Synthesis and optical resolution of 9,9′-spirobifluorene-1,1′- diol

Article abstract of DOI:10.1021/ol0492546

(Equation Presented). 9,9′-Spirobifluorene-1,1′-diol (SBIFOL) was conveniently synthesized from 1,2-dibromobenzene and 3-bromoanisole in high yield. Both enantiomers of SBIFOL were obtained in 99% ee by inclusion resolution with 2,3-dimethoxy-N,N,N′,N′-tetracyclohexylsuccinamide. The absolute configurations were determined by X-ray analysis of a single crystal of molecular complex.

Full text of DOI:10.1021/ol0492546

ORGANIC
LETTERS
2004
Vol. 6, No. 14
2381-2383
Synthesis and Optical Resolution of
9,9′-Spirobifluorene-1,1′-diol
Xu Cheng, Guo-Hua Hou, Jian-Hua Xie, and Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai UniVersity,
Tianjin 300071, China
qlzhou@nankai.edu.cn
Received April 23, 2004
ABSTRACT
9,9′-Spirobifluorene-1,1′-diol (SBIFOL) was conveniently synthesized from 1,2-dibromobenzene and 3-bromoanisole in high yield. Both enantiomers
of SBIFOL were obtained in 99% ee by inclusion resolution with 2,3-dimethoxy-N,N,N′,N′-tetracyclohexylsuccinamide. The absolute configurations
were determined by X-ray analysis of a single crystal of molecular complex.
Molecules with a 9,9′-spirobifluorene backbone are unique
in rigidity and have a wide range of applications in molecular
electronics,1 light-emitting materials,2 enantioselective mo-
lecular recognition,3 and other areas.4 However, to our
knowledge, chiral ligands with a 9,9′-spirobifluorene back-
bone for asymmetric catalysis have not yet been reported.
To form efficient chelating ligands, the coordinating groups
need to be introduced into 9,9′-spirobifluorene at the 1 and
1′ positions, i.e., in the “bay region”. For this purpose, 9,9′-
spirobifluorene-1,1′-diol is a good starting point because the
OH groups can be easily converted to other coordinating
groups.5 However, although 9,9′-spirobifluorene-2,2′-diol was
already reported by Prelog in 1978,6 9,9′-spirobifluorene-
1,1′-diol is still an unknown compound. In this paper, we
describe the synthesis and optical resolution of 9,9′-spiro-
bifluorene-1,1′-diol.
Our first attempt followed the method for building the
structure of 9,9′-spirobifluorene reported by Weisburger
(Scheme 1).7 The substituted biphenyl 1, prepared from
Kumada coupling of 1,2-dibromobenzene and the Grignard
reagent of 3-bromoanisole, was treated with n-BuLi and
reacted with ethyl chloroformate to give ester 2. After
hydrolysis, the obtained carboxylic acid 3 was treated with
bromine followed by cyclization with PPA to give 4-bromo-
1-methoxyfluoren-9-one (5).8 The nucleophilic addition of
(1) (a) Tour, J. M.; Wu, R.-L.; Schumm, J. S. J. Am. Chem. Soc. 1990,
112, 5662. (b) Pei, J.; Ni, J.; Zhou, X.-H.; Cao, X.-Y.; Lai, Y.-H. J. Org.
Chem. 2002, 67, 8112.
(2) (a) Bach, U.; Lupo, D.; Comte, P.; Moser, J. E.; Weissortel, F.;
Salbeck, J.; Spreitzer, H.; Gratzel, M. Nature 1998, 395, 583. (b) Schartel,
B.; Damerau, T.; Hennecke, M. Phys. Chem. Chem. Phys. 2000, 2, 4690.
(c) Wu, C. C.; Lin, Y. T.; Chiang, H. H.; Cho, T. Y.; Chen, C. W. Appl.
Phys. Lett. 2002, 81, 577. (d) Chien, Y.-Y.; Wong, K.-T.; Chou, P.-T.;
Cheng, Y.-M. Chem. Commun. 2002, 2874. (e) Kru¨ger, J.; Plass, R.; Gra¨tzel,
M.; Cameron, P. J.; Peter, L. M. J. Phys. Chem. B 2003, 107, 7536. (f)
Lee, J.-I.; Lee, H.; Oh, J.; Chu, H. Y.; Kim, S. H.; Yang, Y. S.; Kim, G.
H.; Do, L.-M.; Zyung, T. Curr. Appl. Phys. 2003, 3, 469.
(3) (a) Smith, D. K.; Diederich, F. J. Chem. Soc., Chem. Commun. 1998,
2501. (b) Lustenberger, P.; Martinborough, E.; Denti, T. M.; Diederich, F.
J. Chem. Soc., Perkin Trans. 2 1998, 747. (c) Smith, D. K.; Zingg, A.;
Diederich, F. HelV. Chim. Acta 1999, 82, 1225. (d) Tejeda, A.; Oliva, A.
I.; Simo´n, L.; Grande, M.; Caballero, M.-C.; Mora´n, J. R. Tetrahedron Lett.
2000, 41, 4563.
(4) (a) Fournier, J.-H.; Maris, T.; Wuest, J. D. J. Org. Chem. 2003,
68, 241. (b) Poriel, C.; Ferrand, Y.; Le Maux, P.; Raul-Berthelot, J.;
Simonneaux, G. Chem. Commun. 2003, 1105. (c) Poriel, C.; Ferrand, Y.;
Le Maux, P.; Paul, C.; Rault-Berthelot, J.; Simonneaux, G. Chem. Commun.
2003, 2308. (d) Pei, J.; Ni, J.; Zhou, X.-H.; Cao, X.-Y.; Lai, Y.-H. J. Org.
Chem. 2002, 67, 4924. (e) Shu, C.-F.; Wu, S.-C. J. Polym. Sci., Part A:
Polym. Chem. 2003, 41, 1160. (f) Reddy, D. S.; Chou, C.-H.; Shu, C.-F.;
Lee, G.-H. Polymer 2003, 44, 557.
(5) (a) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; Verhoeven,
T. R.; Reider, P. J. J. Org. Chem. 1994, 59, 7180. (b) Cai, D.; Payack, J.
F.; Bender, D. R.; Hughes, D. L.; Verhoeven, T. R.; Reider, P. J. Org.
Synth. 1998, 76, 6. (c) Yuyet, T. M. T.; Harada, T.; Hashimoto, K.; Hatsuda,
M.; Oku, A. J. Org. Chem. 2000, 65, 1335.
(6) (a) Prelog, V. Pure Appl. Chem. 1978, 50, 893. (b) Prelog, V.;
Bedekovic´, D. HelV. Chim. Acta 1979, 62, 2285.
(7) Weisburger, J. H.; Weisburger, E. K.; Ray, F. E. J. Am. Chem. Soc.
1950, 72, 4250.
(8) PPA ) polyphosphoric acid.
10.1021/ol0492546 CCC: $27.50 © 2004 American Chemical Society
Published on Web 06/10/2004

Scheme 1. Synthesis of 9,9′-Spirobifluorene-1,1′-diol through
Scheme 2. Synthesis of 9,9′-Spirobifluorene-1,1′-diol through
a Separated Ring-Closing Route
a Continuous Ring-Closing Route
bifluorene compound 8 in 73% yield at 40-50 °C for 5 h,
and the workup of the reaction mixture was very simple.
Having the key intermediate 8 at hand, the following
debromination by Pd/C-catalyzed hydrogenation and the
demethylation by tribromoboron were easily achieved using
standard conditions.11 The target molecule, 9,9′-spirobi-
fluorene-1,1′-diol (13), was finally obtained in 27% overall
yield from dibromobenzene.
Inclusion crystallization is an effective method for the
separation of enantiomers of racemic chiral compounds and
is much simpler than traditional diastereomeric resolution.12
The choice of chiral host is most important for achieving
differentiation between diastereoisomeric inclusion com-
plexes formed in resolution. After screening different chiral
resolving reagents, 2,3-dimethoxy-N,N,N′,N′-tetracyclohexyl-
succinamide (14)13 was found to have the greatest potential
in the resolution of 9,9′-spirobifluorene-1,1′-diol (13). When
(2R,3R)-14 and racemic diol 13, in a molar ratio of 1:1, were
dissolved in ethanol at rt, a white precipitate appeared after
a few minutes. This slurry was stirred overnight, and crystal
complexes were collected by filtration. The decomposition
of the inclusion complex with 1 N NaOH gave (+)-13 in
85% yield (based on one enantiomer) in 80% ee. The
enantiomeric excess of (+)-13 was further increased to 99%
by repeating the procedure of inclusion crystallization as
mentioned above. The enantiomer (-)-13 (99% ee) was
obtained by inclusion resolution using (2S,3S)-14.
lithium reagent to 5 produced alcohol 6. Compound 6 was
so unstable under the bromination conditions that it dehy-
drated immediately to offer the desired 9,9′-spirobifluorene
compound 8 and byproduct 9 in a 1:3 ratio.9 Because
byproduct 9 could not be converted to the desired compound
8 and was also not easy to separate from compound 8, a
very low overall yield can be expected in the preparation of
9,9′-spirobifluorene-1,1′-diol by this separated ring-closing
method.
To avoid unwanted ring-closing compounds and to facili-
tate the purification of product, a new strategy was designed
as shown in Scheme 2. The Kumada coupling product 1 was
treated with n-BuLi and reacted with 0.5 equiv of dimethyl
carbonate to produce ketone 10 in 70% yield. This ketone
was brominated with NaBr in the presence of H2O2 to give
dibromoketone 11 in a quantitative yield. The brominations
took place exclusively para to the CH3O groups. In the ring-
closing step, PPA was initially tested to cyclize ketone 11
and 9,9′-spirobifluorene compound 8 was produced in 50%
yield. However, the workup of the reaction mixture was
rather troublesome because an emulsion always occurred
during extraction of product. Our second approach was to
use methanesulfonic acid (MsOH), which was reported to
be a good ring-closing reagent in the synthesis of fluoren-
9-ones.10 In MsOH, ketone 11 was cyclized to 9,9′-spiro-
(11) (a) Birman, V. B.; Rheingold, A. L.; Lam, K.-C. Tetrahedron:
Asymmetry 1999, 10, 125. (b) Zhu, S.-F.; Fu, Y.; Xie, J.-H.; Liu, B.; Xing,
L.; Zhou, Q.-L. Tetrahedron: Asymmetry 2003, 14, 3219.
(12) (a) Inclusion Compounds; Atwood, J. L., Davies, J. E. D., MacNicol,
D. D., Eds.; Academic Press: London, 1984; Vols. 1-111; Oxford
University Press: Oxford, 1991; Vols. IV, V. (b) Molecular Inclusion and
Molecular Recognition-Clathrates I and II; Weber, E., Ed.; Topics in Current
Chemistry; Springer: Berlin, 1987, 1988; Vols. 140, 149. (c) Tanaka, K.;
Okada, T.; Toda, F. Angew. Chem., Int. Ed. Engl. 1993, 32, 1147. (d) Toda,
F.; Tanaka, K.; Stein, Z.; Goldberg, I. J. Org. Chem. 1994, 59, 5748. (e)
Toda, F.; Tanaka, K., Chem. Commun. 1997, 1087. (f) Ding, K.; Wang,
Y.; Yun, H.; Liu, J.; Wu, Y.; Terada, M.; Okubo, Y.; Mikami, K. Chem.
Eur. J. 1999, 5, 1734. (g) Periasamy, M.; Venkatraman, L.; Thomas, K. R.
J. J. Org. Chem. 1997, 62, 4302.
(9) Though excess pyridine was present, the ring closure is complete at
0 °C in 5 min.
(10) Tilly, D.; Samanta, S. S.; Faigl, F.; Mortier, J. Tetrahedron Lett.
2002, 43, 8347.
(13) Toda, F.; Tanaka, K. J. Org. Chem. 1988, 53, 3607.
2382
Org. Lett., Vol. 6, No. 14, 2004

(2R,3R)-14 and one (+)-13 through a hydrogen bond between
the hydroxy group of the diol and the carbonyl group of the
amide. The blocks were linked by ethanol as a bridge in a
zigzag manner. The length of the hydrogen bond between
the diol and the carbonyl of the amide OH‚‚‚O was 1.82 Å
and the angle of the bonds O-H‚‚‚O was 173°, which
indicated the existence of a strong hydrogen bond in the
block. The two hydrogen bonds held by ethanol were 2.10
Å long and the two O-H‚‚‚O angles were 179° and 150°,
respectively. These two hydrogen bonds kept the super-
molecule big enough to precipitate out of ethanol. The
absolute configuration of (+)-13 was assigned to be R
unambiguously by relating it to the configuration of (2R,3R)-
14.
In conclusion, we have developed a new strategy toward
the synthesis of 9,9′-spirobifluorene-1,1′-diol with continuous
ring-closing as a feature. The enantiomers of 9,9′-spirobi-
fluorene-1,1′-diol were obtained by inclusion resolution. This
new member of the 9,9′-spirobifluorene family will provide
a potential backbone for chiral ligands and synthetic material.
Acknowledgment. We thank the National Natural Sci-
ence Foundation of China, the Major Basic Research
Development Program (Grant No. G2000077506), and the
Ministry of Education of China for financial support.
Supporting Information Available: The procedure for
the preparation of racemic 9,9′-spirobifluorene-1,1′-diol and
resolution. The analysis data of 1, 7, and 9-12 and the
structure information of crystal complexes. This material is
available free of charge via the Internet at http://pubs.acs.org.
Figure 1. Crystal structure of the molecular complex of (R)-13
and (2R,3R)-14.
OL0492546
To determine the absolute configurations of diols 13, a
single crystal of the molecular complex was prepared from
ethanol and subjected to X-ray diffraction analysis. The
perspective view of the molecular complex is shown in
Figure 1.14 In the crystal, each block was constructed of one
(14) Crystal data for [(R)-13‚(2R, 3R)-14‚EtOH]: C57H74N2O7, Mr )
899.18, T ) 293 K, radiation ) Mo KR, λ ) 0.710 73 Å, crystal dimensions
) 0.22 × 0.20 × 0.18 mm, monoclinic, space group P2(1), a ) 9.718(3)
Å, b ) 25.585 (8) Å, c ) 11.268 (4) Å, V ) 2561.0(14) Å3, Z ) 2, 8644
unique reflections, R1 ) 0.0687. For crystallographic data for the structure,
see the Supporting Information.
Org. Lett., Vol. 6, No. 14, 2004
2383