164
Chemistry Letters Vol.36, No.1 (2007)
Preparation of Zinc–Homoenolate from
ꢀ-Sulfonyloxy Ketone and Bis(iodozincio)methane
Kenichi Nomura and Seijiro Matsubaraꢀ
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoutodaigaku-katsura, Nishikyo-ku, Kyoto 615-8510
(Received October 16, 2006; CL-061217; E-mail: matsubar@orgrxn.mbox.media.kyoto-u.ac.jp)
Table 1. Preparation of cyclopropanol 3a
Treatment of ꢀ-sulfonyloxy ketone with bis(iodozincio)-
methane gives a zinc cyclopropoxide which is formed via a
nucleophilic addition of the reagent to carbonyl group followed
by an intramolecular substitution reaction.
HO
O
CH2
R'
1) CH2(ZnI)2 (1)
2) H3O+
R'
OTs
R
R
3
2
Run
R
R0
Time/h
Yield/%
Ratio
Preparation of cyclopropanol has been well investigated,1
since Cottle reported the first example of cyclopropanol forma-
tion from epichlorohydrin in 1942.2 Various types of cyclopro-
panol preparations have been reported: for example, cyclopropa-
nation of enols by carbenoid,3 treatment of ester derivatives with
Sm–CH2I2,4 chromium-mediated cyclization of ꢀ,ꢁ-unsaturated
enal,5 and Kulinkovich reaction of organotitanium reagent.6
Although these existing methods offer us a variety of methods
for preparation of cyclopropanols, we tried to add a direct
method to prepare cyclopropanol using a reaction of methylene
dianion with a carbonyl compound carrying a leaving group at
ꢀ-position. We have studied the reaction of bis(iodozincio)-
methane (1),7 which is easily prepared from zinc, diiodo-
methane, and a catalytic amount of lead.8 We examined how
to utilize the reagent for a reaction with ꢀ-sulfonyloxy ketone
as a substrate including the enantiomerically pure material.
Zinc–cyclopropoxide, which will be formed in situ, also possess-
es high potential for organic synthesis as a metal–homoenolate
equivalent.9
Bis(iodozincio)methane (1) had been already shown not to
possess enough nucleophilicity to attack a carbonyl group of
simple ketone in its Wittig-type methylenation reaction,7c,7d
but can perform nucleophilic addition into a ketone carrying a
coordinative hetero-atom such as methoxy or hydroxy group at
ꢀ-position by an acceleration effect for nucleophilic attack of
an organometallic reagent through chelation.10,11 Along this line,
it is expected that treatment of ꢀ-sulfonyloxy ketone 2 with
bis(iodozincio)methane (1) affords zinc–cyclopropoxide 3 via
a nucleophilic attack of 1 and an intramolecular substitution
reaction as shown in eq 1.12,13 In other words, a sulfonyloxy
group will act not only as an accelerator of nucleophilic attack
of 1 but also a good leaving group for the cyclopropanation
reaction. The formed zinc–cyclopropoxide can react as zinc–
homoenolate.
1
2
3
4
5
6
7
8
Ph
Ph
H
2a
2
10
15
20
4
56b
3a
3b
3c
3d
3e
3f
—
Me
Me
Me
Me
H
2b
2c
2d
2e
2f
86
99
81
88
38c
31d
48
76/24
67/33
67/33
72/28
—
2-Naphthyl
p-MeOC6H4
p-CF3C6H4
2-Furyl
Octyl
15
15
20
H
Heptyl
2g
2h
3g
3h
—
95/5
Me
aKetone (1.0 mmol), bis(iodozincio)methane (3.0 mmol, 0.5 M in THF),
and THF were used. b3-Phenyl-3-propanone was obtained in 43% yield.
c3-(2-Furyl)-3-propanone was obtained in 50% yield. d3-Undecanone
was obtained in 59% yield.
silica-gel column chromatography gave the corresponding cy-
clopropanol. Substrates having a stereogenic center afforded
the cyclopropanol as a diastereomeric mixture.
Without isolating cyclopropanol, we examined a direct cop-
per-mediated allylation where zinc–cylopropoxide acts as a
homoenolate equivalent.9 The reaction mixture obtained from
the ketone 2 (1.0 mmol) and the reagent 1 (2.0 mmol, ꢁ0.5 M in
.
THF) was treated with CuCN 2LiCl (2.0 mmol) at ꢂ30 C. Allyl
bromide was added to the resulting mixture. As shown in Table 2,
allylated ketones 4 were obtained in good yields.
As shown in eqs 2 and 3, acylation of homoenolate was also
examined. Treatment of zinc–cyclopropoxides obtained from 2a
and 2c with benzoyl chloride in the presence of Pd-catalyst gave
1,4-diketones 5a and 5c.
While the nucleophilic addition of 1 to a simple ketone
Table 2. Homoallylation of ꢀ-tosyloxy ketone 2a
1) CH2(ZnI)2 (1)
O
O
25 °C, t1
h
R'
R'
OTs
R
R
2) allyl bromide
•
H2C
CuCN 2LiCl
4
2
−30 to 25 °C, t2 h
Run
R
R0
t1/h
t2/h
Yield/%
O
IZnO
CH ZnI
2
IZnO
R
1
2
3
4
5
6
7
8
Ph
Ph
H
2a
2b
2c
2d
2e
2f
4
4
4
4
85
4a
4b
4c
4d
4e
4f
CH
2
CH (ZnI) (1)
2
2
R'
R'
R
(1)
Me
Me
Me
Me
H
76
78
55
87
79
84
53
R
THF
OSO R"
2
2-Naphthyl
p-MeOC6H4
p-CF3C6H4
2-Furyl
18
24
3
20
12
5
R'
OSO R"
2
2
3
As shown in Table 1, ꢀ-tosyloxy ketone 2 (1.0 mmol) in
THF (4 mL) was treated with bis(iodozincio)methane (1, 3.0
mmol, 0.5 M in THF) at 25 ꢁC. After being stirred for the period
shown in Table 1, the mixture was treated with saturated aque-
ous NH4Cl. The difficulty of isolation of cyclopropanol was
also observed in Runs 1, 6, and 7 (R0 ¼ H). Purification by short
15
24
72
6
Octyl
Me
H
Heptyl
2g
2h
3
4g
4h
6
aKetone (1.0 mmol), bis(iodozincio)methane (2.0 mmol, 0.5 M in THF),
.
CuCN 2LiCl (2.0 mmol), allyl bromide (2.0 mmol), and THF were used.
Copyright Ó 2007 The Chemical Society of Japan