A new method for synthesis of α,α-disubstituted carbonyl compounds from carbonyl compounds with one-carbon homologation through β-oxido carbenoid rearrangement as the key reaction

Article abstract of DOI:10.1016/j.tet.2005.03.054

The addition reaction of carbonyl compounds with lithium α-sulfinyl carbanions of 1-chloroalkyl p-tolyl sulfoxides gave adducts, α-chloro β-hydroxy sulfoxides, in high to quantitative yields. The adducts were first treated with a base to give alkoxides, which were treated with i-PrMgCl or t-BuLi to give β-oxido carbenoids via a sulfoxide-metal exchange reaction. The β-oxido carbenoid rearrangement then took place to afford the enolates with one-carbon elongation. The enolate intermediates were found to be able to be trapped with electrophiles such as aldehydes, ethyl chloroformate, benzoyl chloride, haloalkanes to give α,α-disubstituted carbonyl compounds in moderate to good yields. This method provides a new and efficient way for synthesis of α,α-disubstituted carbonyl compounds from carbonyl compounds with one-carbon homologation in only two synthetic operations.

Full text of DOI:10.1016/j.tet.2005.03.054

Tetrahedron 61 (2005) 5067–5080
A new method for synthesis of a,a-disubstituted carbonyl
compounds from carbonyl compounds with one-carbon
homologation through b-oxido carbenoid rearrangement as the
key reaction
Kohsuke Miyashita and Tsuyoshi Satoh
*
Department of Chemistry, Faculty of Science, Tokyo University of Science; Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Received 4 February 2005; accepted 9 March 2005
Available online 12 April 2005
Abstract—The addition reaction of carbonyl compounds with lithium a-sulfinyl carbanions of 1-chloroalkyl p-tolyl sulfoxides gave adducts,
a-chloro b-hydroxy sulfoxides, in high to quantitative yields. The adducts were first treated with a base to give alkoxides, which were treated
with i-PrMgCl or t-BuLi to give b-oxido carbenoids via a sulfoxide–metal exchange reaction. The b-oxido carbenoid rearrangement then
took place to afford the enolates with one-carbon elongation. The enolate intermediates were found to be able to be trapped with electrophiles
such as aldehydes, ethyl chloroformate, benzoyl chloride, haloalkanes to give a,a-disubstituted carbonyl compounds in moderate to good
yields. This method provides a new and efficient way for synthesis of a,a-disubstituted carbonyl compounds from carbonyl compounds with
one-carbon homologation in only two synthetic operations.
q 2005 Elsevier Ltd. All rights reserved.
1
. Introduction
For example, as shown in Scheme 1, Taguchi and
Nozaki reported in 1974 a one-carbon ring enlargement
of cyclododecanone 1 to cyclotridecanone 4 with
Carbonyl compounds are undoubtedly of utmost importance
in organic and synthetic organic chemistry and innumerable
studies have been published for their chemistry and
synthesis. Homologation of carbonyl compounds from
lower carbonyl compounds by carbon–carbon coupling is
an important and extensively used method for preparation of
the desired carbonyl compounds. One-carbon ring-
2
expansion or one-carbon homologation of ketones or
aldehydes via a b-oxido carbenoid is one example of the
homologation and a few methods have been reported.
3
a
dibromomethyllithium through the b-oxido carbenoid 2.
This reaction was expected to proceed via an enolate 3.
Cohen and co-workers used bis(phenylthio)methyl-
4
lithium as a source for the b-oxido carbenoid. We
used lithium a-sulfinyl carbanion of 1-chloroalkyl aryl
sulfoxides as the source for the b-oxido carbenoids.
1
5
These reactions were all presumed to proceed via
enolates (lithium enolate 3 in Taguchi and Nozaki’s
case).
3
–5
Scheme 1.
Keywords: Sulfoxide; Sulfoxide–metal exchange; b-Oxido carbenoid; One-carbon homologation; a,a-Disubstituted carbonyl compound.
Corresponding author. Tel.: C3 5228 8272; fax: C3 3235 2214; e-mail: tsatoh@ch.kagu.tus.ac.jp
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.054

5068
K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
Scheme 2.
Enolates are the most useful reactive intermediates for the
reaction of carbonyl compounds. If the enolates generated
from the b-oxido carbenoid rearrangement mentioned above
could be trapped with electrophiles, the reaction would
afford a new method for synthesis of a-substituted carbonyl
compounds from lower carbonyl compounds with one-
carbon homologation. However, no such investigation has
been reported.
focused our attention on trapping the enolate intermediates
9. Namely, we thought that if we could trap the enolate
intermediates 9 with electrophiles, the whole sequence was
a new method for synthesis of a,a-disubstituted carbonyl
compounds 10 from carbonyl compounds 5 with one-carbon
homologation. This idea was investigated, and, indeed, we
were able to obtain the a,a-disubstituted carbonyl com-
7
pounds 10. In this paper details of the results from this
study are reported.
Previously, we reported a new method for synthesis of
a-substituted carbonyl compounds 10 (EZH) from
carbonyl compounds 5 (Scheme 2). Thus, addition reaction
5
2. Results and discussion
of the lithium a-sulfinyl carbanion of 1-chloroalkyl aryl
sulfoxides 6 with the carbonyl compounds 5 gave the
adducts 7 in high to quantitative yields. The adduct 7 was
first converted to alkoxide and then treated with an
2.1. Synthesis of a-deuterio a-methyl cyclic ketones from
cyclic ketones with one-carbon ring expansion
6
alkylmetal. The sulfoxide–metal exchange reaction took
First, we reinvestigated our one-carbon ring expansion of
cyclic ketones 11 with 1-chloroethyl p-tolyl sulfoxide as the
one-carbon homologating agent through the adducts 12 with
various bases and alkylmetals, and the magnesium b-oxido
carbenoids 13 were found to give better yields compared
place to give b-oxido carbenoid 8. The b-oxido carbenoid
rearrangement of 8 proceeded to give the enolate 9, which
was quenched with H O to give the one-carbon homo-
2
logated a-substituted carbonyl compound 10 in good yield.
5
with the former conditions (LDA and t-BuLi). The
representative reaction is as follows (Table 1). To a solution
Recently, we reinvestigated our reaction. Especially, we
Table 1. Synthesis of 2-deuterio-2-methylcycloalkanones 15 from cycloalkanones 11 with one-carbon ring expansion
Entry
Cycloalkanone 11
Adduct 12
15
a
Yield/%
D-content/%
1
2
12a
12b
15a
15b
70
93
75
95
3
4
5
6
Cyclooctanone
Cyclodecanone
Cyclododecanone
Cyclopentadecanone
12c
12d
12e
12f
15c
15d
15e
15f
54
52
82
78
97
65
51
88
a
1
The deuterium incorporation was measured by H NMR.

K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
5069
of the adduct 12, which was synthesized from ketone 11 and
lithium a-sulfinyl carbanion of 1-chloroethyl p-tolyl sulf-
oxide at K70 8C in almost quantitative yield, in THF at
K45 8C was added t-BuMgCl (1.2 equiv) and the reaction
mixture was stirred for 10 min. By this treatment,
magnesium alkoxide was formed. To this solution was
added 2 equiv of i-PrMgCl and the temperature of the
reaction mixture was allowed to warm to room temperature.
chloroformate needs some comment. In the case of the
reaction with 12a and 12b, prepared from 5- and 6-
membered ketones, the products were found to be the enol
carbonates 17a and 17b (entries 2 and 5). No expected
ketones having an ethoxycarbonyl group at the a-position
were obtained. However, the reaction with 12f prepared
from 15-membered ketone gave the 16-membered ketone
having an ethoxycarbonyl group at the a-position 16f,
though the yield was somewhat low (entry 8). The enol
carbonates and a-ethoxycarbonylated ketones were easily
distinguished from their IR spectrum. The carbonyl
6
The sulfoxide–magnesium exchange reaction took place to
afford the magnesium carbenoid 13. The b-oxido carbenoid
rearrangement of the magnesium carbenoid 13 proceeded to
afford the magnesium enolate 14 with concomitant
elimination of magnesium chloride. Finally, the reaction
absorption of the enol carbonates appears at about 1750–
.
K1
1760 cm
was quenched by adding excess CD OD to give 2-deuterio-
3
2
-methylcycloalkanone 15 in good chemical yield. The
The results in entries 1 and 2 are interesting. If one treats
2-tetralone with a base followed by some electrophiles, the
electrophiles must be substituted on the carbon between the
carbonyl carbon and the phenyl ring, because the hydrogen
on the carbon is more acidic than the hydrogen on the
carbon present on the other side of the carbonyl carbon.
Compounds 16a and 17a in entries 1 and 2 are fairly difficult
to synthesize from 2-tetralone by other methods.
study was carried out by using six kinds of cyclic ketones
and the results are summarized in Table 1.
As shown in Table 1, the adducts 12 derived from
5
2
8
-membered ketone to 15-membered ketone gave the
-methylcycloalkanones with one-carbon expansion in 52–
2% chemical yields. The results for the quenching of this
reaction with CD OD are quite interesting. In the cases in
3
entries 1–3 and 6, 2-deuterated cyclic ketones 15 in good to
high deuterium incorporation were obtained. No regio-
isomer was obtained in these cases. From these results it was
anticipated that when this reaction is quenched with some
electrophiles, 2,2-disubstituted ketones could be obtained.
In contrast to these results, the reaction shown in entries 4
and 5 did not give satisfactory deuterium incorporation. The
results were found to be reproducible and not to be
experimental error. We investigated the proton source for
these reactions; however, at this time the real reason for this
low deuterium incorporation is obscure.
2.3. Synthesis of 2-ethyl- and 2-(4-phenylbutyl)-2-
(substituted)cycloheptanones from cyclohexane-1,4-dione
mono-ethylene ketal with one-carbon ring expansion
Encouraged by the results described above, we investigated
the reaction with 1-chloroalkyl p-tolyl sulfoxides having a
longer carbon chain other than the methyl group (Scheme 3).
The adduct 19, derived from 1,4-cyclohexanedione mono-
ethylene ketal 18 and 1-chloropropyl p-tolyl sulfoxide in
quantitative yield, was treated with i-PrMgCl under the
conditions described in Table 2. However, we obtained the
desired product 20 (35%) with an allylic alcohol 21 (65%)
as a main product.
2
1
.2. Synthesis of 2-methyl-2-(substituted)cycloalkanones
6 and enol carbonates 17 from cycloalkanones with one-
carbon ring expansion
This result implied that when the magnesium carbenoid has
a b-hydrogen, the hydrogen migration to give an olefin is a
faster reaction than the b-oxido carbenoid rearrangement.
Therefore, we applied our former conditions (LDA-t-BuLi)
to 19 and the desired product 20 was obtained in 64% yield
without the allylic alcohol 21.
With new and efficient method for the formation of enolates
with one-carbon ring expansion in hand, we next tried to
trap the enolates with aldehydes, benzoyl chloride, and ethyl
chloroformate, and the results are summarized in Table 2.
5
5
By using the former conditions, the effect of the alkyl
We selected three adducts 12a, 12b and 12f (see Table 1),
because, as mentioned above, these adducts gave the
deuterated and expanded cycloalkanones in good yields
with high deuterium incorporation. First, 12 was treated
with 1.2 equiv of t-BuMgCl at K45 8C followed by
i-PrMgCl (2 equiv) and the reaction mixture was slowly
allowed to warm to room temperature. To this reaction
mixture was added the electrophiles (2 equiv) and the
reaction mixture was stirred at room temperature for 30 min.
Propionaldehyde and benzaldehyde reacted with the enolate
intermediates to give the adducts 16a, 16b, 16c and 16e
substituents in this procedure was investigated and the
results are summarized in Table 3. The adduct 19 having an
ethyl group and the adduct 22 having a 4-phenylbutyl group
as R were used. As shown in Table 3, entries 1–4, 2,2-
disubstituted cycloheptanones having an ethyl group were
obtained from 38–64% yields, which indicated the effec-
tiveness of this procedure. However, comparing these
results (entries 2–4) with those in Table 2, entries 3–6, the
yields are somewhat lower. In these cases, the reaction with
ethyl chloroformate gave the ketones having an ethoxy-
carbonyl group at the a-position (23d and 23g) without the
enol carbonates.
(
entries 1, 3, 4, and 7); however, the yields were found to be
somewhat variable. The reaction with acetone did not give
any adduct and only the corresponding protonated ketones
(
16: EZH) were obtained.
Entries 6 and 7 in Table 3 show that the yield of one-
carbon expanded 2,2-disubstituted cycloheptanones having
a 4-phenylbutyl group was markedly diminished. These
results could be explained by the steric hindrance of the
4-phenylbutyl group.
Benzoyl chloride was also found to be effective in this
procedure to give the benzoylated product in up to 71%
yield (entries 6 and 9). The reaction with ethyl

5070
K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
Table 2. Synthesis of 2-methyl-2-(substituted)cycloalkanones 16 and enol carbonates 17 from cycloalkanones 11 with one-carbon ring expansion
Entry
1
Cycloalkanone 11
Electrophile
Product
Yield/%
a
38
CH
3
CH
2
CHO
16a
17a
16b
2
3
2
ClCOOC H
5
40
a
71
CH
3
CH
2
CHO
a
4
5
6
PhCHO
16c
17b
16d
64
ClCOOC
2
H
5
74
63
PhCOCl
a
7
8
CH
3
CH
2
CHO
16e
16f
16g
73
ClCOOC
2
H
5
33
71
9
PhCOCl
a
A single isomer.
Scheme 3.

K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
5071
Table 3. Synthesis of 2-alkyl-2-(substituted)cycloalkanones 23 from the adduct 19 and 22 with one-carbon ring expansion
Entry
1
19 or 22 (R)
Electrophile
23
Yield/%
CH
CH
CH
CH
3
3
3
3
CH
CH
CH
CH
2
2
2
2
CD
3
3
OD
23a
23b
23c
23d
23e
23f
64 (DZ94%)
a
61
2
3
4
5
6
CH
CH
2
CHO
PhCOCl
38
2
ClCOOC H
5
46
Ph(CH
Ph(CH
Ph(CH
2
)
2
)
2
)
4
CD
3
3
OD
66 (DZ94%)
b
13
4
CH
CH
2
CHO
7
4
2
ClCOOC H
5
23g
44
a
About 4:1 mixture of two diastereomers.
A single isomer.
b
2.4. Synthesis of 2,2-dialkylcycloheptanones from
cyclohexane-1,4-dione mono-ethylene ketal with one-
carbon ring expansion
cyclohepanones (24b and 24c) in good yields. However,
this reaction with iodobutane did not afford any desired
alkylated product.
Treatment of enolates with haloalkanes is the most well-
known procedure for the alkylation of carbonyl compounds
at the a-position. We investigated the trapping of the enolate
intermediates mentioned above with haloalkanes and the
results are summarized in Table 4.
In the case of the adduct having an ethyl group (19), the
enolate was generated with LDA-t-BuLi as mentioned in
Scheme 3 and Table 3 (condition B). The trapping of the
enolate intermediate was tried with iodomethane and allylic
iodide; however, the yields of the desired products were not
satisfactory (entries 4 and 5).
The representative procedure is as follows (Table 4, entry
1). The adduct 12b in THF at K45 8C was treated with
t-BuMgCl followed by i-PrMgCl and the temperature of
2.5. Extension of this procedure to aldehydes
the reaction mixture was allowed to warm to room
temperature. HMPA (4 equiv) followed by iodomethane
Next, this procedure was extended to aldehydes. The
addition reaction of 1-chlorobutyl p-tolyl sulfoxide to
p-anisaldehyde 25a and 3-phenylpropanal 25b
afforded two adducts 26 and 27 in quantitative yields
8
(
4 equiv) was added to the reaction mixture and the
reaction mixture was stirred at room temperature
overnight to give the desired 2,2-dimethylcycloheptanone
5
(see Table 5). Previously, we treated these adducts with
2
4a in 73% yield (condition A). When this reaction was
LDA followed by t-BuLi and found that both 26a and
26b gave ketones 28a and 28b stereospecifically in
high yields (Table 5; entries 1 and 3). Interestingly, the
treatment of 27a gave the aldehyde 29a in good yield
carried out without HMPA, almost no 24a was obtained.
Benzyl bromide and allyl iodide reacted with the enolate
intermediate to give the desired 2,2-dialkylated

5072
K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
Table 4. Synthesis of 2,2-dialkylcycloalkanones 24 from the adduct 12b and 19 with one-carbon ring expansion
Entry
1
12b or 19 (R)
Haloalkane
Conditions
A
24
Yield/%
73
CH
CH
CH
CH
CH
3
3
3
3
3
CH
3
I
24a
24b
24c
24d
24e
2
3
4
5
PhCH Br
2
A
A
B
B
75
59
38
29
CH
CH
2
3
CH I
2
Conditions: A: t-BuMgCl (1.2 equiv), i-PrMgCl (2 equiv), K45 8C w rt, then HMPA (4 equiv) and haloalkane (4 equiv), stirred at room temperature
overnight. B: LDA (1.2 equiv), t-BuLi (4 equiv), K70 8C then HMPA (4 equiv) and haloalkane (4 equiv), stirred at K70 8C for 30 min.
with high stereospecificity (entry 5). The treatment of
7b gave mainly ketone 28b with aldehyde 29b
shown in entries 1–4, the reaction with 26a and 26b was
better conducted with i-PrMgCl than with t-BuLi (compare
entries 1 and 3 with entries 2 and 4). In the cases of the
reaction with the diastereomers 27a and 27b, the yields and
the specificity were found to be variable (entries 5–8).
2
5
(
entry 7).
We reinvestigated this reaction with t-BuMgCl followed by
i-PrMgCl (under the conditions shown in Table 1). The
results are summarized in Table 5, entries 2, 4, 6 and 8. As
We tried to trap the enolate intermediate of the reaction of
Table 5. Treatment of the adducts 26 and 27 derived from aldehydes with t-BuLi and i-PrMgCl
Entry
Adduct
Base
Alkylmetal
Product (28 and 29)
Yield/%
28:29
1
2
3
4
5
6
7
8
26a
26a
26b
26b
27a
27a
27b
27b
LDA (1.2 equiv)
t-BuMgCl (1.2 equiv)
LDA (1.2 equiv)
t-BuMgCl (1.2 equiv)
LDA (1.2 equiv)
t-BuMgCl (1.2 equiv)
LDA (1.2 equiv)
t-BuMgCl (1.2 equiv)
t-BuLi (4 equiv)
i-PrMgCl (2 equiv)
t-BuLi (4 equiv)
i-PrMgCl (2 equiv)
t-BuLi (4 equiv)
i-PrMgCl (2 equiv)
t-BuLi (4 equiv)
i-PrMgCl (2 equiv)
80
99
89
88
76
67
89
50
99:1
99:1
96:4
99:1
1:99
31:69
77:23
96:4

K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
5073
2
6a, 27a, and 26b with CD OD, propionaldehyde, and ethyl
3
Finally, trapping the enolate intermediate from the adducts
26a and 26b with haloalkanes was investigated and the
results are summarized in Table 7. As mentioned above in
Table 4, alkylation of the enolate intermediates with
haloalkanes was carried out better with magnesium enolate
than lithium enolate. The adducts 26a and 26b were treated
with t-BuMgCl followed by i-PrMgCl and the reaction
mixture was allowed to warm to room temperature. To the
reaction mixture was added HMPA followed by iodo-
methane, benzyl bromide, and allyl iodide. As shown in
Table 7 these reactions gave the desired a-alkylated ketones
chloroformate and the results are summarized in Table 6.
Considerably good results were obtained from the trial with
2
8
6a and a,a-disubstituted ketones were produced from 67 to
0% (entries 1–5). Again, the product in this reaction with
ethyl chloroformate was found to be the enol carbonate 30
entries 4 and 5). The same results were obtained with
t-BuLi (condition A) and i-PrMgCl (condition B) (entries 2,
and 4, 5).
(
3
In contrast to these results, although quenching of the
intermediate of the reaction of 27a with CD OD gave the
31 in good to quantitative yields.
3
deuterated aldehyde 29b (entry 6), the reaction with
propionaldehyde did not give the desired adduct but
instead protonated aldehyde 29a (EZH) in 59% yield
2.6. Synthesis of silyl enol ethers from carbonyl
compounds with one-carbon elongation
(
entry 7). The reaction of 26b under the conditions A and B
was carried out and the enolate intermediate was
trapped with propionaldehyde (entries 8 and 9). These
reactions gave the desired adduct 28c and it was found
that the magnesium carbenoid gave much better yield
Silyl enol ethers are important compounds in organic
synthesis. We tried to trap the enolate intermediates with
chlorotrialkylsilane and the results are shown in Scheme 4.
At first, the adduct 12b was treated with t-BuMgCl followed
by i-PrMgCl and the generated enolate was treated with
9
(
entry 9).
Table 6. Synthesis of a-substituted ketones 28 and a-substituted aldehydes 29 from aldehydes 25 through the adducts 26 and 27 with one-carbon elongation
a
Entry
1
Adduct
Conditions
Electrophile
Product
Yield/%
26a
A
CD
3
OD
80 (DZ95%)
2
8a
b
2
3
26a
26a
A
B
CH
3
3
CH
2
CHO
CHO
28b
75
b
75
CH
CH
2
28b
c
4
5
26a
26a
A
B
ClCOOC
2
2
H
H
5
5
67
30
30
c
71
ClCOOC
6
27a
27a
A
A
CD
3
3
OD
76 (DZ82%)
2
9b
7
8
CH
CH
2
CHO
59
2
9a
d
54
26b
26b
A
B
CH
3
3
CH
2
2
CHO
CHO
d
83
9
CH
CH
28c
a
Conditions: A: LDA (1.2 equiv), t-BuLi (4 equiv), K70 8C, then electrophile (4 equiv) stirred at K70 8C for 30 min. B: t-BuMgCl (1.2 equiv), i-PrMgCl
2 equiv), -45 8Cw rt, then electrophile (4 equiv) stirred at room temperature for 30 min.
A mixture of two diastereomers (2:1).
A single isomer.
About 1:1 mixture of two diastereomers.
(
b
c
d

5074
K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
Table 7. Synthesis of a-substituted ketones 31 from the adducts 26a and 26b
Entry
1
Adduct
Haloalkane
Product
Yield/%
99
26a
3
CH I
3
1a
a
Br
2
3
26a
26a
PhCH
2
85
96
3
1b
3
1c
4
5
26b
26b
CH
3
l
85
73
3
1d
a
2
PhCH Br
3
1e
6
26b
82
3
1f
a
The reaction mixture was stirred at room temperature for 19 h.
Me SiCl. This treatment gave the desired trimethylsilyl enol
3
synthesized from cyclohexane-1,4-dione mono-ethylene
ketal 18 in two steps in over 70% yield. From the adduct
26a the silyl enol ether 33 was obtained in 87% yield as a
single isomer.
ether; however, as it was unstable on silica gel, we could not
isolate it. After some investigation, the enolate intermediate
was treated with Et SiCl in the presence of HMPA to give
3
the desired triethylsilyl enol ether 32 in 75% yield. When
this reaction was carried out without HMPA, the yield of 32
was reduced to 54%. As a whole, the silyl enol ether 32 was
In conclusion, we were able to trap the enolate intermediate
of the b-oxido carbenoid rearrangement with several
Scheme 4.

K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
5075
1
The chloroalcohols 12a, 12b, 12c, and 12e have been
reported before.
0
10
5
5
electrophiles to give a,a-disubstituted ketones and triethyl-
silyl enol ethers in moderate to high yields. These reactions
presented herein are a new and efficient method for the
synthesis of a,a-disubstituted ketones from carbonyl
compounds with one-carbon homologation in only two
synthetic operations.
3.1.3. 3-Deuterio-3-methyl-2-tetralone (15a). To a sol-
ution of t-BuMgCl (0.36 mmol) in 3 ml of dry THF in a
flame-dried flask at K45 8C under argon atmosphere was
added a solution of the adduct 12a (101 mg; 0.3 mmol) in
2
ml of dry THF dropwise with stirring. The reaction
mixture was stirred at K45 8C for 10 min. To a solution of
the magnesium alkoxide was added i-PrMgCl (0.6 mmol)
dropwise with stirring. The reaction mixture was stirred at
K45 8C for 10 min and slowly allowed to warm to room
temperature for 2.5 h. The reaction was quenched with
3
. Experimental
3
.1. General
1 13
All melting points are uncorrected. H NMR and C NMR
spectra were measured in a CDCl solution with JOEL
3
excess CD OD. The whole was extracted with CHCl and
3
3
the organic layer was washed with sat. aq. NH Cl and dried
4
over MgSO . The product was purified by silica gel flash
4
column chromatography to afford 15a (33 mg; 70%) as a
colorless oil; IR (neat) 2966, 2932, 1714 (CO), 1492, 1456,
JNM-LA 300, 500 and 600 spectrometer. Electron-impact
mass spectra (MS) were obtained at 70 eV by direct
insertion. Silica gel 60 (Merck) containing 0.5% fluor-
escence reagent 254 and a quartz column were used for
column chromatography and the products having UV
absorption were detected by UV irradiation. In experiments
requiring a dry reagent and solvent, diisopropylamine was
K1
1
1
1
120, 747 cm ; H NMR d 1.19 (3H, s), 2.83 (1H, d, JZ
5.3 Hz), 3.08 (1H, d, JZ15.3 Hz), 3.61 (2H, s), 7.12 (1H,
C
m), 7.18–7.22 (3H, m). MS m/z (%) 161 (M , 47), 160 (67),
131 (24), 117 (61), 104 (100), 91 (17), 78 (13). Calcd for
C H DO: M, 161.0949. Found: m/z 161.0948.
distilled from CaH and THF was distilled from diphenyl-
2
11 11
ketyl. Acetone and HMPA were dried over CaSO and
4
distilled before use.
3.1.4. 9-Duterio-9-methyl-1,4-dioxaspiro[4.6]undecan-8-
one (15b). Colorless oil; IR (neat) 2935, 2882, 1704 (CO),
K1
455, 1372, 1259, 1096, 1055, 1001, 948 cm ; H NMR d
1
1
1
3
3
.1.1. 1-[1-Chloro-1-(p-tolylsulfinyl)ethyl]-1-cyclodeca-
.09 (3H, s), 1.65–1.96 (6H, m), 2.41 (1H, ddd, JZ15.0, 7.1,
nol (12d). To a solution of LDA (1.8 mmol) in 3 ml of
dry THF in a flame-dried flask at K70 8C under argon
atmosphere was added a solution of 1-chloroethyl p-tolyl
sulfoxide (304 mg; 1.5 mmol) in 4 ml of dry THF dropwise
with stirring and the solution was stirred at K70 8C for
.0 Hz), 2.68 (1H, ddd, JZ15.0, 11.6, 3.0 Hz), 3.92–3.98
C
(4H, m). MS m/z (%) 185 (M , 11), 157 (32), 128 (9), 99
(100), 86 (73). Calcd for C H DO : M, 185.1162. Found:
m/z 185.1170.
1
0
15
3
1
0 min. To the reaction mixture was added cyclodecanone
278 mg; 1.8 mmol) dropwise with stirring. The reaction
3.1.5. 2-Deuterio-2-methylcyclononanone (15c). Color-
less oil; IR (neat) 2929, 2872, 1702 (CO), 1467, 1445, 1374,
(
mixture was stirred at K70 8C for 30 min. The reaction was
quenched with sat. aq. NH Cl. The whole was extracted
4
with CHCl . The organic layer was washed with sat. aq.
3
NH Cl and dried over MgSO . The product was purified by
4
K1 1
067 cm ; H NMR d 1.04 (3H, s), 1.23–1.90 (12H, m),
1
2
1
.40 (1H, ddd, JZ13.1, 9.5, 3.1 Hz), 2.49 (1H, ddd, JZ
3.1, 9.5, 3.1 Hz). MS m/z (%) 155 (M , 39), 125 (9), 112
C
4
(49), 98 (100), 84 (36). Calcd for C H DO: M, 155.1419.
Found: m/z 155.1419.
10 17
silica gel column chromatography to afford 12d (187 mg;
5%) as colorless crystals; mp 103–104 8C (AcOEt–
hexane); IR (KBr) 3368 (OH), 2934, 1483, 1413, 1043
3
3.1.6. 2-Deuterio-2-methylcycloundecanone (15d). Color-
less oil; IR (neat) 2930, 2868, 1706 (CO), 1471, 1461, 1374,
K1
1
(
SO), 1015, 809 cm ; H NMR d 1.46 (3H, s), 1.50–2.01
(
16H, m), 2.16 (1H, dt, JZ15.3, 6.7 Hz), 2.36 (1H, dt, JZ
K1
056, 1029 cm ; H NMR d 1.05 (3H, s), 1.26–1.88 (16H,
1
1
1
8
0
5.3, 6.7 Hz), 2.44 (3H, s), 4.10 (1H, s), 7.34 (2H, d, JZ
m), 2.36 (1H, ddd, JZ15.7, 8.9, 2.8 Hz), 2.61–2.67 (1H, m).
MS m/z (%) 183 (M , 43), 125 (39), 111 (40), 98 (71), 83
C
.3 Hz), 7.60 (2H, d, JZ8.3 Hz). MS m/z (%) 356 (M ,
.1), 181 (11), 140 (100), 139 (32), 104 (40), 91 (73). Calcd
C
(50), 69 (61), 55 (100). Calcd for C H DO: M, 183.1733.
Found: m/z 183.1734.
12 21
for C H ClO S: M, 356.1577. Found: m/z 356.1569. Anal.
1
Calcd for C H ClO S: C, 63.93; H, 8.19; Cl, 9.93; S, 8.98.
9
9
29
2
1
29
2
Found: C, 63.95; H, 8.26; Cl, 9.89; S, 8.98.
3.1.7. 2-Deuterio-2-methylcyclotridecanone (15e). Color-
less oil; IR (neat) 2931, 2862, 1709 (CO), 1462, 1374,
K1
1
3.1.2. 1-[1-Chloro-1-(p-tolylsulfinyl)ethyl]-1-cyclopenta-
decanol (12f). Colorless crystals; mp 113–114 8C (CHCl3–
729 cm ; H NMR d 1.04 (3H, s), 1.28–1.40 (17H, m),
1.50–1.56 (1H, m), 1.64–1.71 (1H, m), 1.76–1.82 (1H, m),
2.34 (1H, ddd, JZ16.5, 7.7, 4.0 Hz), 2.58–2.67 (1H, m). MS
hexane); IR (KBr) 3395 (OH), 2928, 2857, 1457, 1411,
1
K1 1
039 (SO), 815 cm ; H NMR d 1.25–1.50 (23H, m), 1.52
C
m/z (%) 211 (M , 42), 181 (20), 153 (16), 139 (16), 125
(13), 111 (29), 98 (54), 83 (47), 69 (58), 55 (100). Calcd for
(
(
(
3H, s), 1.63–1.69 (2H, m), 1.82–1.89 (1H, m), 2.12–2.18
1H, m), 2.26–2.32 (1H, m), 2.44 (3H, s), 4.07 (1H, s), 7.34
C H25DO: M, 211.2045. Found: m/z 211.2046.
14
2H, d, JZ7.9 Hz), 7.67 (2H, d, JZ7.9 Hz). MS m/z (%)
C
26 (M , 0.1), 286 (68), 251 (47), 225 (33), 140 (100), 104
4
3.1.8. 2-Deuterio-2-methylcyclohexadecanone (15f).
Colorless oil; IR (neat) 2929, 2857, 1710 (CO),
(
m/z 426.2345. Anal. Calcd for C H ClO S: C, 67.50; H,
39), 92 (84). Calcd for C H ClO S: M, 426.2359. Found:
2
4
39
2
K1 1
1459, cm ; H NMR d 1.04 (3H, s), 1.22–1.36 (23H, m),
2
4
39
2
9
7
.20; Cl, 8.30; S, 7.51. Found: C, 67.48; H, 9.25; Cl, 8.30; S,
.52.
1.49–1.57 (1H, m), 1.66–1.74 (2H, m), 2.37 (1H, dt, JZ
16.8, 6.7 Hz), 2.47–2.53 (1H, m). MS m/z (%) 253 (M ,
C

5076
K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
6
6
0), 223 (26), 139 (22), 125 (21), 111 (28), 98 (54), 73 (80),
9 (57), 55 (100). Calcd for C H DO: M, 253.2515.
Found: m/z 253.2525.
Calcd for C H O : C, 70.32; H, 7.64. Found: C, 70.23; H,
17 22 4
7.62.
1
7 31
3
1
1
.1.13. Enol carbonate (17b). Colorless oil; IR (neat) 2937,
751 (CO), 1371, 1267 (COC), 1234, 1113, 1098, 1050,
035 cm ; H NMR d 1.33 (3H, t, JZ7.0 Hz), 1.65 (3H,
3
.1.9. 3-(1-Hydroxypropyl)-3-methyl-2-tetralone (16a).
K1
1
To a solution of t-BuMgCl (0.36 mmol) in 3 ml of dry THF
in a flame-dried flask at K45 8C under argon atmosphere
was added a solution of the adduct 12a (101 mg; 0.3 mmol)
in 2 ml of dry THF dropwise with stirring. The reaction
mixture was stirred at K45 8C for 10 min. To a solution of
the magnesium alkoxide was added i-PrMgCl (0.6 mmol)
dropwise with stirring. The reaction mixture was stirred at
K45 8C for 10 min. The reaction mixture was slowly
allowed to warm to room temperature. To a solution of the
enolate was added propionaldehyde (0.05 ml; 0.6 mmol)
dropwise at room temperature with stirring. After 30 min,
s), 1.76 (2H, m), 1.84 (2H, m), 2.15 (2H, m), 2.35 (2H, m),
3
1
3
.94 (4H, s), 4.22 (2H, q, JZ7.0 Hz). C NMR d 153.5
CO). MS m/z (%) 256 (M , 54), 184 (31), 167 (35), 166
C
(
(31), 151 (27), 122 (100), 99 (55), 86 (96), 83 (20). Calcd for
C H O : M, 256.1311. Found: m/z 256.1313.
13 20
5
3
8
1
.1.14. 9-Benzoyl-9-methyl-1,4-dioxaspiro[4.6]undecan-
-one (16d). Colorless oil; IR (neat) 2938, 2885, 1709 (CO),
K1 1
672 (CO), 1447, 1249, 1113, 1056 cm ; H NMR d 1.54
(
(
3H, s), 1.66 (1H, ddd, JZ15.0, 10.1, 0.9 Hz), 1.73–1.89
3H, m), 1.93 (1H, ddt, JZ15.0, 10.1, 1.6 Hz), 2.37 (1H,
the reaction was quenched with sat. aq. NH Cl. The whole
4
ddd, JZ13.8, 7.6, 3.7 Hz), 2.64 (1H, ddd, JZ13.8, 10.7,
.7 Hz), 2.74 (1H, ddd, JZ15.5, 9.8, 1.5 Hz), 3.89–3.97
4H, m), 7.41 (2H, t, JZ8.0 Hz), 7.51 (1H, t, JZ8.0 Hz),
was extracted with CHCl and the organic layer was washed
3
3
(
with sat. aq. NH Cl and dried over MgSO . The product was
4
4
purified by silica gel flash column chromatography to afford
1
3
7
(
.78 (2H, dd, JZ8.0, 1.3 Hz). C NMR d 211.8 (CO), 200.3
CO). MS m/z (%) 288 (M , 14), 260 (8), 149 (15), 105
1
2
7
1
6a (25 mg; 38%) as a colorless oil; IR (neat) 3448 (OH),
966, 2935, 1709 (CO), 1458, 1248, 1119, 1097, 976,
49 cm ; H NMR d 0.93 (3H, s), 1.04 (3H, t, JZ7.3 Hz),
.33–1.42 (1H, m), 1.58–1.64 (1H, m), 2.22 (1H, br s), 2.63
C
K1
1
(100), 86 (27), 77 (30). Calcd for C H O : M, 288.1359.
Found: m/z 288.1356.
17 20 4
(
3
(
1H, d, JZ15.3 Hz), 3.38 (1H, d, JZ15.3 Hz), 3.60 (2H, s),
.80 (1H, br d, JZ11.3 Hz), 7.08–7.12 (1H, m), 7.18–7.24
3H, m). MS m/z (%) 218 (M , 5), 200 (9), 160 (92), 145
3
.1.15. 2-(1-Hydroxypropyl)-2-methylcyclohexadeca-
none (16e). Colorless oil; IR (neat) 3480 (OH), 2930,
857, 1698 (CO), 1461, 1111, 973, 757 cm ; H NMR d
.03 (3H, t, JZ7.3 Hz), 1.10 (3H, s), 1.21–1.31 (23H, m),
.43–1.55 (3H, m), 1.62–1.70 (2H, m), 2.20 (1H, d, JZ
C
K1
1
2
1
1
5
(100), 131 (22), 117 (33), 104 (39), 91 (19). Calcd for
C H O : M, 218.1306. Found: m/z 218.1307.
1
4 18 2
.5 Hz), 2.34–2.45 (1H, m), 2.59 (1H, dt, JZ17.9, 7.5 Hz),
3
2
.1.10. Enol carbonate (17a). Colorless oil; IR (neat) 2984,
917, 1752 (CO), 1276, 1243 (COC), 1037, 747 cm ; H
C
K1
1
3.73–3.76 (1H, m). MS m/z (%) 310 (M , 8), 252 (100), 223
(17), 139 (16), 97 (28), 84 (47), 72 (40). Calcd for
C H O : M, 310.2869. Found: m/z 310.2868.
NMR d 1.37 (3H, t, JZ7.0 Hz), 1.74 (3H, s), 3.48–3.50 (2H,
m), 3.55–3.60 (2H, m), 4.27 (2H, q, JZ7.0 Hz), 7.10–7.18
(
1
9
2
2
0 38 2
1
4H, m). C NMR d 153.2 (CO). MS m/z (%) 232 (M , 18),
3
C
3
.1.16. 2-Methyl-2-ethoxycarbonylcyclohexadecanone
16f). Colorless oil; IR (neat) 2929, 2858, 1741 (CO for
88 (11), 173 (14), 160 (57), 145 (100), 131 (37), 115 (25),
1 (22). Calcd for C H O : M, 232.1098. Found: m/z
32.1096.
(
ester), 1713 (CO for ketone), 1241 (COC), 1099, 1023 cm
1
4 16 3
K1
;
1
H NMR d 1.25 (3H, t, JZ7.0 Hz), 1.18–1.38 (25H, m),
1
3
1
.32 (3H, s), 1.64–1.69 (1H, m), 1.80 (1H, dt, JZ13.3,
.4 Hz), 1.98 (1H, dt, JZ13.3, 3.4 Hz), 2.33 (1H, ddd, JZ
7.7, 8.3, 6.4 Hz), 2.55 (1H, dt, JZ17.7, 7.6 Hz), 4.17 (2H,
3
[
.1.11. 9-(1-Hydroxypropyl)-9-methy-1,4-dioxaspiro-
4.6]undecan-8-one (16b). Colorless oil; IR (neat) 3480
K1
1
3
(
OH), 2970, 2879, 1699 (CO), 1464, 1200, 1111, 756 cm
;
q, JZ7.0 Hz). C NMR d 207.9 (CO for ketone), 173.6
1
C
CO for ester). MS m/z (%) 324 (M , 6), 126 (27), 112
H NMR d 1.00 (3H, t, JZ7.3 Hz), 1.08 (3H, s), 1.26–1.31
1H, m), 1.47–1.55 (1H, m), 1.59–1.66 (2H, m), 1.70–1.80
2H, m), 1.83–1.89 (1H, m), 1.91–1.97 (1H, m), 2.19 (1H,
(
(
(
(100), 98 (17). Calcd for C H O : M, 324.2663. Found:
m/z 324.2665.
2
0 36 3
dd, JZ15.3, 10.7 Hz), 2.51 (1H, ddd, JZ12.6, 8.9, 2.2 Hz),
2
1
1
.75 (1H, ddd, JZ12.6, 11.6, 2.5 Hz), 3.54 (1H, d, JZ
3
.1.17. 2-Benzoyl-2-methylcyclohexadecanone (16 g).
Colorless crystals; mp 76–77 8C (hexane); IR (KBr) 2931,
856, 1709 (CO), 1670 (CO), 1468, 1245, 1224, 964,
C
0.7 Hz), 3.96 (4H, s). MS m/z (%) 242 (M , 1), 214 (16),
84 (62), 129 (29), 122 (41), 99 (100), 86 (70). Calcd for
2
K1
1
C H O : M, 242.1517. Found: m/z 242.1524.
1
3
22
4
707 cm ; H NMR d 1.16–1.46 (23H, m), 1.47 (3H, s),
1
.66–1.71 (1H, m), 1.88 (1H, dt, JZ14.0, 4.9 Hz), 2.01 (1H,
3
.1.12. 9-[Hydroxy(phenyl)methyl]-9-methyl-1,4-dioxa-
spiro[4.6]undecan-8-one (16c). Colorless crystals; mp
ddd, JZ17.7, 8.6, 5.5 Hz), 2.14 (1H, dt, JZ14.0, 3.4 Hz),
2.60 (1H, ddd, JZ17.7, 8.6, 6.7 Hz), 7.40 (2H, t, JZ
7.3 Hz), 7.51 (1H, t, JZ7.3 Hz), 7.77 (2H, d, JZ7.3 Hz).
1
1
1
1
49–150 8C (AcOEt–hexane); IR (KBr) 3430 (OH), 2946,
K1
1
C
685 (CO), 1113, 1040, 705 cm ; H NMR d 1.02 (3H, s),
.35 (1H, ddd, JZ15.3, 9.2, 0.9 Hz), 1.64–1.75 (2H, m),
.84–1.93 (2H, m), 2.30 (1H, dd, JZ15.0, 11.0 Hz), 2.52
MS m/z (%) 356 (M , 17), 157 (22), 147 (25), 105 (100), 77
(17). Calcd for C24
356.2723.
H O : M, 356.2713. Found: m/z
36 2
(
2
1H, ddd, JZ12.2, 9.2, 2.2 Hz), 2.67 (1H, d, JZ4.3 Hz),
.83 (1H, dt, JZ12.2, 2.2 Hz), 3.90–3.96 (4H, m), 4.83 (1H,
3.1.18. 8-[1-Chloro-1-(p-tolylsulfinyl)propyl]-1,4-dioxa-
spiro[4.5]decan-8-ol (19). Colorless crystals; mp 127–
129 8C (CHCl –hexane); IR (KBr) 3303 (OH), 2942, 2887,
C
d, JZ4.0 Hz), 7.27–7.34 (5H, m). MS m/z (%) 290 (M ,
trace), 184 (28), 156 (37), 99 (100), 86 (89), 77 (52). Calcd
for C H O : M, 290.1519. Found: m/z 290.1526. Anal.
3
K1
1
1441, 1376, 1101, 1035 (SO), 998, 813 cm ; H NMR d
1
7 22 4

K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
5077
0
3
7
5
.90 (3H, t, JZ7.3 Hz), 1.69–2.32 (10H, m), 2.44 (3H, s),
.92–3.99 (4H, m), 4.06 (1H, br s), 7.33 (2H, d, JZ8.0 Hz),
.65 (2H, d, JZ8.0 Hz). Anal. Calcd for C H ClO S: C,
dry THF in a flame-dried flask at K70 8C under argon
atmosphere was added a solution of the adduct 19 (112 mg;
0.3 mmol) in 2 ml of dry THF dropwise with stirring. The
reaction mixture was stirred at K70 8C for 10 min. To a
solution of the lithium alkoxide was added t-BuLi
1
8
25
4
7.98; H, 6.76; Cl, 9.51; S, 8.60. Found: C, 57.97; H, 6.77;
Cl, 9.47; S, 8.46.
(
1.2 mmol) dropwise with stirring. The reaction mixture
was stirred at K70 8C for 30 min. The reaction was
quenched with excess CD OD. The whole was extracted
with CHCl . The organic layer was washed with sat. aq.
NH Cl and dried over MgSO . The product was purified by
3
8
.1.19. Synthesis of 9-ethyl-1,4-dioxaspiro[4.6]undecan-
-one 20 and 8-(1-propenyl)-1,4-dioxaspiro[4,5]decan-8-
3
ol 21 from the adduct 19. To a solution of t-BuMgCl
0.36 mmol) in 3 ml of dry THF in a flame-dried flask at
3
(
4
4
K45 8C under argon atmosphere was added a solution of the
adduct 19 (112 mg; 0.3 mmol) in 2 ml of dry THF dropwise
with stirring. The reaction mixture was stirred at K45 8C for
silica gel flash column chromatography to afford 23a
(38 mg; 64%) as a colorless oil; IR (neat) 2938, 2877,
K1
1
1699 (CO), 1455, 1111, 1066, 1048, 948 cm ; H NMR d
0.89 (3H, t, JZ7.3 Hz), 1.43 (1H, dq, JZ14.1, 7.3 Hz),
1.64–1.71(3H, m), 1.76–1.91 (4H, m), 2.28–2.36 (1H, m),
1
0 min. To a solution of the magnesium alkoxide was added
i-PrMgCl (0.6 mmol) dropwise with stirring. The reaction
mixture was stirred at K45 8C for 10 min and slowly
allowed to warm to room temperature for 2.5 h. The reaction
C
2.67–2.73 (1H, m), 3.95 (4H, s). MS m/z (%) 199 (M , 71),
157 (38), 143 (37), 137 (18), 115 (28), 99 (100), 86 (73).
was quenched with sat. aq. NH Cl. The whole was extracted
4
Calcd for C11H17DO : M, 199.1316. Found: m/z 199.1309.
3
with CHCl . The organic layer was washed with sat. aq.
3
NH Cl and dried over MgSO . The product was purified by
4
silica gel flash column chromatography to afford 20 (21 mg;
3.2.3. 9-Ethyl-9-(1-hydroxypropyl)-1,4-dioxaspiro-
[4.6]undecan-8-one (23b). Colorless oil (about 4:1 mixture
of two diastereomers); IR (neat) 3479 (OH), 2934, 2881,
4
3
2
0
1
5%) and 21 (39 mg; 65%). 20: Colorless oil; IR (neat)
K1 1
937, 2878, 1704 (CO), 1455, 1100, 1028 cm ; H NMR d
K1 1
1695 (CO), 1108, 975 cm ; H NMR d 0.86 (2.4H, t, JZ
7.6 Hz), 0.90 (0.6H, t, JZ7.3 Hz), 1.01 (3H, t, JZ7.3 Hz),
1.32–1.38 (1H, m), 1.48–1.58 (2H, m), 1.74–1.96 (7H, m),
2.52 (1H, ddd, JZ12.1, 8.9, 3.4 Hz), 2.66–2.72 (2H, m),
3.72 (1H, d, JZ10.7 Hz), 3.96 (4H, s). MS m/z (%) 256
.90 (3H, t, JZ7.3 Hz), 1.43 (1H, quintet, JZ7.3 Hz), 1.65–
.91 (7H, m), 2.31–2.37 (2H, m), 2.67–2.73 (1H, m), 3.95
C
(4H, s). MS m/z (%) 198 (M , 19), 170 (45), 155 (40), 141
(23), 99 (100), 86 (100). Calcd for C H O : M, 198.1256.
1
1 18 3
C
Found: m/z 198.1253. 21: Colorless oil; IR (neat) 3464
(
(M , 0.6), 198 (72), 170 (22), 155 (18), 136 (41), 99 (100),
86 (89). Calcd for C H O : M, 256.1674. Found: m/z
256.1676.
K1 1
OH), 2931, 2883, 1367, 1253, 1097, 972 cm ; H NMR d
1
4 24 4
1
6
.26 (1H, br s, OH), 1.59–1.67 (4H, m), 1.70 (3H, dd, JZ
.4, 1.5 Hz), 1.78 (2H, dt, JZ11.9, 3.4 Hz), 1.92 (2H, dt,
JZ11.9, 3.4 Hz), 3.92–3.98 (4H, m), 5.60 (1H, dq, JZ15.6,
.5 Hz), 5.71 (1H, dq, JZ15.6, 6.4 Hz). MS m/z (%) 198
3.2.4. 9-Benzoyl-9-ethyl-1,4-dioxaspiro[4.6]undecan-8-
one (23c). Colorless oil; IR (neat) 2963, 2881, 1721 (CO),
1
C
M , 0.4), 99 (100), 86 (40), 69 (13). Calcd for C H O :
K1 1
1669 (CO), 1447, 1226, 1113, 701 cm ; H NMR d 0.79
(
M, 198.1255. Found: m/z 198.1261.
1
1 18 3
(3H, t, JZ7.6 Hz), 1.60 (1H, dd, JZ14.1, 10.1 Hz), 1.79–
1
.91 (5H, m), 2.31–2.41 (2H, m), 2.57 (1H, ddd, JZ13.1,
10.1, 4.3 Hz), 2.72 (1H, dd, JZ14.7, 9.8 Hz), 3.88–3.98
4H, m), 7.40 (2H, t, JZ7.3 Hz), 7.51 (1H, dt, JZ7.3,
3
.2. Synthesis of 20 from 19 with LDA-t-BuLi
(
To a solution of LDA (0.36 mmol) in 3 ml of dry THF in a
flame-dried flask at K70 8C under argon atmosphere was
added a solution of the adduct 19 (112 mg; 0.3 mmol) in
1.2 Hz), 7.81 (2H, dd, JZ7.3, 1.2 Hz). MS m/z (%) 302
(M , 11), 274 (7), 197 (7), 180 (6), 149 (18), 105 (100), 77
C
(25). Calcd for C H O : M, 302.1518. Found: m/z
8 22 4
1
2
ml of dry THF dropwise with stirring. The reaction
302.1518.
mixture was stirred at K70 8C for 10 min. To a solution of
the lithium alkoxide was added t-BuLi (1.2 mmol) dropwise
with stirring. The reaction mixture was stirred at K70 8C for
3.2.5. 9-Ethyl-9-ethoxycarbonyl-1,4-dioxaspiro[4.6]un-
decan-8-one (23d). Colorless oil; IR (neat) 2969, 2883,
K1
3
The whole was extracted with CHCl . The organic layer was
0 min. The reaction was quenched with sat. aq. NH Cl.
1733 (CO), 1712 (CO), 1234 (COC), 1113, 1052, 1027 cm
;
4
1
3
H NMR d 0.88 (3H, t, JZ7.3 Hz), 1.26 (3H, t, JZ7.0 Hz),
1.68–1.75 (2H, m), 1.79–1.85 (1H, m), 1.89–2.03 (4H, m),
2.21–2.25 (1H, m), 2.58–2.61 (2H, m), 3.92–3.97 (4H, m),
washed with sat. aq. NH Cl and dried over MgSO . The
4
4
product was purified by silica gel flash column chromato-
graphy to afford 20 (38 mg, 64%).
1
3
4.19 (2H, dq, JZ7.0, 2.1 Hz). C NMR d 209.6 (CO for
ketone), 172.1 (CO for ester); MS m/z (%) 270 (M , 14), 242
C
3
.2.1. 8-[1-Chloro-5-phenyl-1-(p-tolylsulfinyl)pentyl]-
,4-dioxaspiro[4.5]decan-8-ol (22). Colorless amorphous;
(44), 213 (45), 196 (21), 142 (26), 99 (100), 86 (74). Calcd for
C H O : M, 270.1467. Found: m/z 270.1462.
1
IR (KBr) 3393 (OH), 2934, 1453, 1255, 1106, 1037 (SO),
1
4 22 5
K1
01 cm ; H NMR d 1.43–2.50 (17H, m), 2.44 (3H, s),
.92–3.99 (4H, m), 7.09–7.31 (7H, m), 7.59 (2H, d, JZ
.3 Hz). MS (FAB) m/z (%) 477 ([MCH] , 48), 319 (57),
01 (30), 275 (22), 185 (24), 154 (39), 117 (50), 91 (100), 77
1
7
3
8
3
3.2.6. 9-Deuterio-9-(4-phenylbutyl)-1,4-dioxaspiro-
[4.6]undecan-8-one (23e). Colorless oil; IR (neat) 2934,
C
K1 1
2859, 1700 (CO), 1453, 1113, 1069, 750, 700 cm ; H
NMR d 1.23–1.41 (4H, m), 1.59–1.90 (8H, m), 2.29–2.34
(1H, m), 2.59 (2H, t, JZ7.6 Hz), 2.66–2.72 (1H, m), 3.94
(
23). Calcd for C H ClO S: MCH, 477.1866. Found: m/z
26 34 4
4
77.1869.
(4H, s), 7.14–7.19 (3H, m), 7.24–7.29 (2H, m). MS m/z (%)
3
C
04 (M , 22), 276 (18), 246 (15), 171 (22), 156 (25), 130
3.2.2. 9-Deuterio-9-ethyl-1,4-dioxaspiro[4.6]undecan-8-
one (23a). To a solution of LDA (0.36 mmol) in 3 ml of
(15), 109 (18), 99 (96), 86 (100). Calcd for C H DO : M,
19 25 3
303.1942. Found: m/z 303.1938.

5078
K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
3.2.7. 9-(1-Hydroxypropyl)-9-(4-phenylbutyl)-1,4-dioxa-
spiro[4.6]undecan-8-one (23f). Colorless oil; IR (neat)
3.2.11. 9-Allyl-9-methyl-1,4-dioxaspiro[4.6]undecan-8-
one (24c). Colorless oil; IR (neat) 3076, 2938, 2879, 1702
(CO), 1638 (C]C), 1462, 1438, 1366, 1325, 1111, 1049,
3
7
494 (OH), 2933, 1694 (CO), 1454, 1112, 974, 749,
00 cm ; H NMR d 1.01 (3H, t, JZ7.3 Hz), 1.16–2.04
K1
1
K1 1
1001, 911, 756 cm ; H NMR d 1.07 (3H, s), 1.62–1.87
(5H, m), 2.02 (1H, dd, JZ14.7, 10.1 Hz), 2.23 (2H, d, JZ
7.4 Hz), 2.43 (1H, dt, JZ11.5, 2.2 Hz), 2.70 (1H, dt, JZ
11.5, 2.2 Hz), 3.91–4.00 (4H, m), 5.04 (1H, d, JZ18.7 Hz),
5.07 (1H, d, JZ11.3 Hz), 5.67–5.75 (1H, m). MS m/z (%)
(
(
(
(
(
3
15H, m), 2.46–2.52 (1H, m), 2.56–2.62 (2H, m), 2.66–2.72
1H, m), 3.63–3.65 (1H, m), 3.92–3.98 (4H, m), 7.12–7.19
C
3H, m), 7.24–7.29 (2H, m). MS m/z (%) 360 (M , 3), 302
52), 274 (22), 155 (27), 149 (24), 108 (18), 99 (100), 91
C
71). Calcd for C H O : M, 360.2298. Found: m/z
224 (M , 10), 196 (18), 167 (12), 142 (14), 113 (15), 99
(100), 86 (60). Calcd for C H O : M, 224.1411. Found:
m/z 224.1405.
2
2 32 4
60.2289.
1
3 20 3
3.2.8. 9-Ethoxycarbonyl-9-(4-phenylbutyl)-1,4-dioxa-
spiro[4.6]undecan-8-one (23 g). Colorless oil; IR (neat)
3.2.12. 9-Ethyl-9-methyl-1,4-dioxaspiro[4.6]undecan-8-
one (24d). To a solution of LDA (0.36 mmol) in 3 ml of
dry THF in a flame-dried flask at K70 8C under argon
atmosphere was added a solution of the adduct 19 (75 mg;
0.2 mmol) in 2 ml of dry THF dropwise with stirring. The
reaction mixture was stirred at K70 8C for 10 min. To a
solution of the lithium alkoxide was added t-BuLi
(1.2 mmol) dropwise with stirring. The reaction mixture
was stirred at K70 8C for 30 min. To a solution of the
enolate was added HMPA (0.14 ml; 0.8 mmol) dropwise
with stirring. After being stirred for 10 min, to the reaction
mixture was added iodomethane (0.05 ml; 0.8 mmol)
dropwise with stirring. After 30 min, the reaction was
2
1
934, 1733 (CO for ester), 1712 (CO for ketone), 1454,
224 (COC), 1150, 1112, 749, 701 cm ; H NMR d 1.23
K1
1
(
3H, t, JZ7.2 Hz), 1.28–1.37 (3H, m), 1.58–1.72 (4H, m),
1
2
2
.79–1.84 (1H, m), 1.88–1.99 (4H, m), 2.17–2.26 (1H, m),
.57–2.61 (3H, m), 3.90–3.98 (4H, m), 4.16 (2H, dq, JZ7.2,
.2 Hz), 7.15 (3H, m), 7.25 (2H, m). C NMR d 209.5 (CO
1
3
C
for ketone), 172.2 (CO for ester). MS m/z (%) 374 (M , 43),
3
46 (17), 317 (21), 300 (11), 242 (30), 181 (14), 143 (14),
13 (17), 99 (100). Calcd for C H O : M, 374.2091.
Found: m/z 374.2088.
1
2
2 30 5
3
(
.2.9. 9,9-Dimethyl-1,4-dioxaspiro[4.6]undecan-8-one
24a). To a solution of t-BuMgCl (0.24 mmol) in 2 ml of
quenched with sat. aq. NH Cl. The whole was extracted
4
with CHCl . The organic layer was washed with sat. aq.
3
dry THF in a flame-dried flask at K45 8C under argon
atmosphere was added a solution of adduct 12b (72 mg;
NH Cl and dried over MgSO . The products were separated
4
4
by silica gel flash column chromatography to afford 24d
0
.2 mmol) in 2 ml of dry THF dropwise with stirring. The
(
(
(
16 mg; 38%) as a colorless oil; IR (neat) 2965, 2880, 1702
CO), 1464, 1438, 1111, 1088, 1049 cm ; H NMR d 0.82
3H, t, JZ7.6 Hz), 1.04 (3H, s), 1.49–1.64 (4H, m), 1.71–
reaction mixture was stirred at K45 8C for 10 min. To a
solution of the magnesium alkoxide was added i-PrMgCl
K1
1
(
0.4 mmol) dropwise with stirring. The reaction mixture
1
1
.76 (2H, m), 1.85–1.90 (1H, m), 2.03 (1H, dd, JZ15.1,
was stirred at K45 8C for 10 min and slowly allowed to
warm to room temperature for 2.5 h. To a solution of the
enolate was added hexamethylphosphoramide (HMPA)
1.3 Hz), 2.30 (1H, ddd, JZ11.6, 8.6, 2.2 Hz), 2.79 (1H, dt,
C
JZ11.6, 2.2 Hz), 3.92–4.00 (4H, m). MS m/z (%) 212 (M ,
7
), 184 (52), 169 (37), 155 (15), 142 (15), 113 (21), 99
100), 86 (96). Calcd for C H O : M, 212.1410. Found:
(
0.14 ml; 0.8 mmol) dropwise at room temperature. The
reaction mixture was stirred for 10 min and iodomethane
0.05 ml; 0.8 mmol) was added dropwise with stirring. After
(
m/z 212.1406.
1
2 20 3
(
being stirred for 19 h, the reaction was quenched with sat.
aq. NH Cl. The whole was extracted with CHCl . The
organic layer was washed with sat. aq. NH Cl and dried
3.2.13. 9-Allyl-9-ethyl-1,4-dioxaspiro[4.6]undecan-8-one
(24e). Colorless oil; IR (neat) 3076, 2939, 2881, 1701 (CO),
4
3
4
K1
1
over MgSO . The product was purified by silica gel flash
4
1462, 1440, 1112, 1048, 994, 913 cm ; H NMR d 0.79
(3H, t, JZ7.2 Hz), 1.48–1.87 (8H, m), 2.17 (1H, dd, JZ
14.4, 7.8 Hz), 2.39 (1H, t, JZ7.2 Hz), 2.41 (1H, dd, JZ8.4,
1.8 Hz), 2.69 (1H, dt, JZ11.4, 2.4 Hz), 3.92–3.98 (4H, m),
5.04 (1H, d, JZ16.8 Hz), 5.06 (1H, d, JZ7.8 Hz), 5.65–
column chromatography to afford 24a (29 mg, 73%) as
colorless crystals; mp 61–62 8C (hexane); IR (KBr) 2958,
K1
1
2
1
2
6
876, 1699 (CO), 1471, 1112, 1043, 916 cm ; H NMR d
.10 (6H, s), 1.67–1.70 (2H, m), 1.79–1.83 (4H, m), 2.56–
.59 (2H, m), 3.95 (4H, s). Anal. Calcd for C H O : C,
C
5.71 (1H, m). MS m/z (%) 238 (M , 5), 210 (25), 195 (11),
181 (12), 142 (12), 113 (15), 99 (100), 86 (60). Calcd for
1
1 18 3
6.64; H, 9.15. Found: C, 66.63; H, 9.29.
C H O : M, 238.1568. Found: m/z 238.1570.
14 22 3
3
.2.10. 9-Benzyl-9-methyl-1,4-dioxaspiro[4.6]undecan-8-
one (24b). Colorless crystals; mp 97–98 8C (AcOEt–
2
6a, 26b, 27a, 27b, 28a, 28b, 29a, and 29b have been
reported before.
5
hexane); IR (KBr) 2955, 2884, 1695 (CO), 1455, 1436,
1
K1 1
109, 1078, 1061, 703 cm ; H NMR d 1.06 (3H, s), 1.53–
1
.85 (5H, m), 2.06 (1H, dd, JZ15.0, 10.1 Hz), 2.42 (1H,
3.2.14. 2-Deuterio-1-(4-methoxyphenyl)-1-pentanone
(28a). Colorless oil; IR (neat) 2959, 2934, 1679 (CO),
ddd, JZ11.8, 8.9, 2.5 Hz), 2.59 (1H, dt, JZ11.8, 2.5 Hz),
2
3
MS m/z (%) 274 (M , 38), 246 (50), 217 (21), 183 (16), 160
(20), 145 (19), 131 (22), 117 (32), 99 (100), 91 (73), 71 (14).
Calcd for C H O : M, 274.1567. Found: m/z 274.1566.
Anal. Calcd for C H O : C, 74.42; H, 8.08. Found: C,
22
K1
1
.76 (1H, d, JZ13.4 Hz), 2.81 (1H, d, JZ13.4 Hz), 3.89–
1602, 1510, 1258, 1171, 1031, 838 cm ; H NMR d 0.95
(3H, t, JZ7.5 Hz), 1.41 (2H, sextet, JZ7.5 Hz), 1.71 (2H,
quintet, JZ7.5 Hz), 2.91 (1H, t, JZ7.5 Hz), 3.87 (3H, s),
6.93 (2H, d, JZ8.5 Hz), 7.95 (2H, d, JZ8.5 Hz). MS m/z
.99 (4H, m), 7.08 (2H, d, JZ7.0 Hz), 7.20–7.28 (3H, m).
C
C
(%) 193 (M , 3), 150 (27), 136 (9), 135 (100), 107 (7), 92
(7), 77 (12). Calcd for C H DO : M, 193.1211. Found: m/
z 193.1207.
1
7 22 3
17
3
12 15
2
7
4.24; H, 8.07.

K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
5079
3.2.15. 3-Hydroxy-1-(4-methoxyphenyl)-2-propyl-1-pen-
tanone (28b). Colorless oil (about 2:1 mixture of two
0.84 (3H, t, JZ7.3 Hz), 1.20–1.35 (2H, m), 1.47–1.54 (1H,
m), 1.70–1.80 (1H, m), 2.75 (1H, dd, JZ13.7, 7.6 Hz), 3.08
(1H, dd, JZ13.7, 7.6 Hz), 3.68 (1H, quintet, JZ7.6 Hz),
3.84 (3H, s), 6.88 (2H, d, JZ9.2 Hz), 7.12–7.23 (5H, m),
diastereomers). Main product: IR (neat) 3445 (OH), 2960,
2
K1
934, 1661 (CO), 1600, 1260, 1172, 1031, 841 cm ; H
1
C
NMR d 0.89 (3H, t, JZ7.4 Hz), 0.96 (3H, t, JZ7.3 Hz),
7.85 (2H, d, JZ9.2 Hz). MS m/z (%) 282 (M , 5), 240 (18),
1
8
6
.23–1.51 (4H, m), 1.70–1.82 (2H, m), 3.21 (1H, d, JZ
.5 Hz), 3.49–3.53 (1H, m), 3.71–3.76 (1H, m), 3.88 (3H, s),
136 (9), 135 (100), 91 (12), 77 (7). Calcd for C H O : M,
282.1618. Found: m/z 282.1611.
1
9 22 2
.96 (2H, d, JZ8.5 Hz), 7.95 (2H, d, JZ8.5 Hz). MS m/z
C
(
%) 250 (M , trace), 208 (7), 192 (5), 150 (17), 135 (100),
3.2.21. 1-(4-Methoxyphenyl)-2-propylpent-4-en-1-one
(31c). Colorless oil; IR (neat) 3077, 2959, 2873, 1673
9
2
7
1
2 (6), 77 (7). Calcd for C H O : M, 250.1568. Found: m/z
5 22 3
1
1
K1 1
50.1569. Minor product: H NMR d 0.87 (3H, t, JZ
.2 Hz), 0.98 (3H, t, JZ7.5 Hz), 1.19–1.30 (3H, m), 1.45–
,56 (1H, m), 1.67–1.73 (1H, m), 1.81–1.89 (1H, m), 2.79
(CO), 1600, 1248, 1171, 1032, 841 cm ; H NMR d 0.87
(3H, t, JZ7.3 Hz), 1.28 (2H, sextet, JZ7.6 Hz), 1.47–1.54
(1H, m), 1.68–1.80 (1H, m), 2.24 (1H, quintet, JZ7.0 Hz),
2.49 (1H, quintet, JZ7.0 Hz), 3.47 (1H, quintet, JZ
7.3 Hz), 3.87 (3H, s), 4.95 (1H, d, JZ10.1 Hz), 5.02 (1H,
(
1H, br s), 3.49 (1H, dt, JZ9.8, 4.0 Hz), 3.75–3.80 (1H, m),
3
8
.88 (3H, s), 6.96 (2H, d, JZ8.9 Hz), 7.96 (2H, d, JZ
.9 Hz).
d, JZ13.5 Hz), 5.74 (1H, m), 6.94 (2H, d, JZ8.9 Hz), 7.95
C
(
2H, d, JZ8.9 Hz). MS m/z (%) 232 (M , 2), 190 (17), 136
3
2
8
.2.16. Enol carbonate (30). Colorless oil; IR (neat) 2961,
935, 1760 (CO), 1610, 1514, 1251 (COC), 1175, 1018,
37 cm ; H NMR d 0.90 (3H, t, JZ7.3 Hz), 1.28 (3H, t,
(9), 135 (100), 92 (8), 77 (9). Calcd for C H O : M,
15 20 2
232.1462. Found: m/z 232.1468.
K1
1
JZ7.3 Hz), 1.44 (2H, sextet, JZ7.3 Hz), 2.15 (2H, q, JZ
.3 Hz), 3.82 (3H, s), 4.16 (2H, q, JZ7.3 Hz), 5.50 (1H, t,
JZ7.3 Hz), 6.89 (2H, d, JZ8.5 Hz), 7.35 (2H, d, JZ
3.2.22. 4-Methyl-1-phenylheptan-3-one (31d). Colorless
oil; IR (neat) 2961, 2932, 2873, 1712 (CO), 1496, 1455,
7
K1
1
1377, 1082, 750, 700 cm ; H NMR d 0.87 (3H, t, JZ
7.4 Hz), 1.03 (3H, d, JZ7.1 Hz), 1.18–1.32 (3H, m), 1.56–
1.63 (1H, m), 2.50 (1H, sextet, JZ7.1 Hz), 2.75 (2H, dt, JZ
7.6, 3.6 Hz), 2.89 (2H, t, JZ7.6 Hz), 7.15–7.20 (3H, m),
1
3
C
8
1
.5 Hz). C NMR d 159.5 (CO). MS m/z (%) 264 (M , 24),
91 (20), 174 (18), 163 (100), 136 (8), 135 (37), 121 (14), 92
(
7), 77 (11). Calcd for C H O : M, 264.1360. Found: m/z
15 20 4
C
2
64.1357.
.2.17. 2-Deuterio-2-(4-methoxyphenyl)pentanal (29b).
Colorless oil; IR (neat) 2959, 2933, 2714 (CHO), 1722
7.27 (2H, t, JZ7.6 Hz). MS m/z (%) 204 (M , 15), 162
(55), 133 (41), 119 (12), 105 (100), 91 (99), 71 (42). Calcd
for C H O: M, 204.1514. Found: m/z 204.1521.
3
1
4 20
K1 1
(
CO), 1513, 1250, 1180, 1034 cm ; H NMR d 0.91 (3H, t,
3.2.23. 4-Benzyl-1-phenylheptan-3-one (31e). Colorless
oil; IR (neat) 3028, 2958, 2931, 1713 (CO), 1455, 1082,
JZ7.3 Hz), 1.28 (2H, sextet, JZ7.3 Hz), 1.68 (1H, dt, JZ
K1
1
1
3.8, 7.3 Hz), 2.00 (1H, dt, JZ13.8, 8.0 Hz), 3.80 (3H, s),
748, 699 cm ; H NMR d 0.85 (3H, t, JZ7.0 Hz), 1.18–
1.27 (2H, m), 1.35–1.42 (1H, m), 1.57–1.64 (1H, m), 2.39
(1H, ddd, JZ17.7, 9.5, 6.1 Hz), 2.57–2.85 (6H, m), 7.06
(2H, d, JZ7.3 Hz), 7.09 (2H, d, JZ7.3 Hz), 7.14–7.27 (6H,
6
s). MS m/z (%) 193 (M , 15), 164 (58), 163 (20), 122 (100),
.91 (2H, d, JZ8.9 Hz), 7.11 (2H, d, JZ8.9 Hz), 9.63 (1H,
C
121 (88), 92 (10). Calcd for C H DO : M, 193.1211.
12 15 2
Found: m/z 193.1211.
C
m). MS m/z (%) 280 (M , 15), 237 (31), 189 (7), 175 (14),
147 (9), 133 (20), 117 (7), 105 (39), 91 (100), 77 (7). Calcd
for C H O: M, 280.1828. Found: m/z 280.1829.
3
.2.18. 5-Hydroxy-1-phenyl-4-propylheptan-3-one (28c).
2
0 24
Colorless oil (about 1:1 mixture of inseparable two
diastereomers); IR (neat) 3424 (OH), 2964, 2935, 1705
3.2.24. 1-Phenyl-4-propylhept-6-en-3-one (31f). Colorless
oil; IR (neat) 2959, 2932, 2873, 1712 (CO), 1641, 1454,
K1
1
(
0
CO), 1456, 1152, 1114, 1086, 974, 700 cm ; H NMR d
.87 (1.5H, t, JZ7.3 Hz), 0.88 (1.5H, t, JZ7.3 Hz), 0.92
K1
1
1083, 916, 700 cm ; H NMR d 0.86 (3H, t, JZ7.3 Hz),
1.20 (2H, sextet, JZ7.3 Hz), 1.33–1.40 (1H, m), 1.52–1.58
(1H, m), 2.14 (1H, quintet, JZ7.1 Hz), 2.29 (1H, quintet,
JZ7.1 Hz), 2.51–2.57 (1H, m), 2.73 (2H, t, JZ7.4 Hz),
2.87 (2H, t, JZ7.4 Hz), 4.96–5.01 (2H, m), 5.62–5.71 (1H,
m), 7.15–7.22 (3H, m), 7.26–7.29 (2H, m). MS m/z (%) 230
(
(
1.5H, t, JZ7.3 Hz), 0.95 (1.5H, t, JZ7.3 Hz), 1.16–1.71
6H, m), 2.31 (0.5H, m), 2.43 (0.5H, br d, JZ7.3 Hz), 2.57–
2
7
1
.62 (1H, m), 2.74–2.92 (4H, m), 3.57–3.65 (1H, m), 7.18–
.21 (3H, m), 7.27–7.30 (2H, m). MS m/z (%) 248 (M , 2),
90 (38), 148 (28), 133 (37), 105 (81), 91 (100), 77 (15).
C
C
Calcd for C H O : M, 248.1774. Found: m/z 248.1764.
16 24 2
(M , 6), 188 (32), 133 (56), 105 (100), 91 (91), 77 (12).
Calcd for C H O: M, 230.1671. Found: m/z 230.1673.
1
6 22
3
.2.19. 1-(4-Methoxyphenyl)-2-methylpentan-1-one
31a). Colorless oil; IR (neat) 2960, 2932, 1672 (CO),
(
3.2.25. 9-Methyl-8-triethylsiloxy-1,4-dioxaspiro[4.6]un-
dec-8-ene (32). To a solution of t-BuMgCl (0.24 mmol) in
2 ml of dry THF in a flame-dried flask at K45 8C under
argon atmosphere was added a solution of the adduct 12b
(72 mg, 0.2 mmol) in 2 ml of dry THF dropwise with
stirring. The reaction mixture was stirred at K45 8C for
10 min. To a solution of the magnesium alkoxide was added
i-PrMgCl (0.4 mmol) dropwise with stirring. The reaction
mixture was stirred at K45 8C for 10 min and slowly
allowed to warm to room temperature. To a solution of the
enolate was added HMPA (0.14 ml; 0.8 mmol) dropwise at
room temperature with stirring. After being stirred for
K1
600, 1509, 1243, 1214, 1174, 1032, 973, 841 cm ; H
1
1
NMR d 0.90 (3H, t, JZ6.9 Hz), 1.18 (3H, d, JZ6.9 Hz),
1
.27–1.47 (3H, m), 1.68–1.83 (1H, m), 3.44 (1H, sextet, JZ
6
.9 Hz), 3.87 (3H, s), 6.94 (2H, d, JZ8.7 Hz), 7.95 (2H, d,
C
JZ8.7 Hz). MS m/z (%) 206 (M , 2), 164 (18), 136 (9), 135
(100), 92 (8), 77 (10). Calcd for C H O : M, 206.1307.
Found: m/z 206.1307.
13 18 2
3
(
1
.2.20. 2-Benzyl-1-(4-methoxyphenyl)pentan-1-one
31b). Colorless oil; IR (neat) 2958, 2932, 1671 (CO),
K1
600, 1509, 1244, 1170, 1031, 840, 700 cm ; H NMR d
1

5080
K. Miyashita, T. Satoh / Tetrahedron 61 (2005) 5067–5080
10 min, to a solution of the enolate was added triethyl-
silylchloride (0.1 ml; 0.6 mmol) dropwise with stirring.
References and notes
After 30 min, the reaction was quenched with H O. The
2
1. For reviews: (a) William Lever, O., Jr. Tetrahedron 1976, 32,
1943. (b) Martin, S. F. Synthesis 1979, 633. (c) Stowell, J. C.
Chem. Rev. 1984, 84, 409. (d) Badham, N. F. Tetrahedron
2004, 60, 11.
whole was extracted with CH Cl . The organic layer was
2
2
washed with H O and dried over MgSO . The product was
2
4
purified by silica gel flash column chromatography to afford
3
2 (45 mg, 75%) as a colorless oil; IR (neat) 2954, 2877,
2. (a) Krow, G. R. Tetrahedron 1987, 43, 3. (b) Hesse, M. In Ring
Enlargement in Organic Chemistry; VHC: Weinheim, 1991.
(c) Dowd, P.; Zhang, W. Chem. Rev. 1993, 93, 2091.
3. (a) Taguchi, H.; Yamamoto, H.; Nozaki, H. J. Am. Chem. Soc.
1974, 96, 6510. (b) Taguchi, H.; Yamamoto, H.; Nozaki, H.
Tetrahedron Lett. 1976, 2617. (c) Taguchi, H.; Yamamoto, H.;
Nozaki, H. Bull. Chem. Soc. Jpn. 1977, 50, 1592. (d) Villieras, J.;
Perriot, P.; Normant, J. F. Synthesis 1979, 968. (e) Ward, H. D.;
Teager, D. S.; Murray, Jr.; R, K. J. Org. Chem. 1992, 57, 1926.
K1
678, 1377, 1239, 1176, 1110, 1018, 860, 744 cm ; H
1
1
NMR d 0.65 (6H, q, JZ7.9 Hz), 0.98 (9H, t, JZ7.9 Hz),
1
2
2
.64 (3H, s), 1.70–1.73 (2H, m), 1.75–1.78 (2H, m), 2.02–
.06 (2H, m), 2.23–2.28 (2H, m), 3.93 (4H, s). MS m/z (%)
C
98 (M , 100), 253 (24), 237 (81), 207 (36), 197 (25), 183
(22), 123 (25), 115 (45), 99 (66), 87 (78). Calcd for
C H O Si: M, 298.1963. Found: m/z 298.1963.
1
6 30 3
4
. Abraham, W. D.; Bhupathy, M.; Cohen, T. Tetrahedron Lett.
987, 28, 2203.
3
(
1
8
1
.2.26. 1-(4-Methoxyphenyl)-1-triethylsiloxy-1-butene
33). Colorless oil; IR (neat) 2957, 2877, 1609, 1511,
249, 1127, 846, 745 cm ; H NMR d 0.61 (6H, q, JZ
.0 Hz), 0.88 (3H, t, JZ7.3 Hz), 0.93 (9H, t. JZ8.0 Hz),
.39 (2H, sextet, JZ7.3 Hz), 2.07 (2H, q, JZ7.3 Hz), 3.82
1
5
. (a) Satoh, T.; Itoh, N.; Gengyo, K.; Yamakawa, K.
Tetrahedron Lett. 1992, 33, 7543. (b) Satoh, T.; Itoh, N.;
Gengyo, K.; Takada, S.; Asakawa, N.; Yamani, Y.;
Yamakawa, K. Tetrahedron 1994, 50, 11839.
K1
1
(
3H, s), 4.97 (1H, t, JZ7.3 Hz), 6.86 (2H, d, JZ8.9 Hz),
6
. (a) Satoh, T. J. Syn. Org. Chem. Jpn. 1996, 54, 481. (b) Satoh,
T. J. Syn. Org. Chem. Jpn. 2003, 61, 98.
C
7
.33 (2H, d, JZ8.9 Hz). MS m/z (%) 306 (M , 30), 277
100), 249 (49), 135 (24), 115 (23), 87 (28). Calcd for
C H O Si: M, 306.2013. Found: m/z 306.2014.
(
7
. Preliminary results of this study were reported as a
communication: Satoh, T.; Miyashita, K. Tetrahedron Lett.
1
8 30 2
2
004, 45, 4859.
. (a) Pirkle, W. H.; Adams, P. E. J. Org. Chem. 1980, 45, 4111.
b) Acherar, S.; Audran, G.; Cecchin, F.; Monti, H.
8
9
(
Acknowledgements
Tetrahedron 2004, 60, 5907.
. (a) Colvin, E. W. In Silicon in Organic Synthesis; Butterworths:
London, 1981. (b) Weber, W. P. In Silicon Reagents for Organic
Synthesis; Springer: Berlin, 1983. (c) Colvin, E. W. In Silicon
Reagents in Organic Synthesis; Academic: London, 1988.
This work was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan, which is gratefully
acknowledged. We thank Mr. Kei Kobayashi for his
assistance in this study.
10. Satoh, T.; Onda, K.; Yamakawa, K. J. Org. Chem. 1991, 56,
4129.