Elaboration of a Lewis acid-free protocol for the alkylation of silicon-containing π-donors by β-arylthioalkyl chlorides

Article abstract of DOI:10.1016/j.tet.2010.01.045

Hexafluoroisopropanol (HFIP) was found to be a powerful electrophilic activator of covalent reagents. Due to this effect the title reaction was shown to proceed under mild conditions in the absence of any Lewis acid catalysts to give the respective products of C-alkylation in good to excellent yields.

Full text of DOI:10.1016/j.tet.2010.01.045

Tetrahedron 66 (2010) 1832–1836
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Elaboration of a Lewis acid-free protocol for the alkylation of silicon-containing
p
-donors by b-arylthioalkyl chlorides
,
b
b
Maxim O. Ratnikov a , Vasily V. Tumanov , William A. Smit
*
a Department of Chemistry and Biochemistry, 0107 Chemistry Building, University of Maryland, College Park, MD 20742, USA
b N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp., 47, Moscow 119991, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Hexafluoroisopropanol (HFIP) was found to be a powerful electrophilic activator of covalent reagents.
Due to this effect the title reaction was shown to proceed under mild conditions in the absence of any
Lewis acid catalysts to give the respective products of C-alkylation in good to excellent yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 23 November 2009
Received in revised form 21 December 2009
Accepted 8 January 2010
Available online 18 January 2010
Keywords:
Electrophilic addition
Trifluoroethanol
Hexafluoroisopropanol
Hydrogen bonds
1. Introduction
2. Results and discussion
Polyfluorinated alcohols such as trifluoroethanol (TFE) and
hexafluoroisopropanol (HFIP) are known as solvents with a unique
set of properties.1 Due to the presence of electron withdrawing
trifluoromethyl group(s) these compounds exhibit the properties of
highly polar solvents2 with extremely high ionizing power,3 very
low nucleophilicity,4 and the ability to serve as powerful hydrogen-
bond donors toward both neutral and charged nucleophiles.5
These properties of TFE and HFIP allowed their successful ap-
plications as the media to perform such transformations as sol-
volysis,6 nucleophilic opening of oxiranes,7 intramolecular
electrophilic addition to C]C bonds,8 and aromatic electrophilic
substitution4a,9 in the absence of any other activating agents. Re-
cently we have shown that HFIP could be employed as a medium
and an activator for a number of classical C–C bond forming
reactions of carbonyl compounds and their acetals such as Hosomi–
Sakurai acetal allylation, Mykaiyama aldol reaction, and Sakurai–
Mukaiyama conjugate additions that could be carried out in this
solvent without any catalysts under rather mild conditions.10 Here
we present the results of our preceding studies, which had been
aimed at the elaboration of this novel electrophile activation
methodology.
As the case study we have chosen
b-arylthioalkylation of various
p
-donors with a number of -arylthioalkyl chlorides, the reaction
b
that had been thoroughly investigated previously in our group and
was shown to proceed efficiently in the presence of various Lewis
acid catalysts (Scheme 1).11
SiMe3
Y
Y
Y = O or CH2
ArS
ArS
Cl
Lewis acid
-Arylthioalkylation of
Scheme 1.
b
p-donors; general scheme.
b
-Arylthioalkyl chlorides 6–10, which were employed as the
electrophilic components in this study, were prepared in situ in
quantitative yields via the standard AdE reaction of an arylsulfenyl
chloride with the respective alkenes 1–5 (Table 1, for the details see
Ref. 11).
Alkene substrates were selected to represent different classes of
electron rich carbon–carbon double bonds while the aryl moiety of
sulfide (p-chlorophenyl) was chosen on the basis of its minimal
steric demands and intermediate electron withdrawing strength.
The choice of covalent
p-donors was made to demonstrate
different substitution pattern within a range of several orders of
* Corresponding author. Tel.: þ1 301 405 6136; fax: þ1 301 314 9121.
E-mail address: moratn@umd.edu (M.O. Ratnikov).
nucleophilicity magnitude according to Mayr’s scale (Fig. 1).12
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.045

M.O. Ratnikov et al. / Tetrahedron 66 (2010) 1832–1836
1833
Table 1
Preparation of
formed as a major product, albeit the formation of 16 was not totally
suppressed. It was also observed that the order of the reagent
mixing might critically affect the reaction outcome. The best yield
was obtained if TFE was added the last to the solution of 7 and 11 in
CH2Cl2. The reverse order, namely first dissolving 7 in TFE/CH2Cl2
(4:1) and then (after 5–7 min) adding of 11 to this solution resulted
in a nearly complete formation of the solvoadduct 16.
b
-arylthioalkyl chlorides
ArSCl a
ArS
DCM, -20oC
Cl
Alkene
Adduct
Alkene
Adduct
Cl
Cl
The above results attested to the viability of the suggested ap-
4
OMe
1
ArS
9
ArS
6
OMe
proach toward the electrophilic activation of the covalent
b-
arylthioalkyl chlorides and encouraged further development. The
next logical step was a replacement of TFE with less nucleophilic
HFIP.13 This modification turned out to be essential in our efforts to
tweak the reaction toward an exclusive formation of the alkylation
products. In fact, it was discovered that in HFIP/CH2Cl2 medium
SAr
Cl
5
2
Ph
10
ArS
7
Ph
Cl
O
O
Cl
3
ArS
8
Ph
Ph
interaction of b-arylthioalkyl chlorides 7–10 with the carbon nu-
cleophiles 11–14 proceeds smoothly and gives the target products
18–23 in good to excellent yields (see Table 2).
[a] Ar¼p-ClC6H4.
Table 2
b
-Arylthioalkylation in HFIP
OSiMe3
OSiMe3
OMe
OSiMe3
SiMe3
SiMe3
14, N = 1.79
Y
Y
(1.2 equiv.)
11, N = 9.00
12, N = 5.41
13, N = 3.94
ArS
Cl
ArS
HFIP/DCM (4:1),
RT, 5 min.
Figure 1. Carbon nucleophiles employed.
Initially, a reaction between the adduct 6 and the most reactive
nucleophile 11 (in ratio 1:2) was studied in TFE solution at room
temperature. The first results turned out to be rather discouraging
due to an almost instantaneous formation of solvolysis product 15
according to TLC analysis (Scheme 2, Eq. 1). The latter adduct did
not undergo any changes upon the storage of the reaction mixture
overnight at this temperature even if an additional 5 equiv of 11
were added. The product 15 was shown to be unstable during
chromatographic purification but its identity was fully confirmed
by 1H NMR data.
Electrophile
Nucleophile
Product
Yield
88%
O
Ph
7
12
14
ArS
18
Ph
7
8
93%
72%
ArS
19
O
Ph
11
ArS
OMe
O
20
Ph
TFE
RT, 10 min
ArS
ArS
ArS
ArS
(1)
(2)
+
O
CF3
CF3
6
+
+
11
OMe
OMe
15
8
9
9
9
58%
81%
ArS
ArS
Ph
21
Ph
O
TFE
RT, 10 min
O
+
OMe
7
11
17
16
22
7/11
Conditions
16/17
SAr
1 : 2
TFE, RT, 5 min
TFE, RT, 5 min
90 : 10
59 : 32
35 : 62
10
13
62%a
O
O
1 : 10
1 : 10
23
TFE/CH2Cl2,
RT, 5 min
a
In this case the reaction was carried out at 0 ꢁC; otherwise an extensive de-
composition was observed.
Scheme 2.
b-Arylthioalkylation in TFE.
The general reaction procedure involves an in situ preparation of
the electrophiles 7–10 in CH2Cl2 at ꢀ20 ꢁC, followed by the addition
of 1.2 equiv of nucleophilic components 11–14, and introduction of
HFIP at ambient temperature. According to the TLC data, the re-
action is complete within 5 min. Subsequent removal of the solvent
and volatile by-products as a rule is sufficient for the isolation of the
products as individual compounds.
Remarkably, no detectable amounts of solvoadducts were
formed under the above conditions. Moreover, no substantial sol-
volysis of the starting chloroadducts occurred upon their storage
for several hours at room temperature in the absence of an external
nucleophile.
To facilitate the formation of the desired C–C coupling product,
the electrophilic component was changed to the styrene adduct 7
that might form a substantially more stable benzylic cationic in-
termediate and thus should be more prone to react with carbon
nucleophiles. Here again the formation of solvoadduct 16 was ob-
served but at the same time the 1H NMR analysis of the reaction
mixture indicated the presence of some amount (ca. 10%) of the
desired product 17 (Scheme 2, Eq. 2). The yield of the latter could be
increased up to 32% if the reactionwas performed with the use of the
substantial excess of the nucleophile 11 (up to 10 equiv). Since it was
observed that the mixture of 7 and 11 is only partially soluble in TFE
the next runwas carried out in the mixed TFE/CH2Cl2 (4:1) solvent to
ensure homogeneity. Under these conditions the compound 17 was
At the same time, the solvolysis could be easily achieved upon
the addition of equimolar amounts of 2,6-di-tert-butyl-4-

1834
M.O. Ratnikov et al. / Tetrahedron 66 (2010) 1832–1836
methylpyridine (DTBMP) to the above solution as exemplified by
the conversion of 7 into the respective HFIP-derivative 24 (Scheme
force for the formation of the polar transition state 29 additionally
stabilized by the efficient solvation of the chloride anion by the
solvent molecules.17,18 In other words the medium effect of HFIP
could be explained in terms of the electrophilic solvent assistance
in a way similar to the one employed for the interpretation of
solvolytic data of tertiary butyl derivatives (see, for example, data
in Ref. 19).
3). The latter was shown to be totally unreactive toward
philes even upon reflux in HFIP solution.
p-nucleo-
Ph
Cl
DTBMP
RT, 5 min
O
Hfip
ArS
+
ArS
Hfip
O
H
Ph
24, 89%
7
Hfip = (CF3)2CH
Scheme 3. Preparation of the solvoadduct.
3. Conclusion
In conclusion, we have developed a novel method of
b-arylth-
The set of the precursors shown in Table 2 includes the major
structural types of the compounds that have most commonly been
used in the similar transformations conventionally carried out in
the presence of the stoichiometric amounts of various LA.11 Con-
sequently, we may conclude that the above results clearly indicate
the generality of the suggested Lewis acid-free protocol as a con-
ioalkylation of silyl-containing -donors with the readily available
p
covalent electrophiles in the absence of Lewis acids. The essential
role of HFIP as the sole promoter of the reaction was established.
The elaborated procedure allows preparation of the respective
products of C-alkylation in good to excellent yields while avoiding
the utilization of costly and/or toxic heavy metal catalysts. This
study served as a prologue for the further investigation which
revealed the generality of the observed electrophilic activation ef-
fects for a number of other types of Friedel–Crafts alkylations.10
venient and mild procedure in order to perform
b-arylth-
ioalkylation of various
p
-donors.14
The applicability of developed procedure was also tested for the
reaction involving dicobalthexacarbonyl (DCHC) complexes of the
conjugated enynes as the carbon nucleophile in
(see Scheme 4). The presented example demonstrates the oppor-
tunity to perform the acid-free -arylthioalkylation of the alkenes
b-arylthioalkylation
4. Experimental
b
4.1. General information
like 25 that are substantially less nucleophilic than above-shown Si-
capped derivatives.12 In line with the previous evidence11 we sug-
gested that the interaction of 7 with 25 resulted in the initial for-
mation of the cationoid intermediate 26 that should be sufficiently
stable in the solution and could be trapped by external nucleophiles
to give the products of 1,2-addition across the double bond of the
starting substrate 25. It was found that methanol is especially effi-
cient as such a quencher as is shown by the formation of the adduct
27.15 However, the attempts to employ at this step carbon nucleo-
philes (NuC) such as 2-silyloxypropene 12 faileddno reaction oc-
curred at 0 ꢁC and a complete decomposition was observed during
the storage at room temperature.
All experiments were carried out under dry argon using anhy-
drous solvents purified using the standard methods. TLC analysis
was carried out on plates with silica. Column chromatography was
performed using silica gel (220–240 mesh ASTM). Chemical shifts
are reported in parts per million as follows: chemical shift (d),
multiplicity (s¼singlet, d¼doublet, m¼multiplet, etc.), coupling
constant (J, in Hertz), and integration.
p-Chlorobenzene sulfenyl chloride was prepared as described
previously.20 Silyl ketene acetal 1121 and silyl ethers 12,1322 were
prepared using the described methods. Other reagents were used
as received from commercial sources unless otherwise noted.
Co2(CO)6
Co2(CO)6
4.2. Preparation of methyl 2,2-dimethyl-3-phenyl-4-[4-
Co2(CO)6
MeOH
Ph
Ph
25
chlorophenylthio]-butanoate (17) and
a-[2,2,2-trifluoro-
7
ArS
ArS
+
HFIP/DCM (4:1),
0oC, 10 min
ethoxy]- -[4-chlorophenylthio]-ethylbenzene (16)
b
Cl
26
OMe
27, 60%
Method A: biphasic reaction in TFE. A solution of styrene (104 mg,
1.0 mmol) in a dry dichloromethane (2.0 ml) was cooled to ꢀ20 ꢁC
and 4-chlorobenzenesulfenyl chloride (179 mg, 1.0 mmol) was
added. The reaction was stirred for 5 min at ꢀ20 ꢁC and was
warmed to room temperature. The solvent was rapidly evaporated
under reduced pressure. Silyl ketene acetal 11 (1.74 g, 10.0 mmol)
followed by TFE (2.0 ml) were added to the colorless residue. After
15 min the reaction mixture was evaporated on a rotary evaporator.
The residue was dissolved in a small volume of hexane. After pu-
rification with column chromatography (hexane/ethyl acetate,
10:1) a colorless oil of C-adduct 17 (112 mg, 32%) and a colorless oil
of solvoadduct 16 (205 mg, 59%) were obtained.
Method B: monophasic reaction in TFE/DCM (4:1) mixture. A so-
lution of 4-chlorobenzenesulfenyl chloride (90 mg, 0.50 mmol) in
a dry dichloromethane (0.50 ml) was cooled to ꢀ20 ꢁC and styrene
(52 mg, 0.50 mmol) was added. The reaction was stirred for 5 min
at ꢀ20 ꢁC and was warmed to room temperature. Silyl ketene acetal
11 (870 mg, 5.0 mmol) followed by TFE (2.0 ml) was added to the
resulting mixture. After 1 h the reaction mixture was evaporated on
a rotary evaporator. The residue was dissolved in a small volume of
hexane. After purification with column chromatography (hexane/
ethyl acetate, 10:1) a colorless oil of C-adduct 17 (108 mg, 62%) and
a colorless oil of solvoadduct 16 (63 mg, 35%) were obtained.
Compound 17: Rf¼0.34 in hexane/ethyl acetate (10:1).
Scheme 4.
b-Arylthioalkylation of DCHC complex.
We propose that the observed unusual activity pattern of HFIP
is mostly due to its exceptionally high ionizing power2,3 coupled
with its low nucleophilicity4 and extraordinary capacity to form
strong hydrogen bonds with various hydrogen-bond acceptors.5,6a
These unique properties might not only facilitate the trans-
formation of the starting covalent chloride16 into a polarized in-
termediate complex 28 (Scheme 5) thus enhancing the
electrophilicity of the former but also provide an efficient driving
S
Ar
Cl
Hfip-OH
(Hfip-OH)
+
n
δ+
δ-
S
S
Ar
Cl
S
NuC
Ar
Nu
Cl
Ar
Nu
H
O
Hfip
H
28
Hfip
O
29
Scheme 5. A plausible mechanism.

M.O. Ratnikov et al. / Tetrahedron 66 (2010) 1832–1836
1835
1H NMR (CDCl3, 500 MHz): 1.06 and 1.17 (both s, 3H each), 3.22
(m, 2H), 3.30 (m, 1H), 3.63 (s, 3H), 7.12 (d, J¼7.3, 2H), 7.17 and 7.22
(both d, J¼8.2, 2H each), 7.29 (m, 3H).
Anal. Calcd for C18H19ClS: C, 71.38; H, 6.32; found: C, 71.05;
H, 6.14.
13C NMR (CDCl3, 125 MHz): 20.8, 25.0, 35.7, 46.6, 51.9, 52.3,
127.3, 128.0, 128.9, 129.6, 131.1, 132.1, 134.9, 138.4, 177.3.
Anal. Calcd for C19H21ClO2S: C, 65.41; H, 6.07; found: C, 65.24;
H, 6.39.
4.3.5. 4-Methoxy-5-[4-chlorophenylthio]-pentene-1 (22). Yield 81%;
Rf¼0.42 in hexane/ethyl acetate (10:1).
1H NMR (CDCl3, 500 MHz): 1.09 (s, 3H), 1.11 (s, 3H), 1.60 (m, 3H),
2.15 (m, 1H), 2.88 (m, 1H), 3.35 (m, 1H), 3.46 (d, J¼10.4, 1H), 3.96
(m, 1H), 7.25 (m, 4H) 9.63 (s, 1H).
Compound 16: Rf¼0.38 in hexane/ethyl acetate (10:1).
1H NMR (CDCl3, 500 MHz): 3.15 (dd, J1¼13.7, J2¼7.4, 1H), 3.37
(dd, J1¼13.7, J2¼5.5, 1H), 3.65 and 3.72 (both m, 1H each), 4.54 (dd,
J1¼7.4, J2¼5.5, 1H), 7.22–7.40 (m, 9H).
13C NMR (CDCl3, 125 MHz): 16.7, 20.5, 26.7, 32.8, 47.4, 50.2, 68.4,
83.3, 129.1, 131.9, 133.5, 133.7, 202.1.
Anal. Calcd for C15H19ClO2S: C, 60.29; H, 6.41; found: C, 60.58;
H, 6.56.
Anal. Calcd for C16H14ClF3OS: C, 55.41; H, 4.07; found: C, 55.72;
H, 4.25.
4.3.6. 2-[(2R
*
,3R )-3-(4-chlorophenylthio)-tetrahydro-2H-pyran-2-
*
4.3. General procedure for the reactions presented in Table 2.
yl]-2-methyl-propanal (23). Yield 62%; Rf¼0.64 in hexane/ethyl
b-Arylthioalkylation in HFIP
acetate (40:1).
1H NMR (CDCl3, 500 MHz): 2.41 (t, J¼5.9, 2H), 2.99 (dd, J¼13.1
and 5.9, 1H), 3.06 (dd, J¼13.1 and 5.9, 1H), 3.37 (s, 3H), 3.33–3.48
(m, 1H), 5.10 (d, J¼11.1, 1H), 5.11 (d, J¼15.8, 1H), 5.69–5.92 (m, 1H),
7.24 (d, J¼8.5, 2H), 7.30 (d, J¼8.5, 2H).
A
solution of 4-chlorobenzenesulfenyl chloride (90 mg,
0.50 mmol) in dry DCM (0.50 ml) was cooled to ꢀ20 ꢁC and alkene
(0.50 mmol) was added. The mixture was stirred for 5 min at
ꢀ20 ꢁC and was warmed to 0 ꢁC. Nucleophile (0.60 mmol) followed
by HFIP (2.0 ml) were added to the resulting colorless solution.
After 5 min the reaction mixture was evaporated on a rotary
evaporator. The residue was dissolved in a small volume of hexane
and the product was purified with flash chromatography (hexane/
ethyl acetate). Fractions containing the product were combined and
the solvent was evaporated.
13C NMR (CDCl3, 125 MHz): 37.2, 37.6, 57.1, 79.3, 177.8, 128.9,
130.7, 131.9, 133.7, 135.3.
Anal. Calcd for C12H15ClOS: C, 59.37; H, 6.23; found: C, 60.76;
H, 6.76.
4.4. Preparation of
a-[1,1,1,3,3,3-hexafluoroisopropoxy]-b-[4-
chlorophenylthio]-ethylbenzene (24)
4.3.1. 4-Phenyl-5-[4-chlorophenylthio]-pentanone-2 (18). Yield 88%;
Rf¼0.27 in hexane/ethyl acetate (10:1).
A
solution of 4-chlorobenzenesulfenyl chloride (90 mg,
0.50 mmol) in dry DCM (0.50 ml) was cooled to ꢀ20 ꢁC and styrene
(52 mg, 0.50 mmol) was added. The reaction mixture was stirred
for 5 min at ꢀ20 ꢁC and was warmed to room temperature. A so-
lution of 2,6-di-tert-butyl-4-methylpyridine (123 mg, 0.60 mmol)
in HFIP (2.0 ml) was added. After 5 min the reaction mixture was
evaporated on a rotary evaporator. The residue was dissolved in
a small volume of hexane and the product was purified with flash
chromatography (hexane/ethyl acetate, 10:1, Rf¼0.39). Fractions
containing the product were combined and the solvent was evap-
orated under reduced pressure. A colorless oil of solvoadduct
(185 mg, 89%) was obtained.
1H NMR (CDCl3, 500 MHz): 1.98 (s, 3H), 2.75 (dd, J1¼17.1, J2¼7.9,
1H), 2.96 (dd, J1¼17.1, J2¼6.7, 1H), 3.08 (m, 2H), 3.35 (m, 1H), 7.08–
7.34 (m, 9H).
13C NMR (CDCl3, 125 MHz): 30.6, 40.2, 40.3, 48.7, 127.1, 127.5,
128.7, 129.1, 130.7, 132.1, 134.7, 142.6, 206.8.
Anal. Calcd for C17H17ClOS: C, 66.98; H, 5.62; found: C, 67.18;
H, 5.70.
4.3.2. 4-Phenyl-5-[4-chlorophenylthio]-pentene-1 (19). Yield 93%;
Rf¼0.42 in hexane/ethyl acetate (40:1).
1H NMR (CDCl3, 300 MHz): 2.49 and 2.64 (both m,1H each), 2.92
(m, 1H), 3.17 and 3.24 (both dd, J1¼13.4, J2¼7.3, 1H), 5.01 (d, J¼8.8,
1H), 5.05 (d, J¼15.4, 1H), 5.62 (m, 1H), 7.18–7.36 (m, 9H).
13C NMR (CDCl3, 75 MHz): 39.7, 40.1, 45.0, 116.9, 126.7, 127.6,
128.4, 128.9, 130.4, 131.7, 135.7, 142.9.
1H NMR (CDCl3, 500 MHz): 3.22 and 3.51 (both dd, J1¼13.7,
J2¼6.7, 1H each), 4.00 (sept, J¼6.1, 1H), 4.81 (t, J¼6.7, 1H) 7.25 (m,
4H), 7.32 (m, 2H), 7.41 (m, 3H).
13C NMR (CDCl3, 125 MHz): 30.1, 40.8, 72.8 (sept, J¼32.6), 120.8
(q, J¼286.0), 122.0 (q, J¼286.0), 127.9, 129.0, 129.1, 129.8, 131.3,
132.6, 134.0, 136.2.
Anal. Calcd for C17H17ClS: C, 70.69; H, 5.93; found: C, 70.75;
H, 5.93.
19F NMR (CDCl3, 470 MHz): ꢀ68.1, ꢀ66.9.
Anal. Calcd for C17H13ClF6OS: C, 49.23; H, 3.16; found: C, 49.44;
H, 3.35.
4.3.3. 2,2,3-Trimethyl-3-phenyl-4-[4-chlorophenylthio]-butanoate
(20). Yield 72%; Rf¼0.36 in hexane/ethyl acetate (10:1).
1H NMR (CDCl3, 500 MHz) 1.11 (s, 3H), 1.19 (s, 3H), 1.60 (s, 3H),
3.33 (d, J¼12.2, 1H), 3.57 (s, 3H), 4.09 (d, J¼12.2, 1H), 7.20–7.34
(m, 9H).
4.5. Preparation of DCHC complex of 3-methyl-3-methoxy-5-
phenyl-6-[(4-chlorophenylthio)]-hex-1-yne (27)
13C NMR (CDCl3, 125 MHz) 21.3, 21.8, 22.4, 42.7, 47.2, 50.0, 51.6,
126.7, 127.5, 128.2, 128.9, 130.6, 131.6, 136.9, 141.2, 176.6.
Anal. Calcd for C20H23ClO2S: C, 66.19; H, 6.39; found: C, 66.52;
H, 6.54.
A solution of 4-chlorobenzene sulfenyl chloride (90 mg,
0.50 mmol) in dry DCM (0.50 ml) was cooled to ꢀ20 ꢁC and styrene
(52 mg, 0.50 mmol) was added. The reaction mixture was stirred
for 5 min at ꢀ20 ꢁC and was warmed to 0 ꢁC. A solution of DCHC
complex of isopropenylacetylene 25 (176 mg, 0.50 mmol) in DCM
(0.50 ml) followed by HFIP (4.0 ml) were added. After 15 min the
reaction mixture was poured into MeOH (10 ml) at ꢀ30 ꢁC. The
resulting solution was treated with saturated aqueous NaHCO3
(10 ml) and extracted with hexane. The organic phase was filtered
through a plug of silica gel (eluent/hexane/ethyl acetate, 10:1). The
filtrate was evaporated under reduced pressure (bath temperature
was kept below 30 ꢁC to avoid DCHC complex decomposition). The
residue was purified with flash chromatography (hexane/ethyl
4.3.4. 4-Methyl-4-phenyl-5-[4-chlorophenylthio]-pentene-1
(21). Yield 58%; Rf¼0.37 in hexane/ethyl acetate (40:1).
1H NMR (CDCl3, 500 MHz): 1.48 (s, 3H), 2.52 (dd, J1¼13.4, J2¼7.9,
1H), 2.64 (dd, J1¼14.0, J2¼6.7, 1H), 3.21 (d, J¼12.2, 1H), 3.35 (d,
J¼12.2,1H), 5.02 (d, J¼9.8,1H), 5.07 (d, J¼17.0,1H), 5.56 (m,1H), 7.19
(m, 4H), 7.24 (m, 1H), 7.34 (m, 4H).
13C NMR (CDCl3, 125 MHz): 24.3, 42.0, 46.1, 47.9, 118.1, 126.3,
126.4, 128.2, 128.8, 130.7, 131.8, 134.2, 136.4, 145.3.

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M.O. Ratnikov et al. / Tetrahedron 66 (2010) 1832–1836
Knoefel, J.; Feldman, H.; Evans, D. F. J. Phys. Chem. 1973, 77, 366; (d) De-
termination of the gas phase anion-binding energy of some solvents with ha-
lide ions revealed that both TFE and especially HFIP are the strongest hydrogen
bond donors, e.g., the bond strength for the chloride ion >10 kcal greater in
comparison to water or methanol, see: Caldwell, G. W.; Masucci, J. A.; Ikono-
mou, M. G. Org. Mass Spectrom. 1989, 24, 8; (e) For a general discussion of the
TFE and HFIP properties, see also: Eberson, L.; Hartshorn, M. P.; Persson, O.;
Radner, F. Chem. Commun. 1996, 2105.
6. (a) Allard, B.; Casadevall, A.; Casadevall, E.; Largeau, C. Nouv. J. Chim. 1979, 3,
335; (b) Allard, B.; Casadevall, A.; Casadevall, E.; Largeau, C. Nouv. J. Chim. 1980,
4, 539; (c) Leonard, N. J.; Neelima. Tetrahedron Lett. 1995, 36, 7833; (d) Magueur,
G.; Crousse, B.; Oure´vitch, M.; Be´gue´, J.-P.; Bonnet-Delpon, D. J. Org. Chem. 2003,
68, 9763.
acetate, 10:1) to give product 27 as a 3:1 diastereomeric mixture
(inseparable, 379 mg, 60%).
1H NMR (CDCl3, 500 MHz): 1.43 (s), 3H; 2.18 (dd, J1¼14.7,
J2¼3.7), 1H; 2.32 (dd, J1¼14.7, J2¼7.3) and 2.49 (dd, J1¼14.7, J2¼3.6),
1H in total; 2.32 (d, J¼7.0), 1H; 2.49 (d, J¼7.0), 1H; 3.23–3.40 (m),
1H; 6.00 (s) and 6.10 (s), 1H in total; 7.15–7.33 (m), 9H.
13C NMR (CDCl3, 125 MHz): 26.8 and 27.7, 40.9 and 41.3, 41.8 and
42.6, 46.1 and 47.2, 50.0 and 50.1, 64.7, 73.4, 78.8 and 79.2,126.6 and
126.7, 127.7 and 127.8, 128.4 and 128.7, 128.9 and 129.0, 130.6
and 130.8, 132.0, 134.9, 144.6.
´
´
7. Das, U.; Crousse, B.; Kesavan, V.; Bonnet-Delpon, D.; Begue, J.-P. J. Org. Chem.
2000, 65, 6749.
Acknowledgements
8. (a) Trahanovsky, W. S.; Doyle, M. P. Tetrahedron Lett. 1968, 18, 2155; (b) Lambert,
J. B.; Featherman, S. I. J. Am. Chem. Soc. 1977, 99, 1542.
9. (a) Ferber, P. H.; Gream, G. E. Aust. J. Chem. 1981, 34, 1051; (b) Ferber, P. H.;
Gream, G. E. Aust. J. Chem. 1981, 34, 2217.
10. Ratnikov, M. O.; Tumanov, V. V.; Smit, W. A. Angew. Chem., Int. Ed. 2008, 47,
9739.
11. Smit, W. A.; Smolyakova, I. P.; Caple, R. Chem. Rev. 1994, 94, 2359; See also: Smit,
W. A.; Lazareva, M. I.; Smolyakova, I. P.; Caple, R. Russ. Chem. Bull. Int. Ed. 2001,
50, 1949.
Financial support of RFBR (project no 09-03-00666) and the
Presidium RAS Program (18P-2009) is gratefully acknowledged.
References and notes
´
´
1. For a review, see: (a) Begue, J.-P.; Bonnet-Delpon, D.; Crousse, B. Synlett 2004,
18; (b) Shuklov, I. A.; Dubrovina, N. V.; Bo¨rner, A. Synthesis 2007, 2925.
2. According to the results of solvatochromic studies an empirical parameter of
solvent polarity, ETN¼1.068 for HFIP and 0.898 for TFE. Among 360 solvents
tested, HFIP is the sole solvent outside the scale defined by the limiting values
ETN¼0 (for Me4Si) and ETN¼1 (for water), see: Reinhardt, C. Chem. Rev. 1994, 94,
2319.
12. Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irgang, B.; Janker, B.; Kempf, B.; Loos,
R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am. Chem. Soc. 2001, 123, 9500.
13. N (TFE)¼1.2; N (HFIP)¼ꢀ2.4 according to Ref. 4b.
14. A limitation of the reaction scope is also to be commented. In fact, the trial
experiments with the electrophile 6 revealed that its interaction with p-donors
11 and 12 in HFIP proceeds non-selectively to give mixture of products.
15. The compound 27 was obtained previously with the use of equimolar amounts
of TiCl4 as the catalyst; for the details see: Lazareva, M. I.; Nguyen, S. T.; Nguyen,
M. C.; Emiru, H.; McGrath, N. A.; Caple, R.; Smit, W. A. Mendeleev Commun.
2001, 224.
3. From the solvolysis data it was estimated that solvent ionizing power
Y2-AdOTs¼3.61 for HFIP and 1.80 for TFE (cf. with the values ꢀ0.61 for CH3COOH
and 3.04 for HCOOH); for reference see: Schadt, F. L.; Bentley, T. W.; Schleyer, P.
v. R. J. Am. Chem. Soc. 1976, 98, 7667.
16. Notably, one should consider these chlorides as real electrophiles involved
since no reaction with nucleophiles was observed for the respective sol-
voadducts like 24 (and also 16); vide supra.
4. (a) Hoffmann, M.; Hampel, N.; Kanzian, T.; Mayr, H. Angew. Chem., Int. Ed. 2004,
43, 5402; (b) Minegishi, S. S.; Kobayashi, S.; Mayr, H. J. Am. Chem. Soc. 2004, 126,
5174.
17. The use of HFIP as an optimal solvent for the generation of persistent carbo-
cations and cationic radicals is well-documented in the literature; see Ref. 5d
for the pertinent examples, see also: Eberson, L.; Hartshorn, M. P.; Persson, O.
J. Chem. Soc., Perkin Trans. 2 1995, 1735; Eberson, L.; Hartshorn, M. P.; Persson, O.
J. Chem. Soc., Perkin Trans. 2 1996, 141; McClelland, R. A.; Mathivanan, N.;
Steenken, S. J. Am. Chem. Soc. 1990, 112, 4857; Cozens, F. L.; McClelland, R. A.;
Steenken, S. J. Am. Chem. Soc. 1993, 115, 5050; McClelland, R. A.; Chan, C.;
Cozens, F.; Modro, A.; Steenken, N. Angew. Chem., Int. Ed. Engl. 1991, 30, 1337.
18. It should be emphasized that while the involvement of episulfonium ions as the
discrete intermediates had been firmly established for a number of examples of
5. (a) The enhanced ability of TFE and HFIP to donate a proton in a solvent-to-
solute hydrogen bond could be illustrated by the comparison of the values of a-
parameter for these solvents within the general scale containing the data for
more than 300 solvents which was derived from the Kamlet–Taft generalized
solvatochromic equation Kamlet, M. J.; Abboud, J.-L. M.; Abraham, M. H.; Taft,
R. W. J. Org. Chem. 1983, 48, 2877; In fact, it was disclosed that
have the maximal values for TFE and HFIP (
¼1.51 and 1.96 for TFE and HFIP
correspondingly; cf.
a-parameters
a
a
¼0.83 for ethanol, 1.12 for acetic acid and 1.17 for water;
(b) HFIP was shown to form much stronger hydrogen bonds than phenol or
ethanol with a number of neutral acceptors regardless of the experimental
the Lewis acid promoted b-arylthioalkylation reactions (see data in Ref. 11) we
do not see any compelling reasons to consider this mechanism as an alternative
to the one shown in Scheme 5.
parameters employed for the evaluation of this property (ꢀ
DH values from
calorimetric data, shift in O–H -stretching frequencies or hydrogen-bond in-
duced proton chemical shifts), see: Purcell, K. F.; Stikeleather, J. A.; Brunk, S. D.
J. Am. Chem. Soc. 1968, 91, 4019; (c) The data of the conductivity studies for
a number of tetraalkylammonium salts in TFE and especially HFIP shows
a pattern consistent with a good solvation of anions due to the formation of
strong hydrogen bonds and a rather poor cation solvation, see: Evans, D. F.;
Nadas, J. A.; Matesich, M. A. J. Phys. Chem. 1971, 75, 1708; Matesich, M. A.;
ꢀ
19. Farcasiu, D.; Ja¨hme, J.; Ru¨chardt, C. J. Am. Chem. Soc. 1985, 107, 5717.
ꢂ
20. Harpp, D. N.; Friedlander, B. T.; Smith, R. A. Synthesis 1979, 3, 181.
21. Ainsworth, C.; Chen, F.; Kuo, Y. N. J. Organomet. Chem. 1972, 46, 59.
22. Cazeau, P.; Duboudin, F.; Moulines, F.; Babot, O.; Dunogues, J. Tetrahedron 1987,
43, 2075.