Unexpected formation of (E)-4-alkene 1,3-diketones from the three-component reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and aldehydes

Article abstract of DOI:10.1021/jo2005439

A novel three-component stereoselective synthesis of (E)-4-alkene 1,3-diketones from lithium selenolates, 1-(1-alkynyl)cyclopropyl ketones, and aldehydes is reported. This reaction afforded the products in moderate to good yields with the formation of a n

Full text of DOI:10.1021/jo2005439

ARTICLE
pubs.acs.org/joc
Unexpected Formation of (E)-4-Alkene 1,3-Diketones from the
Three-Component Reaction of Lithium Selenolates
with 1-(1-Alkynyl)cyclopropyl Ketones and Aldehydes
Jianfeng Xu,† Luling Wu,*,† and Xian Huang†,‡,§
†Department of Chemistry, Zhejiang University, Xi-xi Campus, Hangzhou 310028, People's Republic of China
‡State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, People's Republic of China
S Supporting Information
b
ABSTRACT: A novel three-component stereoselective synth-
esis of (E)-4-alkene 1,3-diketones from lithium selenolates,
1-(1-alkynyl)cyclopropyl ketones, and aldehydes is reported.
This reaction afforded the products in moderate to good yields
with the formation of a new CꢀSe single bond, a new CꢀC
double bond, and a new CꢀO double bond.
’ INTRODUCTION
spectrum. The 2,4-dinitrophenylhydrazone derivative of 4a
afforded crystalline material 5 for the single-crystal X-ray diffrac-
tion analysis35 and confirmed that the unexpected product 4a is
(E)-5-(4-bromophenyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-
1-(p-tolyl)pent-4-ene-1,3-dione (Figure S1, Supporting In-
formation). Compared with the expected product 4a0, a further
oxygen migration occurred in the subsequent steps (Scheme 2).
We proposed a plausible mechanism to explain this interesting
transformation. After the allenoxy anion 6 was formed as ex-
pected,36,37 because of the electron-withdrawing ability of the
carbonyl group, the oxygen anion underwent a further Michael
addition to furnish an oxetene intermediate 7.38ꢀ40 Then inter-
mediate 7 would undergo either a subsequent enolateꢀketone
isomerization and ring-opening to afford intermediate 8 or an
electrocyclic ring-opening of oxetene to form intermediate 9.41ꢀ43
Protonation of intermediate 8 or 9 finally provided the observed
product 4a (Scheme 3).
Further efforts have been made to optimize the conditions for
this tandem reaction. Once again lithium phenylselenolate 1a,
1-(phenylethynyl)cyclopropyl p-tolyl ketone 2a, and 4-bromo-
benzaldehyde 3a were chosen as the substrates. The results are
summarized in Table 1. This reaction could proceed at room
temperature under a nitrogen atmosphere. A solvent screening
showed that 1,4-dioxane is the best (Table 1, entries 1ꢀ5). Upon
adjustment of the amount of each component, the highest yield
(74%) was obtained with 1.0 equiv of 2a and 1.2 equiv each of the
other two components (Table 1, entries 5ꢀ10). Thus, the optimized
condition for this tandem reaction was defined as follows: 1.2 equiv of
1a, 1.0 equiv of 2a, and 1.2 equiv of 3a in 1,4-dioxane at room
temperature for 20 h.
Compounds with a cyclopropane unit have not only been
discovered in nature and pharmaceuticals1ꢀ3 but also proven to be
versatile intermediates in organic synthesis.4ꢀ7 Because the molecule
is highly strained, because of the influences of different substituents
attached, the three-membered ring could undergo thermal ring clea-
vage,8,9 oxidative10,11 and reductive ring cleavage,12,13 and electro-
philic14ꢀ17 and nucleophilic ring cleavage.18ꢀ20
1-(1-Alkynyl)cyclopropyl ketone, containing both an alkyne
and a cyclopropane unit, is a useful multifunctionalized building
block.21ꢀ27 Recently, Schmalz,21 Zhang,22,23 Zhang,24,25 and Wang26
have reported their facile strategies of using 1-(1-alkynyl)cyclopropyl
ketones as readily available substrates for efficient construction of
highly substituted furans and other cyclic compounds, respectively
(Scheme 1). Our group has also developed a convenient synthesis of
highly substituted furans via the electrophilic cyclization of 1-(1-
alkynyl)cyclopropyl ketones.27 Since there is an electron-withdraw-
ing group adjacent to the cyclopropane ring, we envisaged that when
it is attacked by a strong nucleophile, such as lithium selenolate, the
three-membered ring would open. Subsequent propargylꢀallenyl
isomerization would generate an allene anion, which could be
captured by an aldehyde to form the synthetically attractive multi-
substituted allenol as the expected product.28ꢀ34
’ RESULTS AND DISCUSSION
In order to validate our hypothesis, initially we chose lithium
phenylselenolate 1a (generated in situ by the reaction of diphenyl
diselenide with n-butyllithium), 1-(phenylethynyl)cyclopropyl
p-tolyl ketone 2a, and 4-bromobenzaldehyde 3a to perform this
three-component reaction. Surprisingly, we isolated a completely
unexpected compound 4a, which showed two carbonyl signals
with no allene signal based on the analysis of the 13C NMR
Received: March 11, 2011
Published: May 26, 2011
r
2011 American Chemical Society
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dx.doi.org/10.1021/jo2005439 J. Org. Chem. 2011, 76, 5598–5605
|

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Scheme 1
Table 1. Optimization of Reaction Conditions for the
Three-Component Reaction of Lithium Phenylselenolate
1a, 1-Phenylethynyl)cyclopropyl p-Tolyl Ketone 2a, and
4-Bromobenzaldehyde 3aa
entry
1a:2a:3a (equiv)
solvent
THF
time (h)b
yield of 4a (%)c
1
2
1.0:1.0:1.0
1.0:1.0:1.0
1.0:1.0:1.0
1.0:1.0:1.0
1.0:1.0:1.0
1.2:1.0:1.0
1.0:1.2:1.0
1.0:1.0:1.2
1.2:1.0:1.2
1.4:1.0:1.4
12
36
40
24
20
20
20
20
20
20
52
41
58
48
61
62
54
67
74
72
toluene
3
cyclohexane
Et2O
4
5
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
6
7
8
9
10
a Unless otherwise specified, the reaction was carried out using 1a (0.6
mmol), 2a (0.5 mmol), and 3a (0.6 mmol) in 4 mL of solvent at room
temperature under a nitrogen atmosphere. b The reaction was moni-
tored by TLC. c Isolated yields.
4ꢀ10). Aromatic and heteromatic aldehydes 3 were proven to be
suitable for this three-component reaction, and R4 may be an
ortho-, meta-, or para-substituted benzene ring (Table 2, entries
1, 11ꢀ17). Alkyl aldehydes were also tested. When pivalaldehyde
was used, we were pleased to isolate 4r in 43% yield (Table 2,
entry 18). However, when butyraldehyde was used as substrate 3,
only an unidentified mixture was obtained. We reasoned that the
reaction may be compromised by the acidic R-hydrogen in
butyraldehyde (Scheme 4).
With the above optimized condition in hand, a variety of
lithium selenolates 1, 1-(1-alkynyl)cyclopropyl ketones 2, and
aldehydes 3 were investigated. As shown in Table 2, the yields of
(E)-4-alkene 1,3-diketones 4 ranged from 43% to 85%. Both
lithium arylselenolate and alkylselenolate could be used, and the
arylselenolate gave a slightly better result (Table 2, entries 1ꢀ3).
With regard to the substrates 2, when R2 and R3 are aryl or alkyl
groups, the reaction afforded the corresponding (E)-4-alkene
1,3-diketones 4a and 4dꢀj in moderate yields (Table 2, entries 1,
Many natural products with an (E)-4-alkene 1,3-diketone
moiety have been identified.44,45 In addition, plenty of synthetic
Scheme 2
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ARTICLE
Scheme 3. Proposed Mechanism
boiling point in the range 60ꢀ90 °C. All 1H NMR (400 MHz) and 13
C
Scheme 4
NMR (100 MHz) spectra were measured in CDCl3 with TMS as the
internal standard. Chemical shifts are expressed in ppm, and J values
are given in hertz. 1-(1-Alkynyl)cyclopropyl ketones were prepared accord-
ing to known procedure.21,23 Aldehydes in liquid state were purified by
distillation before use. Aldehydes in solid state were used without further
purification. The other commercially available chemicals were purchased
and used without further purification unless noted otherwise.
General Procedure for the Synthesis of (E)-4-Alkene 1,3-
Diketones 4 via the Three-Component Reaction of Lithium
Selenolates 1 with 1-(1-Alkynyl)cyclopropyl Ketones 2 and
Aldehydes 3. To a dried two-necked round-bottom flask (25 mL)
were added diselenide (0.6 mmol) and 1,4-dioxane (2 mL) under a
nitrogen atmosphere at room temperature. Then a solution of n-BuLi in
n-hexane (2.5 M, 0.24 mL, 0.6 mmol, 1.2 equiv) was added with a syringe to
the reaction mixture to generate lithium selenolate 1 in situ. After 1ꢀ2 min,
to the resulting reaction mixture was added a solution of 1-(1-alky-
nyl)cyclopropyl ketone 2 (0.5 mmol) and aldehyde 3 (0.6 mmol) in
2 mL of 1,4-dioxane at room temperature. After being stirred for 20 h, the
reaction was quenched with an aqueous saturated solution of NH4Cl and
extracted with diethyl ether (3 ꢁ 20 mL). The combined organic phase was
washed with saturated brine and dried over Na2SO4. Filtration, evaporation,
and column chromatography on silica gel (eluent: petroleum ether/ethyl
acetate = 20/1) afforded the final product 4.
strategies using (E)-4-alkene 1,3-diketones as versatile synthons have
been reported.46ꢀ48 Our further experiments demonstrated that
treatment of 4a with dinucleophiles such as hydroxylamine or
hydrazine followed by oxidationꢀelimination gave vinyl-substituted
isoxazole 10 or pyrazole 11 directly.46 Transition metal-catalyzed
cross-coupling reactions of 4a were also investigated, and we were
glad to obtain the corresponding Sonogashira49 coupling product 12
and Suzuki coupling product 13 in 82% and 66% yield, respectively
(Scheme 5).
’ CONCLUSIONS
In summary, we have developed a one-pot efficient method for
the synthesis of (E)-4-alkene 1,3-diketones stereoselectively from
readily available lithium selenolates, 1-(1-alkynyl)cyclopropyl ketones,
and aldehydes. This methodology can tolerate many functionalities in
the substrates. The obtained (E)-4-alkene 1,3-diketones can be useful
intermediates for further transformation to various different products.
Further studies in this area are now in progress in our laboratory.
(E)-5-(4-Bromophenyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-(p-tolyl)-
pent-4-ene-1,3-dione (4a). The reaction of diphenyl diselenide (187 mg,
0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL,
0.6 mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and 4-bromoben-
zaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL) afforded
’ EXPERIMENTAL SECTION
4a (224 mg, 74%). 1H NMR (400 MHz, CDCl3)
δ 7.62
(s, 1H), 7.43ꢀ7.45 (m, 4H), 7.17ꢀ7.23 (m, 8H), 7.02ꢀ7.07 (m, 4H),
Materials. 1,4-Dioxane was distilled from Na/benzophenone im-
mediately prior to use. Petroleum ether refers to the fraction with the
6.80 (d, J = 8.4 Hz, 2H), 5.03ꢀ5.06 (m, 1H), 2.93ꢀ3.07 (m, 2H),
5600
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Table 2. Synthesis of Various (E)-4-Alkene 1,3-Diketones 4a
1
2
3
entry
R1
R2
R3
R4
yield of 4 (%)b
1
Ph (1a)
4-CH3C6H4
Ph (2a)
4-BrC6H4 (3a)
74 (4a)
67 (4b)
58 (4c)
68 (4d)
75 (4e)
74 (4f)
51 (4g)
60 (4h)
54 (4i)
51 (4j)
73 (4k)
85 (4l)
70 (4m)
71 (4n)
82 (4o)
74 (4p)
78 (4q)
43 (4r)
2
4-CH3C6H4 (1b)
2a
3a
3
n-Bu (1c)
1a
2a
3a
4
4-CH3OC6H4
Ph (2b)
Ph (2c)
Ph (2d)
Ph (2e)
Ph (2f)
3a
5
1a
Ph
3a
6
1a
4-FC6H4
3a
7
1a
2-Furyl
3a
8
1a
n-Pr
3a
9
1a
4-CH3C6H4
n-Bu (2g)
n-Bu (2h)
3a
10
11
12
13
14
15
16
17
18
1a
i-Bu
2a
2a
2a
2a
2a
2a
2a
2a
3a
1a
4-CH3OC6H4 (3b)
4-FC6H4 (3c)
3-BrC6H4 (3d)
2-CH3OC6H4 (3e)
1-naphthyl (3f)
2-furyl (3g)
2-thienyl (3h)
t-Bu (3i)
1a
1a
1a
1a
1a
1a
1a
a The reaction was carried out using 1 (0.6 mmol), 2 (0.5 mmol), and 3 (0.6 mmol) in 4 mL of 1,4-dioxane under a nitrogen atmosphere at room
temperature for 20 h. b Isolated yields.
Scheme 5
2.44ꢀ2.51 (m, 1H), 2.33 (s, 3H), 2.04ꢀ2.13 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 196.2, 196.0, 144.0, 140.0, 137.8, 135.6, 133.2, 132.9, 132.2,
132.0, 131.3, 129.9, 129.5, 129.2, 129.1, 129.0, 128.3, 128.2, 126.8, 123.6, 56.2,
29.3, 25.9, 21.5; MS (EI) m/z 602 (Mþ); IR (ATR) νmax (cmꢀ1) 1686,
5601
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ARTICLE
1658, 1264, 1117, 818, 729, 696; HRMS (EI): m/z calcd for C32H27BrO2Se
(Mþ): 602.0360; found: 602.0358.
diselenide (187 mg, 0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane
(2.5 M, 0.24 mL, 0.6 mmol, 1.2 equiv), 2d (132 mg, 0.5 mmol, 1.0 equiv),
and 4-bromobenzaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane
(4 mL) afforded 4f (223 mg, 74%). 1H NMR (400 MHz, CDCl3) δ7.66 (s,
1H), 7.48ꢀ7.51 (m, 2H), 7.42 (d, J = 6.8 Hz, 2H), 7.20ꢀ7.25 (m, 8H),
7.01 (d, J = 6.0 Hz, 2H), 6.89ꢀ6.93 (m, 2H), 6.81 (d, J = 7.6 Hz, 2H),
5.01ꢀ5.04 (m, 1H), 2.94ꢀ3.13 (m, 2H), 2.45ꢀ2.53 (m, 1H), 2.01ꢀ2.06
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 195.8, 194.9, 166.8, 164.3, 139.5,
138.0, 135.6, 133.1, 132.3, 131.9, 131.7, 131.6, 131.4, 130.9, 130.8, 130.0,
129.3, 129.2, 128.3, 126.9, 123.8, 115.5, 115.3, 56.1, 29.0, 25.8; MS (EI) m/z
606 (Mþ); IR(ATR) νmax (cmꢀ1) 1688, 1663, 1595, 1225, 1072, 734, 691;
HRMS (EI): m/z calcd for C31H24BrFO2Se (Mþ): 606.0109; found:
606.0095.
(E)-5-(4-Bromophenyl)-1-(2-furanyl)-4-phenyl-2-(2-(phenylselenyl)-
ethyl)pent-4-ene-1,3-dione (4g). The reaction of diphenyl diselenide
(187 mg, 0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M,
0.24 mL, 0.6 mmol, 1.2 equiv), 2e (118 mg, 0.5 mmol, 1.0 equiv), and
4-bromobenzaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane
(4 mL) afforded 4g (148 mg, 51%). 1H NMR (400 MHz, CDCl3) δ 7.64
(s, 1H), 7.43 (s, 3H), 7.20ꢀ7.27 (m, 8H), 7.07 (d, J = 5.6 Hz, 2H), 6.89
(s, 1H), 6.82 (d, J = 8.0 Hz, 2H), 6.39 (s, 1H), 4.81ꢀ4.84 (m, 1H),
2.93ꢀ2.96 (m, 2H), 2.37ꢀ2.44 (m, 1H), 2.17ꢀ2.22 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 195.6, 184.4, 151.3, 146.6, 139.8, 138.2, 135.5,
133.1, 132.2, 132.1, 131.4, 129.9, 129.4, 129.1, 129.0, 128.3, 126.8, 123.8,
118.0, 112.4, 57.0, 29.1, 25.5; MS (EI) m/z 578 (Mþ); IR (ATR) νmax
(cmꢀ1) 1687, 1662, 1463, 1071, 1008, 734, 696; HRMS (EI): m/z calcd
for C29H23BrO3Se (Mþ): 577.9996; found: 577.9991.
(E)-1-(4-Bromophenyl)-2-phenyl-4-(2-(phenylselenyl)ethyl)oct-1-
ene-3,5-dione (4h). The reaction of diphenyl diselenide (187 mg, 0.6
mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL, 0.6
mmol, 1.2 equiv), 2f (106 mg, 0.5 mmol, 1.0 equiv), and 4-bromo-
benzaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL)
afforded 4h (165 mg, 60%). 1H NMR (400 MHz, CDCl3) δ 7.61 (s,
1H), 7.41ꢀ7.45 (m, 5H), 7.20ꢀ7.27 (m, 5H), 7.09ꢀ7.11 (m, 2H),
6.84 (d, J = 8.4 Hz, 2H), 4.24ꢀ4.27 (m, 1H), 2.80ꢀ2.97 (m, 2H),
2.26ꢀ2.35 (m, 1H), 2.00ꢀ2.13 (m, 2H), 1.82ꢀ1.90 (m, 1H),
1.36ꢀ1.43 (m, 2H), 0.75 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 205.6, 196.4, 140.2, 138.6, 135.8, 133.2, 132.5, 132.3, 131.5,
129.9, 129.4, 129.3, 129.1, 128.4, 127.0, 123.9, 61.2, 43.4, 28.9, 25.7,
16.7, 13.5; MS (EI) m/z 554 (Mþ); IR (ATR) νmax (cmꢀ1) 1712,
1678, 1582, 1481, 1070, 735, 694; HRMS (EI): m/z calcd for
C28H27BrO2Se (Mþ): 554.0360; found: 554.0361.
(E)-4-(4-Bromobenzylidene)-2-(2-(phenylselenyl)ethyl)-1-p-tolyloc-
tane-1,3-dione (4i). The reaction of diphenyl diselenide (187 mg, 0.6
mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL, 0.6
mmol, 1.2 equiv), 2g (120 mg, 0.5 mmol, 1.0 equiv), and 4-bromoben-
zaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL)
afforded 4i (158 mg, 54%). 1H NMR (400 MHz, CDCl3) δ 7.81 (d, J =
8.0 Hz, 2H), 7.46ꢀ7.50 (m, 4H), 7.37 (s, 1H), 7.18ꢀ7.25 (m, 5H), 7.07
(d, J = 8.0 Hz, 2H), 5.40ꢀ5.43 (m, 1H), 3.06ꢀ3.09 (m, 2H), 2.40ꢀ2.45
(m, 7H), 1.28ꢀ1.30 (m, 4H), 0.84 (t, J = 6.4 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 197.4, 195.6, 144.4, 142.7, 138.2, 134.2, 133.4, 132.0,
131.7, 130.7, 129.6, 129.5, 129.3, 128.7, 126.9, 122.9, 54.8, 30.7, 29.6,
26.4, 26.3, 22.8, 21.6, 13.7; MS (EI) m/z 582 (Mþ); IR (ATR) νmax
(cmꢀ1) 1685, 1649, 1606, 1264, 1090, 734, 689; HRMS (EI): m/z calcd
for C30H31BrO2Se (Mþ): 582.0673; found: 582.0700.
(E)-5-(4-Bromophenyl)-4-phenyl-1-p-tolyl-2-(2-(p-tolylselenyl)ethyl)-
pent-4-ene-1,3-dione (4b). The reaction of di(p-tolyl) diselenide (204
mg, 0.6 mmol, 1.2equiv), asolution ofn-BuLiin n-hexane(2.5M, 0.24 mL,
0.6 mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and 4-bromo-
benzaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL)
afforded 4b (207 mg, 67%). 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 1H),
7.44 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.22ꢀ7.25 (m, 5H),
7.00ꢀ7.08 (m, 6H), 6.80 (d, J = 8.4 Hz, 2H), 5.03ꢀ5.07 (m, 1H),
2.89ꢀ3.03 (m, 2H), 2.42ꢀ2.49 (m, 1H), 2.35 (s, 3H), 2.25 (s, 3H),
2.05ꢀ2.12 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 196.2, 196.0, 144.0,
140.1, 137.8, 136.9, 135.7, 133.3, 133.0, 132.6, 132.2, 131.4, 129.9, 129.9,
129.2, 129.0, 128.4, 128.2, 125.6, 123.6, 56.2, 29.4, 26.3, 21.5, 20.9; MS (EI)
m/z 616 (Mþ); IR (ATR) νmax (cmꢀ1) 1686, 1658, 1442, 1231, 1071, 799,
702; HRMS (EI): m/z calcd for C33H29BrO2Se (Mþ): 616.0516; found:
616.0514.
(E)-5-(4-Bromophenyl)-2-(2-(butylselenyl)ethyl)-4-phenyl-1-p-tolyl-
pent-4-ene-1,3-dione (4c). The reaction of di(n-butyl) diselenide
(163 mg, 0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane
(2.5 M, 0.24 mL, 0.6 mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv),
and 4-bromobenzaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-
1
dioxane (4 mL) afforded 4c (170 mg, 58%). H NMR (400 MHz,
CDCl3) δ 7.69 (s, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.23ꢀ7.26 (m, 5H),
7.09ꢀ7.15 (m, 4H), 6.84 (d, J = 8.4 Hz, 2H), 5.07ꢀ5.10 (m, 1H),
2.40ꢀ2.64 (m, 5H), 2.37 (s, 3H), 1.99ꢀ2.07 (m, 1H), 1.56ꢀ1.63 (m,
2H), 1.32ꢀ1.41 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 196.2, 196.1, 144.1, 140.0, 137.8, 135.7, 133.2, 133.0, 132.2,
131.4, 129.9, 129.2, 129.1, 128.4, 128.2, 123.7, 56.5, 32.4, 29.5, 23.7, 22.9,
22.3, 21.6, 13.5; MS (EI) m/z 582 (Mþ); IR (ATR) νmax (cmꢀ1) 1691,
1667, 1606, 1276, 1182, 820, 705; HRMS (EI): m/z calcd for C30H31-
BrO2Se (Mþ): 582.0673; found: 582.0670.
(E)-5-(4-Bromophenyl)-1-(4-methoxyphenyl)-4-phenyl-2-(2-(phenyl-
selenyl)ethyl)pent-4-ene-1,3-dione (4d). The reaction of diphenyl disele-
nide (187 mg, 0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane
(2.5 M, 0.24 mL, 0.6 mmol, 1.2 equiv), 2b (138 mg, 0.5 mmol, 1.0
equiv), and 4-bromobenzaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv)
1
in 1,4-dioxane (4 mL) afforded 4d (210 mg, 68%). H NMR (400
MHz, CDCl3) δ 7.63 (s, 1H), 7.51 (d, J = 7.6 Hz, 2H), 7.43 (d, J = 7.2
Hz, 2H), 7.20ꢀ7.25 (m, 8H), 7.02 (d, J = 6.4 Hz, 2H), 6.80 (d, J = 8.0
Hz, 2H), 6.73 (d, J = 7.6 Hz, 2H), 5.02ꢀ5.05 (m, 1H), 3.81 (s, 3H),
2.94ꢀ3.09 (m, 2H), 2.44ꢀ2.52 (m, 1H), 2.04ꢀ2.10 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 196.2, 194.9, 163.5, 139.9, 137.7, 135.7,
133.3, 132.2, 132.0, 131.4, 130.6, 129.9, 129.5, 129.2, 129.1, 128.3,
128.2, 126.8, 123.6, 113.5, 56.0, 55.4, 29.3, 25.9; MS (EI) m/z 618
(Mþ); IR (ATR) νmax (cmꢀ1) 1688, 1661, 1597, 1259, 1170, 734,
691; HRMS (EI): m/z calcd for C32H27BrO3Se (Mþ): 618.0309;
found: 618.0336.
(E)-5-(4-Bromophenyl)-1,4-diphenyl-2-(2-(phenylselenyl)ethyl)pent-
4-ene-1,3-dione (4e). The reaction of diphenyl diselenide (187 mg, 0.6
mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL, 0.6
mmol, 1.2 equiv), 2c (123 mg, 0.5 mmol, 1.0 equiv), and 4-bromoben-
zaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL)
1
afforded 4e (220 mg, 75%). H NMR (400 MHz, CDCl3) δ 7.65 (s,
1H), 7.51 (d, J = 7.6 Hz, 2H), 7.42ꢀ7.47 (m, 3H), 7.20ꢀ7.26 (m, 10H),
7.02 (d, J = 6.4 Hz, 2H), 6.81 (d, J = 8.4 Hz, 2H), 5.06ꢀ5.10 (m, 1H),
2.94ꢀ3.10 (m, 2H), 2.44ꢀ2.52 (m, 1H), 2.05ꢀ2.10 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 196.5, 196.1, 139.8, 138.0, 135.6, 135.3, 133.2,
132.3, 132.0, 131.4, 129.9, 129.4, 129.2, 129.1, 128.4, 128.2, 128.1, 126.8,
(E)-7-(4-Bromobenzylidene)-2-methyl-5-(2-(phenylselenyl)ethyl)-
undecane-4,6-dione (4j). The reaction of diphenyl diselenide (187 mg,
0.6 mmol, 1.2 equiv), asolution ofn-BuLi in n-hexane (2.5 M, 0.24 mL, 0.6
mmol, 1.2 equiv), 2h (103 mg, 0.5 mmol, 1.0 equiv), and 4-bromoben-
zaldehyde 3a (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL)
afforded 4j (140 mg, 51%). 1H NMR (400 MHz, CDCl3) δ 7.53 (d, J =
8.4 Hz, 2H), 7.46ꢀ7.48 (m, 2H), 7.43 (s, 1H), 7.18ꢀ7.26 (m, 5H),
4.57ꢀ4.60 (m, 1H), 2.87ꢀ2.96 (m, 2H), 2.45ꢀ2.46 (m, 2H), 2.09ꢀ2.27
123.7, 56.2, 29.1, 25.9; MS (EI) m/z 588 (Mþ); IR (ATR) νmax (cmꢀ1
)
1692, 1668, 1580, 1070, 1022, 734, 690; HRMS (EI): m/z calcd for
C31H25BrO2Se (Mþ): 588.0203; found: 588.0207.
(E)-5-(4-Bromophenyl)-1-(4-fluorophenyl)-4-phenyl-2-(2-(phenyl-
selenyl)ethyl)pent-4-ene-1,3-dione (4f). The reaction of diphenyl
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ARTICLE
(m, 5H), 1.34ꢀ1.35 (m, 4H), 0.84ꢀ0.91 (m, 9H); 13C NMR (100 MHz,
CDCl3) δ 205.1, 197.6, 143.1, 139.4, 134.1, 132.5, 131.8, 130.8, 129.4,
129.2, 127.0, 123.1, 60.7, 49.9, 30.9, 29.0, 26.4, 25.8, 23.9, 22.8, 22.4, 22.3,
13.7; MS (EI) m/z 548 (Mþ); IR (ATR) νmax (cmꢀ1) 1715, 1657, 1478,
1073, 1022, 735, 690; HRMS (EI): m/z calcd for C27H33BrO2Se (Mþ):
548.0829; found: 548.0825.
(E)-5-(4-Methoxyphenyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolyl-
pent-4-ene-1,3-dione (4k). The reaction of diphenyl diselenide (187 mg,
0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL,
0.6 mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and 4-methoxy-
benzaldehyde 3b (82 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL)
afforded 4k (201 mg, 73%). 1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H),
7.42ꢀ7.48 (m, 4H), 7.18ꢀ7.25 (m, 6H), 7.07 (d, J = 7.6 Hz, 4H), 6.90 (d,
J = 7.2 Hz, 2H), 6.62 (d, J = 8.4 Hz, 2H), 5.02ꢀ5.05 (m, 1H), 3.69 (s, 3H),
2.95ꢀ3.05 (m, 2H), 2.43ꢀ2.49 (m, 1H), 2.33 (s, 3H), 2.10ꢀ2.17 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 196.0, 160.5, 143.9, 139.4, 137.0, 136.5,
133.1, 132.8, 132.0, 130.0, 129.6, 129.1, 129.0, 129.0, 128.3, 127.8, 126.9,
126.7, 113.7, 56.1, 55.1, 29.4, 25.9, 21.5; MS (EI) m/z 554 (Mþ); IR (ATR)
νmax (cmꢀ1) 1688, 1647, 1599, 1253, 1174, 735, 690; HRMS (EI): m/zcalcd
for C33H30O3Se (Mþ): 554.1360; found: 554.1356.
(E)-5-(4-Fluorophenyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolyl-
pent-4-ene-1,3-dione (4l). The reaction of diphenyl diselenide (187 mg,
0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL,
0.6 mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and 4-fluor-
obenzaldehyde 3c (74 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL)
afforded 4l (231 mg, 85%). 1H NMR (400 MHz, CDCl3) δ 7.69 (s, 1H),
7.43ꢀ7.45 (m, 4H), 7.19ꢀ7.24 (m, 6H), 7.04ꢀ7.07 (m, 4H), 6.92ꢀ6.96
(m, 2H), 6.76ꢀ6.80 (m, 2H), 5.04ꢀ5.07 (m, 1H), 2.94ꢀ3.08 (m, 2H),
2.44ꢀ2.51 (m, 1H), 2.34 (s, 3H), 2.05ꢀ2.11 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 196.2, 196.1, 164.1, 161.6, 144.0, 138.9, 138.9,
138.0, 135.8, 132.9, 132.9, 132.8, 132.0, 131.9, 130.5, 130.4, 130.0, 129.5,
129.2, 129.1, 129.0, 128.3, 128.1, 126.7, 115.4, 115.2, 56.1, 29.3, 25.9, 21.5;
MS (EI) m/z 542 (Mþ); IR (ATR) νmax (cmꢀ1) 1687, 1655, 1598, 1229,
1117, 705, 692; HRMS (EI): m/z calcd for C32H27FO2Se (Mþ):
542.1160; found: 542.1152.
(E)-5-(3-Bbromophenyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolyl-
pent-4-ene-1,3-dione (4m). The reaction of diphenyl diselenide (187 mg,
0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL, 0.6
mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and 3-bromobenzalde-
hyde 3d (111 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL) afforded 4m
(212 mg, 70%). 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.42ꢀ7.46
(m, 4H), 7.19ꢀ7.29 (m, 7H), 6.85ꢀ7.09 (m, 7H), 5.05ꢀ5.08 (m, 1H),
2.93ꢀ3.07 (m, 2H), 2.44ꢀ2.51 (m, 1H), 2.35 (s, 3H), 2.06ꢀ2.14 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 196.2, 196.0, 144.1, 140.8, 137.4, 136.5,
135.4, 133.6, 133.0, 132.1, 132.0, 129.9, 129.6, 129.5, 129.2, 129.2, 129.1,
129.1, 128.4, 128.3, 126.8, 122.1, 56.3, 29.3, 25.9, 21.5; MS (EI) m/z 602
(Mþ); IR (ATR) νmax (cmꢀ1) 1690, 1665, 1605, 1275, 1182, 734, 689;
HRMS (EI): m/z calcd for C32H27BrO2Se (Mþ): 602.0360; found:
602.0363.
(E)-5-(1-Naphthalenyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolyl-
pent-4-ene-1,3-dione (4o). The reaction of diphenyl diselenide (187 mg,
0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL, 0.6
mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and 1-naphthaldehyde
3f (94 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL) afforded 4o (235 mg,
82%). 1H NMR (400 MHz, CDCl3) δ8.27 (s, 1H), 7.94ꢀ7.96 (m, 1H),
7.78ꢀ7.80 (m, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.4 Hz, 2H),
7.45ꢀ7.50 (m, 4H), 7.19ꢀ7.24 (m, 3H), 7.08ꢀ7.11 (m, 6H), 6.96ꢀ6.99
(m, 2H), 6.88ꢀ6.90 (m, 1H), 5.22ꢀ5.25 (m, 1H), 3.01ꢀ3.13 (m, 2H),
2.50ꢀ2.59 (m, 1H), 2.35 (s, 3H), 2.20ꢀ2.27 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 196.8, 196.1, 144.2, 142.3, 137.2, 135.5, 133.2, 133.1, 132.1,
132.0, 131.8, 130.3, 129.5, 129.2, 129.1, 129.0, 128.5, 128.4, 128.1, 127.7,
126.8, 126.5, 126.0, 124.8, 124.0, 56.4, 29.5, 26.0, 21.6; MS (EI) m/z 574
(Mþ); IR (ATR) νmax (cmꢀ1) 1689, 1665, 1604, 1275, 1181, 734, 696;
HRMS (EI): m/z calcd for C36H30O2Se (Mþ): 574.1411; found: 574.1415.
(E)-5-(2-Furanyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolylpent-
4-ene-1,3-dione (4p). The reaction of diphenyl diselenide (187 mg, 0.6
mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL, 0.6
mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and furan-2-
carbaldehyde 3g (58 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL)
afforded 4p (191 mg, 74%). 1H NMR (400 MHz, CDCl3) δ 7.67 (s, 1H),
7.42ꢀ7.45 (m, 4H), 7.35 (s, 1H), 7.19ꢀ7.28 (m, 6H), 7.06ꢀ7.08 (m,
4H), 6.21 (s, 1H), 5.63 (s, 1H), 4.98ꢀ5.01 (m, 1H), 2.91ꢀ3.05 (m, 2H),
2.39ꢀ2.48 (m, 1H), 2.35 (s, 3H), 2.05ꢀ2.14 (m, 1H); 13C NMR (100
MHz, CDCl3) δ 196.0, 195.1, 151.1, 144.7, 144.0, 136.2, 136.0, 133.0,
132.1, 129.6, 129.5, 129.1, 129.0, 128.3, 128.1, 127.2, 126.8, 115.5, 112.3,
56.2, 29.3, 26.0, 21.6; MS (EI) m/z 514 (Mþ); IR (ATR) νmax (cmꢀ1
)
1686, 1604, 1274, 1179, 1020, 735, 697; HRMS (EI): m/z calcd for
C30H26O3Se (Mþ): 514.1047; found: 514.1051.
(E)-4-Phenyl-2-(2-(phenylselenyl)ethyl)-5-(2-thiophenyl)-1-p-tolyl-
pent-4-ene-1,3-dione (4q). The reaction of diphenyl diselenide
(187 mg, 0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane
(2.5 M, 0.24 mL, 0.6 mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0
equiv), and thiophene-2-carbaldehyde 3h (67 mg, 0.6 mmol, 1.2 equiv)
in 1,4-dioxane (4 mL) afforded 4q (207 mg, 78%). 1H NMR (400 MHz,
CDCl3) δ 8.01 (s, 1H), 7.42 (d, J = 8.0 Hz, 4H), 7.28ꢀ7.29 (m, 3H),
7.18ꢀ7.21 (m, 4H), 7.05ꢀ7.14 (m, 5H), 6.89ꢀ6.91 (m, 1H), 4.94ꢀ4.97
(m, 1H), 2.91ꢀ3.05 (m, 2H), 2.40ꢀ2.49 (m, 1H), 2.34 (s, 3H), 2.06ꢀ2.13
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 196.0, 195.1, 143.9, 138.7, 136.2,
135.3, 134.5, 133.1, 132.9, 132.1, 131.4, 130.5, 129.6, 129.5, 129.1, 129.0,
128.6, 128.3, 126.8, 56.5, 29.3, 25.9, 21.5; MS (EI) m/z 530 (Mþ); IR
(ATR) νmax (cmꢀ1) 1685, 1604, 1576, 1179, 907, 728, 705; HRMS (EI):
m/z calcd for C30H26O2SSe (Mþ): 530.0819; found: 530.0817.
(E)-6,6-Dimethyl-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolylhept-
4-ene-1,3-dione (4r). The reaction of diphenyl diselenide (187 mg,
0.6 mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL,
0.6 mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and pivalaldehyde 3i
(52 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL) afforded 4r (109 mg,
43%). 1H NMR (400 MHz, CDCl3) δ 7.43ꢀ7.45 (m, 4H), 7.21ꢀ7.22 (m,
3H), 7.14ꢀ7.15 (m, 3H), 7.07ꢀ7.09 (m, 2H), 6.95ꢀ6.99 (m, 3H),
4.87ꢀ4.90 (m, 1H), 2.87ꢀ3.02 (m, 2H), 2.36ꢀ2.43 (m, 4H), 1.98ꢀ2.07
(m, 1H), 0.85 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 196.7, 196.1, 152.7,
143.9, 138.6, 136.1, 133.2, 132.1, 130.7, 129.7, 129.1, 129.0, 128.4, 127.9,
127.5, 126.8, 56.2, 34.3, 30.3, 29.4, 26.0, 21.6; MS (EI) m/z 504 (Mþ); IR
(ATR) νmax (cmꢀ1) 1692, 1666, 1607, 1276, 1179, 735, 695; HRMS (EI):
m/z calcd for C30H32O2Se (Mþ): 504.1568; found: 504.1571.
(E)-5-(2-Methoxyphenyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolyl-
pent-4-ene-1,3-dione (4n). The reaction of diphenyl diselenide (187 mg, 0.6
mmol, 1.2 equiv), a solution of n-BuLi in n-hexane (2.5 M, 0.24 mL, 0.6
mmol, 1.2 equiv), 2a (130 mg, 0.5 mmol, 1.0 equiv), and 2-methoxybenzal-
dehyde 3e (82 mg, 0.6 mmol, 1.2 equiv) in 1,4-dioxane (4 mL) afforded 4n
(197 mg, 71%). 1H NMR (400 MHz, CDCl3) δ8.09 (s, 1H), 7.60 (d, J = 7.6
Hz, 2H), 7.45 (d, J = 7.2 Hz, 2H), 7.11ꢀ7.23 (m, 9H), 7.04 (d, J = 7.6 Hz,
2H), 6.79 (d, J = 8.0 Hz, 1H), 6.59 (d, J = 8.0 Hz, 1H), 6.49ꢀ6.53 (m, 1H),
5.20ꢀ5.23 (m, 1H), 3.76 (s, 3H), 2.95ꢀ3.09 (m, 2H), 2.45ꢀ2.51 (m, 1H),
2.36 (s, 3H), 2.16ꢀ2.23 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 196.5,
196.0, 158.5, 144.0, 139.4, 136.1, 134.6 133.2, 132.2, 130.7, 130.3, 130.1,
129.6, 129.1, 129.0, 128.7, 128.5, 127.7, 126.7, 123.3, 119.7, 110.4, 55.8, 55.4,
29.6, 26.1, 21.5; MS (EI) m/z 554 (Mþ); IR (ATR) νmax (cmꢀ1) 1686,
1601, 1248, 1180, 1024, 735, 700; HRMS (EI): m/z calcd for C33H30O3Se
(Mþ): 554.1360; found: 554.1353.
(E)-1-(4-Bromophenyl)-4-((Z)-(2-(2,4-dinitrophenyl)hydrazono)(p-
tolyl)methyl)-2-phenyl-6-(phenylselenyl)hex-1-en-3-one (5). To a
25 mL round-bottom flask were added dinitrophenylhydrazine (238
mg, 1.2 mmol), ethanol (10 mL), and concentrated sulfuric acid (1 mL).
When the solid disappeared, a solution of 4a (240 mg, 0.4 mmol) in
ethanol (10 mL) was added. After being stirred for 2 days at room
temperature, the solvent was evaporated and the residue was extracted
with diethyl ether (3 ꢁ 20 mL). The organic phase was washed with
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ARTICLE
saturated brine and dried over Na2SO4. Filtration, evaporation, and
column chromatography on silica gel (eluent: petroleum ether/ethyl
acetate = 9/1) afforded 5 (137 mg, 44% yield). An X-ray quality crystal
of 5 was grown by dissolving in 0.2 mL of EtOAc and allowing the
diffusion of 1.8 mL of petroleum ether into the solution. 1H NMR (400
MHz, CDCl3) δ11.15 (s, 1H), 9.01 (s, 1H), 8.23ꢀ8.26 (m, 1H), 7.86 (d,
J = 9.2 Hz, 1H), 7.70 (s, 1H), 7.38ꢀ7.45 (m, 3H), 7.14ꢀ7.31 (m, 9H),
7.05 (d, J = 7.2 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 8.0 Hz, 2H),
4.45ꢀ4.48 (m, 1H), 2.84ꢀ3.05 (m, 2H), 2.39ꢀ2.47 (m, 4H),
1.88ꢀ1.97 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 197.5, 156.2,
144.6, 140.8, 140.6, 138.1, 137.7, 136.4, 133.3, 132.8, 132.2, 131.6, 130.4,
130.0, 129.9, 129.4, 129.3, 129.2, 129.0, 128.5, 128.4, 127.0, 126.6, 123.9,
123.3, 116.3, 55.0, 29.0, 26.0, 21.4; MS (EI) m/z 782 (Mþ); IR (ATR)
νmax (cmꢀ1) 1687, 1612, 1588, 1331, 1074, 741, 704; HRMS (EI): m/z
calcd for C38H31BrN4O5Se (Mþ): 782.0643; found: 782.0660.
(E)-5-(2-(4-Bromophenyl)-1-phenylvinyl)-3-p-tolyl-4-vinylisoxazole
(10). To a 25 mL round-bottom flask were added 4a (180 mg, 0.3
mmol), hydroxylamine hydrochloride (41 mg, 0.6 mmol), ethanol
(3 mL), and acetic acid (0.3 mL). The reaction mixture was then heated
under reflux for 6 h. When the reaction was completed, the solvent was
evaporated and the residue was extracted with EtOAc (3 ꢁ 20 mL). The
organic phase was dried over Na2SO4. Filtration, evaporation, and
column chromatography on silica gel (eluent: petroleum ether/ethyl
acetate = 9/1) afforded isoxazole product (111 mg, 62% yield). To a
25 mL round-bottom flask were added the above isoxazole product (90 mg,
0.15 mmol), 30% H2O2 (0.5 mL), and THF (4 mL). The reaction mixture
was stirred at room temperature for 2 h. When the reaction was completed,
the solvent was evaporated and the residue was extracted with Et2O (3 ꢁ
20 mL). The organic phase was dried over Na2SO4. Filtration, evaporation,
and column chromatography on silica gel (eluent: petroleum ether/CH2Cl2 =
2/1) afforded 10 (59 mg, 89% yield). 1H NMR (400 MHz, CDCl3) δ
7.48 (d, J = 8.0 Hz, 2H), 7.23ꢀ7.36 (m, 10H), 6.94 (d, J = 8.0 Hz, 2H),
5.81ꢀ5.85 (m, 1H), 4.90ꢀ4.99 (m, 2H), 2.39 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 166.3, 162.3, 139.4, 135.7, 134.4, 132.4, 131.4,
131.3, 130.1, 129.9, 129.2, 129.0, 128.7, 128.5, 126.4, 124.0, 122.1, 119.3,
114.1, 21.4; MS (EI) m/z 441 (Mþ); IR (ATR) νmax (cmꢀ1) 1487,
1109, 1010, 986, 910, 820, 700; HRMS (EI): m/z calcd for
C26H20BrNO (Mþ): 441.0728; found: 441.0731.
(91 mg, 0.9 mmol), phenylacetylene (46 mg, 0.45 mmol), and 4a (180 mg,
0.3 mmol) in DMF (2 mL) was stirred at 80 °C for 3 h under nitrogen.
After complete conversion of the starting materials as monitored by TLC,
the reaction mixture was diluted with 20 mL of Et2O and quenched with
20 mL of water. The organic layer was separated, and the aqueous layer was
extracted with diethyl ether (3 ꢁ 20 mL). The combined organic layer was
dried over Na2SO4. Filtration, evaporation, and column chromatography on
silica gel (eluent: petroleum ether/ethyl acetate = 15/1) afforded 12 (153
mg, 82%). 1H NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.43ꢀ7.46 (m,
6H), 7.30ꢀ7.32 (m, 3H), 7.20ꢀ7.25 (m, 8H), 7.04ꢀ7.09 (m, 4H), 6.93
(d, J = 8.4 Hz, 2H), 5.05ꢀ5.08 (m, 1H), 2.94ꢀ3.08 (m, 2H), 2.44ꢀ2.51
(m, 1H), 2.35 (s, 3H), 2.06ꢀ2.15 (m, 1H); 13C NMR (100 MHz, CDCl3)
δ 196.3, 196.0, 144.1, 140.0, 138.5, 135.9, 134.2, 133.1, 132.1, 131.6, 131.3,
130.8, 130.0, 129.6, 129.2, 129.1, 129.1, 128.4, 128.3, 128.2, 126.8, 124.2,
122.9, 91.4, 89.0, 56.3, 29.4, 26.0, 21.6; MS (EI) m/z 624 (Mþ); IR (ATR)
νmax (cmꢀ1) 1690, 1650, 1601, 1263, 1108, 731, 691; HRMS (EI): m/z
calcd for C40H32O2Se (Mþ): 624.1568; found: 624.1567.
(E)-5-(Biphenyl-4-yl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolyl-
pent-4-ene-1,3-dione (13). A mixture of Pd(PPh3)4 (17 mg, 5 mol %,
0.015 mmol), K3PO4 3H2O (240 mg, 0.9 mmol), H2O (0.1 mL),
3
phenylboronic acid (49 mg, 0.4 mmol), and 4a (180 mg, 0.3 mmol) in
toluene (4 mL) was stirred at 100 °C for 5 h under nitrogen. After
complete conversion of the starting materials as monitored by TLC, the
reaction mixture was diluted with 20 mL of Et2O and quenched with 20 mL
of water. The organic layer was separated, and the aqueous layer was
extracted with diethyl ether (3 ꢁ 20 mL). The combined organic layer was
dried over Na2SO4. Filtration, evaporation, and column chromatography on
silica gel (eluent: petroleum ether/ethyl acetate = 15/1) afforded 13 (118
mg, 66%). 1H NMR (400 MHz, CDCl3) δ 7.76 (s, 1H), 7.43ꢀ7.49 (m,
6H), 7.34ꢀ7.38 (m, 4H), 7.17ꢀ7.27 (m, 7H), 7.02ꢀ7.10 (m, 6H),
5.06ꢀ5.10 (m, 1H), 2.96ꢀ3.06 (m, 2H), 2.45ꢀ2.52 (m, 1H), 2.34 (s,
3H), 2.10ꢀ2.17 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 196.2, 196.0,
144.0, 141.9, 139.9, 139.3, 139.0, 136.2, 133.3, 133.2, 132.1, 131.5, 130.1,
129.6, 129.2, 129.1, 129.0, 128.7, 128.4, 128.1, 127.7, 126.8, 126.8, 126.7,
56.3, 29.5, 26.0, 21.5; MS (EI) m/z 600 (Mþ); IR (ATR) νmax (cmꢀ1
)
1689, 1664, 1603, 1267, 1183, 733, 696; HRMS (EI): m/z calcd for
C38H32O2Se (Mþ): 600.1568; found: 600.1566.
(E)-5-(2-(4-Bromophenyl)-1-phenylvinyl)-3-p-tolyl-4-vinyl-1H-pyr-
azole (11). To a 25 mL round-bottom flask were added 4a (240 mg,
0.4 mmol), hydrazine monohydrate 85% (0.3 mL), and ethanol (3 mL).
The reaction mixture was then heated under reflux for 4 h. When the
reaction was completed, the solvent was evaporated and the residue was
extracted with EtOAc (3 ꢁ 20 mL). The organic phase was dried over
Na2SO4. Filtration, evaporation, and column chromatography on silica
gel (eluent: petroleum ether/ethyl acetate = 4/1) afforded pyrazole
product (137 mg, 57% yield). To a 25 mL round-bottom flask were added
the above pyrazole product (90 mg, 0.15 mmol), 30% H2O2 (0.5 mL), and
THF (4 mL). The reaction mixture was stirred at room temperature for 2 h.
When the reaction was completed, the solvent was evaporated and the
residue was extracted with Et2O (3 ꢁ 20 mL). The organic phase was dried
over Na2SO4. Filtration, evaporation, and column chromatography on silica
gel (eluent: petroleum ether/ethyl acetate/THF = 4/1/1) afforded 11 (53
mg, 81% yield). 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 7.6 Hz, 2H),
7.17ꢀ7.30 (m, 10H), 6.90 (d, J = 8.0 Hz, 2H), 6.89 (s, 1H), 6.38ꢀ6.45 (m,
1H), 5.20ꢀ5.24 (m, 1H), 4.98ꢀ5.02 (m, 1H), 2.37 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 138.0, 137.6, 135.3, 133.2, 131.2, 131.1, 130.1, 129.9,
129.4, 129.2, 129.1, 128.7, 128.3, 128.2, 128.1, 126.9, 121.1, 116.7, 115.2,
21.3; MS (EI) m/z 440 (Mþ); IR (ATR) νmax (cmꢀ1) 1486, 1444, 909,
820, 756, 698; HRMS (EI): m/z calcd for C26H21BrN2 (Mþ): 440.0888;
found: 440.0882.
’ ASSOCIATED CONTENT
Supporting Information. Copies of H and 13C NMR
1
S
b
spectra for 4, 5, 10ꢀ13, NOE spectra for 4i, X-ray crystal-
lographic data (CIF file), and an ORTEP drawing for 5. This
material is available free of charge via the Internet at http://pubs.
acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: wululing@zju.edu.cn.
Notes
§Prof. Xian Huang passed away on March 6, 2010. He had been
fully in charge of this project. At this moment, Prof. Luling Wu is
helping him to finish all the projects with help from Prof.
Shengming Ma.
’ ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of
China (Project Nos. 20872127, 20732005, and J0830431) and
National Basic Research Program of China (973 Program,
2009CB825300) and CAS Academician Foundation of Zhejiang
(E)-4-Phenyl-5-(4-(phenylethynyl)phenyl)-2-(2-(phenylselenyl)ethyl)-
1-p-tolylpent-4-ene-1,3-dione (12). A mixture of Pd(PPh3)2Cl2 (11 mg,
5 mol %, 0.015 mmol), Au(PPh3)Cl (7 mg, 5 mol %, 0.015 mmol), Et3N
5604
dx.doi.org/10.1021/jo2005439 |J. Org. Chem. 2011, 76, 5598–5605

The Journal of Organic Chemistry
ARTICLE
Province and the Fundamental Research Funds for the Central
Universities for financial support.
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