Organozinc alkoxide-promoted aldol-Tishchenko reaction of aliphatic aldehydes: An expedient entry to prepare the α-methylene ketones

Article abstract of DOI:10.1016/j.tet.2005.03.076

i-PrOZnEt is an excellent reagent to promote the aldol-Tishchenko reaction of the aliphatic aldehydes tethered with other labile functional groups. The 1,3-diol monoesters 4 were formed as the major products, which could be converted to α-methylene ketone

Full text of DOI:10.1016/j.tet.2005.03.076

Tetrahedron 61 (2005) 5267–5275
Organozinc alkoxide-promoted aldol-Tishchenko reaction of
aliphatic aldehydes: an expedient entry to prepare the
a-methylene ketones
a,b,
a
Yung-Son Hon
*
and Chun-Ping Chang
a
Department of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi 621, Taiwan, ROC
b
Institute of Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan, ROC
Received 25 January 2005; revised 17 March 2005; accepted 21 March 2005
Available online 19 April 2005
Abstract—i-PrOZnEt is an excellent reagent to promote the aldol-Tishchenko reaction of the aliphatic aldehydes tethered with other labile
functional groups. The 1,3-diol monoesters 4 were formed as the major products, which could be converted to a-methylene ketones 7 in two
steps in good yields.
q 2005 Elsevier Ltd. All rights reserved.
1
. Introduction
We found that the aliphatic aldehyde 1a reacted with a
catalytic amount of diisobutylaluminium hydride (Dibal-H)
in pentane to give ester 2a in good to excellent yields via a
Tishchenko reaction intermediate A in which an intra-
molecular hydride shift took place. The aluminium alkoxide
B formed in the reaction reacted with aldehyde 1a to
establish the catalytic reaction cycle (Fig. 1). This
observation provokes us to investigate the influence of the
metal ions on the metal alkoxides-promoted Tishchenko
reactions. Interestingly, we found that the change of the
metal ion of the alkoxide B will switch the reaction pathway
from Tishchenko reaction to aldol-Tishchenko reaction.
Herein, we wish to report the results of our studies on the
homogeneous aldol-Tishchenko reaction promoted by
magnesium and zinc alkoxides. The further synthetic
For enolizable aldehydes, both aldol addition and
Tishchenko reaction are two major possible pathways. For
the aldol addition, the presence of only basic sites in the
catalysts is sufficient, whereas for the Tishchenko reaction,
the presence of both acidic sites and basic sites in the
catalysts is required. Interestingly, sequential aldol-
Tishchenko reaction can become competing if the catalyst
first, accomplishes the aldol reaction, which is followed by
Tishchenko esterification by the Lewis acidic nature of the
1
4
1
same catalyst. In many cases, traditional Tishchenko and
aldol-Tishchenko reactions are competing with each
2
3
other. However, sequential aldol-Tishchenko reaction can
become competing if the catalyst is sufficiently basic, such
as a basic metal hydroxide catalyst. Some other catalysts,
4
,5
3
a,6
such as metal alkoxides of monofunctional alcohols,
simple metal hydroxides. Lithium monoalcoholate of 1,3-
6
7
diol, LiWO , Cp*2Sm(thf)2, polynuclear carbonyl
8
9
2
1
0
11
ferrate, and arylmagnesium halide in HMPT have also
been used. The aldol-Tishchenko reaction of the aldehyde
gives 1,3-diol monoesters from the trimerization of the
aldehyde. Trimerization of isobutyraldehyde to 2,2,4-
trimethylpentane-1,3-diol mono-isobutyrates, which are
the most common coalescing agents, for example, in latex
1
2
paints, has been industrialized since, 1988 by use of binary
metal oxide BaO–CaO.
1
3
Keywords: Organozinc alkoxide; Aldol-Tishchenko reaction; Tishchenko
reaction; 1,3-Diol monoester; a-Methylene ketones.
*
Corresponding author. Tel.: C886 5 2720411x6412; fax: C886 5
721040; e-mail: cheysh@ccu.edu.tw
Figure 1. The plausible mechanism for the reaction of aldehyde 1a with
catalytic amount of Dibal-H to give the corresponding ester 2a.
2
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.076

5268
Y.-S. Hon, C.-P. Chang / Tetrahedron 61 (2005) 5267–5275
0
Figure 2. The proposed aldol-Tishchenko reaction mechanism for the formation of compounds 4a and 4a from 3-phenylpropanal (1a) promoted by metal
alkoxides.
applications of their products in the synthesis of the
a-methylene ketones will also be discussed.
metal alkoxides were generated from the reaction of
alcohols with phenylmagnesium chloride (2.0 M solution
in THF) or diethylzinc (1.0 M solution in hexanes) at 0 8C in
THF. A solution of the metal alkoxide in THF was added
dropwise in 5 min to 3-phenylpropanal (1a) in THF at 0 8C.
After the addition, the reaction was stirred at ambient
2
. Results and discussions
0
2.1. The reaction pathway is metal ion-dependent in the
reactions of aliphatic aldehydes with metal alkoxides
temperature. A mixture of the 1,3-diol monoesters 4a and
4a were obtained and their yield was shown in Table 1.
A solution of 0.1 mol equiv of Ph(CH ) OMgCl (3a),
2
3
When i-PrOMgCl (0.33 mol equiv) was used as the
promoter to react with aldehyde 1a at 0 8C, a mixture of
the aldol-Tishchenko products 4a and 4a were isolated in
81% yield (entry 1, Table 1). When the mol equiv of
i-PrOMgCl was dropped to 0.17, the chemical yield of the
aldol-Tishchenko products was slightly dropped to 75%
prepared from equal mol of the 3-phenylpropyl alcohol
with MeMgCl in THF at 0 8C, was added dropwise in 5 min
to 3-phenylpropanal (1a) in THF at 0 8C. After the addition,
the reaction was stirred at ambient temperature for 12 h. We
found that no Tishchenko reaction product 2a was formed
0
0
and a mixture of 1,3-diol monoesters 4a and 4a were
(entry 2). When t-BuOMgCl (0.33 mol equiv) was used as
the promoter, we isolated the aldol-Tishchenko products 4a
isolated as major products (Fig. 2). The formation of these
two compounds was rationalized as follows. An aldol
reaction of the aldehyde first takes place and the aldol
reaction product D forms a hemiacetal-like intermediate E
with the free aldehyde. The hemiacetal-like intermediate E
0
and 4a in 73% yield (entry 3). When the mol equiv of
t-BuOMgCl was dropped to 0.17, the chemical yield of the
aldol-Tishchenko products was decreased slightly to 61%
(entry 4). Although the chemical yields are not improved by
using t-BuOMgCl, their reaction times are shorter. When
i-PrOZnEt (0.33 mol equiv) was used as the promoter, we
isolated the aldol-Tishchenko products in 91% yield (entry
0
reacts to give the 1,3-diol monoester 4a via a Tishchenko
reaction in which an intramolecular hydride shift takes
0
via an acyl group migration (Fig. 2). Each of compounds 4a
place. The monoester intermediate F is equilibrated with F
0
5
). When the mol equiv of i-PrOZnEt was dropped to 0.17,
and 4a contain two chiral centers. All these possible isomers
are too close in polarity to be separated by silica gel column
chromatography. In addition, it is very difficult to determine
the chemical yield of the aldol-Tishchenko products was
decreased slightly to 73% (entry 6). The results of Table 1
indicate that i-PrOZnEt is an excellent reagent to promote
the aldol-Tishchenko reaction from aliphatic aldehydes. The
yield is high and the potential side reactions are minimized
when 0.33 mol equiv of this reagent was used (entry 5). This
conclusion is rationalized as follows. The Lewis acidity of
the metal ion is responsible to the formation of the
intermediate E in Figure 2. As for the Lewis acidity, zinc
ion is stronger than that of magnesium ion. The zinc ion may
be the better promoter to generate the hemiacetal inter-
mediate E (MetZZn) from the b-alkoxyaldehyde D and
aldehyde 1a. According to the literature report, the
trimerization of aliphatic aldehydes to 1,3-diol monoesters
is also effected by some sorts of metal alkoxides and
their ratio and identify, which is the major isomer from the
4
1
00 MHz H NMR spectrum of the mixtures.
In order to find an optimal condition for the aldol-
Tishchenko reaction, we tried to employ different kinds of
metal alkoxides. We chose i-propanol or tert-butanol as
reagents to generate the corresponding alkoxide based on
their basicity, steric factor and readily availability. The
Table 1. The effect of the metal alkoxide on the aldol-Tishchenko reaction
of the 3-phenylpropanal (1a) at 0 8C
0
Entry
Base
Mol equiv
Time (h)
4a C4a
%)
(
3
b
3b
phenoxides such as Ca(OEt)2,
1
Mg[Al(OEt)4]2,
However, in these
1
2
3
4
5
6
i-PrOMgCl
i-PrOMgCl
t-BuOMgCl 0.33
t-BuOMgCl 0.17
i-PrOZnEt
i-PrOZnEt
0.33
0.17
12
12
4
5
12
12
81
75
73
61
91
73
1b
11b
PhOMgX,
reactions, significant amounts of esters of the type RCO2-
and Me C H OMgX.
3
6 2
CH R derived by a dismutation of aldehydes are usually
2
produced as by-products, together with significant amounts
of aldol-condensation products. In the present study, we do
0.33
0.17

Y.-S. Hon, C.-P. Chang / Tetrahedron 61 (2005) 5267–5275
18
5269
1
-ketones, -esters, -lactones and its application in the
7
19
not observe the above-mentioned side reactions when
i-PrOZnEt was used. Therefore, we consider adapting the
i-PrOZnEt as promoter to the aldol-Tishchenko reaction.
2
0
total synthesis of the methylenolactocin. There are several
different methods to prepare the a-methylene ketone. The
most general and useful one was the acid-catalyzed
Mannich reaction of the appropriate saturated ketone 9,
formaldehyde, and secondary amine hydrochloride, fol-
lowed by thermal b-elimination from the Mannich base 8
In order to evaluate the possibility of the further synthetic
applications, the ratio of the aldol-Tishchenko products 4a
2
1
0
difficulty in separation and in analyzing the H NMR
spectrum, we did not know the ratio of products 4a and 4a
22
and 4a is an important factor. Unfortunately, due to the
1
or the corresponding quaternary ammonium derivatives
(Pathway A, Fig. 3). Previously, we reported an one pot
0
23
in each cases of the Table 1. Therefore, we tried to use an
indirect method to estimate their ratio based on the yields of
their oxidized products. A mixture of the aldol-Tishchenko
products obtained from entry 5 (Table 1) were treated with
PCC in the presence of 4 A molecular sieves to give a,b-
unsaturated aldehyde 5a in 8% yield and b-acyloxyketone
process to carry out the a-methylenation of the aryl alkyl
ketones with a mixture of dibromomethane and diethyl-
amine under microwave irradiation. The mannich base was
1
7
formed as a transient intermediate before elimination.
˚
Since, b-acyloxyketone 6 can be easily prepared from
simple aldehdye 1 in two steps in high yield. We envisioned
that the b-acyloxyketone 6 is a potential candidate to
prepare a-methylene ketone 7 by the elimination reaction
(Pathway B, Fig. 3). Furthermore, the eliminated by
6
a in 84% yield. Compounds 5a and 6a were easily
separated by simple silica gel column chromatography. The
1
H NMR spectrum of the minor compound 5a is identical to
the one reported in the literature. Presumably, the primary
1
5
0
product, i.e., carboxylic acid 1 , should be easily inter-
0
alcohol 4a was oxidized by PCC to give the corresponding
converted to the corresponding aldehyde 1. We found that
the b-acyloxyketone 6a was treated with 1,8-diaza-
bicyclo[5.4.0]undec-7-ene (DBU) in benzene at rt for 5 h
to give the a-methylene ketone 7a in 75% yield (RZ
b-acyloxyaldehyde, which then simultaneously underwent
b-elimination to give the conjugated aldehyde 5a (Eq. 1).
Therefore, we can estimate the mole ratio of 4a and 4a
0
approximately about 1:10.5. In other words, we have
demonstrated that the i-PrOZnEt is an excellent reagent to
promote the aldol-Tishchenko reaction from aliphatic
aldehyde 1a and the predominant product is 1,3-diol
monoester 4a, which could be converted to b-acyloxyketone
–CH Ph, Eq. 2; entry 1, Table 2). Therefore, this proposed
2
methodology to prepare the a-methylene ketone is com-
pletely different from the common approaches appeared in
the literature.
6
a in excellent yield.
(
2)
i-PrOZnEt can also be applied to promote the aldol-
Tishchenko reaction of the simple aliphatic aldehyde 1b
and aldehyde tethered with olefinic moieties (1c and 1d) to
give the corresponding 1,3-diol monoesters in good to
excellent yields (entries 2–4). These 1,3-diol monoesters
were oxidized by PCC followed by elimination with DBU to
give the corresponding a-methylene ketones 7b–7d in good
yields (entries 2–4) In order to understand how general and
versatile of our methodology in the aldol-Tshchenko
reaction and in their further transformation to the
a-methylene ketones, the starting aldehydes tethered with
several different labile functionalities were employed. By
similar reaction sequences, we were able to prepare the
a-methylene ketones 7e and 7f tethered with methoxy-
carbonyl group (entries 5 and 6), 7g and 7h tethered with
dimethylacetal group (entries 7 and 8), and 7i tethered with
(
1)
2
.2. Organozinc isopropoxide-promoted aldol-
Tishchenko reaction and its application to the formation
of the corresponding a-methylene ketone
In our laboratory, we are interested in developing the
methodology to prepare the a-methylene-aldehydes,
1
6
Figure 3. Retrosynthetic analysis of the preparation of the a-methylene ketone.

5270
Y.-S. Hon, C.-P. Chang / Tetrahedron 61 (2005) 5267–5275
Table 2. i-PrOZnEt-promoted aldol-Tishchenko reaction of aldehydes, followed by oxidation with PCC and elimination with DBU
Entry
RCH
2
CHO 1 RZ
aldol-Tishchenko
Yields (%)
Oxidation
Yield (%)
Elimination
Yield (%)
Time (h)
Time (h)
Time (h)
0
1
2
3
PhCH
2
– 1a
n-Pentyl- 1b
18
12
14
4a C4a 91
4b C4b 90
6
3
6
6a 84
6b 75
6c 80
5
6
7
7a 75
7b 76
7c 70
0
0
4c C4c 56
1
c
0
4
5
6
7
8
9
H
MeO
MeO
(MeO)
(MeO)
MeCO(CH
Br(CH – 1j
2
C]CH(CH
2
)
7
– 1d
18
24
24
20
22
15
20
4d C4d 84
4e C4e 68
5
8
12
4
4
8
12
6d 80
6e 91
6f 56
6g 64
6h 62
6i 85
6j 70
10
10
8
7d 71
7e 75
7f 80
7g 90
7h 92
7i 80
7j 77
0
0
2
C(CH
C(CH
2
)
)
5
– 1e
– 1f
2
2
3
4f C4f 50
4g C4g 73
0
0
2
CH(CH
CH(CH
2
)
)
5
– 1g
– 1h
7
2
2
3
4h C4h 72
0
10
10
12
2
)
7
– 1i
4i C4i 50
0
10
2
)
4
4j C4j 87
Scheme 1. Reagents and conditions: (i) DBU, PhH, 0 8C to rt, 12 h; (ii) DBU, PhH, rt, 6 h.
acetyl group (entry 9) and 7j tethered with bromo group
entry 10).
Therefore, we have developed a new methodology to
prepare the a-methylene ketones 7 from the simple
aldehyde 1 via aldol-Tishchenko, oxidation and elimination
sequences in good yields in three steps.
(
It is worthy to mention that the reaction temperature is
crucial to the formation of the desired elimination product 7j
from compound 6j. When the keto-ester 6j, which was
derived from the aldol-Tishchenko product of the 6-bromo-
hexanal (1j), was treated with DBU at rt, the desired product
4. Experimental
7j was isolated in only 25% yield. We could also isolate an
inseparable mixtures of ester–enone 7j and 7j in 18%
0
00
yield (Scheme 1). The ratio of these two side products is
All reactions were carried out under nitrogen. Unless
otherwise noted, materials were obtained from commercial
suppliers and used without further purification. The H and
1
1
.3:1 as estimated from their H NMR chemical shifts at d
0
1
3
C NMR spectra were recorded on a Bruker Avance
DPX400 spectrometer, and chemical shifts were given in
4
absorption of the methylene groups adjacent to the carboxyl
.14 and 4.06 ppm. These two characteristic peaks are the
1
ppm downfield from tetramethylsilane (TMS). The H and
C NMR spectra were recorded on a Bruker Avance DPX-
0
we do not know the exact structure of the major product.
00
group (–CH OCOR) of compounds 7j and 7j . However,
2
13
0
00
400 and chemical shifts were given in ppm downfield from
tetramethylsilane (TMS). IR spectra were taken with a
Perkin–Elmer 682 spectrophotometer and only noteworthy
absorption was listed. Mass spectra were measured on a
VG-Trio-2000GC/MS spectrometer (National Chiao-Tung
University) by electronic impact at 70 eV (unless otherwise
indicated). High Resolution Mass Spectroscopy (HRMS)
was measured on a Finnigan/Thermo Quest MAT 95XL
The formations of 7j and 7j may be rationalized as
follows. Each one of the bromides in compound 7j is
replaced by 6-bromocarboxylate 1j , a product formed from
0
the elimination of compound 6j by DBU, at rt. Fortunately,
these side products can be avoided by carrying out the
elimination reaction at 0 8C and the a-methylene ketone 7j
was formed in 77% yield (entry 10).
(National Chung Hsing University) and FAB Mass spectra
were recorded with 3-nitrobenzyl alcohol matrix using
argon or xenon as the target gas. Aldehydes used in this
study were either commercially available or prepared by
3
. Conclusions
2
4
We have demonstrated that i-PrOZnEt is an excellent
reagent to promote the aldol-Tishchenko reaction of
aliphatic aldehydes tethered with several functional groups.
the literature method. The undec-10-enal (1d), 10-
were
2
oxoundecanal (1i), and 6-bromohexanal (1j)
5
16b
prepared from their corresponding alcohols by PCC
oxidation. 8-Oxooctanoic acid methyl ester (1e), 6-oxo-
hexanoic acid methyl ester (1f), 8,8-dimethoxyoctanal (1g)
and 6,6-dimethoxyhexanal (1h) were prepared according to
the literature procedure from their corresponding
0
Both 1,3-diol monoesters 4 and 4 were formed and the
primary alkyl carboxylate 4 was formed as the major
0
0:1. The major isomer 4 can be used for the preparation of
product. The ratio of 4 and 4 in each case are approximately
1
the a-methylene ketones 7 by treatment with DBU.
2
6
cycloalkenes.

Y.-S. Hon, C.-P. Chang / Tetrahedron 61 (2005) 5267–5275
5271
4
.1. General procedure to carry out the aldol-
4.1.3. 3,7-Dimethyloct-6-enoic acid 2-(1,5-dimethylhex-
4-enyl)-5,9-dimethyl-3-oxodec-8-enyl ester (6c). Fol-
lowed the general procedure to prepare the aldol-
Tishchenko reaction of the aldehyde and the mixture of
the reaction products were subsequently oxidized by
PCC
0
Tishchenko products (4c and 4c) from the aldehyde 1c in
56% yield. According to the general procedure, the aldol-
0
i-PrOZnEt was obtained from the reaction of Et Zn (1.0 M
2
in hexane, 0.90 mL, 0.90 mmol) and isopropanol (0.07 mL,
0
Tishchenko products (4c and 4c) were then oxidized by
PCC to give compound 6c in 80% yield as a colorless oil;
1
.90 mmol) in THF (3 mL) at rt for 5 min. To a solution of
TLC R Z0.78 (hexane/EtOAcZ10:1); H NMR (CDCl ,
f
3
hydrocinnamaldehyde (1a) (603.8 mg, 4.5 mmol) in 10 mL
of THF, i-PrOZnEt was added the dropwise at 0 8C in a
period of 5 min. The reaction was warmed slowly to rt and
stirred at this temperature for 12 h. The reaction is quenched
with 1 N HCl and extracted with ethyl ether. The organic
400 MHz) d 0.85–0.91 (m, 9H, –CH ), 1.15–1.34 (m, 6H,
–CH ), 1.58 (s, 6H, –CH ), 1.60 (s, 3H, –CH ), 1.67 (s, 6H,
3
2
3
3
CH ), 1.68 (s, 3H, CH ), 1.88–2.07 (m, 10H), 2.21–2.27 (m,
3
3
2H, –CH ), 2.39 (dd, JZ16.7, 5.1 Hz, 1H), 2.72–2.76 (m,
2
1H, –CH), 4.21–4.26 (m, 2H, –CH O C–), 5.04–5.09 (m,
2
2
1
3H, –CH]C(CH3)2); C NMR (CDCl , 100 MHz) d 15.9
3
layer was dried over MgSO , concentrated, and chromato-
4
3
graphed on silica gel column to give a mixture of the 1,3-
diol monoesters 4a and 4a (549.5 mg, 4.09 mmol) in 91%
(18), 17.6 (18), 17.6 (18), 17.7 (18), 19.5 (18), 19.7 (18), 25.4
(28), 25.5 (28), 25.6 (28), 25.7 (18), 28.3 (18), 29.93 (18),
29.98 (38), 32.2 (38), 35.1 (28), 36.8 (28), 37.0 (28), 41.7 (28),
50.6 (28), 55.0 (38), 62.0 (28, –CH O C–), 123.8 (38), 124.2
(38), 124.3 (38), 131.4 (48, –C]C(CH ) ), 131.5 (48,
3 2
–C]C(CH ) ), 131.9 (48, –C]C(CH ) ), 173.0 (48,
3 2 3 2
0
yield. To a mixture of the 1,3-diol monoesters 4a and 4a
0
(
(
549.5 mg, 4.09 mmol) in 10 mL of CH Cl , PCC
2 2
pyridinium chlorochromate, 1102 mg, 5.11 mmol) and
˚
2 2
anhydrous 4 A molecular sieves (500 mg) was added at
8C. The reaction was warmed slowly to rt and stirred at
0
–CO ), 210.8 (48, –C]O); IR (KBr, neat): 2967, 2925,
2
K1
this temperature for 3 h. To the crude reaction mixture, ether
was added and most of the chromium salts were precipitated
out. After filtration, the filtrate was concentrated, and
chromatographed on silica gel column to give the
b-acyloxyketone 6a (1372 mg, 3.43 mmol) in 84% yield
2851, 1739, 1720, 1457, 1378, 1286, 1244, 1152, 986 cm
MS m/z (relative intensity): 461 (M C1, 3), 272 (21), 290
;
C
(21), 109 (65); HRMS Calcd for C H O : 460.3916.
3
0 52 3
Found: 460.3923.
1
5
as a colorless oil and a,b-unsaturated aldehyde 5a
(
4.1.4. Undec-10-enoic acid 2-dec-9-enyl-3-oxotridec-12-
enyl ester (6d). Followed the general procedure to prepare
82.5 mg, 0.33 mmol) in 8% yield.
0
aldehyde 1d in 84% yield. According to the general
procedure, the aldol-Tishchenko products (4d and 4d)
the aldol-Tishchenko products (4d and 4d) from the
4
.1.1. 3-Phenylpropionic acid 2-benzyl-3-oxo-5-phenyl-
0
were then oxidized by PCC to give compound 6d in 80%
pentyl ester (6a). TLC R Z0.60 (hexane/EtOAcZ10:1);
f
1
H NMR (CDCl , 400 MHz) d 2.41–2.49 (m, 1H), 2.54–
3
2
3
7
.59 (m, 2H), 2.61–2.85 (m, 5H), 2.85–2.93 (m, 2H), 3.04–
.12 (m, 1H), 4.20 (d, JZ6.5 Hz, 2H, –CH O C–), 7.06–
yield as a colorless oil; TLC R Z0.63 (hexane/EtOAcZ
f
1
10:1); H NMR (CDCl , 400 MHz) d 1.24–1.36 (m, 30H),
2
2
3
1
.29 (m, 15H, Ph-H); C NMR (CDCl , 100 MHz) d 29.1
3
1.56–1.58 (m, 6H), 2.00 (pseudo q, JZ6.6 Hz, 6H,
CH ]CHCH –), 2.22 (t, JZ6.8 Hz, 2H, –CH), 2.41 (t,
3
(
(
(
28), 30.8 (28), 34.8 (28), 35.6 (28), 45.4 (28), 52.6 (38), 64.3
28, –CH O C–), 126.0 (38), 126.3 (38), 126.7 (38), 128.2
38), 128.3 (38), 128.4 (38), 128.5 (38), 128.7 (38), 128.8 (38),
38.1 (48), 140.2 (48), 140.9 (48), 172.4 (48, –CO –), 210.2
2
2
JZ7.4 Hz, 2H), 2.79 (qu, JZ6.9 Hz, 1H), 4.13 (d, JZ
6.8 Hz, 2H, –CH O C–), 4.88–4.97 (m, 6H, –CH]CH ),
5.71–5.81 (m, 3H, –CH]CH ); C NMR (CDCl3,
2
2
2
2
2
1
3
1
2
2
(
48, –C]O); IR (KBr, neat): 3061, 3027, 2928, 1737, 1720,
100 MHz) d 23.2 (28), 24.8 (28), 27.0 (28), 28.5 (28), 28.75
(28), 28.80 (28), 28.88 (28), 28.96 (28), 28.98 (28), 29.00 (28),
29.09 (28), 29.10 (28), 29.19 (28), 29.23 (28), 29.3 (28),
29.5 (28), 33.6 (28), 33.7 (28), 34.1 (28), 42.9 (28), 50.7 (38),
K1
1
MS m/z (relative intensity): 400 (M , 1), 250 (100), 91 (31);
HRMS Calcd for C H O : 400.2038. Found: 400.2047.
27 28 3
604, 1496, 1454, 1371, 1245, 1160, 1078, 1030, 749 cm
;
C
6
4.5 (28, –CH O C–), 114.0 (28, –CH]CH ), 114.1 (28,
2
2
2
4.1.2. Heptanoic acid 3-oxo-2-pentylnonyl ester (6b).
Followed the general procedure to prepare the aldol-
–CH]CH
–CH]CH
2
), 138.9 (38, –CH]CH
), 173.3 (48, –CO –), 211.7 (48, –C]O); IR
2
2
), 139.0 (38,
2
0
0% yield. According to the general procedure, the aldol-
Tishchenko products (4b and 4b) from the aldehyde 1b in
9
(KBr, neat): 3076, 2926, 2855, 1740, 1717, 1640, 1464,
1167, 994, 909 cm ; MS (FAB) m/z (relative intensity):
K1
0
C
503 (M C1, 5), 319 (55), 149 (25); HRMS (FAB) Calcd
Tishchenko products (4b and 4b) were then oxidized by
PCC to give compound 6b in 75% yield as a colorless oil;
C
for [MCH]
C H O : 503.4464. Found: 503.4453.
33 59 3
1
TLC R Z0.72 (hexane/EtOAcZ10:1); H NMR (CDCl ,
f
3
4
00 MHz) d 0.83–0.87 (m, 9H), 1.21–1.40 (m, 18H), 1.53–
4.1.5. 7-(7-Methoxycarbonylheptanoyloxymethyl)-8-
oxopentadecanedioic acid dimethyl ester (6e). Followed
the general procedure to prepare the aldol-Tishchenko
1
.59 (m, 6H), 2.23 (t, JZ7.6 Hz, 2H, –CO CH –), 2.42 (t,
2
2
JZ7.2 Hz, 2H, –CH ), 2.80 (qu, JZ6.8 Hz, 1H, –CHCO),
4
2
1
3
0
.14 (d, JZ6.8 Hz, 2H, AB system, –CH O C–); C NMR
products (4e and 4e) from the aldehyde 1e in 68% yield.
According to the general procedure, the aldol-Tishchenko
2
2
(
CDCl , 100 MHz) d 13.88 (18), 13.93 (18), 22.3 (28), 22.4
3
0
(
(
(
28), 22.5 (28), 23.3 (28), 24.8 (28), 26.7 (28), 28.6 (28), 28.7
28), 28.8 (28), 31.4 (28), 31.6 (28), 31.8 (28), 34.2 (28), 43.0
28), 50.8 (38), 64.5 (28, –CH O C–), 173.4 (48, C]O),
products (4e and 4e) were then oxidized by PCC to give
compound 6e in 91% yield as a colorless oil; TLC R Z0.79
f
1
(hexane/EtOAcZ1:1); H NMR (CDCl , 400 MHz) d 1.22–
2
2
3
2
11.9 (48, C]O); IR (KBr, neat): 2961, 2930, 2862, 1741
1.54 (m, 24H), 2.15–2.23 (m, 8H, –CH ), 2.37 (t, JZ7.2 Hz,
2
K1
(
C]O), 1720 (C]O), 1469, 1378, 1231, 1167, 1103 cm
;
MS m/z (relative intensity): 340 (M , 1), 113 (100), 85 (31);
2H), 2.73 (qu, JZ6.8 Hz, 1H, –CH), 3.57 (s, 9H, –OCH ),
3
C
13
4.07 (d, JZ6.8 Hz, 2H, –CH O C–); C NMR (CDCl3,
2
2
HRMS Calcd for C H O : 340.2977. Found: 340.2969.
21 40 3
100 MHz) d 22.8 (28), 24.3 (28), 24.4 (28), 24.45 (28), 24.47

5272
Y.-S. Hon, C.-P. Chang / Tetrahedron 61 (2005) 5267–5275
(
2
(
–
28), 26.5 (28), 28.1 (28), 28.43 (28), 28.45 (28), 28.53 (28),
8.7 (28), 28.8 (28), 33.57 (28), 33.65 (28), 33.67 (28), 33.8
28), 42.7 (28), 50.5 (38), 51.1 (18), 51.2 (18), 64.2 (28,
CH O C–), 173.0 (48, –C]O), 173.65 (48, –CO ), 173.74
6H), 1.49–1.57 (m, 12H), 2.21 (t, JZ7.5 Hz, 2H, –CH2),
2.41 (t, JZ7.2 Hz, 2H, –CH ), 2.76 (qu, JZ6.7 Hz, 1H,
2
–CH), 3.24 (s, 18H, –OCH ), 4.10 (d, JZ7.6 Hz, 2H,
3
1
–CH O C–), 4.25–4.30 (m, 3H, –CH(OCH ) ); C NMR
3
2
2
2
2 2 3 2
(
neat): 2938, 2860, 1739, 1437, 1362, 1172, 1011, 879,
7
48, –CO ), 173.75 (48, –CO ), 211.2 (48, –C]O); IR (KBr,
(CDCl , 100 MHz) d 22.1 (28), 23.0 (28), 23.97 (28), 24.02
3
2
2
(28), 24.5 (28), 28.2 (28), 32.0 (28), 32.2 (28), 32.4 (28), 33.9
(28), 42.8 (28), 50.6 (38), 52.58 (18, –OCH ), 52.64 (18,
K1 C
31 cm ; MS (FAB) m/z (relative intensity): 515 (M C1,
3
4
[
), 307 (27), 154 (100), 137 (57); HRMS (FAB) Calcd for
MCH] C H O : 515.3220. Found: 515.3228.
–OCH ), 52.8 (18, –OCH ), 64.3 (28, –CH O C–), 104.0 (38),
3
104.15 (38), 104.19 (38), 173.0 (48, –CO ), 211.2 (48, –C]O);
2
3
2 2
C
2
7
47
9
IR (KBr, neat): 2947, 2830, 1739, 1462, 1386, 1197, 1127,
1054, 957, 736 cm ; MS (FAB) m/z (relative intensity): 478
K1
4.1.6. 5-(5-Methoxycarbonylpentanoyloxymethyl)-6-
oxoundecanedioic acid dimethyl ester (6f). Followed the
C
(M , 2), 351 (28), 127 (73), 75 (100); HRMS (FAB) Calcd for
general procedure to prepare the aldol-Tishchenko products
0
C H O : 478.3142. Found: 478.3132.
24 46 9
(
4f and 4f) from the aldehyde 1f in 50% yield. According to
0
the general procedure, the aldol-Tishchenko products (4f
and 4f) were then oxidized by PCC to give compound 6f in
4.1.9. 10-Oxoundecanoic acid 3,12-dioxo-2-(8-oxononyl)-
tridecyl ester (6i). Followed the general procedure to
0
aldehyde 1i in 50% yield. According to the general
procedure, the aldol-Tishchenko products (4i and 4i) were
5
2
2
6% yield as a colorless oil; TLC R Z0.50 (ether/hexaneZ
prepare the aldol-Tishchenko products (4i and 4i) from the
f
1
:1); H NMR (CDCl , 400 MHz) d 1.56–1.64 (m, 12H),
3
0
then oxidized by PCC to give compound 6i in 85% yield as a
.27–2.34 (m, 8H, –CH ), 2.48–2.51 (m, 2H, –CH ), 2.82
2
2
(
6
qu, JZ6.4 Hz, 1H, –CH), 3.67 (s, 9H, –OCH ), 4.18 (d, JZ
3
1
.3 Hz, 2H, –CH O C–); C NMR (CDCl , 100 MHz) d
3
white solid; mp 55 8C; TLC R Z0.47 (hexane/EtOAcZ
2
2
3
f
1
3:1); H NMR (CDCl , 400 MHz) d 1.15–1.25 (m, 24H),
2
(
2.3 (28), 22.6 (28), 24.16 (28), 24.20 (28), 24.3 (28), 27.8
28), 33.50 (28), 33.58 (28), 33.67 (28), 33.70 (28), 42.3 (28),
3
1.45–1.48 (m, 12H), 2.03 (s, 9H, –CH ), 2.16 (t, JZ7.5 Hz,
3
5
–
1
–
0.5 (38), 51.4 (18, –OCH ), 51.5 (18, –OCH ), 64.2 (28,
3
2H, –O]CCH –), 2.30–2.37 (m, 8H, –CH ), 2.72 (qu, JZ
3
2
2
1
3
CH O C–), 172.8 (48, –CO CH ), 173.3 (48, –CO CH ),
2
6.8 Hz, 1H, –CH), 4.06 (d, JZ6.8 Hz, 2H, –CH O C–); C
2
2
3
2
3
2 2
73.55 (48, –CO CH ), 173.64 (48, –CO CH ), 210.6 (48,
2
NMR (CDCl , 100 MHz) d 23.1 (28), 23.5 (28), 23.6 (18),
3
2
3
3
K1
C]O); IR (KBr, neat): 2952, 1738, 1436, 1368, 1171 cm
;
24.6 (28), 26.8 (28), 28.3 (28), 28.80 (28), 28.83 (28), 28.86
(28), 28.88 (28), 28.90 (28), 28.96 (28), 29.00 (28), 29.03 (28),
29.2 (28), 29.6 (28), 33.9 (28), 42.7 (28), 43.4 (28), 43.5 (28),
50.6 (38), 64.3 (28, –CH O C–), 173.2 (48, –CH CO –),
C
MS (FAB) m/z (relative intensity): 431 (M C1, 29), 271
55), 239 (38), 154 (100), 137 (81), 111 (46); HRMS (FAB)
Calcd for C H O [MCH] : 431.2281. Found: 431.2272.
(
C
2
1
35
9
2
2
2
2
2
08.79 (48, –C]O), 208.84 (48, –C]O), 211.6 (48,
–C]O); IR (KBr, neat): 2931, 2856, 1730, 1717, 1460,
4.1.7. 8,8-Dimethoxyoctanoic acid 2-(6,6-dimethoxy-
heptyl)-10,10-dimethoxy-3-oxodecyl ester (6g). Followed
K1
1413, 1361, 1233, 1168, 735 cm ; MS (FAB) m/z (relative
C
intensity): 551 (M C1, 13), 351 (100), 183 (51), 137 (25);
the general procedure to prepare the aldol-Tishchenko
products (4g and 4g) from the aldehyde 1g in 73% yield.
0
According to the general procedure, the aldol-Tishchenko
products (4g and 4g) were then oxidized by PCC to give
C
HRMS (FAB) Calcd for [MCH]
Found: 551.4321.
C H O : 551.4312.
33 59 6
0
compound 6g in 64% yield as a pale yellow oil; TLC R Z
4.1.10. 6-Bromohexanoic acid 8-bromo-2-(4-bromo-
butyl)-3-oxooctyl ester (6j). Followed the general pro-
cedure to prepare the aldol-Tishchenko products (4j and 4j)
f
1
0
1
2
2
4
–
2
(
3
(
.83 (ether/hexaneZ3:1); H NMR (CDCl , 400 MHz) d
3
0
from the aldehyde 1j in 87% yield. According to the general
procedure, the aldol-Tishchenko products (4j and 4j) were
.20–1.35 (m, 20H), 1.45–1.55 (m, 10H), 2.20 (t, JZ7.5 Hz,
H, –OC]OCH –), 2.39 (t, JZ7.3 Hz, 2H, –CH CO–),
2
2
0
then oxidized by PCC to give compound 6j in 70% yield as a
.76 (qu, JZ6.8 Hz, 1H, –CHC]O), 3.25 (s, 18H, –OCH3),
.10 (d, JZ6.8 Hz, 2H, –CH O C–), 4.27–4.31 (m, 3H,
2
2
1
CH(OCH ) ); C NMR (CDCl , 100 MHz) d 23.1 (28),
3
1
pale yellow oil; TLC R Z0.51 (hexane/EtOAcZ5:1); H
3
2
3
f
4.2 (28), 24.28 (28), 24.31 (28), 24.6 (28), 27.0 (28), 28.4
28), 28.89 (28), 28.96 (28), 29.01 (28), 29.2 (28), 29.4 (28),
2.27 (28), 32.31 (28), 32.33 (28), 34.0 (28), 42.9 (28), 50.7
38), 52.49 (18, –OCH ), 52.52 (18, –OCH ), 64.4 (28,
NMR (CDCl , 400 MHz) d 1.39–1.45 (m, 7H), 1.57–1.62
(m, 5H), 1.81–1.86 (m, 6H), 2.27 (t, JZ7.4 Hz, 2H,
3
–O]CCH –), 2.47 (td, JZ7.2, 1.8 Hz, 2H), 2.80 (quin,
2
JZ5.6 Hz, 1H), 3.37–3.40 (m, 6H, –CH Br), 4.15 (t, JZ
3
3
2
1
3
–
CH O C–), 104.3 (38), 104.4 (38), 173.3 (48, –CO ), 211.6
2
5.2 Hz, 2H, –CH O C–); C NMR (CDCl , 100 MHz) d
2
2
2 2 3
(
1
5
48, –C]O); IR (KBr, neat): 2939, 1739, 1718 (C]O),
22.3 (28), 23.9 (28), 25.6 (28), 27.51 (28), 27.53 (28), 27.6
(28), 32.3 (28), 32.5 (28), 33.1 (28), 33.4 (28), 33.5 (28), 33.8
(28), 42.6 (28), 50.7 (38), 64.3 (28, CH O C–), 172.9 (48,
K1
463, 1385, 1127, 728 cm ; MS m/z (relative intensity):
C C
61 (M K1, 3), 435 (36), 403 (M K159), 391 (16), 307
2
2
C
(
18), 154 (100); HRMS Calcd for (M K159) C H O :
21 39 7
–C]O), 210.9 (48, –C]O); IR (KBr, neat): 2938, 2863,
1736, 1720, 1637, 1457, 1366, 1266, 1173, 737 cm ; MS
K1
4
03.2696. Found: 403.2704.
(FAB) m/z (relative intensity): 539 (5), 537 (10), 535 (11),
533 (5), 453 (8), 341 (37), 177 (49), 137 (18); HRMS (FAB)
Calcd [MCH] for C18H O Br : 532.9902. Found:
32 3 3
4.1.8. 6,6-Dimethoxyhexanoic acid 2-(4,4-dimethoxy-
butyl)-8,8-dimethoxy-3-oxooctyl ester (6h). Followed the
C
79
general procedure to prepare the aldol-Tishchenko products
(
532.9910.
0
to the general procedure, the aldol-Tishchenko products
4h and 4h) from the aldehyde 1h in 72% yield. According
4.2. General procedure to prepare the a-methylene
ketone via elimination of the b-acyloxyketone
0
(
4h and 4h) were then oxidized by PCC to give compound
6
h in 62% yield as a pale yellow oil; TLC R Z0.32 (ether/
f
1
hexaneZ2:1); H NMR (CDCl , 400 MHz) d 1.26–1.33 (m,
To a solution of the b-acyloxyketone 6a (152 mg,
3

Y.-S. Hon, C.-P. Chang / Tetrahedron 61 (2005) 5267–5275
5273
1
0
0
.38 mmol) in 5 mL of benzene was added DBU (0.06 mL,
.42 mmol) and the reaction mixture was stirred at rt for 5 h.
EtOAcZ30:1); H NMR (CDCl , 400 MHz) d 1.27–1.38
3
(m, 20H), 1.54–1.59 (m, 2H), 2.01 (pseudo q, JZ6.8 Hz,
4H, CH ]CHCH –), 2.23 (t, JZ7.5 Hz, 2H, –CH C]O–),
2.63 (t, JZ7.4 Hz, 2H, –CH ), 4.88–4.98 (m, 4H,
–CH]CH ), 5.65 (s, 1H, –C]CH ), 5.72–5.82 (m, 2H,
–CH]CH ), 5.92 (s, 1H, –CH]CH ); C NMR (CDCl3,
2 2
The reaction mixture was concentrated to give the crude
residues, which were chromatographed on silica gel column
to give the a-methylene ketone 7a (71.3 mg, 0.29 mmol) in
2
2
2
2
2
2
1
3
7
5% yield as a pale yellow oil.
1
00 MHz) d 24.6 (28), 28.4 (28), 28.8 (28), 28.98 (28), 29.00
(28), 29.20 (28), 29.25 (28), 29.33 (28), 30.9 (28), 33.7 (28),
37.8 (28), 114.0 (28, –CH]CH ), 123.1 (48, –C]CH ),
139.0 (38, –CH]CH ), 149.1 (48, –C]CH ), 202.2 (48,
2
2d
4
.2.1. 2-Benzyl-5-phenylpent-1-en-3-one (7a).
TLC
1
RfZ0.66 (hexane/EtOAcZ10:1); H NMR (CDCl3,
4
2
2
00 MHz) d 2.99–3.07 (m, 4H, –CH ), 3.69 (s, 2H), 5.67
2
2
2
(
7
3
t, JZ1.32 Hz, 1H, –C]CH ), 6.10 (s, 1H, –C]CH ),
–C]O); IR (KBr, neat): 3078, 2927, 2855, 1679, 1643,
1469, 1433, 1366, 909 cm ; MS (FAB) m/z (relative
2
2
1
.22–7.35 (m, 10H, Ph-H); C NMR (CDCl , 100 MHz) d
3
K1
3
0.2 (28), 37.0 (28), 39.5 (28), 125.2 (38), 125.95 (38), 126.13
intensity): 319 (MC1, 46), 179 (9), 149 (13), 109 (22);
C H39O: 319.3001.
22
C
(
28, –C]CH ), 128.25 (38), 128.33 (38), 128.4 (38), 129.0
2
HRMS (FAB) Calcd for [MCH]
Found: 319.3004.
(
38), 139.0 (48), 141.1 (48), 148.2 (48, –C]CH ), 200.1 (48,
2
–
1
7
C]O); IR (KBr, neat): 3085, 3061, 3027, 2925, 1678,
627, 1603, 1495, 1453, 1432, 1409, 1368, 1078, 941, 745,
4.2.5. 7-Methylene-8-oxo-pentadecanedioic acid
dimethyl ester (7e). Followed the general procedure to
carry out the elimination of b-acyloxy ketone 6e to give
a-methylene ketone 7e in 75% yield as a pale yellow oil;
K1 C
00 cm ; MS m/z (relative intensity): 250 (M , 100), 91
(
22); HRMS Calcd for C H O: 250.1358. Found:
18 18
2
50.1349.
1
TLC R Z0.83 (hexane/EtOAcZ10:1); H NMR (CDCl ,
f
3
4
.2.2. 2-Pentyl-non-1-en-3-one (7b). Followed the general
400 MHz) d 1.27–1.60 (m, 14H), 2.20–2.27 (m, 6H, –CH ),
2
procedure to carry out the elimination of b-acyloxy ketone
b to give a-methylene ketone 7b in 76% yield as a pale
2.61 (t, JZ7.4 Hz, 2H, –CH
1H, –C]CH ), 5.92 (s, 1H, –C]CH
2
100 MHz) d 24.3 (28), 24.59 (28), 24.64 (28), 28.0 (28), 28.7
(28), 28.80 (28), 28.81 (28), 30.6 (28), 33.8 (28), 37.5 (28),
2
), 3.61 (s, 6H, –OCH
3
), 5.65 (s,
); C NMR (CDCl ,
3
1
3
6
2
1
yellow oil; TLC R Z0.70 (hexane/EtOAcZ10:1); H NMR
f
(
CDCl , 400 MHz) d 0.85–0.88 (m, 6H), 1.24–1.40 (m,
3
1
–
–
1
2H), 1.53–1.59 (m, 2H), 2.24 (t, JZ7.8 Hz, 2H,
CH C]CH ), 2.64 (t, JZ7.5 Hz, 2H), 5.67 (s, 1H,
51.3 (18, –OCH
3
), 123.5 (28, –C]CH
), 174.01 (48, –CO
2
2
), 148.7 (48,
–C]CH ), 174.00 (48, –CO
), 201.9
2
2
2
2
1
C]CH ), 5.94 (s, 1H, –C]CH ); C NMR (CDCl3,
3
(48, –C]O); IR (KBr, neat): 2940, 2860, 1739, 1678, 1619,
1437, 1361, 1257, 1173, 1005, 938 cm ; MS (FAB) m/z
2
2
K1
00 MHz) d 13.9 (18), 14.0 (18), 22.4 (28), 22.5 (28), 24.6
C
(relative intensity): 327 (M C1, 60), 149 (100), 137 (71),
(
(
28), 28.1 (28), 29.0 (28), 30.9 (28), 31.5 (28), 31.6 (28), 37.8
28), 123.1 (28, –C]CH ), 149.2 (28, –C]CH ), 202.4 (48,
C
107 (27); HRMS (FAB) Calcd for [MCH]
327.2171. Found: 327.2180.
C H O :
18 31 5
2
2
–
C]O); IR (KBr, neat): 3095, 2928, 2857, 1739, 1679
C]O), 1623, 1464, 1378, 1121, 931 cm ; MS m/z
K1
(
(
C
relative intensity): 210 (M , 100), 125 (11); HRMS
4.2.6. 5-Methylene-6-oxoundecanedioic acid dimethyl
ester (7f). Followed the general procedure to carry out the
elimination of b-acyloxy ketone 6f to give a-methylene
Calcd for C H O: 210.1984. Found: 210.1976.
14 26
4
.2.3. (6R,10R)-2,6,10,14-Tetramethyl-7-methylene-
ketone 7f in 80% yield as a pale yellow oil; TLC R Z0.70
f
1
pentadeca-2,13-dien-8-one (7c). Followed the general
procedure to carry out the elimination of b-acyloxy ketone
6
(ether/hexaneZ2:1); H NMR (CDCl , 400 MHz) d 1.28–
3
1.69 (m, 6H), 2.21–2.27 (m, 6H, –CH ), 2.64 (br t, 2H,
–CH ), 3.59–3.60 (m, 6H, –OCH ), 5.70 (s, 1H, –C]CH ),
2
c to give a-methylene ketone 7c in 70% yield as a pale
2
3
2
1
13
5.96 (s, 1H, –C]CH2); C NMR (CDCl , 100 MHz) d 23.5
yellow oil; TLC R Z0.83 (hexane/EtOAcZ20:1); H NMR
f
3
(
CDCl , 400 MHz) d 0.89 (d, JZ6.6 Hz, 3H, –CH ), 1.01
(28), 23.7 (28), 24.4 (28), 30.1 (28), 33.4 (28), 33.7 (28), 37.1
(28), 51.3 (18, –OCH ), 124.2 (28, –C]CH ), 147.8 (48,
–C]CH ), 173.6 (48, –CO –), 173.7 (48, –CO –), 201.0 (48,
2 2 2
3
3
(
C]C(CH ) ), 1.59 (s, 3H, C]C(CH ) ), 1.67 (s, 6H,
d, JZ6.8 Hz, 3H, –CH ), 1.19–1.48 (m, 5H),1.56 (s, 3H,
3
3
2
3
2
3 2
C]C(CH ) ), 1.87–2.07 (m, 5H), 2.46 (dd, JZ8.1 Hz, 1H),
–C]O); IR (KBr, neat): 2952, 1737, 1677, 1437, 1368,
1199, 1173, 1005, 938 cm ; MS m/z (relative intensity):
3
2
K1
2
.63–2.68 (m, 1H), 2.78–2.84 (m, 1H), 5.08 (br t, 2H,
CH(CH ) ), 5.66 (s, 1H, ]CH ), 5.98 (s, 1H, –C]CH );
3
C
270 (M , 7), 206 (21), 123 (89), 95 (100); HRMS Calcd for
]
3
2
2
2
1
C NMR (CDCl , 100 MHz) d 17.6 (18), 19.8 (18), 20.1
C H O : 270.1467. Found: 270.1476.
14 22 5
3
(
(
18), 20.2 (18), 25.5 (28), 25.7 (18), 25.9 (28), 29.7 (38), 32.6
38), 36.3 (28), 37.2 (28), 45.5 (28), 121.8 (28), 124.40 (38,
4.2.7. 2-(6,6-Dimethoxyhexyl)-10,10-dimethoxydec-1-en-
3-one (7g). Followed the general procedure to carry out the
elimination of b-acyloxy ketone 6g to give a-methylene
–
–
–
1
1
2
CH]C(CH ) ), 124.43 (38, –CH]C(CH ) ), 131.40 (48,
3 2 3 2
CH]C(CH ) ), 131.43 (48, –CH]C(CH ) ), 154.8 (48,
3
2
3 2
2
D
8
C]CH ), 202.2 (48, –C]O); [a] ZK32.7 (cZ3.0!
ketone 7g in 90% yield as a pale yellow oil; TLC R Z0.50
2
f
K4
1
0
677, 1457, 1378, 931 cm ; MS m/z (relative intensity):
, CH Cl ); IR (KBr, neat): 3095, 2967, 2925, 2851,
(hexane/EtOAcZ3:1); H NMR (CDCl , 400 MHz) d 1.30–
2
2
3
K1
1.39 (m, 12H), 1.53–1.57 (m, 6H), 2.23 (t, JZ7.0 Hz, 2H,
–CH ), 2.63 (t, JZ7.4 Hz, 2H, –CH ), 3.28 (s, 12H,
C
90 (M , 13), 233 (20), 207 (31), 165 (38), 109 (70);
2
2
HRMS Calcd for C H O: 290.2610. Found: 290.2613.
0
–OCH ), 4.32 (t, JZ5.7 Hz, 2H, –CH(OCH ) ), 5.66 (s,
3 3 2
13
2
34
1
H, –CH]CH ), 5.93 (s, 1H, –C]CH ); C NMR
2 2
4.2.4. 12-Methylenedocosa-1,21-dien-11-one (7d). Fol-
lowed the general procedure to carry out the elimination
(CDCl , 100 MHz) d 24.3 (28), 24.4 (28), 24.5 (28), 28.4
3
(28), 29.13 (28), 29.19 (28), 29.23 (28), 30.8 (28), 32.39 (28),
32.41 (28), 37.7 (28, –CH C]O), 52.6 (18, –OCH ), 104.5
of b-acyloxy ketone 6d to give a-methylene ketone 7d in
1% yield as a pale yellow oil; TLC R Z0.92 (hexane/
2
3
7
(38, –CH(OCH ) ), 123.3 (28, –C]CH ), 149.0 (48,
3 2 2
f

5274
Y.-S. Hon, C.-P. Chang / Tetrahedron 61 (2005) 5267–5275
–
2
7
2
C]CH ), 202.2 (48, –C]O); IR (KBr, neat): 3060, 2938,
2
Acknowledgements
861, 1739, 1676, 1467, 1394, 1370, 1273, 1127, 1048, 939,
K1 C
39 cm ; MS m/z (relative intensity): 357 (M K1, 3),
We are grateful to the National Science Council, National
Chung Cheng University, and Academia Sinica, Republic of
China for financial support.
C
96 (M K62, 6), 263 (60), 154 (20), 149 (36), 75 (100);
C
HRMS Calcd for (M K62) C H O : 296.2351. Found:
1
8 32 3
2
96.2347.
4
.2.8. 2-(4,4-Dimethoxybutyl)-8,8-dimethoxyoct-1-en-3-
one (7h). Followed the general procedure to carry out the
elimination of b-acyloxy ketone 6h to give a-methylene
References and notes
ketone 7h in 92% yield a pale yellow oil; TLC R Z0.72
f
1
2
. (a) Tishchenko, W. J. Russ. Phys. Chem. Soc. 1906, 38, 355.
b) Lin, I.; Day, A. J. Am. Chem. Soc. 1952, 74, 5133–5135.
. Fouquet, G.; Merger, F.; Platz, R. Liebigs Ann. Chem. 1979,
1
(
ether/hexaneZ4:1); H NMR (CDCl , 400 MHz) d 1.31–
3
(
1
.41 (m, 4H), 1.52–1.60 (m, 6H), 2.23 (t, JZ7.6 Hz, 2H,
CH C]C), 2.63 (t, JZ7.3 Hz, 2H, –CH C]O), 3.26 (s,
2
2
1591–1601.
1
2H, –OCH ), 4.31 (t, JZ5.6 Hz, 2H, –CH(OCH ) ), 5.68
3 3 2
13
3. (a) Villani, F. J.; Nord, F. F. J. Am. Chem. Soc. 1946, 68,
1674–1675. (b) Villani, F. J.; Nord, F. F. J. Am. Chem. Soc.
1947, 69, 2605–2608. (c) Tsuji, H.; Yagi, F.; Hattori, H.; Kita,
H. J. Catal. 1994, 148, 759–770.
(
(
(
s, 1H, –C]CH ), 5.94 (s, 1H, –C]CH ); C NMR
CDCl , 100 MHz) d 23.3 (28), 24.20 (28), 24.22 (28), 30.5
3
28), 32.1 (28), 32.3 (28), 37.5 (28, –CH C]O), 52.61 (18,
2
2 2
–
1
–
1
OCH ), 52.64 (18, –OCH ), 104.3 (38, –CH(OCH ) ),
3
4. Kulpinski, M. S.; Nord, F. F. J. Org. Chem. 1943, 8, 256–270.
5. Schwenk, U.; Becker, A. Liebigs Ann. Chem. 1972, 756,
162–169.
3
3 2
23.7 (28, –C]CH ), 148.5 (48, –C]CH ), 201.7 (48,
2
2
C]O); IR (KBr, neat): 2947, 2830, 1738, 1680, 1458,
386, 1192, 1128, 1072, 953 cm ; MS (FAB) m/z (relative
K1
6. Ito, K.; Kamiyama, N.; Nakanishi, S.; Otsuji, Y. Chem. Lett.
1983, 657–660.
7. (a) T o¨ rm a¨ kangas, O. P.; Koskinen, A. M. P. Org. Process Res.
Dev. 2001, 5, 421–425. (b) T o¨ rm a¨ kangas, O. P.; Saarenketo,
P.; Koskinen, A. M. P. Org. Process Res. Dev. 2002, 6,
C
intensity): 302 (M , 4), 271 (10), 147 (43), 75 (100);
HRMS (FAB) Calcd for C H O : 302.2093. Found:
1
6 30 5
3
02.2095.
1
25–131.
. Villacorta, G. M.; Filippo, J. S., Jr. J. Org. Chem. 1983, 48,
151–1154.
4.2.9. 10-Methyleneheneicosane-2,11,20-trione (7i). Fol-
lowed the general procedure to carry out the elimination of
8
9
1
b-acyloxy ketone 6i to give a-methylene ketone 7i in 80%
yield as a white solid; mp 57–58 8C; TLC R Z0.53 (hexane/
. Miyano, A.; Tashiro, D.; Kawasaki, Y.; Sakaguchi, S.; Ishii, Y.
Tetrahedron Lett. 1998, 39, 6901–6902.
f
1
EtOAcZ3:1); H NMR (CDCl , 400 MHz) d 1.22–1.35 (m,
3
1
1
0. (a) McCain, J. H.; Theiling, L.F. (Union Carbide Corp.). U.S.
Patent 3,718,689, 1973; Chem. Abstr., 1973, 78, P135694k.
(b) Hagemeyer, H. J., Jr.; Lonhview, T. (East-Kodak Co.) U.S.
Patent 2,829,169, 1958; Chem. Abstr., 1958, 52, P12897b.
(c) Tamaru, Y.; Tanaka, A.; Yasui, K.; Goto, S.; Tanaka, S.
Angew. Chem., Int. Ed. Engl. 1995, 34, 787.
1
6H), 1.40–1.60 (m, 6H), 2.09 (s, 6H, –COCH ), 2.20 (t, JZ
3
7
.5 Hz, 2H, –CH ), 2.37 (t, JZ7.4 Hz, 4H, –CH ), 2.61 (t,
2
2
JZ7.4 Hz, 2H, –CH ), 5.65 (s, 1H, –C]CH ), 5.92 (s, 1H,
2
2
1
C]CH2); C NMR (CDCl , 100 MHz) d 23.7 (28), 24.5
3
–
3
(
28), 28.3 (28), 28.99 (28), 29.01 (28), 29.07 (28), 29.13 (28),
2
–
(
9.2 (28), 29.7 (28), 30.8 (28), 37.7 (28), 43.7 (28), 123.3 (28,
C]CH ), 149.0 (48, –C]CH ), 202.3 (48, –C]O), 209.1
48, –C]O); IR (KBr, neat): 3057, 2929, 2855, 1714, 1676,
627, 1410, 1361, 1269, 1166, 937, 737 cm ; MS (FAB)
C
1. (a) Casnati, G.; Pochini, G.; Salerno, G.; Ungaro, R.
Tetrahedron Lett. 1974, 12, 959–962. (b) Casnati, G.; Pochini,
A.; Salerno, G.; Ungaro, R. J. Chem. Soc., Perkin Trans. 1
1975, 1527–1531.
2
2
K1
1
m/z (relative intensity): 351 (M C1, 12), 111 (14), 83 (45);
12. Oxo Chemicals: Isobutyraldehyde. In Chemical Economics
Handbook; Standford Research Institute: International, Menlo
Park, California, November, 2000.
C
HRMS (FAB) Calcd for [MCH] C H O : 351.2899.
Found: 351.2894.
2
2 39 3
1
3. Hattori, H. Appl. Catal., A: Gen. 2001, 222, 247–259.
4. Hon, Y. S.; Chang, C. P.; Wong, Y. C. Tetrahedron Lett. 2004,
1
4.2.10. 10-Bromo-2-(4-bromobutyl)-oct-1-en-3-one (7j).
Followed the general procedure to carry out the elimination
of b-acyloxy ketone 6j to give a-methylene ketone 7j in
4
5, 3313–3315.
1
1
5. Hiyooka, S. I.; Fujimoto, H.; Mishima, M.; Kobayashi, S.;
Uddin, K. M.; Fujio, M. Tetrahedron Lett. 2003, 44, 927–930.
6. (a) Hon, Y. S.; Lu, L. Chem. Commun. 1994, 54, 2041–2042.
7
7% yield as a pale yellow oil; TLC R Z0.82 (hexane/
f
1
EtOAcZ5:1); H NMR (CDCl , 400 MHz) d 1.43–1.66 (m,
3
(b) Hon, Y. S.; Chang, F. J.; Lu, L.; Lin, W. C. Tetrahedron
1998, 54, 5233–5246.
6
7
3
6
H, –CH ), 1.84–1.90 (m, 4H, –CH C]O), 2.29 (t, JZ
2 2
.7 Hz, 2H, –CH –C]CH ), 2.70 (t, JZ7.3 Hz, 2H, –CH ),
2
2
2
17. Hon, Y. S.; Hsu, T. R.; Chen, C. Y.; Lin, Y. H.; Chang, F. J.;
Hsieh, C. H.; Szu, P. H. Tetrahedron 2003, 59, 1509–1520.
18. Hon, Y. S.; Lin, W. C. Tetrahedron Lett. 1995, 36, 7693–7696.
.40 (t, JZ6.8 Hz, 4H, –CH Br), 5.75 (s, 1H, –C]CH ),
2
2
1
.00 (s, 1H, –C]CH2); C NMR (CDCl , 100 MHz) d 23.6
3
3
(
(
28), 27.1 (28), 27.8 (28), 30.0 (28), 32.4 (28), 32.6 (28), 33.4
28), 33.5 (28), 37.4 (28), 124.0 (28, –C]CH ), 148.3 (48,
1
9. Hon, Y. S.; Liu, Y. W.; Hsieh, C. H. Tetrahedron 2004, 60,
4837–4860.
2
–
2
C]CH ), 201.5 (48, –C]O); IR (KBr, neat): 3102, 2937,
2
20. Hon, Y. S.; Hsieh, C. H.; Liu, Y. W. Tetrahedron 2005, 61,
2713–2723.
K1
861, 1677, 1626, 1437, 1366, 1265, 937, 738 cm ; MS
(
FAB) m/z (relative intensity): 343 (36), 341 (100), 339
C
68), 261 (50), 259 (51); HRMS Calcd [MCH] for
21. (a) Tramontini, M. Synthesis 1973, 703–775. (b) Kleinman,
E. F. In Trost, B. M., Ed.; Comprehensive Organic Synthesis;
Pergamon: New York, 1991; Vol. 2, pp 893–951.
(
C H
7
9
Br O: 338.9959. Found: 338.9952.
2
1
2
20

Y.-S. Hon, C.-P. Chang / Tetrahedron 61 (2005) 5267–5275
5275
2
2. (a) Cormier, R. A.; Schreiber, W. L.; Agosta, W. C. J. Am.
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Andrisano, R.; Angeloni, A. S.; De Maria, P.; Tramontini, M.
J. Chem. Soc. C 1967, 2307–2311. (d) Filho, E. P. S.;
Rodrigues, J. A. R.; Moran, P. J. S. Tetrahedron: Asymmetry
Zuman, P. Tetrahedron Lett. 1961, 2, 744–745. (f) Angeloni,
A. S.; Angiolini, L.; De Maria, P.; Fini, A. J. Chem. Soc. C
1968, 2295–2297. (g) Johnson, W. S.; Szmuszkovicz, J.;
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1956, 78, 6285–6289.
24. Sharma, A.; Sankaranarayanan, S.; Chattopadhyay, S. J. Org.
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2
001, 12, 847–852.
3. (a) Farberov, M. I.; Mironov, G. S., Chem. Abstr., 1963, 59,
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2
25. Cottier, L.; Descotes, G. Bull. Soc. Chim. Fr. 1972,
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5
Soc. Chim. Fr. 1970, 2707–2711. (c) Danishefsky, S.;
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