Diethylamino(trimethyl)silane-mediated direct 1,4-addition of naked aldehydes to electron-deficient olefins

Article abstract of DOI:10.1039/b005728m

Diethylamino(trimethyl)silane-mediated direct 1,4-addition of naked aldehydes to electron-deficient olefins was discussed. Results showed that after the reaction the latent formyl groups were transformed back to aldehydes. Conjugated addition of aldehydes to electron-deficient olefins showed no successful precedents of direct 1,4-addition of naked aldehydes.

Full text of DOI:10.1039/b005728m

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Diethylamino(trimethyl)silane-mediated direct 1,4-addition of
naked aldehydes to electron-deficient olefins
a
a
a
b
a
Hisahiro Hagiwara,* Nao Komatsubara, Hiroki Ono, Tomoyuki Okabe, Takashi Hoshi,
a
b
c
1
Toshio Suzuki, Masayoshi Ando and Michiharu Kato
a
b
Graduate School of Science and Technology and Faculty of Engineering, Niigata University,
050, 2-nocho, Ikarashi, Niigata 950-2181, Japan. E-mail: hagiwara@gs.niigata-u.ac.jp;
Fax/tel: ϩ81-25-262-7368
8
c
Institute for Chemical Reaction Science, Tohoku University, Katahira, Aoba-ku,
Sendai 980-8577, Japan
Received (in Cambridge, UK) 17th July 2000, Accepted 20th November 2000
First published as an Advance Article on the web 11th January 2001
Aldehydes directly add in a 1,4-manner to electron-deficient olefins in the presence of diethylamino(trimethyl)silane.
Introduction
Clean and quantitative generation of enolates or enols of alde-
hydes has been difficult because of the high reactivity of the
formyl group under either basic or acidic reaction conditions.
Such lability of the formyl group imposes a difficulty to the
control of nucleophilic reactions of aldehydes. In order to solve
such problems, aldehydes were transformed to stable synthons
Scheme 2
which were then treated with electrophiles. After the reaction,
5
substituted aldehydes 10 (Scheme 2). To the best of our know-
ledge, this is the first example of the synthesis of 5-keto- or
other substituted aldehydes by 1,4-addition of naked aldehydes.
Though there are several examples of a one-pot procedure for
the latent formyl groups were transformed back to aldehydes. In
the case of conjugate addition of aldehydes to electron-deficient
olefins, there have been no successful precedents of direct 1,4-
addition of naked aldehydes. The products, substituted 5-keto
aldehydes such as 3, 5 or 7 (Scheme 1), have been important
1
,4-addition of naked aldehydes followed by intramolecular
aldol condensation, intermediary 5-keto aldehydes have never
been isolated under the reaction conditions.
6
Results and discussion
As new reagents for such purposes, we paid attention to
aminosilane derivatives which so far have been underdeveloped
as reagents for carbon–carbon bond-forming reactions other
7
8
than silylation of an alcohol or amine, dealkylation of an
9
10
ester, ring opening of oxiranes, and synthesis of a silylenol
ether or enamine, though during the course of our study,
Saidi et al. reported some synthetic applications in C–C bond-
forming reactions via iminium cation intermediates generated
by diethylamino(trimethyl)silane (DEATMS).
11
12
13
Conjugate addition of decanal 8a to but-3-en-2-one 9a (᎐2)
᎐
was at first investigated as a probe to investigate optimized reac-
1
2
3
tion conditions (Scheme 2, R = C H , R = R = H, EWG =
8
17
COMe). The results are listed in Table 1. Among the reagents
14
tested, DEATMS was found to give the best result (Table 1,
entry 8). Use of chlorotrimethylsilane, triethylamine or tris(tri-
methylsilyl)amine led to only recovered aldehyde 8a (Table 1,
entry 2, 3 or 4). Other silylamine derivatives such as trimethyl-
silylpyrrolidine or bis(dimethylamino)dimethylsilane provided
2-(3-oxobutyl)decanal 10a in lower yield (Table 1, entry 5
Scheme 1
compounds, especially for syntheses of substituted cyclohex-2-
enone derivatives which have themselves been versatile starting
1
or 7). Diethylamine (Et NH) also gave an unsatisfactory result
2
materials for syntheses of natural products such as terpenoids.
(Table 1, entry 6).
So far, these 5-ketoaldehydes have been prepared mainly by the
Further tuning of the reaction conditions revealed that 0.5
mol equiv. of DEATMS was enough (Table 2, entries 1 and 2).
In entries 2–8, starting aldehyde 8 was recovered without any
side product. The reaction was carried out simply by stirring the
reaction mixture at room temperature overnight under nitrogen
atmosphere, and evaporation of excessive reagents in vacuo
followed by purification by medium-pressure liquid chromato-
graphy of the residue provided 5-keto aldehydes 10. Some
2
1
,4-addition of masked aldehydes, i.e. piperidinoenamine 1
of an aldehyde, trimethylsilylenol ether 4 of an aldehyde in the
3
presence of Lewis acid, or diethylallylamine 6 in the presence
4
of a catalytic amount of Ru complex, to but-3-en-2-one 2
(
Scheme 1).
We disclose herein a novel protocol for direct 1,4-addition
of naked aldehydes 8 to electron-deficient olefins 9 to give
3
16
J. Chem. Soc., Perkin Trans. 1, 2001, 316–322
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b005728m

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Table 3 1,4-Addition of aldehydes 8 with electron-deficient olefins 9 in
a
Table 1 Investigation of reagents for 1,4-addition
a
CH CN at reflux
3
2
-(3-Oxobutyl)decanal 10a
b
3
Olefin 9 (R = H)
Entry
Reagent
Yield (%)
Aldehyde 8
Product 10
1
2
b
Entry
R
EWG
R
Yield (%)
c
1
2
3
4
5
6
7
8
None
ClSiMe3
0
0
0
0
c
c
c
1
2
3
4
5
6
C
C
8
H
H
17
17
17
COMe
COMe
COMe
COMe
COMe
COMe
H
H
H
H
H
H
10a
10a
10a
54
66
78
Et N
3
d
c
8
N(SiMe3)3
C H
8
C H NSiMe
29
35
46 (80)
4
8
3
i
Pr
10e (᎐ 3) 64
Et NH
2
d
PhCH
2
10f
10g
59
96
Me Si(NMe )
2
2
2
d
DEATMS
67
a
b
Reaction was carried out without solvent. Yield is based on initial
c
d
7
8
9
0
11
2
3
4
THPOC
3
H
16
6
COMe
COMe
COEt
COEt
H
H
H
H
H
H
H
Me
10h
10i
89
76
76
68
32
34
55
20
aldehyde 8a. Decanal was recovered completely. Yield in parentheses
based on the aldehyde consumed.
AcOC H
8
C H
8
10j
17
1
PhCH2
C H
10k
10l
10m
10n
10d
a
SO Ph
Table 2 1,4-Addition of aldehydes 8 to vinyl ketones 9
8
17
2
1
1
1
PhCH2
C H
SO Ph
2
CO Me
8
17
17
2
5
-Keto
C H
8
COMe
Vinyl ketone 9
(EWG = COMe)
aldehyde 10a–e
Yield (%)
b
a
b
Entry
Aldehyde 8
1 mol equiv. of DEATMS was used. Yield is based on aldehyde 8.
c
d
Dichloromethane was employed as solvent. 10 mol% of DEATMS
1
2
3
was used.
1
2
3
4
5
6
7
8a R = C H
9a R = R = H (᎐ 2)
10a
10a
10b
10c
10d
67c
22
15
49
35
8
17
17
17
13
17
1
2
3
8a R = C H
9a R = R = H (᎐ 2)
2 3
8
1
8a R = C H
9b R = H, R = Me
a
8
Table 4 1,4-Addition of aldehydes 8 with α-methylenecycloalkanones
1
2
3
8b R = C H
9a R = R = H (᎐ 2)
2 3
6
1
8a R = C H
9c R = Me, R = H
2 3
8
b,c
1
i
Entry
1
Mesyl ester 11
Product 13
8c R = Pr
9a R = R = H (᎐ 2)
10e (᎐ 3) 22
1
2
3
8d R = PhCH
9a R = R = H (᎐ 2)
10f
10g
58
13
2
d
2
3
13a 67% (46%)
8
8e
9a R = R = H (᎐ 2)
a
11a
All reactions were conducted at room temp. overnight with 0.5 mol
equiv. of DEATMS without solvent unless otherwise indicated.
2
3
13b 47%
b
All reagents were used directly from bottles. Yield is based on initial
aldehyde 8. DEATMS (0.2 mol equiv.) was used.
c
1
1b
1c
representative results of the present reaction are shown in Table
2
to but-3-en-2-one 9a (᎐ 2) was not a serious side reaction in
spite of the report by Hosomi and co-workers, probably due
to the lower reaction temperature used here.
13c 69%
. Conjugate addition of the diethylamino group of DEATMS
᎐
15
1
Though the reaction without solvent satisfies the demands
of environmentally benign ‘green’ chemistry, the reactions with
aldehydes having substituents at the β position to the formyl
group such as isovaleraldehyde 8c (Table 2, entry 6), citronellal
8
9
e (Table 2, entry 8), or with less reactive olefins such as 9b or
c (Table 2, entry 3 or 5), were sluggish and gave lower yields.
e
4
5
6
7
8
11d
11d
11d
11d
11d
13d R = C H , 77% (52% )
Our continuing efforts to improve the reaction conditions
revealed that the reaction in refluxing acetonitrile solution
provided improved yields, thereby expanding the generality of
the present reaction as shown in Table 3. The reaction in
dichloromethane gave lower yields (Table 3, entries 1 and 2).
Not only isovaleraldehyde 8c but also citronellal 8e provided
8
17
e R = AcOC H , 67%
8
16
f R = THPOC H , 65%
3
6
g R = PhCH , 56%
2
h R =
, 45%
1
,4-addition product 10e (᎐3) or 10g in good yield (Table 3,
᎐
entry 4 or 6). For medium-scale reaction of citronellal 8e (100
mmol) (Table 3, entry 6), addition of 10 mol% of DEATMS
was sufficient to achieve satisfactory yield after simple bulb-to-
bulb distillation (see Experimental section). The mildness of the
reaction is well exemplified by the successful results of the
reaction with acid- or base-sensitive aldehydes having tetra-
hydropyran-2-yl (THP) or acetyl protecting groups (Table 3,
entries 7 or 8).
9
0
11e
11e
13i R = C
H17, 83%
8
1
a
j R = PhCH , 76%
2
b
DEATMS (2.4 mol equiv.) was used in CH Cl . Yield is based
on initial mesyl 11. A mixture of diastereomers was obtained.
The reaction was carried out in CH CN. Equivalent amounts of
2
2
c
d
e
3
DBU and DEATMS were used in CH Cl .
2
2
Then, conjugate addition to enones having a fixed s-cis
configuration was investigated. Reaction of aldehydes 8 with
α-methylenecycloalkanones 12 generated in situ from the
corresponding mesyl ester 11 and DEATMS in CH Cl pro-
and DEATMS did not give any better yield (Table 4, entry 4).
Products were mixtures of diastereomers. These reactions
proceeded well in CH Cl rather than in CH CN (Table 4,
2
2
vided keto aldehydes 13 in good yield irrespective of ring size
Scheme 3, Table 4). Initial formation of the α-methylene-
cyclohexanone from the mesyl ester 11d with 1,8-diazabicyclo-
5.4.0]undec-7-ene (DBU) followed by addition of aldehyde
2
2
3
(
entry 1).
The 5-keto aldehydes 10a–k and 13a–h thus obtained are
[
useful precursors for several carbocyclic compounds. Intra-
J. Chem. Soc., Perkin Trans. 1, 2001, 316–322
317

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populations of dimethylamino(trimethyl)silane and dimethyl-
17
amine by ab initio calculations at the MP2/6-31G(d) level
indicated that the electron densities on the nitrogen atoms of
both molecules were the same (Ϫ0.59). On the other hand,
charge separation between nitrogen and heteroatoms of Me2-
NSiMe was greater than that of FSiMe which was a stronger
3
3
Lewis acid. This result alludes to the postulate that DEATMS
works as both Lewis base and Lewis acid. However, treat-
ment of decanal 8a with DEATMS in the presence of D O in
2
deuteriochloroform in an NMR tube revealed no deuterium
incorporation at the α position to the formyl group of decanal
8
a. Thus, formation of the enolate of decanal 8a by DEATMS
did not occur.
On the reactivity of aminotrimethylsilanes toward carbonyl
compounds, two inconsistent papers appeared at the same
11a
time. Hellberg and Juarez reported trimethylsilyl enol ether
Scheme 3
formation in the presence of a catalytic amount of toluene-p-
12
sulfonic acid. On the other hand, Weinreb and co-workers
molecular aldol condensation of the 5-keto aldehyde 10g
followed by dehydration provided a 4-substituted cyclohex-
-enone which has been applied to the syntheses of bis-
abolane sesquiterpenoids. The result will be reported in due
course. Similarly, treatment of the keto aldehydes 13a–c with
potassium hydroxide in methanol (Scheme 4) furnished in
reported enamine formation under the same reaction con-
ditions. The reaction was repeated again and it was found that
decanal 8a reacted with DEATMS in deuteriochloroform in an
NMR tube to give enamine 19 (R = C H ) at room temperature
2
16
8
17
after 22 h as shown by the chemical-shift data [δ 4.18 (dt, J 13.8
4,18
and 7 Hz) and 5.86 (d, J 13.8 Hz)]
of olefinic protons
(
(
Scheme 6). The ratio of diethylaminoenamine of decanal 19
R = C H ) to decanal 8a was 1.3:1 according to peak area.
8
17
Addition of D O to this enamine mixture did not show
2
any decrease of peak area for proton(s) α to the formyl group
probably due to trimethylsilanol (TMSOH) or water generated.
Formation of the silyl enol ether of decanal 8a was not
observed. These results suggest the intervention of an enamine
intermediate in the present reaction.
Only 0.1 equiv. of DEATMS was sufficient to promote the
,4-addition reaction in 96% yield (Table 3, entry 6; see
Scheme 4
1
Experimental section). This result suggests that DEATMS
satisfactory yield diastereomeric mixtures of aldols 14a–c
having bicyclo[n ϩ 2.3.1]carbon frameworks which are also
useful core units for terpenoid syntheses. An attempt to
equilibrate the aldols into thermodynamically more stable
diastereomers by prolonging the reaction time did not diminish
the amount of initial diastereomer.
or related intermediates work catalytically, though Et NH
2
itself did not give a satisfactory yield of 1,4-addition product
1
0a (Table 1, entry 6).
Important support for the reaction pathway was obtained by
the following experiment. Diethylaminoenamine 19 of decanal
8
a (R = C H ) was prepared according to the procedure of
8
17
Intramolecular 1,4-conjugate addition was also possible,
as shown in Scheme 5. Treatment of aldehydic enone 15
2
Stork. NMR measurement of diethylaminoenamine 19 soon
after Kugelrohr distillation revealed that the distillate was
obtained as a mixture of enamine 19, decanal 8a (19:8a =
1
.3:1) and diethylamine. In view of the highly volatile nature
of diethylamine, the present NMR observation indicates that
diethylamine was generated by hydrolysis of diethylamino-
enamine 19 by moisture during transfer in spite of initial drying
18
of the NMR tube under vacuum. Reaction of decanal 8a,
but-3-en-2-one 2 and a catalytic amount of mixture of the
enamine 19 and 8a in refluxing acetonitrile provided 1,4-
addition product 10a in 74% yield. Thus, the present reaction
seems to proceed by recycling enamine 19 generated initially
by DEATMS or Et NH. Since it is known that TMSOH
2
dehydrates to trimethylsiloxane under either acidic or basic
19
conditions,
Actually, in the presence of molecular sieves powder 4 Å and
.2 equiv. of DEATMS in refluxing CH CN, citronellal 8e
the resulting water co-catalysed the cycle.
0
3
Scheme 5
provided only 20% of 1,4-addition product 10g along with
4
8% recovery of 8e. Extensive efforts to trap trimethylsiloxane
with DEATMS in MeCN at room temperature afforded keto
aldehyde 16 in 73% yield as a 7:3 diastereomeric mixture.
In the formation of a six-membered ring, the thermo-
dynamically more stable keto aldehyde 18 was obtained as a
single diastereomer by similar 1,4-conjugate addition of the
starting material 17.
Details regarding mechanistic considerations are yet to
be discussed. One obvious question regarding the reaction
pathway is the role of DEATMS. Initially, the ability of
DEATMS as a base was estimated. Comparison of Mulliken
at liquid nitrogen temperature failed during Kugelrohr
distillation.
Thus, a plausible reaction pathway for the present 1,4-
conjugate addition is drawn by regenerating diethylamino-
18
enamine 19 as shown in Scheme 6. A fair degree of instability
of diethylaminoenamine 19 might drive the catalytic cycle
forward.
In summary, a new practical entry to direct 1,4-conjugate
addition of naked aldehydes to electron deficient olefins was
realized for the first time. At the same time, new reactivity of
3
18
J. Chem. Soc., Perkin Trans. 1, 2001, 316–322

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Scheme 6 Plausible reaction pathway.
DEATMS which has been quite limited so far in organic
in vacuo followed by MPLC purification (eluent: n-hexane–ethyl
synthesis was developed. The novelty as well as mildness of the
reaction conditions and simplicity of operation should make
the present reaction highly synthetically useful.
acetate = 4:1) provided the keto aldehyde 10a (150 mg, 67%),
νmax/cm 2958, 2929, 2857, 1724, 1466, 1457, 1366 and 1163;
δH (200 MHz) 0.88 (t, J 6.2, 3H), 1.20–1.50 (br s, 12H), 1.60–
Ϫ1
20
2
(
2
.00 (m, 4H), 2.14 (s, 3H), 2.30 (m, 1H), 2.46 (br t, 2H) and 9.55
d, J 2.8, 1H); δC (50 MHz) 13.9, 22.1, 22.5, 26.8, 28.8,
9.0, 29.2, 29.5, 29.8, 31.6, 40.5, 51, 204.6 and 207.6; m/z 226
Experimental
ϩ
IR spectra were recorded on a JASCO FT/IR 8300 or a
Shimadzu FT/IR-4200 spectrophotometer for solutions in
(M , 3%), 208 (4), 198 (6), 127 (18), 114 (22), 86 (21), 71 (24),
59 (43), 58 (100) and 43 (50) (Found: M , 226.1906. Calc. for
ϩ
1
tetrachloromethane. H NMR spectra were obtained for solu-
C H O : M, 226.1933).
14
26
2
tions in deuteriochloroform with JEOL FX 90Q (90 MHz)
or Varian Gemini 200H (200 MHz) instruments with tetra-
2-(1-Methyl-3-oxobutyl)decanal 10b
13
methylsilane as internal standard. J-Values are given in Hz.
NMR spectra were measured with a Varian Gemini 200H
50 MHz) instrument. Mass spectral data were run on a JEOL
C
Ϫ1
Yield 15% (a mixture of inseparable diastereomers); νmax/cm
2
928, 2710, 1741, 1721, 1466, 1373, 1240, 1164, 1048 and 909;
(
δH (90 MHz) 0.7–1.04 (br, t ϩ d, 6H), 1.05–1.8 (m, 15H), 2.13
JMS-DX300, a JEOL JMS-GCMATE or Hitachi M-80B
instrument. Medium-pressure liquid chromatography (MPLC)
was carried out on a JASCO PRC-50 instrument with a silica
gel packed column.
Repeated elemental analyses of the compounds in this
section provided no satisfactory results probably due to
instabilites of the formyl groups. Efforts to get high-resolution
mass spectral data were also in vain because of the low
intensity of molecular peaks. We are ready to supply copies of
NMR spectral charts for verification of the purity of our
samples.
ϩ
(
6
(
s, 3H), 2.1–2.7 (m, 3H) and 9.6 (d, J 3, 1H); m/z 240 (M ,
%), 183 (19), 154 (18), 128 (19), 110 (22), 109 (29), 97 (29), 95
33), 85 (68), 83 (29), 71 (42), 70 (29), 69 (56), 67 (30), 59 (86),
5
8 (100), 57 (55), 56 (33), 55 (75) and 41 (68).
2
-(3-Oxobutyl)octanal 10c
Ϫ1
Yield 49%; νmax/cm 2931, 1721, 1467, 1457, 1414, 1366, 1162
and 908; δH (90 MHz) 0.87 (br t, J 6.1, 3H), 1.1–2.3 (m, 5H),
1.27 (br s, 10H), 2.14 (s, 3H) and 9.55 (d, J 2.6, 1H); m/z 196
ϩ
(M Ϫ 2 , 8%), 168 (15), 139 (13), 110 (15), 98 (37), 84 (22),
Commercially available aldehydes, electron-deficient olefins
and DEATMS were used as purchased. Commercially available
83 (17), 71 (22), 69 (25), 58 (23), 55 (36) and 43 (100).
special-grade MeCN was used directly from the bottle. CH Cl2
2-(2-Methyl-3-oxobutyl)octanal 10d
2
was distilled from calcium hydride prior to use.
Two diastereomers were isolated and are listed in their order
of elution. Isomer I, yield 17%; νmax/cm 2957, 2726, 1718
Ϫ1
2
-(3-Oxobutyl)decanal 10a
and 1707; δ (200 MHz) 0.88 (t, J 6.1, 3H), 1.10 (d, J 7.0, 3H),
H
Reaction without solvent. To a stirred mixture of decanal
1.20–1.45 (br s, 14H), 1.50–1.71 (m, 2H), 2.15 (s, 3H), 2.25
(m, 1H), 2.50–2.70 (br q, 1H) and 9.54 (d, J 3.1, 1H).
Isomer II, yield 17%; νmax/cm 2957, 2693, 1718 and 1707;
δH (200 MHz) 0.88 (t, J 6.2, 3H), 1.14 (d, J 7.0, 3H), 1.20–1.40
(br s, 14H), 1.40–1.70 (m, 2H), 2.16 (s, 3H), 2.30 (br s, 1H), 2.54
3
3
(
0.190 cm , 1 mmol) and DEATMS (0.085 cm , 0.5 mmol) was
3
Ϫ1
added but-3-en-2-one (0.100 cm , 1.2 mmol) at 0 ЊC under
a nitrogen atmosphere. The resulting mixture was stirred at
room temperature overnight. Evaporation of excess of reagents
J. Chem. Soc., Perkin Trans. 1, 2001, 316–322
319

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(
8
q, J 7.0, 1H) and 9.52 (d, J 3.1, 1H); m/z 128 (4%), 110 (6),
5 (10), 72 (100), 57 (30) and 55 (37).
1.60 (br s, 18H), 1.70–2.00 (m, 2H), 2.26 (m, 1H), 2.35–2.50 (m,
ϩ
2H), 2.42 (q, J 7.3, 2H) and 9.55 (d, J 2.3, 1H); m/z 240 (M ,
4%), 222 (20), 183 (33), 123 (22), 109 (26), 95 (33), 85 (20),
83 (20), 82 (28), 81 (27), 73 (34), 72 (100), 57 (86), 55 (42), 43
33) and 41 (40).
1
2
-Isopropyl-5-oxohexanal 10e (᎐3)
᎐
(
Reaction in MeCN. A stirred solution of isovaleraldehyde
3
3
(
0.107 cm , 1 mmol), but-3-en-2-one (0.100 cm , 1.2 mmol) and
3 3
2-Benzyl-5-oxoheptanal 10k
DEATMS (0.189 cm , 1 mmol) in MeCN (4 cm ) was heated
at reflux for 9 h. The resulting solution was passed through a
short silica gel column and the residue was purified by MPLC
(
1
Ϫ1
Yield 68%; νmax/cm 3067, 3031, 2940, 2710 and 1722; δ (200
H
MHz) 1.02 (t, J 7.3, 3H), 1.70–2.00 (m, 2H), 2.36 (q, J 7.2, 2H),
2.44 (m, 1H), 2.55–2.80 (m, 3H), 3.02 (dd, J 13.0, 6.6, 1H),
7.10–7.35 (m, 5H) and 9.64 (d, J 2.3, 1H); δC (50 MHz) 7.8,
22.3, 35.4, 35.9, 39.2, 52.6, 126.6, 128.6, 128.9, 138.3, 204.0
eluent: n-hexane–ethyl acetate = 4 : 1) to give the keto aldehyde
Ϫ1
0e (᎐ 3) (101 mg, 64%), νmax/cm 2965, 2710, 1723 and 1710;
᎐
δH (200 MHz) 0.97 (d, J 6.6, 3H), 0.99 (d, J 6.0, 3H), 1.70–2.10
m, 3H), 2.13 (s, 3H), 2.28–2.63 (m, 3H) and 9.61 (d, J 2.8, 1H);
ϩ
(
and 210.5; m/z 216 (M Ϫ 2, 6%), 188 (44), 159 (15), 131 (34),
ϩ
ϩ
m/z 154 (M Ϫ 2, 10%), 126 (35), 111 (18), 87 (22), 84 (44), 69
46), 58 (40) and 43 (100).
117 (50), 104 (24), 91 (100) and 57 (73) (Found: M , 218.1337.
(
Calc. for C H O : M, 218.1306).
14
18
2
2
-Benzyl-5-oxohexanal 10f
2-[2-(Phenylsulfonyl)ethyl]decanal 10l
Ϫ1
Ϫ1
Yield 58%; νmax/cm 3031, 2930, 2710, 1720, 1497, 1456, 1356
and 1160; δH (200 MHz) 1.65–2.05 (m, 2H), 2.09 (s, 3H), 2.43
(
Yield 32%; νmax/cm 3070, 2930, 2716, 1728, 1323 and 1154;
δH (200 MHz) 0.88 (t, J 6.3, 3H), 1.20–1.50 (br s, 14H), 1.80–
2.13 (m, 2H), 2.45 (br t, 1H), 3.10 (t, J 9.8, 1H), 3.13 (t, J 8.6,
1H), 7.53–7.72 (m, 3H), 7.91 (dd, J 8.2, 1.6, 2H) and 9.57 (d,
J 1.6, 1H); δ (50 MHz) 14.0, 21.1, 22.6, 26.6, 28.6, 29.1, 29.2,
29.5, 31.7, 49.9, 53.6, 127.9, 129.3, 133.8, 138.8 and 203.2;
m/z 324 (M , 0.5%), 183 (26), 143 (89), 125 (20), 83 (38), 81
(20), 78 (26), 77 (37), 71 (33), 69 (54), 57 (60), 55 (94), 43 (100)
and 41 (93) (Found: M , 324.1805. Calc. for C H O S: M,
dd, J 14.0, 6.3, 1H), 2.55–2.80 (m, 3H), 3.02 (dd, J 14.0, 6.3,
H), 7.10–7.40 (m, 5H) and 9.64 (d, J 2.2, 1H); δ (50 MHz)
1
2
2
9
1
C
2.1, 29.8, 35.2, 40.4, 52.3, 128.3, 128.5, 128.6, 128.8, 203.8 and
C
ϩ
07.6; m/z 204 (M , 9%), 176 (10), 146 (15), 118 (44), 117 (40),
ϩ
ϩ
2 (21), 91 (94), 58 (32) and 43 (100) [Found: (M Ϫ H O),
86.1055. Calc. for C H O: (M Ϫ H O), 186.1045].
2
13
14
2
ϩ
18
28
3
(
2RS,3R)-3,7-Dimethyl-2-(3-oxobutyl)oct-6-enal 10g
3
24.1776).
Medium-scale preparation. A solution of citronellal 8e
3
3
2-Benzyl-4-(phenylsulfonyl)butanal 10m
(
18.1 cm , 100 mmol), DEATMS (1.9 cm , 10 mmol) and but-3-
3 3
en-2-one (12.5 cm , 150 mmol) in MeCN (400 cm ) was refluxed
for 46 h under a nitrogen atmosphere. Evaporation of MeCN
in vacuo followed by Kugelrohr distillation (120–140 ЊC at 1.9
Ϫ1
Yield 34%; νmax/cm 3088, 3069, 2930, 2718, 1728, 1605, 1497,
1
323 and 1088; δH (200 MHz) 1.75–2.15 (m, 2H), 2.68 (dd,
J 13.0, 7.3, 1H), 2.80–3.23 (m, 4H), 7.05–7.45 (m, 5H), 7.50–
7.70 (m, 3H), 7.79 (dd, J 7.0, 1.6, 2H) and 9.66 (d, J 1.2, 1H);
Ϫ1
mmHg) afforded the keto aldehyde 10g (21.6 g, 96%), νmax/cm
2
0
3
930, 2709, 1722, 1450, 1376, 1240 and 1164; δH (200 MHz)
.89 (d, J 6.9, 1.5H), 0.99 (d, J 6.9, 1.5H), 1.60 (s, 3H), 1.69 (s,
H), 1.08–2.10 (m, 7H), 2.13 (s, 3H), 2.26–2.65 (m, 3H), 5.68
δ (50 MHz) 21.2, 35.2, 51.3, 53.4, 126.9, 128.0, 128.8, 128.84,
C
ϩ
1
29.3, 133.8, 137.3, 138.6 and 202.6; m/z 302 (M , 0.3%), 301
(
4), 274 (23), 252 (45), 159 (31), 143 (33), 132 (45), 104 (100)
ϩ
(
m, 1H), 5.68 (m, 1H), 9.60 (d, J 2.4, 0.5H) and 9.64 (d, J 2.9,
and 91 (99) (Found: M , 302.0911. Calc. for C H O S: M,
17
18
3
0
3
2
.5H); δ (50 MHz) 15.9, 16.7, 17.6, 18.0, 19.7, 25.1, 25.6, 29.9,
C
302.0976).
2.2, 33.3, 33.8, 34.4, 41.36, 41.42, 55.9, 56.2, 123.7, 131.9,
ϩ
04.9, 205.2, 207.9 and 208.0; m/z 224 (M , 0.1%), 148 (32), 109
Methyl 4-formyldodecanoate 10n
(
26), 95 (38), 82 (32), 71 (25), 69 (52), 58 (28), 56 (37), 43 (100)
Ϫ1
ϩ
Yield 55%; νmax/cm 2930, 2736, 1741 and 1709; δ (200 MHz)
H
and 41 (68) (Found: M , 224.1798. Calc. for C H O : M,
14
24
2
0
2
.88 (t, J 6.3, 3H), 1.20–1.40 (br s, 14H), 1.75–2.10 (m,
H), 2.25–2.50 (m, 3H), 3.67 (s, 3H) and 9.59 (d, J 2.5, 1H);
2
24.1776).
δC (50 MHz) 14.1, 22.6, 23.5, 26.8, 28.8, 29.2, 29.3, 29.6,
1.4, 31.8, 51.0, 51.6, 76.4, 77.0, 77.7, 173.4 and 204.4; m/z 235
(9%), 227 (6), 208 (11), 184 (13), 152 (43), 146 (57), 138 (32),
5
-Oxo-2-[3-(tetrahydropyran-2-yloxy)propyl]hexanal 10h
3
Ϫ1
Yield 89%; νmax/cm 2948, 2720, 1723, 1138, 1123, 1078 and
1
036; δ (200 MHz) 1.50–2.00 (m, 12H), 2.14 (s, 3H), 2.30 (m,
H
128 (79), 114 (31), 100 (59), 74 (59) and 55 (100) [Found:
1
H), 2.46 (br t, 2H), 3.30–3.55 (m, 2H), 3.60–3.90 (m, 2H), 4.56
ϩ
(
M Ϫ CH ), 227.1657. Calc. for C H O : (M Ϫ CH ),
3
13 23
3
3
(
br t, J 4.1, 1H) and 9.58 (d, J 2.6, 1H); δ (50 MHz) 19.4, 22.0,
C
227.1646].
2
5.2, 25.5, 26.9, 29.7, 30.5, 40.3, 50.6, 62.1, 66.7, 98.6, 204.2
ϩ
and 207.5; m/z 256 (M , 0.5%), 228 (1.5), 155 (14), 154 (19), 101
2
-(2-Oxocyclopentylmethyl)decanal 13a
ϩ
(
11), 97 (100), 85 (88), 88 (45) and 55 (55) (Found: M ,
To a stirred solution of mesyl ester 11a (106 mg, 0.55 mmol)
2
56.1620. Calc. for C H O : M, 256.1674).
14 24 4
3
3
and decanal (0.124 cm , 0.66 mmol) in CH Cl (2 cm ) was
2
2
3
added DEATMS (0.250 cm , 1.3 mmol) at 0 ЊC under a nitrogen
atmosphere and the resulting solution was stirred at room
temperature for 17 h. The solution was passed through a
short column of silica gel and evacuated in vacuo. The resulting
residue was separated by MPLC (eluent: ethyl acetate–
hexane = 1:9) to give two diastereomers of 13a (93 mg, 67%).
The two diastereomers are listed in their order of elution.
1
0-Acetoxy-2-(3-oxobutyl)decanal 10i
Ϫ1
Yield 76%; νmax/cm 2934, 2708, 1740, 1724, 1230 and 1165;
δH (200 MHz) 1.25–1.50 (br s, 13H), 1.55–2.00 (m, 4H), 2.05
(
s, 3H), 2.13 (s, 3H), 2.30 (m, 1H), 2.46 (br t, 2H), 4.05 (t, J 6.7,
1
2
2
H) and 9.55 (d, J 2.8, 1H); δ (50 MHz) 20.6, 22.0, 25.5, 26.6,
8.2, 28.6, 28.8, 28.9, 29.2, 40.3, 50.8, 64.2, 170.7, 204.4 and
07.4; m/z 256 (10%), 149 (10), 139 (18), 138 (44), 114 (20), 109
C
Ϫ1
Isomer I, yield 29%; νmax/cm 2928, 2708, 1744 and 1734;
(
(
21), 97 (54), 95 (42), 83 (83), 81 (56), 71 (52), 69 (59), 67 (50), 58
95) and 55 (100) [Found: (M Ϫ 1), 283.1960. Calc. for
δH (200 MHz) 0.80 (t, J 6.4, 3H), 1.10–1.45 (br s, 14H), 1.45–
ϩ
1
.92 (m, 6H), 1.92–2.32 (m, 4H) and 9.56 (d, J 3.0, 1H).
C H O : (M Ϫ 1), 283.1908].
16
27
4
Isomer II, yield 38%; δ (200 MHz) 0.88 (t, J 6.5, 3H), 1.15–
H
1
.40 (br s, 14H), 1.40–1.95 (m, 6H), 1.95–2.43 (m, 4H) and 9.54
2
-(3-Oxopentyl)decanal 10j
ϩ
(
d, J 3.3, 1H); m/z 252 (M , 12%), 250 (23), 233 (10), 222 (7),
Ϫ1
Yield 76%; νmax/cm 2930, 2857, 1720, 1680, 1458, 1379 and
194 (8), 166 (22), 154 (13), 138 (16), 123 (29), 110 (18), 97 (77),
84 (100), 67 (52) and 55 (51).
1
113; δ (200 MHz) 0.88 (t, J 6.4, 3H), 1.05 (t, J 7.3, 3H), 1.20–
H
3
20
J. Chem. Soc., Perkin Trans. 1, 2001, 316–322

View Article Online
2
-(2-Oxocycloheptylmethyl)decanal 13b
0.88 (s, 9H), 1.03–1.63 (m, 7H), 2.24–2.45 (m, 3H), 2.76 (dd,
J 11.9, 6.4, 1H), 2.88 (m, 1H), 3.00 (dd, J 11.9, 6.4, 1H), 7.15–
Two diastereomers were isolated and are listed in their order
of elution. Isomer I, yield 23%; νmax/cm 2930, 2720, 1725
and 1705; δH (200 MHz) 0.88 (t, J 6.4, 3H), 1.20–1.40 (br s,
7
.38 (m, 5H) and 9.64 (d, J 2.1, 1H).
Group II, yield, 18%; νmax/cm (neat) 3063, 3027, 2955, 2716,
Ϫ1
Ϫ1
1
7
722 and 1713; δH (200 MHz) 0.88 (s, 9H), 0.95–1.60 (m,
H), 1.95–2.45 (m, 4H), 2.73 (dd, J 16.3, 9.5, 1H), 3.02 (dd,
1
2
4H), 1.40–1.95 (m, 10H), 2.24 (m, 1H), 2.40–2.51 (m, 2H),
.60 (m, 1H) and 9.54 (d, J 3.0, 1H).
J 16.3, 9.5, 1H), 7.10–7.35 (m, 5H) and 9.62 (d, J 2.8, 1H).
Group III, yield 12%; δH (200 MHz) 0.88 (s, 9H), 1.40–2.50
Isomer II, yield 24%; δ (200 MHz) 0.88 (t, J 6.4, 3H), 1.40–
H
1
.95 (m, 10H), 2.30–2.63 (m, 4H) and 9.49 (d, J 3.3, 1H).
(
m, 11H), 2.67 (m, 1H), 3.02 (m, 1H), 7.10–7.35 (m, 5H) and
9
.71 (d, J 1.3, 1H).
2
-(2-Oxocyclooctylmethyl)decanal 13c
Two diastereomers were isolated and are listed in their order
of elution. Isomer I, yield 27%; νmax/cm 2930, 2705, 1726
and 1701; δH (200 MHz) 0.88 (t, J 6.4, 3H), 1.05–1.38 (br s,
2
1
-(5-tert-Butyl-2-oxocyclohexylmethyl)-3,7-dimethyloct-6-enal
3h
Ϫ1
Three groups of diastereomers were isolated and are listed
in their order of elution. Group I, yield 21%; δH (200 MHz)
0
3
1
4
4H), 1.38–1.87 (m, 12H), 1.87–2.20 (m, 3H), 2.36 (dd, J 7.5,
.3, 1H) and 9.52 (d, J 3.3, 1H).
Isomer II, yield 42%; νmax/cm 2944, 2705, 1726 and 1703;
Ϫ1
.90 (s, 9H), 1.03 (d, J 6.9, 3H), 1.10–2.20 (m, 12H), 1.61 (s,
H), 1.69 (s, 3H), 2.25–2.50 (m, 4H), 5.07 (br t, 1H) and 9.64
δH (200 MHz) 0.88 (t, J 6.4, 3H), 1.08–1.35 (br s, 14H), 1.35–
.30 (m, 15H), 2.37 (dd, J 7.0, 4.8, 1H) and 9.45 (d, J 3.1, 1H);
ϩ
(d, J 1.7, 1H); m/z 320 (M , 36%), 302 (54), 167 (100), 154
(100), 149 (100), 139 (100), 135 (92), 123 (53), 111 (57), 109
(100), 107 (60), 97 (100), 95 (100), 93 (74), 80 (93), 69 (100),
2
ϩ
ϩ
m/z 294 (M , 3%), 292 (M Ϫ 2, 6), 264 (8), 252 (44), 235 (46),
39 (36), 126 (47), 121 (29), 98 (100), 95 (44), 81 (45), 69 (56)
and 55 (95).
1
5
7 (100), 55 (100) and 41 (100).
Group II, yield 21%; δH (200 MHz) 0.90 (s, 4.5H), 0.91 (s,
2
-(5-tert-Butyl-2-oxocyclohexylmethyl)decanal 13d
4.5H), 0.96 (d, J 6.9, 3H), 1.60 (s, 3H), 1.69 (s, 3H), 1.20–2.40
(
m, 16H), 5.05 (m, 1H), 9.59 (d, J 3.3, 0.5H) and 9.70 (d, 0.5H).
Group III, yield 3%; νmax/cm 2965, 2728, 1723 and 1711;
A mixture of diastereomers was obtained in 77% yield,
νmax/cm 2955, 2720 and 1715; δH (200 MHz) 0.80–1.00 (m,
3
Ϫ1
Ϫ1
δH (200 MHz) 0.91 (s, 9H), 0.97 (d, J 7.0, 3H), 1.20–1.80
H), 0.90 (s, 5H), 0.91 (s, 4H), 1.18–1.40 (br s, 14H), 1.40–1.80
(
(
m, 12H), 1.61 (s, 3H), 1.70 (s, 3H), 2.00–2.60 (m, 4H), 5.08
br s, 1H), 9.58 (d, J 1.7, 0.4H) and 9.63 (d, 0.6H).
(
m, 7H), 2.20–2.50 (m, 4H), 9.51 (d, J 3.3, 0.5H) and 9.62 (d,
ϩ
J 2.1, 0.5H): total 1H; m/z 320 (M Ϫ 2, 19%), 305 (10), 292
36), 279 (21), 252 (41), 250 (40), 235 (36), 233 (39), 167 (80),
54 (93), 139 (100), 109 (60), 98 (75), 81 (56), 69 (48) and 57
51).
(
1
(
2
-(1-Oxo-1,2,3,4-tetrahydro-2-naphthylmethyl)decanal 13i
Yield 83% (a mixture of inseparable diastereomers); νmax/cm
074, 3028, 2930, 2720, 1726 and 1692; δH (200 MHz) 0.88
t, J 6.4, 3H), 1.10–1.45 (br s, 14H), 1.45–2.35 (m, 6H), 2.53 (m,
H), 3.02 (m, 1H), 7.23 (d, J 7.6, 1H), 7.32 (d, J 7.6, 1H), 7.46
Ϫ1
3
(
1
1
0-Acetoxy-1-(5-tert-butyl-2-oxocyclohexylmethyl)decanal 13e
Three groups of diastereomers were isolated and are listed
in their order of elution. Group I, yield 25%; νmax/cm 2934,
2
1
Ϫ1
(dt, J 7.5, 1.5, 1H), 8.01 (dd, J 7.8, 1.5, 1H), 9.59 (d, J 2.9, 0.4H)
ϩ
and 9.64 (d, J 2.7, 0.6H); m/z 314 (M , 10%), 159 (45), 146
720, 1742, 1717 and 1238; δH (200 MHz) 0.90 (s, 9H), 1.10–
.50 (br s, 16H), 1.50–1.72 (m, 7H), 2.05 (s, 3H), 2.27–2.50
(
3
100), 131 (35), 118 (18), 91 (22), 55 (20), 43 (20), 41 (21) and
2 (74).
(
m, 4H), 4.05 (t, J 6.6, 2H) and 9.54 (d, J 3.0, 1H).
Ϫ1
Group II, yield 28%; νmax/cm ; δH (200 MHz) 0.90 (s, 9H),
1
.20–1.82 (m, 23H), 2.05 (s, 3H), 2.25–2.50 (m, 4H), 4.05 (t,
2-(1-Oxo-1,2,3,4-tetrahydro-2-naphthyl)-3-phenylpropanol 13j
J 6.7, 2H) and 9.62 (d, J 2.2, 1H).
Ϫ1
Ϫ1
Yield 76% (a mixture of inseparable diastereomers); νmax/cm
Group III, yield 13%; νmax/cm 2934, 2716, 1742, 1715
3
067, 3031, 2934, 2720, 1726 and 1709; δ (200 MHz) 1.40–2.25
H
and 1243; δ (200 MHz) 0.90 (s, 9H), 1.20–1.88 (m, 23H), 2.05
H
(
m, 4H), 2.35–2.63 (m, 2H), 2.75–3.15 (m, 4H), 7.14–7.35 (m,
7H), 7.45 (dt, J 7.9, 1.3, 1H), 7.97 (dd, J 7.7, 1.3, 0.4H) and 7.99
dd, J 7.9, 1.3, 0.6H), 9.68 (d, J 2.8, 0.6H) and 9.72 (d, J 2.0,
(
s, 3H), 2.20–2.47 (m, 4H), 4.05 (t, J 6.7, 2H) and 9.51 (d, J 3.2,
ϩ
1
2
H); m/z 378 (M Ϫ 2, 7%), 363 (4), 350 (24), 335 (4), 321 (5),
(
0
94 (14), 250 (49), 235 (70), 207 (46), 154 (60), 139 (80), 109
ϩ
.4H); m/z 292 (M , 4%), 264 (4), 252 (4), 235 (3), 159 (20), 146
(
35), 95 (58), 83 (52) and 55 (100).
(
100), 131 (24), 115 (26), 105 (22), 91 (55) and 77 (31).
2
2
-(5-tert-Butyl-2-oxocyclohexylmethyl)-5-(tetrahydropyran-
-yloxy)pentanol 13f
2
-Hydroxy-3-octylbicyclo[3.2.1]octan-8-one 14a
To a solution of keto aldehyde 13a (64 mg, 0.25 mmol) in
methanol (10 cm ) was added potassium hydroxide (70 mg, 1.2
Two groups of diastereomers were isolated and are listed in
their order of elution. Group I, yield 42%; νmax/cm (neat)
3
Ϫ1
mmol) at 0 ЊC. The resulting solution was stirred at room tem-
perature for 23 h. After addition of aq. ammonium chloride,
product was extracted with ethyl acetate twice and the com-
bined organic layer was washed successively with water and
brine. Evaporation of the solvent followed by MPLC purifi-
cation (eluent: ethyl acetate–n-hexane = 1:3) of the residue
provided the aldol product as two groups of diastereomers
2
948, 2811, 1721, 1713, 1138, 1123, 1078 and 1034; δH (200
MHz) 0.90 (s, 9H), 1.35–1.95 (m, 11H), 2.20–2.55 (m, 4H),
.30–3.55 (m, 2H), 3.67–3.93 (m, 2H), 4.55 (br t, 1H) and 9.57
3
ϩ
(
1
(
d, J 2.9, 1H); m/z 352 (M , 1%), 324 (1), 250 (60), 191 (22),
67 (61), 154 (759), 139 (52), 109 (38), 98 (81), 79 (68) and 69
100).
Ϫ1
Group II, yield 23%; νmax/cm (neat) 2940, 2722, 1723,
711, 1138, 1123, 1078 and 1034; δH (200 MHz) 0.90 (s, 9H),
.40–1.90 (m, 11H), 2.15–2.55 (m, 4H), 3.30–3.60 (m, 2H),
.70–3.95 (m, 2H), 4.55 (br t, 1H), 9.58 (d, J 2.3, 0.3H) and
.65 (d, J 2.0, 0.7H).
(
combined yield 61 mg, 95%) which are listed in their order
1
1
3
9
Ϫ1
of elution. Group I, yield 5%; νmax/cm 3440, 2957 and 1746;
δH (200 MHz) 0.88 (t, J 6.4, 3H), 1.15–1.40 (br s, 14H), 1.60–
2
.09 (m, 8H), 2.24 (m, 1H), 2.35 (m, 1H) and 4.10 (m, 1H);
ϩ
m/z 252 (M , 2%), 112 (8), 97 (17), 96 (22), 84 (100), 83 (16),
6
9 (9), 67 (13), 57 (13), 55 (28), 43 (16), 41 (38) and 39 (7).
Group II, yield 90%; νmax/cm 3625, 3504, 2928 and 1755; δH
2
-(5-tert-Butyl-2-oxocyclohexylmethyl)-3-phenylpropanol 13g
Ϫ1
Three groups of diastereomers were isolated and are listed
(200 MHz) 0.88 (t, J 6.4, 3H), 1.10–1.50 (br s, 14H), 1.60–2.14
in their order of elution. Group I, yield 26%; δH (200 MHz)
(m, 8H), 2.25 (m, 1H), 2.36 (m, 1H) and 4.10 (m, 1H).
J. Chem. Soc., Perkin Trans. 1, 2001, 316–322
321

View Article Online
7
-Hydroxy-8-octylbicyclo[4.3.1]decan-10-one 14b
J 2.9, 1H); δ 26.6, 28.9, 29.6, 30.5, 32.0, 38.2, 48.1, 50.8, 69.7,
C
7
3
3.2, 76.6, 127.3, 127.4, 127.5, 128.3, 204.3 and 207.6; m/z
Three groups of diastereomers were isolated and are listed
in their order of elution. Group I, yield 29%; νmax/cm 3630,
17 (12%), 211 (20), 135 (6), 91 (100) and 43 (9) [Found:
Ϫ1
ϩ
ϩ
(
M Ϫ C H ), 380.1984. Calc. for C H O : (M Ϫ C H ),
2
4
24 28
4
2
4
3482, 2926 and 1709; δH (200 MHz) 0.89 (t, J 6.4, 3H), 1.20–
1.50 (br s, 14H), 1.50–2.10 (m, 11H), 2.38 (m, 1H), 2.71 (m,
1H), 3.0 (m, 1H) and 3.55 (dd, J 10.7, 5.8, 1H).
3
80.1986].
Ϫ1
Group II, yield 16%; νmax/cm 3625, 3438, 2928 and 1709;
Acknowledgements
δH (200 MHz) 0.89 (t, J 6.4, 3H), 1.20–1.97 (br s, 14H), 1.97–
2
5
This work was supported by a Grant-in-Aid for Scientific
Research (No. 09640630 for H. H.) from the Ministry of
Education, Science, Sports and Culture, Japan. We thank Soda
Aromatics Co. for mass spectral measurements.
.20 (m, 11H), 2.35 (m, 1H), 2.65–2.87 (m, 2H), 3.56 (dd, J 10.6,
.8, 0.3H) and 3.93 (br s, 0.7H).
Group III, yield 37%; νmax/cm 3625, 3456, 2930 and 1715;
Ϫ1
δH (200 MHz) 0.88 (t, J 6.4, 3H), 1.15–1.45 (br s, 14H),
1
3
.45–2.18 (m, 12H), 2.43–2.68 (m, 2H) and 3.71 (dd, J 7.9,
.1, 1H).
References and notes
1
A. J. Waring, in Comprehensive Organic Synthesis, ed. J. F. Stoddart,
Pergamon Press, Oxford, 1979, vol. 1, p. 1055.
8
-Hydroxy-9-octylbicyclo[5.3.1]undecan-11-one 14c
2
G. Stork, A. Brizzolara, H. Landesman, J. Szmuszkovicz and
R. Terrell, J. Am. Chem. Soc., 1963, 85, 207; M. Brown, J. Org.
Chem., 1968, 33, 162.
P. Duhamel, L. Hennequin, J. M. Poirier, G. Tavel and C. Vottero,
Tetrahedron, 1986, 42, 4777.
Three groups of diastereomers were isolated and are listed in
their order of elution. Group I, yield 57%; νmax/cm 3620,
Ϫ1
3
1
470, 2928 and 1703; δH (200 MHz) 0.89 (t, J 6.3, 3H), 1.10–
.60 (br s, 14H), 1.60–2.20 (m, 14H), 2.43 (m, 1H), 2.75 (m, 1H)
3
and 3.56 (dd, J 10.3, 5.0, 1H).
Group II, yield 12%; νmax/cm 3625, 3420, 2930 and 1703;
δH (200 MHz) 0.89 (t, J 6.4, 3H), 1.20–1.50 (br s, 14H), 1.50–
4 T. Nakajima, Y. Maruyama and I. Shimizu, Abstracts of Papers
of 65th Annual Meeting of Chemical Society of Japan, Tokyo, 1993,
vol. II, p. 335.
Ϫ1
5
Preliminary communication: H. Hagiwara and M. Kato,
Tetrahedron Lett., 1996, 37, 5139.
W. Franke and J. Bueren, Chem. Abstr., 1953, 47, 2205a; E. Eliel
and C. A. Lukach, J. Am. Chem. Soc., 1957, 79, 5986; K. L. Cook
and A. J. Waring, J. Chem. Soc., Perkin Trans. 1, 1973, 529;
M. Pesaro and J.-P. Bachman, J. Chem. Soc., Chem. Commun., 1978,
2
.10 (m, 14H), 2.30 (m, 1H), 2.50 (m, 1H) and 3.93 (m, 1H);
ϩ
m/z 294 (M , 7%), 139 (29), 126 (33), 98 (100), 97 (26), 95 (26),
3 (52), 81 (32), 71 (32), 69 (36), 67 (52), 57 (50), 55 (98), 43 (66)
and 41 (95).
6
8
Ϫ1
Group III, yield 17%; νmax/cm 3455, 2928 and 1703; δ (200
H
2
03.
MHz) 0.88 (t, J 6.4, 3H), 1.15–1.45 (br s, 14H), 1.45–1.90
7
I. Weisz, K. Felfoldi and K. Kovacs, Acta Chim. Acad. Sci. Hung.,
(
m, 11H), 1.90–2.20 (m, 3H), 2.31 (m, 1H), 2.48 (m, 1H) and
1968, 58, 189; D. A. Evans and J. Bartoli, Tetrahedron Lett., 1982,
23, 807; G. Stork and S. D. Rychnovsky, J. Am. Chem. Soc., 1987,
109, 1564.
3
.75 (dd, J 8.3, 5.4, 1H).
3
-Acetonyl-2,3,4,5-tetrahydro-1H-benzocycloheptene-2-
8 Y. Hamada, Y. Yamamoto and H. Shimizu, J. Organomet. Chem.,
1996, 510, 1.
9
carbaldehyde 16
Y. Yamamoto, H. Shimizu and Y. Hamada, J. Organomet. Chem.,
1996, 509, 119.
To a stirred solution of formyl enone 15 (46 mg, 0.2 mmol)
3
3
and DEATMS (0.046 cm , 0.24 mmol) in MeCN (5 cm ) was
stirred at room temperature for 22 h. The resulting solution
was passed through a short silica gel column and evaporated
to dryness. MPLC purification of the residue (eluent: ethyl
acetate–hexane = 1:3) provided aldehyde 16 as an inseparable
10 A. Papini, A. Ricci, M. Taddei, G. Seconi and P. Dembech, J. Chem.
Soc., Perkin Trans. 1, 1984, 2261; J. Ipaktschi and A. Heydari,
Chem. Ber., 1993, 126, 1905; Y. Yamamoto, H. Shimizu, C. Matui
and M. Chinda, Main Group Chem., 1996, 1, 409.
1 (a) L. H. Hellberg and A. Juarez, Tetrahedron Lett., 1974, 3553; (b)
M. Fiorenza, A. Ricci, M. N. Romanelli, M. Taddei, P. Dembech
and G. Seconi, Heterocycles, 1982, 19, 2327; (c) Y. Yamamoto and
C. Matui, Organometallics, 1997, 16, 2204.
2 R. Comi, R. W. Franck, M. Reitano and S. M. Weinreb, Tetrahedron
Lett., 1973, 3107.
3 M. R. Saidi, M. M. Mojtahedi and M. Bolourtchian, Tetrahedron
Lett., 1997, 38, 8071; M. R. Saidi, A. Heydari and J. Ipaktschi,
Chem. Ber., 1994, 127, 1761; M. R. Saidi, H. R. Khalaji and
J. Ipaktschi, J. Chem. Soc., Perkin Trans. 1, 1987, 1983.
1
Ϫ1
mixture of diastereomers (33 mg, 73%); νmax/cm 3069, 3025,
2
1
921, 2710 and 1723; δH (200 MHz) 2.13 (s, 2H) and 2.15 (s,
H), 2.35–3.20 (m, 10H), 7.10–7.20 (m, 4H), 9.45 (br s, 0.3H)
1
1
and 9.60 (d, J 3.3, 0.7H); δ 30.2, 30.5, 30.7, 32.3, 33.4, 33.8,
C
3
1
6.0, 48.5, 55.0, 126.38, 126.42, 127.0, 128.7, 129.2, 129.3,
29.6, 138.2, 142.3, 142.6, 203.2, 204.2 and 207.3; m/z 228
ϩ
(
M Ϫ 2, 78%), 200 (56), 188 (27), 157 (20), 143 (100), 130 (42),
ϩ
9
1 (18) and 43 (44) (Found: M , 230.1341. Calc. for C H O :
14 W. J. Middleton and E. M. Bingham, Org. Synth., 1988, Coll. Vol. VI,
15
18
2
4
40.
M, 230.1306).
1
5 M. Hojo, M. Nagayoshi, A. Fujii, T. Yanagi, N. Ishibashi, K. Miura
and A. Hosomi, Chem. Lett., 1994, 719.
6 H. Hagiwara, V. P. Kamat, H. Ono, T. Hoshi, T. Suzuki and
M. Ando, Abstracts of Papers of 43rd Symposium on Flavour,
Terpenoids and Essential oils, 1999, p. 108.
7 We thank Mrs F. Yoshii for these calculations.
8 K. Tani, T. Yamagata, S. Otshuka, H. Kumobayashi and
S. Akutagawa, Org. Synth., 1993, Coll. Vol. VIII, 183.
19 L. Birkofer and O. Stuhl, in The Chemistry of Organosilicon
Compounds Part 1, ed. S. Patai and Z. Rappoport, Wiley, Chichester,
New York, Brisbane, Toronto, Singapore, 1989, p. 655.
20 Our recent results using DEATMS in nucleophilic reaction of naked
aldehydes: H. Hagiwara, N. Komatsubara, T. Hoshi, T. Suzuki and
M. Ando, Tetrahedron Lett., 1999, 40, 1523; H. Hagiwara, H. Ono,
N. Komatsubara, T. Hoshi, T. Suzuki and M. Ando, Tetrahedron
Lett., 1999, 40, 6627.
(
1R*,2S*)-2-Acetonyl-5,5-bis(benzyloxymethyl)cyclohexane-
1
carbaldehyde 18
To a stirred solution of formyl enone 17 (40 mg, 0.098 mmol)
1
1
3
3
and DEATMS (0.023 cm , 0.12 mmol) in acetonitrile (5 cm )
was stirred at room temperature for 22 h. The resulting
solution was passed through a short silica gel column and
evaporated to dryness. MPLC purification of the residue
(
eluent: ethyl acetate–hexane = 1:5) provided aldehyde 18 as a
Ϫ1
single diastereomer (31 mg, 76%); νmax/cm 3090, 3067, 2926,
2
2
3
710 and 1723; δ (200 MHz) 1.20–1.90 (m, 7H), 2.00–2.20 (m,
H), 2.09 (s, 3H), 2.50 (dt, J 16.6, 2.9, 1H), 3.26 (d, J 4.7, 2H),
.42 (s, 2H), 4.48 (s, 4H), 7.20–7.45 (br s, 10H) and 9.41 (d,
H
3
22
J. Chem. Soc., Perkin Trans. 1, 2001, 316–322