1
224
Chemistry Letters Vol.33, No.9 (2004)
Wittig Type Methylenation of Ketones with Bis(iodozincio)methane and Ionic Liquid
Ã
Hideaki Yoshino, Masami Kobata, Yuhei Yamamoto, Koichiro Oshima, and Seijiro Matsubara
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoutodaigaku-katsura, Nishikyo-ku, Kyoto 615-8510
(Received June 24, 2004; CL-040732)
Ketones were transformed into alkenes via methylenation
(i.e., (–CH2Zn–)n) which is produced by the Schlenk equilibrium
starting from 1. Without THT, a solution of 1 in THF will yield
polymethylene zinc at 60 C. Bis(iodozincio)methane (1) is
much more active for methylenation compared to polymethylene
with bis(iodozincio)methane and ionic liquid, 1-butyl-3-methyl-
imidazolium hexafluorophosphate ([bmim][PF6]) in the absence
of additional metal salt such as titanium chlorides.
ꢀ
zinc. Ionic liquid may also stabilize the structure of 1 even at
ꢀ
60 C to maintain its structure during the reaction at the same
temperature.
Phosphonium ylide has been the most popular reagent for
1
Wittig type olefination of ketones. The ylide, however, was also
ꢀ
Table 1. Methylenation of 2 with 1/Additive at 60 C
Additivea
equipped with a strong basicity which often leads to an enoliza-
tion of the starting carbonyl compound. At the same time, it of-
ten suffers from a lack of nucleophilicity. For these drawbacks
arose the necessity to develop the novel alkylidenation reagents.
Among them, gem-dimetal compound showed the promising re-
Run
Solvent
THFb
Yield of 3 /%
1
2
3
4
none
THT (0.5 mL)
43
86
56
81
THFb
b,c
THF
[bmim][PF6] (0.1 mL)
[bmim][PF6] (0.1 mL)
THF/hexanedd
aTHT: tetrahydrothiophene. [bmim]: 1-butyl-3-methyl- imidazolium. All
2
sults. As the carbon is substituted with a pair of electron posi-
reactions were performed at 60 C. b2 (1.0 mmol), 1 (0.5 M in THF,
ꢀ
tive metal atoms, its nucleophilicity should be increased much
more than a simple organo-monometal species. In addition, care-
ful metal tuning on gem-dimetal species will also solve the prob-
lem caused from strong basicity of the reagent. As such dimetal
2
.0 mmol), and THF (1.0 mL). cThe reaction mixture was monophase.
d2 (1.0 mmol), 1 (0.5 M in THF, 2.0 mmol), and hexane (1.0 mL). The re-
action mixture was biphase.
3
species, the organozinc reagent has played an important role.
3
Table 2. Methylenation of Various Ketones 4 with 1/[bmim][PF6]
a
3b
Nysted reagent-Lewis acid, CH2X2–Zn–TiCl4, the modified
O
CH2
R2
3
c
3d
[bmim][PF6] (0.1 mL)
THF-hexane
CH2X2–Zn–TiCl4 by Lombardo, and CH2(ZnI)2–ꢀ-TiCl3
R1
R2
+ CH2(ZnI)2
R1
have been developed. It is supposed that gem-dizinc species
which is activated with the added metal salt is reactive species.
In all cases, the methylenation reaction proceeds at room tem-
perature. Without an addition of titanium salt, for example, treat-
ment of 2-dodecanone with bis(iodozincio)methane (1) at room
temperature resulted in the sluggish reaction. Even at higher
temperature, the alkene 3 was not obtained in good yield
6
0 °C, 6 h
4
(1.0 mmol) 1 (2.0 mmol)
Ketone 4
5
Run
Yield of 5 /%a
1
2
3
4
5
6
7
8
pentyl phenyl ketone
5-undecanone
cyclohexyl phenyl ketone
cyclododecanone
4-tert-butylcyclohexanone
3-n-octylcyclopentanone
ꢁ-tetralone
84
47
49
55
74
20
63
(
Scheme 1).
b
Methyl 10-oxoundecanoate
72
O
CH2
n-C10H21 CH3
a2 (1.0 mmol), 1 (0.5 M THF solution, 2.0 mmol), hexane (1.0 mL), and
[bmim][PF6] were used. bEster group was intact during the reaction.
Methyl octanoate was also treated with 1/[bmim][PF6] under the same
condition and recovered quantitatively.
+
CH (ZnI)2
2
n-C10H21
CH3
THF
1 (1.0 mmol)
Reaction Condition
5 °C, 15 h
0 °C, 6 h
3
2
(1.0 mmol)
3/%
15
26
2 (Recovery)/%
2
6
10
43
<3
As shown in Table 2, various ketones 4 were converted into
alkenes 5 in good to moderate yields by 1/[bmim][PF6]. Instead
of 1, the Nysted reagent was also examined for the methylena-
tion of 2 in the presence of ionic liquid, but did not give the cor-
responding alkene. Although the titanium salt is still the best ad-
ditive for the effective methylenation of ketones with 1, a use of
ionic liquid shows the new possibility for an activation of gem-
dizinc reagents.
β
-TiCl (1.2 mmol), 25 °C, 0.5 h 84
3
Scheme 1. Methylenation of 2 with 1.
We reported a characteristic effect of tetrahydrothiophene
THT) which activates dizinc 1 to react with acyl chloride. As
(
shown in Table 1 (run 2), an addition of small amount of THT
to the reaction mixture improved the yield of methylenated prod-
uct dramatically. It seems to be a good substitute for ꢀ-TiCl3. As
practical meaning, however, its stinking property makes the ex-
perimental procedure in large scale uncomfortable. Studying the
additive, we found that an ionic liquid, 1-butyl-3-methylimida-
zolium hexafluorophosphate ([bmim][PF6]) plays the same kind
of role. The effect of THT to the structure of 1 was discussed
previously.4 It prevents a formation of polymethylene zinc
References
1
2
3
M. Edmonds and A. Abell, in ‘‘Modern Carbonyl Olefination,’’ ed. by T. Takeda,
Wiley-VCH, Weinheim (2003), p 1.
S. Matsubara, in ‘‘Modern Carbonyl Olefination,’’ ed. by T. Takeda, Wiley-
VCH, Weinheim (2003), p 200.
a) S. Matsubara, M. Sugihara, and K. Utimoto, Synlett, 1998, 313. b) K. Takai, T.
Kakiuchi, Y. Kataoka, and K. Utimoto, J. Org. Chem., 59, 2668 (1994). c) L.
Lombardo, Org. Synth., 65, 81 (1987). d) S. Matsubara and K. Oshima, Proc.
Jpn. Acad. Ser. B, 79, 71 (2003).
4
S. Matsubara, Y. Yamamoto, and K. Utimoto, Synlett, 1998, 1471.
Copyright Ó 2004 The Chemical Society of Japan
Published on the web (Advance View) August 25, 2004; DOI 10.1246/cl.2004.1224
Yoshino, Hideaki
