Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Article abstract of DOI:10.1016/j.tet.2006.08.083

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate

Full text of DOI:10.1016/j.tet.2006.08.083

Tetrahedron 62 (2006) 10311–10320
Reaction of ene-bis(phosphinylallenes): [2D2] versus [4D2]
cycloaddition
*
Shinji Kitagaki, Yuki Okumura and Chisato Mukai
*
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University,
Kakuma-machi, Kanazawa 920-1192, Japan
Received 5 August 2006; revised 25 August 2006; accepted 25 August 2006
Available online 14 September 2006
Abstract—Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investi-
gated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate
in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other
hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of
benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.
Ó 2006 Elsevier Ltd. All rights reserved.
R32PO
OH
1. Introduction
P(O)R3
•
2
R1
R2
R1
R2
R1
R2
R32PCl
base
Recent efforts from this laboratory1,2 disclosed that the peri-
cyclic reaction of ene-bis(sulfinylallenes), derived from the
reaction of ene-bis(propargyl alcohols), enables the rapid
construction of a variety of polycyclic aromatic com-
pounds.1–3 In our contiguous studies on the utility of the
ene-diallene species in organic synthesis, we investigated
the pericyclic reaction of ene-bis(phosphinylallene), which
is an analogue of ene-bis(sulfinylallene), and should be
prepared by the [2,3]-sigmatropic rearrangement4,5 of
a ene-bis(propargyl alcohol) derivative, the same as ene-
bis(sulfinylallene)6 (Scheme 1). This paper describes the
unexpected reactivity of the two types of ene-bis(phosphinyl-
allenes); one is the benzene-bridged derivatives, which
exclusively underwent [2+2] cycloaddition,7 while the other
is the substituted ethylene derivatives and heterocyclic ones
leading to the formation of the [4+2] cycloadducts.
[2,3]
•
P(O)R3
2
R32PO
1'
OH
1
2
P(O)R3
2
R1
R2
polycyclic
compound
cyclization
cycloaddition
P(O)R3
2
3
Scheme 1.
a dienophile) in THF at ꢀ78 ꢁC, and the resulting mixture
was warmed to room temperature to produce the naphtho[b]-
cyclobutene 6aa8 in 85% yield (Scheme 2). The expected
cycloadduct 7aa, predicted on the basis of the reaction of
4a and 5 in the presence of PhSCl, could not be detected.
The reactivity of ene-bis(phosphinylallene) was in sharp
contrast to that of bis(sulfinylallene), despite the similarity
of the electrical nature between the phosphinyl and sulfinyl
groups.9 On the basis of the experiments in Scheme 2, it was
evident that a dienophile did not take part in the formation of
6aa. Thus, the ring-closing reaction using PhSCl and other
chlorophosphines in the absence of the dienophile became
the next subject of interest (Table 1).
2. Results and discussion
According to the previously described procedure for the re-
action with PhSCl,1,6 chlorodiphenylphosphine (Ph2PCl)
was added to the solution of benzene-bridged bis(propargyl
alcohol) 4a, triethylamine, and dimethyl fumarate (5) (as
Keywords: Bisallenes; [2+2] Cycloaddition; Naphtho[b]cyclobutenes; [4+2]
Cycloaddition.
* Corresponding authors. Tel.: +81 76 234 4411; fax: +81 76 234 4410;
e-mail addresses: kitagaki@p.kanazawa-u.ac.jp; cmukai@kenroku.
kanazawa-u.ac.jp
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.08.083

10312
S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
CO2Me
irrespective of the existence of dimethyl fumarate (5)
OH
OH
(Scheme 2, Table 1, entry 1). This result may reflect that
the intramolecular [2+2] cycloaddition of the plausible
biradical intermediate 9 would be much faster than the inter-
molecular [4+2] cycloaddition with the dienophile. The fact
that (EtO)2PCl could not provide the cyclobutene derivative
might be attributable to the comparatively low reactivity in
the [2,3]-sigmatropic rearrangement of 10 to 2 (the second
step in Scheme 1).9
P(O)Ph2
5
MeO2C
Ph2PCl, Et3N, THF
–78 °C, 2 h rt, 2 h
P(O)Ph2
4a
6aa (85%)
P(O)Ph2
CO2Me
CO2Me
Having identified the effect of the phosphinyl group on the
[2+2] cycloaddition, we then synthesized the naphtho[b]-
cyclobutenes possessing certain substituents on the cyclo-
butene ring.11 The results are summarized in Table 2.
Treatment of the monomethyl derivative 4b1 with Ph2PCl
afforded the naphtho[b]cyclobutene 6ba in 84% yield (entry
1). Similarly, another monosubstituted bis(propargyl alco-
hol) 4c furnished 6ca in a high yield (entry 2). The 1,2-disub-
stituted naphtho[b]cyclobutenes 6da and 6ea were obtained
as a mixture of two diastereomers from 1,10-disubstituted
bis(propargyl alcohols) 4d and 4e in high yields (entries 3
and 4). In addition, the 1,1-disubstituted bis(propargyl alco-
hol) 4f provided 6fa without any difficulties (entry 5). How-
ever, fully methyl-substituted bis(propargyl alcohol) 4g
afforded a [1,5] hydrogen-shifted product 10 in 61% yield
as the sole isolable product (entry 6).12
P(O)Ph2
7aa (0%)
Scheme 2.
Table 1. Synthesis of naphtho[b]cyclobutenes 6a
OH
X(O)
X(O)
XCl, Et3N, THF
–78 °C, 2 h rt, 2 h
OH
4a
6
Entry
X
Product
Yield (%)
Stereochemical assignments of 6ea and 6da were unambig-
uously made by a chemical transformation, in particular, us-
ing a dephosphinylation reaction,7 which we have recently
developed. Initially, transformation of the major isomer of
diphenyl-substituted cycloadduct 6ea into the known naph-
tho[b]cyclobutene 113c,13 by LiAlH4 in refluxing dioxane
was examined; however, an inseparable mixture of the cis-
and trans-isomers of 11 and the unknown 12 was obtained
(Scheme 3). This result indicated that ring opening of the
1
2
3
4
5
6
Ph2P
Cy2P
iPr2P
Et2P
(EtO)2P
PhS
6aa
6ab
6ac
6ad
6ae
6af
85
98
81
99
0
0
X(O)
X(O)
X(O)
X(O)
•
Table 2. Synthesis of substituted naphtho[b]cyclobutenes 6
•
OH
X(O)
8
R1
Ph2P(O)
R1
R4
R2
R2
R3
Ph2PCl, Et3N, THF
–78 °C, 2 h rt, 2 h
X(O)
R3
R4
9
Ph2P(O)
a
All reactions were performed on a 0.1 mmol scale (0.1 M) with 6 equiv of
XCl and 7 equiv of Et3N.
OH
4
6
Entry Substrate R1
R2 R3 R4 Product Yield (%)
The reactions with chlorodialkylphosphines instead of
Ph2PCl exclusively afforded the corresponding 3,8-bis(di-
alkylphosphinyl)naphtho[b]cyclobutenes 6ab–6ad in high
yields, regardless of the bulkiness of the alkyl groups on
the phosphorus atom (entries 2–4). However, changing
chlorodialkylphosphine to PhSCl or diethyl chlorophosphite
[(EtO)2PCl] under standard conditions resulted in complex
mixtures of products (entries 5 and 6). A comprehensive
mechanistic discussion is premature at this point, but it
seems reasonable to postulate that the bis(phosphinylallene)
8 [X(O)¼phosphinyl], derived from the bis(propargyl phos-
phinite) by dual [2,3]-sigmatropic rearrangement, would be
converted into the biradical (o-quinodimethane) species 9,
which spontaneously undergoes intramolecular [2+2] cyclo-
addition to produce 6.10 The production of the naphtho[b]-
cyclobutene derivative 6aa as a sole product was observed
1
2
3
4
5
6
4b
4c
4d
4e
4f
Me
H
H
H
H
Me
H
H
Me
Ph
H
H
H
H
H
H
6ba
6ca
6da
6ea
6fa
84
90
CH2OBn
Me
Ph
Me
Me
84a
87b,c
86
4g
Me Me Me 6ga
0b,d
Ph2P(O)
Ph2P(O)
10
a
b
c
d
A mixture of trans- and cis-isomers was obtained in a ratio of 3:2.
Reaction mixture was stirred for an additional 15 h at room temperature.
A mixture of trans- and cis-isomers was obtained in a ratio of 1:2.
Compound 10 was obtained in 61% yield.

S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
10313
Ph2(O)P
Ph2(O)P
Ph2(O)P
Me
Ph2(O)P
Me
H
Ph
Ph
LiAlH4, TiCl4
THF, rt, 2 h
62%
LiAlH4
H
Me
dioxane, reflux, 5 h
Me
NOE
2%
Ph2(O)P
6ea (major isomer)
6da (major isomer)
trans-14
Ph
Ph
Ph2(O)P
Ph2(O)P
unknown
+
+
Me
Me
Me
Me
LiAlH4, TiCl4
THF, rt, 1.5 h
87%
H
H
Ph
Ph
NOE
13%
trans-11
cis-11
12
(10
:
3)
Ph2(O)P
Scheme 3.
6da (minor isomer)
cis-14
Scheme 5.
cyclobutane framework of 6ea and/or 11 occurred under the
reaction conditions.14 Thus, a recently developed monode-
phosphinylation7 under milder conditions was applied to
compound 6ea. Independent exposure of major and minor
isomers of 6ea to LiAlH4–TiCl4 at room temperature
effected the monodephosphinylation without isomerization
to provide the cis- and trans-13, respectively (Scheme 4).
Their stereochemical assignments were unambiguously
established by the NOE experiments as depicted in Scheme
4. As a result, an NOE experiment with cis-13 revealed 15%
enhancement between the two benzylic protons, while 4%
enhancement was observed by irradiation of one of the
two benzylic protons in the NOE experiment with trans-
13. The major and minor isomers of 6da were transformed
to the trans- and cis-14, respectively, under the same reduc-
tive conditions (Scheme 5). The stereochemistry of these
compounds was also determined on the basis of the NOE
experiments. The cis-13 was obtained as a major product
in the reaction of the phenyl derivative 4e, while the major
isomer was found to be the trans-14 in the reaction of the
methyl congener 4d. The preferential formation of the cis-
diphenyl-substituted cycloadduct over the trans-one 6ea in
the [2+2] cycloaddition process is uncertain.15
addition, the reaction of furan and indole derivatives 15e1
and 15f1 afforded [4+2] cycloadducts 17e and 17f as the
sole isolable products in 48% and 77% yields, respectively
(entries 5 and 6). The anisole derivative 15g produced the
[4+2] cycloadduct 17g in 44% yield (entry 7), which was
an unexpected result, because the corresponding benzene
derivatives 4 consistently afforded naphtho[b]cyclobutenes
6 in high yields (see Scheme 2 and Table 2). It should be
mentioned that [2+2] cycloadducts could not be detected
in the reaction mixture even though the reaction ran in the
absence of 5. Cava and Shirley reported that the 2,3-naph-
thoquinodimethane (without a sulfinyl or phosphinyl group)
is subject to the intramolecular [2+2] cycloaddition in the
absence of dienophiles, whereas the o-quinodimethane gen-
erally tends to undergo dimerization (a kind of [4+2] cyclo-
addition) under similar conditions. On the basis of these
experiments, they claimed that the formation of the naph-
tho[b]cyclobutene framework might be attributed to a higher
degree of diradical character of the 2,3-naphthoquinodi-
methane than that of the o-quinodimethane.17 Thus, the for-
mation of the [4+2] cycloadducts in the reaction of 15b, 15c,
and 15d via the corresponding o-quinodimethane species
(entries 2–4) would be tentatively rationalized by Cava
and Shirley’s interpretation, although we have no clues yet
to understand the result of 15a. A similar tendency was re-
corded in the reaction of benzene- and ethylene-bis(pro-
pargyl alcohols) 4b and 20, having a methyl group at the
propargylic position, with PhSCl (Scheme 6).1 The benzene
derivative 4b gave [2+2] cycloadduct 19 (R¼Me) via the
2,3-naphthoquinodimethane intermediate, while ethylene
derivative 20 provided a [4+2] cycloadduct 21 (R¼Me) via
the o-quinodimethane intermediate. However, the reaction
of both 4a and 15a with PhSCl gave the corresponding
[4+2] cycloadducts 18 (R¼H) and 21 (R¼H) in high yields.
As aforementioned, the 2,3-naphthoquinodimethane having
a bis(diphenylphosphinyl) group, derived from the reaction
of 4a with Ph2PCl, furnished the [2+2] cycloadduct 6aa
(Scheme 2), whereas the corresponding phenylsulfinyl con-
gener, derived from the reaction of 4a with PhSCl, provided
the [4+2] cycloadduct 18 (R¼H). The significant difference
in the reactivity observed in these two reactions cannot be
rationalized on the basis of Cava and Shirley’s results. By
taking the similarity of the electrical nature between the
phosphinyl and sulfinyl groups into account, we tentatively
assumed that the much bulkier diphenylphosphinyl groups
might inhibit the approach of dienophiles to the 1,3-
diene moiety of the 2,3-naphthoquinodimethane having
Ph2(O)P
Ph2(O)P
Ph
Ph
Ph
Ph
LiAlH4, TiCl4
THF, rt, 1 h
89%
H
H
NOE
15%
Ph2(O)P
6ea (major isomer)
cis-13
Ph2(O)P
Ph
Ph2(O)P
Ph
H
LiAlH4, TiCl4
THF, rt, 1 h
64%
H
Ph
Ph
NOE
4%
Ph2(O)P
6ea (minor isomer)
trans-13
Scheme 4.
The present [2+2] cycloaddition methodology was found not
to be applied to the synthesis of benzocyclobutenes. Indeed,
the reaction of ethylene-bridged bis(propargyl alcohol)
15a16 with Ph2PCl in the presence of dimethyl fumarate
(5) gave neither [2+2] cycloadducts nor [4+2] cycloadducts
(Table 3, entry 1). Monosubstituted ethylene 15b,1 however,
produced the [4+2] cycloadduct 17b in 88% yield (entry 2).
Cycloalkane derivatives 15c1 and 15d1 (disubstituted ethyl-
ene derivatives) also reacted with 5 to give [4+2] cyclo-
adducts 17c and 17d, respectively (entries 3 and 4). In

10314
S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
OH
R
Table 3. Reaction of various ene-bis(propargyl alcohols) with Ph2PCl
1. PhSCl, Et3N, 5, THF, –78 °C rt
2. mCPBA, CH2Cl2
OH
P(O)Ph2
P(O)Ph2
Ph2PCl
R1
R2
R1
R2
R1
CO2Me
CO2Me
Et3N, 5
+
OH
THF
–78 °C
rt
4b (R=Me)
4a (R=H)
R2
Ph
P(O)Ph2
P(O)
R
2
PhO2S
PhO2S
PhO2S
PhO2S
R
OH
CO2Me
CO2Me
15
16
17
+
Entry
Substrate
OH
Product
18
19
R=Me 0%
R=Me 43%
R=H
84%
R=H
0%
OH
R
1
Complex mixture
1. PhSCl, Et3N
R
SO2Ph
PhO2S
5, THF,
R
CO2Me
–78 °C
rt
+
OH
15a
2. mCPBA
CH2Cl2
CO2Me
OH
OH
PhO2S
SO2Ph
TBDPSO
P(O)Ph2
TBDPSO
OH
21
22
CO2Me
CO2Me
20
R=Me
R=H
42%
73%
0%
0%
15a
2
3
4
5
P(O)Ph2
Scheme 6.
17b (88%)
15b
a bis(diphenylphosphinyl) group resulting in the exclusive
formation of the [2+2] cycloadduct. This would not be the
case with the naphthoquinodimethane having a bis(phenyl-
sulfinyl) group where the less sterically hindered circum-
stances might allow the [4+2] cycloaddition to occur. In
the case of other aromatic compounds 15e and 15f (Table
3, entries 5 and 6), the plausible furanoquinodimethane
and carbazoloquinodimethane intermediates might no lon-
ger suffer from the serious non-bonding interaction between
the diphenylphosphinyl group and the peri-hydrogen atom,
which should be associated with the case of the naphthoqui-
nodimethane intermediate derived from 4. Thus, the rather
bulky diphenyl moiety on the phosphorus atom of 15e and
15f would be allowed to orient opposite to the quinodi-
methane moiety. As a result, dimethyl fumarate (5) would
approach to the 1,3-diene moiety resulting in the [4+2]
cycloaddition. This speculation, however, cannot be used
to explain the result obtained in the reaction of 15g (Table
3, entry 7), because the naphthoquinodimethane intermedi-
ate from 15g has a bulkier methoxy group than a hydrogen
atom at the peri-position.
OH
P(O)Ph2
CO2Me
CO2Me
P(O)Ph2
OH
OH
17c (64%)
15c
P(O)Ph2
CO2Me
CO2Me
P(O)Ph2
OH
OH
17d (87%)
15d
P(O)Ph2
CO2Me
CO2Me
O
O
P(O)Ph2
OH
17e (48%)
15e
OH
Independent treatment of the benzene-bis(propargyl alco-
hol) 4a with Ph2PCl (Scheme 2) and PhSCl (Scheme 6)
gave the respective formation of the [2+2] cycloadduct
6aa and the [4+2] cycloadduct 18 (R¼H). In other words,
the naphthoquinodimethane having a bis(diphenylphos-
phinyl) group afforded the naphthocyclobutene derivative
([2+2] product), while the bis(phenylsulfinyl) derivative fur-
nished the tetrahydroanthracene derivative ([4+2] product).
The outcome of these reactions seems to depend on the prop-
erty of the substituent on the allenyl moiety. Thus, it would
be interesting to examine the reaction of a benzene-bridged
diallene bearing both a sulfinyl group and a phosphinyl
group on the two allenyl groups. Monosilylation of bis(pro-
pargyl alcohol) 4a under the conventional conditions gave
23, which was subsequently treated with Ph2PCl and 10%
P(O)Ph2
CO2Me
CO2Me
6
N
MOM
N
MOM
P(O)Ph2
OH
OH
17f (77%)
15f
OMe P(O)Ph2
OMe
CO2Me
CO2Me
7
P(O)Ph2
17g (44%)
OH
15g

S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
10315
aqueous HCl to give phosphinylallene derivative 24
(Scheme 7). The sequential reaction of 24 with PhSCl was
carried out in the absence of 5 to give, after mCPBA oxida-
tion, the naphtho[b]cyclobutene 25 in 35% yield. When 4a
was directly exposed to PhSCl, no characteristic products
could be detected, whereas upon treatment with Ph2PCl,
4a provided 6aa in 85% yield as mentioned in Table 1. On
the other hand, similar treatment of 24 in the presence of 5
furnished the [4+2] cycloadduct 26 in 53% yield along
with the [2+2] cycloadduct 25 (17%) as a by-product. These
results may reflect both the natures of the sulfinyl group be-
ing susceptible to [4+2] cycloaddition and the phosphinyl
group, which is subject to [2+2] cycloaddition.
(7.26 ppm) for silyl compounds and tetramethylsilane
(0.00 ppm) for compounds without a silyl group were used
as internal standards. 13C NMR spectra were recorded in
CDCl3 with CDCl3 (77.00 ppm) as an internal standard.
All reactions were carried out under a nitrogen atmosphere.
Silica gel (silica gel 60, 230–400 mesh) was used for chro-
matography. Organic extracts were dried over anhydrous
Na2SO4.
4.2. General procedure for reaction of ene-bis(propargyl
alcohols) with chlorodialkylphosphine
To a solution of bis(propargyl alcohol) (0.100 mmol) in THF
(1 mL) were successively added Et3N (0.10 mL, 0.72 mmol)
and chlorodialkylphosphine (0.56 mmol) at ꢀ78 ꢁC. After
being stirred for 2 h, the reaction mixture was allowed to
warm to room temperature. After 2 h, the reaction was
quenched by addition of saturated aqueous NaHCO3, and
the mixture was extracted with AcOEt. The extract was
washed with water and brine, dried, and concentrated to
dryness. Chromatography of the residue with AcOEt–MeOH
gave the cycloadduct. To the reaction in the presence of di-
enophile, to a solution of bis(propargyl alcohol), dienophile
(4 equiv), and Et3N were added chlorodialkylphosphine.
OH
OTBS
1. Ph2PCl, Et3N
NaH
TBSCl
DMF
THF, –78 °C
rt
2. 10% aq. HCl
THF, 0 °C
71%
76% (2 steps)
OH
OH
OH
23
4a
CO2Me
5
MeO2C
1. PhSCl, Et3N, THF, –78 °C
2. mCPBA, CH2Cl2
rt
·
4.2.1. 3,8-Bis(diphenylphosphinyl)-1,2-dihydrocyclo-
buta[b]naphthalene (6aa). Colorless prisms: mp >300 ꢁC
P(O)Ph2
24
1
(AcOEt–MeOH); IR 1439, 1180 cmꢀ1; H NMR d 8.59–
SO2Ph
8.55 (2H, m), 7.70–7.25 (22H, m), 2.06 (4H, s); 13C NMR
d 150.4 (dd, JC–P¼11.7, 11.7 Hz), 134.4 (JC–P¼7.8 Hz),
133.0 (JC–P¼105 Hz), 132.2–131.8 (m), 128.8–128.6 (m),
128.3 (dd, JC–P¼3.4, 3.4 Hz), 126.1 (JC–P¼191 Hz), 30.0;
MS m/z 554 (M+, 32). Anal. Calcd for C36H28O2P2$
1/2H2O: C, 76.72; H, 5.19. Found: C, 76.78; H, 5.30.
SO2Ph
CO2Me
CO2Me
+
P(O)Ph2
P(O)Ph2
25
26
5
yield of 25 (%)
yield of 26 (%)
4.2.2. 3,8-Bis(dicyclohexylphosphinyl)-1,2-dihydrocyclo-
buta[b]naphthalene (6ab). Colorless powders: mp
x
35
17
–
53
1
>300 ꢁC (AcOEt–MeOH); IR 1448, 1150 cmꢀ1; H NMR
d 9.10 (2H, br s), 7.54–7.50 (2H, m), 3.46 (4H, s), 2.20–
1.10 (44H, m); 13C NMR d 145.4 (br), 136.2 (dd,
JC–P¼8.3, 6.1 Hz), 127.8, 125.9 (JC–P¼0.6 Hz), 124.6 (dd,
Scheme 7.
JC–P¼77.1, 2.2 Hz), 37.6 (JC–P¼69.3 Hz), 32.2 (JC–P
¼
3. Conclusions
3.1 Hz), 26.5 (dd, JC–P¼13.4, 3.1 Hz), 25.8, 25.3; MS m/z
578 (M+, 55); HRMS calcd for C36H52O2P2 578.3443, found
578.3436.
We have shown that benzene-bis(phosphinylallenes), de-
rived from benzene-bis(propargyl alcohols) and Ph2PCl,
underwent intramolecular [2+2] cycloaddition leading to
the naphtho[b]cyclobutene derivatives in sharp contrast to
the reaction of benzene-bis(sulfinylallenes), which gave
the corresponding [4+2] cycloadducts. On the other hand,
ethylene-bis(phosphinylallenes) afforded the [4+2] cyclo-
adducts instead of the [2+2] cycloadducts. Thus, the reaction
pathway could be controlled by proper choice of the reagent
(Ph2PCl and PhSCl) for the [2,3]-sigmatropic rearrangement
of the propargyl alcohol moiety. Further studies on the scope
and limitations of this method are currently in progress.
4.2.3. 3,8-Bis(diisopropylphosphinyl)-1,2-dihydrocyclo-
buta[b]naphthalene (6ac). Colorless prisms: mp 223–
225 ꢁC (AcOEt); IR 1464, 1173, 1140 cmꢀ1 1H NMR
;
d 9.12 (2H, br s), 7.54–7.50 (2H, m), 3.50 (4H, s), 2.50–
2.37 (4H, m), 1.33 (6H, d, J¼7.1 Hz), 1.28 (6H, d,
J¼7.1 Hz), 1.15 (6H, d, J¼7.1 Hz), 1.09 (6H, d,
J¼7.1 Hz); 13C NMR d 148.0 (br), 135.8 (br), 127.5, 125.8,
124.4 (dd, JC–P¼77.0, 2.8 Hz), 32.1, 27.6 (JC–P¼66.5 Hz),
16.3, 15.5; MS m/z 418 (M+, 89). Anal. Calcd for
C24H36O2P2: C, 68.88; H, 8.67. Found: C, 68.53; H, 8.75.
4. Experimental
4.1. General
4.2.4. 3,8-Bis(diethylphosphinyl)-1,2-dihydrocyclo-
buta[b]naphthalene (6ad). A colorless oil: IR 1458,
1
1155 cmꢀ1; H NMR d 9.02–8.98 (2H, m), 7.58–7.54 (2H,
m), 3.51 (4H, s), 2.19–2.06 (8H, m), 1.21 (6H, t,
J¼7.6 Hz), 1.15 (6H, d, J¼7.6 Hz); selected characteristic
data for 13C NMR d 31.9 (dd, JC–P¼1.7, 1.7 Hz), 23.4
Melting points are uncorrected. IR spectra were measured in
CHCl3. 1H NMR spectra were taken in CDCl3. CHCl3

10316
S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
(JC–P¼68.7 Hz), 5.9 (JC–P¼5.0 Hz); MS m/z 362 (M+, 100);
4.2.9. 3,8-Bis(diphenylphosphinyl)-1,1-dimethyl-1,2-di-
hydrocyclobuta[b]naphthalene (6fa). Colorless prisms:
HRMS calcd for C20H28O2P2 362.1565, found 362.1567.
mp >300 ꢁC (AcOEt–MeOH); IR 1437, 1167 cmꢀ1 1H
;
NMR d 8.62–8.59 (1H, m), 7.73–7.47 (22H, m), 7.27–7.21
(1H, m), 7.09–7.03 (1H, m), 2.09 (2H, s), 1.49 (6H, s);
4.2.5. 3,8-Bis(diphenylphosphinyl)-1-methyl-1,2-di-
hydrocyclobuta[b]naphthalene (6ba). Colorless prisms:
mp >300 ꢁC (AcOEt–MeOH); IR 1437, 1173 cmꢀ1
;
1H
selected characteristic data for 13C NMR d 47.3 (JC–P
¼
NMR d 8.59 (1H, d, J¼7.6 Hz), 8.38 (1H, d, J¼8.3 Hz),
7.81–7.20 (22H, m), 2.90–2.86 (1H, m), 2.46–2.38 (1H,
m), 1.71–1.65 (1H, m), 0.75 (3H, d, J¼6.9 Hz); selected
characteristic data for 13C NMR d 155.6 (dd, JC–P¼13.5,
8.6 Hz), 148.9 (dd, JC–P¼13.4, 8.5 Hz), 39.4 (d,
JC–P¼4.3 Hz), 38.3 (JC–P¼3.9 Hz), 20.3; MS m/z 568
(M+, 100); HRMS calcd for C37H30O2P2 568.1721, found
568.1725.
4.7 Hz), 45.8, 26.8; MS m/z 582 (M+, 100); HRMS calcd
for C38H32O2P2 582.1878, found 582.1893. Anal. Calcd
for C38H32O2P2: C, 78.34; H, 5.54. Found: C, 78.17; H, 5.57.
4.2.10. 1,4-Bis(diphenylphosphinyl)-2-(1-methyl-
ethenyl)-3-(1-methylethyl)naphthalene (10). A colorless
oil: IR 1437, 1169 cmꢀ1
;
1H NMR d 8.26 (1H, d,
J¼8.8 Hz), 8.00 (1H, d, J¼8.8 Hz), 7.79–7.31 (20H, m),
7.02 (1H, t, J¼7.4 Hz), 6.94 (1H, t, J¼7.4 Hz), 4.94 (1H,
s), 4.81 (1H, s), 3.57 (1H, sep, J¼6.8 Hz), 1.90 (3H, s),
0.95 (3H, d, J¼6.9 Hz), 0.67 (3H, d, J¼6.9 Hz); selected
characteristic data for 13C NMR d 38.3 (JC–P¼8.4 Hz),
29.1, 23.7, 20.4; MS m/z 610 (M+, 45); HRMS calcd for
C40H36O2P2 610.2191, found 610.2192.
4.2.6. 1-(Benzyloxymethyl)-3,8-bis(diphenylphosphinyl)-
1,2-dihydrocyclobuta[b]naphthalene (6ca). Pale yellow
solid: mp 288–293 ꢁC (AcOEt–MeOH); IR 1437,
1
1173 cmꢀ1; H NMR d 8.66 (1H, d, J¼8.5 Hz), 8.22 (1H,
d, J¼8.5 Hz), 7.74–7.02 (27H, m), 4.13 (2H, s), 3.21–3.12
(3H, m), 2.29–2.15 (2H, m); selected characteristic data
for 13C NMR d 151.6 (dd, JC–P¼7.2, 7.2 Hz), 149.6 (dd,
JC–P¼9.3, 4.1 Hz), 72.6, 71.4, 44.4 (d, JC–P¼3.1 Hz), 34.7
(JC–P¼4.1 Hz); MS m/z 674 (M+, 5.4); HRMS calcd for
C44H36O3P2 674.2140, found 674.2132. Anal. Calcd for
C44H36O3P2$1/2H2O: C, 77.29; H, 5.45. Found: C, 77.64;
H, 5.16.
4.2.11. Dimethyl trans-6-(tert-butyldiphenylsiloxy)-
methyl-5,8-bis(diphenylphosphinyl)-1,2,3,4-tetrahydro-
naphthalene-2,3-dicarboxylate (17b). A pale yellow oil:
1
IR 1734, 1437, 1175 cmꢀ1; H NMR d 7.76–7.19 (31H,
m), 4.22 (2H, s), 3.52–3.46 (1H, m), 3.49 (3H, s), 3.45
(3H, s), 3.23–3.06 (3H, m), 2.90–2.82 (2H, m), 0.70 (9H,
s); selected characteristic data for 13C NMR d 174.1,
174.0, 64.7 (JC–P¼4.1 Hz), 51.9, 51.8, 40.9, 40.3, 31.0
(JC–P¼5.2 Hz), 29.8 (JC–P¼5.2 Hz), 26.7, 18.9; FABMS
m/z 917 (M++1, 40); FABHRMS calcd for C55H55O7P2Si
917.3192, found 917.3164.
4.2.7. 3,8-Bis(diphenylphosphinyl)-1,2-dimethyl-1,2-di-
hydrocyclobuta[b]naphthalene (6da): trans-6da. Color-
less prisms: mp >300 ꢁC (AcOEt–MeOH); IR 1437,
1175 cmꢀ1 1H NMR d 8.46–8.42 (2H, m), 7.82–7.23
;
(22H, m), 2.39–2.37 (2H, m), 0.82 (6H, d, J¼6.9 Hz);
selected characteristic data for 13C NMR d 154.7 (dd,
JC–P¼11.2, 11.2 Hz), 48.1 (dd, JC–P¼2.2, 2.2 Hz), 20.1;
MS m/z 582 (M+, 100); HRMS calcd for C38H32O2P2
582.1878, found 582.1891.
4.2.12. Dimethyl trans-4,9-bis(diphenylphosphinyl)-
2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]naphthalene-
6,7-dicarboxylate (17c). A pale yellow oil: IR 1732, 1437,
1
1171 cmꢀ1; H NMR d 7.70–7.47 (20H, m), 3.42 (6H, s),
3.17–3.07 (4H, m), 2.81–2.79 (2H, m), 2.24–2.19 (2H, m),
1.48 (2H, quin, J¼7.1 Hz); selected characteristic data for
13C NMR d 174.2, 51.8, 40.6, 34.2 (dd, JC–P¼1.7, 1.7 Hz),
30.5 (dd, JC–P¼2.8, 2.8 Hz), 25.8; MS m/z 688 (M+, 100);
HRMS calcd for C41H38O6P2 688.2144, found 688.2140.
cis-6da. Colorless prisms: mp >300 ꢁC (AcOEt–MeOH); IR
1437, 1173 cmꢀ1; 1H NMR d 8.32–8.28 (2H, m), 7.85–7.17
(22H, m), 3.26–3.20 (2H, m), 0.71 (6H, d, J¼6.6 Hz);
selected characteristic data for 13C NMR d 154.8 (dd,
JC–P¼11.0, 11.0 Hz), 48.2 (JC–P¼2.5 Hz), 20.0; MS m/z
582 (M+, 100); HRMS calcd for C38H32O2P2 582.1878,
found 582.1875.
4.2.13. Dimethyl trans-9,10-bis(diphenylphosphinyl)-
1,2,3,4,5,6,7,8-octahydroanthracene-2,3-dicarboxylate
1
(17d). A pale yellow oil: IR 1732, 1437, 1165 cmꢀ1; H
4.2.8. 3,8-Bis(diphenylphosphinyl)-1,2-diphenyl-1,2-di-
hydrocyclobuta[b]naphthalene (6ea): trans-6ea. Pale
yellow solid: mp >300 ꢁC (AcOEt–MeOH); IR 1437,
NMR d 7.70–7.47 (20H, m), 3.40 (6H, s), 2.99–2.97 (4H,
m), 2.81–2.78 (2H, m), 2.44–2.41 (4H, m), 1.13–1.05 (4H,
m); selected characteristic data for 13C NMR d 174.3,
1171 cmꢀ1
;
1H NMR d 8.68–8.66 (2H, m), 7.71–7.06
51.8, 40.6, 30.2 (dd, JC–P¼2.8, 2.8 Hz), 28.9 (dd, JC–P¼
(28H, m), 6.50 (4H, d, J¼6.9 Hz), 3.64 (2H, s); selected
2.8, 2.8 Hz), 19.6; MS m/z 702 (M+, 100); HRMS calcd
for C42H40O6P2 702.2300, found 702.2304.
characteristic data for 13C NMR d 150.0 (dd, JC–P¼11.2,
11.2 Hz), 135.5 (dd, JC–P¼7.3, 7.3 Hz), 60.8 (dd, JC–P
¼
2.2, 2.2 Hz); MS m/z 706 (M+, 72); HRMS calcd for
C48H36O2P2 706.2191, found 706.2191.
4.2.14. Dimethyl trans-4,9-bis(diphenylphosphinyl)-
5,6,7,8-tetrahydronaphtho[2,3-b]furan-6,7-dicarboxy-
late (17e). A pale yellow oil: IR 1734, 1437, 1172 cmꢀ1; 1H
NMR d 7.76–7.43 (20H, m), 6.94 (1H, d, J¼2.3 Hz), 5.72
(1H, dd, J¼2.3, 2.1 Hz), 4.00 (1H, dd, J¼16.0, 6.4 Hz),
3.49 (3H, s), 3.45–3.32 (3H, m), 3.43 (3H, s), 3.00–2.91
(1H, m), 2.83–2.75 (1H, m); selected characteristic data
cis-6ea. Colorless solid: mp >300 ꢁC (AcOEt–MeOH);
IR 1437, 1171 cmꢀ1 1H NMR d 8.61–8.58 (2H, m),
;
7.56–7.18 (22H, m), 6.71–6.61 (6H, m), 6.22–6.20 (4H,
m), 4.39 (2H, s); selected characteristic data for 13C NMR
d 150.1 (dd, JC–P¼11.2, 11.2 Hz), 138.0, 135.2 (dd, JC–P
¼
for 13C NMR d 174.4, 174.2, 51.9, 40.5, 30.4 (JC–P
¼
7.3, 7.3 Hz), 55.8; MS m/z 706 (M+, 83); HRMS calcd for
C48H36O2P2 706.2191, found 706.2185.
5.6 Hz), 29.0 (JC–P¼5.0 Hz); MS m/z 688 (M+, 100);
HRMS calcd for C40H34O7P2 688.1780, found 688.1776.

S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
10317
4.2.15. Dimethyl trans-6,11-bis(diphenylphosphinyl)-5-
(methoxymethyl)-7,8,9,10-tetrahydro-5H-benzo[b]car-
bazole-8,9-dicarboxylate (17f). A pale yellow oil: IR 1734,
1437, 1172 cmꢀ1; 1H NMR d 8.38 (1H, d, J¼7.9 Hz), 7.81–
7.13 (22H, m), 6.92 (1H, t, J¼6.3 Hz), 5.50 (1H, d,
J¼10.9 Hz), 5.23 (1H, d, J¼10.9 Hz), 3.59–3.41 (1H, m),
3.59 (3H, s), 3.41 (3H, s), 2.95–2.56 (5H, m), 2.56 (3H, s);
selected characteristic data for 13C NMR d 173.9, 79.3,
55.8, 52.1, 51.9, 40.3 (JC–P¼2.8 Hz), 31.9 (JC–P¼6.7 Hz),
30.1; FABMS m/z 782 (M++1, 2.4); FABHRMS calcd for
C46H42NO7P2 782.2437, found 782.2440.
J¼8.8 Hz), 7.89 (1H, d, J¼8.3 Hz), 7.85 (1H, s), 7.55–
7.04 (20H, m), 6.63 (2H, d, J¼7.1 Hz), 4.34 (1H, d,
J¼2.4 Hz), 4.02 (1H, d, J¼2.4 Hz); selected characteristic
data for 13C NMR
d
151.2 (JC–P¼9.3 Hz), 143.7
(JC–P¼13.4 Hz), 57.3 (JC–P¼4.1 Hz), 53.2; MS m/z 506
(M+, 1.1); HRMS calcd for C36H27OP 506.1800, found
506.1792.
4.4.3. trans-3-(Diphenylphosphinyl)-1,2-dimethyl-1,2-di-
hydrocyclobuta[b]naphthalene (trans-14). A colorless
oil: IR 1437, 1167 cmꢀ1
;
1H NMR d 8.38 (1H, d,
J¼8.4 Hz), 7.85–7.26 (14H, m), 3.02–3.00 (1H, m), 2.71–
2.68 (1H, m), 1.39 (3H, d, J¼6.9 Hz), 0.85 (3H, d,
J¼6.9 Hz); selected characteristic data for 13C NMR
3.9 Hz), 45.2, 19.3, 18.7; MS m/z 382 (M+, 100); HRMS
calcd for C26H23OP 382.1487, found 382.1486.
4.2.16. Dimethyl trans-9,10-bis(diphenylphosphinyl)-5-
methoxy-1,2,3,4-tetrahydroanthracene-2,3-dicarboxy-
late (17g). A pale yellow oil: IR 1732, 1437, 1175 cmꢀ1; 1H
NMR d 8.00–7.03 (22H, m), 6.33 (1H, d, J¼7.7 Hz), 3.89–
2.92 (6H, m), 3.47 (3H, s), 3.41 (3H, s), 2.99 (3H, s); selected
characteristic data for 13C NMR d 174.2, 173.9, 53.3, 52.2,
52.0, 40.0, 39.9; MS m/z 728 (M+, 16); HRMS calcd for
C43H38O7P2 728.2093, found 728.2089.
d 155.5 (JC–P¼8.9 Hz), 146.6 (JC–P¼14.0 Hz), 49.2 (JC–P
¼
4.4.4. cis-3-(Diphenylphosphinyl)-1,2-dimethyl-1,2-di-
hydrocyclobuta[b]naphthalene (cis-14). A colorless oil:
1
IR 1437, 1169 cmꢀ1; H NMR d 8.35 (1H, d, J¼8.6 Hz),
4.3. Dephosphinylation of cis-6ea with LiAlH4
7.86–7.24 (14H, m), 3.66 (1H, quin, J¼7.3 Hz), 3.26 (1H,
quin, J¼7.3 Hz), 1.23 (3H, d, J¼7.3 Hz), 0.75 (3H, d,
J¼7.3 Hz); selected characteristic data for 13C NMR
To a suspension of LiAlH4 (30.4 mg, 0.800 mmol) in 1,4-di-
oxane (2 mL) was added cis-6ea (141 mg, 0.200 mmol), and
the mixture was refluxed for 5 h. The mixture was cooled to
room temperature and quenched by addition of water. Aque-
ous HCl 10% was added, and the mixture was extracted with
AcOEt. The extract was washed with water and brine, dried,
and concentrated. Chromatography of the residue with
hexane afforded an inseparable mixture of the cis- and trans-
isomers of 113c,13 and the unknown 12 (38.0 mg, cis-11:
d 156.7 (JC–P¼8.3 Hz), 147.7 (JC–P¼14.5 Hz), 43.6 (JC–P
¼
7.2 Hz), 39.2, 14.5, 13.7; MS m/z 382 (M+, 100); HRMS
calcd for C26H23OP 382.1487, found 382.1485.
4.5. Reaction of 24 with PhSCl in the presence of 5
To a solution of 24 (91.9 mg, 0.248 mmol) in THF (2.5 mL)
were successively added 5 (71.5 mg, 0.497 mmol), Et3N
(0.21 mL, 1.5 mmol), and a solution of PhSCl (108 mg,
0.747 mmol) in THF (0.5 mL) at ꢀ78 ꢁC. After being stirred
for 2 h, the reaction mixture was allowed to warm to room
temperature. After 13 h, the reaction was quenched by addi-
tion of water, and the mixture was extracted with AcOEt.
The extract was washed with water and brine, dried, and
concentrated to dryness. The residue was passed through
a short pad of silica gel with hexane–AcOEt (1:3) to afford
the crude sulfoxides. To a solution of the crude sulfoxides
in CH2Cl2 (2 mL) was added mCPBA (66.7 mg,
0.386 mmol) at 0 ꢁC, and the reaction mixture was allowed
to warm to room temperature. After 12 h, the reaction was
quenched by addition of saturated aqueous NaHCO3 and
aqueous Na2S2O3, and the mixture was extracted with
CH2Cl2. The extract was washed with water and brine, dried,
and concentrated to dryness. Chromatography of the residue
with hexane–AcOEt (1:2) afforded 26 (83.7 mg, 53%) and
25 (21.3 mg, 17%) as a colorless oils.
1
trans-11¼10:3) as colorless solid: H NMR d 7.88–6.96
(>16H, m), 5.37 (0.46H, s, for cis-11), 4.67 (1.54H, s, for
trans-11), 4.05 (2.5H, s, for 12); MS m/z 306 (M+, 70);
HRMS calcd for C24H18 306.1409, found 306.1410.
4.4. Typical procedure for dephosphinylation with
LiAlH4–TiCl4
To a suspension of LiAlH4 (20.6 mg, 0.544 mmol) in THF
(1 mL) were successively added TiCl4 (0.03 mL,
0.3 mmol) and cis-6ea (48.1 mg, 6.80ꢂ10ꢀ2 mmol), and
the mixture was stirred for 1 h at room temperature. The
reaction was quenched by addition of water, and the mixture
was extracted with AcOEt. The extract was washed with
water and brine, dried, and concentrated. Chromatography
of the residue with hexane–AcOEt (1:3) afforded cis-13
(30.8 mg, 89%) as a colorless oil.
4.4.1. cis-3-(Diphenylphosphinyl)-1,2-diphenyl-1,2-di-
hydrocyclobuta[b]naphthalene (cis-13). A colorless oil:
4.5.1. 3-(Diphenylphosphinyl)-8-(phenylsulfonyl)-1,2-
1
IR 1437, 1169 cmꢀ1; H NMR d 8.56 (1H, d, J¼8.5 Hz),
dihydrocyclobuta[b]naphthalene
(25).
IR
1437,
1
7.91 (2H, s), 7.57–6.70 (20H, m), 6.29 (2H, d, J¼7.3 Hz),
5.17 (1H, d, J¼6.6 Hz), 4.58 (1H, d, J¼6.6 Hz); selected
characteristic data for 13C NMR d 151.2 (JC–P¼8.9 Hz),
143.7 (JC–P¼14.0 Hz), 60.9 (JC–P¼3.9 Hz), 58.2; MS m/z
506 (M+, 2.5); HRMS calcd for C36H27OP 506.1800, found
506.1802.
1148 cmꢀ1; H NMR d 8.66–8.61 (2H, m), 7.96 (2H, d,
J¼6.9 Hz), 7.72–7.34 (15H, m), 3.50–3.46 (2H, m), 2.39–
2.36 (2H, m); selected characteristic data for 13C NMR
d 150.7 (JC–P¼9.5 Hz), 147.7 (JC–P¼14.5 Hz), 141.7, 31.1,
31.0; MS m/z 494 (M+, 70); HRMS calcd for C30H23O3PS
494.1106, found 494.1101.
4.4.2. trans-3-(Diphenylphosphinyl)-1,2-diphenyl-1,2-di-
hydrocyclobuta[b]naphthalene (trans-13). A colorless
4.5.2. Dimethyl trans-9-(diphenylphosphinyl)-10-(phe-
nylsulfonyl)-1,2,3,4-tetrahydroanthracene-2,3-dicarb-
1
oil: IR 1437, 1169 cmꢀ1
;
1H NMR d 8.57 (1H, d,
oxylate (26). IR 1732, 1437, 1175 cmꢀ1; H NMR d 8.94

10318
S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
(1H, d, J¼8.7 Hz), 8.26 (1H, d, J¼8.7 Hz), 7.94 (2H, d,
J¼6.9 Hz), 7.71–7.12 (15H, m), 4.05 (1H, dd, J¼15.3,
6.3 Hz), 3.61 (3H, s), 3.56–3.34 (2H, m), 3.45 (3H, s),
3.14–3.07 (2H, m), 2.91–2.84 (1H, m); selected characteris-
tic data for 13C NMR d 173.9, 173.7, 144.3 (JC–P¼7.8 Hz),
143.3, 140.0 (JC–P¼11.2 Hz), 52.2, 52.0, 39.9, 39.6, 30.4
(JC–P¼6.1 Hz), 27.9; MS m/z 638 (M+, 46); HRMS calcd
for C36H31O7PS 638.1528, found 638.1526.
washed with water and brine, dried, and concentrated to dry-
ness. The residue was passed through a short pad of silica gel
with hexane–AcOEt (7:3) to afford the crude alcohol
(193 mg, 49%) and to recover the ethynylbenzene (125 mg,
51%). To a solution of the above alcohol (193 mg) in
MeOH (10 mL) was added TsOH$H2O (9.5 mg, 5.0ꢂ
10ꢀ2 mmol) at room temperature. After 30 min, the reaction
mixture was diluted with water and extracted with AcOEt.
The extract was washed with water and brine, dried, and con-
centrated to dryness. Chromatography of the residue with
hexane–AcOEt (1:1) gave 4c (125 mg, 82%) as a yellow
4.6. Preparation of propargyl alcohols
1
4.6.1. 1-(4-Benzyloxy-3-hydroxy-1-butynyl)-2-(3-hydroxy-
1-propynyl)benzene (4c). To a solution of 1-bromo-2-iodo-
benzene (1.06 g, 3.75 mmol) and 3-(tetrahydropyran-2-yl)-
oxy-1-propyne (1.05 g, 7.50 mmol) in THF (15 mL) were
successively added Pd(PPh3)2Cl2 (52.6 mg, 7.50ꢂ
10ꢀ2 mmol), CuI (71.4 mg, 0.375 mmol), and Et3N (5.2 mL,
37 mmol) at room temperature. The mixture was stirred for
8 h, and the resulting precipitates were filtered off. The
filtrate was concentrated to leave the residue, which was
chromatographed with hexane–AcOEt (20:1) to afford
1-bromo-2-[3-(tetrahydropyran-2-yl)oxy-1-propynyl]benzene
(988 mg, 89%) as a pale yellow oil: IR 3012, 2237 cmꢀ1; 1H
NMR d 7.59–7.46 (2H, m), 7.28–7.13 (2H, m), 4.99 (1H, t,
J¼3.2 Hz), 4.55 (2H, s), 3.95–3.86 (1H, m), 3.62–3.54
(1H, m), 1.91–1.54 (6H, m); 13C NMR d 133.6, 132.4,
129.5, 126.9, 125.5, 96.7, 89.9, 84.3, 62.1, 54.6, 30.3,
25.4, 19.1; MS m/z 294 (M+, 6.9); HRMS calcd for
C14H15O2Br 294.0255, found 294.0252.
oil: IR 3421, 2231 cmꢀ1; H NMR d 7.37–7.21 (9H, m),
4.82 (1H, br s), 4.62 (2H, s), 4.39 (2H, s), 3.85–3.62 (4H,
m); 13C NMR d 137.4, 131.2, 130.9, 128.4, 128.1, 127.9,
125.7, 125.1, 92.2, 91.2, 84.3, 84.1, 73.5, 73.4, 62.2, 51.2;
FABMS m/z 307 (M++1, 3.2); FABHRMS calcd for
C20H19O3 307.1334, found 307.1347.
4.6.2. 1,2-Bis(3-hydroxy-3-phenyl-1-propynyl)benzene
(4e). To a solution of o-diiodobenzene (387 mg, 1.17 mmol)
and 1-phenyl-2-propyn-1-ol (0.90 mL, 7.0 mmol) in THF
(8.5 mL) were successively added Pd(PPh3)2Cl2 (16.0 mg,
2.34ꢂ10ꢀ2 mmol), CuI (22.0 mg, 0.117 mmol), and iPr2NH
(1.3 mL, 12 mmol) at room temperature. The mixture was
stirred for 16 h, and the resulting precipitates were filtered
off. The filtrate was concentrated to leave the residue, which
was chromatographed with hexane–AcOEt (8:1/1:3) to
afford 4e (380 mg, 96%) as yellow solid: IR 3587, 3384,
1
2199 cmꢀ1; H NMR d 7.54–7.22 (14H, m), 5.59 (2H, s),
3.58 (2H, br s); 13C NMR d 140.4, 140.3, 131.3, 131.2,
128.7, 128.6, 128.5, 128.5, 128.3, 128.2, 128.1, 126.9, 126.8,
126.6, 125.4, 125.3, 93.2, 85.2, 65.0, 64.8; FABMS m/z 339
(M++1, 0.1); FABHRMS calcd for C24H19O2 339.1385,
found 339.1368.
To a solution of the above bromobenzene (295 mg,
1.00 mmol) and (trimethylsilyl)acetylene (0.28 mL,
2.0 mmol) in Et3N (5 mL) were successively added
Pd(PPh3)2Cl2 (35.0 mg, 5.00ꢂ10ꢀ2 mmol), CuI (19.0 mg,
0.100 mmol), and PPh3 (26.3 mg, 0.100 mmol) at room tem-
perature. The mixture was heated under reflux for 15 h, and
the resulting precipitates were filtered off. The filtrate was
concentrated to leave the residue, which was passed through
a short pad of silica gel with hexane–AcOEt (20:1) to afford
the crude diyne (311 mg) as a pale yellow oil. To a solution of
the above diyne (311 mg) in MeOH (10 mL) was added
K2CO3 (152 mg, 1.10 mmol) at room temperature. After
30 min, the reaction mixture was diluted with water and ex-
tracted with AcOEt. The extract was washed with water and
brine, dried, and concentrated to dryness. Chromatography
of the residue with hexane–AcOEt (20:1) gave 1-ethynyl-2-
[3-(tetrahydropyran-2-yl)oxy-1-propynyl]benzene (192 mg,
4.6.3. 1-(3-Hydroxy-3-methyl-1-propynyl)-2-(3-hydroxy-
1-propynyl)benzene (4f). To a solution of 1-(3-hydroxy-
1-propynyl)-2-iodobenzene18 (50.0 mg, 0.194 mmol) and
2-methyl-3-butyn-2-ol (0.06 mL, 0.6 mmol) in THF (2 mL)
were successively added Pd(PPh3)2Cl2 (2.7 mg, 3.9ꢂ
10ꢀ3 mmol), CuI (3.7 mg, 1.9ꢂ10ꢀ2 mmol), and Et3N
(0.3 mL, 2 mmol) at room temperature. The mixture was
stirred for 3 d, and the resulting precipitates were filtered
off. The filtrate was concentrated to leave the residue, which
was chromatographed with hexane–AcOEt (3:1) to afford 4f
(35.3 mg, 85%) as yellow solid: IR 3597, 3383, 2230 cmꢀ1
;
1H NMR d 7.39–7.20 (4H, m), 4.53 (2H, s), 3.91 (2H, br s),
1.63 (6H, s); 13C NMR d 131.1, 131.0, 127.9, 127.8, 125.5,
125.4, 98.2, 91.7, 84.2, 80.8, 65.7, 51.2, 31.2; MS m/z 214
(M+, 25); HRMS calcd for C14H14O2 214.0994, found
214.0998.
80% for two steps) as a colorless oil: IR 3308, 2230 cmꢀ1
;
1H NMR d 7.50–7.45 (2H, m), 7.30–7.25 (2H, m), 5.00
(1H, t, J¼3.4 Hz), 4.55 (2H, s), 3.93–3.88 (1H, m), 3.59–
3.55 (1H, m), 3.28 (1H, s), 1.87–1.55 (6H, m); 13C NMR
d 132.5, 132.1, 128.4, 128.0, 125.7, 124.6, 96.5, 89.3,
84.1, 82.0, 80.9, 62.0, 54.6, 30.2, 25.4, 19.1; MS m/z 240
(M+, 12); HRMS calcd for C16H16O2 240.1150, found
240.1153.
4.6.4. 2,3-Bis(3-hydroxy-1-propynyl)anisole(15g). Toabi-
phasic mixture of 3-methoxycatechol (700 mg, 5.00 mmol)
in toluene (10 mL) and 30% aqueous K3PO4 (20 mL) was
added Tf2O (2.02 mL, 12.0 mmol) at 0 ꢁC. After the mixture
was stirred for 3 h at room temperature, the layer was sepa-
rated. The toluene layer was washed with water and brine,
dried, and concentrated to dryness. The residue was chroma-
tographed with hexane–AcOEt (8:1) to afford 2,3-bis(tri-
fluoromethanesulfonyloxy)anisole (2.05 g, quant.) as pale
yellow solid: 1H NMR d 7.41–7.38 (1H, m), 7.10–7.04
(2H, m), 3.97 (3H, s).
To a solution of the above ethynylbenzene (243 mg,
1.01 mmol) in THF (8 mL) was added EtMgBr in THF
(0.50 M, 2.2 mL, 1.1 mmol) at 0 ꢁC. After 10 min, benzyl-
oxyacetaldehyde (0.16 mL, 1.1 mmol) was added, and the
mixture was stirred for 2 h at room temperature. The reaction
was quenched by addition of saturated aqueous NH4Cl, and
the mixture was extracted with AcOEt. The extract was

S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
10319
To a solution of the above bis(triflate) (992 mg, 2.45 mmol)
in Et3N–DMF (24 mL, 1:5) were successively added tetra-
butylammonium iodide (2.71 g, 7.35 mmol), (trimethylsilyl)-
acetylene (1.38 mL, 9.80 mmol), Pd(PPh3)2Cl2 (172 mg,
0.245 mmol) and CuI (140 mg, 0.735 mmol) at room tem-
perature. After being stirred for 8 h at 70 ꢁC, the mixture
was cooled, diluted with saturated aqueous NH4Cl, and ex-
tracted with Et2O. The extract was washed with water and
brine, dried, and concentrated to dryness. The residue was
passed through a short pad of silica gel with hexane–AcOEt
(20:1) to afford the crude bis[(trimethylsilyl)acetylene]
(720 mg) as a brown oil. To a solution of the above bis[(tri-
methylsilyl)acetylene] (720 mg) in MeOH (15 mL) was
added K2CO3 (728 mg, 5.28 mmol) at room temperature.
After 3 h, MeOH was evaporated off, and the residue was
dissolved in water and extracted with Et2O. The extract
was washed with water and brine, dried, and concentrated
to dryness. The residue was passed through a short pad of sil-
ica gel with hexane–AcOEt (20:1) to afford the crude diyne
(97.1 mg). To a solution of the above diyne (97.1 mg) in
THF (5 mL) was added nBuLi in hexane (1.35 M, 1.01 mL,
1.36 mmol) at ꢀ40 ꢁC. After 30 min, paraformaldehyde
(188 mg, 12.8 mmol) was added to the reaction mixture,
which was stirred for an additional 3 h at room temperature.
The reaction was quenched by addition of saturated aqueous
NH4Cl, and the mixture was extracted with AcOEt. The ex-
tract was washed with water and brine, dried, and concen-
trated to dryness. The residue was chromatographed with
hexane–AcOEt (3:1) to afford 15g (38.5 mg, 7% for three
and concentrated to dryness. The residue was passed through
a short pad of silica gel with hexane–AcOEt (1:1) to afford
the crude phosphinylallene (41.3 mg) as a yellow oil. To a
solution of the above crude phosphinylallene (21.6 mg) in
THF (1 mL) was added 10% aqueous HCl (0.1 mL) at
0 ꢁC. The reaction mixture was stirred for 2 h at that temper-
ature and then diluted with water. The mixture was extracted
with Et2O, and the extract was washed with water and brine,
dried, and concentrated to dryness. The residue was chroma-
tographed with hexane–AcOEt (1:3) to afford 24 (14.9 mg,
76% for two steps) as a yellow oil: IR 3306, 1958, 1927,
1
1439, 1173 cmꢀ1; H NMR d 7.83–7.13 (14H, m), 4.88
(2H, d, JP–H¼10.6 Hz), 4.50 (2H, s), 1.26 (1H, s); character-
istic data for 13C NMR d 213.9 (JC–P¼5.6 Hz), 99.4 (JC–P
¼
100.6 Hz), 93.1, 84.4, 78.0 (JC–P¼12.3 Hz), 51.3; MS m/z
370 (M+, 82); HRMS calcd for C24H19O2P 370.1123, found
370.1129.
Acknowledgements
This work was supported in part by a Grant-in-Aid for Sci-
entific Research from the Ministry of Education, Culture,
Sports, Science, and Technology, Japan, for which we are
thankful.
References and notes
1
steps) as pale yellow solid: IR 3367, 3022 cmꢀ1; H NMR
1. Kitagaki, S.; Katoh, K.; Ohdachi, K.; Takahashi, Y.; Shibata,
D.; Mukai, C. J. Org. Chem. 2006, 71, 6908–6914.
2. Kitagaki, S.; Ohdachi, K.; Katoh, K.; Mukai, C. Org. Lett.
2006, 8, 95–98.
3. (a) Tanaka, K.; Takamoto, N.; Tezuka, Y.; Kato, M.; Toda, F.
Tetrahedron 2001, 57, 3761–3767; (b) Toda, F.; Tanaka, K.;
Sano, I.; Isozaki, T. Angew. Chem., Int. Ed. Engl. 1994, 33,
1757–1758; (c) Sugimoto, Y.; Hanamoto, T.; Inanaga, J.
Appl. Organomet. Chem. 1995, 9, 369–375; (d) Inanaga, J.;
Sugimoto, Y.; Hanamoto, T. Tetrahedron Lett. 1992, 33,
7035–7038; (e) Ezcurra, J. E.; Moore, H. W. Tetrahedron
Lett. 1993, 34, 6177–6180; (f) Braverman, S.; Duar, Y. J. Am.
d 7.22 (1H, t, J¼7.9 Hz), 7.03 (1H, d, J¼7.9 Hz), 6.85 (1H,
d, J¼7.9 Hz), 4.60 (2H, s), 4.54 (2H, s), 3.89 (3H, s), 2.37
(2H, br s); 13C NMR d 129.1, 123.4, 110.7, 96.1, 91.8,
56.0, 52.1, 51.8; MS m/z 216 (M+, 100); HRMS calcd for
C13H12O3 216.0787, found 216.0790.
4.6.5. 1-[1-(Diphenylphosphinyl)-1,2-propadienyl]-2-(3-
hydroxy-1-propynyl)benzene (24). To a suspension of
NaH (60% in oil, 44.0 mg, 1.1 mmol) in THF (5 mL) was
added a solution of 4a (186 mg, 1.00 mmol) in THF
(5 mL) at 0 ꢁC. After 20 min, TBSCl (166 mg, 1.10 mmol)
was added to the mixture, which was stirred for an additional
1 h at room temperature. The reaction was quenched by
addition of saturated aqueous NH4Cl, and the mixture was
extracted with AcOEt. The extract was washed with water
and brine, dried, and concentrated to dryness. The residue
was chromatographed with hexane–AcOEt (5:1) to afford
1-[3-(tert-butyldimethylsiloxy)-1-propynyl]-2-(3-hydroxy-
1-propynyl)benzene (23) (213 mg, 71%) as a pale yellow
€
Chem. Soc. 1990, 112, 5830–5837; (g) Hohn, J.; Weyerstahl,
P. Chem. Ber. 1983, 116, 808–814; (h) Staab, H. A.; Draeger,
B. Chem. Ber. 1972, 105, 2320–2333; (i) Bowes, C. M.;
Montecalvo, D. F.; Sondheimer, F. Tetrahedron Lett. 1973,
3181–3184; (j) Ben-Efraim, D. A.; Sondheimer, F.
Tetrahedron Lett. 1963, 313–315.
4. For the preparation of allenes via the [2,3]-sigmatropic re-
arrangement of propargyl phosphinites, see: Hashmi, A. S. K.
Modern Allene Chemistry; Krause, N., Hashmi, A. S. K.,
Eds.; Wiley-VCH: Weinheim, 2004; Vol. 1, pp 3–50.
5. The tandem formation and intramolecular [4+2] cycloaddition
of 1-phosphinyl-1-vinylallenes, triggered by [2,3]-sigmatropic
rearrangement of the corresponding propargyl phosphinites,
have been reported: (a) Okamura, W. H.; Curtin, M. L.
Synlett 1990, 1–9; (b) Curtin, M. L.; Okamura, W. H. J. Org.
Chem. 1990, 55, 5278–5287.
1
oil: IR 3607, 3421, 2233, 2189 cmꢀ1; H NMR d 7.43–
7.41 (2H, m), 7.27–7.24 (2H, m), 4.59 (2H, s), 4.52 (2H,
br s), 2.37 (1H, br s), 0.94 (9H, s), 0.18 (6H, s); 13C NMR
d 131.8, 131.7, 128.0, 127.9, 125.4, 125.1, 91.7, 91.5,
84.2, 83.4, 52.4, 51.5, 25.8, 14.1, ꢀ5.1; MS m/z 243
t
(M+ꢀ Bu, 99); HRMS calcd for C14H15O2Si 243.0841,
found 243.0846.
To a solution of the above propargyl alcohol 23 (30.0 mg,
0.100 mmol) and Et3N (0.05 mL, 0.4 mmol) in THF
(1 mL) was added Ph2PCl (0.05 mL, 0.3 mmol) at ꢀ78 ꢁC.
After 45 min, the reaction was quenched by addition of sat-
urated aqueous NaHCO3, and the mixture was extracted with
AcOEt. The extract was washed with water and brine, dried,
6. Horner, L.; Binder, V. Liebigs Ann. Chem. 1972, 757, 33–68.
7. Part of this work was published as a preliminary communica-
tion: Kitagaki, S.; Okumura, Y.; Mukai, C. Tetrahedron Lett.
2006, 47, 1849–1852.
8. Production of 6aa from 4a was described in the review article by
Grissom. Grissom, J. W.; Gunawardena, G. U.; Klingberg, D.;

10320
S. Kitagaki et al. / Tetrahedron 62 (2006) 10311–10320
Huang, D. Tetrahedron 1996, 52, 6453–6518. However, no
original manuscript dealing with the details of this reaction is
available.
13. Cava, M. P.; Hwang, B.; Van Meter, J. P. J. Am. Chem. Soc.
1963, 85, 4031–4032.
14. Similar ring opening of cyclobutane was not observed in the
reaction of 3,8-bis(diphenylphosphinyl)-1,2-dimethylnaphtho-
[b]cyclobutene with LiAlH4: see Ref. 7.
9. Mukai, C.; Ohta, M.; Yamashita, H.; Kitagaki, S. J. Org. Chem.
2004, 69, 6867–6873.
10. For the [2+2] cycloaddition of allenes, see: Murakami, M.;
Matsuda, T. Modern Allene Chemistry; Krause, N., Hashmi,
A. S. K., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 2,
pp 727–815.
11. Substrates were prepared by one- or two-step Sonogashira cou-
pling of dihalobenzene with substituted propargyl alcohols.
12. Braverman and Duar have discussed a mechanism for a hydro-
gen-shift reaction of benzene-bridged diallene having four
methyl groups on the allene: see Ref. 3f.
15. It is known that trans-1,2-diphenylnaphtho[b]cyclobutene
slowly isomerizes at room temperature to give an equilibrium
mixture of trans/cis-isomers: see Ref. 3c.
16. Mladenova, M.; Alami, M.; Linstrumelle, G. Synth. Commun.
1996, 26, 2831–2842.
17. Cava, M. P.; Shirley, R. L. J. Am. Chem. Soc. 1960, 82, 654–
656.
18. Grissom, J. W.; Klingberg, D.; Huang, D.; Slattery, B. J. J. Org.
Chem. 1997, 62, 603–626.