Synthesis, Chiral Resolution, and Absolute Configuration of C 2-Symmetric, Chiral 9,9′-Spirobifluorenes

Article abstract of DOI:10.1002/ejoc.201402738

Racemic 2,2′-, 2,2′,7,7′-, and 2,2′,3,3′-substituted 9,9′-spirobifluorenes were synthesised and successfully resolved by HPLC on a Chiralpak IA stationary phase on both analytical and semipreparative scales. Their absolute configurations were determined by comparison of their specific optical rotations with literature data or by comparison of retention times with independently prepared enantiopure material. These compounds are versatile C ₂-symmetric building blocks for the formation of more sophisticated cleft-like, chiral molecular architectures. Dissymmetric difunctionalised 9,9′-spirobifluorene derivatives were prepared and resolved by HPLC on a chiral stationary phase on a semipreparative scale. The absolute configurations of the resolved enantiomers were assigned by comparison of specific optical rotations with literature data or retention times of independently prepared enantiomerically pure material.

Full text of DOI:10.1002/ejoc.201402738

FULL PAPER
DOI: 10.1002/ejoc.201402738
Synthesis, Chiral Resolution, and Absolute Configuration of C2-Symmetric,
Chiral 9,9Ј-Spirobifluorenes
Caroline Stobe,[a] Ryota Seto,[a] Andreas Schneider,[a] and Arne Lützen*[a]
Keywords: Analytical methods / Chiral resolution / Configuration determination / Liquid chromatography / Spiro
compounds
Racemic 2,2Ј-, 2,2Ј,7,7Ј-, and 2,2Ј,3,3Ј-substituted 9,9Ј-spiro-
bifluorenes were synthesised and successfully resolved by
HPLC on a Chiralpak IA stationary phase on both analytical
and semipreparative scales. Their absolute configurations
tions with literature data or by comparison of retention times
with independently prepared enantiopure material. These
compounds are versatile C2-symmetric building blocks for
the formation of more sophisticated cleft-like, chiral molecu-
were determined by comparison of their specific optical rota- lar architectures.
Introduction
tartaric acid derivative must be synthesised in three steps
and tends to racemise during the second step. In fact, the
clathrate formation and its subsequent cleavage have to be
performed very carefully to obtain sufficient enantiomeric
excesses for both enantiomers.
Since 9,9Ј-spirobifluorene was first synthesised in 1930
by Clarkson and Gomberg[1] its derivatives have found a
wide range of applications. After the groups of Prelog[2] and
Diederich[3] had explored their use in the field of molecular
recognition, 9,9Ј-spirobifluorenes found their way into ca-
talysis,[4] coordination,[5] and polymer chemistry.[6] Re-
cently, 9,9Ј-spirobifluorenes have attracted attention be-
cause of their unique (opto-)electronic properties.[7] In fact,
today 2,2Ј,7,7Ј-tetrakis[bis(p-methoxyphenyl)amino]-9,9Ј-
spirobifluorene (spiro-MeOTAD)[8] is the most widely used
hole transport material (HTM) in high-performance solid-
state dye-sensitised solar cells (ssDSCs).[9]
In our group, 9,9Ј-spirobifluorenes have proven their
worth as versatile building blocks for artificial receptors[10]
as well as for metallosupramolecular aggregates.[5e,5h] Being
especially interested in the molecular recognition of chiral
substrates and in the diastereoselective self-assembly of
metallosupramolecular aggregates, dissymmetric 9,9Ј-spiro-
bifluorenes attracted our interest and highlighted a need for
enantiomerically pure derivatives.
Drawing on our experience with HPLC-based resolu-
tions[14] we tried to employ this technique for the direct sep-
aration of racemic 2,2Ј-disubstituted 9,9Ј-spirobifluorenes.
HPLC on chiral stationary phases has proven to be a versa-
tile tool for the resolution of a wide range of compounds.[15]
In 2006, Zhou et al. reported on a new route to chiral dihy-
droxy-9,9Ј-spirobifluorenes. In this study Chiralpak AD-H
was employed as chiral stationary phase for the preparative
resolution of 3,3Ј- and 4,4Ј-dihydroxy-9,9Ј-spirobifluor-
ene.[16] Nevertheless, in the case of chiral 9,9Ј-spirobifluor-
enes, HPLC has primarily been used for analytical pur-
poses.[6h,13] The reason for this is most likely the nature of
the stationary phase Chiralpak AD-H, which has been used
in all resolutions of chiral 9,9Ј-spirobifluorenes so far. In
this phase the chiral selector amylose tris(3,5-dimethylphen-
ylcarbamate) is only physically adsorbed on the silica gel
support. This limits the range of potential eluents to a great
extent – in fact only alkanes, alcohols and acetonitrile can
be applied without destruction of the column. Although
generally exhibiting a good solubility, 9,9Ј-spirobifluorenes
are only poorly soluble in these mobile phases. Conse-
quently, only small amounts of racemate can be applied
even on a preparative column which clearly makes this ap-
proach quite unattractive due to time-consumption and
high costs. Fortunately, in chiral stationary phases of the
next generation such as Chiralpak IA, the selector is im-
mobilised – which means covalently bonded to the silica
substrate. This extends the range of possible mobile phases
enormously and offers new possibilities for the effective
(semi)preparative chiral resolution of many compounds.
In 1988, Toda published a procedure for the resolution
of 2,2Ј-dihydroxy-9,9Ј-spirobifluorene through clathrate
formation with (R,R)-(+)-2,3-dimethoxy-N,N,NЈ,NЈ-tetra-
cyclohexylsuccindiamide,[11] which was refined and im-
proved by Thiemann in 2005.[12] Although this approach
has been applied successfully by us[5e,5h] and others[6e,6h,13]
it is quite tedious. This is not only due to the fact that the
[a] Kekulé-Institut für Organische Chemie und Biochemie,
Rheinische Friedrich-Wilhelms-Universität Bonn,
Gerhard-Domagk-Str. 1, 53121 Bonn, Germany
E-mail: arne.luetzen@uni-bonn.de
http://www.chemie.uni-bonn.de/oc/forschung/arbeitsgruppen/
ak_lue
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402738.
Eur. J. Org. Chem. 2014, 6513–6518
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6513

C. Stobe, R. Seto, A. Schneider, A. Lützen
FULL PAPER
In this work, we present the synthesis and a resolution
approach employing semipreparative HPLC that allowed us
to improve the resolution of C2-symmetric, chiral 9,9Ј-
spirobifluorene derivatives with regard to yield and optical
purity. The absolute configuration of the enantiomers was
determined by comparison of either their optical rotation
with literature data or their retention times with those of
their enantiopure analogues synthesised in advance.
Results and Discussion
Figure 1. Chromatographic resolution of rac-3 by analytical HPLC
on an analytical chiral Chiralpak IA phase with chloroform/2-
propanol (95:5 v/v) as eluent, a flow rate f = 0.5 mLmin–1, and a
detection wavelength λ = 300 nm.
The starting material for the synthesis of all compounds
was 2,2Ј-dihydroxy-9,9Ј-spirobifluorene (3). The synthesis
of the diol 3 starting from 9,9Ј-spirobifluorene[1] (1) accord-
ing to a procedure by Prelog[2c] is well established and has
been applied in our group for years.[12] However, carbon
disulfide, which is needed as solvent in the initial Friedel–
Crafts acylation of 1, is highly toxic. Moreover, the protocol
using carbon disulfide requires a rather extensive workup.
By utilising a mixture of dichloromethane and nitrometh-
ane we were able to both simplify the work-up and improve
the yield of the Friedel–Crafts acylation (Scheme 1).
protocol as used for 3, the dibromo derivative 6 was easily
accessible in enantiopure form (Figure 2). Because this
compound had been synthesised only in racemic form be-
fore, the absolute configuration could not be assigned by
simple comparison of the optical rotations with literature
data. Finding it impossible to resolve either of the com-
pounds used in the synthesis described by Diederich or to
crystallise the enantiopure dibromide 6, we decided to syn-
thesise both enantiomers of 6 starting from enantiopure
diol 3. This enabled us to compare the retention times and
optical rotations of the synthetically obtained enantiopure
compounds with those resolved by HPLC.
Scheme 1. Improved synthesis of 2,2Ј-diacetyl-9,9Ј-spirobifluorene
(2).
Subsequent Baeyer–Villiger oxidation of 2 and saponifi-
cation of the resulting diester finally yields racemic 2,2Ј-
dihydroxy-9,9Ј-spirobifluorene (3). By applying our experi-
ence concerning HPLC-based chiral resolutions, we were
able to establish a very efficient resolution protocol for 3.
Employing Chiralpak IA as stationary phase enabled us to
use a mixture of chloroform and 2-propanol as the mobile
phase. The high solubility of 3 in this eluent together with
a very high selectivity value (α = 4.3) enabled the resolution
of large quantities in a reasonable time (Figure 1). The ab-
solute configuration of the enantiomers could be assigned
by comparison of the specific optical rotations of the two
fractions with literature data.[12]
Figure 2. Chromatographic resolution of rac-6 by analytical HPLC
on an analytical chiral Chiralpak IA phase with chloroform/2-
propanol (95:5 v/v) as eluent, a flow rate f = 0.5 mLmin–1, and a
detection wavelength λ = 300 nm.
Unfortunately, direct 7,7Ј-selective bromination of 3 was
not possible. After several unsuccessful attempts applying
Encouraged by this exciting result, we wanted to explore different halogenation protocols and alcohol protecting
if the strategy of chiral resolution of 9,9Ј-spirobifluorenes groups, we found that pivaloyl ester 4 was a convenient
via HPLC could be extended to higher substituted deriva- starting material. The latter ester is easily prepared from
tives. Due to the orientation of the substituents and because diol 3 through deprotonation with triethylamine and subse-
of the multitude of possible chemical transformations, 2,2Ј- quent treatment with pivaloyl chloride in 92% yield. Estab-
dibromo-7,7Ј-dihydroxy-9,9Ј-spirobifluorene (6) attracted lishing a reliable protocol for the regioselective bromination
our interest. In 1992, Diederich et al. published a synthetic of 4 required some effort but was ultimately successful: By
route to racemic 6 starting from 2,2Ј-diacetyl-9,9Ј-spirobi- using aluminium chloride as Lewis acid and two equivalents
fluorene (2).[3c] By applying the same chiral resolution of bromine at 50 °C for 18 h, 5 could be obtained in a very
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C2-Symmetric, Chiral 9,9Ј-Spirobifluorenes
good yield of 78%. Saponification of the bulky ester 5 re-
quired the use of sodium methoxide as base, giving 6 in
91% yield (Scheme 2).
Figure 3. Chromatographic resolution of rac-7 by analytical HPLC
on an analytical chiral Chiralpak IA phase with chloroform/n-hex-
ane (90:10 v/v) as eluent, a flow rate f = 0.5 mLmin–1, and a detec-
tion wavelength λ = 325 nm.
Conclusions
We were able to synthesise five different chiral dis-
symmetric 9,9Ј-spirobifluorenes. Within the scope of our
attempts to access enantiopure 9,9Ј-spirobifluorenes, we es-
tablished a new route to 2,2Ј-dibromo-7,7Ј-dihydroxy-9,9Ј-
spirobifluorene (6) starting from 3. Additionally, we synthe-
sised a new dibromo derivative with a 2,2Ј,3,3Ј-substitution
pattern 7. Finally, we were able to resolve the racemic diols
3, 6, and 7 by HPLC techniques on an analytical and a
semipreparative scale by using a Chiralpak IA stationary
phase. The absolute configuration of the separated enantio-
mers was determined by comparison of their specific optical
rotation and/or retention times with literature data or with
those of synthetically obtained enantiopure compounds.
The resolution via HPLC gave rise to all enantiomers in
excellent yields and purities. These enantiopure compounds
represent versatile, configurationally stable building blocks
for the synthesis of more sophisticated molecular architec-
tures based on the chiral, cleft-like structure of the 9,9Ј-
spirobifluorene scaffold.
Scheme 2. Synthesis of 2,2Ј-dibromo-7,7Ј-dihydroxy-9,9Ј-spirobi-
fluorene (6).
To explore whether we were able to extend our concept
to different substitution patterns, we synthesised 3,3Ј-di-
bromo-2,2Ј-dihydroxy-9,9Ј-spirobifluorene (7). This com-
pound is easily accessible by applying a bromination proto-
col developed by Kajigaeshi using tetrabutylammonium-
tribomide as halogenation agent (Scheme 3).[17]
Experimental Section
General: Reactions under inert gas atmosphere were performed un-
der argon by using standard Schlenk techniques and oven-dried
glassware prior to use. Thin-layer chromatography was performed
on aluminium TLC plates silica gel 60F254 from Merck. Detection
was carried out under UV light (254 and 366 nm). Products were
purified by column chromatography on silica gel 60 (40–60 mesh)
Scheme 3. Synthesis of 3,3Ј-dibromo-2,2Ј-dihydroxy-9,9Ј-spirobi-
fluorene (7).
1
from Merck. The H and 13C NMR spectra were recorded with a
Bruker DPX 500 spectrometer at 298 K, at 500.1 and 125.8 MHz
or with a Bruker AM 400 at 298 K, at 400.1 MHz and 100.6 MHz,
respectively. The 1H NMR chemical shifts are reported on the δ
scale (ppm) relative to residual non-deuterated solvent as the in-
ternal standard. The 13C NMR chemical shifts are reported on the
δ scale (ppm) relative to deuterated solvent as the internal standard.
Signals were assigned on the basis of 1H, 13C, HMQC-, and HMBC
NMR experiments. Mass spectra were recorded with a Finnigan
MAT 212 and data system MMS-ICIS (EI) or with a Bruker
micrOTOF-Q (ESI). Elemental analyses were carried out with a
For the chiral resolution of 7, we had to change the sepa-
ration protocol slightly with respect to the mobile phase.
Instead of 2-propanol, n-hexane was used as a modifier.
Nevertheless, the racemate could be dissolved in a chloro-
form/2-propanol mixture, ensuring that reasonable amounts
of racemic material could be resolved efficiently (Figure 3).
We applied the same strategy that was used for 7 to assign
the absolute configuration of the enantiomers.
Eur. J. Org. Chem. 2014, 6513–6518
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C. Stobe, R. Seto, A. Schneider, A. Lützen
FULL PAPER
HeraeusVario EL. The HPLC analysis was performed by using
three different systems: The Prominence console from Shimadzu
(binary recycling system) consisting of three pumps (2ϫLC20-AT,
1ϫLC20-AD), degasser (DGU-20A3), diode array detector (SPD-
vents, the crude product was purified by column chromatography
on silica gel (cyclohexane/ethyl acetate, 5:1 v/v; Rf = 0.56), yield
1
1.38 g (2.67 mmol, 92%). H NMR (500.1 MHz, CDCl3): δ = 1.28
(s, 18 H, CH3), 6.50 (dd, 4J1,3 = 2.2, 5J1,4 = 0.4 Hz, 2 H, 1-H), 6.75
3
4
5
M20A), and a fraction collector (FRC-10A). The analytical (ddd, J7,8 = 7.4, J6,8 = 1.0, J5,8 = 0.7 Hz, 2 H, 8-H), 7.11–7.14
KNAUER system (Smartline series) consisting of one S-1000 pump
(with 10 mL pump head), autosampler S-3945, column oven Jets-
tream, photodiode array detector S-2800, chiral detector of IBZ
Meßtechnik and a refraction index detector Ri101 of Shodex. The
semi-preparative KNAUER system (Smartline series) was com-
posed of a two-channel degasser, two pumps S-1000 (50 mL pump
head), a injection assistant 6000 with a feed pump S-100, a mixing
chamber Smartmix 350, an UV-detector S-2500 and a refraction
index detector (Ri)S-2400. Chiral analytical (5 μm, 4.6ϫ250 mm)
and semipreparative (5 μm, 250ϫ10 mm) stationary phases Chi-
(m, 4 H, 3-H, 7-H), 7.38 (ddd, 3J6,7 = 7.5, 3J5,6 = 7.7, 4J6,8 = 1.0 Hz,
3
4
5
2 H, 6-H), 7.82 (ddd, J5,6 = 7.7, J5,7 = 1.1, J5,8 = 0.7 Hz, 2 H,
5-H), 7.84 (dd, 3J3,4 = 8.4, 5J1,4 = 0.4 Hz, 2 H, 4-H) ppm. 13C NMR
(125.8 MHz, CDCl3): δ = 27.2 (C-16), 39.1 (C-15), 66.0 (C-9), 117.5
(C-1), 120.0 (C-5), 120.6 (C-4), 121.6 (C-3), 124.3 (C-8), 128.0 (C-
7), 128.1 (C-6), 139.3 (C-11), 141.0 (C-12), 148.6 (C-13), 149.6 (C-
10), 151.0 (C-2), 176.9 (C-14) ppm. MS (ESI): m/z (%) = 1055.4
(14) [C70H32O4 + Na]+, 539.2 (100) [C35H32O4 + Na]+, 517.2 (3)
[C35H32O4 + H]+, 433.2 (11) [C30H24O3 + H]+. HRMS (EI): m/z
calcd. for [C35H32O4]+· 516.2301; found 516.2300. C35H32O4
ralpak IA from DAICEL were applied, and solvent mixtures of (516.63): calcd. C 81.37, H 6.24; found C 81.17, H 6.71.
n-hexane, chloroform and 2-propanol (HPLC quality) were used.
Compound (+)-(R)-4: [α]2D0 +30.4 (c = 3.64 mgmL–1, CHCl3).
Optical purities were determined by analytical HPLC analysis of
Compound (–)-(S)-4: [α]2D0 –30.4 (c = 3.65 mgmL–1, CHCl3).
resolved material. Most solvents were dried, distilled and stored
under argon according to standard procedures. All chemicals were
2,2Ј-Dibromo-7,7Ј-dipivaloyl-9,9Ј-spirobifluorene (5): Compound 4
(2.00 g, 3.87 mmol) and aluminium chloride (1.21 g, 9.10 mmol)
were dissolved in anhydrous dichloromethane (43 mL) and stirred
at 50 °C for 1 h. A bromine solution (1 m in dichloromethane,
used as received from commercial sources. 9,9Ј-Spirobifluorene,[1]
rac-2,2Ј-diacetoxy-9,9Ј-spirobifluroene,[2c] rac-2,2Ј-dihydroxy-9,9Ј-
spirobifluorene,[2c] and tetrabutylammonium tribromide[18] were
prepared according to literature protocols.
7.75 mL, 7.75 mmol) was added by using a syringe and the re-
rac-2,2Ј-Diacetyl-9,9Ј-spirobifluorene (rac-2): Aluminium chloride
(2.53 g, 19.0 mmol) was dissolved in nitromethane (6 mL) and co-
oled to 0 °C. Acetyl chloride (1.42 mL, 1.49 g, 18.9 mmol) was
slowly added by using a syringe while the temperature was kept
below 0 °C. A solution of 9,9Ј-spirobifluorene (2.00 g, 6.23 mmol)
in anhydrous dichloromethane (6 mL) was then added over 15 min.
The solution was stirred for 1 h at 0 °C, then the solution was
warmed to room temperature and stirred for another 12 h. The
solution was poured over ice and hydrochloric acid (1.0 m,
50.0 mL), the layers were separated, and the aqueous layer was
extracted three times with dichloromethane. The combined organic
layers were washed with hydrochloric acid (1.0 m), water and brine,
and dried with Na2SO4. After evaporation of the solvents, the resi-
due was taken up in a small amount of dichloromethane. Cyclohex-
ane was added until the product started to precipitate. After stand-
ing in the freezer overnight, the precipitate was filtered off, washed
with cyclohexane and dried in vacuo, yield 2.40 g (5.99 mmol,
96%). The analytical data were in accordance with reported da-
ta.[2c]
sulting mixture was stirred at 50 °C for 18 h. The mixture was co-
oled to room temperature, poured into ice water and acidified with
hydrochloric acid (5 m). After phase separation, the aqueous layer
was extracted with dichloromethane (3ϫ 50 mL) and the combined
organic layers were washed with saturated aq. NaHCO3, water and
brine and dried with Na2SO4. The solvent was evaporated and the
crude product was purified by column chromatography on silica
gel [n-heptane/THF, 20:1Ǟ10:1 (v/v); Rf = 0.23 for 10:1 (v/v)],
1
yield 2.04 (3.02 mmol, 78%). H NMR (500.1 MHz, CDCl3): δ =
1.27 (s, 18 H, CH3), 6.47 (d, 4J7,8 = 2.1 Hz, 2 H, 8-H), 6.84 (d, 4J1,3
3
4
= 1.8 Hz, 2 H, 1-H), 7.14 (dd, J5,6 = 8.3, J6,8 = 2.1 Hz, 2 H, 6-
3
4
3
H), 7.51 (dd, J3,4 = 8.2, J1,3 = 1.8 Hz, 2 H, 3-H), 7.67 (d, J3,4
=
8.2 Hz, 2 H, 4-H), 7.80 (d, J5,6 = 8.3 Hz, 2 H, 5-H) ppm. 13C
NMR (125.8 MHz, CDCl3): δ = 27.2 (C-16), 39.2 (C-15), 65.6 (C-
9), 117.5 (C-8), 120.9 (C-5), 121.5 (C-4), 121.7 (C-2), 122.2 (C-6),
127.4 (C-1), 131.6 (C-3), 138.2 (C-12), 140.0 (C-11), 148.5 (C-13),
149.8 (C-10), 151.4 (C-7), 176.8 (C-14) ppm. MS (EI): m/z (%) =
674.1 (60) [C35H30Br2O4]+·, 590.0 (75) [C30H22Br2O3]+, 505.9 (80)
[C25H13Br2O2]+. MS (ESI): m/z (%) = 697.1 (100) [C35H30Br2O4 +
Na]+. HRMS (ESI): m/z calcd. for [C35H30Br2O4 + Na]+ 697.0386;
found 697.0381. C35H30Br2O4·1/2H2O: calcd. C 61.51, H 4.57;
found C 61.50, H 4.77.
3
Separation of Enantiomers of rac-3: HPLC conditions: chiral phase
(semipreparative), Chiralpak IA; CHCl3/2-propanol, 95:5; f =
2.3 mLmin–1; sample solvent: CHCl3/2-propanol, 10:1 (v/v); load-
ing per run: 40 mg of racemic material.
Compound (–)-(S)-3: Retention time: 8.51 min; [α]2D0 –20.3 (c =
2.93 mgmL–1, CHCl3); 99.9%ee.
Compound (–)-(R)-5: [α]2D0 –1.4 (c = 5.55 mgmL–1, CHCl3).
Compound (+)-(S)-5: [α]2D0 +1.8 (c = 3.51 mgmL–1, CHCl3).
2,2Ј-Dibromo-7,7Ј-dihydroxy-9,9Ј-spirobifluorene (6): Compound 5
(0.80 g, 1.19 mmol) was dissolved in anhydrous dichloromethane
(36 mL) and a solution of sodium methoxide (5.4 m in methanol,
5.30 mL) was slowly added by using a syringe. After stirring at
room temperature overnight, the mixture was neutralised by adding
hydrochloric acid (2 m). The layers were separated and the aqueous
phase was extracted with dichloromethane (3ϫ 50 mL). The com-
bined organic phases were washed with saturated aq. NaHCO3,
water and brine, and dried with MgSO4. After evaporation of the
solvents, the crude product was subjected to column chromatog-
raphy on silica gel [cyclohexane/ethyl acetate, 2:1 (v/v); Rf = 0.42],
yield 0.551 g (1.09 mmol, 91%). 1H NMR (500.1 MHz, [D6]acet-
Compound (+)-(R)-3: Retention time: 14.6 min; [α]2D0 +20.4 (c =
2.46 mgmL–1, CHCl3); 99.9%ee.
2,2Ј-Dipivaloyl-9,9Ј-spirobifluorene (4): Compound
3 (1.00 g,
2.90 mmol) was dissolved in dichloromethane (86 mL), triethyl-
amine (2.00 mL, 1.45 g, 14.4 mmol) was added by using a syringe,
and the solution was cooled to –10 °C. A solution of pivaloyl chlor-
ide (0.90 mL, 0.87 g, 7.18 mmol) in dichloromethane (4 mL) was
added over 20 min, then the solution was warmed to room tem-
perature and stirred overnight. Ice-cold aq. hydrochloric acid
(2.0 m, 50.0 mL) was added, the layers were separated, and the
aqueous layer was extracted three times with dichloromethane. The
combined organic layers were washed with saturated aq. NaHCO3
4
5
one): δ = 6.21 (dd, J6,8 = 2.3, J5,8 = 0.4 Hz, 2 H, 8-H), 6.80 (dd,
5
3
4
and brine and dried with Na2SO4. After evaporation of the sol- 4J1,3 = 1.9, J1,4 = 0.4 Hz, 2 H, 1-H), 6.92 (dd, J5,6 = 8.3, J6,8
=
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C2-Symmetric, Chiral 9,9Ј-Spirobifluorenes
3
4
2.3 Hz, 2 H, 6-H), 7.53 (dd, J3,4 = 8.2, J1,3 = 1.9 Hz, 2 H, 3-H),
3
5
3
7.80 (dd, J3,4 = 8.2, J1,4 = 0.4 Hz, 2 H, 4-H), 7.83 (dd, J5,6
=
[1]
[2]
R. G. Clarkson, M. Gomberg, J. Am. Chem. Soc. 1930, 52,
2881–2891.
8.2, 5J5,8 = 0.4 Hz, 2 H, 5-H), 8.50 (br. s, 2 H, OH) ppm. 13C NMR
(125.8 MHz, [D6]acetone): δ = 66.2 (C-9), 111.4 (C-8), 116.6 (C-6),
120.1 (C-2), 121.9 (C-4), 122.6 (C-5), 127.3 (C-1), 132.0 (C-3), 133.0
(C-11), 142.2 (C-12), 150.9 (C-10, C-13), 159.2 (C-7) ppm. MS (EI):
m/z (%) = 506.0 (100) [C25H14Br2O2]+·, 425.1 (40) [C25H14BrO2]+,
345.1 (20) [C25H13O2]+. HRMS (EI): m/z calcd. for [C25H14Br2-
O2]+· 503.9361; found 503.9358. C25H14Br2O2·3/4C4H8O2: calcd. C
58.77, H 3.52; found C 58.80, H 3.55.
a) G. Haas, V. Prelog, Helv. Chim. Acta 1969, 52, 1202–1218;
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Separation of Enantiomers: HPLC conditions: chiral phase (semi-
[3]
preparative), Chiralpak IA; CHCl3/2-propanol, 95:5;
f
=
2.3 mLmin–1; sample solvent: CHCl3/2-propanol, 10:1 (v/v); load-
ing per run: 20 mg of racemic material.
Compound (–)-(S)-6: Retention time: 6.60 min; [α]2D0 –20.4 (c =
3.44 mgmL–1, CHCl3); 99.9%ee.
Compound (+)-(R)-6: Retention time: 16.0 min; [α]2D0 +19.0 (c =
2.16 mgmL–1, CHCl3); 99.9%ee.
3,3Ј-Dibromo-2,2Ј-dihydroxy-9,9Ј-spirobifluorene (7): Compound 3
(0.40 g, 1.15 mmol) was dissolved in methanol (12 mL) and di-
chloromethane (18 mL), then tetrabutylammonium tribromide
(1.11 g, 2.30 mmol) was added in small portions. The solution was
stirred for 30 min until decolouration of the orange solution oc-
curred. The solvents were evaporated and the waxy residue was
taken up in water and diethyl ether. The layers were separated and
the aqueous layer was extracted twice with diethyl ether. The com-
bined organic layers were washed with brine and dried with
MgSO4. After removal of the solvent, the crude product was puri-
fied by column chromatography on silica gel [cyclohexane/ethyl
acetate, 5:1 (v/v); Rf = 0.73], yield 0.482 g (0.95 mmol, 83%). 1H
NMR (400.1 MHz, [D6]acetone): δ = 2.90 (br. s, 2 H, OH), 6.33 (s,
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3
4
2 H, 1-H), 6.68 (dd, J7,8 = 7.6, J6,8 = 0.7 Hz, 2 H, 8-H), 7.11
3
3
4
(ddd, J7,8 = 7.6, J6,7 = 7.5, J5,7 = 1.1 Hz, 2 H, 7-H), 7.38 (ddd,
3J6,7 = 7.5, J5,6 = 7.6, J6,8 = 0.7 Hz, 2 H, 6-H), 7.91 (dd, J5,6
=
3
4
3
7.6, J5,7 = 1.1 Hz, 2 H, 5-H), 8.08 (s, 2 H, 4-H) ppm. 13C NMR
(100.6 MHz, [D6]acetone): δ = 66.2 (C-9), 110.5 (C-3), 112.4 (C-1),
120.6 (C-5), 124.5 (C-8), 125.6 (C-4), 128.1 (C-7), 129.0 (C-6), 136.0
(C-11), 141.6 (C-12), 148.9 (C-13), 150.6 (C-10), 154.7 (C-2) ppm.
MS (EI): m/z (%) = 505.8 (100) [C25H14Br2O2]+·, 488.8 (45)
[C25H13Br2O]+, 424.9 (15) [C25H14BrO2]+. HRMS (EI): m/z calcd.
for [C25H14Br2O2]+· 503.9361; found 503.9362. C25H14Br2O2·
1/6C6H12: calcd. C 60.03, H 3.10; found C 59.94, H 3.30.
4
Separation of Enantiomers: HPLC conditions: chiral phase (semi-
preparative), Chiralpak IA; CHCl3/n-hexane, 95:5;
f
=
[6]
2.3 mLmin–1; sample solvent: CHCl3/2-propanol, 10:1 (v/v); load-
ing per run: 20 mg of racemic material.
Compound (–)-(S)-7: Retention time: 7.90 min; [α]2D0 –34.8 (c =
3.80 mgmL–1, CHCl3); 94.5%ee.
Compound (+)-(R)-7: Retention time: 11.6 min; [α]2D0 +34.3 (c =
3.67 mgmL–1, CHCl3); 99.1%ee.[19]
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra of compounds 4–7.
[7]
Acknowledgments
Financial support for this work by the Deutsche Forschungsge-
meinschaft (DFG) (SFB 624) and the Ministry of Innovation,
Science, and Research of the Federal State of North Rhine-West-
falia, Germany is gratefully acknowledged.
Eur. J. Org. Chem. 2014, 6513–6518
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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Received: June 12, 2014
Published Online: August 29, 2014
6518
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