One-pot synthesis of 1,5-diketones catalyzed by barium isopropoxide

Article abstract of DOI:10.1016/j.tet.2007.04.079

A tandem cross-coupling reaction of aryl methyl ketones with aromatic aldehydes has been accomplished employing barium isopropoxide as a catalyst, in which barium enolates are generated and then three consecutive reactions (aldol reaction/β-elimination/co

Full text of DOI:10.1016/j.tet.2007.04.079

Tetrahedron 63 (2007) 8581–8585
One-pot synthesis of 1,5-diketones catalyzed by
barium isopropoxide
a,*
b
Akira Yanagisawa, Hiroshi Takahashi and Takayoshi Arai
a
a
Department of Chemistry, Faculty of Science, Chiba University, Inage, Chiba 263-8522, Japan
Graduate School of Science and Technology, Chiba University, Inage, Chiba 263-8522, Japan
b
Received 15 March 2007; revised 20 April 2007; accepted 24 April 2007
Available online 29 April 2007
Abstract—A tandem cross-coupling reaction of aryl methyl ketones with aromatic aldehydes has been accomplished employing barium iso-
propoxide as a catalyst, in which barium enolates are generated and then three consecutive reactions (aldol reaction/b-elimination/conjugate
addition) occur; this one-pot procedure is a convenient method to obtain symmetrical 1,5-diketones in good yields. In some cases, addition of
iso-propanol is effective in improving the chemical yield.
Ó 2007 Elsevier Ltd. All rights reserved.
a
1. Introduction
Table 1. Catalytic activity of various barium alkoxides
O
O
O
Ph
O
Ba(OR)2 (0.2 eq)
DMF, r.t.
+
Michael addition of enolates to a,b-unsaturated carbonyl
compounds is a beneficial method to obtain 1,5-dicarbonyl
Ph
Entry
CH3 Ph
H
Ph
Ph
1
compounds, which are further transformable into useful
multifunctional molecules including 2-cyclohexen-1-one
derivatives via a Robinson annelation-type process. We
b
c
Yield (%)
Ba(OR)
2
Time (h)
2
1
2
3
4
5
6
7
8
Ba(OMe)
2
18
22
0.3
8
22
23
22
22
54
60
Ba(O-i-Pr)
Ba(O-i-Pr)
Ba(O-i-Pr)
Ba(O-L-menthyl)2
Ba(O-t-Bu)
Ba(O-1-adamantyl)
Ba(O-2-naphthyl)
2
2
2
have previously reported preliminary results on a barium hy-
dride or barium alkoxide-promoted tandem cross-coupling
reaction of ketones with aldehydes giving symmetrical 1,5-
d
e
57
58
f
e
64
52
65
<1
3
,4
diketones in good yields. We describe here further studies
about the one-pot 1,5-diketone synthesis, which has been
achieved by a catalytic amount of barium isopropoxide
2
2
2
a
(
Eq. 1).
Unless otherwise specified, the reaction was performed employing aceto-
phenone (2.5 equiv), benzaldehyde (1 equiv), and barium alkoxide
(
Prepared from BaH
(0.4 equiv) in dry DMF at rt.
Isolated yield.
Commercially available Ba(O-i-Pr) of 1 equiv was used.
2
The starting substrates and an unknown product except the product were
obtained.
0.2 equiv) in dry DMF at rt.
b
2
(0.2 equiv) and the corresponding alcohol
O
O
cat. Ba(O-i-Pr)2
i-PrOH, DMF, r.t.
O
Ar2
O
c
d
e
+
ð1Þ
Ar1
CH3
Ar2
H
Ar1
Ar1
f
2
Commercially available Ba(O-i-Pr) of 0.1 equiv was used.
2
. Results and discussion
Table 1 shows the catalytic ability of various barium alkox-
ides in the reaction of acetophenone with benzaldehyde.
Among the barium alkoxides tested, barium isopropoxide
has been found to be the most preferable in terms of reactiv-
ity and commercial availability (entries 2–4). For example,
treatment of benzaldehyde with 2.5 equiv of acetophenone
under the influence of 0.1 equiv of Ba(O-i-Pr) in DMF at
room temperature resulted in the formation of the desired
1,5-diketone in 58% yield (entry 4). There seems to be es-
sentially no difference in reactivity between commercially
2
available Ba(O-i-Pr) and the in situ-prepared one (entries
2
2
–4). Steric bulkiness of the barium alkoxide does not affect
Keywords: Aldehydes; Barium isopropoxide; 1,5-Diketones; Enolates;
Ketones; Michael addition; a,b-Unsaturated ketone.
the chemical yield of the product and indeed, the highest
yield (65%) was obtained when barium 1-adamantoxide
was used as a catalyst (entry 7). In contrast, barium
*
Corresponding author. Fax: +81 43 290 2789; e-mail: ayanagi@faculty.
chiba-u.jp
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.04.079

8582
A. Yanagisawa et al. / Tetrahedron 63 (2007) 8581–8585
2-naphthoxide did not provide the targeted 1,5-diketone at
all (entry 8).
ketone and aromatic aldehyde. Selected examples are shown
in Table 4. As a result, addition of i-PrOH was effective for
obtaining higher yields in some cases (compare entries 2 and
7 in Table 4 with entries 2 and 7 in Table 2, respectively).
However, reactions using other combinations of aryl methyl
ketones and aromatic aldehydes were deactivated under the
influence of the alcohol (compare entries 3–6 and 10–12 in
Table 4 with entries 3–6 and 9–11 in Table 2, respectively).
Thus, the barium alkoxide catalyst was fixed for barium iso-
propoxide and we carried out the tandem cross-coupling re-
action between numerous aryl methyl ketones and aromatic
aldehydes. The results are summarized in Table 2. Not only
simple aromatic aldehydes but also benzaldehyde deriva-
tives, which have a potentially labile functional group such
as nitro or fluoro group, also furnished the corresponding
In the present 1,5-diketone synthesis, aldol reaction of an
aryl methyl ketone with an aromatic aldehyde, b-elimination
of the resulting aldol adduct leading to an a,b-unsaturated
ketone, and Michael addition of a barium enolate of the
aryl methyl ketone to the enone are considered to occur se-
1
,5-diketones in moderate yields (entries 6 and 7). Notewor-
thy is the fact that 2-pyridyl group, by which some chelate
effect was anticipated, did not affect the reaction course
and catalytic activity (entry 9).
5
quentially (Fig. 1).
Next, we attempted addition of i-PrOH so as to regenerate
barium isopropoxide smoothly. As a consequence, increase
in the amount of i-PrOH improved the chemical yield of
the desired product (Table 3) and the best result was attained
when 20 equiv of i-PrOH was added (entry 4). However, fur-
ther improvement in the yield was not achieved in the pres-
ence of 50 equiv of the alcohol (entry 5).
To clarify the reaction pathway, we attempted a catalytic Mi-
chael addition of acetophenone to chalcone in the presence
of 0.1 equiv of Ba(O-i-Pr) in DMF at room temperature
for 16 h and found that the anticipated 1,5-diketone formed
in 73% yield (Eq. 2). This result is a positive proof to support
the aforementioned reaction course.
2
Under the optimized reaction conditions, we reexamined the
coupling reaction using diverse combinations of aryl methyl
Ba(O-i-Pr)
2
O
O
O
Ph
O
(0.1 eq)
+
ð2Þ
Ph
DMF, r.t.,
16 h
Ph
CH3 Ph
Ph
Ph
Table 2. Barium isopropoxide-catalyzed tandem coupling reaction of
ketones with aldehydes
7
3% yield
a
O
O
Ba(O-i-Pr)2 (0.1 eq)
O
Ar2
O
Furthermore, synthesis of an unsymmetrical 1,5-diketone
was also achieved by this method. For example, when an
+
Ar1
Ar2
DMF, r.t.
Ar1
Ar1
CH3
H
1
2
Ar
b
Yield (%)
Entry
Ar
Time (h)
Table 4. Barium isopropoxide-catalyzed tandem coupling reaction between
ketones and aldehydes in the presence of i-PrOH
a
c
1
2
3
4
5
6
7
8
9
1
1
Ph
4-MeOC
Ph
Ph
Ph
8
16
16
20
16
16
6
5
5
16
16
58
40
71
72
57
48
56
47
44
74
71
6
H
1-Naphthyl
4
Ba(O-i-Pr) (0.1 eq)
2
O
O
O
Ar2
O
i-PrOH (20 eq)
+
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3 6 4
4-H CC H
Ar1
CH3 Ar2
H
DMF, r.t.
Ar1
Ar1
4-MeOC
4-O NC
4-FC
2-Naphthyl
2-Pyridyl
3-Pyridyl
4-Pyridyl
6 4
H
H
6 4
2
1
Ar
2
b
Yield (%)
6
H
4
Entry
Ar
Time (h)
1
2
3
4
5
6
7
8
9
Ph
4-MeOC
1-Naphthyl
Ph
Ph
Ph
7
16
16
20
24
16
6
16
5
16
18
18
76
51
56
66
51
38
76
86
48
37
47
47
6
H
4
0
1
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
3 6 4
4-H CC H
a
Unless otherwise specified, the reaction was performed employing ketone
3 equiv), aldehyde (1 equiv), and barium isopropoxide (0.1 equiv) in dry
DMF at rt.
Isolated yield.
Acetophenone of 2.5 equiv was used.
4-MeOC
4-O NC
4-FC
1-Naphthyl
2-Naphthyl
2-Pyridyl
3-Pyridyl
4-Pyridyl
6 4
H
H
6 4
(
2
6 4
H
b
c
1
1
0
1
a
12
Table 3. Additive effect of i-PrOH on the chemical yield of 1,5-diketone
Ba(O-i-Pr)2 (0.1 eq)
a
The reaction was performed using ketone (3 equiv), aldehyde (1 equiv),
barium isopropoxide (0.1 equiv), and i-PrOH (20 equiv) in dry DMF at
O
O
O
Ph
O
i-PrOH (x eq)
+
DMF, r.t.
rt for 5–24 h.
Isolated yield.
Ph
CH3 Ph
H
Ph
Ph
b
b
Yield (%)
Entry
x (equiv)
O
O
O
O
OBaO-i-Pr
1
2
3
4
5
0
5
10
20
50
66
68
70
76
64
Ba(O-i-Pr)2
+
Ph
CH3
Ph
H
Ph
Ph
aldol reaction
-
elimination – BaOH(O-i-Pr)
OBaO-i-Pr
Ph
O
O
a
The reaction was performed using acetophenone (3 equiv), benzaldehyde
1 equiv), barium isopropoxide (0.1 equiv), and i-PrOH (0–50 equiv) in
dry DMF at rt for 18–24 h.
Isolated yield.
Ph
(
Ph
Ph
Michael addition
Ph
Ph
b
Figure 1. Plausible reaction pathway.

A. Yanagisawa et al. / Tetrahedron 63 (2007) 8581–8585
8583
a-tetralone-derived a,b-unsaturated ketone was used as
a Michael acceptor, the targeted adduct was obtained in
moderate to high yields of up to 86%; (2) employment of
i-PrOH as an additive is effective in improving the chemical
yield in some cases; (3) unsymmetrical 1,5-diketones are
also able to be prepared by the present method; (4) barium
enolates can be generated directly from the corresponding
ketones with the aforementioned barium alkoxide. Studies
on related reactions using the barium reagent are now in
progress.
8
9% yield (Eq. 3).
O
Ba(O-i-Pr)
O
Ph
O
2
O
+
CH3
(
0.1 eq)
DMF, r.t.,
1 h
Ph
Ph
ð3Þ
Ph
2
89% yield
A suggested catalytic cycle of the present tandem coupling
reaction between acetophenone and benzaldehyde is indi-
cated in Figure 2. First, Ba(O-i-Pr) reacts with acetophe-
4. Experimental
2
4.1. General methods
none to generate barium enolate 1. Subsequently, the
enolate 1 adds to benzaldehyde to give the barium alkoxide
of aldol adduct 2, which is then allowed to be transformed
Column chromatography was conducted with 63–230 mesh
silica gel. Infrared (IR) spectra were recorded on a FTIR
spectrometer. H NMR spectra were recorded on a 400 or
1
into a,b-unsaturated ketone
BaOH(O-i-Pr) from the alkoxide 2. Thus generated enone
is able to undergo Michael addition by another barium
3
by b-elimination of
1
500 MHz spectrometer. Chemical shifts of H NMR spectra
were reported relative to tetramethylsilane (d 0) or chloro-
form (d 7.26). Splitting patterns are indicated as s, singlet;
3
enolate of acetophenone 4 (X¼O-i-Pr or OH) leading to
1
3
the barium enolate of Michael adduct 5. Finally, protonation
of 5 by i-PrOH or H O furnishes the targeted 1,5-diketone 6
d, doublet; t, triplet; q, quartet; m, multiplet; br, broad.
NMR spectra were recorded on a 100 or 125 MHz spectro-
C
2
1
3
and generates BaX (X¼O-i-Pr or OH). In this step, addition
meter. Chemical shifts of C NMR spectra were reported
relative to CDCl (d 77.0). Mass spectra were recorded on
2
of an excess amount of i-PrOH accelerates the protonation.
In the second cycle and thereafter, the barium base BaX2
is recycled and behaves as a catalyst.
3
a JEOL JMS-AX500 mass spectrometer using fast atom
bombardment (FAB) ionization.
All experiments were carried out in a two-necked flask
under an atmosphere of standard grade argon gas (oxygen
3. Conclusion
<
one shown in Eq. 3 was prepared by treatment of 3,4-dihydro-
10 ppm). (E)-2-Benzylidene-3,4-dihydronaphthalen-1(2H)-
We have demonstrated a novel tandem cross-coupling reac-
tion between aryl methyl ketones and aromatic aldehydes
catalyzed by barium isopropoxide, in which aldol reaction,
b-elimination, and Michael addition occur sequentially.
The main features of the present method are: (1) the proce-
dure is operationally simple using readily available chemi-
cals and can provide various symmetrical 1,5-diketones in
naphthalen-1(2H)-one with 1.2 equiv of benzaldehyde in the
presence of 0.1 equiv of Ba(O-i-Pr) in dry DMF at room
2
temperature for 12 h. Barium alkoxides (entries 1, 2, and
5–8 in Table 1) were generated in situ from BaH and 2 equiv
2
of the corresponding alcohol in dry DMF at room tempera-
ture. Other chemicals were used as purchased.
PhCOCH3 i-PrOH
OBaO-i-Pr
Ba(O-i-Pr)2
PhCHO
enolate formation
Ph
aldol
1
reaction
O
OBaO-i-Pr
OBaX
Ph
Ph
2
Ph
-elimination
4
XBaO
Ph
Ph
O
O
BaOH(O-i-Pr)
Michael addition
Ph
Ph
Ph
BaX(OH)
5
3
i-PrOH
-
elimination
O
or
H O
2
OBaX
protonation
Ph
Ph
7
i-PrOH
PhCOCH3 or H O
aldol
O
Ph
O
reaction
2
OBaX
PhCHO
Ph
Ph
BaX2
6
enolate formation Ph
4
(X = O-i-Pr or OH)
2
Figure 2. Suggested catalytic mechanism for the tandem coupling reaction catalyzed by Ba(O-i-Pr) .

8584
A. Yanagisawa et al. / Tetrahedron 63 (2007) 8581–8585
4
.2. Typical experimental procedure for tandem cross-
4.2.6. 3-(4-Nitrophenyl)-1,5-diphenylpentane-1,5-dione
(entry 6 in Table 4, cf. entry 6 in Table 2). IR (CDCl )
3
9
coupling reaction of ketones with aldehydes catalyzed by
barium isopropoxide
ꢀ1
1
3064, 2902, 1682, 1597, 1516, 1344 cm
;
H NMR
(
400 MHz, CDCl ) d¼3.38 (dd, 2H, J¼17.1, 7.3 Hz, CH ),
3
2
4.2.1. Synthesis of 1,3,5-triphenylpentane-1,5-dione (en-
try 1 in Table 4, cf. entries 1–7 in Table 1, entry 1 in Table
3.52 (dd, 2H, J¼17.1, 6.3 Hz, CH ), 4.18 (m, 1H, CH),
2
7.36–7.44 (m, 6H, aromatic), 7.49 (t, 2H, J¼7.4 Hz, aro-
matic), 7.86 (d, 4H, J¼7.1 Hz, aromatic), 8.12 (d, 2H,
6
2
3
, entries 1–5 in Table 3, and Eq. 2). An oven-dried,
0 mL two-necked round-bottomed flask equipped with
1
3
J¼8.5 Hz, aromatic);
C NMR (125 MHz, CDCl )
3
Ò
a Teflon -coated magnetic stirring bar was flushed with
argon. Barium isopropoxide (26 mg, 0.10 mmol) was put
into the apparatus and dry DMF (5 mL) and 2-propanol
d¼36.7, 44.2, 123.8, 128.0, 128.5, 128.7, 133.4, 136.5,
151.7, 197.5; MS (FAB) m/e: 374 (M+H). These spectral
data have not been reported in the literature.
9
(
1.5 mL, 20 mmol) were added, and the mixture was stirred
for 10 min at room temperature. To the resulting solution
were added acetophenone (0.35 mL, 3.0 mmol) and benzal-
dehyde (0.10 mL, 1.0 mmol). After being stirred for 7 h at
room temperature, the mixture was treated with a saturated
4.2.7. 3-(4-Fluorophenyl)-1,5-diphenylpentane-1,5-dione
(entry 7 in Table 4, cf. entry 7 in Table 2). IR (neat)
ꢀ1 1
3060, 2970, 1682, 1598, 1580, 1510, 1448 cm ; H NMR
(400 MHz, CDCl ) d¼3.30 (dd, 2H, J¼16.7, 7.2 Hz, CH ),
3
2
NH Cl aqueous solution (10 mL) at this temperature and
4
3.47 (dd, 2H, J¼16.7, 6.5 Hz, CH ), 4.08 (m, 1H, CH), 6.91
2
the aqueous layer was extracted with ether (20 mL). The
combined organic extracts were dried over anhydrous
Na SO and concentrated in vacuo after filtration. The resid-
(t, 2H, J¼8.8 Hz, aromatic), 7.24 (m, 2H, aromatic), 7.39 (t,
4H, J¼7.6 Hz, aromatic), 7.49 (t, 2H, J¼7.4 Hz, aromatic),
1
3
7.92 (d, 4H, J¼7.2 Hz, aromatic); C NMR (125 MHz,
2
4
ual crude product was purified by column chromatography
on silica gel to give the 1,5-diketone (0.25 g, 76% yield) as
CDCl ) d¼36.4, 44.9, 115.2, 115.4, 128.0, 128.6, 133.1,
3
136.8, 139.4, 198.3; MS (FAB) m/e: 347 (M+H).
1
13
colorless crystals. Spectral data (IR, H NMR, C NMR,
and MS) and melting point of the product have been reported
in the literature.
4.2.8. 3-(Naphthalen-1-yl)-1,5-diphenylpentane-1,5-di-
one (entry 8 in Table 4). IR (CDCl ) 3059, 2893, 1680,
6
3
ꢀ
1
1
1
597, 1448 cm ; H NMR (400 MHz, CDCl ) d¼3.42
3
4.2.2. 1,5-Bis(4-methoxyphenyl)-3-phenylpentane-1,5-di-
one (entry 2 in Table 4, cf. entry 2 in Table 2). IR (KBr)
(dd, 2H, J¼17.1, 6.6 Hz, CH ), 3.52 (dd, 2H, J¼17.1,
2
7
7.1 Hz, CH ), 4.96 (m, 1H, CH), 7.15–7.39 (m, 10H, aro-
2
ꢀ
1 1
2
938, 2880, 2839, 1677, 1598, 1510, 1455, 1421 cm ; H
matic), 7.66 (m, 1H, aromatic), 7.71 (m, 1H, aromatic),
7.93 (m, 4H, aromatic), 8.08 (m, 1H, aromatic); C NMR
1
3
NMR (400 MHz, CDCl ) d¼3.26 (dd, 2H, J¼16.4, 7.2 Hz,
3
CH ), 3.42 (dd, 2H, J¼16.4, 7.0 Hz, CH ), 3.79 (s, 6H,
(125 MHz, CDCl ) d¼37.2, 44.9, 125.5, 125.9, 126.0,
2
2
3
2
7
7
CH ), 4.04 (m, 1H, CH), 6.97 (d, 4H, J¼8.9 Hz, aromatic),
127.6, 127.7, 128.1, 128.3, 128.6, 132.4, 133.1, 133.5,
136.9, 141.3, 198.4; MS (FAB) m/e: 379 (M+H).
3
.14 (t, 1H, J¼6.8 Hz, aromatic), 7.26 (m, 4H, aromatic),
1
3
.92 (d, 4H, J¼8.9 Hz, aromatic); C NMR (125 MHz,
CDCl ) d¼37.6, 44.7, 55.4, 113.7, 126.6, 127.4, 128.6,
4.2.9. 3-(Naphthalen-2-yl)-1,5-diphenylpentane-1,5-di-
one (entry 9 in Table 4, cf. entry 8 in Table 2). IR (KBr)
3055, 2963, 2898, 1677, 1596, 1579, 1508, 1445,
3
1
30.0, 130.4, 144.0, 163.4, 197.2; MS (FAB) m/e: 389
M+H). These spectral data have not been reported in the
(
literature.
7
ꢀ1
1
1409 cm ; H NMR (400 MHz, CDCl ) d¼3.43 (dd, 2H,
3
J¼16.9, 7.2 Hz, CH ), 3.52 (dd, 2H, J¼16.9, 7.0 Hz, CH ),
2
2
4.2.3. 1,5-Di(naphthalen-1-yl)-3-phenylpentane-1,5-di-
one (entry 3 in Table 4, cf. entry 3 in Table 2). IR
4.25 (m, 1H, CH), 7.36–7.53 (m, 9H, aromatic), 7.69–7.78
(m, 4H, aromatic), 7.93 (d, 4H, J¼7.0 Hz, aromatic);
1
3
C
ꢀ1
1
(
CDCl3) 3055, 2956, 1676, 1506 cm
;
H
NMR
NMR (125 MHz, CDCl ) d¼44.4, 123.1, 125.3, 125.6,
3
(
500 MHz, CDCl ) d¼3.39 (dd, 2H, J¼16.4, 7.6 Hz, CH ),
126.3, 127.2, 128.1, 128.5, 129.0, 131.4, 133.0, 134.1,
136.9, 140.0, 198.6; MS (FAB) m/e: 379 (M+H).
3
2
3
7
7
.56 (dd, 2H, J¼16.5, 6.8 Hz, CH ), 4.13 (m, 1H, CH), 7.11–
2
.22 (m, 5H, aromatic), 7.37 (t, 2H, J¼7.4 Hz, aromatic),
.41–7.47 (m, 4H, aromatic), 7.74 (dd, 2H, J¼7.3, 1.2 Hz,
4.2.10. 1,5-Diphenyl-3-(pyridin-2-yl)pentane-1,5-dione
(entry 10 in Table 4, cf. entry 9 in Table 2). IR
1
0
aromatic), 7.75–7.80 (m, 2H, aromatic), 7.88 (d, 2H,
J¼8.3 Hz, aromatic), 8.29–8.34 (m, 2H, aromatic);
1
3
ꢀ1
C
(CDCl ) 3062, 2895, 1680, 1593, 1446 cm ; MS (FAB)
3
1
13
NMR (125 MHz, CDCl ) d¼38.1, 48.2, 124.2, 125.6, 126.3,
m/e: 330 (M+H). Other spectral data ( H NMR and
NMR) and melting point of the product have been reported
C
3
1
1
26.7, 127.3, 127.6, 127.6, 128.2, 128.5, 129.9, 132.4, 133.8,
35.9, 143.2, 202.8; MS (FAB) m/e: 429 (M+H).
1
0
in the literature.
4
Table 4, cf. entry 4 in Table 2).
.2.4. 1,5-Diphenyl-3-p-tolylpentane-1,5-dione (entry 4 in
C NMR (125 MHz,
4.2.11. 1,5-Diphenyl-3-(pyridin-3-yl)pentane-1,5-dione
(entry 11 in Table 4, cf. entry 10 in Table 2). IR (CDCl )
6
b 13
3
ꢀ1
1
CDCl ) d¼21.0, 36.8, 45.0, 125.1, 127.2, 128.1, 128.5,
3059, 2900, 1680, 1595, 1579, 1448 cm
;
H NMR
3
1
29.2, 133.0, 136.9, 140.7, 198.6. Other spectral data (IR,
H NMR, and MS) of the product have been reported in
(500 MHz, CDCl ) d¼3.40 (dd, 2H, J¼17.1, 7.4 Hz, CH ),
3
2
1
3.56 (dd, 2H, J¼17.1, 6.7 Hz, CH ), 4.13 (m, 1H, CH),
2
6
b
the literature.
7.21 (dd, 1H, J¼7.9, 4.9 Hz, aromatic), 7.45 (t, 4H, J¼
7
.9 Hz, aromatic), 7.56 (t, 2H, J¼7.4 Hz, aromatic), 7.67
4.2.5. 3-(4-Methoxyphenyl)-1,5-diphenylpentane-1,5-di-
one (entry 5 in Table 4, cf. entry 5 in Table 2).
(dt, 1H, J¼8.0, 2.1 Hz, aromatic), 7.94 (dd, 4H, J¼8.5,
1.5 Hz, aromatic), 8.44 (dd, 1H, J¼4.8, 1.5 Hz, aromatic),
6
b,8
Spectral
data (IR, H NMR, C NMR, and MS) and melting point of
the product have been reported in the literature.
1
13
13
8.58 (d, 1H, J¼1.9 Hz, aromatic); C NMR (125 MHz,
6
b,8
CDCl ) d¼34.5, 44.2, 123.3, 128.0, 128.6, 133.2, 135.3,
3

A. Yanagisawa et al. / Tetrahedron 63 (2007) 8581–8585
8585
1
(
36.6, 139.2, 148.0, 149.2, 197.8; MS (FAB) m/e: 330
M+H).
Synlett 2005, 1917; (e) Wang, X.; Adachi, S.; Iwai, H.;
Takatsuki, H.; Fujita, K.; Kubo, M.; Oku, A.; Harada, T.
J. Org. Chem. 2003, 68, 10046; (f) Harada, T.; Adachi, S.;
Wang, X. Org. Lett. 2004, 6, 4877; (g) Harada, T.; Yamauchi,
T.; Adachi, S. Synlett 2005, 2151; (h) Jaber, N.; Assi ꢀe , M.;
Fiaud, J.-C.; Collin, J. Tetrahedron 2004, 60, 3075; (i)
Nakagawa, T.; Fujisawa, H.; Nagata, Y.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 2005, 78, 236; (j) Kumaraswamy, G.; Jena,
N.; Sastry, M. N. V.; Padmaja, M.; Markondaiah, B. Adv.
Synth. Catal. 2005, 347, 867; (k) Wang, W.; Li, H.; Wang, J.
Org. Lett. 2005, 7, 1637; (l) Desimoni, G.; Faita, G.; Guala,
M.; Laurenti, A.; Mella, M. Chem.—Eur. J. 2005, 11, 3816;
(m) Tozawa, T.; Yamane, Y.; Mukaiyama, T. Chem. Lett. 2006,
4
.2.12. 1,5-Diphenyl-3-(pyridin-4-yl)pentane-1,5-dione
C NMR
1
1 13
(
(
entry 12 in Table 4, cf. entry 11 in Table 2).
125 MHz, CDCl ) d¼36.1, 43.7, 122.9, 128.0, 128.6,
3
1
33.3, 136.5, 149.9, 152.9, 197.6; MS (FAB) m/e: 330
M+H). Other spectral data (IR and H NMR) and melting
1
(
point of the product have been reported in the literature.
1
1
4.3. Typical experimental procedure for Michael
addition of acetophenone to a,b-unsaturated ketones
catalyzed by barium isopropoxide
3
5, 56; (n) Tozawa, T.; Yamane, Y.; Mukaiyama, T. Chem.
4.3.1. Synthesis of 3,4-dihydro-2-(3-oxo-1,3-diphenylpro-
pyl)naphthalen-1(2H)-one (Eq. 3).
Lett. 2006, 35, 360; (o) Liu, D.; Hong, S.; Corey, E. J. J. Am.
Chem. Soc. 2006, 128, 8160; (p) Mukaiyama, T.; Nagao, H.;
Yamane, Y. Chem. Lett. 2006, 35, 916; (q) Takenaka, N.;
Abell, J. P.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 742.
2. For reviews, see: (a) Heathcock, C. H. Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Heathcock, C. H., Eds.;
Pergamon: Oxford, UK, 1991; Vol. 2, p 133; (b) Jung, M. E.
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Semmelhack, M. F., Eds.; Pergamon: Oxford, UK, 1991;
Vol. 4, p 1.
3. Takahashi, H.; Arai, T.; Yanagisawa, A. Synlett 2006, 2833.
4. For characteristic reactivity and/or selectivity shown by barium
reagents, see: (a) Yanagisawa, A. Science of Synthesis;
Yamamoto, H., Ed.; Thieme: Stuttgart, 2004; Vol. 7, p 695;
(b) Yanagisawa, A. Main Group Metals in Organic Synthesis;
Yamamoto, H., Oshima, K., Eds.; Wiley-VCH: Weinheim,
2004; Vol. 1, p 175; For strontium reagents, see: (c) Miyoshi,
N. Science of Synthesis; Yamamoto, H., Ed.; Thieme:
Stuttgart, 2004; Vol. 7, p 685; (d) Miyoshi, N.; Ikehara, D.;
Matsuo, T.; Kohno, T.; Matsui, A.; Wada, M. J. Synth. Org.
Chem. Jpn. 2006, 64, 845.
5. For reactions via a barium enolate, see: (a) Yamada, Y. M. A.;
Shibasaki, M. Tetrahedron Lett. 1998, 39, 5561; (b)
Yanagisawa, A.; Takahashi, H.; Arai, T. Chem. Commun.
2004, 580; (c) Yamada, Y. M. A.; Uozumi, Y. Org. Lett.
2006, 8, 1375; (d) Saito, S.; Kobayashi, S. J. Am. Chem. Soc.
2006, 128, 8704; (e) Yanagisawa, A.; Shinohara, A.;
Takahashi, H.; Arai, T. Synlett 2007, 141.
6. (a) Boyer, J.; Corriu, R. J. P.; Perz, R.; Reye, C. J. Organomet.
Chem. 1980, 184, 157; (b) Kobayashi, T.; Kawate, H.;
Kakiuchi, H.; Kato, H. Bull. Chem. Soc. Jpn. 1990, 63, 1937;
(c) Shimizu, S.; Shirakawa, S.; Suzuki, T.; Sasaki, Y.
Tetrahedron 2001, 57, 6169.
1
2
An oven-dried,
0 mL two-necked round-bottomed flask equipped with
3
Ò
a Teflon -coated magnetic stirring bar was flushed with ar-
gon. Barium isopropoxide (26 mg, 0.10 mmol) was put into
the apparatus and dry DMF (3 mL) was added, and the
mixture was stirred for 10 min at room temperature. To the
resulting solution were added acetophenone (0.14 mL,
1.2 mmol) and (E)-2-benzylidene-3,4-dihydronaphthalen-
1(2H)-one (235 mg, 1.0 mmol). After being stirred for
21 h at room temperature, the mixture was treated with a sat-
urated NH Cl aqueous solution (10 mL) at this temperature
4
and the aqueous layer was extracted with ether (20 mL). The
combined organic extracts were dried over anhydrous
Na SO and concentrated in vacuo after filtration. The resid-
2
4
ual crude product was purified by column chromatography
on silica gel to give the unsymmetrical 1,5-diketone
(
316 mg, 89% yield). Spectral data of the product (a 1:1 mix-
ture of diastereomers): IR (neat) 3026, 2952, 2816, 1676,
ꢀ1
1
1
597, 1493, 1450 cm
;
H NMR (400 MHz, CDCl3)
d¼1.68 (m, 0.5H, one proton of CH ), 2.02 (m, 1H, one pro-
2
ton of CH ), 2.15 (m, 0.5H, one proton of CH ), 2.72–3.10
2
2
(
m, 3H, CH and CH ), 3.29–3.64 (m, 2H, CH ), 3.96 (m,
2 2
0.5H, CH), 4.22 (m, 0.5H, CH), 7.08–7.29 (m, 7H, aro-
matic), 7.31–7.49 (m, 4H, aromatic), 7.76–8.0 (m, 3H, aro-
1
3
matic); C NMR (125 MHz, CDCl ) d¼25.6, 26.2, 26.8,
3
2
9.4, 39.3, 39.8, 41.0, 43.5, 51.8, 53.2, 126.5, 126.6,
26.7, 127.4, 127.6, 128.0, 128.1, 128.2, 128.3, 128.4,
28.4, 128.5, 128.6, 128.6, 128.7, 132.8, 132.9, 133.0,
33.3, 133.4, 137.0, 142.0, 142.2, 143.5, 144.8, 198.4,
98.9, 199.0, 199.8; MS (FAB) m/e: 355 (M+H). These
1
1
1
1
12
spectral data have not been reported in the literature.
7
8
9
. Fuchigami, T.; Awata, T.; Nonaka, T.; Baizer, M. M. Bull.
Chem. Soc. Jpn. 1986, 59, 2873.
. Tanemura, K.; Suzuki, T.; Nishida, Y.; Horaguchi, T. Chem.
Lett. 2005, 34, 576.
. Pilli, R. A.; Russowsky, D. J. Chem. Soc., Chem. Commun.
Acknowledgements
This paper is dedicated to Professor Hisashi Yamamoto on
the occasion of his receipt of the Tetrahedron Prize for
Creativity in Organic Chemistry.
1
987, 1053.
1
0. Tully, W.; Main, L.; Nicholson, B. K. J. Organomet. Chem.
2005, 690, 3348.
References and notes
1
1. (a) Reichardt, C.; Che, D.; Heckenkemper, G.; Sch €a fer, G. Eur.
J. Org. Chem. 2001, 2343; (b) Katritzky, A. R.; Adamson, J.;
Elisseou, E. M.; Musumarra, G.; Patel, R. C.; Sakizadeh, K.;
Yeung, W. K. J. Chem. Soc., Perkin Trans. 2 1982, 1041.
12. (a) Swamy, V. M.; Sarkar, A. Tetrahedron Lett. 1998, 39, 1261;
(b) Shankar, R.; Jha, A. K.; Singh, U. S.; Hajela, K.
Tetrahedron Lett. 2006, 47, 3077.
1
. For recent examples of Michael addition of enolates, see: (a)
Harada, S.; Kumagai, N.; Kinoshita, T.; Matsunaga, S.;
Shibasaki, M. J. Am. Chem. Soc. 2003, 125, 2582; (b)
Gnaneshwar, R.; Wadgaonkar, P. P.; Sivaram, S. Tetrahedron
Lett. 2003, 44, 6047; (c) Miura, K.; Nakagawa, T.; Hosomi, A.
Synlett 2003, 2068; (d) Miura, K.; Nakagawa, T.; Hosomi, A.