Poly[styrene(iodosodiacetate)]-promoted ring expansion reaction of 1-alkynylcycloalkanols: A novel synthesis of (Z)-2-(1-iodo-1-organyl) methylenecycloalkanones

Article abstract of DOI:10.1055/s-2004-831214

The ring expansion reaction of 1-alkynylcycloalkanols with poly[styrene(iodosodiacetate)] and iodine affords (Z)-2-(1-iodo-1-organyl) methylenecycloalkanones in moderate to good yields.

Full text of DOI:10.1055/s-2004-831214

PAPER
2459
Poly[styrene(iodosodiacetate)]-Promoted Ring Expansion Reaction of 1-Alky-
nylcycloalkanols: A Novel Synthesis of (Z)-2-(1-Iodo-1-organyl)methylene-
cycloalkanones
Synthesis
i
of
(
Z
)
-2
a
-
(1-Iodo-1
n
-
organyl)me
t
g
hylenecycloa
-
lkanone
M
s
in Chen,a,b Xian Huang*a
a
Department of Chemistry, Zhejiang University, Xixi Campus, Hangzhou 310028, P. R. China
b
Department of Chemistry, Gannan Teacher College, Ganzhou 341000, P. R. China
E-mail: huangx@mail.hz.zj.cn
Received 17 May 2004; revised 2 July 2004
With this result in hand, we supposed that ring expansion
products may be obtained from the substrates, 1-alkynyl-
cycloalkanols, which were prepared from the correspond-
ing cycloalkanones. Poly[styrene(iodosodiacetate)] has
the similar reactivity to (diacetoxyiodo)benzene,1b and the
most important is that the byproduct, poly(4-iodostyrene)
can be recycled, which provide an environment benign
system. Considering that five- and six-membered rings
are stable, we carried out the ring expansion reaction
(Scheme 2) with 1-(2-phenylethynyl)cyclopentanol (3a)
in the presence of poly[styrene(iodosodiacetate)] and io-
dine. Luckily, the expected product 4a was obtained in
80% yield (Table 1, entry 1).
Abstract: The ring expansion reaction of 1-alkynylcycloalkanols
with poly[styrene(iodosodiacetate)] and iodine affords (Z)-2-(1-
iodo-1-organyl)methylenecycloalkanones in moderate to good
yields.
Key words, poly[styrene(iodosodiacetate)], ring expansion, 1-alky-
nyl substituted tertiary alcohols, 2-(1-iodo-1-organyl)methylenecy-
cloalkanones
During the last decades, polymer supported hypervalent
iodine reagents have gained an increasing popularity in
organic synthesis on account of their versatile reactivity.1
Among them, poly[styrene(iodosodiacetate)] was widely
used as a mild and clean oxidant. 2-Disubstituted methyl-
enecycloalkanones are very important intermediates in
the synthesis of biologically active natural products,2 but
reports concerning transformations from 1-alkynylcy-
cloalkanols to 2-disubstituted methylenecycloalkanones
are rare.3 To the best of our knowledge, there are no re-
ports on the ring expansion reaction promoted by
poly[styrene(iodosodiacetate)]. Herein, we wish to report
the ring expansion reaction of 1-alkynylcycloalkanols
promoted by poly[styrene(iodosodiacetate)] to give (Z)-2-
(1-iodo-1-organyl)methylenecycloalkanones with the ad-
vantages such as mild reaction conditions, and convenient
manipulation. Moreover, the polymer reagent could be re-
generated and reused.
O
HO
I
I(OAc)
2 , I2
R
CH2Cl2, r.t.
R
n
n
4
3
n = 1, 2, 3
Scheme 2
As a solvent for this reaction, CH2Cl2 was found to be
more efficient than MeCN, CHCl3, and ClCH2CH2Cl.
Various 1-alkynylcycloalkanols 3 were reacted with io-
dine and poly[styrene(iodosodiacetate)] in CH2Cl2 at
room temperature overnight to give (Z)-2-(1-iodo-1-orga-
nyl)methylenecycloalkanones. The stereochemistry of the
products 4d and 4h has been established on the basis of
1H-1H COSY as well as from 1H-1H NOESY experiments
(Figure 1). The results are summarized in Table 1.
First we tried our experiments with 2,4-diphenyl-3-butyn-
2-ol (1), which was treated with iodine and (diacetoxy-
iodo)benzene in dichloromethane at room temperature
overnight. This afforded (Z)-4-iodo-2,4-diphenylbut-3-
en-2-one (2)4 in 77% yield (Scheme 1).
I
O
O
I
O
OH
I
PhI(OAc)2, I2
CH2Cl2, r.t.
NOE
4d
H3C
H3C
Ph
NOE
Ph
Ph
Ph
1
2
4h
Scheme 1
Figure 1 NOESY correlations of 4h and 4d
(Z)-2-(1-Iodo-1-phenyl)methylenecycloalkanones, which
may react with various reagents owing to a vinyl iodine at-
om, can obviously be applied as useful building blocks in
organic synthesis. We examined a Sonogashira cross-cou-
pling reaction of (Z)-2-(1-iodo-1-phenyl)methylenecy-
SYNTHESIS 2004, No. 15, pp 2459–2462
Advanced online publication: 16.09.2004
DOI: 10.1055/s-2004-831214; Art ID: F06904SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
4

2460
J.-M. Chen, X. Huang
PAPER
g, 13.3 mmol) in THF (10 mL) under N2. After the disappearance of
Mg, phenylacetylene (1.36 g, 13.3 mmol) in THF (15 mL) was add-
ed dropwise and the solution was stirred at r.t. for 1 h. Then the so-
lution was cooled to 0 °C and the corresponding cycloheptanone
(1.12 g, 10 mmol) in THF (10 mL) was added dropwise. The mix-
ture was stirred at the same temperature for 2 h, quenched with sat.
aq NH4Cl and extracted with EtOAc (3 × 5 mL). The organic phases
were combined, washed with brine and dried (MgSO4). After evap-
oration of the solvent, the residues were purified via chromatogra-
phy on silica gel with n-hexane–EtOAc (10:1) as the eluent to afford
the tertiary alkynol 3g.
Table 1 Ring Expansion Reaction of 1-(2-Substituted-ethynyl)cy-
cloalkanols
Entry
n
R
Time (h)
Product
(Yield, %)a
1
2
1
1
1
2
2
2
3
3
3
3
3
C6H5
11
14
13
11
12
13
11
12
12
12
11
4a (80)
4b (64)
4c (72)
4d (70)
4e (61)
4f (60)
4g (67)
4h (58)
4i (55)
4j (58)
4g (66)b
n-C4H9
3
p-CH3C6H4OCH2
C6H5
4
IR (neat): 3416, 2932, 2858, 1598, 1489, 1216, 1024, 756 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.44–7.41 (m, 2 H), 7.29–7.25 (m,
3 H), 2.32 (br, 1 H), 2.15–2.09 (m, 2 H), 1.95–1.88 (m, 2 H), 1.71–
1.59 (m, 8 H).
13C NMR (100 MHz, CDCl3): d = 131.6, 128.2, 128.1, 123.0, 93.9,
83.6, 72.2, 43.2, 27.9, 22.3.
MS (EI): m/z (%) = 214 (M+, 19), 197 (39), 157 (100), 129 (84), 115
(55).
5
C6H5CH2OCH2
p-CH3C6H4OCH2
C6H5
6
7
8
n-C4H9
9
p-CH3C6H4OCH2
C6H5CH2OCH2
C6H5
Anal. Calcd for C15H18O: C, 84.07; H, 8.47. Found: C, 83.89; H,
8.53.
10
11
Oxidative Rearrangement Reaction of Tertiary Alkynol 1 Pro-
moted by (Diacetoxyiodo)benzene; (Z)-4-Iodo-2,4-diphenylbut-
3-ene-2-one (2)
a Isolated yields.
b Using the regenerated resin.
A suspension of tertiary alkynol 1 (1.0 mmol), (diacetoxyiodo)ben-
zene (322 mg, 1.0 mmol) and I2 (0.6 mmol) in CH2Cl2 (10 mL) was
stirred at r.t. for 12 h. The mixture was then washed with aq 5%
Na2SO3 (15 mL) and extracted with CH2Cl2 (3 ×). The organic phas-
es were combined and dried (MgSO4). After evaporation of the sol-
vent, the residue was purified via chromatography on silica gel with
n-hexane–EtOAc (20:1) as the eluent to afford 24 (77%).
clooctanone with phenylacetylene. This gave (Z)-2-(1-
phenyl-1-phenylethynyl)methylenecyclooctanone (5g) in
high yield (Scheme 3).
IR (neat): 1666 cm–1 (C=O).
1H NMR (400 MHz, CDCl3): d = 7.32–7.11 (m, 10 H), 2.41 (s, 3 H).
MS (EI): m/z (%) = 348 (M+).
Ph
O
O
I
Ph
H
Ph
Ph
K2CO3/CH3CN
PdCl2(PPh3)2
CuI, 60 °C
12 h
Ring Expansion Reaction of 1-(2-Substituted Ethynyl)cycloal-
kanols 3; (Z)-2-(1-Iodo-1-phenyl)methylenecyclooctanone (4g);
General Procedure
(92%)
5g
4g
A suspension of tertiary alkynol 3g (1.0 mmol), poly[styrene(iodo-
sodiacetate)] (0.4 g, 1.0 mmol) and I2 (0.6 mmol) in CH2Cl2 (10 mL)
was stirred at r.t. for 11 h. The mixture was then washed with aq 5%
Na2S2O3 (15 mL) and extracted with CH2Cl2 (3 × 10 mL). The or-
ganic phases were combined and dried (MgSO4). After evaporation
of the solvent, Et2O was added to cause precipitation, the precipitate
was collected by filtration for reusing, and the filtrate was evaporat-
ed the solvent and the residue was purified via chromatography on
silica gel with n-hexane–EtOAc (20:1) as the eluent to afford 228
mg (67%) of 4g.
Scheme 3
In conclusion, we have developed a convenient and effi-
cient method for the synthesis of 2-(1-iodo-1-organyl)-
methylenecycloalkanones in moderate to good yields by
the ring expansion reaction of 1-alkynylcycloalkanols
with poly[styrene(iodosodiacetate)] and iodine in dichlo-
romethane. The polymer reagent could be regenerated and
reused.
IR (neat): 2927, 2855, 1664, 1596, 1579, 1449, 1239, 734, 693 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.99 (d, 2 H, J = 8.4 Hz), 7.62–
7.58 (m, 1 H), 7.51–7.47 (t, 2 H, J = 7.6 Hz), 2.64–2.61 (t, 2 H,
J = 6.0 Hz), 2.38–2.36 (m, 2 H), 1.79–1.54 (m, 8 H).
13C NMR (100 MHz, CDCl3): d = 193.0, 151.6, 134.4, 134.0, 130.5
129.1, 91.6, 40.9, 33.9, 29.9, 29.0, 27.9, 26.0.
MS (EI): m/z (%) = 341 [(M + 1)+, 35], 340 (M+, 21), 213 (22), 157
(21), 105 (100).
Melting points are uncorrected. 1H NMR spectra were recorded on
a Bruker Avance 400 spectrometer in CDCl3 with TMS as the inter-
nal standard. 13C NMR spectra were recorded on a Bruker AC-400
(100 MHz) spectrometer in CDCl3. IR spectra were recorded on a
Shimadzu IR-408 spectrometer. EIMS were run on a HP 5989B
mass spectrometer. Elemental analyses were performed on an EA-
1110 instrument. Poly[styrene(iodosodiacetate)] was prepared as
described in the literature5 and its loading in terms of the functional
group is 2.50 mmol/g by iodometry.
Anal. Calcd for C15H17IO: C, 52.96; H, 5.04. Found: C, 52.81; H,
5.11.
1-(2-Phenylethynyl)cycloheptanol (3g); Typical Procedure
To a suspension of Mg (319 mg, 13.3 mmol) and catalytic quantities
of I2 in THF (15 mL) was added dropwise a solution of EtBr (1.45
4a
IR (neat): 2938, 1666, 1489, 1090, 908, 733, 688 cm–1.
Synthesis 2004, No. 15, 2459–2462 © Thieme Stuttgart · New York

PAPER
Synthesis of (Z)-2-(1-Iodo-1-organyl)methylenecycloalkanones
2461
1H NMR (400 MHz, CDCl3): d = 7.60–7.56 (m, 2 H), 7.50–7.46 (m,
1 H), 7.42–7.38 (m, 2 H), 3.22 (t, 2 H, J = 5.6 Hz), 2.72 (t, 2 H,
J = 6.4 Hz), 1.95–1.84 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 187.5, 133.5, 131.2, 129.1, 120.3,
91.5, 88.1, 44.6, 32.9, 25.4, 6.3.
4f
IR (neat): 2929, 1698, 1601, 1508, 1398, 1212, 1177, 818 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.07 (d, 2 H, J = 8.0 Hz), 6.84 (d,
2 H, J = 8.4 Hz), 4.74 (s, 2 H), 3.22–3.18 (m, 2 H), 2.81–2.77 (m, 2
H), 2.31 (s, 3 H), 1.89–1.71 (m, 6 H).
MS (EI): m/z (%) = 313 [(M + 1)+, 26.0], 231 (15.8), 185 (49.9), 129
(100).
13C NMR (100 MHz, CDCl3): d = 200.2, 138.3, 131.4, 130.1, 115.4,
96.2, 95.2, 36.3, 33.5, 29.3, 27.4, 23.1, 20.6, 6.8.
Anal. Calcd for C13H13IO: C, 50.02; H, 4.20. Found: C, 50.10; H,
4.12.
MS (EI): m/z (%) = 370 (M+, 3.8), 254 (28.1), 127 (15.2), 91 (100),
55 (19.2), 41 (11.1).
Anal. Calcd for C16H19IO2: C, 51.91; H, 5.17. Found: C, 52.01; H,
5.23.
4b
IR (neat): 2957, 2929, 2870, 1703, 1672, 1401, 1207, 1102 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.24 (t, 2 H, J = 6.8 Hz), 2.84–
2.80 (m, 2 H), 2.71–2.67 (m, 2 H), 1.96–1.91 (m, 2 H), 1.88–1.83
(m, 2 H), 1.81–1.79 (m, 2 H), 1.52–1.45 (m, 2 H), 1.00–0.95 (m, 3
H).
13C NMR (100 MHz, CDCl3): d = 201.1, 100.9, 97.3, 47.8, 37.9,
32.1, 30.6, 24.7, 21.1, 14.3, 6.3.
4h
IR (neat): 2931, 2858, 1703, 909, 732 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.20 (t, 2 H, J = 6.8 Hz), 2.78 (t,
2 H, J = 6.8 Hz), 2.68 (t, 2 H, J = 7.6 Hz), 1.89–1.81 (m, 2 H), 1.74–
1.67 (m, 2 H), 1.61–1.53 (m, 2 H), 1.48–1.36 (m, 6 H), 0.96 (m, 3
H).
MS (EI): m/z (%) = 293 [(M + 1)+, 34.8], 292 (M+, 21.1), 271 (21.4),
211 (23.9), 183 (31.7), 65 (63.9), 109 (100), 41 (71.0).
13C NMR (100 MHz, CDCl3): d = 201.2, 100.4, 93.4, 47.5, 38.8,
33.2, 30.2, 27.9, 23.1, 21.5, 14.0, 7.1.
Anal. Calcd for C11H17IO: C, 45.22; H, 5.86. Found: C, 45.29; H,
5.92.
MS (EI): m/z (%) = 321 [(M + 1)+, 11.2], 320 (M+, 4.8), 239 (16.7),
193 (10.7), 109 (61.1), 81 (38.3), 55 (59.4), 41 (100).
Anal. Calcd for C13H21IO: C, 48.76; H, 6.61. Found: C, 48.69; H,
6.68.
4c
IR (neat): 2922, 1704, 1611, 1509, 1398, 1212, 1175, 817 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.11 (d, 2 H, J = 8.4 Hz), 6.83 (d,
2 H, J = 8.8 Hz), 4.74 (s, 2 H), 3.21 (t, 2 H, J = 6.8 Hz), 2.81 (t, 2
H, J = 6.4 Hz), 2.30 (s, 3 H), 1.93–1.90 (m, 2 H), 1.83–1.80 (m, 2
H).
13C NMR (100 MHz, CDCl3): d = 200.2, 155.3, 131.4, 130.1, 115.4,
96.2, 95.1, 37.3, 32.5, 29.3, 24.1, 20.5, 5.8.
4i
IR (neat): 2930, 2858, 1704, 1611, 1509, 1213, 1176, 908, 733 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.11 (d, 2 H, J = 8.0 Hz), 6.83 (d,
2 H, J = 8.0 Hz), 4.74 (s, 2 H), 3.19 (t, 2 H, J = 6.8 Hz), 2.78 (t, 2
H, J = 7.2 Hz), 2.30 (s, 3 H), 1.87–1.80 (m, 2 H), 1.73–1.69 (m, 2
H), 1.46–1.39 (m, 4 H).
MS (EI): m/z (%) = 356 (M+, 30.9), 244 (12.9), 187 (30.7), 135
(54.1), 107 (88.7), 77 (100), 55 (93.9), 41 (54.1).
13C NMR (100 MHz, CDCl3): d = 200.7, 140.3, 131.3, 130.1, 115.3,
96.9, 96.6, 36.5, 33.2, 31.1, 30.1, 27.8, 23.0, 20.5, 6.9.
Anal. Calcd for C15H17IO2: C, 50.58; H, 4.81. Found: C, 50.64; H,
4.88.
MS (EI): m/z (%) = 384 (M+, 26.7), 239 (9.4), 187 (18.4), 173
(33.5), 159 (21.8), 145 (44.3), 108 (100), 77 (68.8), 41 (73.3).
Anal. Calcd for C17H21IO2: C, 53.14; H, 5.51. Found: C, 53.19; H,
5.58.
4d
IR (neat): 3060, 2931, 2855, 1663, 1597, 1446, 1265, 1220, 700
cm–1.
4j
1H NMR (400 MHz, CDCl3): d = 8.00–7.96 (m, 2 H), 7.62–7.56 (m,
1 H), 7.54–7.47 (m, 2 H), 2.57 (t, 2 H, J = 6.0 Hz), 2.24 (t, 2 H,
J = 6.0 Hz), 1.76–1.72 (m, 2 H), 1.61–1.44 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 193.5, 150.0, 134.4, 134.1, 130.4,
129.1, 88.2, 39.3, 33.6, 27.9, 27.8, 26.2.
IR (neat): 3062, 3029, 2930, 2856, 1703, 1496, 1454, 1396, 1206,
1099, 739, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.49–7.38 (m, 5 H), 4.61 (s, 2 H),
4.38 (s, 2 H), 3.26 (t, 2 H, J = 7.2 Hz), 2.84 (t, 2 H, J = 7.6 Hz), 1.91
(t, 2 H, J = 6.8 Hz), 1.79 (t, 2 H, J = 6.8 Hz), 1.52 (m, 4 H).
MS (EI): m/z (%) = 327 [(M + 1)+, 50.3], 326 (M+, 29.6), 199 (75.9),
157 (22.5), 129 (21.2), 105 (100), 77 (31.1).
13C NMR (100 MHz, CDCl3): d = 200.8, 137.1, 128.5, 128.1, 128.0,
97.7, 95.6, 78.5, 72.1, 38.5, 33.2, 30.2, 27.9, 23.0, 7.1.
Anal. Calcd for C14H15IO: C, 51.55; H, 4.64. Found: C, 51.48; H,
4.70.
MS (EI): m/z (%) = 385 [(M + 1)+, 2.1], 384 (M+, 0.6), 239 (4.1),
181 (6.0), 91 (100), 65 (9.1), 41 (16.6).
Anal. Calcd for C17H21IO2: C, 53.14; H, 5.51. Found: C, 53.08; H,
5.55.
4e
IR (neat): 3029, 2929, 2857, 1703, 1453, 1398, 1105, 738, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.43–7.31 (m, 5 H), 4.55 (s, 2 H),
4.31 (s, 2 H), 3.21 (t, 2 H, J = 6.8 Hz), 2.79 (t, 2 H, J = 6.4 Hz),
1.89–1.86 (m, 2 H), 1.76–1.72 (m, 2 H), 1.51–1.47 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 200.6, 137.1, 128.5, 128.1, 128.0,
97.7, 95.3, 78.5, 72.1, 38.4, 33.2, 29.9, 22.2, 6.5.
MS (EI): m/z (%) = 370 (M+, 1.0), 254 (24.5), 127 (16.7), 91 (100),
55 (13.8), 41 (16.8).
(Z)-2-(1-Phenyl-1-phenylethynyl)methylenecyclooctanone (5g)
Under N2, a slurry of the 4g (170 mg, 0.5 mmol), phenylacetylene
(61 mg, 0.6 mmol), PdCl2(PPh3)2 (17 mg, 5 mol%), CuI (9.5 mg, 10
mol%), K2CO3 (207 mg, 1.5 mmol) in MeCN (15 mL) was stirred
at 60 °C for 12 h. The reaction mixture was filtered through a short
pad of silica gel to remove precipitated inorganic salts. The silica
gel pad was washed three times with a small amount of EtOAc and
the combined solution was evaporated to dryness under reduced
pressure. The residue was chromatographed on silica gel using n-
hexane–EtOAc (20:1) as eluent to give 144 mg (92%) of 5g.
Anal. Calcd for C16H19IO2: C, 51.91; H, 5.17. Found: C, 51.81; H,
5.20.
Synthesis 2004, No. 15, 2459–2462 © Thieme Stuttgart · New York

2462
J.-M. Chen, X. Huang
PAPER
IR (neat): 3059, 2925, 2853, 2193, 1669, 1596, 1489, 1448, 1237,
755, 690 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.06–7.96 (m, 2 H), 7.68–7.25 (m,
8 H), 2.83–2.16 (m, 4 H), 1.82–1.62 (m, 8 H).
13C NMR (100 MHz, CDCl3): d = 194.2, 160.3, 136.7, 133.3, 131.2,
129.9, 128.4, 128.2, 128.1, 123.4, 119.1, 97.5, 86.0, 36.1, 33.0,
29.6, 29.0, 27.4, 26.9.
MS (EI): m/z (%) = 314 (M+, 13.1), 257 (10.3), 105 (100), 91 (14.5),
77 (58.2).
References
(1) (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102,
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McNelis, E. Synth. Commun. 1995, 25, 1223.
Anal. Calcd for C23H22O: C, 87.86; H, 7.05. Found: C, 87.69; H,
7.12.
(4) Janas, J. J.; Asirvatham, E. T.; McNelis, E. Tetrahedron Lett.
1985, 26, 1967.
Acknowledgment
(5) Wang, G. P.; Chen, Z. C. Synth. Commun. 1999, 29, 2859.
This work was supported by the National Natural Science Founda-
tion of China (No. 20332060) and Zhejiang Provence Foundation of
Member of Chinese Academy of Sciences.
Synthesis 2004, No. 15, 2459–2462 © Thieme Stuttgart · New York