Synthesis and Diels-Alder reactions of 1,2-dimethylene[2.n]metacyclophanes

Article abstract of DOI:10.1021/ol0483403

(Chemical Equation Presented) The Diels-Alder reaction of 1,2-dimethylene[2.n]MCPs (MCP = metacyclophane) with suitable dienophiles followed by aromatization and photoinduced or FeCl₃-induced transannular cyclization afforded phenanthrene-anell

Full text of DOI:10.1021/ol0483403

ORGANIC
LETTERS
2005
Vol. 7, No. 1
3-6
Synthesis and Diels−Alder Reactions of
1,2-Dimethylene[2.n]metacyclophanes
Takehiko Yamato,*,† Shinpei Miyamoto,† Tohru Hironaka,† and Yoshinori Miura‡
Department of Applied Chemistry, Faculty of Science and Engineering,
Saga UniVersity, Honjo-machi 1, Saga-shi, Saga 840-8502, Japan,
and Center of AdVanced Instrumental Analysis, Kyushu UniVersity, 6-1,
Kasuga-kohen, Kasuga-shi, Fukuoka 816-8510, Japan
yamatot@cc.saga-u.ac.jp
Received August 20, 2004 (Revised Manuscript Received October 22, 2004)
ABSTRACT
The Diels−Alder reaction of 1,2-dimethylene[2.n]MCPs (MCP ) metacyclophane) with suitable dienophiles followed by aromatization and
photoinduced or FeCl3-induced transannular cyclization afforded phenanthrene-anellated polycyclic aromatic hydrocarbons, which were found
to adopt helical chirality in the solid state.
Although well-established, the Diels-Alder reaction has been
used for a new type of application in recent years. Thus, de
Meijere et al. reported1 that the Diels-Alder reaction of
highly strained 1,2-dimethylene[2.n]paracyclophanes with
dienophiles could be used to prepare arene-anellated [2.n]-
paracyclophanes. 1,2-Dimethylene[2.n]MCPs lower the bar-
riers of the Diels-Alder reactions by virtue of the dienes
adopting a fixed s-cis conformation in the ground and
transition states.2,3
potentially, these two reactions could be combined to
allow the preparation of phenanthrene-anellated polycyclic
aromatic hydrocarbons provided that suitable substituted 1,2-
dimethylene[2.n]MCPs were available. In this paper, we
report on the first successful synthesis of 1,2-dimethylene-
[2.n]MCPs and on their conversion to phenanthrene-anellated
polycyclic aromatic hydrocarbons through Diels-Alder
reaction and photoinduced, or Lewis acid-induced, transan-
nular cyclization.
In cyclophane chemistry, the reductive coupling of car-
bonyl compounds, catalyzed by low-valent titanium,5 has
been used to synthesize cyclophanes with glycol units as
bridges.6 Gru¨tzmacher et al.7 used this method in the
cyclization of suitable dialdehydes to afford unsaturated
cyclophanes. Given these past precedents we decided to
examine the coupling reactions of 1,3-bis(5-acetyl-2-meth-
oxy-phenyl)propane 1a and 1,4-bis(5-acetyl-2-methoxyphe-
It is also well-known that the photoinduced transannular
cyclization reaction of stilbene derivatives affords phenan-
threnes in the presence of an oxidant.4 We reasoned that
† Saga University.
‡ Kyushu University.
(1) (a) Ko¨nig, B.; de Meijere, A. Chem. Ber. 1992, 125, 1895-1898.
(b) de Meijere, A.; Ko¨nig, B. Synthesis 1997, 1221-1232.
(2) (a) Cyclophanes; Keehn, P. M., Rosenfield, S. M., Eds.; Academic
Press: New York, 1983; Vols. 1 and 2. (b) Vo¨gtle, F. Cyclophane-
Chemistry; Wiley: Chichester, 1993. (c) Yamato, T.; Matsumoto, J.; Ide,
S.; Tokuhisa, K.; Suehiro, K.; Tashiro, M. J. Org. Chem. 1992, 57, 5243-
5246. (d) Yamato, T.; Matsumoto, J.; Tokuhisa, K.; Kajihara, M.; Suehiro,
K.; Tashiro, M. Chem. Ber. 1992, 125, 2443-2454. (e) Yamato, T.;
Matsumoto, J.; Sato, M.; Noda, K.; Tashiro, M. J. Chem. Soc., Perkin Trans.
1 1995, 1299-1308.
(5) McMurry, J. E. Chem. ReV. 1989, 89, 1513-1524.
(6) Mitchell, R. H.; Weerawana, S. A. Tetrahedron Lett. 1986, 27, 453-
456.
(7) (a) Gru¨tzmacher, H.-F.; Neumann, E.; Ebmeyer, F.; Albrecht, K.;
Schelenz, P. Chem. Ber., 1989, 122, 2291-2297. (b) Gru¨tzmacher, H.-F.;
Neumann, E. Chem. Ber. 1993, 126, 1495-1497. (c) Gru¨tzmacher, H.-F.;
Nolte, G. Chem. Ber. 1994, 127, 1157-1162. (d) Gru¨tzmacher, H.-F.;
Mehdizadeh, A.; Mu¨lverstedt, A. Chem. Ber. 1994, 127, 1163-1166.
(3) Gru¨tzmacher, H.-F.; Albrecht, K. Chem. Ber. 1989, 122, 2299-2302.
(4) Floyd, A. J.; Dyke, S. F.; Ward, S. E.Chem. ReV., 1976, 76, 509-
562.
10.1021/ol0483403 CCC: $30.25
© 2005 American Chemical Society
Published on Web 12/10/2004

Scheme 1. Synthesis of 1,2-Dimethylene[2.n]MCPs 4
Scheme 2. Synthesis of Areno-Bridged MCPs 6
propanobridge proved the absence of a syn-syn intercon-
version, which would exchange HA and HB of each CH2
group. In contrast, the internal aromatic proton of 2a showed
an upfield shift (δ 5.68 ppm) due to the ring current of the
opposite benzene ring.2b,9 The structure of 2a corresponded
exclusively to the anti conformer. These observations sug-
gested that the introduction of two double bonds of the
ethanobridge might control the syn and anti conformation
of 1,2-dimethylene[2.3]MCP 4a.
nyl)butane 1b,8 respectively, with low-valent titanium (TiCl4/
Zn) and obtained 2a and 2b in good yields. The structures
of 2a and 2b were elucidated on the basis of their elemental
analyses and spectral data. In particular, the mass spectral
data for 2 (M+ ) 308 for 2a and 322 for 2b) strongly
supported the cyclic structure.
Interestingly, bromination of 1,2-dimethyl[2.3]MCP-1-ene
2a with 1 equiv of benzyltrimethylammonium tribromide
(BTMABr3)9,10 at room temperature afforded the correspond-
ing 1,2-dimethylene[2.3]MCP 4a in 50% yield along with a
trace amount of 1,2-bis(bromomethyl)[2.3]MCP-1-ene 3a.
This transformation probably occurred by addition of bro-
mine to the double bond followed by a twofold dehydro-
bromination to give the diene 4a. In fact, the same treatment
of 2a at -10 °C afforded a mixture of the trans adduct to
the bridging double bond and 3a in quantitative yield.11
Similar results were obtained with 2b, which provided 4b
As the temperature of the solution of 4a in CDCl3 was
increased, the individual peak of the benzyl protons merged
and eventually a single peak was observed above 30 °C. This
observation indicated that the rate of conformational ring
flipping of 4a was faster than the NMR time scale at this
temperature. The energy barrier to the conformational ring
flipping estimated from the coalescence temperature (TC) was
14.0 kcal mol-1 lower value than that of anti-1,2-dimethyl-
[2.3]MCP-1-ene 2a (TC ) 70 °C, ∆Gq ) 15.6 kcal mol-1).
Compound 4a is too labile a solid to purify. When in
solution, or in air, compound 4a slowly decomposes.
However, the compound is easily trapped by the reaction
with dimethyl acetylenedicarboxylate to afford 5a in good
yield. Diels-Alder adduct 5a was converted to areno-bridged
MCP 6a by aromatization with dichlorodicyano-p-benzo-
quinone (DDQ). Similarly, 6b was obtained from 4b as
described above. The present Diels-Alder reaction of 4 with
dimethylacetylenedicarboxylate was completed within 2 h
in toluene at reflux, which was much faster than that of 2,3-
diphenyl-1,3-butadiene (12 h). Thus, the Diels-Alder reac-
tivity of 4 exceeds that of 2,3-diphenyl-1,3-butadiene. This
result suggests that the energy of the fixed s-cis conformation
in 4 in the ground and transition state might lower the Diels-
Alder barriers due to the inflexibility of the cyclophane ring.
The Diels-Alder reaction of 4 with suitable dienophiles
followed by aromatization can be used to prepare a range of
areno-bridged [2.n]MCPs. The Diels-Alder reactivities of
4a were tested in reactions with p-benzoquinone and 1,4-
naphthoquinone. Upon heating a mixture of 4a and 0.5 equiv
of p-benzoquinone in toluene at reflux, a Diels-Alder adduct
was formed in 36% yield. Successively, treatment of the
reaction mixture with DDQ led to dehydrogenation to afford
1
in quantitative yield. The 270 MHz H NMR spectrum of
4a in CDCl3 showed a doublet for the intra-annular proton
Hi at δ 6.92 ppm (J ) 2.0 Hz) in addition to the resonances
at δ 6.26 and 6.47 ppm for the other two protons of the
aromatic rings. The exo-methylene protons of the ethano-
bridge were observed as doublets at δ 5.16 and 5.62 ppm (J
) 2.0 Hz), and the methoxy protons appeared at δ 3.60 ppm.
The protons of the trimethylene bridge gave rise to a
complicated signal pattern as expected for a rigid syn-[2.3]-
MCP. The protons of the benzylic CH2 group were observed
as two multiplets centered at δ 2.28 and 3.14 ppm, which
were further split by coupling with the protons of the central
CH2 group. This central CH2 group was also observed as
two multiplets centered at δ 1.32 and 1.83 ppm. The peak
pattern ascribed to the six chemically distinct protons of the
(8) Yamato, T.; Maeda, K.; Kamaimura, H.; Noda, K.; Tashiro, M. J.
Chem. Res., Synop. 1995, 310-311; J. Chem. Res., Miniprint 1995 1865-
1889.
(9) (a) Tashiro, M.; Yamato, T. J. Org. Chem. 1981, 46, 4556-4562.
(b) Tashiro, M.; Yamato, T. J. Org. Chem. 1983, 48, 1461-1468.
(10) Kajigaeshi, S.; Kakinami, T.; Tokiyama, H.; Hirakawa, T.; Okamoto,
T. Chem. Lett. 1987, 627-630.
(11) (a) Yamato, T.; Sato, M.; Noda, K.; Matsumoto, J.; Tashiro, M.
Chem. Ber. 1993, 126, 447-451. (b) Yamato, T.; Matsumoto, J.; Ide, S.;
Suehiro, K.; Tashiro, M. J. Chem. Res., Synop. 1993, 394-395.
4
Org. Lett., Vol. 7, No. 1, 2005

Table 1. Diels-Alder Reaction of 4a and 4b with Dienophiles
in Toluene Followed by Aromatization with DDQ
Table 2. Photoinduced and FeCl3-Induced Transannular
Cyclization Reaction of Areno-Bridged MCPs 6 and 9 to Afford
Phenanthrene-anellated Polycyclic Aromatic Hydrocarbons
a Isolated yields are shown.
a Isolated yields are shown. b Conditions: (A) I2, hν in benzene for 40
h; (B) FeCl3 in CH2Cl2 at room temperature for 3 h. c Reaction time was
12 h. d Starting compound 6b was recovered in quantitative yield.
bis(1,2-naphthoquinono[2.3]MCP, “twin-phane” 8a, in quan-
titative yield. Treatment of 4a with 2.0 equiv of p-
benzoquinone in toluene at reflux followed by dehydroge-
nation yielded a mixture of 1,2-(6,7)naphthoquinono[2.3]-
MCP 7a and bisadduct 8a in 30 and 28% yields, respectively.
Under similar conditions the addition of 4a and 4b to 1,4-
naphthoquinone afforded the cycloadducts 9a and 9b in 48
and 74% yields, respectively.
Examination of molecular models led us to believe that
the transformation of 6a into phenanthrene 10a would be
straightforward, since the p orbitals in the conformationally
rigid stilbene moiety of 6a, which are involved in the
photoinduced disrotatory cyclization leading to the phenan-
threne 10a eventually, are apparently very close in space.
Actually, when 6a was irradiated by a 400 W high-pressure
mercury lamp in the presence of an oxidant under standard
conditions (I2),12 the desired phenanthrene 10a was obtained
in 94% yield. This result is quite different from the
photoinduced transannular cyclizations of 3,3′-disubstituted
stilbenes to afford 4,5-disubstituted phenanthrenes only in
low yields due to the steric hindrance between the two
substituents on the 3,3′-positions.13 However, in the case of
10b only the starting compound was recovered despite the
prolonged reaction time. These findings suggest that the
extent of fixing conformations in the ground and transition
state affect the photoinduced transannular cyclization reac-
tion.
The presently developed method was further applied to
bridge-anellated [2.3]MCP 8a and 9a. Similarly, photoin-
duced transannular cyclization of areno-bridged MCP 9a
afforded phenanthrene-anellated polycyclic aromatic hydro-
carbons 11a in 86% yield. No photoinduced reaction in the
benzoquinone moiety was observed under the conditions
used. However, several attempted photoinduced transannular
cyclizations of “twin-phane” 8a under the various conditions
failed due to low solubility in benzene. Only the recovery
of the starting compound 8a resulted. Several attempts at
using Lewis acids (AlCl3, TiCl4, SnCl4) to catalyze the
transannular cyclization of areno-bridged MCP 6a failed.
Only recovery of the starting compound or the formation of
the intractable mixture of products resulted. Fortunately, we
have found that when the transannular cyclization of 6a is
carried out in CH2Cl2 at room temperature in the presence
of the FeCl314 (10 equiv), the desired phenanthrene-anellated
polycyclic aromatic hydrocarbon 10a is formed in 97% yield
within 3 h. Similarly, FeCl3-induced transannular cyclizations
of 6b and 9a afforded 10b and 11a in 96 and 92% yields,
respectively. Although currently the detailed mechanism has
yet to be clarified, the presently developed method provides
good yields and easily isolated products.
Interestingly, X-ray analysis revealed that triphenylene 10b
adopts helical chirality, yet surprisingly, the dihedral angle
of arylenes connected by the phenyl unit is 33.98°. As a
consequence, the compound is chiral and the (M)- and (P)-
isomers are packed alternatively in the crystal as depicted
schematically in Figure 2.15
(12) Mallory, F. B.; Mallory, C. W. Org. React. 1984, 30, 1-456.
(13) (a) Ben, I.; Castedo, L.; Saa´, J. M.; Seijas, J. A.; Suau, R.; Tojo,
G.J. Org. Chem. 1985, 50, 2236-2240. (b) Cosmo, R.; Hambley, T. W.;
Sternhell, S. J. Org. Chem. 1987, 52, 3119-3123. (c) Armstrong, R. N.;
Ammon, H. L.; Darnow, J. N. J. Am. Chem. Soc. 1987, 109, 2077-2082.
(d) Grimme, S.; Pischel, I.; Nieger, M.; Vo¨gtle, F. J. Chem. Soc., Perkin
Trans. 2 1996, 2771-2774.
(14) Borner, R. R. C.; Jackson, R. F. W. J. Chem. Soc., Chem. Commun.
1994, 845-846.
Org. Lett., Vol. 7, No. 1, 2005
5

Figure 1. ORTEP view of (P)-10b (thermal ellipsoids for 50%
probability). Hydrogens are omitted for clarify.
On the other hand, NMR spectra of 10b show totally
systematic patterns at room temperature. Upon lowering the
temperature, the signals experience broadening to some
extent, although no splitting is observed even at -80 °C.
This phenomenon may possibly be explained in terms of a
rapid fluxional conformational change in solution between
Figure 2. Partial view of 10b in the crystal.
the enantiomeric species that innately should give rise to
unsymmetrical patterns.16
(15) Crystal data for 10b: C28H26O6, M ) 482.52, orthorhombic, Pbca
(No. 61), a ) 24.505(3), b ) 7.3151(8), c ) 25.162(2) Å, V ) 4510.5(8)
Å3, Z ) 8, Dc ) 1.350 g cm-3, µ(Cu KR) ) 1.54184 Å, T ) 291 K,
colorless prisms; 5256 independent observed reflections F2 > 3σ, 2856
parameters. CCDC 246144.
In conclusion, a new synthesis of areno-bridged [2.n]-
MCPs by the Diels-Alder reaction of 4 with suitable
dienophiles has been developed and applied to the synthesis
of phenanthrene-anellated polycyclic aromatic hydrocarbons
by the successive photoinduced or FeCl3-induced transan-
nular cyclization reaction.17 Further investigations are in
progress to widen the range of this new pathway to
phenanthrene-anellated polycyclic aromatic hydrocarbons for
advanced materials.
(16) Mu¨llen, K.; Heinz, W.; Kla¨rner, F. G.; Roth, W. R.; Kindermann,
I.; Adamczak, O.; Wette M.; Lex, J. Chem. Ber. 1990, 123, 2349-2371.
(17) All new compounds have been fully characterized by 1H NMR, IR,
and mass spectroscopy and elemental analyses. Some physical properties
and spectral data of the compounds obtained in the present work were
shown. Spectral data of 2a: colorless prisms (MeOH), mp 122-125 °C;
1H NMR (CDCl3, -40 °C) δ 1.59-1.77 (2H, m), 1.90-2.05 (2H, m), 2.20
(6H, s), 2.86-2.98 (2H, m), 3.85 (6H, s), 5.68 (2H, d, J 2.4), 6.73 (2H, d,
J 8.3), 7.08 (2H, dd, J 8.3, 2.4); MS (EI) m/z 308 (M+). Spectral data of
1
4a: colorless prisms (MeOH), mp 78-79 °C; H NMR (CDCl3, -60 °C)
δ 1.19-1.45 (1H, m), 1.74-1.92 (1H, m), 2.20-2.37 (2H, m), 3.07-3.21
(2H, m), 3.60 (6H, s), 5.16 (2H, d, J 2.0), 5.62 (2H, d, J 2.0), 6.26 (2H, d,
J 8.3), 6.47 (2H, dd, J 2.0, 8.3), 6.92 (2H, d, J 2.0); MS (EI) m/z 306 (M+).
Spectral data of 6a: colorless needles (EtOH/benzene 2:1), mp 273-275
°C; IR (KBr) 1722 cm-1; 1H NMR (CDCl3, 27 °C) δ 1.63-1.87 (2H, m),
1.96-2.11 (2H, m), 2.90-3.14 (2H, m), 3.88 (6H, s), 5.78 (2H, broad s),
6.83 (2H, broad s), 7.08 (2H, broad s), 7.93 (2H, broad s); MS (EI) m/z
446 (M+). Spectral data of 10a: yellow prisms (EtOH), mp 183-184 °C;
IR (KBr) 1720 cm-1; 1H NMR (CDCl3, 27 °C) δ 2.46-2.53 (2H, m), 2.79
(4H, t, J 6.8), 3.99 (12H, s), 7.29 (2H, d, J 8.3), 8.42 (2H, d, J 8.3), 8.77
(2H, s); MS (EI) m/z 444 (M+).
Supporting Information Available: Experimental pro-
cedure of preparation of compounds 1-11, physical data,
spectral data for all new compounds, and crystallographic
data of 10b. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0483403
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