Platinum- and ruthenium-catalyzed aromatization of enediynes via intramolecular nucleophilic additions

Article abstract of DOI:10.1055/s-2007-983739

Catalytic cyclization of enediynes via intramolecular nucleophilic addition was achieved with TpRuPPh₃(MeCN)₂PF₆ and platinum dichloride, giving naphthalene-fused 2,3-dihydrofurans and -pyrroles in good yields. On the basi

Full text of DOI:10.1055/s-2007-983739

2050
SPECIAL TOPIC
Platinum- and Ruthenium-Catalyzed Aromatization of Enediynes via
Intramolecular Nucleophilic Additions
Cyclizationof
E
n
h
ediynes via
a
n
la
r
N
ucleop
u
Department of Chemistry, National Tsing-Hua University, 101 Sec 2, Kuang Fu Rd., Hsinchu 30034, Taiwan
E-mail: rsliu@mx.nthu.edu.tw
Received 1 April 2007
TpRuPPh3(MeCN)2PF6 (10 mol%) in hot pentan-3-one
Abstract: Catalytic cyclization of enediynes via intramolecular nu-
cleophilic addition was achieved with TpRuPPh3(MeCN)2PF6 and
platinum dichloride, giving naphthalene-fused 2,3-dihydrofurans
and -pyrroles in good yields. On the basis of experimental results,
(100 °C, 12 h) afforded cyclized 2,3-dihydrofuran product
4 in 70% yield. The same cyclization was performed more
efficiently with 10% PtCl2 under carbon monoxide (1
the mechanism is proposed to involve nucleophilic addition to a p- atm)6 in hot pentan-3-one (100 °C, 3 h) and gave 4 in 83%
alkyne intermediate, followed by alkyne insertion.
yield.
Key words: enediynes, aromatization, intramolecular nucleophilic
addition, ruthenium, platinum
OH
( )2
I
PdCl2(PPh3)2
CuI, Et2NH
OH
( )2
+
2
Br
Br
The Bergman aromatization of enediynes1 has attracted
considerable attention because of its potential application
in medicinal and materials chemistry.2,3 The Bergman re-
action of unstrained enediynes can be implemented by
metal complexes under mild conditions via metal–
vinylidene intermediates4a,b or through a metal-chelated
effect.4c–f This cyclization is synthetically useful because
organic functional groups can be introduced onto benzene
products via suitable nucleophiles. Recently, we reported
the aromatization of unstrained enediynes via regiocon-
trolled nucleophilic addition catalyzed by the ruthenium
catalyst, TpRuPPh3(MeCN)2PF6 (10 mol%). The mecha-
nism of this cyclization has been elucidated to proceed via
nucleophilic addition to p-alkyne intermediate A, fol-
lowed by an alkyne insertion reaction of intermediate B
(Scheme 1).5 In this investigation, we extend this catalytic
cyclization to intramolecular nucleophilic additions cata-
1
(1)
3 mol% PdCl2(PhCN)2
6 mol% P(tBu)3
O
OH
( )2
TMSC
CH
10 mol% M
CuI, iPr2NH
(2) TBAF
3
4
M = TpRuPPh3(MeCN)2PF6 (70%)
PtCl2/CO (83%)
Scheme 2 Synthesis of 2,3-dihydronaphtho[1,2-b]furan
We also prepared various enediynes 5–12 bearing a
tethered alcohol or amine to examine the generality of this
nucleophilic aromatization. The cyclizations were studied
using PtCl2/carbon monoxide and TpRuPPh3(MeCN)2PF6.
In most cases, the use of the PtCl2 system appeared to be
superior to that of the ruthenium catalyst in terms of the
observed product yields and reaction periods required. As
shown in Table 1 (entries 1–3), this intramolecular cy-
clization was applicable to substrates 5–7 bearing a sec-
ondary alcohol; the yield was particularly low for the
phenyl-substituted product 15. Electron-rich benzene sub-
strates 8 and 9 did not show an enhancement in the cy-
clization efficiency; both catalysts gave desired cyclized
lyzed
by
platinum
dichloride
(PtCl2)
and
TpRuPPh3(MeCN)2PF6.
Scheme 2 shows a typical procedure to prepare enediyne
substrate 3, which was obtained conveniently from se-
quential palladium-catalyzed coupling of 1-bromo-2-io-
dobenzene (1) with but-3-yn-1-ol and then trimethyl-
silylacetylene, followed by desilylation using tetrabutyl-
ammonium fluoride. Treatment of alcohol 3 (0.50 M) with
Nu
R
Nu
Nu
R
Ru+
Nu-H
H+
R1
R2
R1
R2
R1
R2
R
R1
R2
R
Ru+
Ru
H+
B
C
A
Ru
Scheme 1 Ruthenium-catalyzed cyclization of enediynes via nucleophilic addition
SYNTHESIS 2007, No. 13, pp 2050–2054
x
x.
x
x
.
2
0
0
7
Advanced online publication: 26.06.2007
DOI: 10.1055/s-2007-983739; Art ID: C02807SS
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Cyclization of Enediynes via Intramolecular Nucleophilic Addition
2051
Table 1 Ruthenium- and Platinum-Catalyzed Cyclization of Enediynes
R
R
X
XH
Y
Z
Y
Z
13–20
5–11
Entry
Enediynea
Product
Yieldb (%)
Using PtCl2/CO
Using TpRuPPh3(MeCN)2PF6
1
2
3
4
5
6
7
8
X = O, Y = Z = H, R = Me (5)
X = O, Y = Z = H, R = Pr (6)
X = O, Y = Z = H, R = Ph (7)
X = O, Y = OMe, Z = R = H (8)
X = O, Y = R = H, Z = OMe (9)
X = NPh, Y = Z = R = H (10)
X = NPh, Y = R = H, Z = OMe (11)
X = NPh, Y = Z = OMe, R = H (12)
13
14
15
16
17
18
19
20
76
78
51
71
73
79
75
76
72
73
40
70
67
72
68
68
a 10 mol% TpRuPPh3(MeCN)2PF6 or PtCl2/CO, 0.50 M enediyne, pentan-3-one, 100 °C, 12 h for Ru catalyst and 4 h for Pt catalyst.
b Yields were reported after separation using a silica gel column.
products 16 and 17, respectively, in good yields (67– Table 2 shows additional examples of the cyclization us-
73%). This cyclization also worked well for nitrogen- ing platinum and ruthenium catalysts with iodoalkynes
based nucleophiles, as in substrates 10–12; in these cases, 21–23 as the substrates. The corresponding cyclization
TpRuPPh3(MeCN)2PF6 again seemed to be less efficient products 24–26 were obtained without a 1,2-iodo shift ac-
than PtCl2 in producing the corresponding 2,3-dihydropyr- cording to the 1H NOE spectra. The lack of a 1,2-iodo shift
role products 18–20. Table 1 shows that electron-rich suggests that metal–vinylidene is not involved in the cy-
benzenes 8, 9, 11, and 12 (entries 4, 5, 7, and 8, respective- clization. To assert the role of a p-alkyne intermediate, we
ly) work with equal efficiency as unsubstituted benzene prepared enediyne d1-3, bearing a 96% deuterium content
derivatives 5–7 and 11 (entries 1–3 and 6, respectively) at the alkyne terminus; its corresponding platinum cataly-
for both two catalysts; a similar phenomenon was previ- sis gave fused 2,3-dihydrofuran d1-4 which does not show
ously observed for ruthenium-catalyzed intermolecular a 1,2-hydrogen shift. This information clearly excludes
aromatization (see Scheme 1).5
the involvement of a vinylidene intermediate in the reac-
tion mechanism.
Table 2 Aromatization of Enediynes Bearing Deuterium or Iodo Substituents
R
R
O
OH
X
X
X
X
Y
24–26
21–23
Y
Entry
Enediyne
Product
Yield (%)
Using PtCl2/CO
Using TpRuPPh3(MeCN)2PF6
1
2
3
4
X = R = H, Y = I (21)
24
61
62
61
72
52
55
53
–
X = H, R = Me, Y = I (22)
X = OMe, R = H, Y = I (23)
X = R = H, Y = 96% D (d1-3)
25
26
d1-4 (Y = 74% D)
Synthesis 2007, No. 13, 2050–2054 © Thieme Stuttgart · New York

2052
B. P. Taduri et al.
SPECIAL TOPIC
HO
HO
OH
( )2
..
··
·
MeO
X
X
D
E
·
M
M
M
Scheme 3 An alternative mechanism for the aromatization
ed to a 1.0 M THF soln of TBAF (3.0 mL). The mixture was stirred
for 2 h before treatment with H2O (30 mL). The solution was ex-
tracted with Et2O (3 × 15 mL) and the extract was concentrated un-
der reduced pressure. The residue was purified by column
chromatography (Et2O) to afford 3; yield: 1.00 g (69%).
The results in Table 2 support the idea that the intramolec-
ular nucleophilic aromatization proceeds via the same
mechanism as that of the intermolecular process.5 An al-
ternative mechanism involving metal diradical D/car-
benoid intermediate E seems to be incompatible with our
experimental observations (Scheme 3). Although this
mechanism has been postulated in the tethered alkane car-
bon–hydrogen bond insertion,7 it is expected that the elec-
tron-rich benzene (X = OMe) would stabilize carbenoid
intermediate E to facilitate the nucleophilic addition. This
hypothesis is opposed to our observation that electron-
rich benzenes fail to show cyclization enhancement as de-
picted in Table 1.
IR (neat): 3650 (s), 3020 (w), 2112 (w), 1622 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.46 (d, 1 H, J = 7.2 Hz), 7.39 (d,
1 H, J = 7.2 Hz), 7.27–7.20 (m, 2 H), 3.80 (t, 2 H, J = 6.0 Hz), 3.31
(s, 1 H), 2.70 (t, 2 H, J = 6.0 Hz).
13C NMR (100 MHz, CDCl3): d = 132.4, 131.5, 128.5, 127.6, 126.2,
124.5, 91.0, 82.6, 81.2, 80.6, 60.9, 24.0.
HRMS: m/z calcd for C12H10O: 170.0732; found: 170.0729.
Ruthenium-Catalyzed Aromatization of Enediynes; Typical
Procedure
In summary, we report platinum- and ruthenium-cata-
lyzed cyclizations of enediynes via intramolecular nu-
cleophilic addition. This cyclization enables one-pot
syntheses of naphthalene-fused 2,3-dihydrofurans and
-pyrroles. On the basis of experimental results, the mech-
anism is proposed to involve nucleophilic addition to a p-
alkyne intermediate, followed by alkyne insertion, inden-
tical to that reported for the intermolecular process.5
To a solution of enediyne 3 (100 mg, 0.59 mmol) and pentan-3-one
(0.60 mL) was added TpRuPPh3(MeCN)2PF6 (44 mg, 0.059 mmol),
and the mixture was brought to 100 °C and heated at that tempera-
ture for 12 h. The solution was concentrated and eluted through a
silica gel column (hexane–EtOAc, 5:1) to give 2,3-dihydrofuran 4;
yield: 70 mg (70%).
IR (neat): 3016 (w), 1620 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.92 (d, 1 H, J = 8.8 Hz), 7.79 (d,
1 H, J = 8.8 Hz) 7.44–7.39 (m, 2 H), 7.37–7.32 (m, 2 H), 4.76 (t, 2
H, J = 8.8 Hz), 3.37 (t, 2 H, J = 8.8 Hz).
13C NMR (100 MHz, CDCl3): d = 155.3, 133.8, 127.8, 125.5, 125.2,
122.8, 121.3, 120.4, 120.0, 119.8, 71.7, 30.5.
Unless otherwise noted, all reactions were carried out under an N2
atmosphere in oven-dried glassware using standard syringe, cannu-
la and septa apparatus. Benzene, Et2O, THF, and hexane were dried
(sodium benzophenone) and distilled before use. The ruthenium
catalyst, TpRuPPh3(MeCN)2PF6, was prepared by heating Tp-
Ru(PPh3)2Cl with LiPF6 in MeCN.8IR spectra were collected on a
BOMEM MB100 FT-IR spectrometer. NMR spectroscopy was per-
formed on a Varian Mercury-400 spectrometer, with residual un-
deuterated solvent as an internal standard. High-resolution mass
spectrometry was carried out on a Jeol JMS-HX 100 instrument us-
ing electron ionization method.
HRMS: m/z calcd for C12H10O: 170.0732; found: 170.0730.
5-(2-Ethynylphenyl)pent-4-yn-2-ol (5)
IR (neat): 3016 (w), 1620 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.47 (d, 1 H, J = 7.2 Hz), 7.39 (d,
1 H, J = 6.8 Hz), 7.28–7.21 (m, 2 H), 4.10–4.02 (m, 1 H), 3.30 (s, 1
H), 2.67 (dd, 1 H, J = 16.8, 4.8 Hz), 2.55 (dd, 1 H, J = 16.8, 5.6 Hz),
1.32 (d, 3 H, J = 6.0 Hz).
4-(2-Ethynylphenyl)but-3-yn-1-ol (3); Typical Procedure
To an Et2NH soln (40 mL) of 1-bromo-2-iodobenzene (1; 4.00 g,
14.1 mmol) was added PdCl2(PPh3)2 (198 mg, 0.28 mmol) and CuI
(54 mg, 0.28 mmol) at 28 °C, and the mixture was stirred for 5 min
before addition of but-3-yn-1-ol (1.18 g, 16.9 mmol). The solution
was stirred for 12 h and concentrated in vacuo, sat. NaHCO3 soln
was added and the mixture was extracted with Et2O. The Et2O ex-
tract was washed with sat. NaCl soln, dried (anhyd MgSO4), and
concentrated under reduced pressure. The residues were chromato-
graphed through a silica gel column (hexane–EtOAc, 4:1) to afford
compound 2 as a yellow oil; yield: 2.84 g (89%).
13C NMR (100 MHz, CDCl3): d = 132.6, 131.7, 128.6, 127.5, 126.4,
124.6, 90.8, 82.7, 81.7, 80.5, 66.3, 30.3, 22.2.
HRMS: m/z calcd for C13H12O: 184.0888; found: 184.0885.
1-(2-Ethynylphenyl)hept-1-yn-4-ol (6)
IR (neat): 3653 (s), 3019 (w), 2111 (w), 1627 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.47 (d, 1 H, J = 7.2 Hz), 7.39 (d,
1 H, J = 6.8 Hz), 7.28–7.20 (m, 2 H), 3.87–3.81 (m, 1 H), 3.30 (s, 1
H), 2.68 (dd, 1 H, J = 16.8, 4.8 Hz), 2.56 (dd, 1 H, J = 16.8, 5.6 Hz),
2.32 (d, 1 H, J = 5.6 Hz), 1.65–1.55 (m, 2 H), 1.53–1.46 (m, 1 H),
1.43–1.34 (m, 1 H), 0.93 (t, 3 H, J = 7.2 Hz).
13C NMR (100 MHz, CDCl3): d = 132.6, 131.8, 128.7, 127.8, 126.6,
124.8, 91.1, 83.0, 81.9, 80.8, 70.0, 38.6, 28.8, 19.1, 14.2.
To PdCl2(PhCN)2 (195 mg, 0.51 mmol) and CuI (99 mg, 0.51
mmol) was added anhyd toluene (20 mL). Then P(t-Bu)3 (206 mg
1.02 mmol), i-Pr2NH (1.29 g, 12.7 mmol), bromobenzene 2 (1.91 g,
8.49 mmol), and trimethylsilylacetylene (1.20g, 12.2 mmol) were
added via syringe to the stirred mixture. After 10 h, the mixture was
diluted with Et2O (40 mL), filtered through a small pad of silica gel
(with Et2O rinsing), concentrated, and purified by flash chromatog-
raphy. This silyl derivative was dissolved in THF (10 mL) and add-
HRMS: m/z calcd for C15H16O: 212.1201; found: 212.1200.
4-(2-Ethynylphenyl)-1-phenylbut-3-yn-1-ol (7)
IR (neat): 3650 (s), 3017 (w), 2116 (w), 1620 (w) cm–1.
Synthesis 2007, No. 13, 2050–2054 © Thieme Stuttgart · New York

SPECIAL TOPIC
Cyclization of Enediynes via Intramolecular Nucleophilic Addition
2053
1H NMR (400 MHz, CDCl3): d = 7.49–7.40 (m, 3 H), 7.39–7.30 (m,
3 H), 7.30–7.25 (m, 3 H), 4.98–4.96 (m, 1 H), 3.30 (s, 1 H), 2.98–
2.80 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 142.5, 132.4, 132.2, 131.6, 128.4,
127.8, 127.7, 126.2 (× 2), 125.7 (× 2), 124.6, 90.5, 82.6, 82.0, 72.3,
30.9.
2-Methyl-2,3-dihydronaphtho[1,2-b]furan (13)
IR (neat): 3014 (w), 1624 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.92 (d, 1 H, J = 8.2 Hz), 7.77 (d,
1 H, J = 8.2 Hz), 7.42–7.36 (m, 2 H), 7.35–7.27 (m, 2 H), 5.17–5.08
(m, 1 H), 4.48 (dd, 1 H, J = 14.4, 8.8 Hz), 2.97 (dd, 1 H, J = 14.4,
7.2 Hz), 1.54 (d, 3 H, J = 6.8 Hz).
HRMS: m/z calcd for C18H14O: 246.1045; found: 246.1040.
13C NMR (100 MHz, CDCl3): d = 154.7, 133.9, 127.8, 125.4, 125.1,
122.9, 121.4, 120.5, 119.8, 119.7, 80.2, 37.9, 22.0.
4-(2-Ethynyl-5-methoxyphenyl)but-3-yn-1-ol (8)
HRMS: m/z calcd for C13H12O: 184.0888; found: 184.0884.
IR (neat): 3650 (s), 3014 (w), 2110 (w), 1627 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.38 (d, 1 H, J = 8.8 Hz), 6.90 (s,
1 H), 6.78 (d, 1 H, J = 8.8 Hz), 3.81–3.77 (m, 2 H), 3.77 (s, 3 H),
3.22 (s, 1 H), 2.71 (t, 2 H, J = 6.4 Hz).
13C NMR (100 MHz, CDCl3): d = 159.5, 133.8, 127.6, 117.0, 116.2,
114.5, 90.9, 82.6, 81.3, 76.6, 60.9, 55.3, 24.0.
2-Propyl-2,3-dihydronaphtho[1,2-b]furan (14)
IR (neat): 3019 (w), 1626 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.93 (d, 1 H, J = 8.8 Hz), 7.77 (d,
1 H, J = 8.8 Hz), 7.40–7.36 (m, 2 H), 7.34–7.27 (m, 2 H), 5.02–4.95
(m, 1 H), 3.44 (dd, 1 H, J = 15.2, 9.6 Hz), 3.00 (dd, 1 H, J = 15.2,
8.2 Hz), 1.93–1.86 (m, 1 H), 1.75–1.69 (m, 1 H), 1.63–1.49 (m, 2
H), 0.99 (t, 3 H, J = 8.0 Hz).
HRMS: m/z calcd for C13H12O2: 200.0837; found: 200.0834.
4-(2-Ethynyl-4-methoxyphenyl)but-3-yn-1-ol (9)
13C NMR (100 MHz, CDCl3): d = 154.8, 133.8, 127.7, 125.4, 125.0,
122.9, 121.4, 120.5, 119.7, 119.6, 83.3, 38.4, 36.2, 18.6, 14.0.
IR (neat): 3652 (s), 3016 (w), 2113 (w), 1623 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.31 (d, 1 H, J = 8.8 Hz), 6.98 (s,
1 H), 6.82 (d, 1 H, J = 8.8 Hz), 3.81–3.77 (m, 2 H), 3.78 (s, 3 H),
3.29 (s, 1 H), 2.70 (t, 2 H, J = 6.4 Hz).
13C NMR (100 MHz, CDCl3): d = 158.7, 132.8, 125.7, 118.7, 117.0,
115.5, 89.1, 82.5, 81.0, 80.4, 60.9, 55.3, 24.0.
HRMS: m/z calcd for C15H16O: 212.1201; found: 212.1198.
2-Phenyl-2,3-dihydronaphtho[1,2-b]furan (15)
IR (neat): 3026 (w), 1630 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 8.02 (d, 1 H, J = 8.8 Hz), 7.81 (d,
1 H, J = 8.8 Hz), 7.45–7.28 (m, 9 H), 5.96 (t, 1 H, J = 9.6 Hz), 3.82
(dd, 1 H, J = 15.6, 9.6 Hz), 3.36 (dd, 1 H, J = 15.6, 9.6 Hz).
HRMS: m/z calcd for C13H12O2: 200.0837; found: 200.0833.
N-[4-(2-Ethynylphenyl)but-3-ynyl]benzenamine (10)
13C NMR (100 MHz, CDCl3): d = 154.9, 142.3, 134.0, 128.6 (× 2),
127.9, 127.8, 125.7, 125.6 (× 2), 125.3, 122.7, 121.5, 120.3, 119.2,
84.6, 39.4.
IR (neat): 3650 (w), 3285 (s), 2100 (w), 1683 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.49 (d, 1 H, J = 7.6 Hz), 7.48 (d,
1 H, J = 7.2 Hz), 7.29–7.22 (m, 2 H), 7.19 (t, 2 H, J = 7.6 Hz), 6.73
(t, 1 H, J = 7.2 Hz), 6.67 (d, 2 H, J = 7.2 Hz), 3.34 (t, 2 H, J = 6.4
Hz), 3.28 (s, 1 H), 2.77 (t, 2 H, J = 6.4 Hz).
13C NMR (100 MHz, CDCl3): d = 147.7, 132.5, 131.7, 129.2 (× 2),
128.5, 127.5, 126.4, 124.5, 117.7, 113.2 (× 2), 91.7, 82.5, 80.6 (× 2),
42.5, 20.2.
HRMS: m/z calcd for C18H14O: 246.1045; found: 246.1041.
8-Methoxy-2,3-dihydronaphtho[1,2-b]furan (16)
IR (neat): 3023 (w), 1628 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.81 (d, 1 H, J = 8.8 Hz), 7.29–
7.22 (m, 2 H), 7.08–7.05 (m, 2 H), 4.73 (t, 2 H, J = 8.8 Hz), 3.88 (s,
3 H), 3.33 (t, 2 H, J = 8.8 Hz).
13C NMR (100 MHz, CDCl3): d = 157.5, 154.4, 135.2, 123.4, 123.0,
118.9, 118.0, 117.8, 116.0, 105.9, 71.8, 55.2, 30.4.
HRMS: m/z calcd for C18H15N: 245.1204; found: 245.1200.
N-[4-(2-Ethynyl-4-methoxyphenyl)but-3-ynyl]benzenamine
(11)
HRMS: m/z calcd for C13H12O2: 200.0837; found: 200.0833.
IR (neat): 3640 (w), 3282 (s), 2104 (w), 1681 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.40 (d, 1 H, J = 8.4 Hz), 7.18 (t,
2 H, J = 7.2 Hz), 6.91 (s, 1 H), 6.79 (d, 1 H, J = 7.2 Hz), 6.74 (t, 1
H, J = 7.2 Hz), 6.67 (d, 2 H, J = 8.4 Hz), 3.78 (s, 3 H), 3.40 (t, 2 H,
J = 6.4 Hz), 3.19 (s, 1 H), 2.76 (t, 2 H, J = 6.4 Hz).
13C NMR (100 MHz, CDCl3): d = 159.4, 147.7, 133.8, 129.2 (× 2),
127.7, 117.8, 116.9, 116.4, 114.5, 113.3 (× 2), 91.6, 82.6, 80.8, 79.1,
55.3, 42.5, 20.2.
7-Methoxy-2,3-dihydronaphtho[1,2-b]furan (17)
IR (neat): 3020 (w), 1625 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.68 (d, 1 H, J = 8.8 Hz), 7.29 (d,
1 H, J = 8.4 Hz), 7.19 (d, 2 H, J = 8.4 Hz), 7.06 (d, 1 H, J = 8.4 Hz),
4.75 (t, 2 H, J = 9.6 Hz), 3.90 (s, 3 H), 3.36 (t, 2 H, J = 9.6 Hz).
13C NMR (100 MHz, CDCl3): d = 157.3, 154.4, 133.8, 129.6, 128.4,
121.2, 120.4, 120.0, 118.7, 99.0, 71.6, 55.3, 30.7.
HRMS: m/z calcd for C19H17NO: 275.1310; found: 275.1306.
HRMS: m/z calcd for C13H12O2: 200.0837; found: 200.0834.
N-[4-(2-Ethynyl-4,5-dimethoxyphenyl)but-3-ynyl]benzen-
amine (12)
1-Phenyl-2,3-dihydro-1H-benzo[g]indole (18)
IR (neat): 3019 (w), 1614 (s) cm–1.
IR (neat): 3655 (w), 3285 (s), 2105 (w), 1680 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.81 (d, 1 H, J = 8.0 Hz), 7.46 (d,
1 H, J = 8.4 Hz), 7.40–7.31 (m, 3 H), 7.26–7.18 (m, 3 H), 7.1–6.96
(m, 3 H), 4.19 (t, 2 H, J = 8.4 Hz), 3.26 (t, 2 H, J = 8.4 Hz).
13C NMR (100 MHz, CDCl3): d = 149.3, 143.0, 129.0, 128.9 (× 2),
128.6, 128.5, 124.7, 124.4, 124.3, 123.2, 122.8, 122.2 122.0, 121.4
(× 2), 58.5, 30.1.
1H NMR (400 MHz, CDCl3): d = 7.17 (t, 2 H, J = 7.2 Hz), 6.93 (s,
1 H), 6.85 (s, 1 H), 6.71 (t, 1 H, J = 7.2 Hz), 6.66 (d, 2 H, J = 7.2
Hz), 3.84 (s, 6 H), 3.39 (t, 2 H, J = 6.4 Hz), 3.22 (s, 1 H), 2.75 (t, 2
H, J = 6.4 Hz).
13C NMR (100 MHz, CDCl3): d = 149.2, 148.5, 147.7, 129.2 (× 2),
119.5, 117.7, 117.2, 114.5, 113.9, 113.2 (× 2), 90.1, 82.7, 80.7, 79.3,
55.9 (× 2), 42.5, 20.2.
HRMS: m/z calcd for C18H15N: 245.1204; found: 245.1200.
HRMS: m/z calcd for C20H19NO2: 305.1416; found: 305.1411.
Synthesis 2007, No. 13, 2050–2054 © Thieme Stuttgart · New York

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B. P. Taduri et al.
SPECIAL TOPIC
7-Methoxy-1-phenyl-2,3-dihydro-1H-benzo[g]indole (19)
1H NMR (400 MHz, CDCl3): d = 7.85 (d, 1 H, J = 9.2 Hz), 7.76 (s,
1 H), 7.64 (d, 1 H, J = 9.2 Hz), 7.40–7.37 (m, 2 H), 5.18–5.09 (m, 1
H), 3.44 (dd, 1 H, J = 15.2, 9.2 Hz), 2.94 (dd, 1 H, J = 15.2, 9.2 Hz),
1.54 (d, 3 H, J = 6.0 Hz).
13C NMR (100 MHz, CDCl3): d = 153.7, 135.3, 128.1, 126.6, 126.3,
125.5, 124.3, 121.7, 119.9, 89.9, 79.2, 42.4, 22.2.
IR (neat): 3023 (w), 1614 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.70 (d, 1 H, J = 9.2 Hz), 7.40 (d,
1 H, J = 8.0 Hz), 7.25 (t, 3 H, J = 8.4 Hz), 7.02–6.69 (m, 4 H), 6.57
(s, 1 H), 4.16 (t, 2 H, J = 8.8 Hz), 3.50 (s, 3 H), 3.25 (t, 2 H, J = 8.8
Hz).
13C NMR (100 MHz, CDCl3): d = 156.4, 148.9, 142.1, 130.0, 129.5,
129.4, 128.8, 128.5 (× 2), 123.5, 122.0, 121.4 (× 2), 120.8, 117.8,
102.8, 58.4, 55.2, 29.7.
HRMS: m/z calcd for C13H11IO: 309.9855; found: 309.9853.
4-Iodo-7,8-dimethoxy-2,3-dihydronaphtho[1,2-b]furan (26)
IR (neat): 3019 (w), 1613 (s) cm–1.
HRMS: m/z calcd. for C19H17NO: 275.1310; found: 275.1306.
1H NMR (400 MHz, CDCl3): d = 7.19 (s, 1 H), 7.16 (s, 1 H), 7.08
(s, 1 H), 4.73 (t, 2 H, J = 8.8 Hz), 3.96 (s, 3 H), 3.95 (s, 3 H), 3.34
(t, 2 H, J = 8.8 Hz).
8-Dimethoxy-1-phenyl-2,3-dihydro-1H-benzo[g]indole (20)
IR (neat): 3024 (w), 1612 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.30 (d, 1 H, J = 8.4 Hz), 7.26–
7.22 (m, 3 H), 7.09 (s, 1 H), 6.99–6.95 (m, 3 H), 6.57 (s, 1 H), 4.16
(t, 2 H, J = 8.0 Hz), 3.95 (s, 3 H), 3.35 (s, 3 H), 3.22 (t, 2 H, J = 8.0
Hz).
13C NMR (100 MHz, CDCl3): d = 154.5, 153.5, 149.4, 131.3, 129.7,
126.7, 123.2, 121.0, 118.5, 87.0, 71.7, 55.9, 55.8, 30.0.
HRMS: m/z calcd for C14H13IO3: 355.9909; found: 355.9904.
13C NMR (100 MHz, CDCl3): d = 148.7, 148.5, 148.0, 142.0, 129.8,
128.7, 128.5 (× 2), 127.1, 122.0, 121.5, 120.4 (× 2), 117.9, 106.9,
103.6, 58.3, 55.6, 55.2, 30.0.
Acknowledgment
The authors wish to thank the National Science Council, Taiwan,
for supporting this work.
HRMS: m/z calcd for C20H19NO2: 305.1416; found: 305.1412.
4-[2-(Iodoethynyl)phenyl]but-3-yn-1-ol (21)
IR (neat): 3603 (w), 3200 (s), 2104 (w), 1684 (w) cm–1.
References
1H NMR (400 MHz, CDCl3): d = 7.39–7.35 (m, 2 H), 7.24–7.18 (m,
2 H), 3.81 (t, 2 H, J = 6.4 Hz), 2.71 (t, 2 H, J = 6.4 Hz).
13C NMR (100 MHz, CDCl3): d = 132.4, 131.5, 128.3, 127.4, 126.6,
125.7, 93.0, 91.0, 80.8, 60.9, 23.9, 10.0.
(1) (a) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25.
(b) Lockhart, T. P.; Comita, P. B.; Bergman, R. G. J. Am.
Chem. Soc. 1981, 103, 4082.
(2) Reviews: (a) Enediyne Antibiotics as Antitumor Agents;
Borders, D. B.; Doyle, T. W., Eds.; Marcel Dekker: New
York, 1995. (b) Xi, Z.; Goldberg, I. H. In Comprehensive
Natural Product Chemistry, Vol. 7; Barton, D. H. R.;
Nakanishi, K., Eds.; Pergamon: Oxford, 1999, 553.
(3) Recent reviews: (a) Basak, A.; Mandal, S.; Bag, S. S. Chem.
Rev. 2003, 103, 4077. (b) Rawat, D. S.; Zaleski, J. M.
Synlett 2004, 393. (c) Bowles, D. M.; Palmer, G. J.; Landis,
C. A.; Scott, J. L.; Anthony, J. E. Tetrahedron 2001, 57,
3753. (d) Grissom, J. W.; Gunawardena, G. U.; Klingberg,
D.; Huang, D. Tetrahedron 1996, 52, 6453. (e) Wang, K. K.
Chem. Rev. 1996, 96, 207.
(4) For selected examples of stoichiometric metal-mediated
Bergman cyclizations, see: (a) Wang, Y. S.; Finn, M. G. J.
Am. Chem. Soc. 1995, 117, 8045. (b) O’Connor, J. M.;
Friese, S. J.; Tichenor, M. J. Am. Chem. Soc. 2002, 124,
3506. (c) Zaleski, J. M.; Rawat, D. S. J. Am. Chem. Soc.
2001, 123, 9675. (d) Warner, B. P.; Millar, S. P.; Broene, R.
D.; Buchwald, S. L. Science 1995, 269, 814. (e) Konig, B.;
Hollnagel, H.; Ahrens, B.; Jones, P. G. Angew. Chem., Int.
Ed. Engl. 1995, 34, 2538. (f) Landis, C. A.; Payne, M. M.;
Eaton, D. L.; Anthony, J. E. J. Am. Chem. Soc. 2004, 126,
1338.
HRMS: m/z calcd for C12H9IO: 295.9698; found: 295.9693.
4-[2-(Iodoethynyl)phenyl]pent-4-yn-1-ol (22)
IR (neat): 3609 (w), 3203 (s), 2102 (w), 1685 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.41–7.36 (m, 2 H), 7.25–7.19 (m,
2 H), 4.08–4.02 (m, 1 H), 2.71–2.55 (m, 2 H), 1.35 (d, 3 H, J = 6.0
Hz).
13C NMR (150 MHz, CDCl3): d = 132.6, 131.5, 128.5, 127.6, 126.7,
125.8, 93.2, 90.7, 81.5, 66.4, 30.3, 22.3, 10.0.
HRMS: m/z calcd for C13H11IO: 309.9855; found: 309.9851.
4-[2-(Iodoethynyl)-4,5-dimethoxyphenyl]but-3-yn-1-ol (23)
IR (neat): 3609 (w), 3203 (s), 2102 (w), 1685 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = 6.84 (s, 1 H), 6.81 (s, 1 H), 3.84
(s, 6 H), 3.80 (t, 2 H, J = 6.1 Hz), 2.70 (t, 2 H, J = 6.1 Hz).
13C NMR (100 MHz, CDCl3): d = 149.3, 148.4, 119.8, 118.7, 114.4,
113.5, 93.7, 89.4, 80.9, 61.3, 56.1 (× 2), 24.5, 14.1.
HRMS: m/z calcd for C14H13IO3: 355.9909; found: 355.9904.
(5) Odedra, A.; Wu, C.-J.; Pratap, B. P.; Huang, C.-W.; Ran, Y.-
F.; Liu, R.-S. J. Am. Chem. Soc. 2005, 127, 3406.
(6) For the PtCl2/CO system, see (a) Fürstner, A.; Davies, P.
W.; Gress, T. J. Am. Chem. Soc. 2005, 127, 8244.
(b) Fürstner, A.; Aïssa, C. J. Am. Chem. Soc. 2006, 128,
6306. (c) Fürstner, A.; Davies, P. W. J. Am. Chem. Soc.
2005, 127, 15024.
(7) Taduri, B. P.; Ran, Y.-F.; Huang, C.-W.; Liu, R.-S. Org.
Lett. 2006, 8, 883.
(8) Chan, W.-C.; Lau, C.-P.; Chan, Y.-Z.; Fang, Y.-Q.; Ng, S.-
M.; Jia, G. Organometallics 1997, 16, 34.
4-Iodo-2,3-dihydronaphtho[1,2-b]furan (24)
IR (neat): 3026 (w), 1617 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 7.85 (d, 1 H, J = 9.2 Hz), 7.78 (s,
1 H), 7.65 (d, 1 H, J = 9.2 Hz), 7.41–7.38 (m, 2 H), 4.77 (t, 2 H, J =
9.2 Hz), 3.34 (t, 2 H, J = 9.2 Hz).
13C NMR (100 MHz, CDCl3): d = 154.3, 135.3, 128.4, 126.6, 126.4,
125.6, 124.6, 121.6, 91.8, 89.7, 70.5, 35.2.
HRMS: m/z calcd for C12H9IO: 295.9698; found: 295.9694.
4-Iodo-2-methyl-2,3-dihydronaphtho[1,2-b]furan (25)
IR (neat): 3029 (w), 1610 (s) cm–1.
Synthesis 2007, No. 13, 2050–2054 © Thieme Stuttgart · New York