Synthesis of enantiomerically pure dissymmetric 2,2′-disubstituted 9,9′-spirobifluorenes

Article abstract of DOI:10.1002/ejoc.200400796

Racemic dissymmetric 2,2′-dihydroxy-9,9′-spirobifluorene was prepared and resolved by clathrate formation with (R,R)-(+)-2,3-dimethoxy-N,N, N′,N′-tetracyclohexylsuccindiamide, giving rise to both enantiomers in very good yields. The absolute stereochemistry of the resolved material could be assigned by an X-ray structure analysis of single crystals of the clathrate. Enantiomerically pure diols could be transformed into the corresponding ditriflates, which were then used as starting materials in different cross-coupling procedures to provide a number of new enantiomerically pure spiro compounds bearing versatile functional groups suitable for further elaboration, as demonstrated by some examples. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Full text of DOI:10.1002/ejoc.200400796

FULL PAPER
Synthesis of Enantiomerically Pure Dissymmetric 2,2Ј-Disubstituted
9
,9Ј-Spirobifluorenes
[a]
[a]
[a]
[a]
Frank Thiemann, Torsten Piehler, Detlev Haase, Wolfgang Saak, and
Arne Lützen*[
a]
Keywords: Resolution / Clathrates / Dissymmetric molecules / Cross-coupling / Spiro compounds
Racemic dissymmetric 2,2Ј-dihydroxy-9,9Ј-spirobifluorene
was prepared and resolved by clathrate formation with (R,R)-
into the corresponding ditriflates, which were then used as
starting materials in different cross-coupling procedures to
provide a number of new enantiomerically pure spiro com-
pounds bearing versatile functional groups suitable for fur-
ther elaboration, as demonstrated by some examples.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
(+)-2,3-dimethoxy-N,N,NЈ,NЈ-tetracyclohexylsuccindiamide,
giving rise to both enantiomers in very good yields. The ab-
solute stereochemistry of the resolved material could be as-
signed by an X-ray structure analysis of single crystals of the
clathrate. Enantiomerically pure diols could be transformed
Introduction
tedious. In 1996 F. Diederich reported on the use of an
elaborated enantiomerically pure 9,9Ј-spirobifluorene-based
Although now known for 75 years,[1] 9,9Ј-spirobifluorene cleft as a tool for the separation of 2,2Ј-dicarboxy- and 2,2Ј-
[
4f]
(
1) and its derivatives for a long time had to face the fate bis(hydroxymethyl)-9,9Ј-spirobifluorene, although this of
of being regarded as only another rigid, though admittedly course needs resolved material from other approaches in
aesthetic, hydrocarbon. However, this situation has changed advance.
[
2]
dramatically. After the first examples in the area of mol-
ecular recognition were reported by the groups of V. Pre-
For our purposes the 2,2Ј-dibrominated or 2,2Ј-diiodin-
ated spirobifluorenes 2 and 3 seemed to be very promising
candidates with respect to their potential for further func-
tionalization. Since we had had some good experiences with
[
3]
[4]
[5]
log, F. Diederich, and others, these compounds found
a wide range of applications in molecular electronics,
[
6]
[7]
[8]
macromolecular chemistry, light emitting devices, and
[16,17]
resolution procedures based on clathrate formation,
[
9,10,11,12]
other areas.
we were especially interested in evaluating this approach.
Unfortunately, all our attempts to obtain clathrate forma-
tion with cinchonidine derivatives or tartaric acid deriva-
tives proved unsuccessful. In 1988, however, F. Toda had
published a procedure to resolve 2,2Ј-dihydroxy-9,9Ј-spiro-
bifluorene (4) through clathrate formation with (R,R)-(+)-
In the course of our studies concerning the diastereo-
selective formation of self-assembled supramolecular heli-
[
13,14]
cates,
dissymmetric 2,2Ј-disubstituted 9,9Ј-spirobifluo-
renes attracted our interest and prompted us to evaluate the
possibilities of accessing enantiomerically pure derivatives.
V. Prelog prepared the first enantiomerically pure spirobi-
2
,3-dimethoxy-N,N,NЈ,NЈ-tetracyclohexylsuccindiamide
[
3a]
fluorenes in 1969,
by resolving some dicarboxylic acid
[18,19]
(5).
Although he only reported on one enantiomer that
derivatives through diastereoisomer formation with enan-
tiomerically pure dehydroabietylamine.[ A few years later
he was able to develop another method for the resolution
of the 2,2Ј-bis(hydroxymethyl) derivative through esterifica-
he was able to isolate by this method and despite the fact
that he was not able to assign the stereochemistry of the
enantiomerically pure (+)-enantiomer, this procedure still
seemed very attractive since the diol could also serve, after
transformation into a corresponding disulfonate, as a suit-
able starting material for our studies. In this account we
describe how we succeeded in the isolation of both enantio-
mers of 4, the assignment of their absolute stereochemistry,
and the application of the resolved compounds as sub-
strates in transition metal-catalyzed cross-coupling reac-
3a]
tion with camphanic acid, separation of the resulting dia-
stereomers, and subsequent saponification.[
3b,3c]
Although
both approaches have been successfully applied by
[
15,4c,4d]
others,
Prelog himself admitted that they are quite
[
a] University of Oldenburg, Institute of Pure and Applied Chemis- tions and some other transformations in order to gain ac-
try,
cess to a number of enantiomerically pure spiro compounds
bearing versatile functional groups capable of further elabo-
ration.
P. O. Box 2503, 26111 Oldenburg, Germany
Fax: +49-441-798-3706
E-mail: arne.luetzen@uni-oldenburg.de
DOI: 10.1002/ejoc.200400796
Eur. J. Org. Chem. 2005, 1991–2001
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1991

F. Thiemann, T. Piehler, D. Haase, W. Saak, A. Lützen
FULL PAPER
Results and Discussion
The central 9,9Ј-spirobifluorene (1) was readily prepared
in three steps starting from commercially available 2-amino-
biphenyl (Scheme 1). An initial Sandmeyer reaction was fol-
lowed by a Grignard reaction with 9-fluorenone and subse-
quent condensation under acidic conditions to give 1 in an
overall yield of 47%.[
1]
Scheme 2. Synthesis of racemic 2,2Ј-disubstituted 9,9Ј-spirobifluo-
rene derivatives 2, 3, 6, and 7.
oxidation. Although this sequence saves one step the overall
yield is still considerably lower and the reactants are also
Scheme 1. Synthesis of 9,9-spirobifluorene (1).
By F. K. Sutcliffe’s and J. H. Weisburger’s procedures, 1 more expensive.
could easily be subjected to double electrophilic aromatic
substitutions to provide 2,2Ј-dibromo- or 2,2Ј-dinitro-9,9Ј-
spirobifluorene 2 and 6, respectively, in a regioselective
[
20]
manner (Scheme 2). Both 2 and 6 could be employed to
synthesize 2,2Ј-diamino-9,9Ј-spirobifluorene (7), either by
palladium-catalyzed amination[ of the dibromide or by
simple reduction of the dinitro compound with sodium
borohydride and palladium on charcoal,[ which in fact
turned out to be much more efficient to produce the desired
21]
22]
7. Compound 7 could then be transformed into 2,2Ј-diodo-
9,9Ј-spirobifluorene (3) in a Sandmeyer reaction. However,
all of our attempts to resolve these racemic compounds
through clathrate formation with cinchonidine derivatives
or tartaric acid derivatives unfortunately failed, as did our
approach to the preparation of diastereomeric cross-coup-
ling products with enantiomerically pure 2,2Ј-dihydroxy-
1,1Ј-binaphthyl-derivatives, because we were not able to
separate the diastereomers by column chromatography or
by crystallization.
We therefore decided to prepare diol 4 and to try to take
F. Toda’s protocol a step further and isolate both enantio-
mers of 4. The synthesis of 4 started with a double Friedel–
Crafts acylation of 1, by V. Prelog’s procedure,[3c] followed
by a Baeyer–Villiger oxidation to give the corresponding
diacetate with meta-chloroperbenzoic acid. Subsequent sa-
ponification of the diester gave rise to 4 in excellent yield
Scheme 3. Preparation of racemic diol 4.
(Scheme 3). This sequence proved superior to an alternative
route starting from dibromide 2, by which 4 was obtained
The clathrate-forming tartaric acid derivative 5 was pre-
in a one-pot procedure after bromine–lithium exchange, pared in four steps from (R,R)-tartaric acid. Thus, the tar-
subsequent boronic acid ester formation, and immediate taric acid was first transformed into the corresponding di-
1992
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 1991–2001

Enantiomerically Pure Dissymmetric 2,2Ј-Disubstituted 9,9Ј-Spirobifluorenes
FULL PAPER
ethyl ester,[23] after which the hydroxy functions were meth-
[24]
ylated with methyl iodide. After saponification of the es-
[
25]
ter functions
the diacid was converted into the corre-
sponding diacid chloride, which was finally treated with di-
cyclohexylamine to give 5 (Scheme 4).[
18]
Figure 1. X-ray crystal structure analysis of the clathrate formed
by tartaric acid derivative (R,R)-5 and (R)-(+)-2,2Ј-dihydroxy-9,9Ј-
spirobifluorene [(R)-4].
tion of the hydroxy groups by treatment with phosphorus
pentabromide at elevated temperatures by an approach used
Scheme 4. Synthesis of (R,R)-2,3-dimethoxy-N,N,NЈ,NЈ-tetracyclo- by A. Binz and O. v. Schickh.[28] Unfortunately, we were
hexylsuccindiamide [(R,R)-5].
unable to obtain the desired enantiomerically pure dibro-
mide 2 in this way but rather observed decomposition of
With both components to hand we then studied the our starting material. We thus decided to switch to conver-
clathrate formation. Equimolar amounts of the resolving sion to sulfonates, because these have found increasing ap-
agent 5 and racemic 4 were dissolved in ethanol and kept plications in transition metal-catalyzed cross-coupling reac-
[
29]
at room temperature for 12 h. After that period the precipi- tions over the last years.
tate was collected and recrystallized twice from ethanol. poses. Adapting a protocol by A. Abad et al.
The clathrate could be destroyed by dissolving in benzene able to prepare the desired ditriflate 8 in almost quantitative
and treatment with aqueous sodium hydroxide to liberate yield from 4 (Scheme 5).
the (+)-enantiomer in a very good yield of 83% after sepa-
We chose triflates for our pur-
[
30]
we were
[
31]
ration of the aqueous layer, neutralization with hydrochloric
acid, and subsequent extraction. The specific rotation of
2
0
this material {[α] = +27.1 (c = 0.39, methanol)} was in
D
[
18,26]
perfect agreement with that reported by F. Toda.
Furthermore, diamide 5 could be at least in part recovered
from the neutralized organic phase. In order also to recover
the remainder, the original ethanol solution was evaporated
to dryness and the resulting residue was subjected to flash
Scheme 5. Formation of bis(triflate) (R)-8.
Compound 8 was then used as a substrate in different
chromatography on silica gel with a 2:1 mixture of petro- reactions in order to explore its potential for further elabo-
leum ether and ethyl acetate as eluent. After this procedure ration to give enantiomerically pure spiro compounds with
we were able to recover a total of 89% of the tartaric acid various functional groups. We used (R)-8 to perform these
derivative 5. Much more importantly, however, we were also experiments and then repeated some demonstration reac-
able to isolate the (–)-enantiomer from this in enantiomer- tions with (S)-8 in order to establish whether the stereo-
ically pure form and in an excellent yield of 96% as revealed chemical integrity remained intact during these transforma-
2
0
by its specific rotation of [α] = –26.9 (c = 0.92, methanol). tions. Unfortunately, all our attempts to prepare 2,2Ј-dicar-
D
Since we had been able to obtain single crystals suitable boxy-9,9Ј-spirobifluorene (9) or 2,2Ј-diamino-9,9Ј-spirobi-
for an X-ray crystal structure analysis from the clathrate, fluorene (7) by S. Cacchi’s palladium-catalyzed carboxyla-
[
32]
we were also able to assign the absolute stereochemistry of tion protocol
or by the palladium-catalyzed amination
[
33]
[21]
the resolved enantiomers of 4 for the first time (Figure 1). procedures of Y. Murakami or S. L. Buchwald have so
Thus, the (+)-enantiomer of 4 turned out to be (R)-config- far been unsuccessful, since we were only able to recover
ured and the (–)-enantiomer to be (S)-configured by the unconverted starting material or the fully defunctionalized
rules of R. S. Cahn, C. Ingold, and V. Prelog.[
27]
spirobifluorene under these conditions. After several unsuc-
[
34]
In order to gain access to further elaborated spiro com- cessful experiments, however, we were able to achieve the
pounds, especially through the use of cross-coupling reac- synthesis of 2,2Ј-dicyano-9,9Ј-spirobifluorene (10)
[
35]
in an
tions, the hydroxy functions in 4 had to be converted into excellent yield of 89% when we adapted a protocol used by
[
36]
more reactive groups. At first we tried to achieve substitu K. C. Rice (Scheme 6).
www.eurjoc.org
It should be noted at this point,
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1993

F. Thiemann, T. Piehler, D. Haase, W. Saak, A. Lützen
FULL PAPER
however, that the key to this success was to use carefully using a modified nickel-catalyzed Kumada coupling pro-
[
38]
dried lithium chloride, because otherwise only trace cedure reported by D. Xiao with methylmagnesium bro-
amounts of desired 10 could be detected.
mide (Scheme 6). Besides establishing C–C bond formation
2
3
between an sp - and an sp -carbon atom we were also able
2
to achieve the coupling of an sp- and an sp -carbon atom
[
39]
in a palladium-catalyzed Sonogashira reaction to provide
bis(ethynylated) 12 in an excellent yield of 95% when we
[
40]
employed a protocol by M. C. Pirrung. Furthermore, we
were also able to synthesize fully desilylated compound 13
after standard deprotection with potassium carbonate in
methanol/THF (Scheme 6).
Arguably, arylations are combined like no other reaction
with the rise of modern cross-coupling procedures.[
This is especially true for boron-mediated Suzuki reactions,
which have seen a tremendous development recently.[
To apply this reaction to the synthesis of new derivatives of
29c,41]
29c,42]
[
43]
9
,9Ј-spirobifluorene we examined several conditions and
[
44]
found those published by E. Vedejs
especially useful to
provide the desired arylated compounds. By this protocol
we were able to isolate compounds 14–16 upon treatment
of some aryl boronic acid derivatives with 8, with the newly
introduced aryl groups carrying different substituents, in
good to very good yields (Scheme 7). Furthermore, we were
able to demonstrate that the methyl protecting groups could
be removed from 14 to give 17 in an excellent yield of 93%
by application of a standard demethylation procedure with
[
45]
boron tribromide.
Next we tried to prepare a diboronic
acid ester from 8 in order to gain access to another widely
applicable building block for the synthesis of elaborated spi-
robifluorenes. In fact, this kind of transformation had al-
ready been performed by other groups on various triflate
Scheme 6. Transition metal-catalyzed cyanation, alkylation, and
ethynylation of bis(triflate) (R)-8.
[
46]
[46b]
substrates. Among these, T. Ishiyama’s conditions
ap-
Next, we were able to synthesize 2,2Ј-dimethyl-9,9Ј-spiro-
[
37]
peared especially appealing to us because of their usually
bifluorene (11)
from 8 in almost quantitative yield by
Scheme 7. Synthesis of borylated (R)-18 and Suzuki cross-coupling reactions starting from (R)-8 or (R)-18.
994 www.eurjoc.org Eur. J. Org. Chem. 2005, 1991–2001
1
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Enantiomerically Pure Dissymmetric 2,2Ј-Disubstituted 9,9Ј-Spirobifluorenes
FULL PAPER
very high yields. Fortunately, this was also the case when tocols.[20] (rac)-2,2Ј-Dihydroxy-9,9Ј-spirobifluorene [(rac)-4] was
prepared in three steps from 9,9Ј-spirobifluorene (1) by a procedure
we applied these conditions to the palladium-catalyzed bo-
published by V. Prelog.[
3a,3c]
(R,R)-2,3-Dimethoxy-N,N,NЈ,NЈ-tetra-
rylation of 8 with bis(pinacolato)diboron, which provided
the desired diboronic acid ester 18[47] in almost quantitative
cyclohexylsuccindiamide (5) was prepared in four steps from (R,R)-
tartaric
(
acid.[
dppf),[ 2-(dicyclohexylphosphanyl)biphenyl [cHex
P(2-Bph)],
2
18,23–25]
1,1Ј-Bis(diphenylphosphanyl)ferrocene
yield (Scheme 7). To test 18Јs ability to act as a substrate
in Suzuki-type reactions, a demonstration coupling with a
pyrrole-protected p-iodoaniline was performed to provide
the desired bisarylated 19.
50]
[51]
[52]
[53]
[53]
[Pd
2
dba
3
·CHCl
3
],
[Pd(dppf)Cl
2
],
[Pd(PPh
3
)
2
Cl
2
],
[Pd-
[54]
[55]
(PPh
3
)
4
],
and [Pd(PtBu ) ]
3 2
were prepared by published pro-
cedures. Most solvents were dried, distilled, and stored under argon
Finally, we wanted to see whether we could gain access according to standard procedures. Reactions with air- and moist-
to a versatile dibromide derivative of 1, so we chose dimeth- ure-sensitive transition metal compounds were performed under ar-
ylated 11 and subjected it to a double electrophilic aromatic gon in oven-dried glassware by standard Schlenk techniques. Un-
less otherwise noted, quenching, extraction, and washing opera-
substitution to provide 2,2Ј-dibromo-7,7Ј-dimethyl-substi-
tuted 20 in an excellent yield of 95% (Scheme 8).[
48,49]
tions were usually performed with 50–75 mL portions of the sol-
vents or solutions given in the experimental details. Thin layer
chromatography was performed on aluminium TLC plates (Merck
silica gel 60 F254). Detection was usually by UV light (254 or
366 nm); only in the case of the detection of (R,R)-5 was the detec-
tion achieved by treatment with a 5% solution of molydophosph-
oric acid in ethanol. Products were purified by column chromatog-
1
raphy on silica gel 60 (Merck, 70–230 mesh or 230–400 mesh). H,
1
3
11
C, and B NMR spectra were recorded at 300 K in CDCl
3
solu-
tions on a Bruker Avance 500 spectrometer at 500.1, 125.8, and
Scheme 8. Synthesis of (R)-2,2-dibromo-7,7Ј-dimethyl-9,9Ј-spirobi-
fluorene [(R)-20]. Note that the stereodescriptor does not change
in these spiro compounds, although the priority of the substituents
is changed.
1
160.5 MHz, respectively. H NMR chemical shifts are reported on
the δ scale in ppm relative to residual non-deuterated solvent as
1
3
internal standard. C NMR chemical shifts are reported on the δ
1
1
scale in ppm relative to deuterated solvent as internal standard.
B
NMR chemical shifts are reported on δ scale in ppm relative to
1
9
BF
3
·Et
2
O as external standard. F NMR spectra were recorded at
solutions on a Bruker Avance 300 spectrometer at
82.4 MHz. F NMR chemical shifts are reported on the δ scale
F as external standard. IR spectra were
Conclusions
300 K in CDCl
2
3
1
9
In summary, we have been able to demonstrate that F.
Toda’s resolution of racemic 2,2Ј-dihydroxy-9,9Ј-spirobiflu-
orene (4) through clathrate formation with tartaric acid de-
in ppm relative to CCl
3
recorded from potassium bromide pellets on a Bruker Vector 22
FT-IR spectrometer in the transmission mode. The mass spectra
rivative 5 could be extended to isolate both enantiomers were taken on a Finnigan MAT 212 instrument with the MMS data
in very good yields, thereby also allowing recovery of the system and ISIS processing system (EI, CI, isobutane or ammonia)
resolving agent. By X-ray diffraction analysis of single crys- or on a Finnigan MAT 95 with the DEC-Station 5000 data system
(
3
EI, HiRes-EI, CI, HiRes-CI, isobutane or NH ). Melting points
tals of the clathrate we were also able to assign the absolute
stereochemistries of (+)- and (–)-4 for the first time. Enan-
tiomerically pure 4 could then be successfully transformed
into the corresponding bis(triflate) 8, which was sub-
sequently shown to be a versatile substrate in transition me-
were measured with a Leitz SM-Lux hot-stage microscope and are
uncorrected. Elemental analyses were carried out with a Fisons
EA1108 instrument. Specific optical rotations were measured on a
Perkin–Elmer Polarimeter 343 in a 10 cm cuvette.
tal-catalyzed cyanations, borylations, and cross-coupling (rac)-2,2Ј-Diiodo-9,9Ј-spirobifluorene [(rac)-3]: Compound (rac)-7
2
3
2
procedures resulting in sp-, sp -, and sp -sp C–C bond for- (346 mg, 1 mmol) was dissolved in a mixture of conc. aq. HCl
mations and giving rise to further elaborated enantiomer- (10 mL) and water (15 mL). After the system had been cooled to
0
°C, sodium nitrite (159 mg, 2.3 mmol) dissolved in water (5 mL)
ically pure spiro compounds 10–20, some of them carrying
different functional groups for further functionalization, in
one or two steps.
was added dropwise such that the temperature did not rise above
°C. Stirring was maintained for another 45 min after complete
0
addition. After that period, potassium iodide (664 mg, 4 mmol) dis-
solved in water (20 mL) was added and the solution was stirred for
1
6 h. The reaction mixture was extracted four times with diethyl
Experimental Section
ether and the combined organic phases were washed three times
with hydrochloric acid (3 n) and sat. aq. sodium hydrogen carbon-
ate solution. The organic solution was then further washed with
water, Na
After drying with MgSO
General Remarks: Bis(pinacolato)diboron, (4-chlorophenyl)boronic
acid, ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate,
p-iodoaniline, (4-methoxyphenyl)boronic acid, lithium hexamethyl-
disilazide solution (1 m in THF), methylmagnesium bromide solu-
2
S
2
O
3
solution (10%), water again, and finally with brine.
the solvent was removed. The dark
4
tion (3 m in diethyl ether), [Ni(dppp)Cl
fonic anhydride were purchased from ABCR, Lancaster, Sigma–
Aldrich, or Strem and were used as received. 9,9Ј-Spirobifluorene
2
], and trifluoromethanesul-
brown residue was subjected to column chromatography on silica
gel with n-hexane/ethyl acetate (4:1 v/v) as eluent to give the desired
product as an off-white solid, which can be crystallized from a mix-
was prepared in three steps from commercially available 2-amino- ture of n-hexane and dichloromethane (410 mg, 72%). M.p. 264–
biphenyl by the reaction sequence published by M. Gomberg.[
rac)-2,2Ј-Dibromo- [(rac)-2] and (rac)-2,2Ј-dinitro-9,9Ј-spirobiflu-
orene [(rac)-6] could be synthesized from 1 by F. K. Sutcliffe’s pro-
1]
1
3
266 °C. – H NMR (CDCl , 500.1 MHz): δ = 6.70 (dd, J = 7.7,
(
1.1 Hz, 2 H), 7.02 (d, J = 1.7 Hz, 2 H), 7.14 (ddd, J = 7.7, 7.7,
1.1 Hz, 2 H), 7.38 (ddd, J = 7.7, 7.7, 1.1 Hz, 2 H), 7.56 (d, J =
Eur. J. Org. Chem. 2005, 1991–2001
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1995

F. Thiemann, T. Piehler, D. Haase, W. Saak, A. Lützen
FULL PAPER
7
1
1
0
[18]
.7 Hz, 2 H), 7.70 (dd, J = 7.7, 1.7 Hz, 2 H), 7.81 (dd, J = 7.7,
.1 Hz, 2 H) ppm. – 13C NMR (CDCl
, 125.8 MHz): δ = 65.4, 93.0, methanol)}; (–)-(S)-4 [α]
20.2, 121.8, 124.0, 128.2, 128.6, 133.1, 137.1, 140.7, 141.3, 147.5,
(+)-(R)-4 [α]2
D
= +27.1 {c = 0.39, MeOH, ref.
+27.1 (c = 0.88,
20
[26]
3
D
= –26.9 (c = 0.92, MeOH). The spec-
troscopic data were in agreement with those published by V. Prelog
·+
[3c,18]
1
50.0 ppm. MS (EI): m/z (%) = 567.7 (100) [M] . HRMS (EI)
and F. Toda.
·
+
14 2 14 2 2
calcd. for [C25H I ] : 567.9185; found 567.9180. 4C25H I ·H O
(
(
R)-2,2Ј-Bis(trifluoromethylsulfoxy)-9,9Ј-spirobifluorene
[(R)-8]:
(4×612.52 + 18.02 = 2468.10): calcd. C 53.97, H 2.99; found C
R)-2,2Ј-Dihydroxy-9,9-spirobifluorene [(R)-4, 400 mg, 1.14 mmol]
dissolved in abs. dichloromethane (75 mL) was mixed with absol.
triethylamine (0.8 mL, 5.7 mmol), and the mixture was cooled to
54.26, H 2.62%.
(
rac)-2,2Ј-Diamino-9,9Ј-spirobifluorene [(rac)-7]. Method A: Com-
pound (rac)-2 (948 mg, 2 mmol), [Pd dba ·CHCl (21 mg,
mol %), and cHex P(2-Bph) (17 mg, 2.2 mol %) were mixed and
2
3
3
]
–
10 °C. Trifluoromethanesulfonic anhydride (0.5 mL, 2.9 mmol) dis-
1
2
solved in abs. dichloromethane (25 mL) was then added dropwise
over a period of 1–2 h. After complete addition the reaction mix-
ture was stirred for 1 h at –10 °C. The mixture was allowed to warm
up to room temperature and stirred at this temperature for 15 h,
after which the reaction was quenched by pouring into ice cold
hydrochloric acid (5%). The layers were separated and the aqueous
phase was extracted three times with dichloromethane. The com-
bined organic layers were washed with sat. aq. sodium hydrogen
repeatedly (usually three times) evacuated and flushed with argon.
After the mixture had been dissolved in abs. THF (10 mL), a
LiHMDS solution in THF (1 m, 4.8 mL 4.8 mmol) was added by
syringe. The reaction mixture was placed in an oil bath that had
previously been heated to 65 °C and was kept at this temperature
for 15 h. After complete consumption of the starting material the
mixture was allowed to cool to room temperature and treated with
hydrochloric acid (1 m, 20 mL). After stirring for 5 min the mixture
was neutralized with aq. sodium hydroxide and the layers were sep-
arated. The aqueous solution was extracted four times with dichlo-
romethane and the combined organic layers were washed with
2 4
carbonate solution and brine and dried with Na SO , and the sol-
vents were evaporated to dryness under reduced pressure. The re-
sulting product was further purified by column chromatography on
silica gel with hexane/ethyl acetate (5:1, v/v) as eluent. The pure
product was obtained as an amorphous, white, resinous solid
2 4
brine and dried with Na SO . After evaporation of the solvent in
vacuo the resulting residue was subjected to column chromatog-
raphy on silica gel with n-hexane/ethyl acetate (1:1 v/v) containing
20
1
(
D 3
690 mg, 98%). [α] = +4.9 (c = 1.0, THF). H NMR (CDCl ,
5
2
2
2
1
1
1
(
(
[
+
00.1 MHz): δ = 6.59 (d, J = 1.2 Hz, 2 H), 6.73 (dd, J = 7.7, 1.1 Hz,
H), 7.18 (ddd, J = 7.7, 7.7, 1.1 Hz, 2 H), 7.32 (dd, J = 8.2, 1.2 Hz,
0.5% triethylamine as eluent. The pure solid product was finally
obtained after a second chromatographic separation on silica with
toluene/ethyl acetate (5:1 v/v) containing 0.5% triethylamine as elu-
ent (315 mg 45%). Method B: Compound (rac)-6 (406 mg, 1 mmol)
was repeatedly evacuated and flushed with argon. Abs. methanol
H), 7.42 (ddd, J = 7.7, 7.7, 1.1 Hz, 2 H), 7.85 (dd, J = 7.7, 1.1 Hz,
13
H), 7.90 (d,
J
=
8.2 Hz, 2 H) ppm.
3
C NMR (CDCl ,
25.8 MHz): δ = 65.8, 117.3, 118.6 (q, J(C,F) = 321 Hz), 120.7,
21.4, 121.5, 124.1, 128.6, 129.0, 139.8, 142.0, 147.7, 149.0,
(100 mL) and Pd/C (5% Pd, 50 mg) were added. The resulting sus-
19
49.7 ppm. F NMR (CDCl
3
, 282.4 MHz): δ = –72.8 ppm. IR ν˜
ORЈ). MS (CI, isobutane) m/z (%): 613.3
100) [MH] . HRMS (CI, isobutane): calcd. for C27
·H O (2×612.52
18.02 = 1243.06): calcd. C 52.18, H 2.43; found C 52.16, H
pension was cooled in an ice bath. Sodium borohydride (1.25 g, 33
mmol) was added in several portions. After complete addition the
ice bath was removed and the mixture was stirred for 12 h at room
temperature. After that period the mixture was filtered through ce-
lite and the filtrate was evaporated to dryness. The resulting residue
was dissolved in dichloromethane (100 mL) and washed twice with
water. The combined aqueous phases were then extracted with
dichloromethane, and the combined organic layers were then
–1
cm ): 1426, 1212 (RSO
2
+
15 6 6 2
H F O S
MH]+ 613.0214; found 613.0195. 2C27
H
14
F
6
O
6
S
2
2
2
.46%.
(
S)-2,2Ј-Bis(trifluoromethylsulfoxy)-9,9Ј-spirobifluorene
[(S)-8]:
Compound (S)-8 was prepared according to the procedure given
2
0
for the synthesis of its antipode in 97% yield. [α]
D
= –5.0 (c = 1.01,
2 4
washed with water and brine and dried with Na SO . The solid
THF).
product was obtained after evaporation of the solvent and column
chromatography on silica with n-hexane/ethyl acetate (1:1 v/v) con-
taining 0.5% of triethylamine as eluent (265 mg, 76%). The analyti-
cal data were in agreement with those published by F. K. Sut-
(
R)-9,9Ј-Spirobifluorene-2,2Ј-dicarbonitrile [(R)-10]: Anhydrous
lithium chloride (62 mg, 1.46 mmol), (R)-8 (150 mg, 0.25 mmol),
Pd(PPh (22 mg, 10 mol %), and zinc cyanide (112 mg,
.95 mmol) were mixed and repeatedly evacuated and flushed with
[
0
3 4
) ]
[
20]
cliffe.
Optical Resolution of (rac)-2,2Ј-Dihydroxy-9,9Ј-spirobifluorene
(rac)-4]: Compound (R,R)-5 (1.74 g, 3.45 mmol) and (rac)-4 (1.2 g,
.45 mmol) were dissolved in ethanol (15 mL). After 12 h at room
temperature the precipitate was collected and repeatedly recrys-
argon. Abs. dimethylformamide (5 mL) was added by syringe and
the solution was heated to 120 °C for 36 h. After cooling to room
temperature the reaction mixture was partitioned between sat. aq.
sodium hydrogen carbonate solution and dichloromethane. The
phases were separated and the aqueous layer was extracted three
times with dichloromethane. The combined organic layers were
[
3
[
26]
[18]
tallized from ethanol. (m.p. 236–238 °C, ref. 238–243 °C). As
revealed by an X-ray crystal structure analysis, a 1:1 clathrate of
the (R)-4 and (R,R)-5 was obtained. Addition of aq. sodium hy-
droxide (3 n) to a solution of the clathrate in benzene and subse-
quent neutralization of the aqueous phase with aq. hydrochloric
acid allowed isolation of the pure (+)-enantiomer after extraction
with benzene. The (–)-enantiomer of 4 could be isolated from the
ethanolic filtrate of the clathrate formation after concentration in
vacuo and subsequent column chromatography of the resulting res-
idue on silica gel with n-hexane/ethyl acetate (2:1 v/v) as eluent.
The enantiomerically pure products were obtained as white solids.
Furthermore, two portions of (R,R)-5 could be recovered, the first
from the decomposition of the clathrate and the second from the
chromatography [(+)-(R)-4: 500 mg (83%, ref.[ 90%), (–)-(S)-4:
4
washed with brine, dried with MgSO , and the solvent was removed
in vacuo. The resulting residue was subjected to column
chromatography on silica gel with n-hexane/ethyl acetate (5:1, v/v)
as eluent. The pure product was obtained as a white solid (80 mg,
2
0
1
89%). M.p. 230–240 °C. [α]
D 3
= +95.4 (c = 1.00, CHCl ). H NMR
(CDCl , 500.1 MHz): δ = 6.74 (dd, J = 7.7, 1.1 Hz, 2 H), 6.95 (d,
3
J = 1.5 Hz, 2 H), 7.24 (ddd, J = 7.7, 7.7, 1.1 Hz, 2 H), 7.46 (ddd,
J = 7.7, 7.7, 1.1 Hz, 2 H), 7.70 (dd, J = 7.7, 1.5 Hz, 2 H), 7.91 (d,
1
3
J = 7.7 Hz, 2 H), 7.96 (d, J = 7.7 Hz, 2 H) ppm. C NMR
(125.8 MHz, CDCl ): δ = 65.5, 111.2, 118.7, 120.9, 121.4, 124.2,
3
127.6, 128.8, 130.0, 132.6, 139.8, 146.2, 147.8, 148.1 ppm. IR ν˜
18]
–1
(cm ): 2222 (CϵN). MS (CI, ammonia) m/z (%): 384.2 (100)
+
+
580 mg (96%), recovered (R,R)-5: 1.55 g (89%)]. M.p. 271–275 °C.
[MNH
4
18 3 4
] . HRMS (CI, ammonia): calcd. for C27H N [MNH ]
1996
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1991–2001

Enantiomerically Pure Dissymmetric 2,2Ј-Disubstituted 9,9Ј-Spirobifluorenes
FULL PAPER
14 2
H N
·ethyl acetate·n-hexane[56] (R)-2,2Ј-Diethynyl-9,9Ј-spirobifluorene [(R)-13]: (R)-2,2Ј-Bis[(trimeth-
3
(
6
84.1501; found 384.1494. 4C27
4×366.41 + 88.11 + 86.18 = 1639.93): calcd. C 86.42, H 4.79, N
.83; found C 86.81, H 4.43, N 6.61%.
ylsilyl)ethynyl]-9,9Ј-spirobifluorene [(R)-12, 50 mg, 0.108 mmol]
and potassium carbonate (105 mg, 0.757 mmol) were mixed with
THF/MeOH (1:1, 20 mL) and stirred for 3 h at room temperature.
After complete consumption of the starting material the mixture
was diluted with dichloromethane (40 mL). The solution was
(R)-2,2Ј-Dimethyl-9,9Ј-spirobifluorene [(R)-11]: Compound (R)-8
(153 mg, 0.25 mmol) and [Ni(dppp)Cl ] (14 mg, 10 mol %) were re-
2
peatedly evacuated and flushed with argon, and abs. diethyl ether
25 mL) was added by syringe. After the system had been cooled
to 0 °C, a solution of methylmagnesium bromide in diethyl ether
3 m, 1 mL, 3 mmol) was added dropwise over a period of approx.
5 min. After complete addition the reaction mixture was heated
2 4
washed with water, dried with Na SO , and concentrated in vacuo.
(
The resulting residue was subjected to column chromatography on
silica gel with n-hexane/ethyl acetate (5:1, v/v) as eluent. The pure
product was obtained as a slightly brown solid (32 mg, 92%). M.p.
(
1
2
0
1
2
40 °C (decomposition). [α]
D
= +158.7 (c = 1.06, THF). H NMR
to reflux for 24 h. The mixture was carefully quenched with water
at 0 °C and was then diluted with aq. hydrochloric acid (5%). The
aqueous layer was then extracted three times with diethyl ether, and
the combined organic phases were washed consecutively with water,
sat. aq. sodium hydrogen carbonate solution, and brine. After dry-
ing with MgSO , the solvent was removed in vacuo and the residue
4
was subjected to column chromatography on silica gel with hexane/
ethyl acetate (5:1, v/v) as eluent. The pure product was obtained as
(
CDCl , 500.1 MHz): δ = 2.96 (s, 2 H), 6.72 (dd, J = 7.7, 1.1 Hz,
3
2
2
2
H), 6.84 (d, J = 1.1 Hz, 2 H), 7.13 (ddd, J = 7.7, 7.7, 1.1 Hz,
H), 7.38 (ddd, J = 7.7, 7.7, 1.1 Hz, 2 H), 7.51 (dd, J = 8.2, 1.1 Hz,
H), 7.79 (d, J = 8.2 Hz, 2 H), 7.83 (dd, J = 7.7, 1.1 Hz, 2 H) ppm.
1
3
C NMR (125.8 MHz, CDCl
3
): δ = 65.5, 77.4, 83.8, 120.0, 120.4,
1
1
3
[
3
21.2, 124.1, 127.8, 128.1, 128.5, 132.1, 140.9, 142.4, 148.2,
–
1
48.4 ppm. IR ν˜ (cm ): 2102 (CϵC). MS (CI, isobutane) m/z (%):
+
65.5 (100) [MH] . HRMS (CI, isobutane): calcd. for C29
O (364.44 + 18.02 =
82.46): calcd. C 94.03, H 4.53; found C 94.01, H 4.51%.
H
17
2
0
a white solid (84 mg, 98%). M.p. 179–182 °C. [α]
D
= +14.3 (c =
MH]+ 365.1330; found 365.1315. C29
H16·H
1
2
0
6
1
7
.61, CHCl ). H NMR (CDCl , 500.1 MHz): δ = 2.20 (s, 6 H),
3
3
.54 (s, 2 H), 6.70 (d, J = 7.7 Hz, 2 H), 7.07 (ddd, J = 7.7, 7.7,
.1 Hz, 2 H), 7.17 (m, 2 H), 7.34 (ddd, J = 7.7, 7.7, 1.1 Hz, 2 H),
(
S)-2,2Ј-Diethynyl-9,9Ј-spirobifluorene [(S)-13]: Compound (S)-13
1
3
.72 (d, J = 7.7 Hz, 2 H), 7.79 (d, J = 7.7 Hz, 2 H) ppm. C NMR
): δ = 21.5, 65.7, 119.6, 119.6, 124.0, 124.6,
27.3, 127.5, 128.5, 137.8, 139.1, 141.8, 148.9, 149.2 ppm. MS (CI,
was prepared according to the procedure given for the synthesis of
(125.8 MHz, CDCl
3
20
its antipode in 94% yield. [α]
D
= –160.0 (c = 1.02, THF).
1
+
(R)-2,2Ј-Bis(4-methoxyphenyl)-9,9Ј-spirobifluorene [(R)-14]: Com-
pound (R)-8 (153 mg, 0.25 mmol), (4-methoxyphenyl)boronic acid
isobutane) m/z (%): 345.3 (100) [MH] . HRMS (CI, isobutane):
calcd. for C27
+
H
21 [MH] 345.1643; found 345.1622. 3C27
2
H20·H O
(
2
114 mg, 0.75 mmol), [PdCl (dppf)] (10 mg, 5 mol %), and potas-
(3×344.45 + 18.02 = 1051.37): calcd. C 92.53, H 5.94; found C
sium phosphate (212 mg, 1 mmol) were mixed and repeatedly evac-
uated and flushed with argon. Abs. THF (5 mL) was then added
by syringe and the reaction mixture was heated under reflux for
9
2.15, H 6.32%.
(S)-2,2Ј-Dimethyl-9,9Ј-spirobifluorene [(S)-11]: Compound (S)-11
was prepared according to the procedure given for the synthesis of
16 h. After cooling to room temperature the reaction mixture was
its antipode in 99% yield. [α]2
R)-2,2Ј-Bis[(trimethylsilyl)ethynyl]-9,9Ј-spirobifluorene
Compound (R)-8 (150 mg, 0.25 mmol), [PdCl (PPh
.025 mmol, 10 mol %), and CuI (5 mg, 0.025 mmol, 10 mol %)
0
= –14.2 (c = 0.61, CHCl
3
).
[(R)-12]:
3 2
) ] (18 mg,
D
partitioned between sat. aq. sodium hydrogen carbonate solution
and dichloromethane. The phases were separated and the aqueous
phase was extracted three times with dichloromethane. The com-
bined organic layers were washed with water and brine, dried with
Na SO , and concentrated in vacuo. The resulting residue was sub-
2 4
jected to column chromatography on silica gel with n-hexane/ethyl
(
2
0
were mixed and repeatedly evacuated and flushed with argon. Then
abs. dimethylformamide (20 mL) and abs. triethylamine (1 mL)
were added by syringe. After the system had been stirred for 5 min
at room temperature, trimethylsilylacetylene (0.14 mL, 1 mmol)
was added by syringe and the reaction mixture was stirred for 10 h
at 90 °C. After complete consumption of the starting material the
reaction mixture was quenched with brine (20 mL), filtered through
celite, and extracted with dichloromethane. The combined organic
acetate (5:1, v/v) as eluent. The pure product was obtained as an
2
0
off-white solid (115 mg, 87%). M.p. 212–215 °C. [α]
D
= +262.1 (c
, 500.1 MHz): δ = 3.76 (s, 6 H),
.77 (dd, J = 7.7, 0.7 Hz, 2 H), 6.83 (d, J = 8.8 Hz, 4 H), 6.94 (d,
J = 1.8 Hz, 2 H), 7.10 (ddd, J = 7.7, 7.7, 0.7 Hz, 2 H), 7.36 (d, J
8.8 Hz, 4 H), 7.37 (ddd, J = 7.7, 7.7, 0.7 Hz, 2 H), 7.57 (dd, J =
.1, 1.8 Hz, 2 H), 7.85 (dd, J = 7.7, 0.7 Hz, 2 H), 7.88 (d, J =
1
=
3 3
1.01, CHCl ). H NMR (CDCl
6
=
8
8
1
1
2 4
layers were washed with water and brine, dried with Na SO , con-
1
3
centrated in vacuo, and the residue was subjected to column
chromatography on silica gel with n-hexane/ethyl acetate (5:1, v/v)
as eluent. The pure product was obtained as a white solid (120 mg,
3
.1 Hz, 2 H) ppm. C NMR (125.8 MHz, CDCl ): δ = 55.3, 66.1,
14.0, 119.9, 120.2, 122.3, 124.1, 126.4, 127.7, 127.7, 128.1, 133.5,
40.5, 140.6, 141.5, 149.1, 149.5, 159.0 ppm. MS (CI, isobutane)
m/z (%): 529.3 (100) [MH] . HRMS (CI, isobutane): calcd. for
+
5%). M.p. 180–183 °C. [α]2
0
1
9
D
= +26.0 (c = 1.00, THF). H NMR
C
39
H
29
56]
O
2
[MH]+ 529.2168; found 529.2154. 2C39
H
28
O
2
·ethyl ace-
(CDCl
3
, 500.1 MHz): δ = 0.15 (s, 18 H), 6.70 (dd, J = 7.7, 1.1 Hz,
tate[ (2×528.64 + 88.11 = 1145.39): calcd. C 85.99, H 5.63; found
2
H), 6.81 (d, J = 1.6 Hz, 2 H), 7.11 (ddd, J = 7.7, 7.7, 1.1 Hz, 2
C 86.12, H 5.79%.
H), 7.37 (ddd, J = 7.7, 7.7, 1.1 Hz, 2 H), 7.49 (dd, J = 7.7, 1.6 Hz,
2
H), 7.76 (d, J = 7.7 Hz, 2 H), 7.81 (dd, J = 7.7, 1.1 Hz, 2 H) ppm.
(
R)-2,2Ј-Bis(4-chlorophenyl)-9,9Ј-spirobifluorene [(R)-15]: Com-
pound (R)-8 (153 mg, 0.25 mmol), (4-chlorophenyl)boronic acid
94 mg, 0.6 mmol), [PdCl (dppf)] (10 mg, 5 mol %), and potassium
13
C NMR (125.8 MHz, CDCl
3
): δ = –0.1, 65.5, 94.5, 105.2, 119.8,
1
1
20.3, 122.2, 124.1, 127.6, 128.0, 128.3, 132.0, 141.0, 142.1, 148.1,
48.5 ppm. IR ν˜ (cm ): 2154 (CϵC), 732 (SiMe ). MS (CI, isobut-
3
(
2
–1
phosphate (212 mg, 1 mmol) were mixed and repeatedly evacuated
and flushed with argon. Abs. THF (5 mL) was then added by sy-
ringe and the reaction mixture was heated to reflux for 16 h. After
cooling to room temperature the reaction mixture was partitioned
between sat. aq. sodium hydrogen carbonate solution and dichloro-
methane. The phases were separated and the aqueous phase was
extracted three times with dichloromethane. The combined organic
+
ane) m/z (%): 508.8 (100) [MH] . HRMS (CI, isobutane): calcd.
for C35 : calcd.
[MH]+ 509.2120; found 509.2119. C35
C 82.62, H 6.34; found C 82.60, H 6.61%.
H33Si
2
H32Si
2
(S)-2,2Ј-Bis[(trimethylsilyl)ethynyl]-9,9Ј-spirobifluorene
[(S)-12]:
Compound (S)-12 was prepared according to the procedure given
for the synthesis of its antipode in 96% yield. [α]2
.98, THF).
0
= –25.3 (c =
D
0
layers were washed with water and brine, dried with Na
2
SO
4
, and
Eur. J. Org. Chem. 2005, 1991–2001
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1997

F. Thiemann, T. Piehler, D. Haase, W. Saak, A. Lützen
2 4
Na SO , and concentrated in vacuo. The residue was subjected to
FULL PAPER
the solvent was removed in vacuo. The residue was subjected to
column chromatography on silica gel with n-hexane/ethyl acetate
column chromatography on silica gel with n-hexane/ethyl acetate
(
(
5:1, v/v) as eluent. The pure product was obtained as a white solid
(1:2, v/v) as eluent. The pure product was obtained as an off-white
20
20
106 mg, 79%). M.p. 154–157 °C. [α]
D
= +267.9 (c = 0.97, CHCl
, 500.1 MHz): δ = 6.78 (dd, J = 7.7, 0.7 Hz, 2 H), CHCl
.94 (d, J = 1.4 Hz, 2 H), 7.13 (ddd, J = 7.7, 7.7, 0.7 Hz, 2 H), 7.26 6.76 (m, 6 H), 6.91 (d, J = 1.7 Hz, 2 H), 7.09 (ddd, J = 7.7, 7.7,
d, J = 8.4 Hz, 4 H), 7.35 (d, J = 8.4 Hz, 4 H), 7.40 (ddd, J = 7.7, 0.7 Hz, 2 H), 7.30 (d, J = 8.8 Hz, 4 H), 7.36 (ddd, J = 7.7, 7.7,
3
).
D
solid (116 mg, 93%). M.p. 163–165 °C. [α] = +259.3 (c = 0.96,
1
1
H NMR (CDCl
3
3 3
). H NMR (CDCl , 500.1 MHz): δ = 4.84 (br. s, 2 H), 6.74–
6
(
7
0
.7, 0.7 Hz, 2 H), 7.59 (dd, J = 8.1, 1.4 Hz, 2 H), 7.89 (dd, J = 7.7, 0.7 Hz, 2 H), 7.55 (dd, J = 8.2, 1.7 Hz, 2 H), 7.85 (dd, J = 7.7,
.7 Hz, 2 H), 7.92 (d, J = 8.1 Hz, 2 H) ppm. 13C NMR (125.8 MHz,
): δ = 66.1, 120.2, 120.5, 122.5, 124.1, 126.8, 127.9, 128.1,
28.3, 128.7, 133.2, 139.3, 139.7, 141.2, 141.4, 149.0, 149.5 ppm.
0.7 Hz, 2 H), 7.87 (d, J = 8.2 Hz, 2 H) ppm. C NMR (125.8 MHz,
CDCl ): δ = 66.1, 115.4, 119.9, 120.2, 122.3, 124.1, 126.4, 127.7,
13
CDCl
1
3
3
127.7, 128.3, 133,7, 140.5, 140.5, 141.5, 149.1, 149.5, 155.0 ppm.
+
+
MS (CI, isobutane) m/z (%): 537.3 (100) [MH] . HRMS (CI, isobu-
MS (CI, isobutane) m/z (%): 501.2 (100) [MH] . HRMS (CI, isobu-
2 25 2
H23Cl [MH] 537.1177; found 537.1177. tane): calcd. for C37H O
[MH]+ 501.1855; found 501.1859.
+
tane): calcd. for C37
22Cl ·ethyl acetate
C 81.22, H 4.39; found C 81.14, H 4.38%.
[56]
[56]
3
C
37
H
2
(3×537.48 + 88.11 = 1700.55): calcd.
3C37
H
24
O
2
·n-hexane
(3×500.59 + 86.18 = 1587.95): calcd. C
88.50, H 5.46; found C 88.21, H 5.42%.
(
R)-2,2Ј-Bis[4-(ethoxycarbonyl)phenyl]-9,9Ј-spirobifluorene [(R)-16]:
(R)-2,2Ј-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,9Ј-spiro-
bifluorene [(R)-18]: Anhydrous potassium acetate (147 mg,
1.5 mmol), (R)-8 (153 mg, 0.25 mmol), bis(pinacolato)diboron
Compound (R)-8 (153 mg, 0.25 mmol), ethyl 4-(4,4,5,5-tet-
ramethyl-1,3,2-dioxaborolan-2-yl)benzoate (0.15 mL, 0.58 mmol),
[PdCl
2
(dppf)] (10 mg, 5 mol %), and potassium phosphate (212 mg,
2
(140 mg, 0.55 mmol), [PdCl (dppf)] (19 mg, 10 mol %), and dppf
1
mmol) were mixed and repeatedly evacuated and flushed with
(14 mg, 10 mol %) were mixed, repeatedly evacuated, and flushed
with argon. Abs. 1,4-dioxane (5 mL) was then added by syringe and
the reaction mixture was heated to reflux for 12 h. After cooling to
room temperature the reaction mixture was partitioned between
water and dichloromethane. The phases were separated and the
aqueous phase was extracted three times with dichloromethane.
The combined organic layers were washed with brine, dried with
argon. Abs. THF (5 mL) was then added by syringe and the reac-
tion mixture was heated to reflux for 16 h. After cooling to room
temperature the reaction mixture was partitioned between sat. aq.
sodium hydrogen carbonate solution and dichloromethane. The
phases were separated and the aqueous phase was extracted three
times with dichloromethane. The combined organic layers were
washed with water and brine, dried with Na
2
SO
4
, and the solvent
2 4
Na SO , and the solvent was removed in vacuo. The residue was
was removed in vacuo. The residue was subjected to column
subjected to column chromatography on silica gel with n-hexane/
chromatography on silica gel twice, first with n-hexane/ethyl acetate
ethyl acetate (5:1, v/v) as eluent. The product was obtained as an
2
0
(5:1, v/v) and then with THF/toluene (1:1 v/v) and 5% of triethyl-
off-white solid (129 mg, 91%). M.p. 176–178 °C. [α]
3 3
0.96, CHCl ). H NMR (CDCl , 500.1 MHz): δ = 1.25 (s, 24 H),
D
= +53.1 (c =
1
amine as eluent. The pure product was obtained as a yellow solid
2
0
(
93 mg, 61%). M.p. 185–188 °C. [α]
D
= +269.1 (c = 1.02, CHCl
3
).
6.65 (dd, J = 7.7, 0.7 Hz, 2 H), 7.08 (ddd, J = 7.7, 7.3, 0.7 Hz, 2
H), 7.16 (s, 2 H), 7.34 (ddd, J = 7.7, 7.3, 0.7 Hz, 2 H), 7.84 (d, J
1
H NMR (CDCl
3
, 500.1 MHz): δ = 1.36 (t, J = 7.1 Hz, 6 H), 4.34
1
3
(q, J = 7.1 Hz, 4 H), 6.77 (dd, J = 7.7, 0.7 Hz, 2 H), 7.01 (d, J = = 7.7 Hz, 2 H), 7.85 (m, 2 H), 7.85 (d, J = 7.7 Hz, 2 H) ppm.
C
1
7
1
2
.7 Hz, 2 H), 7.14 (ddd, J = 7.7, 7.7, 0.7 Hz, 2 H), 7.40 (ddd, J = NMR (125.8 MHz, CDCl
3
): δ = 24.8, 65.9, 83.6, 119.3, 120.4,
.7, 7.7, 0.7 Hz, 2 H), 7.48 (d, J = 8.2 Hz, 4 H), 7.66 (dd, J = 8.2,
.7 Hz, 2 H), 7.89 (dd, J = 7.7, 0.7 Hz, 2 H), 7.94 (d, J = 8.2 Hz,
124.1, 127.6, 128.3, 128.3, 130.4, 134.7, 141.5, 145.0, 147.5,
1
1
149.5 ppm. B NMR (CDCl
3
, 160.5 MHz): δ = 29.5 ppm. IR ν˜
). MS (CI, ammonia) m/z (%): 586.3 (100)
NO
H), 7.96 (d, J = 8.2 Hz, 4 H) ppm. 13C NMR (125.8 MHz, (cm ): 1355 (RB(ORЈ)
–1
2
+
CDCl
3
): δ = 14.3, 60.9, 66.1, 120.3, 120.5, 122.8, 124.1, 126.9,
[MNH
[MNH
4
] . HRMS (CI, ammonia): calcd. for
C
37
H
42
B
2
4
+
1
1
27.3, 128.0, 128.2, 129.1, 129.9, 139.8, 141.1, 141.9, 145.1, 149.0,
49.4, 166.4 ppm. IR ν˜ (cm ): 1715 (C=O). MS (CI, isobutane)
4
] 586.3300; found 586.3299.
–1
+
(S)-2,2Ј-Bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9,9Ј-spiro-
bifluorene [(S)-18]: Compound (S)-18 was prepared by the pro-
cedure given for the synthesis of its antipode in 99% yield.
m/z (%): 613.2 (100) [MH] . HRMS (CI, isobutane): calcd. for
C
hexane·H
+
43
H
33
O
4
[MH]
613.2379, found 613.2380. 2C43
(2×612.71 + 86.18 + 18.02 = 1329.61): calcd. C
32 4
H O ·n-
O[
56]
2
2
0
D 3
[α] = –53.7 (c = 1.17, CHCl ).
83.11, H 6.06; found C 83.05, H 6.03%.
1
-(2,5-Dimethyl-1H-pyrrol-1-yl)-4-iodobenzene:[57]
4-Iodoaniline
(
S)-2,2Ј-Bis[4-(ethoxycarbonyl)phenyl]-9,9Ј-spirobifluorene [(S)-16]:
(
657 mg, 3 mmol), hexane-2,5-dione (0.37 mL, 3.2 mmol), and p-
Compound (S)-16 was prepared according to the procedure given
for the synthesis of its antipode in 60% yield. [α]2
0
TsOH·H O (10 mg, 0.05 mmol) were dissolved in toluene (8 mL)
2
D
= –267.6 (c =
and heated in a Dean–Stark apparatus for 3 hours. After cooling,
the reaction mixture was washed with sat. aq. sodium hydrogen
carbonate solution, five times with water, and with brine. After the
1
.10, CHCl
3
).
(R)-2,2Ј-Bis(4-hydroxyphenyl)-9,9Ј-spirobifluorene [(R)-17]: Com-
pound (R)-14 (132 mg, 0.25 mmol) was repeatedly evacuated and
flushed with argon. Abs. dichloromethane (5 mL) was then added
by syringe and the solution was cooled to –78 °C. At that tempera-
ture, a boron tribromide solution in dichloromethane (1 m, 1 mL,
4
mixture had been dried with MgSO , the solvent was removed in
vacuo and the residue was subjected to column chromatography on
silica gel with n-hexane/ethyl acetate (5:1, v/v) as eluent. The pure
product was obtained as a slightly brownish solid (871 mg, 87%).
1
1
mmol) were added by syringe. The cooling bath was removed and
M.p. 72–76 °C. H NMR (CDCl
3
, 500.1 MHz): δ = 2.02 (s, 6 H),
the mixture was stirred for 5 h at room temperature. After complete
consumption of the starting material the mixture was quenched
with aq. sodium hydroxide solution (2 n). After addition of THF
5.89 (s, 2 H), 6.95 (d, J = 8.2 Hz, 2 H), 7.78 (d, J = 8.2 Hz, 2
1
3
H) ppm. C NMR (125.8 MHz, CDCl
3
): δ = 13.0, 92.9, 106.1,
128.6, 130.1, 138.3, 138.7 ppm. MS (CI, isobutane) m/z (%): 298.1
+
+
(
(
10 mL) the mixture was acidified (pH 1–2) with hydrochloric acid
6 m) and the aqueous phase was extracted three times with dichlo-
(100) [MH] . HRMS (CI, isobutane): calcd. for C12
H13IN [MH]
298.0093, found 298.0082. 6C12 12IN·n-hexane (6×297.13 + 86.18
H
romethane. The combined organic layers were washed with water,
sat. aq. sodium hydrogen carbonate solution, and brine, dried with
= 1868.98): calcd. C 50.13, H 4.64, N 4.50; found C 50.27, H 4.44,
N 4.43%.
1998
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1991–2001

Enantiomerically Pure Dissymmetric 2,2Ј-Disubstituted 9,9Ј-Spirobifluorenes
FULL PAPER
(R)-2,2Ј-Bis[4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl]-9,9Ј-spirobifluo-
1 α
P4 22. Data collection: STOE-IPDS-diffractometer, Mo-K radia-
rene [(R)-19]: Anhydrous CsF (221 mg, 1.45 mmol), (R)-18 tion, graphite monochromator, imaging plate, crystal dimensions:
(
125 mg, 0.22 mmol), 1-(2,5-dimethyl-1H-pyrrol-1-yl)-4-iodo-
0.45×0.32×0.31 mm, T = 193 K, F(000) = 1840, Θmax = 22.45°,
–9 Ͻ h Ͻ 9; –9 Ͻ k Ͻ9 ; –59 Ͻ l Ͻ 59, 26125 measured reflections,
benzene (157 mg, 0.53 mmol), and [Pd(PtBu ] (5 mg, 4 mol %)
3 2
)
–
1
were mixed, repeatedly evacuated, and flushed with argon. Abs.
THF (5 mL) was then added by syringe and the reaction mixture
was heated to reflux for 24 h. After the system had been cooled to
room temperature, dichloromethane was added and the mixture
was washed twice with sat. aq. sodium carbonate solution. After
separation of the phases the aqueous layer was extracted with
dichloromethane. The combined organic layers were washed with
3025 independent reflections (Rint = 0.1300), μ = 0.077 mm , max.
and min. transmission 0.9764 and 0.9660. Structural analysis and
refinement: All non-hydrogen atoms were anisotropically refined
and the H atoms were inserted in the calculated positions. 2720
2
reflections I Ͼ 2σ(I) and 289 refined parameters, GOF(F ) = 1.119,
final R indices: R
tron density 0.177 and –0.225 e Å . The structures were solved
1 2
= 0.0469, wR = 0.0907, max./min. residual elec-
–
3
by direct phase determination (SHELXS-97[ ) and refined on F .
CCDC-253521 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
58]
2
2 4
brine, dried with Na SO , and the solvent was removed in vacuo.
The residue was subjected to column chromatography on silica gel
with n-hexane/ethyl acetate (5:1, v/v) as eluent. The pure product
was obtained as a white solid (90 mg, 62%). M.p. 151–154 °C.
20
1
D 3 3
[α] = +273.7 (c = 0.52 CHCl ). H NMR (CDCl , 500.1 MHz):
δ = 1.97 (s, 12 H), 5.87 (br. s, 4 H), 6.79 (dd, J = 7.7, 1.1 Hz, 2 H),
7
7
1
2
1
1
.04 (d, J = 1.6 Hz, 2 H), 7.13–7.15 (m, 6 H), 7.41 (ddd, J = 7.7,
.7, 1.1 Hz, 2 H), 7.52 (d, J = 8.2 Hz, 4 H), 7.68 (dd, J = 8.2,
.6 Hz, 2 H), 7.89 (dd, J = 7.7, 1.1 Hz, 2 H), 7.95 (d, J = 8.2 Hz, Acknowledgments
H) ppm. 13C NMR (125.8 MHz, CDCl
): δ = 13,0, 66.1, 105.7,
3
20.2, 120.5, 122.6, 124.2, 126.9, 127.6, 127.9, 128.1, 128.3, 128.8,
We thank Prof. Dr. P. Köll for providing us with excellent working
conditions. Financial support from the DFG and the Fonds der
Chemischen Industrie is gratefully acknowledged. F. T. thanks the
Heinz Neumüller Stiftung, Oldenburg, for a doctoral grant.
38.0, 139.9, 140.1, 141.3, 141.4, 149.0, 149.5 ppm. MS (CI,
+
isobutane) m/z (%): 655.3 (100) [MH] . HRMS (CI, isobutane):
calcd. for
C
+
C
49
H
39
N
2
[MH]
655.3113; found 655.3108.
49
H
38
N
2
·dichloromethane·2 H
2
O[56] (654.84 + 84.93 + 36.04 =
7
3
75.81): calcd. C 77.41, H 5.72, N 3.61; found C 77.34, H 5.95, N
.29%.
[
1] R. G. Clarkson, M. Gomberg, J. Am. Chem. Soc. 1930, 52,
2881–2891.
(
R)-2,2Ј-Dibromo-7,7Ј-dimethyl-9,9Ј-spirobifluorene [(R)-20]: Com-
[2] A CAS inquiry on November 4, 2004 found that more than
1000 derivatives of 9,9Ј-spirobifluorene have been described in
more than 350 publications so far. It has been especially the
last few years (2000–2004), however, that have witnessed a tre-
mendous development of this class of compounds, with 120
patents filed and in total more than 220 publications published.
pound (R)-11 (120 mg, 0.35 mmol) was dissolved in dichlorometh-
ane (4.5 mL), and iron(iii) chloride hexahydrate (0.3 mg,
0
.3 mol %) was added. The flask was covered with aluminium foil
to protect the reaction from light. Bromine (38 μL, 119 mg,
.74 mmol) dissolved in dichloromethane (0.5 mL) was then added
0
[
3] a) G. Haas, V. Prelog, Helv. Chim. Acta 1969, 52, 1202–1218;
b) V. Prelog, Pure Appl. Chem. 1978, 50, 893–904; c) V. Prelog,
D. Bedekovi c´ , Helv. Chim. Acta 1979, 62, 2285–2302; d) K.
Neupert-Laves, M. Dobler, Helv. Chim. Acta 1981, 64, 1653–
1662; e) W. Bussmann, W. Simon, Helv. Chim. Acta 1981, 64,
2101–2108; f) V. Prelog, S. Mutak, Helv. Chim. Acta 1983, 66,
and the mixture was stirred for 24 h. After cooling, the mixture
was washed consecutively with sat. aq. sodium hydrogen carbonate
solution (10 mL), with sat. aq. sodium thiosulfate solution (10 mL),
2 4
and water (10 mL), dried with Na SO , and the solvent was re-
moved in vacuo. The resulting residue was subjected to column
chromatography on silica gel with n-hexane/ethyl acetate (5:1, v/v)
as eluent. The pure product was obtained as a white solid (167 mg,
2274–2278; g) M. Dobler, M. Dumi c´ , M. Egli, V. Prelog, An-
gew. Chem. 1985, 97, 793–794; Angew. Chem. Int. Ed. Engl.
1
1
985, 24, 792–794; h) M. Egli, M. Dobler, Helv. Chim. Acta
986, 69, 626–631; i) V. Prelog, M. Kova cˇ evi c´ , M. Egli, Angew.
9
5%). Suitable single crystals to perform an X-ray crystal structure
[49]
20
analysis were obtained from n-hexane. M.p. 241–246 °C. [α]
+
(
2
7
=
1
(
D
=
Chem. 1989, 101, 1173–1178; Angew. Chem. Int. Ed. Engl. 1989,
1
19.2 (c = 0.77, CHCl
3 3
). H NMR (CDCl , 500.1 MHz): δ = 2.21
2
8, 1147–1152.
s, 6 H), 6.98 (s, 2 H), 6.80 (d, J = 1.7 Hz, 2 H), 7.18 (d, J = 7.7 Hz,
[
4] a) V. Alcázar Montero, L. Tomlinson, K. N. Houk, F. Dieder-
ich, Tetrahedron Lett. 1991, 32, 5309–5312; b) V. Alcázar, J. R.
Morán, F. Diederich, Isr. J. Chem. 1992, 32, 69–77; c) V. Al-
cázar, F. Diedrich, Angew. Chem. 1992, 104, 1503–1505; Angew.
Chem. Int. Ed. Engl. 1992, 31, 1521–1523; d) J. Cuntze, L. Ow-
ens, V. Alcázar, P. Seiler, F. Diederich, Helv. Chim. Acta 1995,
78, 367–390; e) B. Winter-Werner, F. Diedrich, V. Gramlich,
Helv. Chim. Acta 1996, 79, 1338–1360; f) J. Cuntze, F. Diede-
rich, Helv. Chim. Acta 1997, 80, 897–911; g) P. Lustenberger,
E. Martinborough, T. Mordasini Denti, F. Diederich, J. Chem.
Soc. Perkin Trans. 2 1998, 747–761; h) D. K. Smith, F. Diede-
rich, Chem. Commun. 1998, 2501–2502; i) D. K. Smith, A.
Zingg, F. Diederich, Helv. Chim. Acta 1999, 82, 1225–1241; j)
F. Diederich, B. Felber, Proc. Natl. Acad. Sci. USA 2002, 99,
H), 7.47 (dd, J = 7.7, 1.7 Hz, 2 H), 7.64 (d, J = 7.7 Hz, 2 H),
.68 (d, J = 7.7 Hz, 2 H) ppm. 13C NMR (125.8 MHz, CDCl
): δ
21.5, 65.4, 119.9, 120.9, 121.1, 124.7, 127.2, 129.1, 131.0, 138.0,
38.5, 140.8, 148.1, 150.1 ppm. MS (CI, isobutane) m/z (%): 501.0
3
+
79
+
79
67) [MH] containing 2× Br, 503.0 (100) [MH] containing Br
81
+
81
and Br, 501.0 (45) [MH] containing 2× Br. HRMS (CI, isobut-
79
+
ene): calcd. for C27
18Br ·H O (502.24 + 18.02 = 520.26): calcd. C 62.33, H 3.87;
found C 62.33, H 3.67%.
2
H18 Br [MH] 500.9854; found 500.9851.
C
27
H
2
2
(S)-2,2Ј-Dibromo-7,7Ј-dimethyl-9,9Ј-spirobifluorene [(S)-20]: Com-
pound (S)-20 was prepared according to the procedure given for
the synthesis of its antipode in 94% yield. [α]2
CHCl ).
0
= –19.5 (c = 0.29,
D
4778–4781.
3
[5] a) M. Czugler, J. J. Stezowski, E. Weber, J. Chem. Soc. Chem.
Commun. 1983, 154–155; b) E. Weber, J. Ahrendt M. Czugler,
I. Csöregh, Angew. Chem. 1986, 98, 719–721; Angew. Chem.
Int. Ed. Engl. 1986, 25, 746–748; c) G. Das, A. D. Hamilton,
Tetrahedron Lett. 1997, 38, 3675–3678; d) J. V. Hernández, M.
Almaraz, C. Raposo, M. Martín, A. Lithgow, M. Crego, C.
X-ray Crystallographic Study of the Clathrate Formed from (R)-4
and (R,R)-5: Crystal data: C55 , M = 853.11, a =
.1776(6), b = 9.1776(6), c = 55.718(6) Å, α = β = γ = 90°, V =
H
68
N
2
O
6
r
9
4
3
–3
693.1(6) Å , Z = 4, ρcalcd. = 1.207 mgm , tetragonal, space group
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1991–2001
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1999

F. Thiemann, T. Piehler, D. Haase, W. Saak, A. Lützen
FULL PAPER
Caballero, J. R. Morán, Tetrahedron Lett. 1998, 39, 7401–7404;
e) A. Tejeda, A. I. Oliva, L. Simón, M. Grande, C. Caballero,
J. R. Morán, Tetrahedron Lett. 2000, 41, 4563–4566.
[15] N. Harada, H. Ono, T. Nishiwaki, H. Uda, J. Chem. Soc.
Chem. Commun. 1991, 1753–1755.
[16] a) D. Worsch, F. Vögtle, Top. Curr. Chem. 1987, 140, 21–41; b)
F. Toda, Top. Curr. Chem. 1987, 140, 43–69.
[17] Resolution of 2,2Ј-dihydroxy-1,1Ј-binaphthyl, e. g.: a) K.
Tanaka, T. Okada, F. Toda, Angew. Chem. 1993, 105, 1266–
1267; Angew. Chem. Int. Ed. Engl. 1993, 32, 1147–1148; b) Q.-
S. Hu, D. Vitharana, L. Pu, Tetrahedron: Asymmetry 1995, 6,
2123Ϫ2126; c) A. Lützen, F. Thiemann, S. Meyer, Synthesis
2002, 2271–2277.
[
6] a) J. M. Tour, R. Wu, J. S. Schumm, J. Am. Chem. Soc. 1990,
1
12, 5662–5663; b) J. M. Tour, R. Wu, J. S. Schumm, J. Am.
Chem. Soc. 1991, 113, 7064–7066; c) J. Guay, A. Diaz, R. Wu,
J. M. Tour, J. Am. Chem. Soc. 1993, 115, 1869–1874; d) R. Wu,
J. S. Schumm, D. L. Pearson, J. M. Tour, J. Org. Chem. 1996,
6
1, 6906–6921; e) U. Bach, K. De Cloedt, H. Spreitzer, M.
Grätzel, Adv. Mater. 2000, 12, 1060–1063; f) J. Pei, J. Ni, X.-
H. Zhou, X.-Y. Cao, Y.-H. Lai, J. Org. Chem. 2002, 67, 8104–
[18] F. Toda, K. Tanaka, J. Org. Chem. 1988, 53, 3607–3609.
[19] In ref.[
16b]
8
113; g) C.-c. Wu, T.-L. Liu, W.-Y. Hung, Y.-T. Lin, K.-T.
Wong, R.-T. Chen, Y.-M. Chen, Y.-Y. Chien, J. Am. Chem. Soc.
003, 125, 3710–3711.
F. Toda also reported on an approach to resolve
racemic 2,2Ј-dihydroxy-9,9Ј-spirobifluorene (4) through clath-
rate formation with (–)-sparteine. Unfortunately, the experi-
mental details were never published except for a patent that
was filed on the use of enantiomerically pure 4 to resolve race-
mic sparteine (F. Toda, (Nippon Steel Chemical Co., Ltd., Ja-
pan), JP-A2–61268633, 1986 [Chem. Abstr. 1986, 106, 195559]).
However, we were not successful when we tried to apply the
described method for the resolution of 4 with enantiomerically
pure (–)-sparteine.
2
[
7] a) D. S. Reddy, C.-F. Shu, F.-I. Wu, J. Polym. Sci. Part A: Po-
lym. Chem. 2002, 40, 262–268; b) C.-H. Chou, D. S. Redy, C.-
F. Shu, J. Polym. Sci. Part A: Polym. Chem. 2002, 40, 3615–
3
621; c) S.-C. Wu, C.-F. Shu, J. Polym. Sci. Part A: Polym.
Chem. 2003, 41, 1160–1166; d) C.-H. Chen, C.-F. Shu, J. Po-
lym. Sci. Part A: Polym. Chem. 2004, 42, 3314–3322.
[
8] Some recent examples: a) N. Johansson, D. A. dos Santos, S.
Guo, J. Cornil, M. Fahlman, J. Salbeck, H. Schenk, H. Arwin,
J. L. Brédas, W. R. Salanek, J. Chem. Phys. 1997, 107, 2542–
[
20] a) F. K. Sutcliffe, H. M. Shahidi, D. Patterson, J. Soc. Dyers
Colour. 1978, 94, 306–309; b) J. H. Weisburger, E. K. Weis-
burger, F. E. Ray, J. Am. Chem. Soc. 1950, 72, 4253–4255.
21] X. Huang, S. L. Buchwald, Org. Lett. 2001, 3, 3417–3419.
22] F. K. Sutcliffe and J. H. Weisburger were also able to prepare
2
549; b) N. Johansson, J. Salbeck, J. Bauer, F. Weissörtel, P.
[
[
Bröms, A. Andersson, W. R. Salaneck, Adv. Mater. 1998, 10,
1
136–1141; c) R. E. Martin, F. Diederich, Angew. Chem. 1999,
7
through reduction of 6; however, they used hydrazine or iron
111, 1440–1469; Angew. Chem. Int. Ed. 1999, 38, 1350–1377;
and hydrochloric acid as reducing agents, respectively (see
d) F. Steuber, J. Staudigel, M. Stössel, J. Simmerer, A. Win-
ref.[ ).
20]
nacker, H. Spreitzer, F. Weissörtel, J. Salbeck, Adv. Mater. 2000,
[
[
23] L. F. Tietze, T. Eicher, Reaktionen und Synthese im organisch-
1
2, 130–133; e) W.-L. Yu, J. Pei, W. Huang, A. J. Heeger, Adv.
nd
chemischen Praktikum,
pp. 446–451.
2
ed., Thieme, Stuttgart, 1991,
Mater. 2000, 12, 828–831; f) Y.-H. Kim, D.-C. Shin, S.-H. Kim,
C.-H. Ko, H.-S. Yu, Y.-S. Chae, S.-K. Kwon, Adv. Mater. 2001,
24] K. Shishido, K. Takahashi, K. Fukumoto, T. Kametani, T.
13, 1690–1693; g) S. Setayesh, A. C. Grimsdale, T. Weil, V. En-
Honda, J. Org. Chem. 1987, 52, 5704–5714.
kelmann, K. Müllen, F. Meghdadi, E. J. W. List, G. Leising, J.
Am. Chem. Soc. 2001, 123, 946–953; h) C. D. Müller, A. Fal-
cou, N. Reckefuss, M. Rojahn, V. Wiederhirn, P. Rudati, H.
Frohne, O. Nuyken, H. Becker, K. Meerholz, Nature 2003, 421,
[25] I. Felner, K. Schenker, Helv. Chim. Acta 1970, 53, 754–763.
[26] These values were obtained in repeated attempts and were
found to be identical no matter whether the clathrate had been
recrystallized twice or even more often before it was dissolved
again to give (R)-4 and (R,R)-5. Furthermore, the melting
point of the clathrate was found to be constant after two
crystallizations and corresponds well to that published by F.
Toda.
829–833; i) H. Lee, J. Oh, Y. Chu, J.-I. Lee, S. H. Kim, Y. S.
Yang, G. H. Kim, L.-M. Do, T. Zyung, J. Lee, Y. Park, Tetrahe-
dron 2003, 59, 2773–2779; j) C.-C. Wu, Y.-T. Lin, K.-T. Wong,
R.-T. Chen, Y.-Y. Chien, Adv. Mater. 2004, 16, 61–65.
[
9] a) A. Osuka, K. Ida, K. Maruyama, Chem. Lett. 1989, 741–
[
27] a) R. S. Cahn, C. Ingold, V. Prelog, Angew. Chem. 1966, 78,
7
44; b) C. Poriel, Y. Ferrand, P. Le Maux, J. Rault-Berthelot,
4
13–447; Angew. Chem. Int. Ed. Engl. 1966, 5, 385–415; b)
G. Simonneaux, Tetrahedron Lett. 2003, 44, 1759–1761; c) C.
Poriel, Y. Ferrand, P. Le Maux, J. Raul-Berthelot, G. Simon-
neaux, Chem. Commun. 2003, 1104–1105; d) C. Poriel, Y. Fer-
rand, P. Le Maux, C. Paul, J. Raul-Berthelot, G. Simonneaux,
Chem. Commun. 2003, 2308–2309; e) C. Poriel, Y. Ferrand, P.
Le Maux, G. Simonneaux, Synlett 2003, 71–74; f) C. Poriel, Y.
Ferrand, S. Juillard, G. Simonneaux, Tetrahedron 2004, 60,
E. L. Eliel, S. H. Wilen, Stereochemistry of Organic Compounds,
Wiley, New York, 1994, pp. 1138–1142.
[
28] A. Binz, O. v. Schickh, Ber. Dtsch. Chem. Ges. 1935, 68, 315–
324.
[
29] a) K. Ritter, Synthesis 1993, 735–762; b) N. Miyaura (Ed.),
Cross-Coupling Reactions – A Practical Guide (Topics, in: Cur-
rent Chemistry, Vol. 219), Springer-Verlag, Berlin 2002; c) A.
Suzuki “The Suzuki Reaction with Arylboron Compounds in Ar-
ene Chemistry” in “Modern Arene Chemistry” (Ed.: D. Astruc),
Wiley-VCH, Weinheim 2002, pp. 53–106; d) J. F. Hartwig, Pal-
ladium-Catalysed Amination of Aryl Halides and Sulfonates in
Modern Arene Chemistry, D. Astruc (Ed.), Wiley-VCH,
Weinheim 2002, pp. 107–168.
1
45–158; g) C. Poriel, Y. Ferrand, P. Le Maux, J. Raul-Ber-
thelot, G. Simonneaux, Inorg. Chem. 2004, 43, 5086–5095.
10] a) F. Wu, E. C. Riesgo, R. P. Thummel, A. Juris, M. Hissler,
A. El-ghayoury, R. Ziessel, Tetrahedron Lett. 1999, 40, 7311–
[
[
7314; b) A. Juris, L. Prodi, A. Harriman, R. Ziessel, M. Hissler,
A. El-ghayoury, F. Wu, E. C. Riesgo, R. P. Thummel, Inorg.
Chem. 2000, 39, 3590–3598.
[30] A. Abad, C. Agulló, A. C. Cunat, R. H. Perni, Tetrahedron:
Asymmetry 2000, 11, 1607–1615.
11] a) U. Bach, D. Lupo, P. Comte, J. E. Moser, F. Weissörtel, J.
Salbeck, H. Spreitzer, M. Grätzel, Nature 1998, 395, 583–585;
b) H. Tian, B. Chen. P.-H. Liu, Chem. Lett. 2001, 990–991;
c) I. Franco, S. Tretiak, J. Am. Chem. Soc. 2004, 126, 12130–
[
31] Parallel to our work, T. Fujita and K. Suyama also succeeded
in the preparation of (rac)-8 and filed a patent: T. Fujita, K.
Suyama (Toray Industries, Inc.), JP-A2–2004155732, 2004;
1
2140.
12] J.-H. Fournier, T. Maris, J. D. Wuest, J. Org. Chem. 2004, 69,
762–1775.
13] C. A. Schalley, A. Lützen, M. Albrecht, Chem. Eur. J. 2004, 10,
072–1080.
[
Chem. Abstr. 2004, 141, 6930].
32] S. Cacchi, G. Fabrizi, A. Goggiamani, Org. Lett. 2003, 5, 4269–
272.
[
[
[
[
1
4
[
33] J.-S. Yang, K. Kondo, Y. Murakami, Collect. Czech. Chem.
1
Commun. 2000, 65, 549–554.
[
36]
14] A. Lützen, M. Hapke, J. Griep-Raming, D. Haase, W. Saak,
[34] Besides the successfully employed procedure of K. C. Rice
Angew. Chem. 2002, 114, 2190–2194; Angew. Chem. Int. Ed.
2002, 41, 2086–2089.
we also tested some other Pd/phosphane systems and some
other cyanides with regard to their performance in this reac-
2000
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1991–2001

Enantiomerically Pure Dissymmetric 2,2Ј-Disubstituted 9,9Ј-Spirobifluorenes
FULL PAPER
tion. However, neither S. P. Maddaford’s protocol with
2
Pd (PtBu ], Zn(CN) , and Zn in DMF (no conversion of 8:
[46] a) K. Ishihara, S. Kondo, H. Yamamoto, Synlett 2001, 1371–
1374; b) T. Ishiyama, K. Ishida, N. Miyaura, Tetrahedron 2001,
57, 9813–9816.
[
2
3
)
2
J. Ramnauth, N. Bhardwaj, P. Renton, S. Rakhit, S. P. Madda-
ford, Synlett 2003, 2237–2239), nor K. Takagi’s procedure em-
[47] Racemic 18 has recently been prepared from (rac)-2: W.-J.
Shen, R. Dodda, C.-C. Wu, F.-I. Wu, T.-H. Liu, H.-H. Chen,
C.-H. Chen, C.-F. Shu, Chem. Mater. 2004, 16, 930–934.
[48] We again employed F. K. Sutcliffe’s protocol (ref.[ ). However,
the yields in this case were found to be even higher than with
unsubstituted 1.
[49] We obtained single crystals suitable to perform an X-ray dif-
fraction analysis, but we were not able to solve this structure
because the bromo and the methyl substituents happened to be
isosteric and were therefore found to be statistically distributed,
not allowing assignment of the stereochemistry of the com-
pound, although an unambiguous specific optical rotation was
observed.
2 3 3
ploying [Pd (dba) ·CHCl ], dppf, and KCN in NMP (no for-
mation of 10, but only hydrolysis of 8: K. Takagi, K. Sasaki,
Y. Sakakibara, Bull. Chem. Soc. Jpn. 1991, 64, 1118–1121), nor
the use of [Ni(PPh ) Br ], PPh , Zn, and KCN in acetonitrile
3 2 2 3
20]
(
no formation of 10, but only hydrolysis of 8: K. Takagi, Y.
Sakakibara, Chem. Lett. 1989, 1957–1958) proved effective.
[
35] Racemic 10 had already been prepared by F. K. Sutcliffe from
[
20a]
(
rac)-2 (see ref.
).
[
[
36] H. Kubota, K. C. Rice, Tetrahedron Lett. 1998, 39, 2907–2910.
37] Racemic 11 had already been prepared in another way by V.
[
3c]
Prelog (see ref. ).
[
[
38] D. Xiao, Z. Zhang, X. Zhang, Org. Lett. 1999, 1, 1679–1681.
39] Sonogashira-type cross couplings involving triflates are also re-
ferred to as Cacchi coupling reactions; see, for example, S. Cac-
chi, Synthesis 1986, 320–322.
[50] J. D. Unruh, J. R. Christenson, J. Mol. Catal. 1982, 14, 19–34.
[51] J. P. Wolfe, R. A. Singer, B. H. Yang, S. L. Buchwald, J. Am.
Chem. Soc. 1999, 121, 9550–9561.
[52] M. Schlosser, Organometalics in Synthesis – A Manual, John
Wiley & Sons, New York, 1997, p. 448.
[
40] M. C. Pirrung, L. Fallon, J. Zhu, Y. R. Lee, J. Am. Chem. Soc.
2001, 123, 3638–3643.
[
41] a) K. Tamao, T. Hiyama, E. Negishi, 30 years of the cross- [53] L. Brandsma, S. F. Vasilevsky, H. D. Verkruijsse, Application of
coupling reaction, J. Organomet. Chem. 2002, 653, 1–301; b)
A. de Meijere, F. Diederich, Metal-Catalyzed Cross-Coupling
Reactions, Wiley-VCH, Weinheim, 2004.
Transition Metal Catalysts in Organic Synthesis, Springer,
Berlin, 1999.
[54] D. R. Coulson, Inorg. Synth. 1990, 121–124.
[
42] a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457–2483; b)
F. Bellina, A. Carpita, R. Rossi, Synthesis 2004, 2419–2440.
43] a) A. F. Littke, C. Dai, G. C. Fu, J. Am. Chem. Soc. 2000, 122,
[55] C. Dai, G. C. Fu, J. Am. Chem. Soc. 2001, 123, 2719–2724.
[56] The solvents found to be present in the samples of the elemen-
tal analyses were, of course, also found in the NMR analyses.
[57] Although this compound was described as a reactant by O.
Pushechnikow et al. (O. Pushechnikov, S. P. Ivonin, A. A. Chai-
kovskaya, T. N. Kudrya, V. V. Pirozhenko, A. A. Tolmachev,
Chem. Heterocycl. Comp. 1999, 35, 1313–1318), its synthesis
and characterization have not been described so far.
[58] G. M. Sheldrick, SHELXL-97, Program for Structure Solu-
tions, University of Göttingen, 1997.
[
4
020–4028; b) O. Takahashi, M. Kameda, K. Maruoka, J. Am.
Chem. Soc. 2003, 125, 5139–5151; c) M. Leclerc, J.-F. Morin
Sidley Austin Brown & Woods LLP), US A1 200309288,
(
2
003]. [Chem. Abstr. 2003, 138, 369682].
[
[
44] E. Vedejs, D. A. Barda, Org. Lett. 2000, 2, 1033–1035.
45] a) E. H. Vickery, L. F. Pahler, E. J. Eisenbraun, J. Org. Chem.
1
979, 44, 4444–4446; b) M. V. Bhatt, S. U. Kulkarni, Synthesis
1
983, 249–282.
Received: November 11, 2004
Eur. J. Org. Chem. 2005, 1991–2001
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2001