Synthesis of a sterically crowded atropisomeric 1,8-diacridylnaphthalene for dual-mode enantioselective fluorosensing

Article abstract of DOI:10.1021/jo0600353

An efficient synthetic route to a sterically crowded 1,8- diheteroarylnaphthalene-derived enantioselective fluorosensor that operates in two different detection modes utilizing fluorescence lifetime and intensity has been developed. Screening of palladium-catalyzed Negishi, Kumada, Suzuki, Hiyama, and Stille coupling methods showed that the latter affords highly congested 1,8-diarylnaphthalenes in superior yields. Despite severe steric hindrance, axially chiral 1,8-bis(3-(3′,5′-dimethylphenyl)-9- acridyl)naphthalene, 1, was obtained in 68% yield from 1,8-dibromonaphthalene, 14, and 3-(3′,5′-dimethylphenyl)-9-tributyl-stannylacridine, 13, via two consecutive Stille cross-coupling steps using tetrakis(triphenylphosphine)- palladium(0) as catalyst in the presence of copper(II) oxide. The preparation of 1 involved formation of 4-(3′,5′-dimethylphenyl)-2-chlorobenzoic acid, 7, through microwave-assisted Suzuki coupling of 4-bromo-2-chlorobenzoic acid, 10, and 3,5-dimethylphenylboronic acid, 11, followed by regioselective amination with aniline and acridine ring construction in phosphorus oxybromide. Lithiation, subsequent treatment with trimethylstannyl chloride, and Stille cross-coupling then completed the five-reaction sequence providing 1 in 57% overall yield. The enantiomers of 1 were separated by semipreparative HPLC on a (R,R)-Whelk-O 1 column and successfully employed in enantioselective fluorosensing of N-t-Boc-protected serine, 20, glutamine, 22, proline, 23, and 2-hydoxy-2-methylsuccinic acid, 21. Fluorescence titration experiments with 23 revealed that both static and dynamic quenching occur with distinctive enantioselectivity. Addition of (R)-23 to a solution of (+)-1 in acetonitrile resulted in stronger fluorescence quenching than titration with the (S)-enantiomer of 23. The fluorescence lifetime, τ, of 1 was determined as 18.8 ns and steadily decreased to 7.5 and 6.8 ns in the presence of 0.1 M of (S)-23 and (R)-23, respectively.

Full text of DOI:10.1021/jo0600353

Synthesis of a Sterically Crowded Atropisomeric
1,8-Diacridylnaphthalene for Dual-Mode Enantioselective
Fluorosensing
Xuefeng Mei, Rhia M. Martin, and Christian Wolf*
Department of Chemistry, Georgetown UniVersity, Washington, D.C. 20057
cw27@georgetown.edu
ReceiVed January 6, 2006
An efficient synthetic route to a sterically crowded 1,8-diheteroarylnaphthalene-derived enantioselective
fluorosensor that operates in two different detection modes utilizing fluorescence lifetime and intensity
has been developed. Screening of palladium-catalyzed Negishi, Kumada, Suzuki, Hiyama, and Stille
coupling methods showed that the latter affords highly congested 1,8-diarylnaphthalenes in superior yields.
Despite severe steric hindrance, axially chiral 1,8-bis(3-(3′,5′-dimethylphenyl)-9-acridyl)naphthalene, 1,
was obtained in 68% yield from 1,8-dibromonaphthalene, 14, and 3-(3′,5′-dimethylphenyl)-9-tributyl-
stannylacridine, 13, via two consecutive Stille cross-coupling steps using tetrakis(triphenylphosphine)-
palladium(0) as catalyst in the presence of copper(II) oxide. The preparation of 1 involved formation of
4-(3′,5′-dimethylphenyl)-2-chlorobenzoic acid, 7, through microwave-assisted Suzuki coupling of 4-bromo-
2-chlorobenzoic acid, 10, and 3,5-dimethylphenylboronic acid, 11, followed by regioselective amination
with aniline and acridine ring construction in phosphorus oxybromide. Lithiation, subsequent treatment
with trimethylstannyl chloride, and Stille cross-coupling then completed the five-reaction sequence
providing 1 in 57% overall yield. The enantiomers of 1 were separated by semipreparative HPLC on a
(R,R)-Whelk-O 1 column and successfully employed in enantioselective fluorosensing of N-t-Boc-protected
serine, 20, glutamine, 22, proline, 23, and 2-hydoxy-2-methylsuccinic acid, 21. Fluorescence titration
experiments with 23 revealed that both static and dynamic quenching occur with distinctive enantiose-
lectivity. Addition of (R)-23 to a solution of (+)-1 in acetonitrile resulted in stronger fluorescence quenching
than titration with the (S)-enantiomer of 23. The fluorescence lifetime, τ, of 1 was determined as 18.8 ns
and steadily decreased to 7.5 and 6.8 ns in the presence of 0.1 M of (S)-23 and (R)-23, respectively.
Introduction
a variety of advantages over traditional chromatographic and
NMR spectroscopic techniques including different detection
modes (fluorescence quenching, enhancement, and lifetime),
high sensitivity, low cost of instrumentation, waste reduction,
time efficiency, and the possibility of real-time analysis. To date,
few enantioselective fluorosensors2 including binaphthyl-derived
The development of sensitive essays for fast determination
of the enantiomeric composition of chiral compounds has
attracted increasing attention due to potential applications in
high-throughput screening of asymmetric reactions.1 Enantio-
selective fluorescence spectroscopy with chiral sensors offers
10.1021/jo0600353 CCC: $33.50 © 2006 American Chemical Society
Published on Web 03/01/2006
2854
J. Org. Chem. 2006, 71, 2854-2861

Synthesis of a Sterically Crowded Atropisomeric 1,8-Diacridylnaphthalene
SCHEME 1. Retrosynthesis of 1,8-Bis(3-(3′,5′-dimethylphenyl)-9-acridyl)naphthalene, 1
macrocycles,3 dendrimers,4 oligomers,5 or chiral bisboronic
acids6 and C2-symmetric diacridylnaphthalenes7 have been
developed. We have recently reported a synthetic route to highly
congested axially chiral 1,8-diarylnaphthalenes8 including fluo-
rescent diacridylnaphthalenes that do not show any sign of syn/
anti-isomerization and subsequent racemization even at high
temperatures.9 The incorporation of bulky aryl rings into the
peri positions of naphthalene via two consecutive cross-coupling
steps is synthetically challenging due to severe steric hindrance
to carbon-carbon bond formation. As a consequence, attempts
to prepare conformationally stable 1,8-diarylnaphthalenes have
often been unsuccessful or resulted in very low yields, which
has limited the use of this class of compounds as asymmetric
sensors and catalysts.10 Herein, we wish to report a significantly
improved procedure that provides efficient access to a highly
congested 1,8-diacridylnaphthalene fluorosensor. The sensor has
been applied in sensing studies of chiral amino and hydroxy
acids showing both enantioselective fluorescence quenching and
enantioselective fluorescence lifetime changes. To the best of
our knowledge, this is the first example of a chiral fluorosensor
that operates in two different detection modes.
(1) (a) Korbel, G. A.; Lalic, G.; Shair, M. D. J. Am. Chem. Soc. 2001,
123, 361-362. (b) Matsushita, M.; Yoshida, K.; Yamamoto, N.; Wirsching,
P.; Lerner, R. A.; Janda, K. D. Angew. Chem., Int. Ed. 2003, 42, 5984-
5987. (c) Li, Z.-B.; Qin, Y.-C.; Pu, L. Org. Lett. 2005, 7, 3441-3444. (d)
Tumambac, G. E.; Wolf, C. Org. Lett. 2005, 7, 4045-4048.
Results and Discussion
(2) (a) Irie, M.; Yorozu, T.; Hayashi, K. J. Am. Chem. Soc. 1978, 100,
2236-2237. (b) Gafni, A. J. Am. Chem. Soc. 1980, 102, 7367-7368. (c)
Yorozu, T.; Hayashi, K.; Irie, M. J. Am. Chem. Soc. 1981, 103, 5480-
5484. (d) Corradini, R.; Sartor, G.; Marchelli, R.; Dossena, A.; Spisni, A.
J. Chem. Soc., Perkin Trans. 2 1992, 1979-1983. (e) James, T. D.;
Sandanayake, K. R. A. S.; Shinkai, S. Nature 1995, 374, 345-347. (f) Yan,
Y.; Myrick, M. L. Anal. Chem. 1999, 71, 1958-1962. (g) Beer, G.; Rurack,
K.; Daub, J. J. Chem. Soc., Chem. Commun. 2001, 1138-1139. (h) Reetz,
M.; Sostmann, S. Tetrahedron 2001, 57, 2515-2520. (i) Lin, J.; Hu, Q.-
S.; Xu, M.-H.; Pu, L. J. Am. Chem. Soc. 2002, 124, 2088-2089. (j) Pu, L.
Chem. ReV. 2004, 104, 1687-1716.
(3) (a) Tundo, P.; Fendler, J. H. J. Am. Chem. Soc. 1980, 102, 1760-
1762. (b) Grady, T.; Harris, S. J.; Smyth, M. R.; Diamond, D. Anal. Chem.
1996, 68, 3775-3782. (c) D’Souza, F.; Deviprassad, G. R.; Hsieh, Y.-Y.
Chem. Commun. 1997, 533-534. (d) Narita, M.; Mima, S.; Ogawa, N.;
Hamada, F. Anal. Sci. 2001, 17, 379-385. (e) Lynam, C.; Jennings, K.;
Nolan, K.; Kane, P.; McKervey, M. A.; Diamond, D. Anal. Chem. 2002,
74, 59-66. (f) Lee, S. J.; Lin, W. J. Am. Chem. Soc. 2002, 124, 4554-
4555. (g) Lin, J.; Zhang, H.-C.; Pu, L. Org. Lett. 2002, 4, 3297-3300. (h)
Li, Z.-B.; Lin, J.; Zhang, H.-C.; Sabat, M.; Hyacinth, M.; Pu, L. J. Org.
Chem. 2004, 69, 6284-6293. (i) Lin, J.; Li, Z.-B.; Zhang, H.-C.; Pu, L.
Tetrahedron Lett. 2004, 45, 103-106. (j) Wong, W.-L.; Huang, K.-H.; Teng,
P.-F.; Lee, C.-S.; Kwong, H.-L. Chem. Commun. 2004, 384-385. (k) Li,
Z.-B.; Lin, J.; Pu, L. Angew. Chem., Int. Ed. 2005, 44, 1690-1693.
(4) (a) Pugh, V. J.; Hu, Q.-S.; Pu, L. Angew. Chem., Int. Ed. 2000, 39,
3638-3641. (b) Gong, L.-Z.; Hu, Q.-S.; Pu, L. J. Org. Chem. 2001, 66,
2358-2367. (c) Pugh, V. J.; Hu, Q.-S.; Zuo, X.; Lewis, F. D.; Pu, L. J.
Org. Chem. 2001, 66, 6136-6140. (d) Xu, M.-H.; Lin, J.; Hu, Q.-S.; Pu,
L. J. Am. Chem. Soc. 2002, 124, 14239-14246.
Our initial retrosynthetic analysis of 1,8-bis(3-(3′,5′-dimeth-
ylphenyl)-9-acridyl)naphthalene, 1, suggested cross-coupling of
1,8-dibromonaphthalene with 9-acridylstannanes which can be
prepared via ring construction of the corresponding 9-bro-
moacridine 2 from readily available anthranilic acid, 3, followed
by lithiation and subsequent treatment with trimethylstannyl
chloride (Scheme 1). This approach involves Cu/Cu2O-catalyzed
amination of 2-chlorobenzoic acid, 5, with 3-(3′,5′-dimethylphe-
nyl)aniline, 6, and ring construction in the presence of phos-
phorus oxybromide.11 The formation of 2 from N-3-(3′,5′-
dimethylbiphenyl)anthranilic acid, 3, turned out to be very
inefficient due to low regioselectivity, and we obtained equal
amounts of 9-bromoacridyl derivatives 2 and 9 (Scheme 2).
Apparently, ring closure proceeds with similar rates at both
ortho-positions of the aniline moiety of 3. We envisioned that
construction of 2 from anthranilic acid 4 would avoid this issue
and provide much more effective access to acridyl bromide 2
(Scheme 1). A synthetically much more challenging problem
was to improve the yield of the final cross-coupling step.
Because of severe steric hindrance, Stille cross-coupling of 1,8-
dibromo- or 1,8-diiodonaphthalene and 3-(3′,5′-dimethylphenyl)-
9-tri-n-methylstannylacridine, 12, affords 1 in only 30%. We
therefore decided to reevaluate the feasibility of 1,8-diarylnaph-
thalene formation through screening of a range of reaction
conditions and explored the use of other palladium-catalyzed
cross-coupling methods.
(5) (a) Ma, L.; White, P. S.; Lin, W. J. Org. Chem. 2002, 67, 7577-
7586. (b) Pu, L. J. Photochem. Photobiol. A: Chem. 2003, 155, 47-55.
(6) (a) James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 1910-1922. (b) Takeuchi, M.; Yoda, S.; Imada,
T.; Shinkai, S. Tetrahedron 1997, 53, 8335-8348. (c) Zhao, J.; Fyles, T.
M.; James, T. D. Angew. Chem., Int. Ed. 2004, 43, 3461-3464. (d) Zhao,
J.; Davidson, M. G.; Mahon, M. F.; Kociok-Kohn, G.; James, T. D. J. Am.
Chem. Soc. 2004, 126, 16179-16186.
(10) Pritchard, R. G.; Steele, M.; Watkinson, M.; Whiting, A. Tetrahedron
Lett. 2000, 41, 6915-6918. (b) Cross, W.; Hawkes, G. E.; Kroemer, R. T.;
Liedl, K. R.; Loerting, T.; Nasser, R.; Pritchard, R. G.; Steele, M.;
Watkinson, M.; Whiting, A. J. Chem. Soc., Perkin Trans. 2 2001, 459-
467. (c) Steele, M.; Watkinson, M.; Whiting, A. J. Chem. Soc., Perkin Trans.
1 2001, 588-598. (d) Thirsk, C.; Hawkes, G. E.; Kroemer, R. T.; Liedl,
K. R.; Loertig, T.; Nasser, R.; Pritchard, R. G.; Steele, M.; Warren, J. E.;
Whiting, A. J. Chem. Soc., Perkin Trans. 2 2002, 1510-1519.
(11) Mei, X.; August, A. T.; Wolf, C. J. Org. Chem. 2006, 71, 142-
149.
(7) (a) Mei, X.; Wolf, C. J. Am. Chem. Soc. 2004, 126, 14736-14737.
(b) Mei, X.; Wolf, C. Chem. Commun. 2004, 2078-2079.
(8) (a) Wolf, C.; Ghebremariam, B. T. Synthesis 2002, 749-752. (b)
Wolf, C.; Ghebremariam, B. T. Tetrahedron: Asymmetry 2002, 13, 1153-
1156. (c) Wolf, C.; Tumambac, G. E. J. Phys. Chem. A 2003, 107, 815-
817. (d) Tumambac, G. E.; Wolf, C. J. Org. Chem. 2004, 69, 2048-2055.
(e) Tumambac, G. E.; Wolf, C. J. Org. Chem. 2005, 70, 2930-2938.
(9) (a) Wolf, C.; Mei, X. J. Am. Chem. Soc. 2003, 125, 10651-10658.
(b) Mei, X.; Wolf, C. J. Org. Chem. 2005, 70, 2299-2305.
J. Org. Chem, Vol. 71, No. 7, 2006 2855

Mei et al.
SCHEME 2. Ring Construction of 9-Bromoacridine 2 Using Anthranilic Acid 3
SCHEME 3. Synthesis of 1,8-Diacridylnaphthalene 1
Microwave-assisted Suzuki cross-coupling of 4-bromo-2-
chlorobenzoic acid, 10, and 3,5-dimethylphenylboronic acid, 11,
gave 4-(3′,5′-dimethylphenyl)-2-chlorobenzoic acid, 7, in 96%.
Regioselective Cu/Cu2O-catalyzed amination of 7 with aniline
yielded anthranilic acid 4 in 89%, which was then quantitatively
converted to 9-bromoacridyl derivative 2 using phosphorus
oxybromide as solvent. Noteworthy, all reaction products are
easily purified by crystallization eliminating the need for
cumbersome chromatographic workup. Since cyclization of 4
occurs with an unsubstituted aniline moiety, this route exclu-
sively forms acridyl bromide 2, thus significantly enhancing
overall yields while chromatographic separation of 2 from 9
becomes unnecessary. Treatment of 2 with butyllithium followed
by addition of trialkylstannyl chlorides was found to afford
9-acridylstannanes 12 and 13 in high yields (Scheme 3). The
stannanes were then employed in Stille cross-couplings with
1,8-dibromonaphthalene, 14, vide infra.
Recent advances in Pd-catalyzed C-C bond-forming reac-
tions12 and the development of practicable Negishi,13 Kumada,14
Suzuki,15 Stille,16 and Hiyama coupling procedures17 encouraged
us to improve the final step in the synthesis of 1,8-diacridyl-
naphthalene 1. Based on our previous studies, we knew that
the unsatisfactory yields of 1 obtained by Stille coupling of 12
and 14 are mostly due to homocoupling of aryl stannanes,
transfer of a methyl group instead of an acridyl ring during
transmetalation, and dehalogenation. To limit synthetic efforts,
we chose to study formation of 1,8-diphenylnaphthalene, 19,
somewhat resembling the crowded structure of 1. Since we
observed that the synthesis of 1,8-diarylnaphthhalenes 1 and
19 via palladium-catalyzed cross-coupling suffers from the same
side reactions, formation of the latter was considered an ideal
reaction for screening and optimization studies. We envisioned
that a procedure that affords 19 in excellent yields could also
(14) (a) Huang, J.; Nolan, S. P. J. Am. Chem. Soc. 1999, 121, 9889-
9890. (b) Bohm, V. P. W.; Weskamp, T.; Gstottmayr, C. W. K.; Herrmann,
W. A. Angew. Chem., Int. Ed. 2000, 39, 1602-1604. (c) Bonnet, V.;
Mongin, F.; Trecourt, F.; Queguiner, G.; Knochel, P. Tetrahedron Lett. 2001,
42, 5717-5719. (d) Li, G. Y. J. Organomet. Chem. 2002, 653, 63-68. (e)
Bonnet, V.; Mongin, F.; Trecourt, F.; Queguiner, G.; Knochel, P. Tetra-
hedron 2002, 58, 4429-4438. (f) Frisch, A. C.; Shaikh, N.; Zapf, A.; Beller,
M. Angew. Chem. Int. Ed. 2002, 41, 4056-4059. (g) Bonnet, V.; Mongin,
F.; Trecourt, F.; Breton, G.; Marsais, F.; Knochel, P.; Queguiner, G. Synlett.
2002, 6, 1008-1010. (h) Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J.
Am. Chem. Soc. 2003, 125, 5646-5647.
(15) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483. (b)
Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 1998, 37, 3387-3388. (c)
Blettner, C. G.; Konig, W. A.; Stenzel, W.; Schotten, T. J. Org. Chem.
1999, 64, 3885-3890. (d) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem.
Soc. 2000, 122, 4020-4028. (e) Nguyen, H. N.; Huang, X.; Buchwald, S.
L. J. Am. Chem. Soc. 2003, 125, 11818-11819. (f) Li, J.-H.; Liu, W.-J.;
Xie, Y.-X. J. Org. Chem. 2005, 70, 5409-5412.
(16) (a) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002,
124, 6343-6348. (b) Menzel, K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125,
3718-3719. (c) Wolf, C.; Lerebours, R. J. Org. Chem. 2003, 68, 7077-
7084. (d) Wolf, C.; Lerebours, R. J. Org. Chem. 2003, 68, 7551-7554. (e)
Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 4704-
4734. (f) Powell, D. A.; Maki, T.; Fu, G. C. J. Am. Chem. Soc. 2005, 127,
510-511. (g) Lerebours, R.; Camacho-Soto, A.; Wolf, C. J. Org. Chem.
2005, 70, 8601-8604.
(17) (a) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684-
1688. (b) Mowery, M. E.; DeShong, P. Org. Lett. 1999, 1, 2137-2140. (c)
Lee, H. M.; Nolan, S. P. Org. Lett. 2000, 2, 2053-2055. (d) Wolf, C.;
Lerebours, R.; Tanzini, E. H. Synthesis 2003, 2069-2073. (e) Lee, J. Y.;
Fu, G. C. J. Am. Chem. Soc. 2003, 125, 5616-5617. (f) Lerebours, R.;
Wolf, C. Org. Lett. 2004, 6, 1147-1150. (g) Lerebours, R.; Wolf, C.
Synthesis 2005, 2287-2292.
(12) (a) Stanforth, S. P. Tetrahedron 1998, 54, 263-303. (b) Hassan,
J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. ReV. 2002,
102, 1359-1469. (c) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002,
41, 4176-4211. (d) Newkome, G. R.; Patri, A. K.; Holder, E.; Schubert,
U. S. Eur. J. Org. Chem. 2004, 235-254.
(13) (a) Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719-2724.
(b) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 14726-14727. (c)
Negishi, E. J. Organomet. Chem. 2002, 653, 34-40. (d) Milne, J. E.;
Buchwald, S. L. J. Am. Chem. Soc. 2004, 126, 13028-13032.
2856 J. Org. Chem., Vol. 71, No. 7, 2006

Synthesis of a Sterically Crowded Atropisomeric 1,8-Diacridylnaphthalene
FIGURE 1. Comparison of cocatalysts employed in the Pd(PPh3)4-catalyzed Stille coupling of 1,8-dibromonaphthalene and phenyltrimethylstannane.
Reaction conditions: A mixture of 1,8-dibromonaphthalene (0.17 mmol), phenyltrimethylstannane (0.51 mmol), Pd(PPh3)4 (0.05 mmol), and cocatalyst
(0.25 mmol) in anhydrous DMF (3 mL) was stirred at 130 °C for 20 h under inert atmosphere. Yields were determined by GC using individual
response factors and anthracene as internal standard.
be successfully applied in the synthesis of other sterically
crowded 1,8-diarylnaphthalenes such as 1. We found that 19
and the corresponding cross-coupling byproducts 16-18 can
be quantitatively analyzed by GC using anthracene as internal
standard, which proved invaluable for time-efficient screening
of coupling methods and reaction conditions. Initially, we
examined Kumada, Negishi, Suzuki, and Hiyama coupling of
1,8-dibromonaphthalene and phenyl- or pyridylmagnesium, zinc,
boronic acid, and siloxane derivatives employing Pd(PPh3)4,
PdCl2dppf, or Pd2(dba)3/t-Bu3P as catalyst as well as t-BuOK,
K3PO4, or Cs2CO3 as base in THF, DME, and DMF, respec-
tively. Unfortunately, 19 was obtained in only moderate yields
by Hiyama or Suzuki cross-coupling reactions, and no sign of
formation of 1 was observed when arylmagnesium and zinc
analogues were employed.
By contrast, Stille coupling of 1,8-dibromonaphthalene and
phenyltrimethylstannane proved to be superior over the above
methods, and we therefore decided to optimize reaction condi-
tions through screening of various catalyst sources, solvents,
and cocatalysts. The formation of considerable amounts of
1-methyl-8-phenylnaphthalene, 18, during cross-coupling of 1,8-
dibromonaphthalene, 14, and phenyltrimethylstannane, 15,
indicated that steric hindrance to transmetalation results in
undesirable methyl rather than acridyl transfer. Liebeskind et
al. reported that copper(I) salts facilitate Stille cross-couplings
through formation of intermediate organocopper species that
undergo transmetalation at a higher rate than arylstannanes.18
Although the exact mechanism of the copper-mediated trans-
metalation remains elusive, various additives have successfully
been employed as cocatalysts in Stille coupling reactions.19
Employment of five different metal salts in the Ph(PPh3)4-
catalyzed coupling of 14 and 15 showed that 19 is produced in
35-60% in the presence of CuI, Cu2O, and CuBr, while lower
yields were obtained with CuO and Ag2O (Figure 1). Methyl
transfer resulting in the formation of 18 was found to become
the dominant reaction outcome when Ag2O was used. As
expected, considerable amounts of homocoupling product 16
were produced due to the use of excess of stannane 15, but
more importantly, less than 10% of dehalogenation product 17
was observed in all cases.
We then employed various palladium catalysts in the coupling
reaction of 14 and 15 using CuBr as cocatalyst and DMF as
solvent (Figure 2). While Stille coupling with tris(dibenzylide-
neacetone)dipalladium(0), Pd2(dba)3, in the presence of 1,1′-
bis(diphenylphosphino)ferrocene, dppf, proved unsuccessful,
1,8-diphenylnaphthalene 19 was obtained in 40% yield when
Pd(OAc)2 was used, but this catalyst also produced 32% of
1-methyl-8-phenylnaphthalene 18. Fortunately, the undesirable
methyl transmetalation could be suppressed with other catalysts
such as Pd(t-Bu3P)2 or combinations of Pd2(dba)3 and 2-di(tert-
butyl)phosphinobiphenyl, 2-dicyclohexylphosphinobiphenyl, or
triphenylarsine providing 19 with 34-47% yield.20 The best
results were obtained with tetrakis(triphenylphosphine)palladium-
(0), Pd(PPh3)4, which gave the desired cross-coupling product
19 in 58% yield in the presence of copper(I) bromide. Again,
dehalogenation played only a minor role in the palladium-
catalyzed Stille coupling of 14 and 15, and 1-phenylnaphthalene
(19) (a) Scott, W. J.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 3033-
3040. (b) Liebeskind, L. S.; Fengl, R. W. J. Org. Chem. 1990, 55, 5359-
5364. (c) Hanack, M.; Renz, G.; Strahle, J.; Schmid, S. J. Org. Chem. 1991,
56, 3501-3509. (d) Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113,
9585-9595. (e) Malm, J.; Bjork, P.; Gronowitz, S.; Hornfeldt, A. B.
Tetrahedron Lett. 1992, 33, 2199-2202. (f) Liebeskind, L. S.; Riesinger,
S. W. J. Org. Chem. 1993, 58, 408-413. (g) Gronowitz, S.; Bjork, P.;
Malm, J.; Hornfeldt, A. B. J. Organomet. Chem. 1993, 460, 127-129. (h)
Ye, J.; Bhatt, R. K.; Falck, J. R. J. Am. Chem. Soc. 1994, 116, 1-5. (i)
Roth, G. P.; Farina, V. Tetrahedron Lett. 1995, 36, 2191-2194. (j)
Alphonse, F.-A.; Suzenet, F.; Keromnes, A.; Lebret, B.; Guillaumet, G.
Org. Lett. 2003, 5, 803-805. (k) Casado, A. L.; Espinet, P. Organomet.
2003, 22, 1305-1309. (l) Kim, W.-S.; Kim, H.-J.; Cho, C.-G. J. Am. Chem.
Soc. 2003, 125, 14288-14289. (m) Mazzola, R. D., Jr.; Giese, S.; Benson,
C. L.; West, F. G. J. Org. Chem. 2004, 69, 220-223. (n) Mee, S. P. H.;
Lee, V.; Baldwin, J. E. Angew. Chem., Int. Ed. 2004, 43, 1132-1132.
(20) We did not observe any formation of coupling products 17-19 from
14 and 15 using Pd(OAc)2, Pd(1,5-cyclooctadiene)Cl2, and Pd2(dba)3 in
the presence of 2-dicyclohexylphosphino-2′,6′-diisopropoxy-1,1′-biphenyl
in refluxing DMF after 20 h.
(18) (a) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebeskind, L.
S. J. Org. Chem. 1994, 59, 5905-5911. (b) Allred, G. D.; Liebeskind, L.
S. J. Am. Chem. Soc. 1996, 118, 2748-2749.
J. Org. Chem, Vol. 71, No. 7, 2006 2857

Mei et al.
FIGURE 2. Stille cross-coupling of 1,8-dibromonaphthalene and phenyltrimethylstannane using various Pd catalysts. Reaction conditions: A
mixture of 1,8-dibromonaphthalene (0.17 mmol), phenyltrimethylstannane (0.51 mmol), Pd catalyst (0.05 mmol), and CuBr (0.25 mmol) in anhydrous
DMF (3 mL) was stirred at 130 °C for 20 h under nitrogen. Yields were determined by GC using individual response factors and anthracene as
internal standard.
TABLE 1. Pd-Catalyzed Formation of 1,8-Diacridylnaphthalene 1a
entry
stannane
solvent
catalyst (mol %)
additives
T (°C)
1 (% yield)d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
12
12
12
12
12
13
13
13
13
13
13
13
13
13
dioxane
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
dioxane
DMF
DMF
Pd(PPh3)4 (36)
Pd(PPh3)4 (36)
Pd(PPh3)4 (36)
CuBr, CsF
CuBr, CsF
CuBr
CuO
CuBr
CuO
CuBr
Cu2O
CuO
CuO
CuO
CuO
CuO
100
130
130
130
130
130
130
130
130
130
100
100
100
100
0
0
31
32
20
66c
35
5
Pd(PPh3)4 (36)
Pd2(dba)3 (36) + DHPPb (52)
Pd(PPh3)4 (36)
Pd(PPh3)4 (36)
Pd(PPh3)4 (36)
Pd2(dba)3 (36) + P(n-Bu)3 (52)
Pd[P(t-Bu)3]2 (36)
Pd(PPh3)4 (36)
Pd(PPh3)4 (36)
Pd(PPh3)4 (15)
Pd(PPh3)4 (5)
0
10
68c
48c
53c
24
CuO
a Reactions were conducted with 1,8-dibromonaphthalene (0.25 mmol), acridyl stannane 12 or 13 (1.0 mmol), Pd catalyst, cocatalyst, and additive (0.5
mmol) in DMF or dioxane (3 mL) for 48 h under nitrogen. b DHPP is 2-dicyclohexylphosphinobiphenyl. c Reaction was performed for 20 h under nitrogen.
d Isolated yields.
CHART 1. Structures of Carboxylic Acids 20-23 Used in Enantioselective Sensing Studies
17 was observed in less than 5% in all cases. Employing
Pd(PPh3)4 and CuBr in refluxing THF, DMA, and dioxane for
20 h yielded 19 in 41, 51, and 57% yield, respectively. To our
delight, the yield of 19 further increased to 97% through addition
of cesium fluoride, which may be attributed to activation of
fluorophilic stannane 15.21
of 12 and 14 using Pd(PPh3)4 in the presence of CuBr and CuO
gave 1 in 31-32% yield, while addition of cesium fluoride for
activation of the stannane for the transmetalation step did not
result in the formation of the desired cross-coupling product
(Table 1, entries 1-4). The striking difference in the results
obtained by cesium fluoride-promoted Stille coupling with
phenyl- and acridylstannanes can probably be attributed to the
low stability of the latter. We have observed that acridylstan-
nanes easily decompose when stored in solution at room
temperature and therefore assume that this occurs even more
The most promising reaction conditions were then applied
in the synthesis of 1,8-diacridylnaphthalene 1. Stille coupling
(21) Littke, A. F.; Schwarz, L.; Fu, G. C. J. Am. Chem. Soc. 2002, 124,
6343-6348.
2858 J. Org. Chem., Vol. 71, No. 7, 2006

Synthesis of a Sterically Crowded Atropisomeric 1,8-Diacridylnaphthalene
FIGURE 3. Stern-Volmer plots showing enantioselective fluorescence quenching of (+)-1 in the presence of the enantiomers of carboxylic acids
20, 21, and 22. The concentration of (+)-1 in acetonitrile was 2.6 × 10-6 M. Excitation (emission) wavelength was 360 nm (550 nm).
FIGURE 4. Stern-Volmer plots showing enantioselective fluorescence quenching of (+)-1 (left) and (-)-1 (right) in the presence of (R)- and
(S)-23. The concentration of 1 in acetonitrile was 2.6 × 10-6 M. Excitation (emission) wavelength was 360 nm (550 nm).
rapidly in the presence of fluoride. We also noticed that other
phosphine ligands such as 2-dicyclohexylphosphinobiphenyl,
DHPP, tri-tert-butyl phosphine, and tri-n-butyl phosphine do
not improve coupling yields (entries 5, 9, and 10). However,
Pd(PPh3)4-catalyzed cross-coupling of 3-(3′,5′-dimethylphenyl)-
9-tributylstannylacridine, 13, and dibromide 14 in DMF at 100
or 130 °C gave 1,8-diacridylnaphthalene 1 in 66-68% yield
after 20 h, which corresponds to remarkable 82% for each
individual coupling step (entries 6 and 11). As expected,
decreased yields of 1 were obtained at lower catalyst loadings
(entries 13 and 14). The excellent results obtained with
tributylstannylacridine 13 can be attributed to limited formation
of byproducts since we did not observe any traces of dehalo-
genation and butyl transmetalation products. Apparently, trans-
metalation of the butyl groups of stannane 13 is significantly
less favored than methyl transfer from acridylstannane 12. The
FIGURE 5. Fluorescence lifetime titration of (+)-1 in the presence
revised synthetic strategy toward 1,8-diacridylnaphthalene 1 and
of the enantiomers of 23 in acetonitrile. Fluorescence lifetime, τ, of
the significantly improved Stille coupling procedure thus
increased the overall yield from 12% to 57%.
(+)-1 in the presence of various amounts of (R)-23 (blue box) and
(S)-23 (red box); ratio of the fluorescence lifetime of (+)-1 in the
absence and in the presence of (R)-23 (blue triangle) and (S)-23 (red
triangle). Sensor 1 exhibits a single-componential decay that was fitted
at 550 nm. The sample was excited at 370 nm.
Having developed a practicable synthetic route to axially
chiral 1,8-diacridylnaphthalene 1, we decided to study its use
for enantioselective fluorosensing of N-t-Boc-protected serine
20, glutamine 22, proline 23, and 2-hydoxy-2-methylsuccinic
acid, 21 (Chart 1). The enantiomers of 1 were separated on a
(R,R)-Whelk-O 1 column, and the dextrorotatory enantiomer
was employed in fluorescence titration experiments using
acetonitrile as solvent. We were delighted to observe enanti-
oselective fluoresence quenching in all cases (Figures 3 and
4). Both enantiomers of amino acids 20 and 21 gave linear
Stern-Volmer plots, which can be attributed to static quenching
due to formation of diastereomeric 1:1 hydrogen bond adducts
with (+)-1.7 By contrast, the (R)-enantiomer of both 22 and 23
showed nonlinear quenching indicating either formation of 1:2
adducts or significant dynamic quenching contributions. As
expected, opposite behavior was observed when (-)-1 was used
for enantioselective sensing of the enantiomers of 23 (Figure
4). In this case, addition of (R)-23 to a solution of the
levorotatory sensor resulted in linear quenching, whereas (S)-
23 gave an exponential Stern-Volmer curve.
Static and dynamic quenching exhibit two different fluores-
cence sensing modes. While static quenching results from
formation of a complex between the fluorosensor and the
J. Org. Chem, Vol. 71, No. 7, 2006 2859

Mei et al.
treated with charcoal, and filtrated through Celite. The crude product
was obtained by precipitation upon acidification with dilute HCl.
The desired product was re-crystallized from EtOAc to afford 4
(561 mg, 89%) as white crystals: 1H NMR (300 MHz, CDCl3) δ
) 2.35 (s, 6H), 6.90 (dd, J ) 1.5 Hz, 8.5 Hz, 1H), 7.00 (s, 1H),
7.13 (s, 2H), 7.30-7.44 (m, 6H), 8.07 (d, J ) 8.6 Hz, 1H), 9.40
(bs, 1H); 13C NMR (75 MHz, CDCl3) δ ) 22.1, 110.0, 113.1, 117.4,
123.5, 124.6, 125.8, 130.2, 130.6, 133.7, 139.0, 141.0, 141.2, 149.0,
149.6, 173.6. Anal. Calcd for C20H18NO2: C, 79.47; H, 6.03; N,
4.41. Found: C, 79.07; H, 6.47; N, 4.09.
quencher, dynamic quenching refers to collisional encounters
between the analyte and the sensor during the lifetime of the
excited state of the fluorophore. Fluorescence lifetime measure-
ments of (+)-1 in the absence and presence of various amounts
of the enantiomers of 23 revealed enantioselective dynamic
quenching. The fluorescence lifetime, τ, of 1 was determined
as 18.8 ns and steadily decreased upon addition of either
enantiomer of 23. Interestingly, (R)-23 was found to more
effectively reduce the fluorescence lifetime of (+)-1 than the
(S)-enantiomer of 23. Fluorescence lifetimes of (+)-1 were
determined as 7.5 and 6.8 ns in the presence of 0.1 M of (S)-23
and (R)-23, respectively (Figure 5). To the best of our
knowledge, this is the first example of enantioselective fluoro-
sensing based on lifetime measurements.
9-Bromo-3-(3′,5′-dimethylphenyl)acridine, 2. Anthranilic acid
4 (140 mg, 0.44 mmol) was added to phosphorus oxybromide (1.4
g, 4.9 mmol) in a three-neck round-bottom flask equipped with a
reflux condenser. The mixture was heated to 120 °C for 2 h. Excess
of phosphorus oxybromide was removed by distillation and the
residual solution was poured into aqueous ammonium hydroxide
and extracted with CH2Cl2. The combined organic layers were dried
over MgSO4 and dried in vacuo to give 5 (160 mg, >99%) as a
yellow powder: 1H NMR δ ) 2.44 (s, 6H), 7.09 (s, 1H), 7.46 (s,
2H), 7.63 (ddd, J ) 1.1 Hz, 6.6 Hz, 8.8 Hz, 1H), 7.82 (dd, J ) 6.9
Hz, 8.5 Hz, 1H), 7.94 (dd, J ) 1.6 Hz, 9.1 Hz, 1H), 8.27 (d, J )
8.8 Hz, 1H) 8.39-8.47 (m, 3H); 13C NMR δ ) 22.0, 125.3, 125.5,
126.0, 126.7, 127.0, 127.2, 127.5, 127.8, 129.9, 130.2, 130.4, 135.4,
138.6, 139.3, 142.8, 149.2, 149.2. Anal. Calcd for C21H16NBr: C,
69.61; H, 4.42; N, 3.87. Found: C, 70.03; H, 4.30; N, 3.40.
3-(3′,5′-Dimethylphenyl)-9-trimethylstannylacridine, 12. A
solution of 9-bromo-3-(3′,5′-dimethylphenyl)acridine 2 (0.6 g, 1.6
mmol) in 10 mL of anhydrous diethyl ether/THF (1:1) was cooled
to -78 °C under nitrogen. To the solution was added dropwise 1.6
M of n-BuLi in hexanes (1.5 mL, 2.4 mmol) over a period of 15
min, and the reaction mixture was stirred for 1 h. A 1.0 M solution
of Me3SnCl in hexanes (3 mL, 3 mmol) was then added in one
portion. The reaction mixture was allowed to warm to room
temperature, stirred for 18 h, and concentrated under vacuum.
Purification of the orange residue by flash chromatography (100:
30:1 hexanes/ethyl acetate/triethylamine) afforded 12 (0.65 g, 91%)
as yellow crystals. GC-MS analysis revealed the presence of
5-10% of 3-(3′,5′-dimethylphenyl)acridine that could not be
separated by chromatography. The stannane was therefore employed
in the Stille coupling with 1,8-dibromonaphthalene without further
purification: 1H NMR δ ) 0.70 (s, 9H), 2.44 (s, 6H), 7.08-7.10
(m, 1H), 7.49-7.56 (m, 3H), 7.76 (ddd, J ) 1.4 Hz, 6.6 Hz, 8.8
Hz, 1H), 7.88 (dd, J ) 1.9 Hz, 9.1 Hz, 1H), 8.13 (d, J ) 8.5 Hz,
1H), 8.22 (d, J ) 9.1 Hz, 1H), 8.27 (d, J ) 8.5 Hz, 1H), 8.49 (m,
1H); 13C NMR δ ) -4.2, 21.8, 125.3, 125.4, 125.5, 127.7, 129.6,
129.8, 130.1, 130.4, 130.8, 132.8, 133.5, 138.4, 139.8, 142.0, 148.2,
148.2, 156.4.
3-(3′,5′-Dimethylphenyl)-9-tri-n-butylstannylacridine, 13. A
solution of 9-bromo-3-(3′,5′-dimethylphenyl)acridine, 2 (0.6 g, 1.6
mmol), in 10 mL of anhydrous diethyl ether/THF (1:1) was cooled
to -78 °C under nitrogen. To the solution was added dropwise 1.6
M n-BuLi in hexanes (2.4 mmol, 1.5 mL) over a period of 15 min
and the mixture stirred at the same temperature for 1 h. Then, (n-
Bu)3SnCl (975 mg, 3 mmol) dissolved in 2 mL of diethyl ether
was added in one portion. The reaction mixture was allowed to
warm to room temperature, stirred for 18 h, and concentrated in
vacuo. Purification of the orange residue by flash chromatography
(95:5 methylene chloride/triethylamine) afforded 13 (0.9 g, 98%)
as yellow crystals: 1H NMR δ ) 0.87 (t, J ) 7.1 Hz, 7.3 Hz, 9H),
1.30-1.70 (m, 18H), 2.41 (s, 6H), 7.04 (s, 1H), 7.50-7.54 (m,
3H), 7.71-7.77 (m, 1H), 7.86 (dd, J ) 2.0 Hz, 9.0 Hz, 1H), 8.09
(d, J ) 8.5 Hz, 1H), 8.15 (d, J ) 9.0 Hz, 1H), 8.26 (d, J ) 8.5 Hz,
1H), 8.49 (d, J ) 1.7 Hz, 1H); 13C NMR δ ) 14.1, 14.2, 22.1,
27.9, 29.7, 125.7, 125.9, 126.0, 128.1, 130.2, 130.3, 131.0, 131.1,
131.3, 133.9, 134.6. 139.1, 140.5, 142.6, 148.7, 148.8, 158.9.
1,8-Bis(3-(3′,5′-dimethylphenyl)-9-acridyl)naphthalene, 1. A
three-neck round-bottom flask equipped with a reflux condenser
was charged with 1,8-dibromonaphthalene (72 mg, 0.25 mmol),
Pd(PPh3)4 (102 mg, 0.09 mmol), CuO (40 mg, 0.5 mmol), and 3
Conclusion
Screening of the usefulness of palladium-catalyzed Negishi,
Kumada, Suzuki, Hiyama, and Stille coupling procedures for
the construction of highly congested 1,8-diarylnaphthalenes
showed that superior results are obtained with arylstannanes,
in particular when undesirable alkyl transfer during transmeta-
lation and dehalogenation can be controlled. Despite severe
steric hindrance, 1,8-bis(3-(3′,5′-dimethylphenyl)-9-acridyl)-
naphthalene, 1, was obtained in 68% yield from 1,8-dibro-
monaphthalene, 14, and 3-(3′,5′-dimethylphenyl)-9-tributylstan-
nylacridine, 13, using Pd(PPh3)4 as catalyst in the presence of
copper(II) oxide. We believe that our Stille coupling procedure
will also be useful for the synthesis of other sterically crowded
biaryls. Fluorescence titration experiments with enantiopure 1
and N-t-Boc-protected serine, 20, glutamine, 22, proline, 23,
and 2-hydroxy-2-methylsuccinic acid, 21, showed enantiose-
lective static and enantioselective collisional quenching, dem-
onstrating the versatility of both fluorescence spectroscopy and
our diacridylnaphthalene-derived sensor, which operates in two
different fluorescence detection modes. Further studies of new
sensing applications and the underlying chiral recognition
mechanism of 1 are currently underway in our laboratories.
Experimental Section
4-(3′,5′-Dimethylphenyl)-2-chlorobenzoic Acid, 7. Into a glass
vessel (capacity 10 mL) were placed 4-bromo-2-chlorobenzoic acid,
10 (235 mg, 1.0 mmol), 3,5-dimethylphenylboronic acid, 11 (150
mg, 1.0 mmol), tetrabutylammonium bromide (332 mg, 1.0 mmol),
Pd(PPh3)4 (10 mg, 0.01 mmol), Na2CO3 (403 mg, 3.8 mmol), and
deionized water (2 mL). The mixture was heated to 130 °C (100
W) for 20 min using a continuous focused microwave power
delivery system. The cooled reaction mixture was poured into water
and extracted with Et2O. The combined organic layers were dried
over MgSO4 and removed in vacuo. Recrystallization of the residue
from EtOAc gave 7 (250 mg, 96%) as white crystals: 1H NMR
(300 MHz, CDCl3) δ ) 2.40 (s, 6H), 7.07 (s, 1H), 7.22 (s, 2H),
7.57 (dd, J ) 2.0 Hz, 8.3 Hz, 1H), 7.71 (d, J ) 2.0 Hz, 1H), 8.10
(d, J ) 8.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ ) 11.1, 114.8,
115.0, 116.0, 119.6, 120.1, 122.7, 124.9, 128.0, 128.4, 136.7, 159.5.
Anal. Calcd for C15H13ClO2: C, 69.10; H, 5.03. Found: C, 69.31;
H, 4.95.
4-(3′,5′-Dimethylphenyl)-2-(N-phenylamino)benzoic Acid, 4.
Chlorobenzoic acid 7 (520 mg, 2.0 mmol) was mixed with aniline
(205 mg, 2.2 mmol), Cu (12 mg, 0.18 mmol), Cu2O (13 mg, 0.09
mmol), K2CO3 (276 mg, 2 mmol), and 2-ethoxyethanol (1 mL) in
a three-neck round-bottom flask equipped with a reflux condenser.
The reaction mixture was heated to 130 °C for 24 h under inert
atmosphere. The cooled reaction mixture was poured into water,
2860 J. Org. Chem., Vol. 71, No. 7, 2006

Synthesis of a Sterically Crowded Atropisomeric 1,8-Diacridylnaphthalene
mL of DMF. The solution was stirred at 130 °C for 5 min, and a
solution of 3-(3′,5′-dimethylphenyl)-9-tri-n-butylstannylacridine, 13
(600 mg, 1.0 mmol), in 2 mL of DMF was added in one portion.
The reaction mixture was stirred at 130 °C for 20 h, quenched with
10% aqueous ammonium hydroxide, and extracted with methylene
chloride. The combined organic layers were dried over MgSO4 and
concentrated in vacuo. Purification of the residue by flash chro-
matography (35:25:35:5 hexanes/ethyl acetate/methylene chloride/
triethylamine) afforded equal amounts of the syn- and anti-
diastereomers of 1 (118 mg, 68%) as yellow crystals.
4H), 7.91 (d, J ) 1.7 Hz, 2H), 8.27 (dd, J ) 1.1 Hz, 8.4 Hz, 2H);
13C NMR δ ) 22.0, 124.8, 125.3, 125.4, 125.5, 125.8, 126.1, 126.3,
126.4, 126.9, 129.4, 129.7, 130.1, 130.4, 131.1, 134.2, 134.7, 135.5,
138.8, 140.7, 142.1, 146.1, 147.4, 147.5; mp 255 °C Anal. Calcd
for syn-C52H38N2: C, 90.43; H, 5.55; N, 4.06. Found: C, 90.70;
H, 5.40; N, 4.36.
Acknowledgment. Funding from the National Science
Foundation (CAREER Award, CHE-0347368) and the donors
of the Petroleum Research Fund, administered by the American
Chemical Society (PRF40897-G4), is gratefully acknowledged.
R.M.M. thanks the Petroleum Research Fund for a SUMR
Fellowship. We thank Drs. Gerald J. Terfloth and Leo Hsu,
GlaxoSmithKline, King of Prussia, for help with the enantio-
separation of 1.
anti-Isomer: 1H NMR δ ) 2.45 (s, 12H), 6.62-6.68 (m, 2H),
6.83-6.86 (m, 4H), 7.00-7.03 (m, 2H), 7.07 (s, 2H), 7.31-7.39
(m, 8H), 7.67 (d, J ) 9.1 Hz, 2H), 7.73-7.78 (m, 2H), 7.91 (s,
2H). 8.31 (d, J ) 8.2 Hz, 2H); 13C NMR δ ) 22.3, 124.8, 125.4,
125.5, 125.6, 125.9, 126.2, 126.3, 126.6, 127.0, 129.3, 129.8, 130.1,
130.5, 131.2, 134.2, 134.6, 135.5, 139.0, 140.8, 141.9, 146.1, 147.5,
147.6; mp >260 °C; LC/APCI/MS m/z ) 691(M + H). Anal. Calcd
for anti-C52H38N2: C, 90.43; H, 5.55; N, 4.06. Found: C, 90.64;
H, 5.30; N, 4.11.
Supporting Information Available: UV, CD, polarimetry, and
fluorescence spectroscopy measurements of 1 and NMR spectra
of all products. This material is available free of charge via the
Internet at http://pubs.acs.org.
syn-Isomer: 1H NMR δ ) 2.26 (s, 12H), 6.65-6.70 (m, 2H),
6.75-6.78 (m, 2H), 6.85-6.88 (m, 2H), 6.96-6.99 (m, 4H), 7.12
(s, 4H), 7.28-7.31 (m, 2H), 7.36-7.42 (m, 2H), 7.69-7.75 (m,
JO0600353
J. Org. Chem, Vol. 71, No. 7, 2006 2861