Novel synthetic route to dihydropyrenes

Article abstract of DOI:10.1055/s-0028-1087363

We developed a new and short synthetic route to 2,7-di-tert-butyl-trans-15, 16-dimethyldihydropyrene (DHP) via tetrahydroxy[2.2]metacyclophane in four reaction steps with a total yield of 37%. 2,7-Di-tert-butyl-trans-15,16- dimethyldihydropyrene functionalized by acetoxy groups at 4-, 5-, 9-, 10-positions was synthesized via 5,13-di-tert-butyl-8,16-dimethyl-1,2,9,10- tetrahydroxy[2.2]MCP in five reaction steps with a yield of 24%, and its DHP structure was determined by ¹H NMR spectroscopy and X-ray crystal-structure analysis. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087363

LETTER
3153
Novel Synthetic Route to Dihydropyrenes
S
ynthetic Route to
a
D
ihydropy
z
renes ufumi Chifuku, Tsuyoshi Sawada,* Takao Kihara, Kentaro Shimojo, Hidetoshi Sonoda, Yutaka Kuwahara,
Hideto Shosenji, Hirotaka Ihara
Department of Applied Chemistry and Biochemistry, Kumamoto University, 2-39-1 Kurokami, Kumamoto-shi,
Kumamoto 860-8555, Japan
Fax +81(96)3423679; E-mail: sawada@gpo.kumamoto-u.ac.jp
Received 12 August 2008
bridge positions, the reduction of which would afford a
[2.2]MCP-diene, which is an equivalent of 3.
Abstract: We developed a new and short synthetic route to 2,7-di-
tert-butyl-trans-15,16-dimethyldihydropyrene (DHP) via tetra-
hydroxy[2.2]metacyclophane in four reaction steps with a total
yield of 37%. 2,7-Di-tert-butyl-trans-15,16-dimethyldihydro-
pyrene functionalized by acetoxy groups at 4-, 5-, 9-, 10-positions
was synthesized via 5,13-di-tert-butyl-8,16-dimethyl-1,2,9,10-
tetrahydroxy[2.2]MCP in five reaction steps with a yield of 24%,
and its DHP structure was determined by 1H NMR spectroscopy and
X-ray crystal-structure analysis.
However, the benzene-annulated DHP at the [e]-position
showed a high quantum yield of photoisomerization6 and
possessed suitable properties to qualify as switching
materials.2b,d,e It is also expected that DHP substituted at
the [e]-position or 4-, 5-, 9-, 10-positions could be pre-
pared by using 6 as the intermediate in short reaction
steps, and these DHP could be investigated for the various
purposes. In this paper, we present a simple and short syn-
thetic route to 3 and 9, which is substituted by acetoxy
groups at 4-, 5-, 9-, 10-positions, via 6 as the intermediate.
Key words: cyclophanes, arenes, photochemistry, reduction,
oxidations
The synthesis of 3 was shown in Scheme 2. 2,6-Bis(bromo-
methyl)-4-tert-butyltoluene (4) and 2,6-di-formyl-4-tert-
butyltoluene (5) were synthesized with yields of 90% and
70%, respectively.4,5a Pinacol coupling of 5 in an ice bath
afforded 6 in 79% yield, while previously reported meth-
ods afforded 6 only in 33% yield at room temperature.5a,b
The MCP 6 was reduced to 3 using imidazole, chlo-
rodiphenylphosphine, iodine, and Zn powder. This meth-
od, which produced cis-olefin from trans-diol of
carbohydrate, has been reported by Zhengchun.7 A sus-
pension of 6, imidazole, and chlorodiphenylphosphine in
toluene was added to iodine at reflux temperature and
stirred for 1 hour. Zinc powder was added, and the mix-
ture was stirred for 8 hours to afford 3 and 7 in 75% and
7% yields, respectively.8 This synthetic route afforded 3
with a total yield of 37%.
Dihydropyrene (DHP) derivatives have been attracting
considerable interests in various fields2a–f due to their
photochromic property between DHP and [2.2]metacyclo-
phane-1,9-dienes ([2.2]MCP-diene) since 1967.1
The synthetic route to di-tert-butyldimethylDHP (3),
which was the parent compound of DHP, was developed
by Tashiro3 and improved by Mitchell.4 This route via
dithia[3.3]MCP 2 required six reaction steps, and a total
yield of 45% was achieved from 4-tert-butyltoluene 1
(Scheme 1). Each reaction yield of this route was over
76%, but the long reaction sequence and requirement of
highly skilled techniques restricted the practical applica-
tions of DHP as advanced materials.
Previously, we have reported facile and one-step synthesis
of 5,13-di-tert-butyl-8,16-dimethyl-1,2,9,10-tetrahydroxy-
[2.2]MCP (6) from the bezenedialdehyde derivative 5.5a,b
The MCP 6 has the potential to be the intermediate in
DHP formation because it has two trans-diols at both its
The expected reaction mechanism from 6 to 3 is shown in
Scheme 3. As a first step, chlorodiphenylphosphine and
imidazole gave imidazolium-solvated complex 8.9 The
reaction of 6 and 8 was guessed to form cyclic phosphoni-
um ion 9 and iodo-phosphinate 10 as the intermediates.7,10
The elimination of iodine and diphenylphosphinic acid
from iodo-phosphinate 10 provided corresponding olefin.
t-Bu
t-Bu
Me
3 steps
3 steps
Me
Me
Me
S
S
Me
The synthesis of 12 is shown in Scheme 4. Previously, we
have reported the two-step oxidation of 6 to 11 with a
yield of 31%.11 Here, we developed a one-step oxidation
of 6 using Ac2O and DMSO.12 A solution of 6 in DMSO
and Ac2O was degassed in vacuo, and the reaction mixture
was stirred under a nitrogen atmosphere to afford 11 in
98% yield.13 Treatment of 11 with zinc powder, Ac2O,
and Et3N14a,b afforded 12 functionalized by acetoxy
moieties at 4-, 5-, 9-, 10-positions in 50% yield.15 This
synthetic route afforded 12 in 24% yield from 1.
t-Bu
1
t-Bu
t-Bu
3
2
Scheme 1
SYNLETT 2008, No. 20, pp 3153–3156
1
6
.1
2
.2
0
0
8
Advanced online publication: 27.11.2008
DOI: 10.1055/s-0028-1087363; Art ID: U08508ST
© Georg Thieme Verlag Stuttgart · New York

3154
K. Chifuku et al.
LETTER
Me
Me
1) pyridine, reflux
2) Me2NC6H4NOHCl, EtOH, r.t.
Br
Br
ZnBr2, (CH2O)3
HBr in AcOH (30%)
reflux, N2 atmosphere
70%
t-Bu
t-Bu
90%
4
1
OH
Me
t-Bu
Me
imidazole, Ph2PCl,
Al powder,
OHC
CHO
HO
OH
Me
NaOH aq (10 wt%)
I2, Zn powder
toluene
reflux
MeOH
0 °C
t-Bu
t-Bu
HO
79%
5
6
t-Bu
Me
t-Bu
O
O P Ph
Ph
Me
Me
Me
+
t-Bu
t-Bu
3
7
75%
7%
Scheme 2
I–
I
Ph
P+
Ph
NH+
Cl–
HN
I–
N
HN
N
N
Ph2PCl
+
I2
+
+
2
8
OH
Ph
I
P+
+
N
N
OH
NH
N
– HI, –
Ph
6
8
Ph
O
Ph
O
O
9
Ph
Ph
HI
P
P+
I–
– I2
– Ph2POOH
O
I
3
10
Scheme 3 Reaction mechanism from vicinal diol to olefin
In 1H NMR spectra, the chemical shifts of two signals of
methyl groups in 7 and one signal of 12 were observed at
d = –4.10, –4.17, and –3.28 ppm, respectively. This result
estimated that 7 and 12 had DHP forms in which internal
methyl groups were influenced by a strong shielding
effect. The chemical shifts of the internal methyl protons
of 7 shifted to higher magnetic fields than those of 3
(d = –4.04 ppm)4 by 0.06–0.13 ppm. In contrast, the sig-
nal of internal methyl protons of 12 shifted downfield
when compared to those of 3 by 0.75 ppm. These upfield
and downfield shifts suggested that the aromaticity of
DHP was influenced by the electron-donating16 or elec-
tron-withdrawing groups at 4-, 5-, 9-, 10-positions.
Figure 1 Crystal structure of 12 and chloroform: (a) top view; (b)
side view
X-ray crystallography also clarified that 12 formed the
DHP structure (Figure 1).17 A larger alternation of the
short and long bonds was observed for the periphery of 12
(1.346–1.432 Å) than the periphery of 3 (1.387–1.402
Å).18 This result also confirmed that the aromaticity of 12
decreased in comparison to that of 3 due to the acetoxy
groups at 4-, 5-, 9-, 10-positions of 12.
In summary, we developed a new and short synthetic
method to 3. This synthetic route afforded 3 in four reac-
Synlett 2008, No. 20, 3153–3156 © Thieme Stuttgart · New York

LETTER
Synthetic Route to Dihydropyrenes
3155
t-Bu
O
O
OH
OH
Me
t-Bu
Me
t-Bu
Zn powder
AcO
OAc
OAc
Ac2O, DMSO
Ac2O, Et3N
O
HO
Me
Me
r.t., N2 atmosphere
CH2Cl2
r.t., N2 atmosphere
t-Bu
Me
AcO
t-Bu
Me
98%
O
HO
50%
t-Bu
11
6
12
Scheme 4
over MgSO4, evaporated in vacuo, and purified by TLC to
afford 3 (63 mg, 75%) and 7 (8 mg, 7%) as green powders.
Compound 3: mp (from n-hexane) 201–203 °C (lit.4 mp
203–204 °C). 1H NMR (400 MHz, 25 °C, CDCl3): d = –4.04
(s, 6 H), 1.69 (s, 18 H), 8.46 (s, 4 H), 8.54 (s, 4 H).
tion steps with a total yield of 37%. In addition, function-
alized DHP 12 was synthesized in five reaction steps from
1 with a total yield of 24%. X-ray structure analysis and
1H NMR spectrum of 12 confirmed the DHP structure of
12 and proved that the aromaticity of 12 decreased in
comparison to that of 3. We believe that these novel syn-
thetic routes to DHP could be useful for practical applica-
tions of DHP in various fields.
Compound 7: mp (from n-hexane) 104–105 °C. FT-IR: 697,
732, 1026, 1109, 1130, 1161, 1236, 1360, 1437, 2861, 2906,
2926, 2967 cm–1. 1H NMR (400 MHz, 25 °C, CDCl3): d =
–4.17 (s, 3 H), –4.10 (s, 3 H), 1.57 (s, 9 H), 1.60 (s, 9 H),
7.27–7.39 (m, 4 H), 7.40–7.58 (m, 4 H), 8.00–8.22 (m, 2 H),
8.33 (d, J = 7.80 Hz, 1 H), 8.38 (d, J = 7.84 Hz, 1 H), 8.43
(s. 1 H), 8.45 (s, 1 H), 8.49 (s, 1 H), 8.67 (s, 1 H), 8.82 (s,
1 H). 13C NMR (100 MHz, 25 °C, CDCl3): d = 29.53, 29.68,
31.81, 31.86, 31.89, 31.96, 36.00, 36.03, 115.85, 120.48,
121.04, 121.59, 122.50, 122.80, 123.26, 124.51, 128.39,
128.70, 131.80, 132.26, 135.14, 136.54, 137.47, 142.10,
144,59, 146.91. HRMS–FAB+: m/z calcd for C38H41O2P +
Na: 583.2775; found: 583.2776 [M+ + Na].
Acknowledgment
This study was financially supported by Venture Business Labora-
tory (VBL) of Kumamoto University, and Grant-in-Aid for Scienti-
fic research (C).
References and Notes
(9) Garegg, P. J.; Samuelsson, B. Synthesis 1979, 469.
(10) Fox, D. J.; Pedersen, D. S.; Petersen, A. B.; Warren, S. Org.
(1) Boekelheide, V.; Phillips, J. B. J. Am. Chem. Soc. 1967, 89,
1695.
Biomol. Chem. 2006, 4, 3117.
(11) Tsukamoto, K.; Sahade, D. A.; Taniguchi, M.; Sawada, T.;
Thiemann, T.; Mataka, S. Tetrahedron Lett. 1999, 40, 4691.
(12) Albright, J. D.; Goldman, L. J. Am. Chem. Soc. 1967, 89,
2416.
(2) (a) Zhao, P.; Fang, C.; Xia, C.; Liu, D.; Xie, S. Chem. Phys.
Lett. 2008, 453, 62. (b) Andreasson, J.; Straight, S. D.;
Bandyopadhyay, S.; Mitchell, R. H.; Moore, T. A.; Moore,
A. L.; Gust, D. Angew. Chem. Int. Ed. 2007, 46, 958.
(c) Lee, H.; Robinson, S. G.; Bandyopadhyay, S.; Mitchell,
R. H.; Sen, D. J. Mol. Biol. 2007, 371, 1163. (d) Straight,
A. D.; Andreasson, J.; Kodis, G.; Bandyopadhyay, S.;
Mitchell, R. H.; Moore, T. A.; Moore, A. L.; Gust, D. J. Am.
Chem. Soc. 2005, 127, 9403. (e) Liddell, P. A.; Kodis, G.;
Andreasson, J.; Garza, L. D. L.; Bandyopadhyay, S.;
Mitchell, R. H.; Moore, T. A.; Moore, A. L.; Gust, D. J. Am.
Chem. Soc. 2004, 126, 4803. (f) Marsella, M. J.; Wang, Z.;
Mitchell, R. H. Org. Lett. 2000, 2, 2979.
(3) Tashiro, M.; Yamato, T. J. Am. Chem. Soc. 1982, 104, 3701.
(4) Mitchell, R. H.; Ward, T. R.; Chen, Y.; Wang, Y.;
Weerawarna, S. A.; Dibble, P. W.; Marsella, M. J.;
Almutairi, A.; Wang, Z. J. Am. Chem. Soc. 2003, 125, 2974.
(5) (a) Sahade, D. A.; Tsukamoto, K.; Thiemann, T.; Sawada,
T.; Mataka, S. Tetrahedron 1999, 55, 2573. (b) Sahade,
D. A.; Mataka, S.; Sawada, T.; Tsukinoki, T.; Tashiro, M.
Tetrahedron Lett. 1997, 38, 3745.
(13) Oxidation of 6 to 11
A solution of 6 (1.00 g, 2.40 mmol) in DMSO (100 mL) was
degassed in vacuo, Ac2O (10.0 ml, 97.2 mmol) was added,
and the mixture was degassed in vacuo. The reaction mixture
was stirred for 20 h under nitrogen at r.t. Then, H2O (100
mL) was added and the reaction mixture was neutralized by
aq NH3. The reaction mixture was then filtered, and the
precipitate was washed with H2O and cold MeOH, and dried
in vacuo to afford 11 (959 mg, 98%) as a yellow powder; mp
233–240 °C (dec.); lit11 mp 230–240 °C (dec.). 1H NMR
(400 MHz, 25 °C, CDCl3): d = 0.89 (s, 6 H), 1.29 (s, 18 H),
7.58 (s, 4 H).
(14) (a) Phillips, K. E. S.; Katz, T. J.; Jockusch, S.; Lovinger,
A. J.; Turro, N. J. J. Am. Chem. Soc. 2001, 123, 11899.
(b) Fox, J. M.; Katz, T. J.; Van Elshocht, S.; Verbiest, T.;
Kauranen, M.; Persoons, A.; Thongpanchang, T.; Krauss,
T.; Brus, L. J. Am. Chem. Soc. 1999, 121, 3453.
(15) Synthesis of 12 from 11
(6) Sheepwash, M. A. L.; Ward, T. R.; Wang, Y.;
Bandyopadhyay, S.; Mitchell, R. H.; Bohne, C. Photochem.
Photobiol. Sci. 2003, 2, 104.
(7) Zhengchun, L.; Classon, B. J. Org. Chem. 1990, 55, 4273.
(8) Synthesis of 3 from 6
To a suspension of 11 (500 mg, 0.25 mmol) and zinc powder
(1.61 g, 25.0 mmol) in dry CH2Cl2 (50 mL) was added Ac2O
(2.5 mL, 24.3 mmol) and Et3N (5.0 mmol, 37.5 mmol). The
mixture was stirred for 2.5 h under nitrogen at r.t., and then
filtered through Celite. The filtrate was washed with 10 wt%
aq HCl (50 mL) and sat. aq NaHCO3 (50 mL). The organic
layer was dried over MgSO4 and evaporated in vacuo; the
residue was recrystallized with hexane–CH2Cl2 to afford 12
(203 mg, 50%) as green needles.
To a stirred suspension of 6 (100 mg, 0.24 mmol), imidazole
(196 mg, 2.88 mmol), and chlorodiphenylphosphine (235
mg, 1.00 mol) in toluene (50 mL) was added iodine (243 mg,
1.00 mmol) portionwise at reflux temperature, and the
mixture was refluxed for 1 h. Zinc powder (667 mg, 9.76
mmol) was added, and the mixture was refluxed for 8 h. The
mixture was cooled to r.t. and washed with 1 M NaOH (50
mL), H2O (50 mL), and brine. The organic layer was dried
Dihydropyrene 12: mp (from n-hexane–CH2Cl2): 257–258
°C. FT-IR: 1003, 1215, 1479, 1661, 2957, 3672 cm–1. 1H
NMR (400 MHz, 25 °C, CDCl3): d = –3.28 (s, 6 H), 1.61 (s,
Synlett 2008, No. 20, 3153–3156 © Thieme Stuttgart · New York

3156
K. Chifuku et al.
LETTER
18 H), 2.58 (s, 12 H), 8.45 (s, 4 H). 13C NMR (100 MHz, 25
°C, CDCl3): d = 20.56, 29.90, 31.05, 31.70, 36.25, 116.00,
125.75, 134.93, 147.02, 169.15. MS–FAB+: m/z = 576 [M+].
Anal. Calcd for C34H40O8: C, 70.81; H, 6.99. Found: C,
70.55; H, 7.14.
nonhydrogen atoms were refined anisotropically. Hydrogen
atoms were included, but not refined. The weighting scheme
w = 1/[s2 (Fo2) + (0.2000P)2 + 0.0000P] where P = (Fo2 –
Fc2)2. Supplementary data of 12 have been deposited with
the CCDC in the CIF format (deposit No. CCDC671306).
X-ray analysis for 12: C36H42O8Cl6 (C34H40O8 + 2CHCl3),
MW = 815.44, green needles, monoclinic, P21/n (# 14),
Z = 2, a = 14.220 (4) Å, b = 10.2485 (19) Å, c = 14.012 (2)
Å, b = 93.051 (17)°, V = 2039.1 (7) Å3, Dcalcd = 1.328
g cm–3, T = 298 K, m(Moka) = 4.669 cm–1, Rigaku AFC7R,
Moka (l = 0.71069 Å), 254 parameters, R1 = 0.1193,
wR2 = 0.4244, GOF = 0.901.
(16) Chevykalova, M. N.; Manzhukova, L. F.; Artemova, N. V.;
Luzikov, Yu. N.; Nifant, I. E.; Nifant, E. E. Russ. Chem.
Bull. 2003, 52, 78.
(17) Single crystals of 12 suitable for X-ray analysis were
prepared by recrystallization from CHCl3. Diffraction data
were collected on a Regaku AFC’R diffractometer at 25 °C
with graphite monochromated Moka (l = 0.71069 Å)
radiation. For structure analysis and refinement,
(18) Williams, R. V.; Armantrout, J. R.; Twamley, B.; Mitchell,
R. H.; Ward, T. R.; Bandyopadhyay, S. J. Am. Chem. Soc.
2002, 124, 13495.
computations were performed using the Crystal Structure
crystallographic software package of Rigaku Corporation.
The structure was solved by the direct method (SIR92). All
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