for the reaction. Experiments
ciency of palladium-catalyzed cross-coupling reactions with a combination of Pd(OAc)2 and PPh3 instead of
for the preparation of aryl ethers and aniline derivatives Pd(PPh3)4 gave the same results. Because of the much
has improved greatly,[4] analogous methods for the for- lower costs, we chose the combination Pd(OAc)2 and
mation of aryl sulfides[5] and especially arenethiols PPh3 instead of Pd(PPh3)4 in our later experiments. Be-
have lagged behind.[6] The first report of a mild palladi- sides triisopropylsilanethiol, tert-butyldimethylsilane-
um-catalyzed synthesis of arenethiols came from Soder- thiol (TBDMSSH) and potassium trimethylsilanethio-
quist et al.[7] followed by reports from a Zeneca Pharma late[10] (TMSSK) were screened as reagents. While
group[8] and a Merck group.[9]
TBDMSSH showed good results, comparable to those
The major disadvantage of the former procedures is of TIPSSH, the utilization of TMSSK resulted in low
the synthesis of potassium or sodium triisopropylsilane- yields with numerous by-products. Since TIPSSH is
thiolate (MSTIPS, M¼Na or K) from triisopropylsila- commercially available, we preferred it to TBDMSSH.
nethiol (TIPSSH) and sodium or potassium hydride pri-
Thus, the optimized reaction conditions utilized
or to the reaction. These silanethiolates are difficult to 5 mol % Pd(OAc)2, 22 mol % PPh3, Cs2CO3 (1.3
utilize, because they are highly sensitive towards mois- equivs.) and triisopropylsilanethiol (1.3 equivs.) in dry
ture. Furthermore we found that potassium hydride in- and degassed toluene at 1008C under an argon atmos-
hibits the cross-coupling reaction when not fully re- phere.[14] In the first part of this study we applied the re-
moved. We herein report an improved one-pot cross- action conditions to a variety of aryl bromides as shown
coupling procedure for the synthesis of triisopropylsil- in Table 1. The results prove that the process is extreme-
yl-protected arenethiols starting from aryl bromides, ly tolerant towards a variety of common functional
aryl iodides, and aryl triflates.
groups. Aryl bromides containing ether, amino, nitrile,
aldehyde or ester groups, or aromatics derived from pyr-
idine, thiophene or [2.2]paracyclophane are all well con-
verted into the corresponding protected thiols. A de-
Adv. Synth. Catal. 2005, 47, 313–319
DOI: 10.1002/adsc.200404299
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Michael Kreis, Stefan Brꢀse
UPDATES
Table 1. Pd-catalyzed carbon-sulfur bond formation of aryl
crease in conversion is observed for 2-bromoanisole (en-
try 8) as starting material. This decrease in reactivity can
only be attributed to a steric hindrance caused by the oc-
cupation of the ortho position, rather than the electronic
characteristics of the starting material. Both electron-
rich starting materials, such as (4-bromophenyl)-dime-
thylamine (entries 3 and 4), 2-bromothiophene (en-
try 12) and 4-bromo[2.2]paracyclophane (entry 9), as
well as electron-deficient starting materials, like 2-bro-
mopyridine (entry 2) and 4-bromobenzoic acid ethyl es-
ter (entry 7), gave excellent conversion under the reac-
tion conditions.
bromides.[a]
Entry ArBr
1[d],[9]
Product
Conversion[b] Yield[c]
quant.
66%
The decrease of the isolated yield compared to the
conversion is due to the lability of the sulfur-silicon
bond.[15] Under the non-polar chromatography condi-
tions used here, silica gel becomes nucleophilic and
2[11]
98%
86%
3
quant.
quant.
99%
65%
91%
43%
80%
ꢀ
therefore cleaves the Si S bond under formation of an
ꢀ
Si O bond with the silica gel. Electron-deficient prod-
ucts like (2-triisopropylsilanylsulfanyl)-pyridine and
triisopropyl-(3-nitrophenylsulfanyl)-silane are com-
pletely deprotected to the corresponding 1H-pyridine-
2-thione (entry 2) and 3-nitrobenzenethiol (entry 11)
during flash chromatography. The deprotected products
of the other reactions were obtained as by-products over
a wide range of fractions, which points towards a slower
deprotection along the column. Further evidence that
the decrease in the yields is only due to work-up prob-
lems is the excellent yield of dimethyl-(4-methylsulfan-
yl-phenyl)-amine (91%, entry 4), which was synthesized
from (4-bromo-phenyl)-dimethylamine according to
the general protocol followed by treatment of the crude
product with tetrabutylammonium fluoride (TBAF)
and MeI in THF. The overall yield of these two subse-
quent reactions is higher than the yield of the cross-cou-
pling alone (65%, entry 3), which proves the effective-
ness of the general protocol.
4[e],[12]
5
6
quant.
7[8]
quant.
66%
8
9
70%
99%
33%
71%
The reaction with 2-bromoacetophenone gave an un-
expected result, leading directly to (benzo[b]thiophen-
3-yloxy)-triisopropylsilane (entry 10). This provides an
easy and elegant route for the synthesis of benzo[b]thio-
phen-3-ones.[16] The method reported herein should en-
able us to synthesize benzo[b]thiophen-3-ones contain-
ing base-labile and electrophilic groups like esters, alde-
hydes and nitriles. Further investigations of this reaction
are in progress.
10
98%
60%
11[13]
12
quant.
88%
76%
60%
After having studied the cross-coupling reaction with
aryl bromides, we applied the general protocol to aryl io-
dides. Like aryl bromides, aryl iodides are also excellent
ꢀ
substrates for the C S bond formation, even exceeding
the results of aryl bromides (Table 2).
[a]
Reaction conditions: ArBr (1.0 equiv.), TIPSSH (1.3
We chose 4-iodoanisole as substrate to optimize the
reaction conditions (entry 1). 2-Iodoanisole was tested
(entry 2) because the results with 2-bromoanisole were
quite disappointing leading to only 70% conversion
and 33% yield (entry 7, Table 1). 2-Iodoanisole (entry 2,
Table 2) greatly surpassed this result, giving full conver-
sion and a satisfying yield of 62%, hinting that iodides
equivs.), Cs2CO3 (1.3 equivs.), Pd(OAc)2 (5 mol %), PPh3
(22 mol %) in toluene at 1008C under argon.
MS.
[b]
By GC-
[c]
[d]
Isolated yield.
The reaction was easily up scale-
able, giving still full conversion in
a 10-mmol scale.
[e]
Crude product of the cross-coupling reaction was dis-
solved in THF with TBAF (2 equivs.) and MeI (2 equivs.)
and stirred for 2 h at room temperature.
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Silyl-Protected Arenethiols from Aryl Halides or Triflates
UPDATES
Table 2. Pd-catalyzed carbon-sulfur bond formation of aryl iodides.[a]
Entry
1
ArI
Product
Conversion[b]
quant.
Yield[c]
86%
2
3
4
quant.
95%
62%
69%
quant.
quant.
90%
97%
5[d]
[a]
Reaction conditions: ArI (1.0 equiv.), TIPSSH (1.3 equivs.), Cs2CO3 (1.3 equivs.), Pd(OAc)2 (5 mol %), PPh3 (22 mol %)
in toluene at 1008C under argon.
By GC-MS.
[b]
[c]
[d]
Isolated yield.
Synthesized according to ref.[17]
are better substrates than bromides. Even when applied was not fully converted after 8 h. However, it is impor-
to more complex substrates like the tricyclic carbamate tant to note that catalyst loading showed non-uniform
(entry 3)[17] or 4-iodo[2.2]paracyclophane (entry 4), we results. While 4-bromoanisole still showed full conver-
achieved full conversion and good to excellent yields sion at a catalyst loading of 2 mol % compared to only
(69–90%). 2-Iodobenzoic acid methyl ester was tested 90% for 4-iodoanisole, the results for 0.5 mol % catalyst
as an electron-deficient substrate with steric hindrance were reversed, showing 59% conversion for bromoani-
and a possibly labile ester group. To our delight we ach- sole and 70% for iodoanisole.
ieved full conversion and an excellent yield (97%),
With these results we compared the reactivity of bro-
which further underpins that both electron-deficient as mide to iodide in the same molecule (Scheme 1). Anal-
well as electron-rich aryl halides are excellent substrates ysis by GC-MS showed that we were able to selectively
for the reaction.
form a carbon-sulfur bond from the iodide, leaving the
Following these results, we compared aryl bromides bromide untouched. With excess of TIPSSH, base and
and iodides under the same conditions. We chose 4-bro- catalyst, a disubstitution of bromide and iodide was ach-
moanisole and 4-iodoanisole as a testing system for the ieved.
temperature and catalyst loading dependence and for
Finally, we applied the general protocol to aryl tri-
the kinetics of the reaction. While 4-iodoanisole still flates. They, too, were excellent substrates for the palla-
showed full conversion at 708C and a reaction time of dium catalyzed cross-coupling reaction (Table 3).
16 h, 4-bromoanisole only gave 77% conversion under
Again, we chose 4-trifluoromethanesulfonic acid 4-
these conditions. The differences were eminentconcern- methoxyphenyl ester as substrate to optimize the reac-
ing the reaction speed. While 4-iodoanisole showed full tion conditions (entry 1). With both electron-deficient
conversion after only 2 h at 1008C, 4-bromoanisole still (entry 2) and electron-rich 4-substituted aryl triflates
Adv. Synth. Catal. 2005, 47, 313–319
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315

Michael Kreis, Stefan Brꢀse
UPDATES
interesting as a starting material (entry 5), because we
were able to synthesize both enantiomers in high enan-
tiomeric purity.
For the synthesis of enantiomerically pure trifluoro-
methanesulfonic acid (4-[2.2]paracyclophane) ester we
started from racemic 4-acetoxy-[2.2]paracyclophane[20]
and applied the literature known enzymatic resolution
with Candida cylindracea lipase (CCL).[21] (Sp)-4-Hy-
droxy-[2.2]paracyclophane was obtained in 40% yield
and 90% ee. The remaining (Rp)-acetoxy[2.2]paracyclo-
phane was obtained in 42% yield with an enantiomeric
excess of >99%. Hydrolysis to the phenol proceeded
in quantitative yield and without any racemization.
The resulting enantiomerically pure phenols were then
Scheme 1. Chemoselectivity of aryl bromides and iodides.
(entry 3) we achieved high conversion and good yields converted to the corresponding triflates in excellent
(81–90%). (S)-Trifluoromethanesulfonic acid 2-(iso- yields (97%) by treatment with sodium hydride followed
propyliminomethyl)-phenyl ester (entry 4) was chosen by the addition of triflate anhydride. Cross-coupling of
as a substrate, because the resulting arenethiol, is a po- the triflate employing the general protocol gave enan-
tential catalyst ligand for the 1,4-addition to a,b-unsatu- tiomerically pure (R)-4-triisopropylsilanylsulfuryl[2.2]-
rated ketones, showing structural similarities to the sys- paracyclophane in good yields (59%). Deprotection
tems of van Koten[18] and Pfaltz.[19] Trifluoromethanesul- with TBAF in THF to yield (R)-[2.2]paracyclophane-
fonic acid (4-[2.2]paracyclophane) ester was especially 4-thiol proceeded quantitatively. This represents the
Table 3. Pd-catalyzed carbon-sulfur bond formation of aryl triflates.[a]
Entry
1
ArOTf
Product
Conversion[b]
75%
Yield[c]
57%
2
3
quant.
96%
90%d
81%
4
94%
82%
79%
5
59% for (R), 62% for (rac)
{a}
Reaction conditions: ArOTf (1.0 equiv.), TIPSSH (1.3 equivs.), Cs2CO3 (1.3 equivs.), Pd(OAc)2 (5 mol %), PPh3
(22 mol %) in toluene at 1008C under argon.
By GC-MS.
Isolated yield.
[b]
[c]
[d]
Yield of protected (56%) and unprotected (34%) thiol combined.
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Silyl-Protected Arenethiols from Aryl Halides or Triflates
UPDATES
fluoromethanesulfonic acid (4-[2.2]paracyclophane) ester;
yield: 74 mg (97%).
first synthesis of enantiomerically pure [2.2]paracy-
clophane-4-thiol which, up until now, could only be syn-
thesized as a racemate.[22]
The racemate was prepared accordingly. Rf ¼0.10 (cyclo-
1
293
hexane); [a] : þ18.078 (c 1.0, CHCl3); H NMR (250 MHz,
589
CDCl3): d¼6.93 (dd, J¼7.9 Hz, 1.6 Hz, 1H), 6.65–6.55 (m,
3H), 6.53–6.51 (m, 1H), 6.50 (dd, J¼4.1 Hz, 1.9 Hz, 1H),
6.48 (d, J¼1.9 Hz, 1H), 3.44 (ddd, J¼13.7 Hz, 9.7 Hz, 3.6 Hz,
1H), 3.25–2.97 (m, 6H); 2.83 (ddd, J¼13.8 Hz, 9.7 Hz,
6.4 Hz, 1 H); 13C NMR (62.5 MHz, CDCl3) d¼148.0, 142.9,
139.3139.1, 136.0, 133.5, 132.5, 132.3, 131.9, 129.4, 127.7, 118.5
(q, J¼320.8 Hz, 1C), 35.1, 34.6, 34.0, 31.5; 19F NMR
(376.5 MHz, CDCl3) d¼ ꢀ74.9 (s, 3F); FT-IR (neat): n¼
3016, 2929, 2859, 1605, 1415, 1210, 975, 885 cmꢀ1; MS: m/z
(rel. int. %)¼356 (13), 223 (17), 104 (100); HR-MS: m/z calcu-
lated for C17H15SO3F3: 356.0694; found: 356.0692.
Conclusion
In summary, we have developed a general and efficient
palladium-catalyzed carbon-sulfur bond formation pro-
tocol for aryl bromides, iodides, and triflates. This meth-
od is particularly noteworthy given its experimental sim-
plicity, high generality, and high level of functional
group toleration. Therefore, it represents a convenient
route from phenols to arenethiols via the corresponding
triflates. Additionally, we herein report the first syn-
thesis of enantiomerically pure [2.2]paracyclophane-4-
thiol, providing the starting point for a new generation
of sulfur-containing [2.2]paracyclophane ligands which
can be used in asymmetric catalysis.[23]
General Procedure for the Cross-Coupling Reaction
A
sealable tube was charged with Pd(OAc)2 (5.6 mg,
0.025 mmol), PPh3 (29 mg, 0.11 mmol) Cs2CO3 (212 mg,
0.65 mmol) and aryl halide or aryl triflate (0.50 mmol) and
was sealed afterwards. The sealed tube was evacuated and re-
filled with argon. This procedure was repeated three times.
Dry toluene (5 mL) and triisopropylsilanethiol (124 mg,
0.65 mmol) were added subsequently via syringe. The solution
turned deep red and was warmed to 1008C for 16 h. After cool-
ing to room temperature, 5 mL of aqueous NH4Cl were added.
The reaction contents were transferred to a separatory funnel
and extracted twice with diethyl ether. The collected organic
layers were dried with Na2SO4, filtered, and concentrated un-
der vacuum. The crude product was purified by flash chroma-
tography (cyclohexane/ethylene glycol dimethyl ether, 20:1)
to yield triisopropylsilyl arenethiol. Deprotection to the corre-
sponding arenethiols was achieved by stirring in THF with
TBAF at room temperature for 2 hours.
Experimental Section
General Remarks
All catalysis reactions were performed in 10-mL vials under an
argon atmosphere. Substrates were purchased from commer-
cial sources and were used without further purification. Enan-
tiomeric excesses were determined by GC on a chiral station-
ary phase (CP-Chirasil-Dex). GC-MS was measured on a HP
5890 Series II GC with an HP 5972 MS. 1H and 13C NMR spec-
tra were recorded on Bruker AC300 (250 MHz/67 MHz),
Bruker AM400 (400 MHz/100 MHz) or Bruker DRX500
(500 MHz/125 MHz), using CDCl3 as the solvent and shift ref-
erence (CHCl3 7.26 ppm/77.00 ppm). The mass spectra were
recorded on a Finnigan MAT 90. Elemental analyses were
measured on a Heraeus CHN-O-Rapid. The IR spectra were
recorded on a Bruker IFS 88. Optical rotations were deter-
mined on a Perkin Elmer 241 polarimeter (Na, 589 nm). Sol-
vents were purified according to standard procedures.
Dimethyl-(4-triisopropylsilanylsulfanyl-phenyl)-amine
(Table 1, entry 3): yield: 65%; Rf ¼0.11 (cyclohexane/ethylene
1
glycol dimethyl ether, 100:1); H NMR (500 MHz, CDCl3):
d¼7.32 (d, J¼8.2 Hz, 2H), 6.59 (d, J¼8.2 Hz, 2H), 2.92 (s,
6H), 1.22 (sept, J¼7.5 Hz, 3H), 1.08 (d, J¼7.5 Hz, 18H); 13C
NMR: d¼149.5, 136.2, 115.8, 112.9, 40.5, 18.5, 12.9; FT-IR
(neat): n¼2944, 2866, 1596, 1503, 1352, 1193, 882, 812 cmꢀ1
;
MS: m/z (rel. int. %)¼309 (100), 266 (95), 224 (19), 148 (23),
105 (19); HR-MS: m/z calculated for C17H31NSSi: 309.1947;
found: 309.1945.
(R)-Trifluoromethanesulfonic Acid (4-[2.2]Paracyclo-
phane) Ester (Table 3, entry 4, starting material)
4-Triisopropylsilanylsulfanyl-benzonitrile (Table 1, en-
try 5): yield: 43%; Rf ¼0.27 (cyclohexane/ethylene glycol di-
methyl ether, 50:1); 1H NMR (250 MHz, CDCl3): d¼7.57 (d,
J¼8.5 Hz, 1H), 7.48 (d, J¼8.5 Hz, 1H), 1.4–1.2 (m, 3 H),
1.08 (d, J¼6.7 Hz, 18H); 13C NMR (62.5 MHz, CDCl3): d¼
140.1, 135.5, 131.9, 118.7, 110.1, 18.4, 13.2; FT-IR (neat): n¼
3065, 2948, 2228, 1591, 1485, 1086, 1018, 884, 676 cmꢀ1; MS:
m/z (rel. int. %)¼291 (28), 248 (100), 220 (19), 206 (27), 178
(44), 135 (29); HR-MS: m/z calculated for C16H25NSSi:
291.1477; found: 291.1473.
2-Methoxy-5-triisopropylsilanylsulfanyl-benzaldehyde
(Table 1, entry 6): yield: 80%; Rf ¼0.45 (cyclohexane/ethylene
glycol dimethyl ether, 20/1); 1H NMR (250 MHz, CDCl3): d¼
10.38 (s, 1H), 7.91 (d, J¼2.3 Hz, 1H), 7.63 (dd, J¼8.6 Hz,
2.3 Hz, 1H), 6.86 (d, J¼8.6 Hz, 1H), 3.90 (s, 3H), 1.30–1.11
(m, 3H), 1.06 (d, J¼6.4 Hz, 18H); 13C NMR (62.5 MHz,
A 50-mL Schlenk-flask was flame-dried under a stream of ar-
gon and allowed to cool to room temperature. It was charged
with enantiomerically pure (R)-4-hydroxy-[2.2]paracy-
clophane (50 mg, 0.223 mmol) and dry toluene (30 ml). Miner-
al oil-free NaH (24 mg, 1.00 mmol) was added carefully under
a stream of argon. The reaction mixture was cooled to 08C and
trifluoromethanesulfonic acid (189 mg, 0.669 mmol) was add-
ed slowly. The mixture was stirred for another 10 min at 08C
and was then warmed to room temperature and stirred for
24 h. Saturated aqueous NH4Cl and diethyl ether were added
and the mixture was transferred into a separatory funnel and
the organic layer was washed with brine. The collected organic
layers were dried with Na2SO4, filtered, and concentrated un-
der vacuum. The crude product was purified by flash chroma-
tography (cyclohexane) to afford as a colourless oil (R)-tri-
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Michael Kreis, Stefan Brꢀse
UPDATES
CDCl3): d¼189.0, 160.8, 142.5, 135.0, 124.8, 123.0, 112.1, 55.7,
18.4, 12.9; FT-IR (neat): n¼2945, 2867, 1678, 1588, 1480, 1244,
1021, 883, 826, 644 cmꢀ1; MS: m/z (rel. int. %)¼324 (54), 281
(100), 239 (27), 181 (23), 167 (20); HR-MS: m/z calculated
for C17H28SO2Si: 324.1579; found: 324.1581; anal. calcd. C
62.91, H 8.70; found: C 62.86, H 8.25.
Triisopropyl-(2-methoxyphenylsulfanyl)-silane (Table 1,
entry 8 and Table 2 entry 2): yield: 62%; Rf ¼0.51 (cyclohex-
ane/ethylene glycol dimethyl ether, 20/1); 1H NMR
(250 MHz, CDCl3): d¼7.35 (dd, J¼7.9 Hz, 1.5 Hz, 1H), 7.06
(ddd, J¼7.8 Hz, 7.8 Hz, 1.5 Hz, 1H), 6.79–6.69 (m, 2H), 3.78
(s, 3H), 1.3–1.1 (m, 3H), 0.93 (d, J¼7.0 Hz, 18H); 13C NMR
(62.5 MHz, CDCl3): d¼137.5, 133.8, 133.5, 128.4, 120.5,
110.7, 55.4, 18.3, 13.3; FT-IR (neat): n¼3060, 2945, 2866,
1581, 1478, 1246, 1066, 1028, 882, 750, 673 cmꢀ1; MS: m/z
(rel. int. %)¼296 (2), 262 (11), 253 (51), 238 (20), 183 (50),
167 (58), 77 (60), 43 (100); HR-MS: m/z calculated for
C16H28SOSi: 296.1630; found: 296.1634.
n¼2945, 2866, 1471, 1009, 816, 671 cmꢀ1; MS: m/z (rel.
int.)¼346 (34), 344 (32), 303 (100), 301 (88), 261 (25), 259
(25), 233 (22), 231 (22); HRMS: m/z calculated for C15H25
BrSSi: 344.0630; found: 344.0627.
(S)-Isopropyl-(2-triisopropylsilanylsulfanylbenzylidene)-
293
amine (Table 3, entry 4): yield: 79% yield; >98% ee; [a]
:
589
ꢀ318 (c 1.0, CHCl3); Rf ¼0.38 (cyclohexane/ethylene glycol di-
methyl ether/triethylamine, 60:3:1); 1H NMR (400 MHz,
CDCl3): d¼8.00 (dd, J¼7.3 Hz, 2.2 Hz, 1H), 7.42 (dd, J¼
7.2 Hz, 1.8 Hz, 1H) 7.4–7.1 (m, 7 H), 4.55 (q, J¼6.6 Hz, 1
H), 1.53 (d, J¼6.6 Hz, 3H), 1.2–1.0 (m, 3H), 0.96 (d, J¼
7.4 Hz, 9H), 0.95 (d, J¼7.4 Hz, 9H); 13C NMR (100 MHz,
CDCl3): d¼159.5, 136.8, 133.8, 133.6, 130.1, 128.7, 128.5,
128.3, 127,3. 126.7, 126.6, 69.8, 24.7, 18.3, 13.3; FT-IR (neat):
n¼2944, 2866, 1633, 1462, 882, 758, 698, 673 cmꢀ1, MS: m/z
(rel. int. %)¼397 (1), 354 (4), 250 (12), 105 (49), 43 (100);
HRMS: m/z calculated for C24H35NSSi: 397.2259; found:
397.2255.
(R)-(4-Triisopropylsilanylsulfanyl)-[2.2]paracyclophane
(Benzo[b]thiophen-3-yloxy)-triisopropylsilane
(Table 1,
293
entry 10): yield: 60%; Rf ¼0.53 (cyclohexane); 1H NMR
(250 MHz, CDCl3): d¼7.85–7.79 (m, 1H), 7.78–7.71 (m,
1H), 7.43–7.30 (m, 2H), 6.42 (s, 1H), 1.46–1.29 (m, 3H), 1.16
(d, J¼7.0 Hz, 18H); 13C NMR (62.5 MHz, CDCl3) d¼146.8,
137.2, 134.1, 124.7, 123.6, 122.9, 121.1, 102.3, 17.9, 12.6; FT-IR
(neat): n¼2945, 2867, 1568, 1524, 1463, 1431, 1357, 1180, 881,
727 cmꢀ1; MS: m/z (rel. int. %)¼306 (100), 263 (97), 235
(28), 207 (21); HR-MS: m/z calculated for C17H26OSSi:
306.1474; found: 306.1476; anal. calcd. C 66.61, H 8.55; found:
C 66.74, H 8.30.
(Table 3, entry 5): yield: 90%; ee, [a] : ꢀ368 (c 1.0, CHCl3);
589
Rf ¼0.64 (cyclohexane/ethylene glycol dimethyl ether, 20:1);
1H NMR (500 MHz, CDCl3): d¼7.06 (dd, J¼7.8 Hz, 1.6 Hz,
1H), 6.55–6.50 (m, 2H), 6.48 (dd, J¼8.8 Hz, 1.9 Hz, 1H),
6.45 (dd, J¼8.2 Hz, 1.6 Hz, 1H), 6.42 (d, J¼1.6 Hz, 1H), 6.41
(d, J¼7.8 Hz, 1H), 3.80 (ddd, J¼12.9 Hz, 10.4 Hz, 2.5 Hz,
1H), 3.25 (ddd, J¼13.1 Hz, 10.3 Hz, 5.9 Hz, 1H), 3.2–3.0 (m,
4H), 2.94–2.85 (m, 1H), 2.78 (ddd, J¼13.0 Hz, 10.4 Hz,
5.9 Hz, 1H), 1.20–1.05 (m, 3H), 1.03 (d, J¼6.90 Hz, 9H),
0.97 (d, J¼7.2 Hz, 9H); 13C NMR (62 MHz, CDCl3): d¼
144.0, 142.2, 139.7, 139.3, 139.0, 134.3, 132.9, 132.6, 132.3,
131.4, 131.4, 129.1, 35.5, 35.4, 34.8, 34.0, 18.3, 18.2, 13.0; FT-
Triisopropyl-(thiophen-2-ylsulfanyl)-silane (Table 1, en-
try 12): yield: 60%; Rf ¼0.77 (cyclohexane/ethylene glycol di-
methyl ether, 20/1); 1H NMR (250 MHz, CDCl3): d¼7.19
(dd, J¼5.4 Hz, 1.2 Hz, 1H), 7.04 (dd, J¼3.5 Hz, 1.2 Hz), 6.90
(dd, J¼5.4 Hz, 3.5 Hz, 1H), 1.3–1.15 (m, 3H), 1.10 (d, J
IR (neat): n¼2945, 1892,1586, 1499, 1018, 884, 720 cmꢀ1
;
MS: m/z (rel. int. %)¼396 (3), 288 (14), 286 (14), 262 (24),
104 (100); HR-MS: m/z calculated for C25H36SSi: 396.2307;
found: 396.2303.
6.9 Hz, 18H); 13C NMR (62.5 MHz, CDCl3): d¼133.91,
¼
(R)-[2.2]Paracyclophane-4-thiol (Table 3, entry 4): 59%
129.25, 127.53, 127.3, 18.36, 12.90; FT-IR (neat): n¼2945,
2867, 1462, 1406, 1215, 985, 882, 692 cmꢀ1; MS: m/z (rel. int.
%) ¼272 (100), 229 (60), 187 (23), 159 (26), 157 (58), 115
(45); HRMS: m/z calculated for C13H24S2Si: 272.1089; found:
272.1093.
yield. >98% ee, [a] : þ7.28 (c 1.0, CHCl3); 1H NMR
293
589
(250 MHz, CDCl3): d¼7.21 (dd, J¼7.9 Hz, 1.8 Hz, 1H), 6.57
(dd, J¼7.63 Hz, 1.83 Hz, 1H), 6.5–6.3 (m, 4H), 6.21 (d, J¼
1.6 Hz, 1H), 3.5–2.7 (m, 8H). This compound yielded spectral
data consistent with literature reports for the racemate, see, for
example: Hopf et al.[22]
7-Triisopropylsilanylsulfanyl-3,3a,4,5-tetrahydro-oxazo-
lo[3,4-a]quinolin-1-one (Table 2, entry 3): yield: 69%; Rf ¼
0.02 (cyclohexane/dichloromethane, 1:1); 1H NMR
(500 MHz, CDCl3): d¼8.11 (d, J¼8.7 Hz, 1H), 7.33 (dd, J¼
8.6 Hz, 2.1 Hz, 1H), 7.28 (d, J¼2.1 Hz, 1H), 4.59 (dd, J¼
8.5 Hz, 8.4 Hz, 1H), 4.18 (dddd, J¼11.8 Hz, 8.6 Hz, 8.4 Hz,
2.8 Hz, 1H), 4.04 (dd, J¼8.6 Hz, 8.5 Hz, 1H), 2.97–2.86 (m,
2H), 2.19 (dddd, J¼12.6 Hz, 12.2 Hz, 11.8 Hz, 5.7 Hz, 1H),
1.82 (dddd, J¼12.6 Hz, 12.2 Hz, 11.8 Hz, 5.7 Hz, 1H), 1.24
(sept, J¼7.5 Hz, 3H), 1.09 (d, J¼7.5 Hz, 9H), 1.08 (d, J¼
7.5 Hz, 9H); 13C NMR (125 MHz, CDCl3): d¼154.2, 135.9,
134.1, 133.7, 125.4, 125.0, 118.2, 67.4, 54.4, 26.4, 26.3, 18.4,
12.9; FT-IR (neat): n¼2944, 2867, 1740, 1487, 1395, 1323,
1218, 1036, 882, 829, 752, 652 cmꢀ1; MS: m/z (rel. int. %)¼
377 (84), 334 (100), 290 (52), 262 (58), 220 (84); HR-MS: m/z
calculated for C20H31NSiO2S: 377.1845; found: 377.1849; anal.
calcd. N 3.71, C 63.61, H 8.27; found: N 3.55, C 63.25, H 7.86.
(4-Bromophenylsulfanyl)-triisopropylsilane (3): 52% yield.
Rf ¼0.82 (cyclohexane/ethylene glycol dimethyl ether, 20:1);
1H NMR (250 MHz, CDCl3) d¼7.5–7.3 (m, 4 H), 1.3–1.15
(m, 3 H), 1.07 (d, J¼6.7 Hz, 18 H); 13C NMR (62.5 MHz,
CDCl3) d¼136.9, 132.2, 131.6, 120.9, 18.4, 13.0; FT-IR (neat):
Acknowledgements
We thank the research student Alexander Tung-Quiang Wong
for his helpful assistance. We thank Pia Lang for recording the
NMR spectra.
References and Notes
[1] For reviews, see: a) J. L. Wardell, The Chemistry of the
Thiol Group, Vol. 1, Wiley, London, 1974, p. 163;
b) G. C. Barrett, Thiols, in: Comprehensive Organic
Chemistry, Vol. 3, (Eds.: D. Barton, W. D. Ollis), Perga-
mon Press, Oxford, 1979, p. 3; c) K.-D. Gundermann,
K. Hꢁmke, in: Houben-Weyl, Vol. E 11/1, (Ed.: D. Kla-
mann), Thieme, Stuttgart, 1985, p. 32; d) T. Kondo, T.-
A. Mitsudo, Chem. Rev. 2000, 100, 3205; e) K. Kunz, U.
318
ꢂ 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2005, 47, 313–319

Silyl-Protected Arenethiols from Aryl Halides or Triflates
UPDATES
Scholz, D. Ganzer, Synlett 2003, 2428; f) S. V. Ley, A. W.
Thomas, Angew. Chem. Int. Ed. 2003, 42, 5400.
[2] a) L. Testaferri, M. Tingoli, M. Tiecco, Tetrahedron Lett.
1980, 21, 3099; b) M. S. Sorokin, M. G. Voronkov, Zh.
Obshch. Khim. 2001, 71, 1988; c) L. Testaferri, M. Tiecco,
M. Tingoli, D. Chianelli, M. Montanucci, Synthesis 1983,
751.
[3] a) M. S. Newman, H. A. Karnes, J. Org. Chem. 1966, 31,
3980; b) S. Cossu, O. De Lucchi, D. Fabbri, G. Valle, G. F.
Painter, R. A. J. Smith, Tetrahedron 1997, 53, 6073; c) G.
Delogu, D. Fabbri, M. A. Dettori, Tetrahedron: Asymme-
try 1998, 9, 2819; d) H. M. Relles, G. Pizzolato, J. Org.
Chem. 1968, 33, 2249.
[10] Synthesized according to the literature: L.-L. Lai, P.-Y.
Lin, W.-H. Huang, M.-J. Shiao, J. R. Hwu, Tetrahedron
Lett. 1994, 35, 3545.
[11] P. K. Baker, M. E. Harman, S. Hughes, M. B. Hurst-
house, K. M. A. Malik, J. Organomet. Chem. 1995, 498,
257.
[12] P. F. Ranken, B. G. McKinnie, J. Org. Chem. 1989, 54,
170.
[13] S. Oae, H. Togo, Tetrahedron Lett. 1982, 23, 4701.
[14] Control experiments under air reduced the yield drasti-
cally and resulted in the oxidative coupling product, di-
sulfide (TIPSS-STIPS), as the major product.
[15] J. Feixas, A. Capdevilla, F. Camps, A. Guerrero, J. Chem.
Soc. Chem. Commun. 1992, 1451.
[4] For reviews, see: a) A. R. Muci, S. L. Buchwald, Top.
Curr. Chem. 2002, 219, 131; b) J. F. Hartwig, Angew.
Chem. Int. Ed. 1998, 37, 2046.
[16] For an alternative synthesis see, for example: C. Mukher-
jee, S. Kamila, A. De, Tetrahedron 2003, 59, 4767.
[17] F. J. Baerlocher, M. O. Baerlocher, R. F. Langler, S. L.
MacQuarrie, M. E. Marchand, Aust. J. Chem. 2000, 53, 1.
[18] a) M. van Klaveren, E. S. M. Persson, A. del Villar,
D. M. Grove, J.-E. Bꢀckvall, G. van Koten, Tetrahedron
Lett. 1995, 36, 3059; b) A. M. Arink, T. W. Braam, R.
Keeris, J. T. B. H. Jastrzebski, C. Benhaim, S. Rosset,
A. Alexakis, G. van Koten, Org. Lett. 2004, 1959.
[19] Q.-L. Zhou, A. Pfaltz, Tetrahedron Lett. 1993, 34, 7725.
[20] Synthesized according to the literature, see: a) D. J.
Cram, A. C. Day, J. Org. Chem. 1966, 31, 1227; b) H. J.
Reich, D. J. Cram, J. Am. Chem. Soc. 1969, 91, 1077.
[21] a) A. Cipiciani, F. Fringuelli, V. Mancini, O. Piermatti,
A. M. Scrappini, R. Ruzziconi, Tetrahedron 1997, 53,
11853; b) D. Pamperin, C. Schulz, H. Hopf, C. Syldatk,
M. Pietzsch, Eur. J. Org. Chem. 1998, 1441.
[22] V. V. Kane, A. Gerdes, W. Grahn, L. Ernst, I. Dix, P. G.
Jones, H. Hopf, Tetrahedron Lett. 2001, 42, 373.
[23] a) S. E. Gibson, J. D. Knight, Org. Biomol. Chem. 2003,
1, 1256; b) P. J. Pye, K. Rossen, R. A. Reamer, N. N.
Tsou, R. P. Volante, P. J. Reider, J. Am. Chem. Soc. 1997,
119, 6207; c) S. Dahmen, S. Brꢀse, J. Am. Chem. Soc.
2002, 124, 5940; d) S. Hçfener, F. Lauterwasser, S. Brꢀse,
Adv. Synth. Catal. 2004, 346, 755; for an account, see:
e) S. Brꢀse, S. Dahmen, S. Hçfener, F. Lauterwasser,
M. Kreis, R. E. Ziegert, Synlett 2004, 2647.
[5] a) N. Zheng, J. C. McWilliams, F. J. Fleitz, J. D. Arm-
strong, R. P. Volante, J. Org. Chem. 1998, 63, 9606;
b) P. S. Herradura, K. A. Pendola, R. K. Guy, Org. Lett.
2001, 3, 2019; c) G. Y. Li, Angew. Chem. Int. Ed. 2001,
40, 1513; d) G. Y. Li, G. Zheng, A. F. Noonan, J. Org.
Chem. 2001, 66, 8677; e) G. Y. Li, J. Org. Chem. 2001,
66, 3643; f) U. Schopfer, A. Schlapbach, Tetrahedron
2001, 57, 2069; g) L. Wang, Z.-C. Chen, Synth. Commun.
2001, 31, 1227; h) C. G. Bates, R. K. Gujadhur, D. Venka-
taraman, Org. Lett. 2002, 4, 2803. i) F. Y. Kwong, S. L.
Buchwald, Org. Lett. 2002, 4, 3517; j) J. C. McWilliams,
F. J. Fleitz, N. Zheng, Org. Synth. 2002, 79, 43; k) D.
Prim, J.-M. Campagne, D. Joseph, B. Andrioletti, Tetra-
hedron 2002, 58, 2041; l) C. Savarin, J. Srogl, L. S. Liebe-
skind, Org. Lett. 2002, 4, 4309; m) T. Itoh, T. Mase, Org.
Lett. 2004, 6, 4587; n) N. Taniguchi, J. Org. Chem. 2004,
69, 6904.
[6] For review, see: J. F. Hartwig, Handbook of Organopalla-
dium Chemistry for Organic Synthesis, Vol. 1, (Ed. E.-I.
Negishi), Wiley-Interscience, Hoboken, 2002, p. 1097.
[7] A. M. Rane, E. I. Miranda, J. A. Soderquist, Tetrahedron
Lett. 1994, 35, 3225.
[8] J. C. Arnould, M. Didelot, C. Cadilhac, M. J. Pasquet,
Tetrahedron Lett. 1996, 37, 4523.
´
[9] Y. Gareau, J. Pellicelli, S. Laliberte, D. Gauvreau, Tetra-
hedron Lett. 2003, 44, 7821.
Adv. Synth. Catal. 2005, 47, 313–319
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