Palladium-catalyzed Mizoroki-Heck reactions of 2-methylene-1,3-dithiane 1-oxide with aryl iodides

Article abstract of DOI:10.1246/cl.2009.624

Treatment of 2-methylene-1,3-dithiane 1-oxide with aryl iodides under palladium catalysis in the presence of potassium carbonate and tetrabutylammonium bromide leads to the Mizoroki-Heck arylation to yield 2-(arylmethylene)-1,3-dithiane 1-oxides in high y

Full text of DOI:10.1246/cl.2009.624

624
Chemistry Letters Vol.38, No.6 (2009)
Palladium-catalyzed Mizoroki–Heck Reactions
of 2-Methylene-1,3-dithiane 1-Oxide with Aryl Iodides
Eiji Morita, Masayuki Iwasaki, Suguru Yoshida, Hideki Yorimitsu,ꢀ and Koichiro Oshimaꢀ
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510
(Received April 9, 2009; CL-090352; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp, oshima@orgrxn.mbox.media.kyoto-u.ac.jp)
Treatment of 2-methylene-1,3-dithiane 1-oxide with aryl
iodides under palladium catalysis in the presence of potassium
carbonate and tetrabutylammonium bromide leads to the
Mizoroki–Heck arylation to yield 2-(arylmethylene)-1,3-
dithiane 1-oxides in high yields.
Table 1. Reactions of 2-methylene-1,3-dithiane 1-oxide (1)
with aryl iodidesa
cat. Pd(OAc)2
cat. DPPE
K2CO3, TBAB
S
S
+
S+
O–
S+
O–
DMF, 100 °C, 24 h
I
R
R
2
1
Ketene dithioacetals and their derivatives are useful two-
carbon building blocks as ketene equivalents in organic synthe-
sis.1 Recently, we have been developing the synthetic utility of
ketene dithioacetal monoxides.2 Among them, 2-methylene-
1,3-dithiane 1-oxide (1) showed excellent reactivity as an acti-
vated alkene in rhodium-catalyzed arylation with arylboronic
acids.2a,2d The rhodium-catalyzed reaction implied that 1 can un-
dergo smooth insertion to carbon–transition metal bonds without
suffering from possible catalyst poisoning by the cyclic sulfide
moiety of 1. Here we report that 1 also serves as a good substrate
in palladium-catalyzed Mizoroki–Heck reactions.3,4 The reac-
tions afford synthetically useful arylketene equivalents.
Treatment of 1 with 4-iodoanisole in the presence of potas-
sium carbonate, tetrabutylammonium bromide (TBAB), and cat-
alytic amounts of palladium acetate and 1,2-bis(diphenylphos-
phino)ethane (DPPE) in DMF at 100 ꢁC for 24 h provided the
corresponding arylated product 2a in 99% yield (Table 1,
Entry 1).5 The use of bidentate phosphine ligands such as
BINAP and 1,10-bis(diphenylphosphino)ferrocene also afforded
2a in high yields ranging from 70 to 90%, whereas monodentate
phosphine ligands including triphenylphosphine gave poor con-
versions (<50%). DMF was the best solvent among tested. The
reactions in nonpolar toluene and in dimethyl sulfoxide led to no
and 22% conversions, respectively. The combination of potassi-
um carbonate and TBAB is important. Potassium carbonate
alone was ineffective to yield 2a in 40% yield. TBAB would
act as a phase-transfer catalyst to solubilize carbonate anion
and would accelerate reductive dehydroiodination from the
H–PdII–I intermediate in the conventional catalytic cycle.6
A variety of aryl iodides participated in the reaction
(Table 1). Electron-rich aryl iodides (Entries 1–3) as well as
electron-deficient ones (Entries 5–7) underwent the arylation
reaction smoothly. Chloro and fluoro moieties remained intact
under the reaction conditions (Entries 8 and 9). The reaction
with sterically demanding 2-iodotoluene proceeded efficiently
(Entry 10). Intriguingly, the hydroxy group of 4-iodobenzyl
alcohol was compatible under the reaction conditions without
significant decrease in yield (Entry 11). Unfortunately, aryl bro-
mides were much less reactive under the reaction conditions
(Entry 12). The reactions of 1-alkenyl iodides resulted in very
low conversions (Entry 13).
Entry
R
2
Yield/%
E/Z
1
2
3
4
5
6
7
8
9
10
11
12
13
4-MeO
4-Me2N
4-Me
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2a
2l
99
83
95
92
75
89
88
78
90
93
68
8
88:12
84:16
85:15
90:10
85:15
88:12
89:11
88:12
88:12
86:14
87:13
88:12
—
4-CO2Et
4-CN
4-CF3
4-Cl
3-F
2-Me
4-CH2OH
(4-MeOC6H4Br)b
((E)-PhCH=CHI)c
trace
aReagents: 1 (0.50 mmol), aryl iodide (1.2 equiv), palladium
acetate (5 mol%), DPPE (5 mol%), potassium carbonate (1.2
equiv), TBAB (1.2 equiv), DMF (2.0 mL). 4-Bromoanisole
was used. (E)-ꢀ-Iodostyrene was used.
b
c
conditions. Although 2 may undergo further arylation, no di-
arylated ketene dithioacetal monoxides were detected.
The cyclic structure of 1 is important, as the reaction of
methylsulfanyl- and methylsulfinyl-substituted 3 was low yield-
ing (eq 1). The reaction of 3 gave a more complex mixture than
that of 1, which indicates side reactions proceeded. Notably, 2-
methylene-1,3-dithiane failed to react under the reaction condi-
tions, which underscores the importance of the electron-deficient
alkenyl sulfoxide moiety in this reaction.
MeO
5 mol% Pd(OAc)2
5 mol% DPPE
1.2 equiv K2CO3
1.2 equiv TBAB
I
(1.2 equiv)
+
SMe
MeO
SMe
SMe
ð1Þ
DMF, 100 °C, 24 h
O
4 17%
SMe
3 O
The products, 2-arylmethylene-1,3-dithiane 1-oxides 2, are
arylketene equivalents, which can undergo numerous transfor-
mations. For instance, treatment of (E)-2g with di-t-butyl malo-
nate in the presence of potassium t-butoxide afforded the corre-
sponding Michael adduct 5 in 91% yield (eq 2).7 The rhodium-
The E/Z stereoselectivities of the arylation range from
84:16 to 90:10, and were not controlled by changing the reaction
Copyright Ó 2009 The Chemical Society of Japan

Chemistry Letters Vol.38, No.6 (2009)
625
catalyzed addition of 4-methoxyphenylboronic acid to (E)-2g
yielded 6, a diarylacetaldehyde equivalent, in high yield
(eq 3).2a,2d,8 Each of the addition reactions inherently created
an array of three contiguous stereogenic centers and, interesting-
ly, afforded one of the possible diastereomers almost exclusive-
ly. The exact relative stereochemistries of 5 and 6 are not clear at
this stage.
Catalyzed Cross-Coupling Reactions, 2nd ed., ed. by A.
de Meijere, F. Diederich, Wiley-VCH, Weinheim, 2004,
Chap. 5. b) R. F. Heck, Org. React. 1982, 27, 345. c) I. P.
Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009.
d) M. Beller, T. H. Riermeier, G. Stark, in Transition Metals
for Organic Synthesis, ed. by M. Beller, C. Bolm, Wiley-
VCH, Weinheim, 1998, Vol. 1, Chap. 2.13. e) Handbook
of Organopalladium Chemistry for Organic Synthesis, ed.
by E. Negishi, Wiley, New York, 2002, Vol. 1, Chap. IV.2.
Typical experimental procedure: Palladium acetate (5.6 mg,
0.025 mmol), DPPE (10 mg, 0.025 mmol), potassium car-
bonate (83 mg, 0.60 mmol), and TBAB (190 mg, 0.60 mmol)
were placed in a 20-mL reaction flask quipped with a Dim-
roth condenser. The flask was filled with argon by using a
standard Schlenk technique. Ketene dithioacetal monoxide
1 (74 mg, 0.50 mmol) and 4-iodoanisole (140 mg, 0.60
mmol) were dissolved in DMF (2.0 mL), and the solution
was transferred to the reaction flask. The resulting mixture
was stirred for 24 h at 100 ꢁC. The reaction was quenched
with water (20 mL), and the product was extracted with ethyl
acetate (10 mL ꢂ 3). The combined organic layer was dried
over sodium sulfate and concentrated in vacuo. Silica gel
column purification of the crude oil by using hexane/ethyl
acetate = 1:2 yielded 2a (126 mg, 0.50 mmol) in 99% yield.
The stereochemistry of 2 was determined according to the
S
1.2 equiv t-BuOK,
1.5 equiv CH2(CO2-t-Bu)2
4-CF3C6H4
S+
O–
5
(E)-2g
THF, 55 °C, 14 h
ð2Þ
t-BuO2C CO2-t-Bu
5
91%
(single isomer)
10 mol% [Rh(OH)(cod)]2
5 equiv 4-MeOC6H4B(OH)2
S
4-CF3C6H4
4-MeOC6H4 O–
92%
(E)-2g
S+
1,4-dioxane/H2O = 10:1
50 °C, 17 h
ð3Þ
6
(>95% diastereoselectivity)
In summary, 2-methylene-1,3-dithiane 1-oxide (1) proved to
serve as a good substrate in palladium-catalyzed Mizoroki–Heck
reactions, which represents additional importance of 1 as a reac-
tive two-carbon unit. Further investigations on the utility of 1
and other ketene dithioacetal monoxides are under way.
literature: T. Wedel, M. Muller, J. Podlech, H. Goesmann,
¨
C. Feldmann, Chem.—Eur. J. 2007, 13, 4273. Characteriza-
tion data of (E)-2a: mp 74–75 ꢁC; IR (nujol): 2920, 2853,
2398, 1609, 1507, 1457, 1260, 1226, 1171, 1114, 1054,
;
876 cmꢃ1 1H NMR (CDCl3): ꢁ 2.45–2.60 (m, 3H), 2.80–
The work is supported by Grants-in-Aid for Scientific Re-
search and GCOE Research. M. I. and S. Y. acknowledge JSPS
for financial support.
2.87 (m, 2H), 3.36–3.42 (m, 1H), 3.84 (s, 3H), 6.91–6.94
(m, 2H), 7.43 (s, 1H), 7.76–7.80 (m, 2H); 13C NMR (CDCl3):
ꢁ 27.2, 31.9, 55.2, 55.5, 114.0, 126.7, 132.1, 133.6, 134.3,
160.5. Found: C, 56.67; H, 5.45%. Calcd for C12H14O2S2:
C, 56.66; H, 5.55%.
References and Notes
1
´
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3
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¨
Published on the web (Advance View) May 23, 2009; doi:10.1246/cl.2009.624