Silver-Promoted Oxidative Ring Opening/Alkynylation of Cyclopropanols: Facile Synthesis of 4-Yn-1-ones

Article abstract of DOI:10.1055/s-0035-1560374

A new silver-promoted oxidative ring opening/alkynylation of cyclopropanols with ethynylbenziodoxolones (EBX) is described. This method enables the formation of alkylated alkynes via a sequence of ring opening and alkynylation. Control experiments support

Full text of DOI:10.1055/s-0035-1560374

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, 223–230
paper
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C.-Y. Wang et al.
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Synthesis
Silver-Promoted Oxidative Ring Opening/Alkynylation of Cyclo-
propanols: Facile Synthesis of 4-Yn-1-ones
Cheng-Yong Wang
O
R2
R1 OH
Ren-Jie Song
Ye-Xiang Xie*
Jin-Heng Li*
AgNO3, K2S2O8
R1
+
I
R3
CH2Cl2, 30 °C, 16 h
R2
O
R3
O
22 examples, up to 81% yield
State Key Laboratory of Chemo/Biosensing and Chemometrics,
College of Chemistry and Chemical Engineering, Hunan University,
Changsha 410082, P. R. of China
jhli@hnu.edu.cn
xieyexiang520@126.com
Received: 19.09.2015
Accepted after revision: 16.10.2015
Published online: 17.11.2015
Herein, we report a new oxidative ring opening/alky-
nylation of cyclopropanols with ethynylbenziodoxolones
for the synthesis of alkylated alkynes using a combination
of silver(I) nitrate and potassium persulfate as the catalytic
system (Scheme 1);6 this method allows selective radical
cleavage of the C–C bond in a wide range of cyclopropanols7
by various terminal alkynes, including aryl- and alkyl-
substituted alkynes, and represents a mild and practical
route for the assembly of alkylated alkynes.8
DOI: 10.1055/s-0035-1560374; Art ID: ss-2015-h0552-op
Abstract A new silver-promoted oxidative ring opening/alkynylation
of cyclopropanols with ethynylbenziodoxolones (EBX) is described. This
method enables the formation of alkylated alkynes via a sequence of
ring opening and alkynylation. Control experiments support a radical
mechanism in this silver-promoted method.
Key words silver, ring opening, alkynylation, cyclopropanol, alkyne
O
R2
R1 OH
AgNO3, K2S2O8
Alkynes are common and versatile building blocks with
wide application in synthesis.1 Therefore, the development
of new efficient methods for their synthesis continues to
receive the attention of synthetic chemists.1–3 Although the
Sonogashira cross-coupling reaction,2,3 which starts from
aryl or alkenyl halides and terminal alkynes, is well-estab-
lished for the incorporation of alkyne moieties into organic
molecules, the synthesis of aliphatic alkynes from alkyl
electrophiles remains a formidable challenge.3 For example,
the Fu group has extended the Sonogashira cross-coupling
reaction to the use of primary alkyl halides as the electro-
phile.3a The Hu group has also reported an efficient nickel-
catalyzed Sonogashira cross-coupling of alkyl halides for
the construction of alkylated alkynes.3b,c However, the ma-
jority of these transformations require a copper cocatalyst,
base, and a ligand to improve the yield. To overcome these
disadvantages, the development of new electrophilic alky-
nylating reagents, particularly with special reaction charac-
teristics for the formation of the C(sp)–C(sp3) bond, have
gained wide interest in the past decade.4,5 Typically, attrac-
tive electrophilic alkynylating reagents include ethynylben-
ziodoxolones (EBX),4 which are appealing alkynylating re-
agents for the construction of diverse ynone molecules by
C-alkynylation with aldehydes.
R1
+
I
R3
CH2Cl2, 30 °C, 16 h
R2
O
R3
O
1
2
3
Scheme 1 The ring opening and alkynylation reaction
We began our study by investigating the reaction be-
tween 1-(4-methoxyphenyl)cyclopropan-1-ol (1a) and 1-
(phenylethynyl)-1,2-benziodoxol-3(1H)-one (2a, Ph-EBX)
to optimize the reaction conditions (Table 1). The results
demonstrated that the ring opening/alkynylation reaction
occurred in the presence of silver(I) nitrate alone and it en-
abled the formation of the desired product 3aa in 33% yield
(entry 1). Gratifyingly, the addition of oxidants, such as po-
tassium persulfate, sodium persulfate, ammonium persul-
fate, and dibenzoyl peroxide (BPO), improved the yield of
3aa (entries 2–5), and potassium persulfate showed the
most reactivity. Identical results to those obtained using
two equivalents of potassium persulfate were obtained
when using three equivalents of potassium persulfate (cf.
entries 2 and 6). A number of other silver catalysts (entries
7–10), including silver(I) acetate, tetrafluoroborate, triflate,
and carbonate, also had high catalytic activity in this reac-
tion, but they were less effective than silver(I) nitrate. We
found that the amount of silver(I) nitrate used also affected
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the reaction result: using 30 mol% of silver(I) nitrate did not
improve the yield compared to the use of 20 mol% of sil-
ver(I) nitrate (entry 11), but using 10 mol% of silver(I) ni-
trate reduced the yield to 60% (entry 12). Surprisingly, the
reaction took place in the absence of a silver salt, albeit
with lower yield (45%) (entry 13). A similar yield (49%) of
3aa was isolated when three equivalents of potassium per-
sulfate were used in the absence of silver(I) nitrate (entry
14). The results suggest that silver(I) nitrate may play two
roles, both as a accelerator and an oxidant. The use of other
solvents, dichloromethane–water, 1,2-dichloroethane, ace-
tonitrile, tetrahydrofuran, and N,N-dimethylformamide,
was also examined, but the yields of 3aa were lower than
with dichloromethane (entries 15–19). Screening the ef-
fects of the reaction temperature revealed that a reaction
temperature of 30 °C gave optimal results (entries 2, 20,
and 21).
With the optimal conditions in hand, we set out to in-
vestigate the scope and limitations of this oxidative ring
opening/alkynylation protocol with regard to cyclopropa-
nols 1 and 1-(substituted ethynyl)-1,2-benziodoxol-3(1H)-
one 2 (Tables 2 and 3). As shown in Table 2, a variety of 1-
(arylethynyl)-1,2-benziodoxol-3(1H)-ones 2b–h and 1-
(3,3-dimethylbut-1-ynyl)-1,2-benziodoxol-3(1H)-one (2i)
were viable for the construction of the corresponding
alkynes 3ab–ai in moderate to good yields, however, 1-
Table 1 Optimization of the Reaction Conditionsa
O
Ph
I
O
[Ag], [O]
30 °C
OH
O
+
Ph
MeO
MeO
1a
2a
3aa
Entry
[Ag] (mol%)
[O] (equiv)
Solvent
Yieldb (%)
1
2
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgOAc (20)
AgBF4 (20)
AgOTf (20)
Ag2CO3 (20)
AgNO3 (30)
AgNO3 (10)
–
−
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
33
81
73
43
65
80
53
20
52
47
78
60
45
49
50
70
19
35
61
67
62
K2S2O8 (2)
Na2S2O8 (2)
(NH2)2S2O8 (2)
BPO (2)
3
4
5
6
K2S2O8 (3)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (3)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
K2S2O8 (2)
7
8
9
10
11
12
13
14
15c
16
17
18
19
20d
21e
–
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
AgNO3 (20)
CH2Cl2/H2O
DCE
[(trimethylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one
(2j;
TMS-EBX) did not give 3aj. Using 1-(phenylethynyl)-1,2-
benziodoxol-3(1H)-ones 2b–h, several substituents, such as
Me, Br, CN, Ac, and Ph groups, on the phenyl ring attached
to the acetylene were well tolerated giving products 3ab–
ah. For example, 1-(p-tolylethynyl)-1,2-benziodoxol-3(1H)-
one (2b) gave 3ab in 70% yield. 1-(4-Cyanophenylethynyl)-
1,2-benziodoxol-3(1H)-one (2f) and 1-(3-acetylphenyl-
ethynyl)-1,2-benziodoxol-3(1H)-one (2g) with a para-cya-
no or para-acetyl group were also converted into products
3af and 3ag in moderate yields. Importantly, bromo-substi-
tuted 1-(phenylethynyl)-1,2-benziodoxol-3(1H)-ones 2c–e
utilized under the optimal conditions gave bromo-substi-
tuted products 3ac–ae that could undergo subsequent
modifications at the halogenated positions. In the case of 1-
MeCN
THF
DMF
CH2Cl2
CH2Cl2
a Reaction conditions: 1a (0.3 mmol), 2a (1.5 equiv), [Ag], oxidant, solvent
(1 mL), 30 °C, under argon, 16 h.
b Isolated yield.
c CH2Cl2–H2O (1:1).
d At r.t.
e At 40 °C.
several substituents, such as OMe, Cl, F, and CF3, were toler-
ated on the phenyl ring. 1-Phenylcyclopropanol (1b) dis-
played high reactivity and furnished the desired product
3ba in 78% yield. A substrate containing a bulky ortho
group, 2-methoxybenzyl-substituted cyclopropanol 1c,
gave 3ca in moderate (60%) yield. Using 4-chlorophenyl-, 4-
fluorophenyl-, and 4-(trifluoromethyl)benzyl-substituted
cyclopropanols 1d–f gave 3da–fa in 72%, 75%, and 53%
yields, respectively. The reaction was applicable to hetero-
cycle-containing substrates 1g and 1h, and successfully de-
livered products 3ga and 3ha in good yields. We were
pleased to find that 1-(4-methoxyphenyl)-2-pentylcyclo-
propan-1-ol (1i) was a suitable substrate and it successfully
gave product 3ia. The optimal conditions were compatible
with 1-alkylcyclopropanols 1j–l, even bulky 1-(1-adaman-
(biphenyl-2-ylethynyl)-1,2-benziodoxol-3(1H)-one
(2h)
containing an ortho phenyl group the desired product 3ah
was obtained in 51% yield. We found that the optimal con-
ditions were compatible with 1-(3,3-dimethylbut-1-ynyl)-
1,2-benziodoxol-3(1H)-ones (2i) giving product 3ai in
moderate yield.
The optimal conditions were applicable to a wide range
of cyclopropanols, namely 1-arylcyclopropanols 1b–i and
1-alkylcyclopropanols 1j–m (Table 3). Initially, a variety of
1-arylcyclopropanols 1b–f were investigated in the pres-
ence of 1-(phenylethynyl)-1,2-benziodoxol-3(1H)-one (2a),
silver(I) nitrate, and potassium persulfate. We found that
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Table 2 Variation of the Ethynylbenziodoxolone 2a
O
R3
I
O
AgNO3, K2S2O8
OH
+
O
CH2Cl2, 30 °C, 16 h
R3
MeO
MeO
1a
2
3
O
O
O
Br
MeO
MeO
MeO
MeO
3ad, 69%
Br
3ab, 70%
3ac, 73%
O
O
O
Br
MeO
MeO
3ag, 69%
3ae, 63%
3af, 63%
CN
O
O
O
O
Ph
TMS
MeO
MeO
MeO
3ai, 50%
3aj, trace
3ah, 51%
a Reaction conditions: 1a (0.3 mmol), 2 (1.5 equiv), AgNO3 (20 mol%), K2S2O8 (2 equiv), CH2Cl2 (1 mL), 30 °C under argon, 16 h.
tyl)cyclopropan-1-ol (1l), affording products 3ja–la in high
yields. Gratifyingly, 1-styrylcyclopropan-1-ol (1m) was also
a viable substrate for the construction of 3ma in 55% yield.
As shown in Scheme 2, the reaction of cyclopropanol 1a
with 1-(phenylethynyl)-1,2-benziodoxol-3(1H)-one (2a)
was completely suppressed when using a stoichiometric
amount of radical inhibitor (3 equiv), including 2,2,6,6-te-
tramethylpiperidin-1-oxyl (TEMPO) and 2,6-di-tert-butyl-
4-methylphenol (BHT). The results suggest that this reac-
tion involves a free radical process.
Therefore, the proposed mechanism outlined in Scheme
2 for this ring opening of cyclopropanols 1 by silver(I) ni-
trate and potassium persulfate begins by the formation of
the alkyl radical intermediate A. The addition of intermedi-
Ph
I
O
O
additive (3 equiv)
OH
AgNO3, K2S2O8
O
+
CH2Cl2, 30 °C, 16 h
Ph
MeO
MeO
2a
1a
3aa
Yield
Additive
TEMPO
trace
trace
2,6-di-tert-butyl-4-methylphenol (BHT)
R2
I
R3
O
O
R2
O
R2
R1
O
O
AgNO3, K2S2O8
I
2
O
R1
R1
OH
R3
A
B
1
I
O
e–, H+
I
OH
O
O
O
R2
C
R1
R3
3
Scheme 2 Control experiments and possible mechanism
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Table 3 Variation of the Cyclopropanol 1a
Ph
I
O
R2
O
R2
AgNO3, K2S2O8
O
O
+
R1
CH2Cl2, 30 °C, 16 h
R1
OH
Ph
1
2a
3
O
O
Ph
Ph
OMe
Ph
Cl
3ba, 78%
3da, 72%
3ca, 60%
O
O
F3C
O
O
Ph
Ph
O
F
Ph
3fa, 53%
3ea, 75%
3ga, 70%
O
O
O
Ph
Ph
O
Ph
Ph
MeO
3ja, 61%
3ha, 57%
3ia, 50%
O
O
O
Ph
Ph
Ph
Ph
3ma, 55%
3la, 77%
3ka, 72%
a Reaction conditions: 1 (0.3 mmol), 2a (1.5 equiv), AgNO3 (20 mol%), K2S2O8 (2 equiv), CH2Cl2 (1 mL), 30 °C, under argon, 16 h.
ate A to the C≡C bond in 2 produces the vinyl radical inter-
mediate B, followed by C–I bond cleavage by single-electron
transfer and this is followed by β-elimination to give the de-
sired products 3 and radical C. Within this process, silver
salts might play at least two roles: as the catalyst to initiate
the formation of the radical intermediate A and as Lewis
acid to stabilize the radical intermediates.
In summary, we have developed a new silver-promoted
oxidative ring opening/alkynylation of cyclopropanols with
ethynylbenziodoxolones for the synthesis of alkylated
alkynes in the presence of potassium persulfate. In this
method, both silver(I) nitrate and potassium persulfate
have two roles as catalysts and oxidants, thus achieving
ring opening and alkynylation with broad substrate scope
and excellent selectivity.
charged with argon (1 atm) and stirred at 30 °C for 16 h until com-
plete consumption of the starting material (TLC monitoring). When
the reaction had finished, the mixture was washed with aq sat.
NaHCO3. The aqueous phase was re-extracted with CH2Cl2. The com-
bined organic extracts were dried (Na2SO4), concentrated under vacu-
um, and the resulting residue was purified by column chromatogra-
phy (silica gel, hexane–EtOAc) to afford the desired product.
1-(4-Methoxyphenyl)-5-phenylpent-4-yn-1-one (3aa)9
White solid; yield: 64.2 mg (81%); mp 52.9–54.0 °C.
IR (KBr): 1677 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.8 Hz, 2 H), 7.39–7.37 (m, 2
H), 7.26–7.25 (m, 3 H), 6.93 (d, J = 8.8 Hz, 2 H), 3.84 (s, 3 H), 3.27–3.23
(m, 2 H), 2.84–2.81 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 196.4, 163.5, 131.5, 130.2, 129.6,
128.1, 127.6, 123.6, 113.7, 89.0, 80.9, 55.4, 37.4, 14.3.
LR-MS (EI, 70 eV): m/z (%) = 264 (M+, 37), 233 (18), 221 (18), 135
(100).
NMR spectroscopy was performed on a Bruker advanced spectrome-
ter operating at 400 MHz (1H NMR) and 100 MHz (13C NMR) or 500
MHz (1H NMR) and 125 MHz (13C NMR). MS analysis was performed
on GC-MS analysis (Shimazu GCMS-QP2010) and ESI-Q-TOF (Bruker
MicroQTOF-II). All melting points are uncorrected.
HRMS (ESI): m/z [M + H]+ calcd for C18H17O2: 265.1223; found:
265.1230.
1-(4-Methoxyphenyl)-5-(p-tolyl)pent-4-yn-1-one (3ab)
White solid; yield: 58.4 mg (70%); mp 72.5–74.2 °C.
IR (KBr): 1675 cm–1
.
Silver-Promoted Oxidative Ring Opening/Alkynylation of Cyclo-
propanols; Typical Procedure
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.8 Hz, 2 H), 7.27 (d, J = 8.0
Hz, 2 H), 7.07 (d, J = 8.0 Hz, 2 H), 6.94 (d, J = 8.8 Hz, 2 H), 3.87 (s, 3 H),
3.28–3.24 (m, 2 H), 2.82 (t, J = 8.0 Hz, 2 H), 2.32 (s, 3 H).
To a Schlenk tube were added 1 (0.3 mmol), 2 (0.45 mmol), AgNO3
(0.06 mmol), K2S2O8 (0.6 mmol), and CH2Cl2 (1 mL). The tube was
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13C NMR (100 MHz, CDCl3): δ = 196.6, 163.5, 137.6, 131.4, 130.2,
LR-MS (EI, 70 eV): m/z (%) = 289 (M+, 30), 288 (23), 258 (29), 135
129.7, 128.9, 120.5, 113.7, 88.2, 81.0, 55.4, 37.5, 21.4, 14.4.
(100).
LR-MS (EI, 70 eV): m/z (%) = 278 (M+, 52), 235 (23), 135 (100).
HRMS (ESI): m/z [M + H]+ calcd for C19H16NO2: 290.1176; found:
290.1186.
HRMS (ESI): m/z [M + H]+ calcd for C19H19O2: 279.1380; found:
279.1385.
5-(4-Acetylphenyl)-1-(4-methoxyphenyl)pent-4-yn-1-one (3ag)
Light yellow solid; yield: 63.4 mg (69%); mp 56.6–57.8 °C.
5-(4-Bromophenyl)-1-(4-methoxyphenyl)pent-4-yn-1-one (3ac)
White solid; yield: 74.9 mg (73%); mp 112.6–113.7 °C.
IR (KBr): 1685, 1600 cm–1
.
IR (KBr): 1683 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.8 Hz, 2 H), 7.70 (d, J = 8.0
Hz, 2 H), 7.45 (d, J = 8.4 Hz, 2 H), 6.95 (d, J = 8.8 Hz, 2 H), 3.88 (s, 3 H),
3.31–3.27 (m, 2 H), 2.87 (t, J = 7.2 Hz, 2 H), 2.59 (s, 3 H).
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.8 Hz, 2 H), 7.39 (d, J = 8.4
Hz, 2 H), 7.23 (d, J = 8.4 Hz, 2 H), 6.94 (d, J = 8.8 Hz, 2 H), 3.87 (s, 3 H),
3.27–3.24 (m, 2 H), 2.84–2.80 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 197.4, 196.3, 163.7, 135.8, 131.7,
130.3, 129.6, 128.7, 128.1, 113.8, 92.9, 80.5, 55.5, 37.2, 26.6, 14.5.
LR-MS (EI, 70 eV): m/z (%) = 306 (M+, 27), 291 (28), 263 (12), 135
13C NMR (100 MHz, CDCl3): δ = 196.3, 163.6, 133.0, 131.4, 130.3,
129.6, 122.6, 121.7, 113.7, 90.4, 79.9, 55.4, 37.2, 14.4.
(100).
LR-MS (EI, 70 eV): m/z (%) = 344 (M+ + 2, 20), 342 (M+, 18), 313 (10),
311 (9), 135 (100).
HRMS (ESI): m/z [M + H]+ calcd for C20H19O3: 307.1329; found:
307.1335.
HRMS (ESI): m/z [M + H]+ calcd for C18H16BrO2: 343.0328; found:
343.0335.
5-(Biphenyl-2-yl)-1-(4-methoxyphenyl)pent-4-yn-1-one (3ah)
Yellow liquid; yield: 52.0 mg (51%).
5-(3-Bromophenyl)-1-(4-methoxyphenyl)pent-4-yn-1-one (3ad)
White solid; yield: 70.8 mg (69%); mp 78.2–79.5 °C.
IR (KBr): 1684 cm–1
.
IR (KBr): 1678 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 9.2 Hz, 2 H), 7.56 (d, J = 7.2
Hz, 2 H), 7.49 (d, J = 7.6 Hz, 1 H), 7.38–7.29 (m, 5 H), 7.28–7.24 (m, 1
H), 6.94 (d, J = 8.8 Hz, 2 H), 3.88 (s, 3 H), 3.10–3.06 (m, 2 H), 2.73–2.69
(m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 196.5, 163.6, 143.7, 140.8, 132.9,
130.3, 129.7, 129.3 (2C), 127.9, 127.8, 127.2, 126.9, 122.0, 113.7, 92.1,
80.6, 55.5, 37.1, 14.5.
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.8 Hz, 2 H), 7.51 (s, 1 H),
7.39 (d, J = 8.0 Hz, 1 H), 7.29 (d, J = 8.0 Hz, 1 H), 7.13 (t, J = 8.0 Hz, 1 H),
6.95 (d, J = 8.8 Hz, 2 H), 3.87 (s, 3 H), 3.26 (t, J = 7.6 Hz, 2 H), 2.83 (t,
J = 7.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 196.3, 163.6, 134.4, 130.8, 130.3,
130.1, 129.6 (2 C), 125.7, 122.0, 113.8, 90.6, 79.6, 55.5, 37.2, 14.4.
LR-MS (EI, 70 eV): m/z (%) = 340 (M+, 12), 339 (14), 135 (100).
HRMS (ESI): m/z [M + H]+ calcd for C24H21O2: 341.1536; found:
LR-MS (EI, 70 eV): m/z (%) = 344 (M+ + 2, 15), 342 (M+, 15), 313 (11),
311 (10), 135 (100).
341.1538.
HRMS (ESI): m/z [M + H]+ calcd for C18H16BrO2: 343.0328; found:
343.0336.
1-(4-Methoxyphenyl)-6,6-dimethylhept-4-yn-1-one (3ai)
Colorless liquid; yield: 36.7 mg (50%).
5-(2-Bromophenyl)-1-(4-methoxyphenyl)pent-4-yn-1-one (3ae)
White solid; yield: 64.6 mg (63%); mp 83.6–85.2 °C.
IR (KBr): 1711 cm–1
.
IR (KBr): 1671 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.8 Hz, 2 H), 6.94 (d, J = 8.8
Hz, 2 H), 3.87 (s, 3 H), 3.14–3.10 (m, 2 H), 2.58–2.55 (m, 2 H), 1.17 (s, 9
H).
13C NMR (100 MHz, CDCl3): δ = 197.2, 163.5, 130.4, 130.2, 113.7, 89.5,
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.8 Hz, 2 H), 7.54 (d, J = 8.0
Hz, 1 H), 7.41 (d, J = 7.6 Hz, 1 H), 7.21 (t, J = 7.2 Hz, 1 H), 7.11 (t, J = 7.6
Hz, 1 H), 6.94 (d, J = 8.4 Hz, 2 H), 3.87 (s, 3 H), 3.31 (t, J = 7.6 Hz, 2 H),
2.92–2.88 (m, 2 H).
77.2, 55.5, 38.0, 31.3, 27.3, 14.0.
13C NMR (100 MHz, CDCl3): δ = 196.3, 163.6, 133.3, 132.2, 130.3,
LR-MS (EI, 70 eV): m/z (%) = 244 (M+, 7), 229 (21), 135 (100).
129.6, 128.8, 126.9, 125.7, 125.4, 113.7, 94.2, 79.7, 55.4, 37.2, 14.6.
LR-MS (EI, 70 eV): m/z (%) = 344 (M+ + 2, 4), 342 (M+, 4), 264 (20), 263
HRMS (ESI): m/z [M + H]+ calcd for C16H21O2: 245.1536; found:
245.1541.
(100), 135 (95).
1,5-Diphenylpent-4-yn-1-one (3ba)8c
HRMS (ESI): m/z [M + H]+ calcd for C18H16BrO2: 343.0328; found:
343.0333.
White solid; yield: 54.8 mg (78%); mp 57.7–58.7 °C.
IR (KBr): 1685 cm–1
.
4-[5-(4-Methoxyphenyl)-5-oxopent-1-ynyl]benzonitrile (3af)
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.0 Hz, 2 H), 7.57 (t, J = 7.2
Hz, 1 H), 7.47 (t, J = 7.6 Hz, 2 H), 7.39–7.37 (m, 2 H), 7.27–7.25 (m, 3
H), 3.31 (t, J = 7.2 Hz, 2 H), 2.85 (t, J = 7.2 Hz, 2 H).
White solid; yield: 54.6 mg (63%); mp 108.3–109.5 °C.
IR (KBr): 1669 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.8 Hz, 2 H), 7.56 (d, J = 8.4
Hz, 2 H), 7.45 (d, J = 8.0 Hz, 2 H), 6.96 (d, J = 8.8 Hz, 2 H), 3.88 (s, 3 H),
3.28 (t, J = 7.2 Hz, 2 H), 2.87 (t, J = 7.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 197.9, 136.5, 133.2, 131.5, 128.6,
128.1, 128.0, 127.7, 123.6, 88.8, 81.0, 37.8, 14.3.
LR-MS (EI, 70 eV): m/z (%) = 234 (M+, 49), 233 (64), 128 (32), 105
(100), 77 (73).
13C NMR (100 MHz, CDCl3): δ = 196.1, 163.7, 132.1, 131.9, 130.3,
129.5, 128.7, 118.6, 113.8, 111.0, 94.2, 79.7, 55.5, 37.0, 14.0.
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HRMS (ESI): m/z [M + H]+ calcd for C17H15O: 235.1117; found:
HRMS (ESI): m/z [M + H]+ calcd for C19H16F3O: 317.1148; found:
235.1124.
317.1143.
1-(2-Methoxyphenyl)-6-phenylhex-5-yn-2-one (3ca)
1-(1,3-Benzodioxol-5-yl)-5-phenylpent-4-yn-1-one (3ga)
Light yellow liquid; yield: 50.1 mg (60%).
White solid; yield: 58.4 mg (70%); mp 79.6–82.3 °C.
IR (KBr): 1683 cm–1
.
IR (KBr): 1674 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.37–7.35 (m, 2 H), 7.27–7.25 (m, 4 H),
7.14 (t, J = 7.2 Hz, 1 H), 6.94–6.87 (m, 2 H), 3.80 (s, 3 H), 3.71 (s, 2 H),
2.78–2.74 (m, 2 H), 2.67–2.63 (m, 2 H).
1H NMR (400 MHz, CDCl3): δ = 7.60–7.58 (m, 1 H), 7.46 (d, J = 1.2 Hz, 1
H), 7.39–7.37 (m, 2 H), 7.27–7.26 (m, 3 H), 6.85 (d, J = 8.0 Hz, 1 H),
6.03 (s, 2 H), 3.23 (t, J = 7.2 Hz, 2 H), 2.82 (t, J = 7.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 206.8, 157.3, 131.5, 131.2, 128.6,
128.2, 127.7, 123.6, 123.2, 120.7, 110.5, 88.8, 80.8, 55.3, 44.7, 40.7,
14.0.
13C NMR (100 MHz, CDCl3): δ = 196.0, 151.8, 148.2, 131.5, 131.4,
128.1, 127.7, 124.3, 123.6, 107.9, 107.8, 101.8, 88.9, 81.0, 37.5, 14.4.
LR-MS (EI, 70 eV): m/z (%) = 278 (M+, 53), 277 (41), 235 (20), 149
(100).
LR-MS (EI, 70 eV): m/z (%) = 278 (M+, 23), 157 (82), 115 (100), 91 (91).
HRMS (ESI): m/z [M + H]+ calcd for C19H19O2: 279.1380; found:
HRMS (ESI): m/z [M + H]+ calcd for C18H15O3: 279.1016; found:
279.1384.
279.1022.
1-(4-Chlorophenyl)-5-phenylpent-4-yn-1-one (3da)9
1-(Furan-2-yl)-5-phenylpent-4-yn-1-one (3ha)
White solid; yield: 57.9 mg (72%); mp 49.8–52.4 °C.
Light yellow liquid; yield: 38.3 mg (57%).
IR (KBr): 1688 cm–1
.
IR (KBr): 1663 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.4
Hz, 2 H), 7.38–7.36 (m, 2 H), 7.28–7.26 (m, 3 H), 3.29 (t, J = 7.6 Hz, 2
H), 2.85 (t, J = 7.2 Hz, 2 H).
1H NMR (400 MHz, CDCl3): δ = 7.60 (s, 1 H), 7.38–7.36 (m, 2 H), 7.27–
7.24 (m, 4 H), 6.56–6.54 (m, 1 H), 3.17 (t, J = 7.2 Hz, 2 H), 2.83 (t,
J = 7.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 196.8, 139.7, 134.9, 131.5, 129.5,
13C NMR (100 MHz, CDCl3): δ = 187.2, 152.5, 146.5, 131.6, 128.2,
129.0, 128.2, 127.8, 123.5, 88.5, 81.2, 37.8, 14.3.
127.7, 123.6, 117.3, 112.3, 88.4, 81.2, 37.5, 14.2.
LR-MS (EI, 70 eV): m/z (%) = 270 (M+ + 2, 15), 268 (M+, 45), 233 (49),
LR-MS (EI, 70 eV): m/z (%) = 224 (M+, 54), 223 (100), 181 (75), 167
111 (52).
(64), 128 (54), 95 (63).
HRMS (ESI): m/z [M + H]+ calcd for C17H14ClO: 269.0728; found:
HRMS (ESI): m/z [M + H]+ calcd for C15H13O2: 225.0910; found:
269.0736.
225.0917.
1-(4-Fluorophenyl)-5-phenylpent-4-yn-1-one (3ea)9
1-(4-Methoxyphenyl)-3-(phenylethynyl)octan-1-one (3ia)
Colorless liquid; yield: 56.7 mg (75%).
Colorless liquid; yield: 50.1 mg (50%).
IR (KBr): 1690 cm–1
.
IR (KBr): 1680 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.04–8.00 (m, 2 H), 7.37 (d, J = 3.6 Hz, 2
H), 7.27 (d, J = 3.2 Hz, 3 H), 7.14 (t, J = 8.4 Hz, 2 H), 3.29 (t, J = 8.0 Hz, 2
H), 2.85 (t, J = 7.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 196.4, 166.3 (d, JC-F = 253.0 Hz), 133.0
(d, JC-F = 2.0 Hz), 131.5, 130.7 (d, JC-F = 9.0 Hz), 128.2, 127.7, 123.5,
115.7 (d, JC-F = 21.0 Hz), 88.6, 81.1, 37.7, 14.3.
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.8 Hz, 2 H), 7.34–7.31 (m, 2
H), 7.26–7.24 (m, 3 H), 6.94 (d, J = 8.8 Hz, 2 H), 3.87 (s, 3 H), 3.32–3.26
(m, 2 H), 3.11–3.04 (m, 1 H), 1.64–1.61 (m, 1 H), 1.56–1.52 (m, 1 H),
1.39–1.23 (m, 6 H), 0.92–0.86 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 196.7, 163.5, 131.6, 130.5, 130.2,
128.1, 127.5, 123.8, 113.7, 92.7, 81.8, 55.5, 43.6, 34.9, 31.6, 28.2, 27.1,
22.6, 14.0.
19F NMR (375 MHz, CDCl3): δ = –104.9.
LR-MS (EI, 70 eV): m/z (%) = 252 (M+, 58), 251 (78), 209 (20), 128 (27),
LR-MS (EI, 70 eV): m/z (%) = 334 (M+, 4), 263 (83), 215 (23), 135 (100).
HRMS (ESI): m/z [M + H]+ calcd for C23H27O2: 335.2006; found:
123 (100), 95 (57).
335.2011.
HRMS (ESI): m/z [M + H]+ calcd for C17H14FO: 253.1023; found:
253.1029.
1,7-Diphenylhept-6-yn-3-one (3ja)
White solid; yield: 48.0 mg (61%); mp 63.4–64.8 °C.
6-Phenyl-1-[4-(trifluoromethyl)phenyl]hex-5-yn-2-one (3fa)
Light yellow solid; yield: 50.3 mg (53%); mp 50.6–52.4 °C.
IR (KBr): 1690 cm–1
.
IR (KBr): 1669 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.37–7.34 (m, 2 H), 7.28–7.25 (m, 5 H),
7.20–7.16 (m, 3 H), 2.92 (t, J = 7.6 Hz, 2 H), 2.78 (t, J = 7.6 Hz, 2 H),
2.72–2.63 (m, 4 H).
1H NMR (400 MHz, CDCl3): δ = 7.58 (d, J = 8.0 Hz, 2 H), 7.35–7.32 (m, 4
H), 7.28–7.25 (m, 3 H), 3.82 (s, 2 H), 2.82–2.78 (m, 2 H), 2.69–2.65 (m,
2 H).
13C NMR (100 MHz, CDCl3): δ = 207.8, 140.8, 131.5, 128.5, 128.3,
128.2, 127.7, 126.1, 123.5, 88.5, 81.0, 44.3, 41.7, 29.6, 13.9.
LR-MS (EI, 70 eV): m/z (%) = 262 (M+, 14), 171 (60), 157 (100), 105
13C NMR (100 MHz, CDCl3): δ = 205.1, 137.7, 131.5, 129.8, 129.5 (q,
JC-F = 32.3 Hz), 128.2, 127.8, 125.6 (q, JC-F = 3.8 Hz), 123.8 (q, JC-F
=
251.0 Hz), 123.4, 88.1, 81.2, 49.6, 41.2, 14.0.
(92), 91 (82).
19F NMR (375 MHz, CDCl3): δ = –62.5.
HRMS (ESI): m/z [M + H]+ calcd for C19H19O: 263.1430; found:
263.1438
LR-MS (EI, 70 eV): m/z (%) = 316 (M+, 7), 157 (73), 128 (25), 115 (100).
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1-Phenylundec-1-yn-5-one (3ka)
Reference
Light yellow liquid; yield: 52.3 mg (72%).
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IR (KBr): 1710 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.38–7.36 (m, 2 H), 7.27–7.26 (m, 3 H),
2.74–2.65 (m, 4 H), 2.45 (t, J = 7.5 Hz, 2 H), 1.61–1.57 (m, 2 H), 1.30–
1.26 (m, 6 H), 0.89–0.86 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 209.0, 131.5, 128.1, 127.6, 123.6, 88.6,
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80.8, 42.8, 41.4, 31.5, 28.8, 23.7, 22.4, 13.9.
LR-MS (EI, 70 eV): m/z (%) = 242 (M+, 14), 171 (16), 157 (100), 129
(27), 115 (35).
HRMS (ESI): m/z [M + H]+ calcd for C17H23O: 243.1743; found:
243.1747.
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1-(Adamantan-1-yl)-5-phenylpent-4-yn-1-one (3la)
Colorless liquid; yield: 67.5 mg (77%).
IR (KBr): 1700 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.38–7.36 (m, 2 H), 7.27–7.25 (m, 3 H),
2.80–2.77 (m, 2 H), 2.65–2.61 (m, 2 H), 2.07–2.02 (m, 3 H), 1.85–1.82
(m, 5 H), 1.81–1.68 (m, 7 H).
13C NMR (100 MHz, CDCl3): δ = 213.4, 131.5, 128.1, 127.6, 123.7, 89.3,
80.7, 46.2, 38.1, 36.5, 35.5, 27.9, 14.0.
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LR-MS (EI, 70 eV): m/z (%) = 292 (M+, 5), 157 (7), 135 (100).
HRMS (ESI): m/z [M + H]+ calcd for C21H25O: 293.1900; found:
293.1908.
(E)-1,7-Diphenylhept-1-en-6-yn-3-one (3ma)
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Yellow solid; yield: 42.9 mg (55%); mp 46.7–47.9 °C.
IR (KBr): 1696 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.61 (d, J = 16.4 Hz, 1 H), 7.57–7.55 (m,
2 H), 7.41–7.37 (m, 5 H), 7.27–7.26 (m, 3 H), 6.78 (d, J = 16.0 Hz, 1 H),
3.04–3.01 (m, 2 H), 2.81–2.77 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 198.1, 143.1, 134.4, 131.6, 130.6,
129.0, 128.3, 128.2, 127.7, 125.9, 123.6, 88.8, 81.1, 39.7, 14.3.
LR-MS (EI, 70 eV): m/z (%) = 260 (M+, 4), 217 (81), 203 (42), 131 (56),
103 (100).
HRMS (ESI): m/z [M + H]+ calcd for C19H17O: 261.1274; found:
261.1280.
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Acknowledgment
We thank the Natural Science Foundation of China (Nos. 21472039
and 21172060) and Hunan Provincial Natural Science Foundation of
China (No. 13JJ2018) for financial support.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560374.
S
u
p
p
ortiInfogrmoaitn
S
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, 223–230