Synthesis and structures of diindeno-fused 1,12-diphenylbenzo[c] phenanthrene and 1,14-diphenyl[5]helicene bearing severe helical twists

Article abstract of DOI:10.1021/ol063056s

(Chemical Equation Presented) Diindeno-fused 1,12-diphenylbenzo[c] phenanthrene 15 and 1,14-diphenyl[5]helicene 20 were prepared in a four-step synthetic sequence from 2,7-naphthalenedicarboxylic acid and 3,6-phenanthrenedicarboxylic acid, respectively. T

Full text of DOI:10.1021/ol063056s

ORGANIC
LETTERS
2007
Vol. 9, No. 6
1025-1028
Synthesis and Structures of
Diindeno-Fused
1,12-Diphenylbenzo[c]phenanthrene and
1,14-Diphenyl[5]helicene Bearing Severe
Helical Twists
Yanzhong Zhang, Jeffrey L. Petersen,† and Kung K. Wang*
C. Eugene Bennett Department of Chemistry, West Virginia UniVersity,
Morgantown, West Virginia 26506-6045
kung.wang@mail.wVu.edu
Received December 18, 2006
ABSTRACT
Diindeno-fused 1,12-diphenylbenzo[c]phenanthrene 15 and 1,14-diphenyl[5]helicene 20 were prepared in a four-step synthetic sequence from
2,7-naphthalenedicarboxylic acid and 3,6-phenanthrenedicarboxylic acid, respectively. The X-ray structures of 15 and 20 show that the fused
ring systems possess severe helical twists. The rotational barriers of the phenyl substituents were determined by the analysis of temperature-
dependent 1H NMR spectra.
The sterically congested 1,12-dimethylbenzo[c]phenanthrene
(1a) (Figure 1) was first synthesized by Newman and Wolf
in 1952.1 The X-ray crystallographic structure of 1a exhibited
out-of-plane deformation.2 The resolution of an acetic acid
derivative, 1,12-dimethylbenzo[c]phenanthrene-5-acetic acid
(1b), provided the initial evidence of the helical shape of
the molecule.3 The corresponding methyl ester was found
to be of high configurational stability, undergoing only slow
racemization even at 250 °C. The stability of the structure
and the ready availability of optically pure 5,8-disubstituted
1,12-dimethylbenzo[c]phenanthrenes (1c) make them excel-
lent chiral building blocks for a variety of derivatives.4 The
synthesis of an interesting 1,12-bis(2-pyridyl) derivative was
also reported.5
A computational study of substituted dibenzo[c,g]phenan-
threnes ([5]helicenes) also showed that 1,14-dimethyl[5]-
helicene (2a) has a high racemization barrier.6 While the
(4) (a) Yamaguchi, M.; Okubo, H.; Hirama, M. Chem. Commun. 1996,
1771-1772. (b) Cheung, J.; Field, L. D.; Hambley, T. W.; Sternhell, S. J.
Org. Chem. 1997, 62, 62-66. (c) Okubo, H.; Yamaguchi, M.; Kabuto, C.
J. Org. Chem. 1998, 63, 9500-9509. (d) Okubo, H.; Nakano, D.; Anzai,
S.; Yamaguchi, M. J. Org. Chem. 2001, 66, 557-563. (e) Saiki, Y.;
Nakamura, K.; Nigorikawa, Y.; Yamaguchi, M. Angew. Chem., Int. Ed.
2003, 42, 5190-5192. (f) Sugiura, H.; Nigorikawa, Y.; Saiki, Y.; Nakamura,
K.; Yamaguchi, M. J. Am. Chem. Soc. 2004, 126, 14858-14864. (g)
Sugiura, H.; Takahira, Y.; Yamaguchi, M. J. Org. Chem. 2005, 70, 5698-
5708. (h) Nakano, D.; Hirano, R.; Yamaguchi, M.; Kabuto, C. Tetrahedron
Lett. 2003, 44, 3683-3686 and references therein.
† To whom correspondence concerning the X-ray structures should be
addressed. Phone: (304) 293-3435, ext 6423. Fax: (304) 293-4904.
E-mail: jeffrey.petersen@mail.wvu.edu.
(1) Newman, M. S.; Wolf, M. J. Am. Chem. Soc. 1952, 74, 3225-3228.
(2) Hirshfeld, F. L.; Sandler, S.; Schmidt, G. M. J. J. Chem. Soc. 1963,
2108-2125.
(3) Newman, M. S.; Wise, R. M. J. Am. Chem. Soc. 1956, 78, 450-
454.
(5) Fields, D. L.; Regan, T. H. J. Heterocycl. Chem. 1973, 10, 195-
199.
(6) Janke, R. H.; Haufe, G.; Wu¨rthwein, E.-U.; Borkent, J. H. J. Am.
Chem. Soc. 1996, 118, 6031-6035.
10.1021/ol063056s CCC: $37.00
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four congested phenyl substituents and possessing a severe
helical twist of the fused ring system was likewise synthe-
sized from p-dipivalobenzene in 18% overall yield.12 The
structure of 6 resembles that of a segment of a spiral staircase
with the four phenyl groups mimicking the four parallel steps.
We now have successfully extended this three-step reaction
sequence to the synthesis of a diindeno-fused 1,12-diphen-
ylbenzo[c]phenanthrene and 1,14-diphenyl[5]helicene bear-
ing severe helical twists.
The requisite 2,7-dipivalonaphthalene (8) was prepared by
converting 2,7-naphthalenedicarboxylic acid (7)13 to the
corresponding acid chloride followed by treatment with tert-
butylcopper, prepared from tert-butyllithium and CuBr‚SMe2
(Scheme 1). Condensation between 8 and 2 equiv of lithium
Scheme 1
Figure 1. 1,12-Dimethylbenzo[c]phenanthrenes 1, 1,14-disubstituted-
[5]helicenes 2, and related compounds 3 and 4.
synthesis of 2a has not been reported, photodehydrocycliza-
tion of a stilbene-like derivative produced 1,14-dimethoxy-
[5]helicene (2b) in 61% yield.7 Other closely related
compounds, including 2c,d and 3, have also been synthesized
by photodehydrocyclization or by the Diels-Alder reac-
tion.8,9 For 14,15-diphenyldibenzo[f,j]picene (4) with the two
phenyl substituents at the most sterically hindered positions,
the use of the photodehydrocyclization method gave only
very low yield (<1%).10
We recently reported the use of p-dipivalobenzene in a
three-step synthetic sequence for the preparation of the
diindeno-fused 4,5-diphenylphenanthrene 5 (Figure 2) in 38%
Figure 2. Structures of 4,5-diphenylphenanthrenes 5 and 6.
acetylide 9 furnished the benzannulated enediynyl alcohol
10 as an essentially 1:1 mixture of two diastereomers.
Treatment of 10 with triethylsilane in the presence of
trifluoroacetic acid at room temperature for 10 min produced
the benzannulated enediyne 11 also as an essentially 1:1
mixture of two diastereomers. On exposure to potassium tert-
overall yield.11 The X-ray structure of 5 shows a severe
helical twist of the fused ring system. Similarly, 6 bearing
(7) Liu, L.; Yang, B.; Katz, T. J.; Poindexter, M. K. J. Org. Chem. 1991,
56, 3769-3775.
(8) (a) Yamamoto, K.; Ikeda, T.; Kitsuki, T.; Okamoto, Y.; Chikamatsu,
H.; Nakazaki, M. J. Chem. Soc., Perkin Trans. 1 1990, 271-276. (b)
Nakazaki, M.; Yamamoto, K.; Ikeda, T.; Kitsuki, T.; Okamoto, Y. J. Chem.
Soc., Chem. Commun. 1983, 787-788. (c) Minuti, L.; Taticchi, A.;
Marrocchi, A.; Gacs-Baitz, E.; Galeazzi, R. Eur. J. Org. Chem. 1999, 3155-
3163.
(9) Sudhakar, A.; Katz, T. J. J. Am. Chem. Soc. 1986, 108, 179-181.
(10) Laarhoven, W. H.; Boumans, P. G. F. Recl. TraV. Chim. Pays-Bas
1975, 94, 114-118.
(11) Li, H.; Petersen, J. L.; Wang, K. K. J. Org. Chem. 2001, 66, 7804-
7810.
(12) Dai, W.; Petersen, J. L.; Wang, K. K. Org. Lett. 2004, 6, 4355-
4357.
(13) (a) Honzawa, S.; Okubo, H.; Nakamura, K.; Anzai, S.; Yamaguchi,
M.; Kabuto, C. Tetrahedron: Asymmetry 2002, 13, 1043-1052. (b) Katz,
T. J.; Liu, L.; Willmore, N. D.; Fox, J. M.; Rheingold, A. L.; Shi, S.;
Nuckolls, C.; Rickman, B. H. J. Am. Chem. Soc. 1997, 119, 10054-10063.
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Org. Lett., Vol. 9, No. 6, 2007

butoxide in refluxing toluene for 3 h, 11 was transformed to
the diindeno-fused 1,12-diphenylbenzo[c]phenanthrene 15 in
a single operation in 10% yield. While the yield of the
reaction is not high, it is significantly better than the yield
of less than 1% of 4 by the photodehydrocyclization method.
The transformation from 11 to 15 likely involved initial
prototropic rearrangements to form the benzannulated enyne-
allene 12 as described previously for 5 and 6. An intramo-
lecular Diels-Alder reaction, presumably proceeding through
a Schmittel cyclization reaction14 to generate the correspond-
ing biradical followed by an intramolecular radical-radical
coupling involving a sterically more hindered R-carbon of
the naphthyl ring, then produced 13. The higher reactivity
of the R-position than the â-position of the naphthyl ring in
the homolytic addition reaction was reported previously.15
A subsequent prototropic rearrangement to regain aromaticity
then led to 14. A similar cascade sequence of the second
benzannulated enyne-allene unit then furnished 15. The
preferential attack of the sterically more hindered C4 position
of the phenanthryl ring in 14 was also observed previously.16
It is worth noting that without a prior prototropic rearrange-
ment of 13 to form 14, the C4 carbon of 13 could only be
regarded as a member of a benzene ring. Consequently, it
could be anticipated that the sterically less hindered C2
position of 13 would have been attached preferentially.
Similarly, by starting from 3,6-phenanthrenedicarboxylic
acid (16) (Figure 3),17 3,6-dipivalophenanthrene (17) was
83% yield. On treatment of 19 with potassium tert-butoxide
in refluxing toluene for 3 h, the diindeno-fused 1,14-
diphenyl[5]helicene 20 was produced in 47% yield.
As in the cases of 5 and 6, the structures of 15 and 20
were established by X-ray structure analyses (Figure 4). The
Figure 4. ORTEP drawings of the crystal structures of 15 and 20
with hydrogen atoms omitted for clarity.
X-ray structure of 5 showed a helical twist of the phenan-
threne ring system with a 46.1° acute dihedral angle between
the mean planes of the two outer benzene rings bearing the
phenyl substituents. A more pronounced 59.2° twist angle
was observed for 6. The X-ray structure of 15 also showed
a severe helical twist of the benzo[c]phenanthrene ring
system with a 59.9° acute dihedral angle between the mean
planes of the two outer benzene rings bearing the phenyl
substituents. The phenyl substituents are oriented in such a
way that each is at a 60.8° angle from the benzene ring to
Figure 3. 3,6-Phenanthrenedicarboxylic acid (16), 3,6-di-
pivalophenanthrene (17), benzannulated enediynyl alcohol 18,
benzannulated enediyne 19, and 1,14-diphenyl[5]helicene 20.
obtained in 43% yield and then was used for condensation
with 2 equiv of 9 to produce the benzannulated enediynyl
alcohol 18 in 91% yield. Subsequent reduction with trieth-
ylsilane in the presence of trifluoroacetic acid gave 19 in
(15) (a) Tinnemans, A. H. A.; Laarhoven, W. H. J. Chem. Soc., Perkin
Trans. 2 1976, 1115-1120. (b) Tinnemans, A. H. A.; Laarhoven, W. H. J.
Am. Chem. Soc. 1974, 96, 4617-4622.
(16) Yang, H.; Petersen, J. L.; Wang, K. K. Tetrahedron 2006, 62, 8133-
8141.
(14) (a) Schmittel, M.; Strittmatter, M.; Vollmann, K.; Kiau, S. Tetra-
hedron Lett. 1996, 37, 999-1002. (b) Schmittel, M.; Strittmatter, M.; Kiau,
S. Angew. Chem., Int. Ed. Engl. 1996, 35, 1843-1845. (c) Schmittel, M.;
Vavilala, C. J. Org. Chem. 2005, 70, 4865-4868.
(17) (a) Du Vernet, R. B.; Wennerstro¨m, O.; Lawson, J.; Otsubo, T.;
Boekelheide, V. J. Am. Chem. Soc. 1978, 100, 2457-2464. (b) Khalaf, A.
I.; Pitt, A. R.; Scobie, M.; Suckling, C. J.; Urwin, J.; Waigh, R. D.; Fishleigh,
R. V.; Young, S. C.; Wylie, W. A. Tetrahedron 2000, 56, 5225-5239.
Org. Lett., Vol. 9, No. 6, 2007
1027

which it is connected but is roughly parallel to the opposite
side of the twisted benzo[c]phenanthrene ring system with
a distance of ca. 2.94 Å at the closest points, which is shorter
than the usual π-system van der Waals contact distance of
ca. 3.4 Å between parallel aromatic hydrocarbons in crys-
tals.18 For the [5]helicene ring system of 20, the acute
dihedral angle between the mean planes of the two outer
benzene rings bearing the phenyl substituents is 57.8°. In
comparison, the parent [5]helicene has a corresponding acute
dihedral angle of only ca. 30°.19 In addition, each of the
phenyl substituents of 20 is at a 60.2° angle from the benzene
ring to which it is attached, but is in roughly parallel
orientation to the opposite side of the twisted[5]helicene ring
system with a distance of ca. 3.00 Å at the closest points.
mol of 512 and ca. 13 kcal/mol of several 1-phenylbenzo[c]-
phenanthrene derivatives reported earlier.20 As expected, the
AB quartet signals remained unaffected due to the slow rate
of racemization.
In the case of 20 in CDCl3 recorded on a 600 MHz NMR
spectrometer, the ortho hydrogens appeared as a very broad
hump at δ 6.1, barely discernible from the baseline, and the
meta hydrogens also appeared as a broad peak at δ 6.79. At
-30 °C, a doublet at δ 5.58 and a signal overlapping with
other signals at δ 6.65, attributable to the ortho hydrogens
were observed. For the meta hydrogens, an overlapping
signal at δ 6.65 and an overlapping triplet at δ 6.98 could
be discerned. The coalescence temperatures of the ortho and
meta hydrogens were determined to be at 20 and 5 °C,
respectively, corresponding to a rotational barrier of 12.9
kcal/mol. It is interesting to note that this rotational barrier
is significantly lower than that of 15 and is also lower than
the rotational barrier of ca. 16 kcal/mol of a 1-phenyl[5]-
helicene derivative reported earlier.20 One possible explana-
tion for this unexpected observation is the lack of a more
stable ground state that is accessible to the rotating phenyl
substituents in 20, reminiscent of a faster rate of rotation in
a 1-triptycyl[4]helicene system as a molecular ratchet than
that of 4-(9-triptycyl)phenanthrene reported previously.21 In
1,1,2,2-tetrachloroethane-d2 and recorded on a 270 MHz
NMR spectrometer at 100 °C, a doublet at δ 6.18 from the
ortho hydrogens and a triple at δ 6.83 from the meta
hydrogens could be clearly discerned. The AB quartet signals
also remained unaffected due to the slow rate of racemiza-
tion.
As observed previously in 5 and 6, the existence of a
helical twist was also manifested with a set of AB quartet
1H NMR signals from the diastereotopic methylene hydro-
gens on the five-membered rings of 15 or 20. For 15 in
CDCl3, the AB quartet signals recorded on a 600 MHz NMR
spectrometer appeared at δ 4.26 and 4.09 with a large
geminal coupling constant of 21.0 Hz, whereas those for 20
appeared at δ 4.43 and 4.22 (J ) 21.0 Hz). In addition, the
upfield-shift aromatic signal of 15 at δ 6.31, attributable to
the two hydrogens closest to the phenyl substituents on the
two outermost benzene rings, also indicates that each of the
phenyl substituents is oriented, to a large degree (60.8° from
the X-ray structure), perpendicular to the benzene ring to
which it is connected. As a result, the two neighboring
hydrogens are located in shielding regions, giving an upfield-
shift signal. In the case of 20, the signal of the corresponding
aromatic hydrogens appeared even more upfield at δ 5.19.
The 1H NMR signals of the ortho hydrogens on the phenyl
substituents of 15 in CDCl3 appeared at δ 7.88 and 5.71 as
doublets. The fact that two distinct signals were observed
for the ortho hydrogen indicates restricted rotation of the
phenyl group on the NMR time scale, causing the two ortho
hydrogens on the same phenyl group to be located in very
different magnetic environments. The upfield-shift signal at
δ 5.71 is attributable to the two ortho hydrogens pointing in
the direction of the inner benzene rings of the fused ring
system, placing them in the shielding regions of the aromatic
ring current. The other two ortho hydrogens, pointing away
from the inner benzene rings, appear to be in the deshielding
regions, giving a downfield shift signal at δ 7.88. Similarly,
the signals of the meta hydrogens appeared at δ 6.96 and
6.76. In 1,1,2,2-tetrachloroethane-d2 and recorded on a 270
MHz NMR spectrometer, the signals of the meta hydrogens
at δ 7.01 and 6.76 coalesced at 95 °C, whereas those of the
ortho hydrogens at δ 7.88 and 5.72 coalesced at ca. 125 °C,
corresponding to a rotational barrier of 18.5 kcal/mol, which
is significantly higher than the rotational barriers of 12.5 kcal/
In conclusion, two polycyclic aromatic hydrocarbons
possessing severe helical twists were readily synthesized. The
X-ray structures of these two molecules permitted direct
measurements of the extents of distortion from planarity. The
convergent nature of the synthetic sequence could also allow
easy placement of functional groups at various positions of
the aromatic ring systems for synthetic elaborations.
Acknowledgment. K.K.W. thanks the National Science
Foundation (CHE-0414063) for financial support. J.L.P.
acknowledges the support (CHE-9120098) provided by the
National Science Foundation for the acquisition of a Siemens
P4 X-ray diffractometer. The financial support of the NSF-
EPSCoR (1002165R) for the purchase of a 600 MHz NMR
spectrometer is also gratefully acknowledged.
Supporting Information Available: Experimental pro-
1
cedures, spectroscopic data, and H and 13C NMR spectra
of 8, 10, 11, 15, and 17-20; ORTEP drawings of the crystal
structures of 15 and 20 in PDF format; and X-ray crystal-
lographic data of 15 and 20 (CIF). This material is available
free of charge via the Internet at http://pubs.acs.org.
OL063056S
(18) Robertson, J. M. Organic Crystals and Molecules; Cornell University
Press: Ithaca, NY, 1953; pp 206-214.
(19) (a) Kuroda, R. J. Chem. Soc., Perkin Trans. 2 1982, 789-794. (b)
Frimer, A. A.; Kinder, J. D.; Youngs, W. J.; Meador, M. A. B. J. Org.
Chem. 1995, 60, 1658-1664.
(20) Laarhoven, W. H.; Peters, W. H. M.; Tinnemans, A. H. A.
Tetrahedron 1978, 34, 769-777.
(21) Kelly, T. R.; Sestelo, J. P.; Tellitu, I. J. Org. Chem. 1998, 63, 3655-
3665.
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