Synthesis of naphtho[b]cyclobutenes from 1,2-bis(3-propynol)benzenes

Article abstract of DOI:10.1016/j.tetlet.2005.12.121

We have demonstrated that the reaction of benzene-bridged bis(propargyl alcohol)s with chlorodialkylphosphines exclusively afforded 3,8- bis(dialkylphosphinyl)naphtho[b]cyclobutenes via the [2+2] cycloaddition of 1,2-bis(α-phosphinylallenyl)benzenes. Deph

Full text of DOI:10.1016/j.tetlet.2005.12.121

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1849–1852
Synthesis of naphtho[b]cyclobutenes from
1,2-bis(3-propynol)benzenes
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 6 December 2005; accepted 22 December 2005
Available online 26 January 2006
Abstract—We have demonstrated that the reaction of benzene-bridged bis(propargyl alcohol)s with chlorodialkylphosphines
exclusively afforded 3,8-bis(dialkylphosphinyl)naphtho[b]cyclobutenes via the [2+2] cycloaddition of 1,2-bis(a-phosphinylallenyl)-
benzenes. Dephosphinylation of the product has also been achieved.
Ó 2006 Elsevier Ltd. All rights reserved.
Recent efforts from this laboratory disclosed the novel
one-pot synthesis of the polycyclic aromatic compounds
based on the sequential pericyclic reaction of the ene-
bis(sulfinylallene) intermediates 3,1 derived from the
ene-bis(propargyl alcohol) 1 and benzenesulfenyl chlo-
ride (PhSCl) via the ene-bis(propargyl sulfenate) 2.
Thus, the consecutive sequences, which entirely involves
the sulfenic ester formation (first step), dual [2,3]-sigma-
tropic rearrangement of 2 (second step), 6p-electrocyclic
reaction of ene-diallenes 3 (third step), and intramole-
cular [4+2] cycloaddition of o-quinodimethanes 4 (fourth
step), enabled the one-pot construction of the polycyclic
compounds 5 from 1 (Scheme 1). The intermolecular
version of this methodology was also realized as exem-
plified by the conversion of 6 into the tetrahydroanthra-
cene derivative 8.
According to the procedure for the reaction with
PhSCl,1,3 chlorodiphenylphosphine (Ph2PCl), to the
solution of benzene-bridged bis(propargyl alcohol) 6,
triethylamine, and dimethyl fumarate (as a dienophile)
was added in THF at À78 °C, and the resulting mixture
was warmed to room temperature. Despite the similarity
in electronic nature between phosphinyl and sulfinyl
groups,4 the isolated product from the reaction mixture
was not the expected cycloadduct 10a, but the naph-
tho[b]cyclobutene 9a5 in a high yield (Scheme 2). This
result obviously indicated that a dienophile did not take
part in the formation of 9a. Thus, the ring-closing reac-
tion using PhSCl and other chlorophosphines in the
absence of the dienophile became the next subject (Table
1).
The reactions with PhSCl and diethyl chlorophosphite
[(EtO)2PCl] under the standard conditions resulted in
the complex mixtures of products (entries 5 and 6). In
contrast to these results, the reactions with chloro-
dialkylphosphines exclusively afforded the correspond-
ing 3,8-bis(dialkylphosphinyl)naphtho[b]cyclobutenes
9a–d in high yields, regardless of the bulkiness of the
alkyl groups on phosphorus atom (entries 1–4).6 A full
mechanistic discussion is premature at this point, but
it might be rationalized that the bis(phosphinylallene)
11, derived from the bis(propargyl phosphinite) by dual
[2,3]-sigmatropic rearrangement,3,7 would be converted
into the biradical (o-quinodimethane) species 12, which
subsequently undergo intramolecular [2+2] cycloaddi-
tion to produce 9 (Scheme 3). Although there are several
precedents that the o-quinodimethanes, possessing the
In the course of our studies on further development of
the above procedure, we investigated the pericyclic reac-
tion of the ene-bis(phosphinylallene) instead of the ene-
bis(sulfinylallene). This letter describes the unexpected
reactivity of the ene-bis(phosphinylallene), which led
to the exclusive construction of the naphtho[b]cyclo-
butenes, useful molecules for Diels–Alder reaction or
other transformations.2
Keywords: Bisallenes; [2+2] Cycloaddition; Naphtho[b]cyclobutenes;
Dephosphinylation.
*
Corresponding authors. Tel.: +81 76 234 4411; fax: +81 76 234
4410; e-mail: cmukai@kenroku.kanazawa-u.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.121

1850
S. Kitagaki et al. / Tetrahedron Letters 47 (2006) 1849–1852
PhS
O
OH
OH
Ph(O)S
R1
R1
R2
R1
R2
.
.
PhSCl
R2
Ph(O)S
[2,3]-sigmatropic
rearrangement
Et3N
THF
PhSO
1
2
3
Ph(O)S
R1
Ph(O)S
R1
R2
R2
6π electrocyclization
[4+2]
cycloaddition
Ph(O)S
Ph(O)S
5
4
Ph(O)mS
PhSCl, Et3N, THF
OH
OH
CO2Me
CO2Me
°
→
–78 C rt
CO2Me
Ph(O)mS
mCPBA
MeO2C
6
7: m=1
8: m=2
84% (2 steps)
Scheme 1. Construction of polycyclic skeleton based on ene-diallene formation.
Ph2P(O)
Ph2P(O)
Ph2PCl, Et3N, THF
OH
OH
CO2Me
CO2Me
→
rt
–78 °C
CO2Me
Ph2P(O)
Ph2P(O)
10a: 0%
MeO2C
6
9a: 85%
Scheme 2.
highly substituted exo-methylene unit, are subjected to
[2+2] cycloaddition (or [1,5] hydrogen shift) rather than
[4+2] cycloaddition with dienophiles,8,9 the exclusive
[2+2] cycloaddition of unsubstituted ones is rare to the
best of our knowledge. Of particular interest is that
the reaction mode of the intermediacy of the quinodi-
methanes is completely controlled by the nature of the
substituents on the benzene ring (phosphinyl vs sulfinyl).
The fact that (EtO)2PCl could not provide the cyclo-
butene derivative might be due to the comparatively
low reactivity of the propargylic ester (e.g., first step in
Scheme 1) for [2,3]-sigmatropic rearrangement.3
Table 1. Synthesis of naphtho[b]cyclobutene 9
R2P(O)
X(O)
OH
X-Cl, Et3N, THF
R2P(O)
→
–78 C
rt
R2P(O)
˚
9
•
OH
X(O)
•
6
9
R2P(O)
10
R2P(O)
Entry
X
Product
Yield (%)
1
2
3
4
5
6
Ph2P
Cy2P
(i-Pr2)P
Et2P
(EtO)2P
PhS
9a
9b
9c
9d
9e
9f
85
98
81
99
0
11
R2P(O)
12
0
Scheme 3.

S. Kitagaki et al. / Tetrahedron Letters 47 (2006) 1849–1852
1851
Having identified the effectiveness of the phosphinyl
group on the [2+2] cycloaddition, we then investigated
the synthesis of naphtho[b]cyclobutenes possessing some
substituents on the cyclobutene ring.10 The results are
summarized in Table 2. Mono-, 1,2-di-, and 1,1-di-
substituted naphtho[b]cyclobutenes 14a–e were obtained
from substituted bis(propargyl alcohol)s 13a–e in high
yields. However, fully methyl-substituted bis(propargyl
alcohol) 13f afforded hydrogen-shifted product 15 as
the sole isolable product.
The next phase of this program was to search the con-
ditions for the removal of the phosphinyl moiety on
the naphthalene ring. The reaction of the naphtho[b]-
11
cyclobutene derivative 9a with LiAlH4 under reflux-
ing conditions was screened (Table 3). As a result,
1,4-dioxane12 was found to effectively provide the bis-
dephosphinylated naphtho[b]cyclobutene 1613 (entries
1 and 2).14 A similar result was obtained when refluxed
in THF (entry 3). Although the LiAlH4 reduction in a
mixed solvent of butyl ether and benzene (1:1) was re-
ported to be effective for the conversion of triphenyl-
phosphine oxide to triphenylphosphine,15 the
transformation of 9a into 16 could not be realized
(entry 4). The isopropyl derivative 9c underwent the
similar bisdephosphinylation to furnish 16 in a lower
yield (entry 8). Alternatively, a selective monodephos-
phinylation of 9a was achieved by treatment with
LiAlH4–metal halide systems as shown in entries 5–7.
The best result was obtained when 9a was exposed to
Table 2. Synthesis of naphtho[b]cyclobutene 14
R1 R2
Ph2P(O)
R1
OH
Ph2PCl, Et3N, THF
R2
R3
–78
→
C rt
˚
R4
OH
R3 R4
13a-f
Ph2P(O)
14a-f
Entry
Substrate
R1
R2
R3
R4
Yield (%)
1
2
3
4
5
6
13a
13b
13c
13d
13e
13f
Me
CH2OBn
Me
Ph
Me
H
H
H
H
Me
Me
H
H
Me
Ph
H
H
H
H
H
H
Me
84
90
16
84a
87b
86
LiAlH4–TiCl4 in THF at room temperature to give
3-(diphenylphosphinyl)naphtho[b]cyclobutene (17a) in
88% yield (entry 5). The application of these conditions
to 9c afforded 17c in 79% yield (entry 9). LiAlH4–
Me
Me
0c
17
18
CuCl2 and LiAlH4–NiCl2 in refluxing THF were
also effective in this conversion (entries 6 and 7). In
addition, reaction of the dimethyl congener, 1,2-dimeth-
ylnaphtho[b]cyclobutene 14c, with LiAlH4 in refluxing
dioxane gave 18 in 52% yield (Scheme 4).19 The treat-
ment of 1-methylnaphtho[b]cyclobutene 14a with
LiAlH4–TiCl4 furnished 19 and 20 in the yields of
40% and 40%, respectively.
a Diastereomer ratio = 3:2. The relative configuration at two isomers
was not determined.
b Diastereomer ratio = 2:1. The relative configuration at two isomers
was not determined.
c Compound 15 was obtained in 61% yield.
Ph2P(O)
In summary, we have developed a novel and general
procedure for the construction of naphtho[b]cyclo-
butene derivatives from benzene-bridged bis(propargyl
Ph2P(O)
15
Table 3. C–P bond cleavage of 9 with LiAlH4
R12P(O)
H
LiAlH4, additive
solvent
R12P(O)
R2
9
16, 17
Entry
Substrate
Solvent
Additive
Temp (°C)
Time (h)
Product
R1
R2
Yield (%)
1
2
3
4
5
6
7
8
9
9a
9a
9a
9a
9a
9a
9a
9c
9c
Ph
Ph
Ph
Ph
Ph
Ph
Ph
i-Pr
i-Pr
Diglyme
Dioxane
THF
None
None
None
None
TiCl4
CuCl2
NiCl2
None
TiCl4
162
101
65
100
23
65
65
101
23
5
5
5
5
1
7
2
7
16
16
H
H
H
H
50
70
49
0
88
68
41
41
79
16
16
Bu2O/benzenea
THF
b
17a
17a
17a
16
P(O)Ph2
P(O)Ph2
P(O)Ph2
H
b
THF
THF
Dioxane
THF
c
0.5
17c
P(O)(i-Pr)2
a Volume ratio = 1:1.
b Molar ratio of LiAlH4–metal halide = 2:1.
c Molar ratio of LiAlH4–metal halide = 1:1.

1852
S. Kitagaki et al. / Tetrahedron Letters 47 (2006) 1849–1852
aqueous NaHCO3, and the mixture was extracted with
Ph2P(O)
AcOEt. The extract was washed with water and brine,
dried over Na2SO4, and concentrated. Chromatography of
the residue with AcOEt–MeOH (90:1) afforded 9 (47.0 mg,
LiAlH4
dioxane, reflux
52%
1
85%) as a colorless solid: H NMR (270 MHz, CDCl3) d
Ph2P(O)
8.59–8.55 (2H, m), 7.70–7.25 (22H, m), 2.09 (4H, s);
18
13C NMR (67.8 MHz, CDCl3) d 133.8 (JC–P = 7.3), 132.4
14c
(JC–P = 11.0), 131.8 (JC–P = 106.2), 131.6, 128.7 (JC–P
=
R1
12.2), 127.8 (JC–P = 6.1), 126.2, 124.7 (JC–P = 3.5), 29.8.
Anal. Calcd for C36H28O2P2Æ1/2H2O: C, 76.72; H, 5.19.
Found: C, 76.78; H, 5.30.
Ph2P(O)
LiAlH4, TiCl4
7. For the preparation of allenes via the [2,3]-sigmatropic
rearrangement of propargyl phosphinites, see: Hashmi, A.
S. K. In Modern Allene Chemistry; Krause, N., Hashmi,
A. S. K., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 1, pp 3–
50.
THF, 23
80%
C
˚
R2
Ph2P(O)
19: R1 = H, R2 = P(O)Ph2
20: R1 = P(O)Ph2, R2 = H
14a
(19 : 20 = 1 : 1)
8. For examples, see: (a) Lenihan, B. D.; Shechter, H. J. Org.
Chem. 1998, 63, 2072–2085; (b) Lenihan, B. D.; Shechter,
H. J. Org. Chem. 1998, 63, 2086–2093.
Scheme 4.
9. For the [2+2] cycloaddition of quinodimethanes derived
from ene-diallenes, see: (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. Organo-
met. 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. Chem.
Soc. 1990, 112, 5830–5837; (g) Ho¨hn, J.; Weyerstahl, P.
Chem. Ber. 1983, 116, 808–814; (h) Staab, H. A.; Draeger,
B. Chem. Ber. 1972, 105, 2320–2333.
alcohol)s via the consecutive pericyclic reactions, in
which the 1,2-bis(a-phosphinylallenyl)benzenes effec-
tively underwent the intramolecular [2+2] cycloaddition
to give 3,8-diphosphinylnaphtho[b]cyclobutenes in
sharp contrast to the case of the 1,2-bis(a-sulfinylallen-
yl)benzenes. The resulting phosphoryl groups on the
naphthalene ring could be arbitrarily removed by proper
choice of reducing conditions resulting in the selective
preparation of monophosphinylated or dephosphinyl-
ated naphtho[b]cyclobutenes, the former of which may
be useful as the precursors of new ligands or reagents.
Studies on the reaction process of ene-bis(phosphinyl-
allene) and related compounds are currently underway.
10. Substrates were prepared by one- or two-step Sonogashira
coupling of diiodobenzene with substituted propargyl
alcohols.
11. Ring opening of dibenzo[b,f]phosphepin using LiAlH4 in
refluxing diglyme has been reported: (a) Segall, Y.; Shirin,
E.; Granoth, I. Phosphorus Sulfur 1980, 8, 243–254; (b)
Granoth, I.; Segall, Y.; Leader, H. J. Chem. Soc., Chem.
Commun. 1976, 74–75.
12. LiAlH4 in refluxing dioxane reduces phosphine sulfides to
phosphines: King, R. B.; Cloyd, J. C., Jr. J. Am. Chem.
Soc. 1975, 97, 53–60.
Acknowledgments
This work was supported in part by a Grant-in Aid for
Scientific Research from the Ministry of Education, Cul-
ture, Sports, Science, and Technology, Japan, for which
we are thankful.
13. Cava, M. P.; Shirley, R. L. J. Am. Chem. Soc. 1960, 82,
654–656.
References and notes
14. Typical procedure: To a suspension of LiAlH4 (45.5 mg,
1.20 mmol) in dioxane (3 mL), 9a (165 mg, 0.300 mmol)
was added at 0 °C, and the mixture was refluxed for 5 h.
The mixture was cooled to room temperature and
quenched by the addition of water. 10% aqueous HCl
was added, and the mixture was extracted with AcOEt.
The extract was washed with water and brine, dried over
Na2SO4, and concentrated. Chromatography of the resi-
due with hexane afforded 16 (32.3 mg, 70%) as a colorless
solid.
1. Kitagaki, S.; Ohdachi, K.; Kato, K.; Mukai, C. Org. Lett.
2006, 8, 95–98.
2. (a) Sadana, A. K.; Saini, R. K.; Billups, W. E. Chem. Rev.
2003, 103, 1539–1602; (b) Cava, M. P.; Hwang, B.; Van
Meter, J. P. J. Am. Chem. Soc. 1963, 85, 4031–4032.
3. Horner, L.; Binder, V. Liebigs Ann. Chem. 1972, 757, 33–
68.
4. Mukai, C.; Ohta, M.; Yamashita, H.; Kitagaki, S. J. Org.
Chem. 2004, 69, 6867–6873.
15. Horner, L.; Hoffmann, H.; Beck, P. Chem. Ber. 1958, 91,
1583–1588.
5. Production of 9a from 6 was described in the review article
by Grissom (Grissom, J. W.; Gunawardena, G. U.;
Klingberg, D.; Huang, D. Tetrahedron 1996, 52, 6453–
6518). However, no original manuscript dealing with the
details of this reaction is available.
16. LiAlH4–TiCl4 reagent is effective for reduction of aryl
sulfides, aryl halides, and olefins: (a) Mukaiyama, T.;
Hayashi, M.; Narasaka, K. Chem. Lett. 1973, 291–294; (b)
Chum, P. W.; Wilson, S. E. Tetrahedron Lett. 1976, 15–16.
17. LiAlH4–CuCl2 reagent is effective for reductive fission of
sulfides: Mukaiyama, T.; Narasaka, K.; Maekawa, K.;
Furusato, M. Bull. Chem. Soc. Jpn. 1971, 44, 2285.
18. LiAlH4–NiCl2 reagent is effective for reduction of alkene,
alkynes, and halides: Ashby, E. C.; Lin, J. J. Tetrahedron
Lett. 1977, 4481–4484.
6. Typical procedure: To
0.102 mmol) and Et3N (0.10 mL, 0.72 mmol) in THF
(1 mL) was added solution of Ph2PCl (0.10 mL,
a solution of 6 (19.0 mg,
a
0.56 mmol) in THF (0.5 mL) at À78 °C. The reaction
mixture was stirred at that temperature for 2 h and
allowed to warm to room temperature. After 2 h, the
reaction was quenched by the addition of saturated
19. The diastereomer ratio of 14c was as same as that of 18.