Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles

Article abstract of DOI:10.1039/c2ob25071c

A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E⁺ = PhSe⁺) and 2-alkynyl ketones (E⁺ = F ⁺, Cl⁺, active halides) as the final products, respectively.

Full text of DOI:10.1039/c2ob25071c

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PAPER
Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and
2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)
cyclopropyl ketones and electrophiles†
Jianfeng Xu, Shugao Zhu, Luling Wu* and Xian Huang‡
Received 11th January 2012, Accepted 14th March 2012
DOI: 10.1039/c2ob25071c
A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the
subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of
electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E+ = PhSe+) and
2-alkynyl ketones (E+ = F+, Cl+, active halides) as the final products, respectively.
Introduction
The cleavage of cyclopropane ring is of great importance in
organic chemistry due to its potential for the synthesis of various
products, and therefore has attracted much attention during the
past three decades.1 1-(1-Alkynyl)cyclopropyl ketone, contain-
ing both an alkyne and a cyclopropane unit, is a useful multi-
functionalized building block.2 Recently, Schmalz and Zhang,2a
Zhang et al.,2b,c Zhang et al.,2d,e and Wang et al.2f have reported
their facile strategies of using 1-(1-alkynyl)cyclopropyl ketones
as readily available substrates for efficient construction of highly
Scheme 1 Previous work and our proposal.
substituted furans and other cyclic compounds, respectively. Our
group has also reported a novel synthesis of 4(E)-alken-1,3-
diones from the three-component reaction of lithium selenolates
with 1-(1-alkynyl)cyclopropyl ketones and aldehydes.3 Since the
homo-conjugate addition4 of lithium selenolates to 1-(1-alkynyl)
cyclopropyl ketones would form an alkynyl enolate intermediate
A, which has two resonance structures B and C, we envisioned
that when different electrophiles are used to capture these inter-
mediates, it may form substituted 1,2-allenyl ketones5 or 2-
Scheme 2
alkynyl ketones6 as the expected products, depending on the
nature of the electrophiles (Scheme 1).
Results and discussion
Initially we used lithium phenylselenolate 1a to react with
1-(phenylethynyl)cyclopropyl p-tolyl ketone 2a for 15 min, then
phenylselenyl bromide 3 was added. After reacting for additional
4 h, we were pleased to obtain 1,2-allenyl ketone 4a in 69%
yield exclusively (Scheme 2).
Further efforts was then made to optimize the conditions for
this reaction, the results are summarized in Table 1. A solvent
screening showed that anhydrous THF is the best (Table 1,
entries 1–5). Surprisingly, when the amount of 3 was raised to
1.6 equiv, furan product 5a was also formed and isolated in 19%
Department of Chemistry, Zhejiang University (Xixi Campus),
Hangzhou, 310028 Zhejiang, P.R. China. E-mail: wululing@zju.edu.cn;
Fax: (+86) 571-88807077
†Electronic supplementary information (ESI) available: 1H and 13C
NMR spectra for 4, 5, 6, and 8, 19F NMR spectra for 8a–j, X-ray crystal-
lographic data (CIF file), and an ORTEP drawing for 6a. CCDC
821931. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2ob25071c
‡Professor Huang passed away on March 6, 2010. He was fully in
charge of this project. Professor Luling Wu is helping to finish all the
projects with assistance from Professor Shengming Ma.
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Table 1 Optimization of reaction conditions for the reaction of lithium phenylselenolate (1a), 1-(phenylethynyl)cyclopropyl p-tolyl ketone (2a) and
phenylselenyl bromide (3)a
Entry
1a : 2a : 3 (equiv)
Solvent
Timeb (h)
Yield of 4ac (%)
Yield of 5ac (%)
1
2
3
4
5
6
7
8
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 : 1.2
1.0 : 1.2 : 1.0
1.2 : 1.0 : 1.4
1.2 : 1.0 : 1.6
1.2 : 1.0 : 1.8
1.2 : 1.0 : 2.0
1.2 : 1.0 : 2.2
THF
Et2O
Toluene
Cyclohexane
1,4-Dioxane
THF
THF
THF
THF
THF
4
7
6
11
4
7
7
24
24
24
24
24
69
61
62
52
66
76
68
74
52
19
3
—
—
—
—
—
—
—
Trace
19
57
71
72
9
10
11
12
THF
THF
3
a Unless otherwise specified, the reaction was carried out using 1a (0.6 mmol), 2a (0.5 mmol), and 3 (0.6 mmol) in 4 mL of solvent at room
temperature under a nitrogen atmosphere. b The reaction was monitored by TLC. c Isolated yields.
Table 2 Synthesis of various 1,2-allenyl ketones (4)a
yield (Table 1, entry 9). After several attempts, we were pleased
to define two sets of the optimal reaction conditions for the
selective formation of 4a and 5a: at room temperature under a
nitrogen atmosphere, the reaction of 1.2 equiv of 1a, 1.0 equiv
of 2a, and 1.2 equiv of 3 in anhydrous THF for 7 h afforded 1,2-
allenyl ketone 4a as the sole product (Table 1, entry 6); the reac-
tion of 1.2 equiv of 1a, 1.0 equiv of 2a, and 2.0 equiv of 3 in
anhydrous THF for 24 h gave the highest yield of furan 5a
(Table 1, entry 11).
1
2
Entry
R1
R2
R3
Yield of 4b (%)
With the above optimized conditions in hand, the reaction of
several lithium selenolates 1 and 1-(1-alkynyl)cyclopropyl
ketones 2 followed by the addition of PhSeBr was investigated.
As shown in Table 2, the yields of 1,2-allenyl ketones 4 ranged
from 46% to 76%. Both lithium arylselenolate and alkylseleno-
late could be used, and the arylselenolate gave a much better
result (Table 2, entries 1–2). With regard to the substrates 2, no
matter R2 and R3 are alkyl, aryl, or heteroaryl groups, all of
them could afford the corresponding allenyl ketone products 4a
and 4c–i in moderate yields (Table 2, entries 1 and 3–9).
At the meantime, we observed that the reaction with 2.0 equiv
of PhSeBr afforded furans 5 as the products, the results are listed
in Table 3. Compared with lithium phenylselenolate 1a, lithium
n-butylselenolate 1b showed a much poorer reactivity in forming
the corresponding furans (Table 3, entries 1–2). This reaction
could tolerate various 1-(1-alkynyl)cyclopropyl ketones 2: the
R2 and R3 substituents could be alkyl, aryl, or heteraryl groups
(Table 3, entries 1 and 3–10).
1
2
3
4
5
6
7
8
9
Ph (1a)
n-Bu (1b)
4-MeC6H4
2a
4-MeOC6H4
4-FC6H4
2-Furyl
n-Pr
t-Bu
4-MeC6H4
i-Bu
Ph (2a)
76 (4a)
46 (4b)
68 (4c)
59 (4d)
55 (4e)
61 (4f)
67 (4g)
65 (4h)
64 (4i)
1a
1a
1a
1a
1a
1a
1a
Ph (2b)
Ph (2c)
Ph (2d)
Ph (2f)
Ph (2g)
n-Bu (2h)
n-Bu (2i)
a The reaction was carried out using 1 (0.6 mmol), 2 (0.5 mmol), and 3
(0.6 mmol) in 4 mL of THF under a nitrogen atmosphere at room
temperature for 7 h. b Isolated yields.
We proposed a mechanism to explain the formation of furan 5.
The allenyl moiety in ketone 4a would interact with phenylsele-
nyl bromide 3, which would be followed by the attacking of the
carbonyl group in 4a to form intermediate 12 or 13. Elimination
of a phenylselenyl cation finally afforded furan product 5a
(Scheme 4). The higher loading of PhSeBr required indicates
that the interaction between 3 and PhSeBr is rather slow.
As expected, when other electrophiles such as NIS, NBS
and CuCl2 were used instead of phenylselenyl bromide to react
with 4a, the corresponding halogen-substituted furans 6a–c
were formed, respectively (Scheme 5). The structure of
These reactions indicate that the excess amount of PhSeBr
may catalyse or promote the transformation from allenyl ketones
4 to furans 5. Thus, we first applied 0.1 equiv of phenylselenyl
bromide 3 to a solution of 4a in THF. The reaction is catalytic,
but slow: after 1 day, only 27% of 5a was obtained with 29% of
4a being recovered. By increasing the amount of 3 to 1.0 equiv,
furan 5a could be isolated in 63% yield (Scheme 3).
3706 | Org. Biomol. Chem., 2012, 10, 3705–3714
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Table 3 Synthesis of various furans (5)a
Scheme 4
1
2
Entry
R1
R2
R3
Yield of 5b (%)
1
2
3
4
5
6
7
8
9
Ph (1a)
n-Bu (1b)
4-MeC6H4
2a
4-MeOC6H4
4-FC6H4
2-Furyl
2-Thienyl
n-Pr
t-Bu
4-MeC6H4
i-Bu
Ph (2a)
71 (5a)
46 (4b)
65 (5c)
58 (5d)
52 (5e)
49 (5f)
65 (5g)
64 (5h)
68 (5i)
51 (5j)
1a
1a
1a
1a
1a
1a
1a
1a
Ph (2b)
Ph (2c)
Ph (2d)
Ph (2e)
Ph (2f)
Ph (2g)
n-Bu (2h)
n-Bu (2i)
Scheme 5
10
a The reaction was carried out using 1 (0.6 mmol), 2 (0.5 mmol), and 3
(1.0 mmol) in 4 mL of THF under a nitrogen atmosphere at room
temperature for 24 h. b Isolated yields.
Fig. 1 ORTEP representation of furan 6a.
afforded 8a in 30% yield (Table 4, entries 2–5). The amount of
7a did not have much influence on the reaction (Table 4, entries
1, 6, and 7). When 7a was replaced with N-fluorodi(benzenesul-
fonyl) amine 7b, the highest yield (57%) was observed when the
reaction of 1.2 equiv of 1a, 1.0 equiv of 2a, and 1.2 equiv of 7b
in anhydrous THF was conducted at room temperature for 11 h
(Table 4, entries 8–11). Thus, the reaction conditions presented
in entry 9 of Table 4 were defined as the standard conditions for
further study.
The reactions of organo lithium selenolates 1 and 1-(1-
alkynyl)cyclopropyl ketones 2 with 7b were then conducted by
applying the standard reaction conditions. As listed in Table 5,
lithium phenylselenolate 1a gave a much better result than
lithium n-butylselenolate 1b (Table 5, entries 1–2). 1-(1-
Alkynyl)cyclopropyl ketones 2 with alkyl, aryl, and heteroaryl
substituents could all afford the corresponding fluoro-substituted
2-alkynyl ketones 8c–j successfully, but when R3 is an alkyl
group, the yield was lower than when it is an aryl group
(Table 5, entries 1 and 3–10).
Scheme 3
iodo-substituted furan 6a was confirmed by its single-crystal X-
ray diffraction analysis (Fig. 1).§
Fluorinated organic compounds are of current interest due to
the rapidly increasing number of examples of these compounds
with interesting and useful biological activities.7 Thus, the reac-
tion of lithium phenylselenolate 1a with 1-(phenylethynyl)
cyclopropyl p-tolyl ketone 2a and Selectfluor (1-chloromethyl-4-
fluoro-1,4-diazonia-bicyclo[2.2.2]octanebis-(tetrafluoroborate))
7a in anhydrous THF was studied. Unexpectedly, the reaction
afforded fluoro-substituted 2-alkynyl ketone 8a in 51% yield
(Table 4, entry 1). We reasoned that this result maybe caused by
the small size and hard nature of the F+. Further study showed
that the reaction in solvent such as Et2O, toluene, and cyclo-
hexane did not afford 8a at all, while that in 1,4-dioxane
Other electrophiles such as NCS, allylic bromide, and benze-
nyl bromide were also tested, and the result showed that they all
followed path b to form the corresponding substituted 2-alkynyl
ketones 8k–m (Scheme 6).
§X-ray crystal data for 6a: C25H21IOSe, M = 543.28, monoclinic, space
group P21/n, final R indices [I > 2σ(I)]: R1 = 0.0368, wR2 = 0.0816, R
indices (all data): R1 = 0.0564, wR2 = 0.0921, a = 16.1185(6) Å, b =
5.7251(2) Å, c = 24.3065(9) Å, α = 90°, β = 106.365(4)°, γ = 90°, V =
2152.12(14) Å3, T = 293(2) K, Z = 4, reflections collected/unique: 9508/
3928 (Rint = 0.0326), number of observations [I > 2σ(I)]: 2996, para-
meters: 262.
Conclusions
In summary, we have developed an efficient method for the syn-
thesis of highly substituted 1,2-allenyl ketones, furans, and 2-
alkynyl ketones chemoselectively from readily available lithium
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Table 4 Optimization of reaction conditions for the reaction of lithium phenylselenolate (1a), 1-(phenylethynyl)cyclopropyl p-tolyl ketone (2a) and
F+ source (7)a
Entry
1a : 2a : 7 (equiv)
Solvent
Timeb (h)
F+ source 7
Yield of 8ac (%)
1
2
3
4
5
6
7
8
1.2 : 1.0 : 2.0
1.2 : 1.0 : 2.0
1.2 : 1.0 : 2.0
1.2 : 1.0 : 2.0
1.2 : 1.0 : 2.0
1.2 : 1.0 : 1.6
1.2 : 1.0 : 2.4
1.2 : 1.0 : 1.0
1.2 : 1.0 : 1.2
1.2 : 1.0 : 1.4
1.2 : 1.0 : 1.6
THF
Et2O
Toluene
Cyclohexane
1,4-Dioxane
THF
THF
THF
THF
THF
8
Selectfluor (7a)
7a
7a
7a
7a
7a
7a
51
—
—
—
30
45
48
51
57
54
50
24
24
24
7
8
8
11
11
11
11
NFSI (7b)
9
10
11
7b
7b
7b
THF
a Unless otherwise specified, the reaction was carried out using 1a (0.6 mmol), 2a (0.5 mmol), and 7 (0.6 mmol) in 4 mL of solvent at room
temperature under a nitrogen atmosphere. b The reaction was monitored by TLC. c Isolated yields.
Table 5 Synthesis of various fluoro-substituted 2-alkynyl ketones (8)a
1
2
Entry
R1
R2
R3
Yield of 8b (%)
1
2
3
4
5
6
7
8
9
Ph (1a)
n-Bu (1b)
4-MeC6H4
2a
4-MeOC6H4
4-FC6H4
2-Furyl
2-Thienyl
n-Pr
t-Bu
4-MeC6H4
i-Bu
Ph (2a)
57 (8a)
42 (8b)
52 (8c)
49 (8d)
53 (8e)
50 (8f)
53 (8g)
43 (8h)
43 (8i)
33 (8j)
1a
1a
1a
1a
1a
1a
1a
1a
Ph (2b)
Ph (2c)
Ph (2d)
Ph (2e)
Ph (2f)
Ph (2g)
n-Bu (2h)
n-Bu (2i)
Scheme 6
CDCl3 with TMS as the internal standard, CF3COOH was
employed as external standard for the 19F NMR measurement.
Chemical shifts were expressed in ppm and J values were given
in Hz. 1-(1-Alkynyl)cyclopropyl ketones were prepared accord-
ing to the known procedure.7 The other commercially available
chemicals were purchased and used without further purification
unless noted otherwise. Melting points were uncorrected.
10
a The reaction was carried out using 1 (0.6 mmol), 2 (0.5 mmol), and 7b
(0.6 mmol) in 4 mL of THF under a nitrogen atmosphere at room
temperature for 11 h. b Isolated yields.
selenolates, 1-(1-alkynyl)cyclopropyl ketones, and electrophiles.
The structures for the products are substrate-dependent. Further
studies in this area are now in progress in our laboratory.
General procedure for the synthesis of 1,2-allenyl ketones
(4a–i). To a dried two-necked round-bottom flask (25 mL) were
added diselenide (0.6 mmol, 1.2 equiv) and THF (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 1–2 min, to the resulting reaction
mixture was added a solution of 1-(1-alkynyl)cyclopropyl
ketone 2 (0.5 mmol, 1.0 equiv) in 2 mL of THF at room temp-
erature. The resulting reaction mixture was stirred for additional
15 min before phenylselenyl bromide (0.6 mmol, 1.2 equiv) was
added. After being stirred for 7 h, the reaction was quenched
Experimental
General
THF was distilled from Na/benzophenone immediately prior to
use. Petroleum ether refers to the fraction with the boiling point
in the range 60–90 °C. All 1H NMR (400 MHz), 13C NMR
(100 MHz) and 19F NMR (376 MHz) spectra were measured in
3708 | Org. Biomol. Chem., 2012, 10, 3705–3714
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with H2O and extracted with diethyl ether (3 × 20 mL). The
combined organic phase was washed with brine and dried over
Na2SO4. Filtration, evaporation, and column chromatography on
silica gel (eluent: petroleum ether–ethyl acetate = 50 : 1) afforded
the final product 4.
6.87–6.91 (m, 2H), 2.68–3.00 (m, 4H); 13C NMR (100 MHz,
CDCl3) δ 210.6, 191.9, 165.1 (d, J = 252.1 Hz), 134.2 (d, J =
3.2 Hz), 133.1, 132.8, 132.5, 131.2 (d, J = 9.0 Hz), 129.9,
129.3, 129.2, 129.1, 128.8, 128.6, 128.0, 127.7, 126.9, 115.0 (d,
J = 21.4 Hz), 107.8, 101.2, 29.5, 25.4; MS (EI, m/z): 578 (M+);
IR (ATR, neat, cm−1): 1916, 1648, 1264, 759, 735, 689; HRMS
(EI): m/z calcd for C30H23FOSe2 (M+): 578.0063; Found:
578.0078.
4-Phenyl-4-(phenylselenyl)-2-(2-(phenylselenyl)ethyl)-1-p-tolyl-
buta-2,3-dien-1-one (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 phenylselenyl bromide 3 (142 mg, 0.6 mmol, 1.2
1-(2-Furanyl)-4-phenyl-4-(phenylselenyl)-2-(2-(phenylselenyl)
ethyl)buta-2,3-dien-1-one (4e). 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), 2d (118 mg,
0.5 mmol, 1.0 equiv), and phenylselenyl bromide 3 (142 mg,
0.6 mmol, 1.2 equiv) in THF (4 mL) afforded 4e (151 mg,
1
equiv) in THF (4 mL) afforded 4a (218 mg, 76%). Liquid. H
NMR (400 MHz, CDCl3) δ 7.66 (d, J = 7.6 Hz, 2H), 7.50 (d, J
= 7.2 Hz, 2H), 7.44 (d, J = 5.6 Hz, 2H), 7.15–7.31 (m, 9H),
7.01–7.09 (m, 4H), 2.69–2.99 (m, 4H), 2.29 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 210.6, 192.9, 142.9, 135.4, 133.0, 132.9,
132.4, 130.0, 129.5, 129.1, 129.0, 128.8, 128.7, 128.3, 127.7,
126.7, 107.7, 100.5, 29.6, 25.4, 21.5; MS (EI, m/z): 574 (M+);
IR (ATR, neat, cm−1): 1916, 1646, 1269, 756, 734, 689; HRMS
(EI): m/z calcd for C31H26OSe2 (M+): 574.0314; Found:
574.0312.
1
55%). Liquid. H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 7.6
Hz, 2H), 7.49 (s, 1H), 7.31–7.42 (m, 7H), 7.18–7.24 (m, 5H),
7.12–7.16 (m, 2H), 6.37–6.38 (m, 1H), 2.70–2.89 (m, 3H),
2.51–2.57 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 208.5,
178.6, 151.6, 146.5, 134.2, 132.7, 132.3, 129.9, 129.3, 129.0,
128.9, 128.8, 128.7, 128.4, 127.7, 126.7, 118.4, 112.0, 107.8,
102.4, 29.3, 25.1; MS (EI, m/z): 550 (M+); IR (ATR, neat,
cm−1): 1919, 1636, 1290, 759, 734, 689; HRMS (EI): m/z calcd
for C28H22O2Se2 (M+): 549.9950; Found: 549.9959.
2-(2-(Butylselenyl)ethyl)-4-phenyl-4-(phenylselenyl)-1-p-tolylbuta-
2,3-dien-1-one (4b). 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 phenylselenyl bromide 3 (142 mg, 0.6 mmol, 1.2
1-Phenyl-1-(phenylselenyl)-3-(2-(phenylselenyl)ethyl)hepta-1,2-
dien-4-one (4f). 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 phenylselenyl bromide 3 (142 mg, 0.6 mmol, 1.2
1
equiv) in THF (4 mL) afforded 4b (127 mg, 46%). Liquid. H
NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.4 Hz, 2H), 7.52 (d, J
= 7.6 Hz, 2H), 7.19–7.33 (m, 6H), 7.10–7.14 (m, 2H), 7.03 (d, J
= 8.0 Hz, 2H), 2.68–2.84 (m, 2H), 2.53–2.63 (m, 4H), 2.32 (s,
3H), 1.57–1.65 (m, 2H), 1.34–1.42 (m, 2H), 0.89 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 210.8, 193.1, 143.0, 135.5,
133.0, 132.8, 129.7, 129.1, 128.8, 128.7, 128.7, 128.3, 127.7,
127.6, 107.9, 100.2, 32.5, 30.0, 23.8, 23.0, 21.5, 21.4, 13.6; MS
(EI, m/z): 554 (M+); IR (ATR, neat, cm−1): 1916, 1647, 1268,
759, 736, 689; HRMS (EI): m/z calcd for C29H30OSe2 (M+):
554.0627; Found: 554.0623.
1
equiv) in THF (4 mL) afforded 4f (160 mg, 61%). Liquid. H
NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.6 Hz, 2H), 7.48 (d, J
= 7.2 Hz, 2H), 7.17–7.40 (m, 11H), 2.72–2.85 (m, 2H),
2.57–2.64 (m, 1H), 2.39–2.49 (m, 3H), 1.48–1.57 (m, 2H), 0.82
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 209.4,
199.9, 134.2, 132.8, 132.4, 130.0, 129.3, 129.1, 129.0, 128.8,
128.5, 128.4, 127.5, 126.7, 109.8, 101.8, 41.7, 28.2, 25.3, 17.8,
13.7; MS (EI, m/z): 526 (M+); IR (ATR, neat, cm−1): 1918,
1674, 1439, 1125, 735, 689; HRMS (EI): m/z calcd for
C27H26OSe2 (M+): 526.0314; Found: 526.0318.
1-(4-Methoxyphenyl)-4-phenyl-4-(phenylselenyl)-2-(2-(phenylsel-
enyl)ethyl)buta-2,3-dien-1-one (4c). The reaction of diphenyl dis-
elenide (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 phenylselenyl bromide 3 (142 mg,
0.6 mmol, 1.2 equiv) in THF (4 mL) afforded 4c (201 mg,
2,2-Dimethyl-6-phenyl-6-(phenylselenyl)-4-(2-(phenylselenyl)
ethyl)hexa-4,5-dien-3-one (4g). 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), 2g (113 mg,
0.5 mmol, 1.0 equiv), and phenylselenyl bromide 3 (142 mg,
0.6 mmol, 1.2 equiv) in THF (4 mL) afforded 4g (181 mg,
1
68%). Liquid. H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.8
Hz, 2H), 7.52 (d, J = 7.2 Hz, 2H), 7.43–7.46 (m, 2H), 7.18–7.33
(m, 9H), 7.07–7.11 (m, 2H), 6.70 (d, J = 8.8 Hz, 2H), 3.74 (s,
3H), 2.70–3.00 (m, 4H); 13C NMR (100 MHz, CDCl3) δ 210.2,
191.6, 163.0, 133.0, 132.7, 132.4, 131.1, 130.6, 130.0, 129.6,
129.2, 129.0, 128.7, 128.4, 127.7, 127.6, 126.7, 113.2, 107.4,
100.3, 55.3, 29.8, 25.4; MS (EI, m/z): 590 (M+); IR (ATR, neat,
cm−1): 1916, 1642, 1251, 1025, 757, 735, 690; HRMS (EI): m/z
calcd for C31H26O2Se2 (M+): 590.0263; Found: 590.0272.
1-(4-Fluorophenyl)-4-phenyl-4-(phenylselenyl)-2-(2-(phenylsel-
enyl)ethyl)buta-2,3-dien-1-one (4d). The reaction of diphenyl dis-
elenide (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 (132 mg,
0.5 mmol, 1.0 equiv), and phenylselenyl bromide 3 (142 mg,
0.6 mmol, 1.2 equiv) in THF (4 mL) afforded 4d (171 mg,
59%). Liquid. 1H NMR (400 MHz, CDCl3) δ 7.72–7.75 (m,
2H), 7.44–7.51 (m, 4H), 7.19–7.35 (m, 9H), 7.09–7.13 (m, 2H),
1
67%). Liquid. H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.6
Hz, 2H), 7.15–7.44 (m, 13H), 2.67–2.82 (m, 2H), 2.56–2.64 (m,
1H), 2.38–2.46 (m, 1H), 1.18 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 208.0, 205.0, 133.4, 132.7, 132.3, 130.0, 129.5, 129.2,
129.0, 128.8, 128.3, 128.0, 127.6, 126.7, 104.7, 99.8, 44.9,
30.7, 27.4, 25.4; MS (EI, m/z): 540 (M+); IR (ATR, neat, cm−1):
1913, 1663, 1475, 1108, 734, 689; HRMS (EI): m/z calcd for
C28H28OSe2 (M+): 540.0471; Found: 540.0474.
4-(Phenylselenyl)-2-(2-(phenylselenyl)ethyl)-1-p-tolylocta-2,3-
dien-1-one (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), 2h (120 mg, 0.5 mmol, 1.0
equiv), and phenylselenyl bromide 3 (142 mg, 0.6 mmol, 1.2
1
equiv) in THF (4 mL) afforded 4h (175 mg, 65%). Liquid. H
NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.0 Hz, 2H), 7.49
Org. Biomol. Chem., 2012, 10, 3705–3714 | 3709
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3-(2-(Butylselenyl)ethyl)-5-phenyl-4-(phenylselenyl)-2-p-tolyl-
furan (5b). 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 phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0
(d, J = 7.2 Hz, 2H), 7.13–7.28 (m, 10H), 2.84–2.97 (m, 2H),
2.60–2.74 (m, 2H), 2.40 (s, 3H), 2.23–2.26 (m, 2H), 1.40–1.45
(m, 2H), 1.14–1.20 (m, 2H), 0.80 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 207.3, 194.2, 142.5, 135.9, 134.2, 132.4,
130.2, 129.1, 129.0, 128.9, 128.6, 128.6, 128.0, 126.7, 106.6,
99.5, 33.6, 30.3, 29.3, 25.7, 21.8, 21.6, 13.7; MS (EI, m/z): 554
(M+); IR (ATR, neat, cm−1): 1932, 1645, 1270, 830, 734, 689;
HRMS (EI): m/z calcd for C29H30OSe2 (M+): 554.0627; Found:
554.0632.
1
equiv) in THF (4 mL) afforded 5b (86 mg, 31%). Liquid. H
NMR (400 MHz, CDCl3) δ 8.09 (d, J = 7.6 Hz, 2H), 7.62 (d, J
= 8.8 Hz, 2H), 7.38 (t, J = 7.2 Hz, 2H), 7.14–7.31 (m, 8H),
3.02–3.06 (m, 2H), 2.60–2.64 (m, 2H), 2.51 (t, J = 7.2 Hz, 2H),
2.40 (s, 3H), 1.54–1.60 (m, 2H), 1.32–1.39 (m, 2H), 0.88 (t, J =
7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 154.4, 148.9,
137.6, 132.5, 130.4, 129.5, 129.4, 128.4, 128.3, 128.2, 128.1,
126.5, 126.0, 125.5, 125.3, 106.8, 32.8, 27.4, 23.7, 23.1, 22.5,
21.3,13.6; MS (EI, m/z): 554 (M+); IR (ATR, neat, cm−1): 1576,
1477, 818, 765, 733, 685; HRMS (EI): m/z calcd for
C29H30OSe2 (M+): 554.0627; Found: 554.0624.
2-Methyl-7-(phenylselenyl)-5-(2-(phenylselenyl)ethyl)undeca-5,6-
dien-4-one (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), 2i (103 mg, 0.5 mmol, 1.0
equiv), and phenylselenyl bromide 3 (142 mg, 0.6 mmol, 1.2
1
equiv) in THF (4 mL) afforded 4i (168 mg, 64%). Liquid. H
NMR (400 MHz, CDCl3) δ 7.52 (d, J = 7.2 Hz, 2H), 7.45 (d, J
= 6.0 Hz, 2H), 7.21–7.29 (m, 6H), 2.68–2.82 (m, 2H),
2.25–2.52 (m, 6H), 2.02–2.09 (m, 1H), 1.53–1.60 (m, 2H),
1.34–1.39 (m, 2H), 0.85–0.92 (m, 9H); 13C NMR (100 MHz,
CDCl3) δ 205.1, 200.6, 135.3, 132.3, 130.3, 129.2, 129.0, 128.6,
128.2, 126.7, 109.2, 100.8, 48.3, 33.7, 30.7, 27.9, 25.5, 25.4,
22.7, 22.6, 22.2, 13.8; MS (EI, m/z): 520 (M+); IR (ATR, neat,
cm−1): 1933, 1670, 1472, 1021, 735, 690; HRMS (EI): m/z
calcd for C26H32OSe2 (M+): 520.0784; Found: 520.0786.
2-(4-Methoxyphenyl)-5-phenyl-4-(phenylselenyl)-3-(2-(phenyl-
selenyl) ethyl)furan (5c). 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), 2b (138 mg, 0.5 mmol,
1.0 equiv), and phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0
equiv) in THF (4 mL) afforded 5c (192 mg, 65%). Pale solid,
1
mp 94–96 °C (petroleum ether–ethyl acetate = 50 : 1). H NMR
(400 MHz, CDCl3) δ 8.07 (d, J = 7.6 Hz, 2H), 7.44–7.50 (m,
4H), 7.36 (t, J = 7.6 Hz, 2H), 7.12–7.29 (m, 9H), 6.86 (d, J =
8.4 Hz, 2H), 3.82 (s, 3H), 3.01–3.05 (m, 2H), 2.91–2.95 (m,
2H); 13C NMR (100 MHz, CDCl3) δ 159.0, 154.0, 148.8, 133.3,
132.4, 130.3, 129.6, 129.3, 128.9, 128.4, 128.3, 128.1, 126.9,
126.4, 126.0, 124.1, 123.5, 114.1, 106.7, 55.3, 27.0, 26.7; MS
(EI, m/z): 590 (M+); IR (ATR, neat, cm−1): 1577, 1474, 1065,
765, 733, 689; HRMS (EI): m/z calcd for C31H26O2Se2 (M+):
590.0263; Found: 590.0264.
General procedure for the synthesis of furans (5a–j). To a
dried two-necked round-bottom flask (25 mL) were added di-
selenide (0.6 mmol, 1.2 equiv) and THF (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 1–2 min, to the resulting reaction mixture was
2-(4-Fluorophenyl)-5-phenyl-4-(phenylselenyl)-3-(2-(phenyl-
selenyl)ethyl)furan (5d). 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 (132 mg, 0.5 mmol,
1.0 equiv), and phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0
equiv) in THF (4 mL) afforded 5d (167 mg, 58%). Pale solid,
added
a solution of 1-(1-alkynyl)cyclopropyl ketone 2
(0.5 mmol, 1.0 equiv) in 2 mL of THF at room temperature. The
resulting reaction mixture was stirred for additional 15 min
before phenylselenyl bromide (1.0 mmol, 2.0 equiv) was added.
After being stirred for 24 h, the reaction was quenched with H2O
and extracted with diethyl ether (3 × 20 mL). The combined
organic phase was washed with brine and dried over Na2SO4.
Filtration, evaporation, and column chromatography on silica gel
(eluent: petroleum ether–ethyl acetate = 50 : 1) afforded the final
product 5.
1
mp 93–95 °C (petroleum ether–ethyl acetate = 50 : 1). H NMR
(400 MHz, CDCl3) δ 8.06 (d, J = 8.8 Hz, 2H), 7.46–7.49 (m,
4H), 7.36 (t, J = 7.6 Hz, 2H), 7.12–7.30 (m, 9H), 7.00 (t, J = 8.8
Hz, 2H), 3.00–3.05 (m, 2H), 2.89–2.93 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 162.0 (d, J = 246.5 Hz), 154.7, 147.9,
133.5, 132.2, 130.1, 129.4 (d, J = 9.4 Hz), 128.9, 128.5, 128.4,
127.4, 127.3, 127.1, 126.9 (d, J = 2.5 Hz), 126.5, 126.2, 125.3,
115.9, 115.7 (d, J = 21.6 Hz), 106.9, 27.0, 26.6; MS (EI, m/z):
578 (M+); IR (ATR, neat, cm−1): 1574, 1499, 1475, 1070, 838,
738, 689; HRMS (EI): m/z calcd for C30H23FOSe2 (M+):
578.0063; Found: 578.0072.
2-Phenyl-3-(phenylselenyl)-4-(2-(phenylselenyl)ethyl)-5-p-tolyl-
furan (5a). 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 phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0
equiv) in THF (4 mL) afforded 5a (204 mg, 71%). Pale solid,
1
mp 90–92 °C (petroleum ether–ethyl acetate = 50 : 1). H NMR
5-Phenyl-4-(phenylselenyl)-3-(2-(phenylselenyl)ethyl)-2,2′-bifuran
(5e). 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), 2d (118 mg, 0.5 mmol, 1.0 equiv), and
phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0 equiv) in THF
(4 mL) afforded 5e (143 mg, 52%). Pale solid, mp 55–57 °C
(400 MHz, CDCl3) δ 8.07 (d, J = 8.4 Hz, 2H), 7.42–7.47 (m,
4H), 7.35 (t, J = 7.6 Hz, 2H), 7.10–7.29 (m, 11H), 3.03–3.07
(m, 2H), 2.91–2.95 (m, 2H), 2.35 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 154.3, 148.9, 137.5, 133.2, 132.4, 130.3, 129.6, 129.4,
129.3, 128.9, 128.4, 128.3, 128.2, 127.9, 126.9, 126.5, 126.0,
125.4, 125.0, 106.8, 27.0, 26.6, 21.3; MS (EI, m/z): 574 (M+);
IR (ATR, neat, cm−1): 1575, 1472, 1015, 765, 729, 684; HRMS
(EI): m/z calcd for C31H26OSe2 (M+): 574.0314; Found:
574.0319.
1
(petroleum ether–ethyl acetate = 50 : 1). H NMR (400 MHz,
CDCl3) δ 8.05 (d, J = 7.6 Hz, 2H), 7.45–7.47 (m, 2H),
7.28–7.39 (m, 4H), 7.13–7.23 (m, 8H), 6.54 (d, J = 3.6 Hz, 1H),
6.45–6.46 (m, 1H), 3.08–3.12 (m, 2H), 2.91–2.95 (m, 2H); 13C
3710 | Org. Biomol. Chem., 2012, 10, 3705–3714
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NMR (100 MHz, CDCl3) δ 154.4, 146.2, 142.1, 142.0, 132.7,
132.1, 130.0, 129.9, 129.4, 128.9, 128.5, 128.4, 128.3, 126.7,
126.5, 126.2, 125.4, 111.3, 106.6, 106.4, 26.7, 26.3; MS (EI,
m/z): 550 (M+); IR (ATR, neat, cm−1): 1575, 1472, 1434, 1015,
765, 729, 684; HRMS (EI): m/z calcd for C28H22O2Se2 (M+):
549.9950; Found: 549.9957.
(4 mL) afforded 5i (188 mg, 68%). Pale solid, mp 42–44 °C
(petroleum ether–ethyl acetate = 50 : 1). H NMR (400 MHz,
1
CDCl3) δ 7.41 (d, J = 7.6 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H),
7.10–7.21 (m, 10H), 2.90–2.99 (m, 4H), 2.81 (t, J = 7.6 Hz,
2H), 2.34 (s, 3H), 1.59–1.67 (m, 2H), 1.31–1.39 (m, 2H), 0.88
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 160.1,
148.2, 136.9, 133.0, 132.9, 129.7, 129.3, 129.1, 128.9, 128.5,
128.3, 126.8, 125.8, 125.1, 122.6, 106.6, 30.6, 27.1, 26.9, 26.6,
22.3, 21.2, 13.8; MS (EI, m/z): 554 (M+); IR (ATR, neat, cm−1):
1571, 1473, 1437, 1066, 823, 738, 690; HRMS (EI): m/z calcd
for C29H30O80Se2 (M+): 554.0627; Found: 554.0634.
2-Phenyl-3-(phenylselenyl)-4-(2-(phenylselenyl)ethyl)-5-(thiophen-
2-yl)furan (5f). 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 (126 mg, 0.5 mmol, 1.0
equiv), and phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0
equiv) in THF (4 mL) afforded 5f (139 mg, 49%). Pale solid,
2-Butyl-5-isobutyl-3-(phenylselenyl)-4-(2-(phenylselenyl)ethyl)
furan (5j). 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), 2i (103 mg, 0.5 mmol, 1.0
equiv), and phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0
1
mp 96–98 °C (petroleum ether–ethyl acetate = 50 : 1). H NMR
(400 MHz, CDCl3) δ 8.06 (d, J = 7.6 Hz, 2H), 7.43–7.45 (m,
2H), 7.32–7.36 (m, 2H), 7.10–7.28 (m, 11H), 6.96–6.98 (m,
1H), 3.02–3.06 (m, 2H), 2.87–2.91 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 154.2, 145.0, 133.3, 132.6, 132.1, 129.9,
129.6, 129.3, 128.9, 128.5, 128.3, 127.6, 126.9, 126.4, 126.1,
124.9, 124.7, 123.4, 106.7, 26.8, 26.2; MS (EI, m/z): 566 (M+);
IR (ATR, neat, cm−1): 1573, 1476, 1438, 1020, 766, 737, 684;
HRMS (EI): m/z calcd for C28H22OSSe2 (M+): 565.9722;
Found: 565.9721.
1
equiv) in THF (4 mL) afforded 5j (132 mg, 51%). Liquid. H
NMR (400 MHz, CDCl3) δ 7.37–7.39 (m, 2H), 7.11–7.19 (m,
8H), 2.86–2.89 (m, 2H), 2.70 (t, J = 7.6 Hz, 2H), 2.61–2.66 (m,
2H), 2.37 (d, J = 6.8 Hz, 2H), 1.89–1.98 (m, 1H), 1.52–1.59 (m,
2H), 1.21–1.33 (m, 2H), 0.84–0.88 (m, 9H); 13C NMR
(100 MHz, CDCl3) δ 159.3, 150.4, 133.3, 132.2, 130.3, 129.0,
128.9, 128.2, 126.5, 125.6, 121.7, 103.7, 35.5, 30.7, 28.2, 27.5,
26.7, 25.9, 22.3, 22.2, 13.7; MS (EI, m/z): 520 (M+); IR (ATR,
neat, cm−1): 1578, 1476, 1437, 1065, 1021, 732, 689; HRMS
(EI): m/z calcd for C26H32OSe2 (M+): 520.0784; Found:
520.0783.
2-Phenyl-3-(phenylselenyl)-4-(2-(phenylselenyl)ethyl)-5-propyl-
furan (5g). 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 phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0
equiv) in THF (4 mL) afforded 5g (171 mg, 65%). Pale solid,
1
mp 36–38 °C (petroleum ether–ethyl acetate = 50 : 1). H NMR
Transformation of 4a into 5a. To a dried two-necked round-
bottom flask (25 mL) were added 4a (116 mg, 0.2 mmol, 1.0
equiv) and THF (4 mL) under a nitrogen atmosphere at room
temperature. Then phenylselenyl bromide 3 (47 mg, 0.2 mmol,
1.0 equiv) was added and the reaction mixture was stirred for
additional 0.5 h. When the reaction was complete, the reaction
mixture was transferred to a pear-shaped flask. Evaporation and
column chromatography on silica gel (eluent: petroleum ether–
CH2Cl2 = 15 : 1) afforded 5a (73 mg, 63%).
(400 MHz, CDCl3) δ 7.96 (d, J = 8.0 Hz, 2H), 7.39–7.41 (m,
2H), 7.33 (t, J = 7.2 Hz, 2H), 7.11–7.27 (m, 9H), 2.91 (t, J = 7.2
Hz, 2H), 2.74 (t, J = 8.4 Hz, 2H), 2.58 (t, J = 7.2 Hz, 2H),
1.67–1.75 (m, 2H), 0.75 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 154.0, 152.2, 132.7, 132.3, 130.6, 130.2,
129.3, 128.9, 128.3, 128.2, 127.8, 126.6, 126.2, 125.9, 123.6,
104.3, 28.6, 27.6, 25.8, 21.8, 13.8; MS (EI, m/z): 526 (M+); IR
(ATR, neat, cm−1): 1575, 1476, 1436, 1069, 766, 737, 687;
HRMS (EI): m/z calcd for C27H26OSe2 (M+): 526.0314; Found:
526.0324.
General procedure for the synthesis of halogen-substituted
furans (6a–c). To a dried two-necked round-bottom flask
(25 mL) were added 4a (172 mg, 0.3 mmol, 1.0 equiv) and THF
2-Phenyl-3-(phenylselenyl)-4-(2-(phenylselenyl)ethyl)-5-propyl-
furan (5h). 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 (113 mg, 0.5 mmol, 1.0
equiv), and phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0
equiv) in THF (4 mL) afforded 5h (172 mg, 64%). Pale solid,
(4 mL) under
a nitrogen atmosphere. Then electrophile
(0.45 mmol, 1.5 equiv) was added and the reaction mixture was
stirred at room temperature. When the reaction was complete as
monitored by TLC, the reaction mixture was transferred to a
pear-shaped flask. Evaporation and column chromatography on
silica gel (eluent: petroleum ether–CH2Cl2 = 15 : 1) afforded
final product 6 and 5a.
1
mp 82–84 °C (petroleum ether–ethyl acetate = 50 : 1). H NMR
(400 MHz, CDCl3) δ 7.98 (d, J = 7.6 Hz, 2H), 7.43–7.45 (m,
2H), 7.33 (t, J = 8.0 Hz, 2H), 7.11–7.26 (m, 9H), 2.84–2.91 (m,
4H), 1.34 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 157.4, 152.8,
133.1, 132.7, 130.6, 129.8, 129.3, 128.9, 128.3, 128.2, 127.8,
126.8, 126.1, 125.9, 122.0, 105.6, 34.3, 29.7, 27.9, 26.7; MS
(EI, m/z): 540 (M+); IR (ATR, neat, cm−1): 1573, 1478, 1440,
1110, 802, 737, 685; HRMS (EI): m/z calcd for C28H28OSe2
(M+): 540.0471; Found: 540.0477.
2-Butyl-3-(phenylselenyl)-4-(2-(phenylselenyl)ethyl)-5-p-tolylfuran
(5i). 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), 2h (120 mg, 0.5 mmol, 1.0 equiv), and
phenylselenyl bromide 3 (236 mg, 1.0 mmol, 2.0 equiv) in THF
3-Iodo-2-phenyl-4-(2-(phenylselenyl)ethyl)-5-p-tolylfuran (6a).
The reaction of 4a (172 mg, 0.3 mmol, 1.0 equiv) and NIS
(101 mg, 0.45 mmol, 1.5 equiv) in THF (4 mL) afforded 6a
(99 mg, 61%) and 5a (5 mg, 3%). 6a: Pale solid, mp 96–98 °C
(petroleum ether–CH2Cl2 = 15 : 1). 1H NMR (400 MHz, CDCl3)
δ 8.01 (d, J = 7.6 Hz, 2H), 7.58 (s, 2H), 7.28–7.43 (m, 8H), 7.12
(d, J = 8.0 Hz, 2H), 3.04–3.09 (m, 4H), 2.36 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 150.0, 148.9, 137.7, 133.7, 130.2, 129.4,
129.3, 129.0, 128.3, 128.1, 127.6, 127.2, 126.3, 125.5, 123.9,
70.4, 28.6, 26.1, 21.3; MS (EI, m/z): 544 (M+); IR (ATR, neat,
This journal is © The Royal Society of Chemistry 2012
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cm−1): 1501, 1477, 1440, 1109, 763, 732, 690; HRMS (EI): m/z
calcd for C25H21IOSe (M+): 543.9802; Found: 543.9800.
3-Bromo-2-phenyl-4-(2-(phenylselenyl)ethyl)-5-p-tolylfuran (6b).
The reaction of 4a (172 mg, 0.3 mmol, 1.0 equiv) and NBS
(80 mg, 0.45 mmol, 1.5 equiv) in THF (4 mL) afforded 6b
(94 mg, 63%) and 5a (9 mg, 5%). 6b: Pale solid, mp 72–74 °C
(petroleum ether–CH2Cl2 = 15 : 1). 1H NMR (400 MHz, CDCl3)
δ 7.99 (d, J = 7.2 Hz, 2H), 7.55–7.57 (m, 2H), 7.39–7.43 (m,
4H), 7.26–7.32 (m, 4H), 7.13 (d, J = 8.0 Hz, 2H), 3.02–3.13 (m,
4H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 148.4, 147.0,
137.8, 133.5, 129.7, 129.5, 129.4, 129.0, 128.4, 127.8, 127.6,
127.2, 125.5, 125.4, 121.7, 101.1, 26.5, 25.9, 21.3; MS (EI,
m/z): 496 (M+); IR (ATR, neat, cm−1): 1504, 1480, 1441, 1107,
817, 735, 689; HRMS (EI): m/z calcd for C25H21BrOSe (M+):
495.9941; Found: 495.9940.
(d, J = 29.2 Hz), 39.0 (d, J = 24.4 Hz), 21.7, 20.4 (d, J = 2.7
Hz); 19F NMR (376 MHz, CDCl3) δ −143.0; MS (EI, m/z): 436
(M+); IR (ATR, neat, cm−1): 2227, 1690, 1605, 1256, 754, 738,
689; HRMS (EI): m/z calcd for C25H21FOSe (M+): 436.0742;
Found: 436.0747.
2-(2-(Butylselenyl)ethyl)-2-fluoro-4-phenyl-1-p-tolylbut-3-yn-1-one
(8b). 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 7b
(188 mg, 0.6 mmol, 1.2 equiv) in THF (4 mL) afforded 8b
(87 mg, 42%). Liquid. 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J
= 7.6 Hz, 2H), 7.42 (d, J = 6.8 Hz, 2H), 7.29–7.36 (m, 5H),
2.88–2.93 (m, 1H), 2.60–2.79 (m, 5H), 2.42 (s, 3H), 1.63–1.70
(m, 2H), 1.38–1.44 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 191.6 (d, J = 27.0 Hz), 144.7, 131.8 (d, J
= 3.4 Hz), 130.5 (d, J = 3.3 Hz), 130.4 (d, J = 5.0 Hz), 129.5,
129.1, 128.4, 121.0 (d, J = 4.2 Hz), 93.6 (d, J = 187.1 Hz), 92.3
(d, J = 9.8 Hz), 84.0 (d, J = 28.9 Hz), 39.5 (d, J = 23.7 Hz),
32.5, 23.8, 23.0, 21.7, 16.3 (d, J = 2.8 Hz), 13.5; 19F NMR
(376 MHz, CDCl3) δ −143.2; MS (EI, m/z): 416 (M+); IR (ATR,
neat, cm−1): 2228, 1690, 1606, 1257, 1021, 754, 689; HRMS
(EI): m/z calcd for C23H25FOSe (M+): 416.1055; Found:
416.1049.
2-Fluoro-1-(4-methoxyphenyl)-4-phenyl-2-(2-(phenylselenyl)-
ethyl)but-3-yn-1-one (8c). 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), 2b (138 mg, 0.5 mmol,
1.0 equiv), and 7b (188 mg, 0.6 mmol, 1.2 equiv) in THF
(4 mL) afforded 8c (117 mg, 52%). Liquid. 1H NMR (400 MHz,
CDCl3) δ 8.21 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 7.6 Hz, 2H),
7.39 (d, J = 7.6 Hz, 2H), 7.23–7.34 (m, 6H), 6.92 (d, J = 8.8
Hz, 2H), 3.85 (s, 3H), 3.23–3.30 (m, 1H), 3.09–3.17 (m, 1H),
2.63–2.74 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 190.1 (d, J
= 26.7 Hz), 164.0, 132.7 (d, J = 4.7 Hz), 132.2, 131.8 (d, J =
2.0 Hz), 129.6, 129.5, 129.1, 128.4, 126.8, 125.7 (d, J = 3.2
Hz), 120.9 (d, J = 3.4 Hz), 113.6, 93.6 (d, J = 182.3 Hz), 92.4
(d, J = 10.2 Hz), 84.0 (d, J = 29.0 Hz), 55.4, 39.9 (d, J = 24.3
Hz), 20.4 (d, J = 2.2 Hz); 19F NMR (376 MHz, CDCl3) δ
−142.4; MS (EI, m/z): 452 (M+); IR (ATR, neat, cm−1): 2228,
1682, 1597, 1253, 1171, 736, 689; HRMS (EI): m/z calcd for
C25H21FO2Se (M+): 452.0691; Found: 452.0686.
2-Fluoro-1-(4-fluorophenyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)-
but-3-yn-1-one (8d). 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 (132 mg, 0.5 mmol,
1.0 equiv), and 7b (188 mg, 0.6 mmol, 1.2 equiv) in THF
(4 mL) afforded 8d (108 mg, 49%). Liquid. 1H NMR
(400 MHz, CDCl3) δ 8.24–8.27 (m, 2H), 7.51–7.53 (m, 2H),
7.23–7.40 (m, 8H), 7.11–7.15 (m, 2H), 3.22–3.29 (m, 1H),
3.09–3.16 (m, 1H), 2.64–2.74 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 190.2 (d, J = 27.0 Hz), 166.0 (d, J = 255.7 Hz), 133.1
(q, J = 8.8 Hz), 132.3, 131.8 (d, J = 2.3 Hz), 129.7, 129.6, 129.3
(t, J = 3.5 Hz), 129.2, 128.4, 127.0, 120.7 (d, J = 4.0 Hz), 115.6
(d, J = 20.7 Hz), 93.5 (d, J = 182.6 Hz), 92.9 (d, J = 9.9 Hz),
83.5 (d, J = 29.0 Hz), 38.8 (d, J = 24.3 Hz), 20.4 (d, J = 2.7
Hz); 19F NMR (376 MHz, CDCl3) δ −103.3, −142.8; MS (EI,
m/z): 440 (M+); IR (ATR, neat, cm−1): 2228, 1694, 1596, 1238,
755, 735, 688; HRMS (EI): m/z calcd for C24H18F2OSe (M+):
440.0491; Found: 440.0499.
3-Chloro-2-phenyl-4-(2-(phenylselenyl)ethyl)-5-p-tolylfuran (6c).
The reaction of 4a (172 mg, 0.3 mmol, 1.0 equiv) and CuCl2
(61 mg, 0.45 mmol, 1.5 equiv) in THF (4 mL) afforded 6c
(87 mg, 64%) and 5a (18 mg, 10%). 6c: Pale solid, mp
104–106 °C (petroleum ether–CH2Cl2 = 15 : 1). 1H NMR
(400 MHz, CDCl3) δ 8.08 (d, J = 7.6 Hz, 2H), 7.63 (d, J = 8.0
Hz, 2H), 7.37 (t, J = 7.6 Hz, 2H), 7.26–7.36 (m, 5H), 7.14–7.21
(m, 3H), 3.55 (t, J = 8.0 Hz, 2H), 3.15 (t, J = 8.0 Hz, 2H), 2.39
(s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.6, 150.0, 138.0,
132.1, 10.2, 129.6, 129.4, 128.5, 128.4, 127.7, 126.5, 126.2,
125.7, 121.8, 106.7, 42.9, 29.2, 21.3; MS (EI, m/z): 452 (M+);
IR (ATR, neat, cm−1): 1507, 1477, 1440, 1168, 817, 729, 683;
HRMS (EI): m/z calcd for C25H21ClOSe (M+): 452.0446;
Found: 452.0445.
General procedure for the synthesis of fluoro-substituted 2-
alkynyl ketones (8a–j). To a dried two-necked round-bottom
flask (25 mL) were added diselenide (0.6 mmol, 1.2 equiv) and
THF (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 1–2 min,
to the resulting reaction mixture was added a solution of 1-(1-
alkynyl)cyclopropyl ketone 2 (0.5 mmol, 1.0 equiv) in 2 mL of
THF at room temperature. The resulting reaction mixture was
stirred for additional 15 min before N-fluorodi(benzenesulfonyl)
amine 7b (0.6 mmol, 1.2 equiv) was added. After being stirred
for 11 h, the reaction was quenched with H2O and extracted with
diethyl ether (3 × 20 mL). The combined organic phase was
washed with brine and dried over Na2SO4. Filtration, evapor-
ation, and column chromatography on silica gel (eluent: pet-
roleum ether–ethyl acetate = 50 : 1) afforded the final product 8.
2-Fluoro-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolylbut-3-yn-1-
one (8a). 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 7b (188 mg, 0.6 mmol, 1.2 equiv) in THF (4 mL)
afforded 8a (124 mg, 57%). Liquid. 1H NMR (400 MHz,
CDCl3) δ 8.11 (d, J = 7.2 Hz, 2H), 7.51 (d, J = 6.4 Hz, 2H),
7.40 (d, J = 7.2 Hz, 2H), 7.23–7.36 (m, 8H), 3.22–3.29 (m, 1H),
3.08–3.16 (m, 1H), 2.62–2.77 (m, 2H), 2.41 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 191.4 (d, J = 26.3 Hz), 144.8, 132.2, 131.8
(d, J = 2.8 Hz), 130.4, 130.3, 129.6, 129.5, 129.1, 129.0, 128.4,
126.9, 120.9, 93.6 (d, J = 183.3 Hz), 92.5 (d, J = 10.1 Hz), 83.9
3712 | Org. Biomol. Chem., 2012, 10, 3705–3714
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2-Fluoro-1-(2-furanyl)-4-phenyl-2-(2-(phenylselenyl)ethyl)but-3-
yn-1-one (8e). 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), 2d (118 mg, 0.5 mmol, 1.0
equiv), and 7b (188 mg, 0.6 mmol, 1.2 equiv) in THF (4 mL)
afforded 8e (110 mg, 53%). Liquid. 1H NMR (400 MHz,
CDCl3) δ 7.68 (s, 1H), 7.49–7.68 (m, 3H), 7.41 (d, J = 6.8 Hz,
2H), 7.22–7.37 (m, 6H), 6.56–6.57 (m, 1H), 3.19–3.26 (m, 1H),
3.06–3.13 (m, 1H), 2.61–2.72 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 180.4 (d, J = 27.5 Hz), 148.4 (d, J = 2.8 Hz), 148.0,
132.3, 131.8 (d, J = 3.7 Hz), 129.5, 129.4, 129.1, 128.3, 126.9,
122.4 (d, J = 9.5 Hz), 120.7 (d, J = 3.5 Hz), 112.4, 93.4 (d, J =
183.5 Hz), 91.1 (d, J = 9.5 Hz), 83.2 (d, J = 29.2 Hz), 38.9 (d, J
= 23.9 Hz), 20.1 (d, J = 2.4 Hz); 19F NMR (376 MHz, CDCl3)
δ −146.3; MS (EI, m/z): 412 (M+); IR (ATR, neat, cm−1): 2230,
1678, 1459, 1023, 757, 735, 689; HRMS (EI): m/z calcd for
C22H17FO2Se (M+): 412.0378; Found: 412.0374.
2-Fluoro-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-(thiophen-2-yl)-
but-3-yn-1-one (8f). 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 (126 mg, 0.5 mmol,
1.0 equiv), and 7b (188 mg, 0.6 mmol, 1.2 equiv) in THF
(4 mL) afforded 8f (107 mg, 50%). Liquid. 1H NMR (400 MHz,
CDCl3) δ 8.12 (s, 1H), 7.72 (d, J = 4.8 Hz, 1H), 7.50 (d, J = 7.6
Hz, 2H), 7.42 (d, J = 7.6 Hz, 2H), 7.24–7.37 (m, 6H), 7.16 (t, J
= 4.4 Hz, 1H), 3.21–3.28 (m, 1H), 3.08–3.15 (m, 1H),
2.63–2.72 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 180.2 (d, J
= 28.5 Hz), 138.8 (d, J = 4.1 Hz), 135.6, 135.5, 132.3, 131.9 (d,
J = 2.1 Hz), 129.5, 129.4, 129.2, 128.4, 127.0, 120.8 (d, J = 2.5
Hz), 94.0 (d, J = 183.3 Hz), 91.6 (d, J = 9.4 Hz), 83.5 (d, J =
28.3 Hz), 39.2 (d, J = 24.0 Hz), 20.2 (d, J = 2.0 Hz); 19F NMR
(376 MHz, CDCl3) δ −142.9; MS (EI, m/z): 428 (M+); IR (ATR,
neat, cm−1): 2229, 1668, 1409, 1253, 755, 727, 688; HRMS
(EI): m/z calcd for C22H17FOSSe (M+): 428.0149; Found:
428.0148.
3-Fluoro-1-phenyl-3-(2-(phenylselenyl)ethyl)hept-1-yn-4-one (8g).
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 7b
(188 mg, 0.6 mmol, 1.2 equiv) in THF (4 mL) afforded 8g
(102 mg, 53%). Liquid. 1H NMR (400 MHz, CDCl3) δ
7.49–7.51 (m, 2H), 7.43 (d, J = 8.0 Hz, 2H), 7.23–7.37 (m, 6H),
3.13–3.20 (m, 1H), 2.98–3.05 (m, 1H), 2.66–2.79 (m, 2H),
2.39–2.55 (m, 2H), 1.62–1.72 (m, 2H), 0.95 (t, J = 5.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 203.6 (d, J = 28.2 Hz), 132.4,
131.9 (d, J = 3.1 Hz), 129.5, 129.4, 129.2, 128.4, 127.0, 120.8
(d, J = 3.6 Hz), 94.4 (d, J = 182.8 Hz), 90.3 (d, J = 9.8 Hz),
82.8 (d, J = 29.5 Hz), 38.8, 38.2 (d, J = 23.5 Hz), 20.3 (d, J =
2.1 Hz), 16.7 (d, J = 1.5 Hz), 13.5; 19F NMR (376 MHz,
CDCl3) δ −150.2; MS (EI, m/z): 388 (M+); IR (ATR, neat,
cm−1): 2229, 1731, 1401, 1024, 755, 735, 689; HRMS (EI): m/z
calcd for C21H21FOSe (M+): 388.0742; Found: 388.0746.
4-Fluoro-2,2-dimethyl-6-phenyl-4-(2-(phenylselenyl)ethyl)hex-5-
yn-3-one (8h). 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 (113 mg, 0.5 mmol, 1.0
equiv), and 7b (188 mg, 0.6 mmol, 1.2 equiv) in THF (4 mL)
afforded 8h (86 mg, 43%). Liquid. 1H NMR (400 MHz, CDCl3)
δ 7.49 (d, J = 6.8 Hz, 2H), 7.40 (d, J = 7.6 Hz, 2H), 7.24–7.35
(m, 6H), 3.12–3.19 (m, 1H), 2.95–3.02 (m, 1H), 2.48–2.58 (m,
2H), 1.32 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 207.9 (d, J =
25.8 Hz), 132.2, 131.7 (d, J = 2.4 Hz), 129.6, 129.4, 129.1,
128.3, 126.9, 121.0 (d, J = 4.2 Hz), 96.0 (d, J = 187.3 Hz), 90.6
(d, J = 10.0 Hz), 83.5 (d, J = 28.0 Hz), 40.9 (d, J = 3.8 Hz),
39.8 (d, J = 23.9 Hz), 26.6 (d, J = 4.0 Hz), 20.3; 19F NMR
(376 MHz, CDCl3) δ −149.5; MS (EI, m/z): 402 (M+); IR (ATR,
neat, cm−1): 2228, 1690, 1605, 1257, 801, 754, 689; HRMS
(EI): m/z calcd for C22H23FOSe (M+): 402.0898; Found:
402.0891.
2-Fluoro-2-(2-(phenylselenyl)ethyl)-1-p-tolyloct-3-yn-1-one (8i).
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), 2h (120 mg, 0.5 mmol, 1.0 equiv), and 7b
(188 mg, 0.6 mmol, 1.2 equiv) in THF (4 mL) afforded 8i
(89 mg, 43%). Liquid. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J
= 8.0 Hz, 2H), 7.48 (d, J = 8.0 Hz, 2H), 7.22–7.25 (m, 5H),
3.14–3.21 (m, 1H), 3.01–3.08 (m, 1H), 2.50–2.61 (m, 2H), 2.40
(s, 3H), 2.22–2.27 (m, 2H), 1.43–1.50 (m, 2H), 1.31–1.38 (m,
2H), 0.86 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
191.9 (d, J = 27.4 Hz), 144.5, 132.2, 130.5 (d, J = 2.9 Hz),
130.4 (d, J = 4.1 Hz), 129.8, 129.1, 128.9, 126.8, 94.6 (d, J =
10.0 Hz), 93.5 (d, J = 181.8 Hz), 75.8 (d, J = 28.8 Hz), 39.0 (d,
J = 25.3 Hz), 29.9 (d, J = 1.4 Hz), 21.8, 21.7, 20.5(d, J = 3.6
Hz), 18.5 (d, J = 3.4 Hz), 13.4; 19F NMR (376 MHz, CDCl3) δ
−142.3; MS (EI, m/z): 416 (M+); IR (ATR, neat, cm−1): 2235,
1690, 1606, 1260, 735, 690; HRMS (EI): m/z calcd for
C23H25FOSe (M+): 416.1055; Found: 416.1057.
5-Fluoro-2-methyl-5-(2-(phenylselenyl)ethyl)undec-6-yn-4-one (8j).
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), 2i (103 mg, 0.5 mmol, 1.0 equiv), and 7b
(188 mg, 0.6 mmol, 1.2 equiv) in THF (4 mL) afforded 8j
(63 mg, 33%). Liquid. 1H NMR (400 MHz, CDCl3) δ 7.47–7.49
(m, 2H), 7.24–7.29 (m, 3H), 3.05–3.12 (m, 1H), 2.90–2.98 (m,
1H), 2.47–2.62 (m, 2H), 2.15–2.38 (m, 5H), 1.35–1.53 (m, 4H),
0.89–0.95 (m, 9H); 13C NMR (100 MHz, CDCl3) δ 203.5 (d, J
= 28.2 Hz), 132.3, 129.6, 129.1, 127.0, 94.4 (d, J = 181.6 Hz),
92.3 (d, J = 10.3 Hz), 74.5 (d, J = 29.0 Hz), 45.6, 38.1 (d, J =
24.2 Hz), 30.0 (d, J = 1.9 Hz), 23.8, 22.4, 22.3, 21.9, 20.3 (d, J
= 3.1 Hz), 18.4 (d, J = 3.6 Hz), 13.5; 19F NMR (376 MHz,
CDCl3) δ −149.4; MS (EI, m/z): 382 (M+); IR (ATR, neat,
cm−1): 2237, 1731, 1464, 1364, 735, 690; HRMS (EI): m/z
calcd for C20H27FOSe (M+): 382.1211; Found: 382.1205.
General procedure for the synthesis of substituted 2-alkynyl
ketones (8k–m). To a dried two-necked round-bottom flask
(25 mL) were added diselenide (0.6 mmol, 1.2 equiv) and THF
(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 gener-
ate lithium selenolate 1 in situ. After 1–2 min, to the resulting
reaction mixture was added a solution of 1-(1-alkynyl)cyclopro-
pyl ketone 2 (0.5 mmol, 1.0 equiv) in 2 mL of THF at room
temperature. The resulting reaction mixture was stirred for
additional 15 min before electrophile (1.0 mmol, 2.0 equiv) was
added. After being stirred for 24 h, the reaction was quenched
with H2O and extracted with diethyl ether (3 × 20 mL). The
combined organic phase was washed with brine and dried over
This journal is © The Royal Society of Chemistry 2012
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Na2SO4. Filtration, evaporation, and column chromatography on
silica gel (eluent: petroleum ether–ethyl acetate = 50 : 1) afforded
the final product 8.
(m, 1H); 13C NMR (100 MHz, CDCl3) δ 199.3, 143.1, 136.2,
134.3, 131.9, 131.2, 130.7, 130.1, 129.6, 129.0, 128.5, 128.3,
128.2, 127.9, 126.9, 126.6, 122.9, 90.7, 89.2, 53.9, 45.5, 40.2,
22.6, 21.6; MS (EI, m/z): 508 (M+); IR (ATR, neat, cm−1): 1673,
1604, 1439, 1180, 754, 734, 692; HRMS (EI): m/z calcd for
C32H28OSe (M+): 508.1305; Found: 508.1306.
2-Chloro-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolylbut-3-yn-1-
one (8k). 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 NCS (133 mg, 1.0 mmol, 2.0 equiv) in THF (4 mL)
afforded 8k (142 mg, 63%). Liquid. 1H NMR (400 MHz,
CDCl3) δ 8.29 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 7.6 Hz, 2H),
7.24–7.37 (m, 10H), 3.26–3.31 (m, 2H), 2.67–2.86 (m, 2H),
2.42 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 188.3, 144.5,
132.1, 131.7, 130.9, 130.1, 129.8, 129.5, 129.1, 128.7, 128.4,
126.8, 121.2, 91.8, 86.1, 64.5, 42.1, 22.0, 21.7; MS (EI, m/z):
452 (M+); IR (ATR, neat, cm−1): 2226, 16 878, 12 394, 1183,
755, 734, 688; HRMS (EI): m/z calcd for C25H21ClOSe (M+):
452.0446; Found: 452.0447.
2-(Phenylethynyl)-2-(2-(phenylselenyl)ethyl)-1-p-tolylpent-4-en-1-
one (c). 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
allyl bromide (121 mg, 1.0 mmol, 2.0 equiv) in THF (4 mL)
afforded 8l (158 mg, 69%). Liquid. 1H NMR (400 MHz, CDCl3)
δ 8.16 (d, J = 8.4 Hz, 2H), 7.44–7.45 (m, 2H), 7.35–7.37 (m,
2H), 7.20–7.31 (m, 8H), 5.79–5.90 (m, 1H), 5.06–5.11 (m, 2H),
3.01–3.06 (m, 2H), 2.81–2.97 (m, 1H), 2.54–2.66 (m, 2H), 2.39
(s, 3H), 2.16–2.24 (m, 1H); 13C NMR (100 MHz, CDCl3) δ
197.8, 143.4, 133.5, 132.8, 131.9, 131.4, 130.1, 129.8, 129.0,
128.7, 128.3, 126.5, 122.9, 119.0, 90.4, 88.0, 51.7, 43.1, 38.9,
22.3, 21.6; MS (EI, m/z): 458 (M+); IR (ATR, neat, cm−1): 1675,
1604, 1438, 1181, 7548, 734, 689; HRMS (EI): m/z calcd for
C28H26OSe (M+): 458.1149; Found: 458.1154.
Acknowledgements
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
Province and the Fundamental Research Funds for the Central
Universities for financial support.
Notes and references
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2-Benzyl-4-phenyl-2-(2-(phenylselenyl)ethyl)-1-p-tolylbut-3-yn-1-
one (8m). 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 benzyl bromide (171 mg, 1.0 mmol, 2.0 equiv) in
THF (4 mL) afforded 8m (163 mg, 64%). Liquid. 1H NMR
(400 MHz, CDCl3) δ 7.89 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 6.8
Hz, 2H), 7.27–7.30 (m, 5H), 7.20–7.22 (m, 8H), 7.12 (d, J = 8.4
Hz, 2H), 3.41 (d, J = 13.2 Hz, 1H), 3.09 (d, J = 13.2 Hz, 1H),
2.97–3.06 (m, 2H), 2.60–2.67 (m, 1H), 2.35 (s, 3H), 2.13–2.60
7 P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, 1st
edn, 2004.
3714 | Org. Biomol. Chem., 2012, 10, 3705–3714
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