PtCl2-catalyzed cyclization of o-diethynylbenzene derivatives triggered by intramolecular nucleophilic attack

Article abstract of DOI:10.1080/00397911003797817

(Chemical Equation Presented) PtCl₂-catalyzed cyclization of o-diethynylbenzene derivatives bearing a hydroxyethyl group yielded naphthofuran derivatives by initial intramolecular cyclization of the hydroxy group to an activated ethynyl group followed by attack of the second ethynyl group to a vinylplatinum intermediate. When the ethynyl terminal is substituted by a hydroxypropyl group, not only homologous naphthodihydropyran but also indenylidenete-trahydrofuran derivatives were formed. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911003797817

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PtCl2-Catalyzed Cyclization of o-
Diethynylbenzene Derivatives Triggered
by Intramolecular Nucleophilic Attack
Koji Miki a , Hiroyuki Kuge a , Rui Umeda a , Motohiro Sonoda a &
Yoshito Tobe a
a Division of Frontier Materials Science, Graduate School of
Engineering Science , Osaka University , Toyonaka , Osaka , Japan
Published online: 03 Mar 2011.
To cite this article: Koji Miki , Hiroyuki Kuge , Rui Umeda , Motohiro Sonoda & Yoshito Tobe
(2011) PtCl2-Catalyzed Cyclization of o-Diethynylbenzene Derivatives Triggered by Intramolecular
Nucleophilic Attack, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:7, 1077-1087, DOI: 10.1080/00397911003797817
To link to this article: http://dx.doi.org/10.1080/00397911003797817
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Synthetic Communications1, 41: 1077–1087, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003797817
PtCl2-CATALYZED CYCLIZATION OF
o-DIETHYNYLBENZENE DERIVATIVES TRIGGERED BY
INTRAMOLECULAR NUCLEOPHILIC ATTACK
Koji Miki, Hiroyuki Kuge, Rui Umeda, Motohiro Sonoda, and
Yoshito Tobe
Division of Frontier Materials Science, Graduate School of Engineering
Science, Osaka University, Toyonaka, Osaka, Japan
GRAPHICAL ABSTRACT
Abstract PtCl2-catalyzed cyclization of o-diethynylbenzene derivatives bearing
a
hydroxyethyl group yielded naphthofuran derivatives by initial intramolecular cyclization
of the hydroxy group to an activated ethynyl group followed by attack of the second ethynyl
group to a vinylplatinum intermediate. When the ethynyl terminal is substituted by a
hydroxypropyl group, not only homologous naphthodihydropyran but also indenylidenete-
trahydrofuran derivatives were formed.
Keywords Cyclization; dihydronaphthofuran; Lewis acid; nucleophilic addition;
o-diethynylbenzene
INTRODUCTION
Bergman reaction of o-diethynylbenzene derivatives has been recognized as one
of the potential methods for preparation of naphthalene derivatives.[1] Diradical
intermediates formed in this reaction can be trapped by unsaturated pendant groups,
and by judicious design of substrates, polycyclic carbon skeletons can be con-
structed.[2] A major drawback of this method, however, is the high temperatures
Received December 19, 2009.
Address correspondence to Yoshito Tobe, Division of Frontier Materials Science, Graduate School
of Engineering Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka 560-8531, Japan.
E-mail: tobe@chem.es.osaka-u.ac.jp
1077

1078
K. MIKI ET AL.
required to drive the reaction if substituents of ethynyl groups are not hydrogen.
Although tellurium-mediated formal Bergman cyclization via telluracycle intermedi-
ates has been developed by Landis et al.,[3] the scope of substrates is also limited. For
enediynes bearing at least one terminal ethynyl group, transition metal–mediated
cyclizations that take place via matal-vinylidene intermediates have been extensively
developed.[4] For enediynes that do not bear a terminal ethynyl group, nucleophilic
attack of an internal or external anionic nucleophile to a triple bond has been shown
to trigger the bond formation between the triple bonds, yielding naphthalene deriva-
tives via formal Bergman reactions.[5] Utimoto et al. reported intramolecular
addition of alkynols catalyzed by PdCl2 to furnish dihydrofuran derivatives via a
5-endo process.[6] We envisioned that the use of this reaction as a trigger of double
cyclization of an o-diethynylbenzene bearing a hydroxyethyl group would enable the
preparation of a naphthofuran derivative by attack of the second ethynyl group to
the initially formed vinylplatinum intermediate through a 6-endo cyclization mode
(Scheme 1).[7] Indeed, while our research was in progress, Liu et al. reported the for-
mation of naphthodihydrofurans by PtCl2-catalyzed cyclization of o-diethynylben-
zene derivatives and proposed two types of mechanisms: one through carbene
intermediates and the other via Lewis acid coordination.[8] Whereas in the Liu’s
reports the second ethynyl terminal groups are hydrogen or halogen, we found that
substrates having an alkyl group also undergo this reaction. Moreover, when the
ethynyl terminal is substituted by a hydroxypropyl group, instead of a hydroxyethyl,
not only homologous naphthodihydropyran but also indenylidenetetrahydrofuran
derivatives were formed. These results extend the scope and limitation of PtCl2-
catalyzed cyclization of o-diethynylbenzene derivatives triggered by intramolecular
nucleophilic attack.
Scheme 1. PtCl2-catalyzed double cyclization pathways of o-diethynylbenzenes.

Pt-CATALYZED CYCLIZATION OF o-DIETHYNYLBENZENES
1079
RESULTS AND DISCUSSION
The reaction conditions were optimized using the most readily available diyne,
1,2-bis(4-hydroxybut-1-ynyl)benzene (1a). First, a solution of 1a with 5 mol% of
CuCl2 or PtCl2 was heated in chlorobenzene at 150 ꢀC with an excess amount of
1,4-cyclohexadiene, giving naphthodihydrofuran 2a in 34% or 56% yield, respect-
ively. (During the initial experiments, 1,4-cyclohexadiene was added to intercept a
possible diradical intermediate formed by thermal Bergman reaction. However, it
turned out that even at 150 ꢀC, no thermal reaction took place. In the subsequent
experiments, therefore, cyclohexadiene was omitted.) The formation of 2a can be
interpreted in terms of an initial 5-endo cyclization followed by a 6-endo cyclization
as we expected (Scheme 2). The same product was isolated when CuCl,
PdCl2(PhCN)2, Pd(OAc)2 (at 120 ꢀC), or ZnCl2 (at 120 ꢀC) was used as a catalyst,
but the yields of 2a were less (<20%) because of the formation of unidentified
by-products. Next, the reaction was performed by heating a toluene solution of 1a
and 5 mol% of a catalyst, PtCl2, CuCl2, ZnCl2, PdCl2(COD), or Pd(OAc)2, at
80 ꢀC. Under these conditions, only PtCl2 was effective, furnishing 2a in 41% yield.
Under the same conditions, monohydroxydiyne 1b gave the corresponding aromati-
zation product 2b in 76% yield. These results indicate that the alkyne units do not
have to be terminated with hydrogen or halogen. Similarly, diyne 1c, having substi-
tuents at the benzene ring, afforded the aromatization product 2c, albeit in a lower
yield (11%), presumably because of steric hindrance to the cyclization. On the other
hand, phenol derivative 1d did not react under similar conditions, indicating that phe-
nol is not nucleophilic enough to promote the initial 5-endo cyclization. Moreover,
the reaction of endiyne 3 resulted in the formation of a complex mixture of products.
Next, to investigate the effect of the length of the methylene chains on this reac-
tion, bis(5-hydroxypent-1-ynyl)benzene (4) was examined. The reaction of 4 with
PtCl2 under similar conditions afforded naphthodihydropyran 5, a homolog of 2a,
as the major product in 43% yield (Scheme 3). The structure of 5 was elucidated
1
on the basis of the presence of characteristic naphthalene proton signals in the H
NMR spectrum, which were similar to that of 2a. However, beside 5, two products
(6a and 6b) having an indenylidenetetrahydrofuran backbone were isolated in 29 and
19% yields, respectively, and their structures were assigned mainly on the basis of
1H NMR spectra. Namely, (E)-olefin 6a exhibits the vinyl proton (Ha) signal at
6.47 ppm (s, 1H) besides aromatic proton (Hb-He) signals in the low-field region.
The six methylene signals appear at 4.40 (t), 3.73 (t), 3.28 (t), 2.86 (td), 2.26 (tt),
and 1.93 (tt) ppm, which are assigned to Hf to Hk shown in Scheme 3. The stereo-
chemistry of the double bond was determined on the basis on the nuclear Overhauser
Scheme 2. PtCl2-catalyzed cyclization of o-diethynylbenzenes.

1080
K. MIKI ET AL.
Figure 1. Structures of substrates 1d and 3.
Scheme 3. PtCl2-catalyzed cyclization of o-diethynylbenzene 4.
effect (NOE): Correlation was observed between He and Hk, indicating that these
1
protons are located in close proximity. The H NMR signals of the diastereomer
6b are similar to those of 6a except for the aromatic proton He (7.99–8.04 ppm):
It appears distinctly downfield relative to that of 6a (7.36–7.40 ppm) owing to the
deshielding effect of the proximate oxygen atom of the furan ring, indicating the
Z stereochemistry of the exocyclic double bond. The formation of both E and Z iso-
mers is ascribed to an equilibrium, because leaving a CDCl3 solution of either 6a or
6b at room temperature for a few days led to the formation of an equilibrium mix-
ture of them. (A small amount of unidentified product also formed during the
equilibration.)
The formation of 5 is explained in terms of sequential 6-endo cyclizations as
described previously. On the other hand, furan derivatives 6a and 6b are formed by
initial 5-exo followed by second 5-endo cyclizations. Thus the second cyclization
mode is related to the first one, because the position of the nucleophilic center in
the intermediate, at either benzylic or homobenzylic position, is governed by the mode
of the first step. Elongation of the methylene units allowed two modes of the initial
cyclization step to occur because of increased flexibility of the methylene chains.
CONCLUSIONS
PtCl2-catalyzed cyclization of o-diethynylbenzene derivatives bearing a hydro-
xyethyl group gave naphthofuran derivatives by initial 5-endo followed by 6-endo

Pt-CATALYZED CYCLIZATION OF o-DIETHYNYLBENZENES
1081
cyclizations. On the other hand, the reaction of an o-diethynylbenzene derivative
bearing a hydroxypropyl group yielded not only naphthodihydropyran via sequen-
tial 6-endo cyclizations but also indenylidenetetrahydrofuran derivatives via tandem
5-exo followed by 5-endo cyclizations. These results extend the scope and limitation
of PtCl2-catalyzed aromatization of o-diethynylbenzene derivatives triggered by
intramolecular nucleophilic attack.
EXPERIMENTAL
1H and 13C NMR spectra were recorded on a Varian Mercury 300, a JEOL
JNM-GSX-270, or a JEOL JNM AL-400 spectrometer in CDCl3 and with Me4Si
or residual solvent as an internal standard at 30 ꢀC. Infrared (IR) spectra were taken
with a JASCO Fourier transform (FT)=IR-410 spectrometer, and mass spectra were
obtained on a JEOL JMS-700 spectrometer. Preparative GPC separation was under-
taken with a JAI LC-908 chromatograph using 600 mm ꢁ 20 mm JAIGEL-1H and
2H gel permeation chromatography (GPC) columns with CHCl3 as an eluent. All
reagents were obtained from commercial suppliers and used as received. Solvents
were dried (drying agent in parentheses) and distilled prior to use: Tetrahydrofuran
(THF) (sodium benzophenone ketyl), diethylamine (KOH), piperidine (KOH), and
toluene (CaH2).
General Procedure for the Pd-Cu–Catalyzed Coupling Reaction (GP1)
An acetylene derivative was added to a solution of an aromatic iodide,
Pd(PPh3)4, and CuI in solvent and=or amine under an argon atmosphere at the indi-
cated temperature. After being stirred for the indicated time, 1 N aqueous HCl was
added, and the reaction mixture was extracted with CHCl3. The organic layer was
washed with saturated aqueous NaHCO3 and dried over anhydrous MgSO4. After
removal of the solvent under reduced pressure, the residue was passed through a
silica-gel column followed by preparative GPC to afford the coupling product.
General Procedure for the Pt-Catalyzed Cyclization (GP2)
A solution of PtCl2 (5 mol%) and diyne 1 in toluene (1.0 mL) was stirred for the
indicated time under an argon atmosphere at 80 ꢀC. After removal of the solvent
Scheme 4. Preparation of diynes 1b–d.

1082
K. MIKI ET AL.
under reduced pressure, the residue was purified on a silica-gel column to give
dihydronaphthofuran derivative 2.
Synthesis of Diyne 1a
Compound 1a was obtained using o-diiodobenzene (0.33 g, 1.0 mmol),
3-butyn-1-ol (175 mg, 2.50 mmol), Pd(PPh3)4 (11 mg, 9.5 mmol), CuI (4 mg,
0.02 mmol), and piperidine (1.0 mL) by applying GP1 (reaction time: 18 h, reaction
1
temperature: rt) in 76% yield (163 mg) as a yellow oil. H NMR (270 MHz, CDCl3)
0
d 7.40 and 7.22 (AA0BB0, JAB ¼ 7.2, JAB ¼ 1.4 Hz, 4H), 3.82 (t, J ¼ 6.0 Hz, 4H), 2.74
(t, J ¼ 6.0 Hz, 4H), 2.23 (brs, 2H). 13C NMR (67.5 MHz, CDCl3) d 131.5, 127.4,
125.7, 90.7, 81.5, 60.7, 24.0. IR (neat) 3356, 2884, 2233, 1929, 1822, 1635, 1592,
1480, 1442, 1332, 1291, 1186, 1105, 1040, 950, 877, 846, 758 cmꢂ1. MS (EI) m=z
214 (Mþ). HRMS (EI) calcd. for C14H14O2: 214.0994. Found: 214.0974.
PtCl2-Catalyzed Cyclization of 1a: Synthesis of
Dihydronaphthofuran 2a
Dihydronaphthofuran 2a was obtained using 1a (53.3 mg, 0.25 mmol) and
PtCl2 (3.3 mg, 0.013 mmol) by applying GP2 (reaction time: 1 h) in 41% yield
1
(21.6 mg) as a white solid. Mp 64–65 ꢀC. H NMR (300 MHz, CDCl3) d 7.93–7.89
(m, 1H), 7.78–7.72 (m, 1H), 7.44–7.36 (m, 2H), 7.21 (s, 1H), 4.76 (t, J ¼ 9.0 Hz,
2H), 3.90 (t, J ¼ 6.6 Hz, 2H), 3.30 (t, J ¼ 9.0 Hz, 2H), 2.95 (t, J ¼ 6.6 Hz, 2H).
13C NMR (75 MHz, CDCl3) d 155.3, 134.0, 133.0, 127.2, 125.7, 124.6, 121.2,
119.9, 119.4, 119.3, 71.7, 62.3, 37.1, 29.5. IR (KBr) 3312, 2961, 1596, 1571, 1519,
1401, 1386, 1341, 1284, 1072, 942, 924, 841, 749, 608, 527 cmꢂ1. MS (EI) m=z 214
(Mþ). HRMS (EI) calcd. for C14H14O2: 214.0994. Found: 214.0982.
Synthesis of Diyne 1b
Compound 7b was obtained using o-diiodobenzene (3.03 g, 9.2 mmol), 1-(tert-
butyldimethylsilyloxy)but-3-yne (1.65 g, 8.95 mmol), Pd(PPh3)4 (0.29 g, 0.25 mmol),
CuI (0.14 g, 0.75 mmol), and piperidine (5.0 mL) by applying GP1 (reaction time:
18 h, reaction temperature: rt) in 42% yield (1.5 g) as a yellow oil together with a
disubstitution product (0.29 g, 7% yield) as a yellow oil.
1
Compound 7b: H NMR (300 MHz, CDCl3) d 7.82 (dd, J ¼ 7.5, 1.5 Hz, 1H),
7.40 (dd, J ¼ 7.5, 1.5 Hz, 1H), 7.26 (ddd, J ¼ 7.5, 7.5, 1.5 Hz, 1H), 6.95 (ddd,
J ¼ 7.5, 7.5, 1.5 Hz, 1H), 3.87 (t, J ¼ 7.2 Hz, 2H), 2.70 (t, J ¼ 7.2 Hz, 2H), 0.92 (s,
9H), 0.11 (s, 6H). 13C NMR (75 MHz, CDCl3) d 138.5, 132.4, 130.2, 128.7, 127.6,
100.9, 91.4, 83.8, 61.8, 26.0, 24.1, 18.4, ꢂ5.1. IR (neat) 2955, 2929, 2857, 2231,
1472, 1385, 1254, 1106, 915, 837, 777, 756, 661 cmꢂ1
.
Disubstitution product: 1H NMR (300 MHz, CDCl3) d 7.37 (dd, J ¼ 5.7,
13
3.6 Hz, 2H), 7.18 (dd, J ¼ 5.7, 3.6 Hz, 2H), 3.85 (t, J ¼ 7.5 Hz, 4H), 2.68 (t,
J ¼ 7.5 Hz, 4H), 0.92 (s, 18H), 0.10 (s, 12H). C NMR (75 MHz, CDCl3, 30 ꢀC) d
131.7, 127.2, 126.1, 90.7, 80.5, 62.1, 26.0, 24.2, 18.4, ꢂ5.1. MS (EI) m=z 442 (Mþ).
HRMS (EI) calcd. for C26H42O2Si2: 442.2723. Found: 442.2718.

Pt-CATALYZED CYCLIZATION OF o-DIETHYNYLBENZENES
1083
Compound 8b (0.34 g) was obtained using 7b (0.39 g, 1.0 mmol), 1-hexyne
(180 mg, 2.2 mmol), Pd(PPh3)4 (29 mg, 0.025 mmol), CuI (14 mg, 0.075 mmol),
Et2NH (0.5 mL), and toluene (2.0 mL) by applying GP1 (reaction time: 3.5 h, reac-
tion temperature: rt). The crude product was used in the next step without further
purification.
A solution of tetra-n-butylammonium fluoride (TBAF) (1 M in THF, 1.2 mL,
1.2 mmol) was added dropwise to a solution of the crude 8b (0.34 g) in THF (2.0 mL)
at room temperature under a nitrogen atmosphere. After being stirred for 15 min, the
solvent was removed under reduced pressure. The residue was subjected to chroma-
tography on silica gel (n-hexane=AcOEt 4:1 to 1:1) to give 1b (0.21 g, 93% for two
steps) as a yellow oil.
1
Compound 1b: H NMR (300 MHz, CDCl3) d 7.37–7.41 (m, 2H), 7.18–7.23
(m, 2H), 3.82 (t, J ¼ 6.0 Hz, 2H), 2.74 (t, J ¼ 6.0 Hz, 2H), 2.48 (t, J ¼ 6.9 Hz, 2H),
1.92 (br s, 1H), 1.45–1.67 (m, 4H), 0.96 (t, J ¼ 7.2 Hz, 3H). 13C NMR (75 MHz,
CDCl3, 30 ꢀC) d 131.8, 131.4, 127.5, 127.1, 126.6, 125.3, 94.4, 89.9, 82.1, 79.7,
61.0, 30.9, 24.2, 22.1, 19.4, 13.8. IR (neat) 3389, 2957, 2932, 2872, 2231, 1480,
1442, 1046, 758 cmꢂ1. MS (EI) m=z 226 (Mþ). HRMS (EI) calcd. for C16H18O:
226.1358. Found: 226.1381.
PtCl2-Catalyzed Cyclization of 1b: Synthesis of
Dihydronaphthofuran 2b
Dihydronaphthofuran 2b was obtained using 1b (22.3 mg, 0.10 mmol), PtCl2
(26.8 mg, 0.10 mmol), and toluene (1.0 mL) by applying GP2 (reaction time: 40 h)
1
in 76% yield (16.9 mg) as a white solid. Mp 60–61 ꢀC. H NMR (400 MHz, CDCl3)
d 7.93–7.89 (m, 1H), 7.78–7.73 (m, 1H), 7.42–7.34 (m, 2H), 7.18 (s, 1H), 4.79 (t,
J ¼ 8.8 Hz, 2H), 3.34 (t, J ¼ 8.8 Hz, 2H), 2.72 (t, J ¼ 7.6 Hz, 2H), 1.68 (tt, J ¼ 7.6,
7.6 Hz, 2H), 1.44 (qt, J ¼ 7.6, 7.6 Hz, 2H), 0.98 (t, J ¼ 7.6 Hz, 3H). 13C NMR
(100 MHz, CDCl3) d 155.2, 137.6, 134.3, 127.3, 125.6, 124.3, 121.3, 119.9, 119.1,
118.5, 71.7, 33.6, 32.2, 29.5, 22.6, 14.0. IR (KBr): 3047, 2951, 2924, 2856, 1593,
1514, 1387, 1284, 1066, 1048, 1012, 982, 918, 843, 750, 736, 576 cmꢂ1. MS (EI)
m=z 226 (Mþ). HRMS (EI) calcd. for C16H18O: 226.1358. Found: 226.1342.
Synthesis of Diyne 1c
Compound 7c was obtained using 5-tert-butyl-1-bromo-2,3-diiodobenzene[2c]
(909 mg, 1.95 mmol), 1-(tert-butyldimethylsilyloxy)but-3-yne (437 mg, 2.37 mmol),
Pd(PPh3)4 (33.0 mg, 28.6 mmol), CuI (27.0 mg 142 mmol), and piperidine (3.0 mL)
by applying GP1 (reaction time: 20 h, reaction temperature: 60 ꢀC) in 87% yield
1
(885 mg) as a yellow oil. H NMR (300 MHz, CDCl3) d 7.52 (d, J ¼ 2.1 Hz, 1H),
7.34 (d, J ¼ 2.1 Hz, 1H), 3.87 (t, J ¼ 6.9 Hz, 2H), 2.71 (t, J ¼ 6.9 Hz, 2H), 1.28 (s,
9H), 0.92 (s, 9H), 0.11 (s, 6H). 13C NMR (100 MHz, CDCl3) d 152.4, 129.0, 128.0,
127.9, 125.5, 102.6, 91.4, 80.4, 62.0, 34.8, 30.8, 25.9, 24.0, 18.3, ꢂ0.0, ꢂ5.2.
Compound 8c was obtained using 7c (260 mg, 499 mmol), 1-hexyne (56 mg,
680 mmol), Pd(PPh3)4 (25.0 mg, 21.6 mmol), CuI (50.4 mg, 264 mmol), and piperidine
(3.0 mL) by applying GP1 (reaction time: 20 h, reaction temperature: 60 ꢀC) in 43%
yield (103 mg) as a yellow oil. 1H NMR (300 MHz, CDCl3) d 7.48 (d, J ¼ 2.1 Hz, 1H),

1084
K. MIKI ET AL.
7.34 (d, J ¼ 2.1 Hz, 1H), 3.85 (t, J ¼ 7.5 Hz, 2H), 2.68 (t, J ¼ 7.5 Hz, 2H), 2.52
(t, J ¼ 7.5 Hz, 2H), 1.70–1.48 (m, 4H), 1.27 (s, 9H), 0.96 (t, J ¼ 7.2 Hz, 3H), 0.92
(s, 9H), 0.10 (s, 6H). 13C NMR (75 MHz, CDCl3) d 152.3, 128.9, 127.9, 127.8,
125.4, 124.4, 102.4, 102.0, 91.3, 80.4, 62.0, 34.7, 31.0, 30.8, 26.0, 24.1, 22.0, 19.6,
18.4, 0.11, ꢂ5.1. IR (neat) 2957, 2857, 2232, 1590, 1529, 1462, 1397, 1362, 1255,
1208, 1106, 1058, 1006, 913, 836, 777, 665 cmꢂ1. MS (EI) m=z 474 (Mþ).
A solution of TBAF (1 M in THF, 1.0 mL, 1.0 mmol) was added dropwise to a
solution of 8c (106 mg, 223 mmol) in THF (3.0 mL) at 0 ꢀC under a nitrogen atmos-
phere. After being stirred for 1 h, water was added to the reaction mixture, and the
mixture was extracted with CHCl3. The organic layer was washed with brine and
dried over anhydrous MgSO4. After removal of the solvent under reduced pressure,
the residue was subjected to chromatography on silica gel (n-hexane=AcOEt 2:1) fol-
1
lowed by preparative GPC to afford 1c (68.1 mg, 85%) as a colorless oil. H NMR
(300 MHz, CDCl3) d 7.51 (d, J ¼ 1.8 Hz, 1H), 7.35 (d, J ¼ 1.8 Hz, 1H), 3.81 (t,
J ¼ 5.4 Hz, 2H), 2.73 (t, J ¼ 6.0 Hz, 2H), 2.52 (t, J ¼ 6.9 Hz, 2H), 2.17 (brs, 1H),
1.69–1.48 (m, 4H), 1.27 (s, 9H), 0.96 (t, J ¼ 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3)
d 151.4, 129.1, 127.5, 126.7, 125.4, 125.3, 98.6, 90.1, 82.0, 78.8, 60.9, 34.7, 31.0, 30.7,
24.2, 22.0, 19.5, 13.7. IR (neat) 3397, 2960, 2933, 2871, 2230, 1718, 1590, 1528, 1455,
1397, 1178, 1048, 874, 647 cmꢂ1. MS (EI) m=z 360 (Mþ). HRMS (EI) calcd. for
C16H17O79Br: 360.1089. Found: 360.1076.
PtCl2-Catalyzed Cyclization of 1c
Dihydronaphthofuran 2c was obtained using 1c (36.1 mg, 100 mmol), PtCl2
(3.0 mg, 11 mmol), and toluene (1.0 mL) by applying GP2 (reaction time: 24 h) in
1
11% yield (4.0 mg) as a white solid. Mp 119–120 ꢀC. H NMR (300 MHz, CDCl3)
d 7.80 (d, J ¼ 1.8 Hz, 1H), 7.76 (d, J ¼ 1.8 Hz, 1H), 7.48 (s, 1H), 4.80 (t, J ¼ 9.0 Hz,
Hz, 2H), 3.34 (t, J ¼ 9.0 Hz, 2H), 2.72 (t, J ¼ 7.8 Hz, 2H), 1.71–1.41 (m, 4H), 1.38
(s, 9H), 0.97 (t, J ¼ 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3) d 147.7, 138.2, 130.8,
129.5, 128.8, 128.7, 122.2, 120.9, 117.7, 116.2, 72.0, 35.0, 34.0, 32.4, 31.3, 29.5,
22.7, 14.1. IR (KBr) 2958, 2928, 2860, 1597, 1496, 1463, 1416, 1375, 1311, 1281,
1253, 1208, 1059, 965, 874, 755, 618 cmꢂ1. MS (EI) m=z 360 (Mþ). HRMS (EI) calcd.
for C20H25O79Br: 360.1089. Found: 360.1101.
Synthesis of Diyne 1d
Compound 7d was obtained using o-diiodobenzene (3.79 g, 1.2 mmol),
(2-ethynylphenoxy)-tert-butyldimethylsilane[9] (2.3 g, 10 mmol), Pd(PPh3)4 (0.29 g,
0.25 mmol), CuI (0.14 g, 0.75 mmol), and piperidine (5.0 mL) by applying GP1 (reac-
1
tion time: 30 min, reaction temperature: rt) in 36% yield (1.5 g) as a yellow oil. H
NMR (270 MHz, CDCl3) d 7.92–7.85 (m, 1H), 7.59 (dd, J ¼ 7.6, 1.6 Hz, 1H), 7.50
(dd, J ¼ 7.6, 1.6 Hz, 1H), 7.32 (ddd, J ¼ 7.6, 7.6, 1.1 Hz, 1H), 7.27–7.20 (m, 1H),
7.06–6.93 (m, 2H), 6.89–6.84 (m, 1H), 1.05 (s, 9H), 0.28 (s, 6H).
Compound 8d (0.52 g) was obtained using 7d (0.65 g, 1.5 mmol), 1-hexyne
(164 mg, 2.00 mmol), Pd(PPh3)4 (43 mg, 0.037 mmol), CuI (21 mg, 0.11 mmol), and
piperidine (2.0 mL) by applying GP1 (reaction time: 30 min, reaction temperature:
rt). The crude product was used in the next step without further purification.

Pt-CATALYZED CYCLIZATION OF o-DIETHYNYLBENZENES
1085
A solution of TBAF (1 M in THF, 1.2 mL, 1.2 mmol) was added dropwise to a
solution of 8d (0.52 g) in THF (5.0 mL) at 0 ꢀC under a nitrogen atmosphere. After
being stirred for 15 min, the solvent was removed under reduced pressure. The resi-
due was subjected to chromatography on silica gel (n-hexane=AcOEt 50:1) to give 1d
1
(0.23 g, 56% for two steps) as a yellow oil. H NMR (270 MHz, CDCl3) d 7.53–7.47
(m, 2H), 7.42 (dd, J ¼ 5.1, 1.1 Hz, 2H), 7.30–7.25 (m, 2H), 7.00 (d, J ¼ 5.7 Hz, 1H),
6.92–6.89 (m, 1H), 6.57 (brs, 1H), 2.56 (t, J ¼ 4.9 Hz, 2H), 1.65 (tt, J ¼ 4.9, 4.9 Hz,
2H), 1.50 (qt, J ¼ 4.9, 4.9 Hz, 2H), 0.94 (t, J ¼ 4.9, 4.9 Hz, 3H). 13C NMR
(67.5 MHz, CDCl3) d 157.2, 132.2, 130.9, 130.9, 130.6, 128.3, 127.5, 126.3, 124.7,
120.1, 114.6, 109.5, 95.9, 95.6, 87.0, 80.0, 25.6, 22.1, 19.3, 13.6. IR (neat) 3456,
3061, 2957, 2931, 2871, 2210, 1574, 1490, 1474, 1347, 1291, 1241, 1195, 1144, 806,
753 cmꢂ1. MS (EI) m=z 226 (Mþ). HRMS (EI) calcd. for C20H18O: 274.1358. Found:
274.1360.
Synthesis of Diyne 3
Compound 3 was obtained using 1,2-dichloroethylene (291 mg, 3.0 mmol),
3-butyn-1-ol (537 mg, 7.66 mmol), Pd(PPh3)4 (0.17 g, 0.15 mmol), CuI (86 mg,
0.45 mmol), Et2NH (3.1 mL), and toluene (5.0 mL) by applying GP1 (reaction time:
24 h, reaction temperature: rt) in 56% yield (0.28 g) as a yellow oil. 1H NMR
(270 MHz, CDCl3) d 5.78 (s, 2H), 3.75 (t, J ¼ 5.9 Hz, 4H), 2.66 (t, J ¼ 5.9 Hz, 4H),
2.49 (brs, 2H). 13C NMR (67.5 MHz, CDCl3) d 119.5, 94.5, 80.4, 60.7, 24.1. IR (neat)
3364, 2944, 2887, 2216, 1419, 1043, 848, 750 cmꢂ1. MS (EI) m=z 164 (Mþ). HRMS
(EI) calcd. for C10H12O2: 164.0837. Found: 164.0816.
Synthesis of Diyne 4
Compound 4 was obtained using o-diiodobenzene (0.99 g, 3.0 mmol), 4-pentyn-
1-ol (606 mg, 7.2 mmol), Pd(PPh3)4 (0.17 g, 0.15 mmol), CuI (86 mg, 0.45 mmol),
Et2NH (3.1 mL), and toluene (5.0 mL) by applying GP1 (reaction time: 24 h, reaction
1
temperature: rt) in 86% yield (0.63 g) as a yellow oil. H NMR (270 MHz, CDCl3) d
7.37 (dd, J ¼ 5.7, 3.5 Hz, 2H), 7.19 (dd, J ¼ 5.7, 3.5 Hz, 2H), 3.85 (t, J ¼ 6.2 Hz, 4H),
2.70 (brs, 2H), 2.61 (t, J ¼ 6.2 Hz, 4H), 1.86 (tt, J ¼ 6.2, 6.2 Hz, 4H). 13C NMR
(67.5 MHz, CDCl3) d 131.9, 127.4, 126.0, 93.2, 80.3, 61.5, 31.2, 16.2. IR (neat)
3349, 2947, 2226, 1480, 1442, 1058, 958, 924, 759 cmꢂ1. MS (FAB) m=z 243
(M þ Hþ). HRMS (FAB) calcd. for C16H19O2: 243.1385. Found: 243.1380.
PtCl2-Catalyzed Cyclization of 4
The reaction of 4 (61 mg, 0.25 mmol), PtCl2 (3.3 mg, 0.013 mmol), and toluene
(1.0 mL) by applying GP2 (reaction time: 2 h) gave dihydronaphthofuran 5 in 43%
yield (26 mg) as a white solid together with indenylidenetetrahydrofurans 6a
(18 mg, 29%) and 6b (12 mg, 19%) both as yellow solids.
Compound 5: mp 62–63 ꢀC. 1H NMR (270 MHz, CDCl3) d 8.13–8.10 (m, 1H),
7.68–7.66 (m, 1H), 7.41–7.37 (m, 2H), 7.21 (s, 1H), 4.35 (t, J ¼ 5.1 Hz, 2H), 3.77
(t, J ¼ 6.2 Hz, 2H), 2.85 (t, J ¼ 6.5 Hz, 2H), 2.79 (t, J ¼ 7.8 Hz, 2H), 2.14 (tt,
J ¼ 6.5, 5.1 Hz, 2H), 1.94 (tt, J ¼ 7.8, 6.2 Hz, 2H), 1.62 (s, 1H). 13C NMR

1086
K. MIKI ET AL.
(67.5 MHz, CDCl3) d 150.1, 138.9, 132.8, 126.8, 125.7, 124.4, 124.1, 121.4, 118.5,
115.3, 66.1, 62.6, 32.9, 29.0, 22.5, 22.2. IR (KBr) 3326, 3070, 3048, 2964, 2926,
2873, 1706, 1634, 1598, 1497, 1471, 1446, 1404, 1323, 1282, 1177, 1116, 1078,
1053, 956, 919, 906, 738 cmꢂ1. MS (EI) m=z 242 (Mþ). HRMS (EI) calcd. for
C16H18O2: 242.1307. Found: 242.1309.
1
Compound 6a: mp 92–93 ꢀC. H NMR (400 MHz, CDCl3) d 7.36–7.40 (m,
1H), 7.28 (dd, J ¼ 7.2, 1.6 Hz, 1H), 7.13 (ddd, J ¼ 7.2, 7.2, 1.6 Hz, 1H), 7.09 (ddd,
J ¼ 7.2, 7.2, 1.6 Hz, 1H), 6.47 (s, 1H), 4.40 (t, J ¼ 7.2 Hz, 2H), 3.73 (t, J ¼ 6.4 Hz,
2H), 3.28 (t, J ¼ 7.6 Hz, 2H), 2.86 (td, J ¼ 7.6, 1.0 Hz, 2H), 2.26 (tt, J ¼ 7.6, 7.2 Hz,
2H), 1.93 (tt, J ¼ 7.6, 6.4 Hz, 2H), 1.58 (s, 1H). 13C NMR (100 MHz, CDCl3) d
162.8, 142.1, 141.3, 136.8, 124.3, 122.8, 122.7, 120.2, 119.9, 113.0, 72.0, 63.0, 32.7,
31.2, 27.2, 23.8. IR (KBr) 3316, 3089, 3059, 2934, 2902, 2872, 1707, 1632, 1455,
1181, 1045, 997, 752 cmꢂ1. MS (EI) m=z 242 (Mþ). HRMS (EI) calcd. for
C16H18O2: 242.1307. Found: 242.1331.
1
Compound 6b: mp 69–72 ꢀC. H NMR (270 MHz, CDCl3) d 7.99–8.04 (m,
1H), 7.25 (dd, J ¼ 6.5, 1.8 Hz, 1H), 7.10–7.15 (m, 2H), 6.46 (s, 1H), 4.46 (t,
J ¼ 6.8 Hz, 2H), 3.79 (t, J ¼ 6.5 Hz, 2H), 3.17 (t, J ¼ 7.6 Hz, 2H), 2.72 (td, J ¼ 6.8,
1.0 Hz, 2H), 2.23 (tt, J ¼ 6.8, 6.8 Hz, 2H), 1.96 (tt, J ¼ 7.6, 6.5 Hz, 2H), 1.56 (s,
1H). 13C NMR (75 MHz, CDCl3) d 163.3, 140.9, 140.2, 135.6, 124.8, 123.5, 123.2,
122.7, 119.2, 113.7, 71.7, 62.6, 32.2, 30.5, 26.5, 24.3. IR (KBr) 3344, 3071, 3041,
2940, 2867, 1709, 1644, 1450, 1189, 1019, 930, 858, 766, 737 cmꢂ1. MS (EI) m=z
242 (Mþ). HRMS (EI) calcd. for C16H18O2: 242.1307. Found: 242.1284.
ACKNOWLEDGMENT
This work was supported by a Grant-in-Aid for Scientific Research from the
Ministry of Education, Culture, Sports, Science, and Technology, Japan.
REFERENCES
1. For reviews, see (a) Wang, K. K. Cascade radical cyclization via biradicals generated from
enediynes, enyne-allenes, and enyne-ketenes. Chem. Rev. 1996, 96, 207–222; (b) Basak, A.;
Mandal, S.; Bag, S. S. Chelation-controlled Bergman cyclization: Synthesis and reactivity
of enediynyl ligands. Chem. Rev. 2003, 103, 4077–4094.
2. (a) Grisson, J. W.; Calkins, T. L.; Egan, M. Synthetic studies of the tandem enediyne-
mono- and bis-radical cyclizations. J. Am. Chem. Soc. 1993, 115, 11744–11752; (b) Grisson,
J. W.; Calkins, T. L.; Huang, D.; McMillen, H. High temperature radical cyclization
anomalies in the tandem enediyne-bis-radical cyclization. Tetrahedron 1994, 50, 4635–
4650; (c) Chow, S.-Y.; Palmer, G. J.; Bowles, D. M.; Anthony, J. E. Perylene synthesis
by the parallel cycloaromatization of adjacent endiynes. Org. Lett. 2000, 2, 961–963; (d)
Bowles, D. M.; Palmer, G. J.; Landis, C. A.; Scott, J. L.; Anthony, J. E. The Bergman reac-
tion as a synthetic tool: Advantages and restrictions. Tetrahedron 2001, 57, 3753–3760; (e)
Scott, J. L.; Pakin, S. R.; Anthony, J. E. Radical-induced cycloaromatization: Routes to
fluoranthenes and acephenanthrylenes. Synlett 2004, 161–164.
3. Landis, C. A.; Payne, M. M.; Eaton, D. L.; Anthony, J. E. Tellurium-mediated cyclo-
aromatization of acyclic endiynes under mild conditions. J. Am. Chem. Soc. 2004, 126,
1338–1339.

Pt-CATALYZED CYCLIZATION OF o-DIETHYNYLBENZENES
1087
4. (a) Wang, Y.; Finn, M. G. An organometallic diradical cycloaromatization reaction. J. Am.
Chem. Soc. 1995, 117, 8045–8046; (b) Ohe, K.; Kojima, M.-A.; Yonehara, K.; Uemura, S.
Rhodium(I)-catalyzed cycloaromatization of acyclic 3-ene-1,5-diynes. Angew. Chem. Int.
Ed. 1996, 35, 1823–1825; (c) Manabe, T.; Yanagi, S.-I.; Ohe, K.; Uemura, S. New examples
of 1,6- and 1,7-hydrogen transfer promoted by an a-silyl group in rhodium(I)-catalyzed
radical reactions of acyclic enediynes. Organometallics 1998, 17, 2942–2944; For reviews,
see (d) Konig, B. Changing the reactivity of enediynes by metal-ion coordination. Eur. J.
¨
Org. Chem. 2000, 381–385; (e) Trost, B. M.; McClory, A. Metal vinylidenes as catalytic
species in organic reactions. Chem. Asian J. 2008, 3, 164–194.
5. (a) Wu, M.-J.; Lee, C.-Y.; Lin, C.-F. A route to 5-substituted dibenzofurans by anionic
cycloaromatization of 2-(6-substituted 3-hexen-1,5-diynyl)phenyl tert-butyldimethyl ethers
and related molecules. Angew. Chem. Int. Ed. 2002, 41, 4077–4079; (b) Wu, M.-J.; Lin,
C.-F.; Lu, W.-D. Anionic cycloaromatization of 1-aryl-3-hexen-1,5-diynes initiated by
methoxide addition: Synthesis of phenanthridinones, benzo[c]phenanthridinones, and biar-
yls. J. Org. Chem. 2002, 67, 5907–5912.
6. (a) Utimoto, K. Palladium-catalyzed synthesis of heterocycles. Pure Appl. Chem. 1983, 55,
1845–1852; (b) Wakabayashi, Y.; Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H.
Preparation of furans from alkynols utilyzing palladium-catalyzed intramolecular addition
of alcohols to acetylene as a key reaction. Tetrahedron 1985, 41, 3655–3661.
7. Kuge, H.; Miki, K.; Sonoda, M.; Tobe, Y. Synthesis of dihydronaphthofuran derivatives
via tandem cyclization of diethynylbenzene. Paper presented at the 86th annual meeting
of the Chemical Society of Japan, 27–30, March 2006.
8. (a) Taduri, B. P.; Ran, Y. F.; Huang, C.-W.; Liu, R.-S. Platinum-catalyzed aromatization
of endiynes via a CꢀH bond insertion of tethered alkanes. Org. Lett. 2006, 8, 883–886; (b)
Taduri, B. P.; Odedra, A.; Lung, C.-Y.; Liu, R.-S. Platinum- and ruthenium-catalyzed aro-
matization of endiynes via intramolecular nucleophilic additions. Synthesis 2007, 2050–
2054; For a review, see (c) Liu, R.-S. Catalytic transformations of terminal alkynes by
cationic tris(1-propazolyl)borate ruthenium catalysts: Versatile chemistry via catalytic
allenylidene, vinylidene, and p–alkyne intermediates. Synlett 2008, 801–812.
9. Vedejs, E.; Steck, P. L. Unusual oxaphosphoranes by acyl transfer from o-acetoxy-
o0-diphenylphosphanyltolane. Angew. Chem. Int. Ed. 1999, 38, 2788–2791.