An activated catalyst RhH(PPh3)4-dppe-Me 2S2 for α-methylthiolaton of α-phenyl ketones

Article abstract of DOI:10.1002/hc.20650

In the presence of catalytic amounts of RhH(PPh₃)₄, 1,2-bis(diphenylphosphino)ethane (dppe), and dimethyl disulfide, cyclic and acyclic α-phenyl ketones reacted with p-cyano-α- methylthioacetophenone giving α-methylthio-α-phenylketones. The activated catalyst containing dimethyl disulfide was effective for the α-methylthiolation reaction of these less reactive substrates.

Full text of DOI:10.1002/hc.20650

Heteroatom Chemistry
Volume 22, Number 1, 2011
An Activated Catalyst RhH(PPh ) -dppe-
3 4
Me S for α-Methylthiolaton of α-Phenyl
2 2
Ketones
Mieko Arisawa,1 Fumihiko Toriyama,1 and Masahiko Yamaguchi1,2
1Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences,
Tohoku University, Aoba, Sendai 980-8578, Japan
2WPI Research Center, Advanced Institute for Materials Research, Tohoku University,
Sendai 980-8577, Japan
Received 20 July 2010; revised 27 September 2010
able. Examining a diversity of substrates should
ABSTRACT: In the presence of catalytic amounts
lead to the development of various synthetic meth-
of RhH(PPh3)4, 1,2-bis(diphenylphosphino)ethane
ods, and simultaneously should broaden and deepen
(dppe), and dimethyl disulfide, cyclic and acyclic
our understanding of transition-metal-catalyzed re-
α-phenyl ketones reacted with p-cyano-α-methylthioa-
actions. We proposed a strategy for developing ef-
cetophenone giving α-methylthio-α-phenylketones.
ficient catalytic methods in which substrates were
The activated catalyst containing dimethyl disulfide
changed from reactive to less reactive, and success-
was effective for the α-methylthiolation reaction of
fully applied it to the development of phosphonium
ꢀ
C
these less reactive substrates. 2010 Wiley Periodicals,
salt synthesis [4].
Inc. Heteroatom Chem 22:18–23, 2011; View this article
We previously reported the α-methylthiolation
online at wileyonlinelibrary.com. DOI 10.1002/hc.20650
reaction of α-phenylthio dialkyl ketones, giving
α-methylthio α-phenylthio dialkyl ketones, which
employed p-cyano-α-methylthioacetophenone 1 as
INTRODUCTION
the methylthiolating reagent [3]. The equilibrat-
ing methylthio transfer reaction between the ke-
tone α-positions was catalyzed by RhH(PPh3)4 and
1,2-diphenylphosphinoethane (dppe). In the current
study, this method was applied to α-phenyl ke-
tones, which were less reactive substrates than α-
phenylthio ketones. An activated catalyst system de-
rived from RhH(PPh3)4, dppe, and dimethyl disulfide
3 was employed in this reaction (Scheme 1).
The conversion of organic C H bonds to C S bonds
is a straightforward method for the synthesis of
organosulfur compounds, and we have been inves-
tigating transition-metal-catalyzed methods to con-
duct this transformation [1–3]. Among such C S
bond formation reactions, the reaction at the car-
bonyl α-position is interesting, since various car-
bonyl derivatives with different reactivities are avail-
1,2-Diphenyl-1-ethanone 2 (5 equiv) was reacted
with 1 (1 equiv; concentration, 0.125 M) and 3
(2 equiv) in the presence of RhH(PPh3)4 (4 mol%)
and dppe (8 mol%) in refluxing THF for 6 h. 2-
Methylthio-1,2-diphenyl-1-ethanone 4 was obtained
in 78% yield based on 1, which was accompa-
nied by p-cyanoacetophenone 5 (78%) and p-cyano-
α,α-di(methylthio)acetophenone 6 (6%) (Table 1,
Correspondence to: Masahiko Yamaguchi; e-mail: yama@mail
.pharm.tohoku.ac.jp
Contract grant sponsor: Grant-in-Aid for Scientific Research.
Contract grant number: 21229001 and 22689001.
Contract grant sponsor: GCOE Program.
Contract grant sponsor: WPI Initiative.
2010 Wiley Periodicals, Inc.
c
ꢀ
18

An Activated Catalyst RhH(PPh3)4-dppe-Me2S2 for α-Methylthiolaton of α-Phenyl Ketones 19
yield of 4 (Table 1, entries 4–6). The importance of
the combined use of the rhodium complex, dppe, and
3 was also confirmed under these conditions (entries
6, 7, and 9). The reaction of 1 and 2 using diethyl
disulfide or diisopropyl disulfide (entries 10, 11) gave
similar results without 3 (entry 9), which indicated
the critical effect of 3. Also noticed was the formation
of comparable amounts of 4 and 5 under the condi-
tions including 3, which in contrast to the previous
method [3] formed considerably larger amounts of
5 than the methylthiolated products. Such changes
in the reaction course may be ascribed to the forma-
tion of a methylthiorhodium complex as an active
species. That the use of different amounts of 3 did
SCHEME 1
not markedly change the efficiency of the reaction
(entries 4–6 and 8) supported the formation of such
novel catalytic species.
entry 1). No reaction occurred without either
RhH(PPh3)4 or dppe. The reaction in the absence
of 3 gave 4 only in 8% yield (entry 2). When 2 and 3
(2 equiv) were reacted under the rhodium catalysis
conditions, the yield of 4 was 17% (entry 3). Thus,
the combination of 1 and 3 was effective in this α-
methylthiolation reaction of α-phenylketones. It was
also noted that the synthesis of 4 was previously con-
ducted not by the methylthiolation of 2 [5], and that
the transition-metal-catalyzed method was effective
for the transformation.
The equilibrating nature of this catalytic reac-
tion was confirmed by the following experiments. (1)
The yield of 4 decreased to 46% in the reaction us-
ing a 1:2 = 1:3 ratio and to 23% in the reaction using
1:2 = 1:1 (cf. Table 1, entry 6). (2) When equimolar
amounts of 4 and 5 were treated with RhH(PPh3)4
(4 mol%), dppe (8 mol%), and 3 (12 mol%) in reflux-
ing THF, 1 (13%) and 2 (61%) were obtained along
with 6 (17%) (Scheme 2).
Notably, the amount of dimethyl disulfide 3
could be reduced to 0.12 equiv at a higher concen-
tration (1 M) of 1 without significantly affecting the
Other α-phenyl ketones, i.e., 1,3-diphenyl-2-
propanone and 1-phenyl-2-butanone, gave the
TABLE 1 α-Methylthiolation Reaction of 1,2-Diphenyl-1-ethanone 2 with 1
Amount
Concentration
Yield (%)
Entry
3 (equiv)
1 (M)
Time (h)
4
5
6
1
2
0
2
0.125
0.125
0.125
6
6
6
3
3
3
3
3
3
3
3
78
8
78
14
ND
78
75
75
ND
65
55
62
48
6
4
ND
4
5
5
ND
6
6
4
6
2
3a
4
17
69
69
68
7
58
43
46
34
2
1
1
1
1
1
1
1
1
5
0.2
0.12
0.2
0.08
0
0.12
0.12
6
7b
8
9
10c
11d
ND: not detected.
aWithout 1, the molar ratio of 3/2 = 2.
bWithout 1, the molar ratio of 2/3 = 5.
c (EtS)2 used instead of 3.
d (i-PrS)2 used instead of 3.
Heteroatom Chemistry DOI 10.1002/hc

20 Arisawa, Toriyama, and Yamaguchi
SCHEME 2
SCHEME 4
In the presence of a rhodium–phosphine com-
plex and dimethyl disulfide 3, the less reactive
α-phenyl ketones are α-methylthiolated with the
methylthio transfer reagent 1. A methylthiorhodium
species was considered to be involved in the cataly-
sis, which suggested a critical role of organothiolate
ligands in rhodium catalysis.
At this stage, it may be worth noting the appli-
cation of the methyl transfer reagent systems de-
rived from 1 and 3 to α-phenylthioacetophenone
9, which possessed a similar pKa value, 17.1
with 2, 17.7 [7]. The reaction of 9 (3 equiv),
1 (1 equiv), and 3 (2 equiv) in the presence
of RhH(PPh3)4 (10 mol%) and dppe (20 mol%)
gave α,α-dimethylthioacetophenone 10 (41%) and
α-methylthio-α-phenylthioacetophenone 11 (32%)
(Scheme 5). The product 10 should be formed by the
rhodium-catalyzed methylthio exchange reaction of
11 [8]. In the absence of 3, 10 (trace) and 11 (24%)
were obtained in considerably lower total yields. The
increase in the total yields of 10 and 11 in the pres-
ence of 3 may be due to equilibrium shift as well as
to the catalyst activation. To further shift the equi-
librium to form 10 from 11, excess 3 was added to
the reaction mixture. Thus, 9 (3 equiv), 1 (1 equiv),
and 3 (2 equiv) were heated in THF at reflux for 1 h
in the presence of RhH(PPh3)4 (2 mol%) and dppe
(4 mol%). Then, 3 (8 equiv) was added, and heating
was continued for one additional hour. By this mod-
ified procedure, 10 was obtained in 90% yield based
on 1, which was accompanied by the formation of
a small amount of 11. The catalyst loading could be
reduced to 2 mol% in this reaction with a turnover
number of 45 for the formation of 10. It should be
noted that, in the reaction of 9, the addition of 3 by
appropriate methods substantially enhanced the ef-
ficiency of the reaction by shifting the equilibrium
to form 10.
SCHEME 3
methylthiolated products in 82% and 64% yields,
respectively (Scheme 3) [6]. 2-Phenylcyclohexanone
was converted to 2-methylthio-2-phenylcycl-
ohexanone in 36% yield after 3 h and 50%
yield after 9 h. 2-Phenylcycloheptanone was α-
methylthiolated in 35% yield in 9 h. The reaction of
2-phenycyclopentanone was faster, and 68% yield
of the α-methylthiolated product was obtained after
1 h, which probably is related to the higher acidity
of cyclopentanone compared to other cyclic ketones
[7].
The reaction of (2R∗,4S∗)-4-(t-butyl)-2-phenyl-1-
cyclohexanone cis-7 provided a comparable amount
of axial-methylthio isomer trans-8 (32%) and
equatorial-isomer cis-8 (21%) (Scheme 4). The stere-
ochemistry was in contrast to the reaction of 4-(t-
butyl)-2-phenylthio-1-cyclohexanone, which selec-
tively gave the axial-methylthio isomer [3]. The
epimerization reaction of cis-7 was conducted in
the presence of RhH(PPh3)4 (0.8 mol%) under
THF reflux and yielded a 4:1 mixture of cis-7
and trans-7, which supported the formation of
rhodium enolate. Ketones lacking the α-phenyl
group, such as acetophenone, propiophenone, α-
methoxyacetophenone, and 1-phenyl-3-buten-1-one
provided no α-methylthioketones under the present
conditions.
In the development of the catalytic method for
the synthesis of organosulfur compounds from the
less reactive ketonic substrates than α-phenyl ke-
tones and α-phenylthio ketones, kinetic control to
Heteroatom Chemistry DOI 10.1002/hc

An Activated Catalyst RhH(PPh3)4-dppe-Me2S2 for α-Methylthiolaton of α-Phenyl Ketones 21
(tt, J = 7.4, 1.7 Hz, 1H), 7.97 (dd, J = 8.2, 1.4 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ: 14.4, 56.5, 127.9,
128.6, 128.8, 128.9, 128.9, 133.2, 135.7, 136.2, 194.9.
IR (KBr): 3024, 2916, 1667, 1595, 1447, 1287, 1200,
998, 764, 739, 692 cm−1. MS (EI) m/z: 242 (M+, 5%),
137 (M+– PhCO, 100%). HRMS Calcd for C15H14OS:
242.0765. Found: 242.0758.
The Reverse Reaction Using 4
In a two-necked flask equipped with a reflux
condenser, RhH(PPh3)4 (4 mol%, 11.5 mg), dppe
(8 mol%, 8.0 mg), 4 (0.25 mmol, 60.6 mg), 5 (0.25
mmol, 36.3 mg), and 3 (12 mol%, 2.7 L) in THF
(0.25 mL) under an argon atmosphere were placed,
and the solution was heated at 90◦C for 3 h. The sol-
vent was removed under reduced pressure, and the
residue was purified by flash column chromatogra-
phy on silica gel giving 2 (29.8 mg, 61%), 1 (6.1
mg, 13%), and 6 (10.1 mg, 17%) with recovered 4
SCHEME 5
(24.5 mg, 40%) and 5 (23.8 mg, 66%).
develop more reactive catalysts and thermodynamic
control to shift equilibria should be considered.
1-Methylthio-1,3-diphenyl-2-propanone [6]
EXPERIMENTAL
1
Colorless crystals. mp 70–71◦C (hexane). H NMR
1H NMR and 13C NMR spectra were recorded on
a Varian Mercury (400 MHz) and JEOL JNM-
ECA600 (600 MHz). IR spectra were measured
on a JASCO FT/IR-410 spectrophotometer. Melt-
ing points were determined with a Yanagimoto
micromelting point apparatus without correction.
High- and low-resolution mass spectra were mea-
sured on a JEOL JMS-DX-303, a JEOL JMS-700, or
a JEOL JMS-T100GC.
(400 MHz, CDCl3) δ: 1.95 (s, 3H), 3.69 (d, J =
15.2 Hz, 1H), 3.87 (d, J = 15.2 Hz, 1H), 4.64 (s,
1H), 7.10 (d, J = 7.2 Hz, 2H), 7.22–7.39 (m, 8H).
13C NMR (100 MHz, CDCl3) δ: 14.4, 46.4, 60.1, 127.0,
128.1, 128.6, 128.7, 128.9, 129.5, 133.8, 135.1, 202.2.
IR (KBr): 3025, 2912, 1709, 1497, 1488, 1452, 1403,
1052, 733, 699 cm−1. MS (EI) m/z: 256 (M+, 14%),
137 (M+ – BnCO, 100%). HRMS Calcd for C16H16OS:
256.0922. Found: 256.0912.
1-Methylthio-1-phenyl-2-butanone
Typical Procedures for α-Methylthiolation
Reaction of α-Phenylketone
1
Colorless oil. H NMR (400 MHz, CDCl3) δ: 1.02 (t,
J = 7.0 Hz, 3H), 2.00 (s, 3H), 2.47 (dq, J = 18.4, 7.3
Hz, 1H), 2.59 (dq, J = 17.6, 7.3 Hz, 1H), 4.56 (s, 1H),
7.28–7.39 (m, 5H). 13C NMR (100 MHz, CDCl3) δ:
8.1, 14.5, 32.9, 61.0, 128.0, 128.5, 128.8, 135.8, 206.0.
IR (neat): 2978, 2918, 1716, 1495, 1453, 1346, 1106,
1031, 745, 700 cm−1. MS (EI) m/z: 194 (M+, 7%),
137 (M+– EtCO, 100%). HRMS Calcd for C11H14OS:
194.0765. Found: 194.0757.
In a two-necked flask equipped with a reflux
condenser, RhH(PPh3)4 (4 mol%, 11.5 mg), dppe
(8 mol%, 8.0 mg), 1,2-diphenyl-1-ethanone 2 (1.25
mmol, 245.3 mg), 1 (0.25 mmol, 47.8 mg), and 3
(12 mol%, 2.7 L) in THF (0.25 mL) under an ar-
gon atmosphere were placed, and the solution was
heated at 90◦C for 3 h. The solvent was removed
under reduced pressure, and the residue was puri-
fied by flash column chromatography on silica gel,
giving 2-methylthio-2-phenylacetophenone 4 (40.9
mg, 68%), p-cyano-α,α-di(methylthio)acetophenone
6 (3.1 mg, 5%), and 5 (27.3 mg, 75%) with the re-
covery of 2 (210.4 mg, 86%) and 1 (8.2 mg, 17%).
2-Methylthio-2-phenylcyclopentanone
Synthesized from 2-phenylcyclopentanone [9,10].
1
Colorless oil. H NMR (400 MHz, CDCl3) δ: 1.80 (s,
3H), 1.92–1.99 (m, 1H), 2.13–2.41 (m, 4H), 2.78 (dd,
J = 19.0, 8.2 Hz, 1H), 7.26 (t, J = 7.4 Hz, 1H), 7.35
(t, J = 7.6 Hz, 2H), 7.54 (d, J = 8.0 Hz, 2H). 13C
NMR (150 MHz, CDCl3) δ: 12.2, 18.7, 37.3, 40.8,
58.3, 127.1, 127.9, 128.4, 138.7, 208.6. IR (neat):
4 [5]: Colorless crystals. mp 66–67◦C (hexane). H
1
NMR (400 MHz, CDCl3) δ: 2.05 (s, 3H), 5.48 (s, 1H),
7.27 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.2 Hz, 2H), 7.41
(t, J = 7.4 Hz, 2H), 7.46 (d, J = 7.2 Hz, 2H), 7.52
Heteroatom Chemistry DOI 10.1002/hc

22 Arisawa, Toriyama, and Yamaguchi
3057, 2958, 2920, 1722, 1493, 1444, 1155, 1130, 756,
2.8 Hz, 1H), 2.07–2.12 (m, 1H), 2.18 (dt, J = 14.1, 3.1
Hz, 1H), 2.47 (ddd, J = 16.1, 4.4, 2.8 Hz, 1H), 3.27
(ddd, J = 16.4, 14.1, 6.1 Hz, 1H), 7.25 (t, J = 7.4 Hz,
1H), 7.36 (t, J = 7.9 Hz, 2H), 7.48 (d, J = 7.6 Hz,
2H). 13C NMR (100 MHz, CDCl3) δ: 12.8, 26.8, 27.3,
32.1, 37.2, 42.2, 44.6, 62.7, 126.9, 128.3, 128.5, 140.4,
203.4. IR (KBr): 3059, 2955, 2862, 1701, 1495, 1442,
1411, 1365, 1234, 1139, 749, 700, 555 cm−1. MS (EI)
m/z: 276 (M+, 29%), 230 (M+ – CH2S, 100%), 219 (M+
– C4H9, 93%). HRMS Calcd for C17H24OS: 276.1548.
Found: 276.1562. NOESY was observed between the
axial 6-proton (δ 3.27) and SMe protons (δ 1.73). cis-
8: Colorless oil. 1H NMR (600 MHz, CDCl3) δ: 0.94 (s,
9H), 1.56 (qd, J = 12.4, 4.7 Hz, 1H), 1.63 (tt, J = 12.1,
2.8 Hz, 1H), 1.82 (s, 3H), 1.90 (dd, J = 13.9, 12.2 Hz,
1H), 1.95–2.00 (m, 1H), 2.44 (td, J = 13.3, 6.3 Hz,
1H), 2.52 (ddd, J = 14.0, 4.4, 3.4 Hz, 1H), 2.91 (dt, J
= 14.0, 3.0 Hz, 1H), 7.22 (d, J = 7.6 Hz, 2H), 7.28 (t,
J = 7.6 Hz, 1H), 7.38 (t, J = 7.9 Hz, 2H). 13C NMR
(100 MHz, CDCl3) δ: 12.5, 27.4, 28.4, 32.6, 38.5, 39.3,
42.8, 63.4, 127.2, 127.4, 128.8, 138.3, 208.9. IR (neat):
3059, 2960, 2870, 1714, 1446, 1367, 1230, 1142, 744,
700, 565 cm−1. MS (EI) m/z: 276 (M+, 32%), 230
(M+ – CH2S, 100%), 219 (M+ – C4H9, 79%). HRMS
Calcd for C17H24OS: 276.1548. Found: 276.1540.
NOESY was observed between the axial 4-proton (δ
1.63) and Ph ortho-protons (δ 7.22), and between
the axial 6-proton (δ 2.44) and Ph ortho-protons
(δ 7.22).
700 cm−1. MS (EI) m/z: 206 (M+, 48%), 163 (M+
–
C3H7, 88%), 160 (M+ – CH2S, 100%). HRMS Calcd
for C12H14OS: 206.0765. Found: 206.0755.
2-Methylthio-2-phenylcyclohexanone
1
Colorless oil. H NMR (400 MHz, CDCl3) δ: 1.68–
1.78 (m, 1H), 1.77 (s, 3H), 1.86–2.00 (m, 3H), 2.13–
2.20 (m, 1H), 2.40–2.54 (m, 2H), 2.92 (ddd, J = 14.7,
9.1, 5.5 Hz, 1H), 7.24–7.28 (m, 1H), 7.34–7.38 (m,
4H). 13C NMR (100 MHz, CDCl3) δ: 12.5, 21.8, 26.7,
38.6, 40.4, 63.6, 127.2, 127.9, 128.5, 139.1, 205.8. IR
(neat): 3058, 2939, 2863, 1714, 1697, 1493, 1446,
1121, 747, 700 cm−1. MS (EI) m/z: 220 (M+, 29%),
177 (M+ – C3H7, 26%), 174 (M+ – CH2S, 99%), 145
(M+ – MeSC2H4, 100%). HRMS Calcd for C13H16OS:
220.0922. Found: 220.0914.
2-Methylthio-2-phenylcycloheptanone
Synthesized from 2-phenylcycloheptanone [9,11].
Colorless oil. 1H NMR (400 MHz, CDCl3) δ: 1.36–1.73
(m, 4H), 1.69 (s, 3H), 1.79–1.86 (m, 1H), 1.96–2.14
(m, 3H), 2.54 (dd, J = 11.0, 8.2 Hz, 1H), 3.07 (td, J =
11.7, 2.1 Hz, 1H), 7.25 (t, J = 6.8 Hz, 1H), 7.35 (t, J =
7.6 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H). 13C NMR (100
MHz, CDCl3) δ: 13.3, 24.3, 25.7, 30.1, 39.4, 40.4, 64.4,
126.9, 128.1, 129.2, 138.5, 203.5. IR (neat): 2929,
2856, 1685, 1493, 1456, 1444, 1157, 941, 752, 702
cm−1. MS (EI) m/z: 234 (M+, 100%), 191 (M+– C3H7,
88%), 163 (M+ – C5H11, 50%), 159 (M+ – MeSC2H4,
77%). HRMS Calcd for C14H18OS: 234.1078. Found:
234.1081.
δ1.56 H
δ1.90
δ2.47
H
O
H
δ0.88
2.10
δ
H
δ7.25
(2S∗,4S∗)- and (2R∗,4S∗)-4-(t-Butyl)-2-methyl-
thio-2-phenylcyclohexanone Trans-8 and Cis-8
H
H
δ7.36
δ7.48
δ2.18
3.27S
δ
In
a
two-necked flask equipped with
a
re-
2.02
δ
H
flux condenser, RhH(PPh3)4 (4 mol%, 11.5 mg),
dppe (8 mol%, 8.0 mg), (2R∗,4S∗)-4-(t-butyl)-2-
phenylcyclohexanone cis-7 [12] (1.25 mmol, 287.9
mg), 1 (0.25 mmol, 47.8 mg), and 3 (12 mol%, 2.7
L) in THF (0.25 mL) under an argon atmosphere
were placed, and the solution was heated at 90◦C
for 9 h. The solvent was removed under reduced
pressure, and the residue was purified by flash col-
umn chromatography on silica gel giving trans-8
(22.2 mg, 32%), cis-8 (14.4 mg, 21%), 6 (3.7 mg,
6%), 5 (24.8 mg, 68%) as well as the recovery of cis-7
(214.3 mg, 74%), trans-7 (43.2 mg, 15%), and 1 (8.5
mg, 18%). trans-8: Colorless crystals. mp 99–100◦C
(hexane). 1H NMR (600 MHz, CDCl3) δ: 0.88 (s, 9H),
1.56 (tdd, J = 13.5, 12.0, 4.5 Hz, 1H), 1.73 (s, 3H),
1.90 (dd, J = 14.1, 12.7 Hz, 1H), 2.02 (tt, J = 12.3,
H3C
NOESY
δ1.73
trans-8
δ1.56 H
δ2.52
δ1.90
O
H
H
δ1.97
δ0.94
δ1.82
H
SMe
H
H
δ2.91
2.44
δ
δ1.63
H
H
Hδ7.22
H δ7.38
NOESY
H
δ7.28
H
cis-8
Heteroatom Chemistry DOI 10.1002/hc

An Activated Catalyst RhH(PPh3)4-dppe-Me2S2 for α-Methylthiolaton of α-Phenyl Ketones 23
ACKNOWLEDGMENTS
Equilibration of Cis-7 and Trans-7
MA expresses her thanks to the Grant-in-Aid for Sci-
entific Research and the Asahi Glass Foundation.
In a two-necked flask equipped with a reflux con-
denser, RhH(PPh3)4 (0.8 mol%, 11.5 mg) and cis-7
(1.25 mmol, 287.9 mg) in THF (0.25 mL) under an
argon atmosphere were placed, and the solution was
heated at 90◦C for 3 h. The solvent was removed
under reduced pressure, and the residue was puri-
fied by flash column chromatography on silica gel
giving cis-7 (233.8 mg, 81%) and trans-7 (48.0 mg,
17%).
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Typical Procedures for α,α-Dimethylthiolation
Reaction of α-Phenylthioacetophenone 9 using 1
and 3
In a two-necked flask equipped with a reflux con-
denser, RhH(PPh3)4 (2 mol%, 2.9 mg), dppe (4 mol%,
2.0 mg), 9 (0.375 mmol, 85.5 mg), and 1 (0.125
mmol, 23.9 mg) under an argon atmosphere were
placed. THF (1 mL) and 3 (0.25 mmol, 22.5 L)
were added, and the solution was heated at re-
flux for 1 h. Then, another portion of 3 (1 mmol,
90 L) was added, and the mixture was heated at
reflux for 1 h. After removal of the solvents, flash
column chromatography on silica gel giving 10
(23.8 mg, 90%) and 11 (1.7 mg, 5%). 10: Color-
1
less crystals. mp 66–67◦C (hexane). H NMR (400
MHz, CDCl3) δ: 2.14 (s, 6H), 5.34 (s, 1H), 7.48
(t, J = 8.0 Hz, 2H), 7.59 (t, J = 8.0 Hz, 1H),
8.01 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ: 12.4, 57.1, 128.7, 128.8, 133.5, 134.3,
190.8. IR (KBr): 2917, 1672, 1278, 1003 cm−1. MS
(EI) m/z: 212 (M+, 9%), 107 (M+ – PhCO, 100%).
HRMS Calcd for C10H12S2O: 212.0330. Found:
212.0334.
Heteroatom Chemistry DOI 10.1002/hc