S. Matsubara et al.
FULL PAPERS
purification by silica gel
column chromatography gave
a-homoallylated ketone 22aa
in 69% yield (Table 4, entry 1).
In the cases of a-methyl-a,b-
epoxy ketone 19b and 19c, b-
hydroxy ketones having a qua-
ternary carbon at the a-posi-
Scheme 5. Preparation of chiral homoenolate from (R)-17 and 1, and its reaction with allyl bromide.
mix-b to form enantiomeric enriched a-hydroxy ketone,[9]
followed by mesylation of the hydroxy group. As shown in
Scheme 5, after the preparation of the zinc alkoxide of cy-
clopropanol from the optically active a-mesyloxy ketone
(R)-17 with 1, the resulting mixture was treated with allyl
bromide in the presence of CuCN·2 LiCl. The optically
active a-tertiary ketone (R)-18 was obtained without loss of
enantiomeric purity.
tion were obtained (entries 2 and 3). Cyclic have a higher
reactivity compared with acyclic homoenolates: Treatment
of 1-acetyl-1-cyclohexene oxide (19d) under the same condi-
tions gave the corresponding a-quaternary ketone 22da in
67% yield (entry 4). Instead of allyl bromide, other electro-
philes were also examined: Treatment of methallyl bromide
with 20d also afforded the corresponding product 22db in
good yield (entry 5). The reaction of prenyl bromide with
20d proceeded regioselectively (entry 6). In the case of
propargyl bromide and 1-bromo-2-butyne, the reaction with
20d proceeded regioselectively in an SN2’ manner to give
the corresponding allenes 22dd and 22de (entries 7 and 8).
The reactions of electrophiles with a homoenolate prepared
from 1-acetyl-1-cyclopentene oxide (19e) with 1 also afford-
ed the corresponding a-quaternary ketones in good yields
(entries 9 and 10).
An optically active a,b-epoxy ketone can be prepared
easily by Katsuki–Sharpless asymmetric epoxidation of a
corresponding allyl alcohol 23, followed by Swern oxidation.
As shown in Scheme 7a, treatment of allyl bromide with a
homoenolate prepared from (S)-19a and 1 under the same
conditions, afforded (R)-2-(hydroxymethyl)-1-phenyl-5-
hexen-1-one ((R)-22aa), which possesses an optically active
tertiary carbon at the a-position, in good yield. High enan-
tiomeric excess was retained. In the case of (1S,2R)-1-acetyl-
1-cyclohexene oxide ((1S,2R)-19d), the reaction gave opti-
cally active a-quaternary ketone (1R,2R)-22da without loss
of enantiomeric excess (Scheme 7b). The ORTEP figure of
a compound derived from (1R,2R)-22da and 3,5-dinitroben-
zoyl chloride is shown in Figure 1.
Though this method worked well to construct a chiral ter-
tiary carbon at the a-position of a ketone, it was difficult to
apply for the construction of a chiral quaternary carbon at
the a-position from a a-sulfonyloxy ketone: Treatment of 2-
mesyloxy-2-methyl-1-phenyl-1-propanone with the dizinc 1
resulted in complete recovery of the starting material. That
is, the preparation of zinc homoenolate equivalent contain-
ing a quaternary carbon in a cyclopropane ring is difficult
from a reaction of a,a-dialkyl-a-sulfonyloxy ketone with 1.
Meanwhile, as we reported previously, the reaction of an a-
alkyl-a,b-epoxy ketone 19 with 1 proceeds smoothly to
afford a 2-(1-hydroxyalkyl)-1,2-dialkylcyclopropanol having
a quaternary center in the cyclopropane ring in a high
yield.[4] An epoxide is superior as a leaving group. The zinc
alkoxide of 2-(1-hydroxyalkyl)-1,2-dialkylcyclopropanol 20
would act as a homoenolate equivalent. We speculated that
the treatment of electrophiles with the obtained zinc alkox-
ide of cyclopropanol 20 in the presence of CuCN·2 LiCl
would afford a-quaternary ketone 22 as shown in Scheme 6.
So, the reactions of a zinc homoenolate, which was prepared
from a,b-epoxy ketone 19 and the dizinc 1, with electro-
philes were examined.
A solution of a,b-epoxy ketone 19a (1.0 mmol) in THF
(4 mL) was treated with the dizinc(1, 1.2 mmol, 0.5m in
THF) at 258C for 1 h. Then, the mixture was treated with
CuCN·2 LiCl (2.4 mmol) at À308C for 10 min. Allyl bro-
mide was added to the resulting mixture, and everything
was stirred at 258C for 12 h. After an aqueous work-up, a
Conclusions
We demonstrate the preparation of a zinc homoenolate
equivalent from a-sulfonyloxy ketone and bis(iodozincio)-
methane. The prepared zinc
homoenolate reacts with allyl
bromide mediated by CuCN·2
LiCl to give an a-tertiary
ketone. The reaction proceeds
regioselectively and chemose-
lectively. The zinc homoeno-
late, prepared by the reaction
of an a,b-epoxy ketone with
the dizinc, also reacts with var-
ious electrophiles under the
same condition to give an a-
tertiary or -quaternary ketone.
Scheme 6. Strategy for the construction of a chiral tertiary or quaternary carbon at the a-position of a ketone
by nucleophilic cyclopropanation of a,b-epoxy ketone 19 with 1.
150
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Chem. Asian J. 2010, 5, 147 – 152