Benzoannelated cis,cis,cis,trans- [5.5.5.6]fenestranes: Syntheses, base lability, and flattened molecular structure of strained epimers of the all-cis series

Article abstract of DOI:10.1002/1521-3765(20010803)7:15<3387::AID-CHEM3387>3.0.CO;2-6

Tribenzofenestranes possessing the strained cis,cis,cis,trans-[5.5.5.6]-fenestrane skeleton have been synthesized from cis-2,6-diphenylspiro[cyclohexane-1,2′-indane]-1′,3′-diols by two-fold cyclodehydration, in striking analogy to the strategy used previo

Full text of DOI:10.1002/1521-3765(20010803)7:15<3387::AID-CHEM3387>3.0.CO;2-6

FULL PAPER
Benzoannelated cis,cis,cis,trans-[5.5.5.6]Fenestranes:
Syntheses, Base Lability, and Flattened Molecular Structure of
Strained Epimers of the all-cis Series
Björn Bredenkötter,[a] Ulrich Flörke,[b] and Dietmar Kuck*[a]
Abstract: Tribenzofenestranes possess-
ing the strained cis,cis,cis,trans-[5.5.5.6]-
fenestrane skeleton have been synthe-
sized from cis-2,6-diphenylspiro[cyclo-
hexane-1,2'-indane]-1',3'-diols by two-
fold cyclodehydration, in striking anal-
ogy to the strategy used previously to
construct the stereoisomeric all-cis-tri-
benzo[5.5.5.6]fenestranes from the cor-
responding trans-diphenylspirodiols. In
this manner, both of the parent hydro-
carbons, all-cis-tribenzo[5.5.5.6]fenestrane
3 and cis,cis,cis,trans-tribenzo[5.5.5.6]fe-
nestrane 4, have been made accessible
from the spirodiketones 5 and 6, respec-
tively. The C6-functionalized derivatives
of 4Ðcis,cis,cis,trans-fenestranol 9 and
cis,cis,cis,trans-fenestranone 12Ðwere
prepared through cis-diphenylspirotriol
8 and cis-diphenyldispiroacetaldiol 11,
by using the same strategy. The cis,cis,-
cis,trans-[5.5.5.6]fenestrane framework
readily epimerizes to the more stable
all-cis isomers under basic conditions,
but is stable under neutral or acidic
conditions. For example, cis,cis,cis,trans-
fenestranone 12 yielded all-cis fenes-
trane 3 under Wolff ± Kishner condi-
tions, but cis,cis,cis,trans-isomer 4 under
Clemmensen conditions. Epimerization
was also circumvented by radical-in-
duced desulfurization of fenestrane di-
thiolane 15 with nBu3SnH/AIBN, pro-
ducing 4 in excellent yields. A single-
crystal X-ray structure analysis of 4
revealed that, in accordance with force
field and semi-empirical MO calcula-
tions, the extra strain of the benzoanne-
lated
cis,cis,cis,trans-[5.5.5.6]fenestra-
triene
framework
[Estrain(4)
1
Estrain(3) ˆ 46 kJmol ] is due both to
the almost perfect boat conformation of
the six-membered ring and to consider-
able bond angle widening at the central,
non-bridged C4b C15d C11b unit
(1218). H/D exchange experiments with
the cis,cis,cis,trans hydrocarbon 4 under
basic conditions demonstrated that the
strain-induced epimerization to 3 occurs
through direct deprotonation of the
ªepimericº benzylic bridgehead C7a H
bond, which was found to be more acidic
than the two C H bonds at the benzhy-
drylic bridgeheads.
Keywords: C H acidity ´ cyclode-
hydration ´ fenestranes ´ polycycles
´ strained molecules
of fenestrane chemistry[3] remain unexplored experimental-
ly.[4] As far as the strained stereoisomers of the most stable all-
cis fenestranes are concerned, a few small-ring cis,cis,cis,trans
isomers of the [4.5.5.5]fenestrane series are known, synthe-
sized by photoinduced [2 ‡ 2] cycloaddition or by Claisen
rearrangement of suitable precursors.[5±7] However, except for
a particular polycondensed derivative reported recently,[8] no
normal ring [m.n.o.p]fenestranes (m, n, o, p ˆ 5 and/or 6)
containing a trans-fused bicyclic subunit are known exper-
imentally to date.[9] However, extensive computational work
has been published on stereoisomeric [5.5.5.5]fenestranes[2, 3]
and also on [6.6.6.6]fenestranes,[1] demonstrating that the
strain of the trans-bicyclo[3.3.0]octane (fuso-diquinane)
unit[10] and even of the trans-bicyclo[4.3.0]nonane (hydrin-
dane) unit,[11] respectively, is considerably increased by
merging them into a cis,cis,cis,trans-fenestrane skeleton.
Moreover, the calculations point to a sizeable increase in
the non-bridged C C C bond angles at the central bridge-
head atom of the [5.5.5.5]- (and smaller) fenestrane cores.
Introduction
The carbon framework of [m.n.o.p]fenestranes is defined not
only by the characteristic mutual fusion of their four rings
along all of the four neopentane C C bonds in a ªtetrafusoº-
tetracyclic framework,[1] but also by the stereochemistry of its
four peripheral bridgehead atoms.[2] Given the numerous
possibilities offered by varying the ring sizes and the relative
configuration of the bridgeheads, major areas of the potential
[a] Priv.-Doz. Dr. D. Kuck, Dr. B. Bredenkötter
Fakultät für Chemie, Universität Bielefeld
Universitätsstrasse 25, 33501 Bielefeld (Germany)
Fax : (‡49) 521-106-6417
E-mail: dietmar.kuck@uni-bielefeld.de
[b] Dr. U. Flörke
Fachbereich Chemie und Chemietechnik
Universität-Gesamthochschule Paderborn
Warburger Strasse 100, 33098 Paderborn (Germany)
Fax : (‡49) 5251-60-3423
E-mail: uf@chemie.uni-paderborn.de
Chem. Eur. J. 2001, 7, No. 15
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D. Kuck et al.
FULL PAPER
Therefore, fenestranes bearing at least one trans fusion at the
neopentane core have been of considerable interest in the
context of the planar tetracoordinate carbon problem.[12, 13]
Benzoannelated fenestranes[3a] have been shown to be
versatile substrates for exploration of the stereochemistry of
the tetrafuso-tetracyclic framework.[14, 15] A particularly chal-
lenging goal in the [5.5.5.5]fenestrane series is a strained
stereoisomer of all-cis-[5.5.5.5]fenestrindane (1),[14d, 17] in the
form of its cis,cis,cis,trans-isomer 2 (dubbed ªepi-fenestrinda-
neº[3a]). Semi-empirical calculations[3a] suggest a considerable
1
increase of strain (DEstrain ˆ 148.5 kJmol ) associated with
epimerization of one of the peripheral bridgeheads of 1, thus
generating 2. This parallels the value calculated for the
corresponding [5.5.5.5]fenestratetraenes (DEstrain ˆ 150.2 kJ
1
mol ) and significantly exceeds the increase in strain
previously calculated for the epimerization of a bridgehead
in the saturated [5.5.5.5]fenestranes (DEstrain ꢀ 79.9 kJ
1
mol ).[2, 3a, 3d] In this paper, we report on the first examples
of [5.5.5.6]fenestranes possessing a trans-fused central C C
bond, including cis,cis,cis,trans-tribenzo[5.5.5.6]fenestrane 4
Abstract in German: Tribenzofenestrane mit dem gespannten
cis,cis,cis,trans-[5.5.5.6]Fenestran-Gerüst lassen sich aus cis-
2,6-Diphenylspiro[cyclohexan-1,2'-indan]-1',3'-diolen durch
zweifache Cyclodehydrierung synthetisierenÐin überraschend
einfacher Analogie zu der Strategie, die sich beim Aufbau der
stereoisomeren all-cis-Tribenzo[5.5.5.6]fenestrane aus den ent-
sprechenden trans-Diphenylspirodiolen bewährt hat. So sind
beide Grundkörper, das all-cis-Tribenzo[5.5.5.6]-fenestran 3
und das cis,cis,cis,trans-Tribenzo[5.5.5.6]fenestran 4, aus den
entsprechenden Spirodiketonen 5 bzw. 6 zugänglich. Auf diese
Weise lassen sich auch C6-funktionalisierte Derivate von 4, wie
das cis,cis,cis,trans-Fenestranol 9 und das cis,cis,cis,trans-Fene-
stranon 12, über das cis-Diphenylspirotriol 8 bzw. das cis-
Diphenyldispiroacetaldiol 11 darstellen. Cis,cis,cis,trans-
[5.5.5.6]Fenestrane epimerisieren unter basischen Bedingun-
gen leicht zu den thermodynamisch stabileren all-cis Isomeren;
im neutralen oder sauren Milieu sind sie jedoch beständig. So
führt die Wolff ± Kishner-Reaktion von cis,cis,cis,trans-Fene-
stranon 12 zum all-cis-Fenestran 3, während die Clemmensen-
Reduktion das cis,cis,cis,trans Isomer 4 ergibt. Die Epimerisie-
rung läût sich auch durch Radikal-induzierte Desulfurierung
des Fenestran-Dithiolans 15 mit nBu3SnH/AIBN umgehen,
wobei 4 in hoher Ausbeute entsteht. Die Einkristall-Röntgen-
strukturanalyse von 4 belegt in Übereinstimmung mit Kraft-
feld- und semiempirischen MO-Rechnungen die erhöhte
Spannung des benzoannellierten cis,cis,cis,trans-[5.5.5.6]Fene-
and several C6-functionalized derivatives.[16] The solid-state
molecular structure of 4 demonstrates some detailed features
of this strained hydrocarbon framework, and H/D exchange
experiments have revealed the enhanced acidity of the
epimeric bridgehead C H bond. Although the trans-hydrin-
dene unit in 4, a stereoisomer of the known all-cis-[5.5.5.6]fen-
estrane (3),[14d, 17] is certainly less strained than the related
diquinene unit in 2, the amplification of strain induced by its
incorporation into a [5.5.5.6]fenestrane framework will be-
come obvious.
Results and Discussion
Synthesis and conformation of C6-functionalized cis,cis,cis,-
trans-tribenzo[5.5.5.6]fenestranes: Synthetic access to cis,cis,-
cis,trans-[5.5.5.6]fenestranes is simple. It is, in fact, perplex-
ingly simple, since it follows the same strategy as the synthesis
of the corresponding all-cis isomers, which was based on the
stereochemistry of spirotriketone
5
(Scheme 1).[14d, 17, 18]
1
stratrien-Gerüstes [Estrain(4) Estrain(3) ˆ 46 kJmol ], die
Whereas the spatial orientation of both of the phenyl groups
in 5 appeared to be essential to achieve the single-step
construction of the all-cis fenestrane skeleton of 7, use of the
cis-isomer 6 for this purpose seemed to be impossible since, in
this case, both of the phenyl groups point towards the same
oxo-functionalized position (C-1 or C-3) of the indane moiety.
In fact, trans-spirotriones such as 5 are, in general, the
products of kinetic control[19, 20] and formation of the more
thermodynamically stable cis-diarylspirotriones such as 6 has
to be prevented carefully. This prerequisite being fulfilled, the
twofold cyclodehydration of appropriate trans-2,6-diphenyl-
durch die nahezu ideale Boot-Konformation des sechsglied-
rigen Ringes und die beträchtliche Aufweitung des nicht
überbrückten Winkels C4b-C15d-C11b ˆ 1218 am zentralen
Kohlenstoff-Atom hervorgerufen wird. H/D-Austauschexperi-
mente mit dem cis,cis,cis,trans-Kohlenwasserstoff 4 unter
basischen Bedingungen zeigen, dass die Spannungs-induzierte
Epimerisierung zu 3 durch direkte Deprotonierung des
¹epimerenª benzylischen Brückenkopfs C7a H erfolgt, der
weitaus acider ist als die C H-Bindungen an den beiden
benzhydrylischen Brückenköpfen.
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Fenestranes
3387±3400
Scheme 1. Construction of the all-cis-tribenzo[5.5.5.6]fenestrane frame-
work, with the trans-diaryl stereochemistry of 5 as a prerequisite.
spiro[cyclohexan-1,2'-indane]-1',3'-diols derived from
proved to be highly efficient (yield >90%).[3a, 17, 21]
5
Scheme 2. Construction of the cis,cis,cis,trans-fenestrane framework.
We have now discovered that the cis-diphenylspirotrike-
tone 6 and related compounds represent excellent starting
materials for the synthesis of strained cis,cis,cis,trans-
[5.5.5.6]fenestranes such as 4. As shown in Scheme 2, spiro-
triketone 6 may be reduced directly to a mixture of spirotriols
8, which, under acid catalysis and with a limited reaction time,
give fenestranol 9 in 73% isolated yield. Interestingly, this
compound represents the 6b-alcohol (see below); the epi-
meric 6a-fenestranol was observed in very minor amounts but
not isolated. Oxidation with CrO3/H2SO4 converted fenestra-
nol 9 into the cis,cis,cis,trans-[5.5.5.6]fenestranone 12 in good
yield. It is noteworthy that the triols 8 were found to be much
more sensitive to decomposition (presumably by further
elimination of water and subsequent oligomerization) than
the corresponding all-cis fenestranol, which essentially per-
sists under the relatively harsh cyclodehydration conditions.[17]
Therefore, the alternative route via ethylene acetal 10 and
dispiroindanediol 11Ðformed as a mixture of stereoisom-
ersÐand final cyclodehydration with concomitant hydrolysis
proved to be more convenient. In this way, fenestrane ketone
12 was obtained from 6 in an overall yield of 80%. In fact, the
efficiencies of both sequences 6 ! 12 proved to be similar, and
also about the same as those of the analogous syntheses of the
all-cis isomer of 12.[17]
reduces the C2 molecular symmetry of 7 to C1 in the case of 12.
The same reduction of symmetry holds for the parent
hydrocarbons 3 (C2) and 4 (C1), as well as for other derivatives
of 4 possessing no additional stereogenic center at C6, such as
1,3-dithiolanes 15 and 16, as is again reflected by NMR
spectroscopy (see below and Experimental Section).
It is also remarkable that reduction of 12 with lithium
aluminum hydride (Scheme 2) produces the same single
diastereomeric fenestranol, 9, that was obtained by cyclo-
dehydration of spirotriol 8. This finding indicates that steric
shielding at the diastereofacial sides of the carbonyl group in
12 is more different than presumed for a half-chair confor-
mation of the cyclohexanone ring, as was found to be present
in 7.[17] In fact, force field and semi-empirical MO calcula-
tions[22] on fenestranol 9 and fenestranone 12 suggest that the
most stable conformers adopt nearly ideal boat conformations
(Figure 1). In the case of fenestranone 12, one of the lateral
indane units efficiently suppresses the hydride transfer to the
b side of the carbonyl group and steric approach control
results in preferential hydride attack at the a side, thus
exclusively generating the 6b-fenestranol with an axial
hydroxy group (Figure 1, partb). Analysis of the vicinal
1H,1H coupling in 9 clearly corroborates the boat conforma-
tion (Figure 1, partc). Among others, the small coupling
constants of JH(4ba),H(5a) ꢀ JH(5a),H(6a) ꢀ 0 Hz and the extremely
large value of JH(7b),H(7aa) ˆ 14.0 Hz are indicative of this
conformation. The fact that the axial hydroxy group in 9
persists in the thermodynamically less favorable axial (6b)
Spectroscopic analysis of the new tribenzofenestranes 9 and
12 unequivocally confirmed their structures. In particular, the
benzhydrylic protons of ketone 12 were evident as two distinct
singlet resonances in its 1H NMR spectrum, in contrast to the
identical benzhydryl resonances of the all-cis stereoisomer 7.
Clearly, formal inversion of the relative configuration at C7a
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D. Kuck et al.
FULL PAPER
Figure 1. a) Stereoview of fenestranol 9, b) its formation by stereo-
1
controlled attack of AlH4 at 8, c) H,1H coupling within the cyclohexane
ring of 9.
Scheme 3. Reduction of the stereoisomeric ketones 7 and 12 through their
hydrazones and concomitant epimerization of the cis,cis,cis,trans-isomer 13
to the all-cis fenestrane 3.
orientation[23] under the relatively harsh acidic conditions
points to the equatorial position of the cyclohexanol func-
tionality in the precursor spirotriol 8 (cf. Scheme 2). Thus, the
C4 OH functionality in the spirotriols 8 probably survives the
cyclodehydration process and is translated into the axial
position at C6 of fenestranol 9 without intermediate acid-
induced epimerization. The boat conformation of the cyclo-
hexane ring in the cis,cis,cis,trans-tribenzo[5.5.5.6]fenestranes
1
suggested by H NMR spectroscopy and by calculations was
confirmed by single-crystal X-ray analysis of the parent
hydrocarbon 4 (see below).
Reduction of the base-labile cis,cis,cis,trans-[5.5.5.6]fenes-
trane derivatives: First attempts to remove the carbonyl
functionality from the cis,cis,cis,trans-fenestrane framework of
12 by Wolff ± Kishner reduction failed (Scheme 3). Instead of
the desired cis,cis,cis,trans-[5.5.5.6]fenestrane 4, the all-cis
isomer 3 was formed exclusively. The sensitivity of the
methine group at the C7a bridgehead toward base-catalyzed
epimerization has also been revealed by reduction of hydra-
zone 13 at low temperature.[24] This hydrazone was obtained
from the cis,cis,cis,trans-fenestrane ketone 12 without epime-
rization of the fenestrane skeleton, as shown by a control
experiment starting from the all-cis-[5.5.5.6]fenestrane ketone
(7), which furnished a different hydrazone, 14. The latter
compound was found to exhibit distinct physical and spectro-
scopic properties and the all-cis stereochemistry can be
assigned to it unambiguously. As expected, reduction of 14
also furnished the all-cis fenestrane 3.
Scheme 4. Reduction of the stereoisomeric ketones 7 and 12 through their
dithioacetals and concomitant epimerization of the cis,cis,cis,trans-isomer
15 to the all cis-fenestrane 3.
The all-cis stereoisomer 3 was also obtained in high yield
from dithioacetalization of the cis,cis,cis,trans- and the all-cis-
[5.5.5.6]fenestranones 12 and 7Ðwhich yielded the two
corresponding diastereomeric spirofenestranes 15 and 16Ð
and subsequent reduction with neutral Raney nickel[25a]
(Scheme 4). These results may be considered advantageous,
since both of the sequences furnish the all-cis-[5.5.5.6]fenes-
trane framework of 3 in good overall yields, rendering control
over the stereochemistry of the starting spirotriketones
superfluous when the all-cis fenestrane skeleton is to be
constructed. Apparently, however, either the strained cis,cis,-
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Fenestranes
3387±3400
cis,trans-fenestrane skeleton of fenestranone 12 or its deriv-
atives 13 and 15 are too labile to persist under the basic
reaction conditions so far used in attempting to generate
hydrocarbon 4.[25b]
A straightforward procedure that did allow us to reduce the
carbonyl group of 12 consisted of the radical-induced
reduction of the 1,3-dithiolane 15 with Bu3SnH and AIBN
in benzene[26] (Scheme 5). In this case, no epimerization took
below for further evidence) was also generated, as shown by
mass spectrometry and H NMR spectroscopy. Attempts to
1
separate this from 4 by chromatography failed, but hydro-
genation of the mixture over palladium on charcoal[25b]
accomplished this alternative, five-step synthesis of cis,cis,cis,-
trans-tribenzo[5.5.5.6]fenestrane 4 from cis-diphenylspirotri-
ketone 6 in good overall yield.
In view of the presence of additional unsaturation in
cis,cis,cis,trans-tribenzo[5.5.5.6]fenestrenes such as 18, it ap-
peared interesting to perform a directed 1,2-elimination of
Scheme 6. Synthesis of 4 by reduction of 9, via tosylhydrazone 17.
water from cis,cis,cis,trans-fenestranol 9. As reported earlier,
the corresponding C2-symmetrical all-cis fenestranol 22, on
being heated in a dipolar aprotic solvent (HMPT), is
converted to the all-cis-tribenzo[5.5.5.6]fenestrene 23
(Scheme 7, bottom).[17] Similar treatment of the C1-symmet-
rical fenestranol 9 produced a mixture of the three isomeric
[5.5.5.6]fenestranes 18, 19, and 20 in a ratio of 72:21:7, by
1H NMR spectroscopy (Scheme 7, top). Column chromatog-
raphy and additional HPLC yielded the pure isomers in a
ratio of 82:12:6 and enabled structure elucidation to be
accomplished. Remarkably, neither the cis,cis,trans-fused
bridgehead olefin 21 nor the all-cis isomer 23 were formed.
Scheme 5. Synthesis of 4 with retention of the cis,cis,cis,trans stereo-
chemistry.
place and the cis,cis,cis,trans-fenestrane 4 was obtained in
good yield. Not surprisingly, the stereoisomeric dithiolane 16
could also be reduced in a straightforward manner using this
method. Thus, non-basic conditions and the presence of mild
radicals do not induce epimeri-
zation of the strained cis,cis,cis,-
trans-fenestrane skeleton. In
further agreement with these
findings, the strongly acidic me-
dia present during the Clem-
mensen reduction of 12 also
allowed a highly efficient, albeit
tedious, conversion to the cis,-
cis,cis,trans-hydrocarbon 4 with-
out epimerization (Scheme 5).
A classical alternative to the
1,3-dithiolane reduction in-
volved the reduction of the
tosylate 17, which was easily
prepared from fenestranol 9
(Scheme 6). When 17 was sub-
jected to LiAlH4 reduction
in tetrahydrofuran, cis,cis,cis,-
trans-[5.5.5.6]fenestrane 4 was
formed as the major product;
however, the fenestrene 18 (see
Scheme 7. Formation of tribenzo[5.5.5.6]fenestrenes. (Note that atom numbering depends on the position of the
double bond.)
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D. Kuck et al.
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The major isomers 18 and 19 both represented D(6,7)
isomers, possessing the unperturbated cis,cis,cis,trans fusion
pattern in the [5.5.5.6]fenestrane framework. According to
force field and semi-empirical MO calculations (Table 1),[22]
18 and 19 have similar strain energies, with a slight preference
A straighforward synthesis of cis,cis,cis,trans-[5.5.5.6]fenes-
trane 4: We have also developed an independent synthesis of
4, which allowed us to circumvent the formation of stereo-
chemically labile C6-functionalized cis,cis,cis,trans-tribenzo-
fenestrane intermediates. To this end, the cyclohexanone
functionality of spirotriketone 6 had to be removed prior to
the cyclodehydration step, to furnish the target hydrocarbon 4
directly. The same strategy has been used previously by
Ten Hoeve and Wynberg in their attempts to synthesize
[6.6.6.6]- and [5.6.6.6]fenestranes.[27] We first tested this route
in experiments aimed at the conversion of trans-spirotrike-
tone 5 into all-cis-[5.5.5.6]fenestrane 3 (Scheme 8). Ironically,
this approach turned out to be non-trivial for the low-strain,
all-cis-fenestrane series. Treatment of 5 with p-toluenesulfon-
yl hydrazide in ethanol followed by reduction of the
tosylhydrazone furnished cis-diphenylspirodiketone 27 in
high yield. The same spirodiketone was obtained, using the
same method but starting from the cis-diphenylspirotriketone
6. In analogy to the partial trans ! cis isomerization previ-
ously reported to occur during the conversion of the
corresponding di(5-methylfuryl)spirotriketone,[27] we assume
that epimerization occurs in the first stepÐformation of the
cis-diphenyl tosylhydrazone 26Ðalthough the stereochemis-
try of this compound could not be determined unequivocally.
However, all attempts to suppress the trans ! cis isomer-
ization in the stepwise reduction of 5 via an isolated
tosylhydrazone failed.[28]
Table 1. Flattening of the geometry at the central carbon atom and relative
strain energies of the isomeric tribenzo[5.5.5.6]fenestrenes (by AM1 and
PM3 calculations).
Compound
Upper
non-bridged
C-C-C angle [8][a]
Lower
non-bridged
C-C-C angle [8][a]
DEstrain
[kJmol ]
1
AM1
PM3
AM1
PM3
AM1
PM3
18
19
20
21
23
119.3
120.6
115.5
126.0
110.9
120.7
120.7
115.5
124.9
110.2
119.7
117.1
112.5
124.8
110.3
117.9
117.2
112.2
125.7
109.2
‡ 62.8
‡ 60.7
‡ 66.9
‡ 65.7
0
0
‡ 141.0 ‡ 136.8
‡ 2.9 ‡ 6.7
[a] C-C-C bond angles at C15d opened to the top and bottom, respectively,
of the structures shown in Scheme 7.
1
(DEstrain
ˆ
4.2 kJmol ) for isomer 18, with the double bond
remote from the epimeric, strain-inducing bridgehead C4b.
The relative yields of 18 and 19 apparently reflect their
relative stabilities. However, the minor isomer 20, as the
D(7,7a) isomerÐthat is, a bridgehead olefinÐwas calculated
Retention of the trans orientation in the desired trans-
diphenylspirodione 24 was eventually achieved in a one-pot
procedure, by treating 5 with p-toluenesulfonyl hydrazide,
sodium cyanoborohydride, and p-toluenesulfonic acid in
dimethylformamide/sulfolane[29] (Scheme 8). Subsequent re-
duction of 24 to the corresponding spirodiols 25, which were
obtained as a mixture of stereoisomers, followed by cyclo-
dehydration, furnished the all-cis-tetrabenzo[5.5.5.6]fenes-
to be considerably more stable than 18 (DEstrain
ˆ
1
62.8 kJmol ). Obviously, removal of the proton at the
strain-inducing bridgehead in the course of a formal 1,2-H
shift in 19 is thermodynamically favorable, since it releases the
strain energy from the cis,cis,cis,trans-fenestrane skeleton. In
turn, the bridgehead olefin 21, featuring both a D(7,7a) double
bond and the strain-inducing bridgehead C4b was calculated
to be the least stable isomer
1
[DEstrain ˆ ‡138.1 kJmol ]
and, accordingly, this isomer
was not formed. Thus, it is
remarkable that the most sta-
ble isomer within the series of
cis,cis,cis,trans-[5.5.5.6]triben-
zofenestrenes is the bridge-
head olefin 19, which, accord-
ing to the calculations, is even
slightly less strained than the
all-cis-[5.5.5.6]tribenzofenes-
trene 23. As well as the rela-
tive strain energies of the five
[5.5.5.6]fenestrenes, the un-
bridged C C C bond angles
at the central carbon atoms
C15d of these olefins have
been calculated (Table 1).
These geometrical parameters
are discussed below, together
with those relating to the sa-
turated tribenzo[5.5.5.6]fenes-
Scheme 8. Directed syntheses of all-cis- and cis,cis,cis,trans-fenestranes 3 and 4, featuring prevention of
trane 4.
epimerization.
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Fenestranes
3387±3400
trane 3 in excellent yield. Selective reduction of cis-diphenyl-
spirotriketone 6 was achieved through tosylhydrazone 26 (see
above), by treatment with sodium borohydride in methanol,
or, alternatively, with catecholborane in trichloromethane,
giving the cis-diphenylspirodione 27 in good yield. Subse-
quent reduction with lithium aluminum hydride furnished
spirodiol 28, again as a mixture of diastereomers. As expected,
in analogy with the behavior of the C4-functionalized cis-
diphenylspirodiols 8 and 11 (Scheme 2), cyclodehydration of
28 furnished the cis,cis,cis,trans-tribenzo[5.5.5.6]fenestrane 4
in excellent yield and with perfect stereospecificity. In view of
our original expectation that the trans orientation of the
phenyl groups would be a conditio sine qua non, it is worth
noting (and also amusing) that the overall yields of the
stereochemically analogous four-step sequences 5 ! 3 and
6 ! 4 are almost the same (30 and 28%, respectively).
Next, we treated both the all-cis- and the cis,cis,cis,trans-
fenestranes 3 and 4 with potassium tert-butoxide in [D6]di-
methyl sulfoxide at ambient temperature (Scheme 10). Start-
ing from 3, all-cis-[11b,15b-D2]tribenzo[5.5.5.6]fenestrane 3a,
Mechanism of the base-induced cis,cis,cis,trans ! all-cis epi-
merization: Because of the facile epimerization occurring
during the reduction of fenestranone 12 and its derivatives
under basic conditions, we first suspected that the functional
group at C6 might be responsible for this effect. For example,
a-deprotonation at C7 might induce a transitory heterolytic
cleavage of the C7a C15d bond, which could give rise to
epimerization. Alternatively, the formation of a D(6,7) double
bond through enolization might contribute by allylic activa-
tion of the bridgehead C7a H bond. In fact, we found that the
cis,cis,cis,trans-fenestranone 12 could be epimerized to the all-
cis isomer 7 by treatment with potassium tert-butoxide in
DMSO at ambient temperature (Scheme 9). This conversion
Scheme 10. Selective H/D exchange in isomeric fenestranes.
with two deuterium atoms in the benzhydrylic positions
(D content >97% as determined by 1H NMR spectroscopy),
was isolated after 2 h in >90% yield. The same treatment of
the cis,cis,cis,trans isomer 4 furnished another isotopomer of
3, all-cis-[7a,11b,15b-D3]tribenzo-[5.5.5.6]fenestrane (3b),
again exhibiting complete deuterium incorporation at the
two benzhydrylic bridgeheads but also at one of the benzylic
positions. Obviously, base-induced epimerization of the
benzylic bridgehead C7a H of the strained isomer 4 is faster
than the deprotonation/reprotonation sequence involving the
benzhydrylic C H bonds of the relatively unstrained all-cis
isomer 3.
Scheme 9. Directed epimerization of cis,cis,cis,trans-fenestranone 12.
This result was clearly confirmed when the cis,cis,cis,trans-
fenestrane 4 was allowed to react with the weaker base
potassium deuteroxide in [O,O-D2]-diethylene glycol at
1808C; that is, under classical Wolff ± Kishner conditions.
After 3 h, only one of the benzylic bridgehead C H bonds had
incorporated deuterium, while none of the benzhydrylic ones
had, and all-cis-[7a-D]tribenzo[5.5.5.6]fenestrane 3c was iso-
lated as the sole all-cis isotopomer, with an isotopic purity of
>95% (1H NMR), along with unreacted 4. Forcing conditions
(2408C, >4 h) were required to convert the all-cis-[D1]
isotopomer 3c into 3b (Scheme 10).[31] Thus, H/D exchange
experiments had clearly demonstrated that the C H bond at
the epimeric bridgehead C7a of the strained cis,cis,cis,trans-
fenestrane 4 is considerably more kinetically acidic not only
than those at the benzhydrylic bridgeheads in the same
stereoisomer but also than the benzhydrylic C H bonds of the
low-strain all-cis-fenestrane 3.
has proven to be an important tool in the synthesis of
benzoannelated all-cis-fenestranes when the trans-diarylspiro-
triketones are not accessible (cf. Scheme 1).[30] However, the
aforementioned assumptions do not explain all of the
observations reported above. We therefore subjected the
cis,cis,cis,trans-fenestrane hydrocarbon 4 itself (obtained by
the independent syntheses described above) to the basic
conditions existing during Wolff ± Kishner and modified
Wolff ± Kishner reductions.
In fact, when 4 was dissolved in a solution of potassium tert-
butoxide in dimethyl sulfoxide at ambient temperature, the
all-cis-tribenzo[5.5.5.6]fenestrane 3 was formed and isolated
in almost quantitative yield. Thus, the strained hydrocarbon 4
proved to be sufficiently acidic to undergo epimerization after
its formation from the respective cis,cis,cis,trans-fenestrane
derivatives.
Chem. Eur. J. 2001, 7, No. 15
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D. Kuck et al.
FULL PAPER
Table 3. Flattening of the geometry at the central carbon atom and relative
strain energies of stereoisomeric tribenzo[5.5.5.6]fenestranes 3 and 4.
Molecular structure of cis,cis,cis,trans-tribenzo[5.5.5.6]fenes-
trane 4: Attempts to obtain single crystals from the all-cis-
tribenzo[5.5.5.6]fenestrane 3 were not successful; fortunately,
however, the cis,cis,cis,trans-isomer 4 furnished beautiful
crystals upon recrystallization from n-hexane/ethyl acetate.
Pertinent crystallographic data and selected geometrical data
are given in Table 2, Table 3, and Table 4.[32] Figure 2 illus-
trates the solid-state molecular structure of 4 as viewed from
the upper (a) face of the fenestrane core; that is, with three
bridgehead hydrogens pointing above the plane.
Compound Method aC4b-C15d-C11b aC7a-C15d-C15b DEstrain
1
[8]
[8]
[kJmol
]
4
4
X-ray
AM1
PM3
MM‡
AM1
PM3
120.8
119.4
120.0
118.7
110.2
108.8
109.3
115.5
117.8
116.5
115.8
111.7
111.1
112.9
±
‡ 49.8
‡ 43.5
‡ 38.1
0
3
0
0
MM‡
The solid-state molecular structure of 4 clearly confirms
both the relative configurations at the four peripheral bridge-
heads of the [5.5.5.6]fenestratriene framework and the boat
conformation deduced above for the corresponding fenestra-
nol 9. In fact, the cyclohexane boat in 4 is fused into the
angular triindane skeleton in such a way as to impose a rigid
and nearly perfect boat conformation.[33] As the most
remarkable geometrical parameter, the unbridged C C C
bond angles at the central carbon atom C15d of 4 are
considerably increased. In particular, aC4b-C15d-C11b is
opened to 120.8(1)8, whereas the other angle, aC7a-C15d-
C15b, is widened to 115.5(1)8 only (Table 3). These values
may be compared to those of the corresponding angles in
fenestrindane 1 (116.58)[14d] and its derivative bearing four
bromine atoms at the bridgehead positions (121.48).[3a, 34]
Table 4. C C Bond distances [pm] and C C C bond angles [8] at the
peripheral bridgeheads of cis,cis,cis,trans-[5.5.5.6]fenestrane 4, as deter-
mined by single-crystal X-ray structure analysis. The data for the ªstrainedº
bridgehead C7a are given in italics.
Bond distances [pm]
Bond angles [8]
C4b C15d
C4b C4a
C4b C5
C7a C15d
C7a C7
156.6(2)
151.1(2)
155.5(3)
153.9(2)
151.1(2)
149.7(2)
156.8(2)
152.8(2)
150.8(2)
157.9(2)
151.6(2)
150.9(2)
C4a-C4b-C5
C4a-C4b-C15d
C5-C4b-C15d
C7-C7a-C7b
C7-C7a-C15d
C7b-C7a-C15d
C11a-C11b-C1c
C11a-C11b-C15d
C11c-C11b-C15d
C15a-C15b-C15c
C15a-C15b-C15d
C15c-C15b-C15d
111.3(1)
105.2(1)
107.8(1)
122.4(1)
114.0(1)
104.1(1)
107.8(1)
102.6(1)
105.7(1)
111.3(1)
105.3(1)
105.7(1)
C7a C7b
C11b C15d
C11b C11a
C11b C11c
C15b C15d
C15b C15a
C15b C15c
Table 2. Crystal data and structure refinement for cis,cis,cis,trans-triben-
zo[5.5.5.6]fenestrane 4 (4ba,7aa,11ba,15bb)-5,6,7,7a,11b,15b-hexahydro-
4bH-dibenzo[2,3:4,5]pentaleno[1,6-jk]fluorene.
empirical formula
formula weight
T [K]
C26H22
334.44
203(2)
0.71073
monoclinic
P2(1)/c
Hence, taking both angles into account, the cis,cis,cis,trans-
[5.5.5.6]fenestrane skeleton of 4 is more flattened than the all-
cis-[5.5.5.5] congeners such as 1, but significantly less than the
sterically overcrowded fourfold bridgehead derivatives in that
series.
Unfortunately, experimental data for the all-cis-triben-
zo[5.5.5.6]fenestrane 3 are lacking, because the crystals
obtained were not suitable for X-ray analysis. However, as
also shown in Table 3, semi-empirical and force field calcu-
lations satisfactorily reproduced the widening effects found
for 4, PM3 calculations affording the closest agreement in this
case. On this basis, computation also allowed us to predict that
the all-cis-tribenzo[5.5.5.6]fenestrane 3 would be much less
flattened than the cis,cis,cis,trans-isomer 4, the unbridged
angles of the former isomer being opened by 15 ± 178 less than
those of the latter.
It may be noted that the carbon triad C4a-C15d-C11b
comprising the strongly widened angle does not contain the
strain-inducing bridgehead C7a, an observation that may
appear counterintuitive. Obviously, the extra strain induced
by the attachment of the trimethylene unit at the b position of
C7a, rather than at its a position as in 3, gives rise to bending
of the C4b bridgehead more ªdownwardsº to the fenestrane
mean plane than bending of the C7a bridgehead ªupwardsº
to it.
l [Š]
crystal system
space group
unit cell dimensions
a ˆ 9.066(1) Š
b ˆ 19.600(2) Š
c ˆ 9.930(3) Š
a ˆ 908
b ˆ 102.79(2)8
g ˆ 908
V [Š3]
1720.7(6)
Z
4
3
1calcd [Mgm
]
1.291
0.073
712
0.23 Â 0.60 Â 0.25
2.08 to 26.998
1 ꢁ h ꢁ 11,
25 ꢁ k ꢁ 1,
12 ꢁ l ꢁ 12
4718
1
absorption coefficient [mm
F(000)
crystal size [mm3]
q range for data collection
index ranges
]
reflections collected
independent reflections
completeness to q ˆ 26.998
absorption correction
refinement method
3755 [R(int) ˆ 0.0154]
99.9%
none
full-matrix,
least-squares on F2
3755/0/236
1.056
R1 ˆ 0.0451, wR2 ˆ 0.1070
R1 ˆ 0.0764, wR2 ˆ 0.1334
0.0159(18)
data/restraints/parameters
Goodness-of-fit on F2
final R indices [I > 2s(I)]
R indices (all data)
extinction coefficient
largest diff. peak and hole
A more detailed analysis of the geometry of the neopentane
core of 4 reveals that the cis,cis,cis,trans configuration gives
rise to a significant decrease in the sp3 character of the
3
0.253 and 0.181 eŠ
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Fenestranes
3387±3400
Conclusion
The directed synthesis of ben-
zoannelated cis,cis,cis,trans-
[5.5.5.6]fenestranes has been
achieved by simple condensa-
tion strategies involving acid-
catalyzed, twofold cyclodehy-
dration. The base-lability of
these strained stereoisomers of
the previously described all-cis-
[5.5.5.6]fenestranes is remarka-
ble; it gives rise to facile epi-
merization of the C H bond of
the ªinvertedº benzylic bridge-
head, generating the all-cis-
[5.5.5.6]fenestrane
skeleton.
The kinetic C H acidity of this
bridgehead is higher than that
of the benzhydrylic bridge-
heads, and epimerization oc-
Figure 2. X-ray molecular structure (ORTEP plot) of cis,cis,cis,trans-fenestrane 4.
curs through a simple deproto-
nation/reprotonation mecha-
strained bridgehead carbon atom C7a. This is most evident
from the data collected in Table 4. In particular, the average
of the C-C-C bond angles at C7a, namely 113.5(1)8, is
significantly larger than the mean of the corresponding angles
at the other peripheral bridgehead positions, namely 108.1(1)8
for C4b, 105.3(1)8 for C11b, and 107.4(1)8 for C15b. As
expected, effects on the C C bond distances within the
fenestrane core are only minor; however, one slight but
significant effect may be noted. Among the four central C C
bonds, those involving the peripheral bridgeheads possessing
ªnormalº configuration, namely C4b C15d, C11b C15d, and
C15b C15d, have virtually the same lengths, ranging from
156.6(2) to 157.9(2) pm. In contrast, the bond connecting the
strained bridgehead to the central one and thus involving the
trans ring junction, C7a C15d, is significantly shortened: to
153.9(2) pm. The two lateral C C bonds at the strained
bridgehead C7a are also shorter than the respective C C
bonds at the other benzylic bridgehead C4b: 151.1(2) pm
versus 155.5(3) pm and 149.7(2) pm versus 151.1(2) pm. All
these observations suggest that the hybridization of the C7a
atom is of partial sp2 character.
Also on the basis of the compatibility of the experimental
and computational data, the flattening effects in the triben-
zo[5.5.5.6]fenestrenes 18 ± 21 and 23 may be ascertained by
semi-empirical calculation. The data obtained by AM1 and
PM3 calculations (Table 1) clearly reflect the correlation of
strain with the flattening at the central carbon atom and
suggest that, according to the calculations, the synthetically
accessible fenestrenes 18 and 19 are actually somewhat more
flattened than fenestrane 4. The much more highly strained
nism at the benzylic bridgehead. Experimental and
computational analysis of the stereochemistry of the cis,cis,-
cis,trans-[5.5.5.6]fenestrane framework has demonstrated the
increased sp2 character of the carbon atom at the inverted
bridgehead and the limited but significant flattening of the
coordination of the central carbon atom. It is obvious from the
results presented here that attempts to construct the highly
strained cis,cis,cis,trans-[5.5.5.5]fenestranes, such as ªepi-fen-
estrindaneº 2, will have to cope with the paradox that
benzoannelation of fenestranes has opened a viable route to
these interesting polycyclic hydrocarbons but that it also
increases their chemical lability in the strained cis,cis,cis,trans-
fused stereoisomers. Thus, experimental efforts to convert
benzoannelated cis,cis,cis,trans-[5.5.5.6]fenestranes to the cis,-
cis,cis,trans-[5.5.5.5]fenestrane congeners represents a true
challenge.
Experimental Section
General procedures: Melting points (uncorrected) Electrothermal melting
point apparatus. IR spectra: Perkin ± Elmer model IR 841. 1H,13C NMR,
1H,1H COSY, and 1H,1H NOESY measurements: Bruker AM 250; TMS (as
internal standard) and Bruker DRX 500 (solvent used as internal stand-
ard). 13C NMR spectra were recorded as broad-band decoupled in
combination with the DEPT or APT technique, respectively. MS and exact
mass measurements: VG Autospec, Fisons, electronic ionization (EI,
70 eV). Perfluorokerosene (PFK) was used as a reference for exact mass
measurements. Combustion analyses: Perkin ± Elmer 240. TLC: silica gel
(Kieselgel 60 F254) on aluminum foils (Merck). Column chromatography:
silica gel (Kieselgel 60, 0.063 ± 0.200 mm, Merck and Machery ± Nagel).
cis-2,6-Diphenyl-1',3'-dihydrospiro[cyclohexane-1,2'-[2H]indene]-1',3',4-
isomer 21, which was not observed in the experiments, was
calculated to be considerably more flattened than the former
cis,cis,cis,trans isomers. Interestingly, the similarity of strain in
the stereoisomeric bridgehead olefins 20 and 23 is not
reflected in the size of the unbridged angles at the central
carbon atom.
triol (8):
A solution of spirotriketone 6 (20.0 g, 52.5 mmol) in dry
tetrahydrofuran (200 mL) was added over 3 h to a stirred suspension of
lithium aluminum hydride (4.2 g, 110 mmol) in dry THF (500 mL). The
mixture was then heated to reflux for 15 h. The major part of the solvent
was then distilled off and replaced by diethyl ether (200 mL). The mixture
was cooled with ice/water, hydrolyzed carefully by adding water, and
extracted several times with diethyl ether. The combined organic layers
Chem. Eur. J. 2001, 7, No. 15
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D. Kuck et al.
FULL PAPER
were dried with sodium sulfate and the solvent was evaporated to give an
oily residue from which a colorless precipitate (16.6 g, 82%) formed upon
addition of chloroform. This material constitutes a mixture of isomers and
may be used directly for cyclodehydration. Repeated crystallization from
chloroform gave a mixture of isomers (m.p. 238 ± 2408C), from which the
major isomer (ca. 90%) could be identified by NMR spectroscopy:
1H NMR (250 MHz, CDCl3): d ˆ7.39 ± 7.13 (m, 7H), 7.03 ± 6.73 (m, 6H),
6.65 ± 6.63 (m, 1H), 5.41 (s, 1H), 4.78 (d, J ˆ 8.1 Hz, 1H), 4.09 (dd, J ˆ 5.0,
10.8 Hz, 1H), 3.39 (dd, J ˆ 3.6, 13.7 Hz, 1H), 3.36 (dd, J ˆ 2.9, 13.7 Hz, 1H),
3.05 ± 2.90 (m, 1H), 2.79 (brs, 1H, -OH), 2.78 ± 2.63 (m, 1H), 2.38 ± 2.24 (m,
1H), 2.24 (brs, 1H, -OH), 2.04 ± 1.97 (m, 1H), 1.77 (brs, 1H, -OH);
13C NMR (62.9 MHz, CDCl3): d ˆ143.2, 142.0, 141.7, 141.3, 130.2, 128.4,
127.6, 127.2, 126.9, 125.4, 121.4, 120.9, 75.2, 74.6, 70.9, 62.6, 48.1, 46.9, 41.0,
38.7; IR (KBr): nÄ ˆ 3542, 3390, 2876, 1493, 1031, 746 cm 1; MS (EI, 70 eV):
sodium sulfate and the solvent was distilled off to give crude dispirodiole 11
(10.5 g, 93%) as a colorless mixture of two isomers (m.p. 245 ± 2488C).
Repeated recrystallization from ethyl acetate furnished a mixture of
isomers (m.p. 252 ± 2548C), from which the major isomer (ca. 90%) could
be identified by NMR spectroscopy: 1H NMR (250 MHz, CDCl3): d ˆ
7.55 ± 7.52 (m, 2H), 7.22 ± 7.09 (m, 4H), 6.97 ± 6.74 (m, 8H), 5.66 (d, J ˆ
10.0 Hz, 1H), 5.54 (d, J ˆ 9.0 Hz, 1H), 4.04 ± 3.93 (m, 4H), 3.67 (dt, J ˆ 3.3,
13.8 Hz, 2H), 3.00 (quasi-t, J ꢀ 13.3 Hz, 1H), 2.62 (quasi-t, J ꢀ 13.8 Hz,
1H), 2.17 (dt, J ˆ 2.6, 13.1 Hz, 1H), 2.14 (d, J ˆ 9.0 Hz, 1H, OH), 1.90 (dt,
J ˆ 3.1, 13.7 Hz, 1H), 1.11 (d, J ˆ 10.0 Hz, 1H, OH); 13C NMR (62.9 MHz,
CDCl3): d ˆ 144.5, 143.2, 142.1, 141.6, 131.1, 129.2, 128.8, 127.8, 127.5, 127.4,
126.3, 126.0, 124.5, 122.0, 108.7, 77.8, 77.1, 64.6, 64.5, 58.0, 47.1, 46.3, 40.0,
38.0; IR (KBr): nÄ ˆ 3464, 2934, 2900, 1148, 1090, 1017, 749, 699 cm 1; MS
‡
(EI, 70 eV): m/z (%): 428 (11) [M] , 410 (23), 392 (3), 366 (14), 348 (11),
‡
m/z (%): 386 (16) [M] , 368 (61), 350 (52), 332 (7), 290 (57), 220 (100), 147
237 (100), 220 (55), 191 (37), 104 (51), 91 (55), 87 (77); elemental analysis
calcd (%) for C28H28O4 (428.53): C 78.48, H 6.59; found: C 78.66, H 6.50.
(84), 105 (57), 91 (91); elemental analysis calcd (%) for C26H26O3 (386.50):
C 80.80, H 6.72; found: C 80.77, H 6.78.
(4ba,7aa,11ba,15bb)-4b,5,7,7a,11b,15b-Hexahydro-6H-dibenzo-
[2,3:4,5]pentaleno[1,6-jk]fluorene-6-one (12)
(4ba,7aa,11ba,15bb)-5,6,7,7a,11b,15b-Hexahydro-4H-dibenzo[2,3:4,5]-
pentaleno[1,6-jk]fluorene-6b-ol (9)
a) By oxidation of fenestranol 9: A suspension of fenestranol 9 (300 mg,
86 mmol) in freshly distilled acetone (10 mL) was added slowly to a stirred
solution of an excess of chromium trioxide (120 mg, 1.20 mmol) in 2n
sulfuric acid (5.0 mL). The mixture was stirred at ambient temperature
until TLC (n-hexane/ethyl acetate 3:1) indicated the absence of starting
material (ca. 4 h). In some cases, additional reagent and prolongation of the
reaction time were necessary. The solid phase was filtered by suction,
washed several times with water and dried in vacuo to give crude
fenestrane ketone 12 (290 mg, 97%) as a colorless solid (m.p. 290 ± 2948C).
Recrystallization from ethyl acetate gave a sample of m.p. 293 ± 2968C.
a) By cyclodehydration of 8:
A suspension of spirotriol 8 (20.0 g,
51.6 mmol) in xylene (80 mL) and orthophosphoric acid (85%, 4.0 mL)
was stirred vigorously and heated to reflux temperature for 3 h in a reaction
vessel equipped with a water separator. The hot solution was carefully
decanted from the oily, brown residue and the solvent was distilled off. The
crude product was recrystallized from ethyl acetate to yield pure 9 (31.2 g,
73%) as a colorless solid. M.p. 228 ± 2408C (decomp), 1H NMR and 1H,1H-
COSY (250 MHz, CDCl3), 1H,1H-NOESY and 1H,13C-COSY (500 MHz,
CDCl3): d ˆ7.49 ± 7.44 (m, 4H), 7.29 ± 6.99 (m, 8H), 4.44 (s, 1H), 4.40 (s,
1H), 4.27 (ddd, J ˆ 10.1, 5.5, 4.0 Hz, 1H), 3.84 (d, J ˆ 4.1 Hz, 1H), 3.50 (dd,
J ˆ 14.0, 2.6 Hz, 1H), 2.95 (ddd, J ˆ 13.8, 10.1, 2.6 Hz, 1H), 2.56 (ddd, J ˆ
15.3, 5.5, 4.1 Hz, 1H), 2.28 (d, J ˆ 15.3 Hz, 1H), 1.42 (ddd, J ˆ 14.0, 13.8,
4.0 Hz, 1H), 0.95 (brs, 1H); 13C NMR (62.9 MHz, CDCl3): d ˆ 147.5, 145.8,
144.5, 144.4, 142.6, 127.8, 127.6, 126.9, 126.8, 126.7, 126.4, 125.5, 125.3, 124.5,
123.8, 123.4, 120.9, 68.1, 67.8, 58.8, 56.8, 46.3, 44.4, 36.9, 31.6; IR (KBr): nÄ ˆ
3567, 2890, 1472, 1453, 1446, 1074, 770, 756 cm 1; MS (EI, 70 eV): m/z (%):
b) By cyclodehydration of dispirodiol 11: In a reaction vessel equipped with
a water separator, dispirodiole 11 (10.4 g, 24.3 mmol) and orthophosphoric
acid (85%, 16 mL) in toluene (600 mL) were heated to reflux for 15 h. The
hot solution was carefully decanted from the oily brown residue, and the
solvent was then distilled off and the residue recrystallized from ethyl
acetate to yield fenestrane ketone 12 (7.33 g, 87%) as a colorless powder.
M.p. 293 ± 2978C; 1H NMR (250 MHz, CDCl3): d ˆ 7.50 ± 7.47 (m, 1H),
7.41 ± 7.38 (m, 1H), 7.21 ± 7.02 (m, 10H), 4.58 (s, 1H), 4.43 (s, 1H), 4.28 (dd,
J ˆ 3.4, 14.6 Hz, 1H), 4.06 (d, J ˆ 5.1 Hz, 1H), 3.38 (dd, J ˆ 6.2, 15.1 Hz,
1H), 2.94 (dd, J ˆ 3.6, 18.6 Hz, 1H), 2.70 (dd, J ˆ 1.8, 15.1 Hz, 1H), 2.27
(dd, J ˆ 14.8, 18.6 Hz, 1H); 13C NMR (62.9 MHz, CDCl3): d ˆ 145.7, 145.1,
144.8, 144.0, 143.8, 141.1, 127.9, 127.8, 127.3, 127.2, 127.1, 126.7, 125.6, 125.1,
124.5, 123.3, 123.2, 121.0, 67.3, 58.8, 56.8, 47.2, 47.0, 44.4, 37.9; IR (KBr): nÄ ˆ
2962, 2901, 1715, 1471, 760, 752, 746 cm 1; MS (EI, 70 eV): m/z (%): 348
‡
350 (95) [M] , 332 (100), 303 (62), 291 (72), 215 (42), 91 (24); elemental
analysis calcd (%) for C26H22O (382.46): C 89.11, H 6.33; found: C 89.18, H
6.55.
b) By reduction of 12: A mixture of fenestranone 12 (1.00 g, 2.88 mmol)
and lithium aluminum hydride (0.10 g, 2.60 mmol) in THF (350 mL) was
refluxed for 6 h. The reaction mixture was cooled with ice/water, carefully
hydrolyzed with water, and extracted several times with diethyl ether. The
combined organic layers were dried with sodium sulfate and the solvent
was evaporated to give pure 9 (1.00 g, 99%) as a colorless solid. M.p. 231 ±
2398C (decomp).
‡
(100) [M] , 305 (37), 290 (39); elemental analysis calcd (%) for C26H20O
(348.45): C 89.62, H 5.79; found: C 89.69, H 6.04.
(4ba,7aa,11ba,15bb)-4b,5,7,7a,11b,15b-Hexahydro-6H-dibenzo-
cis-3',5'-Diphenyldispiro[1,3-dioxolane-2,1'-cyclohexane-4',2''-[2H]-
indene]-1'',3''-dione (10): In a reaction vessel equipped with a water
separator containing freshly dried molecular sieves (4 Š, 15 g), a solution
of spirotriketone 6 (10.2 g, 26.8 mmol), ethylene glycol (1.86 g, 30.0 mmol),
and p-toluenesulfonic acid (50 mg) in dichloromethane (150 mL) was
heated to reflux for 15 h. The solution was washed with aqueous sodium
bicarbonate and water and dried with sodium sulfate, and the solvent was
evaporated to yield dispiroacetal 10 (11.2 g, 99%) as a colorless powder.
M.p. 262 ± 2638C; 1H NMR (250 MHz, CDCl3): d ˆ 7.54 ± 7.51 (m, 1H),
7.45 ± 7.31 (m, 3H), 7.04 ± 6.86 (m, 10H), 4.04 (s, 4H), 3.78 (dd, J ˆ 3.3,
13.8 Hz, 2H), 3.09, (quasi-t, J ˆ 13.5 Hz, 2H), 1.94 (dd, J ˆ 2.0, 13.0 Hz,
2H); 13C NMR (62.9 MHz, CDCl3): d ˆ 203.4, 203.2, 142.8, 142.1, 139.1,
134.8, 134.7, 128.5, 128.1, 127.0, 122.1, 121.8, 108.6, 64.7, 64.6, 62.6, 46.8, 36.4;
IR (KBr): nÄ ˆ 2889, 1741, 1696, 1255, 1145, 1073, 765 cm 1; MS (EI, 70 eV):
[2,3:4,5]pentaleno[1,6-jk]fluorene-6-one hydrazone (13): A solution of
fenestrane ketone 12 (1.00 g, 2.87 mmol) and hydrazine hydrate (180 mg,
3.59 mmol) in ethanol (70 mL) was heated to reflux temperature for 5 h.
The mixture was cooled at 158C overnight. The resulting product was
filtered by suction and recrystallized from ethanol to give hydrazone 13
(0.82 g, 79%) as colorless crystals. M.p. 174 ± 1798C (decomp); 1H NMR
(500 MHz, CDCl3): d ˆ 7.47 ± 7.46 (m, 1H), 7.36 ± 7.35 (m, 1H), 7.19 ± 7.10
(m, 8H), 7.06 ± 7.03 (m, 2H), 4.74 (brs, 2H, -NH), 4.53 (s, 1H), 4.36 (s, 1H),
4.09 (dd, J ˆ 3.5, 13.9 Hz, 1H), 3.93 (d, J ˆ 4.8 Hz, 1H), 3.27 (dd, J ˆ 5.1,
14.5 Hz, 1H), 2.92 (dd, J ˆ 3.1, 17.1 Hz, 1H), 2.61 (dd, J ˆ 14.6, 1.6 Hz, 1H),
2.15 (quasi-t, J ˆ 14.9, 16.2 Hz, 1H); 13C NMR (125.8 MHz, CDCl3): d ˆ
151.2, 146.0, 145.7, 144.9, 144.1, 141.6, 127.5, 127.3, 127.0, 126.9, 126.8, 126.5,
125.5, 125.0, 124.5, 123.2, 122.8, 120.9, 67.4, 59.0, 56.4, 45.9, 45.7, 39.2, 24.0;
IR (KBr): nÄ ˆ 3392, 3069, 3023, 2956, 2892, 1473, 1454, 757 cm 1; MS (EI,
‡
‡
m/z (%): 424 (2) [M] , 364 (1), 320 (13), 233 (7), 175 (100), 86 (56);
70 eV): m/z (%): 362 (100) [M] , 346 (47), 345 (21), 331 (46), 305 (61), 289
‡
elemental analysis calcd (%) for C28H24O4 (424.50): C 79.23, H 5.70; found:
C 79.35, H 5.94.
(55); exact mass measurement (EI-MS): m/z: calcd for [M] 362.1783;
found: 362.1783.
cis-3',5'-Diphenyl-1'',3''-dihydrodispiro[1,3-dioxolane-2,1'-cyclohexane-
4',2''-[2H]indene]-1'',3''-diol (11): A solution of dispiroacetal 10 (11.2 g,
26.4 mmol) in dry tetrahydrofuran (350 mL) was added to a suspension of
lithium aluminum hydride (2.0 g, 53.0 mmol) in dry THF (100 mL) and the
mixture was heated to reflux for 4 h. The major part of the solvent (ca.
300 mL) was distilled off and replaced with diethyl ether (150 mL). The
mixture was carefully hydrolyzed by addition of water and extracted
several times with diethyl ether. The combined extracts were dried with
(4ba,7ab,11ba,15bb)-4b,5,7,7a,11b,15b-Hexahydro-6H-dibenzo-
[2,3:4,5]pentaleno[1,6-jk]fluorene-6-one hydrazone (14): A solution of
fenestrane ketone 7 (1.00 g, 2.87 mmol) and hydrazine hydrate (180 mg,
3.59 mmol) in ethanol (70 mL) was heated to reflux temperature for 5 h.
The product precipitated over 15 h on standing at 158C. It was filtered by
suction, washed with a little ethanol, and then recrystallized from ethanol
to give hydrazone 13 (0.73 g, 70%) as a colorless solid. M.p. 337 ± 3418C
1
(decomp); H NMR (500 MHz, CDCl3): d ˆ 7.38 ± 7.31 (m, 4H), 7.26 ± 7.17
3396
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0947-6539/01/0715-3396 $ 17.50+.50/0
Chem. Eur. J. 2001, 7, No. 15

Fenestranes
3387±3400
(m, 8H), 5.00 (brs, 2H, -NH), 4.48 (s, 1H), 4.47 (s, 1H), 3.58 (t, J ˆ 6.8 Hz,
1H), 3.49 (t, J ˆ 7.1 Hz, 1H), 2.70 ± 2.57 (m, 4H); 13C NMR (125.8 MHz,
CDCl3): d ˆ 143.6, 143.1, 142.6, 142.4, 142.2, 141.9, 127.4, 127.2, 126.9, 125.3,
which contained three isomeric olefins (18:19:20) in the ratio of 21:6:2 (as
determined by 1H NMR. Isomer 18 was isolated by column chromatog-
raphy (n-hexane/ethyl acetate 50:1); isomers 19 and 20 were isolated by
HPLC (cyclohexane), yielding 18 (197 mg, 593 mmol, 41%), 19 (28 mg,
84 mmol, 6%) and 20 (14 mg, 42 mmol, 3%) as colorless solids.
125.2, 124.7, 124.6, 124.3, 123.9, 123.8, 67.0, 59.8, 59.0, 58.7, 57.9, 37.5, 35.8;
1
IR (KBr): nÄ ˆ 3072, 3023, 2881, 1650, 1476, 1457, 1443, 754, 738, 638 cm
;
‡
MS (EI, 70 eV): m/z (%): 362 (10) [M] , 346 (91), 332 (98), 305 (78), 303
(4ba,7aa,11bb,15ba)-5,7a,11b,15b-Tetrahydro-4bH-dibenzo[2,3:4,5]-
pentaleno[1,6-jk]fluorene (18): M.p. 222 ± 2238C; 1H NMR (500 MHz,
CDCl3): d ˆ 7.45 (d, J ˆ 7.4 Hz, 1H), 7.39 (d, J ˆ 7.3 Hz, 1H), 7.26 (d, J ˆ
7.6 Hz, 1H), 7.17 ± 7.05 (m, 9H), 5.88 (dd, J ˆ 9.7, 1.7 Hz, 1H), 5.81 (dd, J ˆ
9.6, 2.6 Hz, 1H), 4.66 (s, 1H), 4.33 (s, 1H), 3.87 (dd, J ˆ 12.7, 3.2 Hz, 1H),
2.73 (ddd, J ˆ 16.4, 3.4, 3.2 Hz, 1H), 2.39 (ddd, J ˆ 16.4, 12.6, 1.9 Hz, 1H);
13C NMR (125.8 MHz, CDCl3): d ˆ 147.0, 146.3, 146.1, 145.1, 145.0, 142.0,
136.0, 127.9, 126.72, 126.67, 126.6, 126.1, 125.7, 124.9, 124.2, 124.0, 122.8,
120.8, 63.7, 61.3, 55.5, 54.2, 50.6, 23.9; IR (KBr): nÄ ˆ 3019, 1471, 1453,
(89), 291 (100), 290 (75), 289 (86), 215 (41); exact mass measurement (EI-
‡
MS): m/z: calcd for [M] 362.1783; found: 362.1790.
(4b'a,7a'a,11b'a,15b'b)-4b',5',7',7a',11b',15b'-1,3-Dithiolane-2,6'-hexa-
hydro-6'H-dibenzo[2',3':4',5']pentaleno[1',6'-jk]fluorene (15): A mixture of
fenestrane ketone 12 (500 mg, 1.44 mmol), 1,2-ethanedithiol (0.50 mL,
5.94 mmol), BF3 ´ Et2O (50% BF3, 0.5 mL), and acetic acid (5 mL) was
stirred at ambient temperature for 2 h. The crude product was separated by
filtration, washed with ethanol, and recrystallized from ethyl acetate to give
dithiolane 15 (579 mg, 95%) as a colorless powder. M.p. 268 ± 2698C;
1H NMR (500 MHz, CDCl3): d ˆ 7.46 ± 7.45 (m, 2H), 7.29 ± 7.23 (m, 3H),
7.15 ± 7.00 (m, 7H), 4.42 (s, 1H), 4.34 (s, 1H), 3.89 (d, J ˆ 4.1 Hz, 1H), 3.76
(d, J ˆ 13.1 Hz, 1H), 3.29 ± 3.23 (m, 3H), 3.10 ± 3.06 (m, 2H), 2.99 ± 2.96
(dd, J ˆ 2.2, 13.9 Hz, 1H), 2.67 (dd, J ˆ 1.8, 15.0 Hz, 1H), 2.26 (t, J ˆ
13.6 Hz, 1H); 13C NMR (125.8 MHz, CDCl3): d ˆ 145.8, 144.9, 144.4,
144.2, 142.3, 127.7, 126.9, 126.79, 126.75, 126.5, 125.5, 124.5, 123.3, 121.0,
67.5, 64.1, 58.3, 57.3, 45.6, 45.4, 44.1, 42.7, 41.6, 36.2; IR (KBr): nÄ ˆ 2913,
1484, 1477, 1466, 1455, 1445, 1431, 762, 743, 733 cm 1; MS (EI, 70 eV): m/z
‡
768, 745, 727, 698 cm 1; MS (EI, 70 eV): m/z (%): 332 (100) [M] , 331
(10), 317 (11), 304 (16), 303 (25), 302 (13), 291 (12), 289 (13); exact
‡
mass measurement (EI-MS): m/z: calcd for [M] 332.1565; found:
332.1565.
(4ba,7aa,11ba,15bb)-5,7a,11b,15b-Tetrahydro-4bH-dibenzo[2,3:4,5]-
1
pentaleno[1,6-jk]fluorene (19): M.p. 2328C; H NMR (500 MHz, CDCl3):
d ˆ 7.52 (d, J ˆ 6.9 Hz, 1H), 7.48 ± 7.46 (m, 1H), 7.44 ± 7.42 (m, 1H), 7.25 ±
7.12 (m, 9H), 6.32 (dd, J ˆ 7.9, 2.8 Hz, 1H), 4.57 (s, 1H), 4.49 (s, 1H), 3.78
(d, J ˆ 3.8 Hz, 1H), 2.20 (dd, J ˆ 12.6, 2.5 Hz, 1H), 2.02 (ddd, J ˆ 12.0, 8.2,
3.8 Hz, 1H), 1.81 (tdd, J ˆ 12.6, 5.0, 3.8 Hz, 1H), 1.72 (tt, J ˆ 12.6, 3.1 Hz,
1H); 13C NMR (125.8 MHz, CDCl3): d ˆ 145.8, 145.6, 145.1, 144.9, 144.1,
144.0, 140.3, 127.8, 127.3, 127.1, 127.0, 124.9, 124.3, 124.2, 124.0, 121.9, 120.2,
65.7, 63.1, 60.1, 46.4, 28.7, 26.9, 20.8; IR (KBr): nÄ ˆ 2935, 1479, 1466, 751,
‡
(%): 424 (8) [M] , 363 (17), 331 (100), 289 (19), 215 (13); exact mass
‡
measurement (EI-MS): m/z: calcd for [M] 424.1320; found: 424.1325;
elemental analysis calcd (%) for C28H24S2 (424.62): C 79.20, H 5.70; found:
C 79.10, H 5.60.
(4b'a,7a'b,11b'a,15bb)-4b',5',7',7a',11b',15b'-1,3-Dithiolane-2,6'-penta-
hydro-6'H-dibenzo[2',3':4',5']pentaleno[1',6'-jk]fluorene (16): A mixture of
fenestrane ketone 7 (500 mg, 5.94 mmol), 1,2-ethanedithiol (0.50 mL,
5.94 mmol), BF3 ´ Et2O (50% BF3, 0.5 mL), and acetic acid (5 mL) was
stirred at ambient temperature for 2 h. The crude product was separated by
filtration, washed with ethanol, and recrystallized from ethyl acetate to
yield dithiolane 16 (522 mg, 85%) as a colorless powder. M.p. 247 ± 2498C;
1H NMR (500 MHz, CDCl3): d ˆ 7.37 ± 7.31 (m, 4H), 7.26 ± 7.16 (m, 8H),
4.44 (s, 2H), 3.55 (quasi-t, J ˆ 6.5 Hz, 2H), 3.25 (s, 4H), 2.51 (dd, J ˆ 6.2,
14.2 Hz, 2H), 2.34 (dd, J ˆ 7.0, 14.2 Hz, 2H); 13C NMR (125.8 MHz,
CDCl3): d ˆ 145.4, 143.4, 142.8, 127.3, 127.2, 126.7, 125.0, 124.6, 124.4, 65.8,
64.8, 59.2, 46.0, 43.3, 38.4; IR (KBr): nÄ ˆ 3021, 2928, 1476, 755 cm 1; MS (EI,
‡
734, 645 cm 1; MS (EI, 70 eV): m/z (%) 332 (100) [M] , 331 (7), 317 (12),
304 (12), 303 (25), 302 (15), 291 (14), 289 (16); elemental analysis calcd (%)
for C26H20 (332.45): C 93.94, H 6.06; found: C 93.59, H 6.27.
(4ba,11ba,15bb)-5,6,11b,15b-Tetrahydro-4bH-dibenzo[2,3:4,5]pentale-
no[1,6-jk]fluorene (20): M.p. 2028C; 1H NMR (500 MHz, CDCl3): d ˆ
7.42 ± 7.40 (m, 2H), 7.29 ± 7.27 (m, 1H), 7.23 ± 7.13 (m, 9H), 6.12 (d, J ˆ 9.7,
1H), 5.85 (ddd, J ˆ 10.0, 5.0, 2.5 Hz, 1H), 4.51 (s, 1H), 4.36 (s, 1H), 3.76 (s,
1H), 3.25 (t, J ˆ 7.5 Hz, 1H), 2.51 (dt, J ˆ 18.2, 6.3 Hz, 1H), 2.10 (ddd, J ˆ
18.2, 7.5, 2.5 Hz, 1H); 13C NMR (125.8 MHz, CDCl3): d ˆ 148.0, 146.3,
143.8, 143.7, 142.6, 142.5, 127.6, 127.2, 127.1, 127.0, 126.9, 126.8, 125.5, 124.8,
124.7, 124.6, 124.3, 124.1, 123.4, 65.7, 60.3, 59.3, 45.3, 42.1, 29.2; IR (KBr):
nÄ ˆ 3027, 1474, 1454, 769, 757, 738, 714cm 1; MS (EI, 70 eV): m/z (%): 332
‡
70 eV): m/z (%): 424 (34) [M] , 363 (29), 331 (100), 289 (22), 215 (10); exact
‡
(100) [M] , 331 (7), 317 (14), 304 (11), 303 (23), 302 (12), 291 (15), 289 (15);
‡
mass measurement (EI-MS): m/z: calcd for [M] 424.1320; found:
‡
exact mass measurement (EI-MS): m/z: calcd for [M] 332.1565; found:
424.1325; elemental analysis calcd (%) for C28H24S2 (424.62): C 79.20, H
5.70; found: C 79.07, H 5.85.
332.1573.
trans-2,6-Diphenylspiro[cyclohexane-1,2'-[2H]indene]-1',3'-dione
(24):
(4ba,7aa,11ba,15bb)-5,6,7,7a,11b,15b-Hexahydro-4bH-dibenzo-
[2,3:4,5]pentaleno[1,6-jk]fluorene-6-yl para-toluenesulfonate (17): Fenes-
trans-Diphenylspirotriketone (4.00 g, 10.5 mmol), p-toluenesulfonyl
5
hydrazide (2.68 g, 14.40 mmol), sodium cyanoborohydride (2.43 g,
46.00 mmol), and p-toluenesulfonic acid (192 mg) were dissolved in
dimethylformamide/sulfolane (1:1, 64 mL) and the mixture was heated to
1108C for 2.5 h. The hot solution was poured into water (800 mL) with
vigorous stirring. The precipitate formed was filtered by suction, washed
with water, and dissolved in dichloromethane (200 mL). The organic layer
was separated and dried over sodium sulfate. Removal of the solvent gave a
product which was purified by column chromatography (silica gel, n-
hexane/ethyl acetate 3:1) to give trans-diphenylspirodiketone 24 (1.24 g,
32%) as a colorless powder. M.p. 169 ± 1708C; 1H NMR (500 MHz,
CDCl3): d ˆ 7.51 ± 7.42 (AA'BB', 4H), 7.02 ± 6.97 (m, 8H), 6.95 ± 6.92 (m,
2H), 3.64 (dd, J ˆ 2.9 Hz, J ˆ 12.6, 2H), 2.71 ± 2.62 (m, 2H), 2.10 ± 2.04 (m,
2H), 1.96 ± 1.90 (m, 2H); 13C NMR (125.8 MHz, CDCl3): d ˆ 203.8, 142.1,
140.6, 134.8, 128.5, 127.8, 126.5, 121.1, 62.9, 44.7, 23.6, 21.0; IR (KBr): nÄ ˆ
2947, 1732, 1697, 1258, 760, 700cm 1; MS (EI, 70 eV): m/z (%): 366 (79)
tranol
9 (1.00 g, 2.86 mmol) and p-toluenesulfonyl chloride (2.30 g,
12.00 mmol) were dissolved in dry pyridine (20 mL). The solution was
stirred at ambient temperature for 4 h, and then poured into ice/water
(75 mL) and extracted several times with dichloromethane. The combined
organic layers were washed with hydrochloric acid (10%), aqueous sodium
bicarbonate, and water, and then dried over sodium sulfate. Evaporation of
the solvent and recrystallization of the residue from n-hexane/ethyl acetate
3:1 gave tosylate 17 (1.17 g, 81%) as a colorless solid. M.p. 166 ± 1678C
(decomp); 1H NMR (500 MHz, CDCl3): d ˆ 7.48 (AA'BB', 2H), 7.42 (d,
J ˆ 7.4 Hz, 1H), 7.35 (d, J ˆ 7.4 Hz, 1H), 7.48 (AA'BB', 2H), 7.27 ± 7.02 (m,
9H), 6.98 (d, J ˆ 7.2 Hz, 1H), 5.15 (ddd, J ˆ 5.2, 5.7, 10.4 Hz, 1H), 4.37 (s,
1H), 4.35 (s, 1H), 3.80 (d, J ˆ 4.8 Hz, 1H), 3.43 (d, J ˆ 13.9 Hz, 1H), 2.80
(ddd, J ˆ 2.7, 10.5, 10.8 Hz, 1H), 2.49 (dt, J ˆ 5.5, 15.9 Hz, 1H), 2.44 (s, 3H),
2.31 (d, J ˆ 15.8 Hz, 1H), 1.72 (ddd, J ˆ 14.1, 14.0, 6.0 Hz, 1H); 13C NMR
(125.8 MHz, CDCl3): d ˆ 145.9, 144.5, 144.1, 144.0, 141.5, 134.5, 129.4, 127.5,
127,2, 127.0, 126.9, 126.7, 126.4, 125.5, 125.4, 124.5, 123.2, 122.9, 120.8, 67.3,
58.8, 56.8, 45.5, 44.0, 34.2, 27.9, 21.6; IR (KBr): nÄ ˆ 2894, 1173, 912, 896,
‡
[M] , 275 (94), 235 (100), 91 (75); elemental analysis calcd (%) for
C26H22O2 (366.46): C 85.22, H 6.05; found: C 85.05, H 6.06.
750 cm 1; MS (EI, 70 eV): m/z (%): 504 (3) [M] , 334 (100), 332 (51), 215
(35), 91 (45); elemental analysis calcd (%) for C33H28O3S (504.65): C 78.54,
H 5.59; found: C 78.39, H 5.74.
‡
trans-2,6-Diphenylspiro[cyclohexane-1,2'-[2H]indene]-1',3'-diol (25):
A
solution of spirodiketone 24 (720 mg, 1.97 mmol) in tetrahydrofuran
(15 mL) was added to a suspension of an excess of lithium aluminum
hydride (0.30 g) in dry THF (20 mL), and the mixture was heated at reflux
for 18 h. A portion (ca. 20 mL) of the solvent was then removed and
replaced by diethyl ether (15 mL). The suspension was carefully hydrolyzed
with water, the colorless precipitate was dissolved by adding 2n hydro-
chloric acid, and the solution was extracted several times with diethyl ether.
The combined organic layers were washed with aqueous sodium bicar-
Dehydration of fenestranol 9 with HMPT: A solution of fenestranol 9
(500 mg, 1.43 mmol) in hexamethylphosphorous triamide (25 mL) was
stirred and heated at reflux for 18 h. The reaction mixture was allowed to
cool and then poured into water (120 mL). The mixture was extracted with
n-hexane/diethyl ether 10:1, and the organic layer was washed with water
and dried with Na2SO4. Evaporation of the solvent gave a crude product
Chem. Eur. J. 2001, 7, No. 15
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2001
0947-6539/01/0715-3397 $ 17.50+.50/0
3397

D. Kuck et al.
FULL PAPER
bonate and with water and dried over sodium sulfate. Evaporation of the
solvent gave spirodiol 25 (725 mg, 99%) as a colorless powder (m.p. 164 ±
1658C), which, upon recrystallization from n-hexane/ethyl acetate 3:1, was
obtained as pure, colorless crystals (700 mg, 96%). M.p. 164 ± 1658C;
1H NMR (500 MHz, CDCl3): d ˆ 7.40 ± 7.38 (m, 4H), 7.10 ± 7.08 (m, 4H),
7.04 ± 7.03 (m, 2H), 6.89 (brs, 4H), 5.30 (s, 2H), 3.84 ± 3.81 (m, 2H), 2.14 ±
2.08 (m, 2H), 2.04 ± 1.98 (m, 4H), 1.21 (brs, 2H); 13C NMR (125.8 MHz,
CDCl3): d ˆ 144.3, 142.9, 130.3, 128.0, 127.9, 126.1, 123.6, 78.2, 57.2, 42.5,
29.5, 21.3; IR (KBr): nÄ ˆ 3538, 3434, 3030, 2924, 1450, 1175, 1015, 759, 707,
(4ba,7ab,11ba,15bb)-5,6,7,7a,11b,15b-Hexahydro-4bH-dibenzo-
[2,3:4,5]pentaleno[1,6-jk]fluorene (3)[17]
a) By Wolff ± Kishner reduction of fenestranone 12: A mixture of 12
(140 mg, 400 mmol), triethylene glycol (4.0 mL), hydrazine hydrate (150 ml),
and finely powdered potassium hydroxide (100 mg) was stirred and heated
at 1308C for 3 h. The temperature was then slowly raised to 1808C, while
the volatile components were distilled off, and the mixture was kept at this
temperature for a further 2 h. The mixture was allowed to cool, the solid
residue was dissolved in water and the solution was acidified with
hydrochloric acid (10%) and extracted several times with dichlorome-
thane. The combined organic layers were washed with water and dried with
sodium sulfate. The solvent was removed and the residue was recrystallized
from diethyl ether/tetrahydrofuran 4:1 to give all-cis-fenestrane 3 (98 mg,
73%). M.p. 203 ± 2078C (204 ± 2058C).[17]
‡
696 cm 1; MS (EI, 70 eV): m/z (%): 370 (3) [M] , 352 (88), 334 (17), 237
(52), 147 (100), 117 (54), 91 (91); exact mass measurement (EI): m/z: calcd
‡
for [M] 370.1933; found: 370.1934; elemental analysis calcd (%) for
C26H26O2 (370.50): C 84.29, H 7.07; found: C 84.12, H, 7.05.
cis-2,6-Diphenylspiro[cyclohexane-1,2'-[2H]indene]-1',3'-dione (27)
b) By reduction of dithiolane 15 with Raney nickel: Raney nickel, freshly
prepared from nickel/aluminum alloy (15.0 g) and washed to pH 7.0, was
added to a solution of 15 (580 mg, 1.37 mmol) in 1,4-dioxane (100 mL). The
mixture was heated to reflux for 15 h and after cooling to ambient
temperature the catalyst was filtered off and washed twice with 25 mL
portions of hot 1,4-dioxane. The combined organic solutions were
combined, the solvent was evaporated, and the residue was recrystallized
from ethanol to give all-cis-fenestrane 3 (367 mg, 80%), m.p. 203 ± 2058C
(see above).
a) Tosylhydrazone 26: A mixture of trans-diphenylspirotrione 5 or cis-
diphenylspirotrione 6 (2.00 g, 5.26 mmol in each case), p-toluenesulfonyl
hydrazide (1.17 g, 6.31 mmol), and ethanol (40 mL) was heated at reflux for
3 h. The mixture was allowed to cool and then kept at 158C overnight.
The precipitate was filtered by suction, washed, and recrystallized from
ethanol to give a colorless powder (2.52 g, 96%, from 5 and 2.23 g, 88%,
from 6) of m.p. 146 ± 1508C (decomp).
ba) Reduction of tosylhydrazone 26 with sodium borohydride: Tosylhy-
drazone 26 (200 mg, 413 mmol) was dissolved in methanol (20 mL). Sodium
borohydride (0.5 g) was carefully added in small portions and the mixture
was heated at reflux temperature for 15 h. The suspension was allowed to
cool, 15 mL of water were added, and the mixture was extracted several
times with diethyl ether. The combined extracts were washed with aqueous
sodium bisulfate and with water and then dried over sodium sulfate.
Evaporation of the solvent and recrystallization of the residue from ethanol
gave cis-diphenylspirodiketone 27 (82 mg, 54%). M.p. 197 ± 1998C.
c) By reduction of dithiolane 16 with Raney nickel: A solution of 16
(920 mg, 2.17 mmol) was reduced by following the procedure described
above for 15, to give all-cis-fenestrane 3 (632 mg, 87%), m.p. 204 ± 2058C
(see above).
d) By reduction of dithiolane 16 with Bu3SnH:. Azoisobutyronitrile
(AIBN, 15 mg) and tri(n-butyl)tin hydride (0.40 mL, 1.49 mmol) were
added to a solution of 16 (130 mg, 307 mmol) in dry benzene (15 mL) and
the mixture was refluxed for 5 h. The solvent was distilled off to give an oily
residue, which crystallized within a few hours upon standing. Ethanol
(5 mL) was added and the mixture was stirred at ambient temperature
overnight, during which most of the by-products, such as bis(tributystan-
nyl)ethanedithiolate and bis[tri-(n-butyl)tin] sulfide, dissolved. The re-
maining organotin compounds were separated by column chromatography
(silica gel, n-hexane), and subsequent elution with ethyl acetate gave pure 3
(82 mg, 80%), m.p. 202 ± 2058C (see above).
bb) Reduction of tosylhydrazone 26 with catecholborane: Tosylhydrazone
26 (1.60 g, 3.30 mmol) was dissolved in dry chloroform (40 mL) at 08C. A
solution of catecholborane (1m, 8.0 mL, 8.0 mmol) in tetrahydrofuran was
added under argon and the mixture was stirred at ambient temperature for
5 h. Sodium acetate trihydrate (2.18 g, 16.0 mmol) was added and the
reaction mixture was heated at gentle reflux for 2 h. The solution was
allowed to cool and kept at ambient temperature overnight. The organic
layer was washed with water, aqueous sodium bicarbonate, and again with
water. The solvent was distilled off and the residue was crystallized from
ethanol to give spirodiketone 27 (0.88 g, 73%) as a colorless powder. M.p.
e) By cyclodehydration of trans-diphenylspirodiol 25: In a reaction vessel
equipped with a water separator, spirodiol 25 (300 mg, 811 mmol) and
orthophosphoric acid (85%, 1.5 g) were refluxed in toluene (40 mL) for
15 h. The hot solution was carefully decanted from the brownish residue,
the solvent was distilled off, and the crude product was recrystallized from
ethanol to yield pure all-cis-fenestrane 3 (244 mg, 90%), m.p. 204 ± 2068C
(see above).
1
198 ± 1998C; H NMR (500 MHz, CDCl3): d ˆ 7.51 ± 7.50 m, 1H), 7.39-7.31
m, 3H), 7.00 ± 6.99 (m, 4H), 6.95 ± 6.92 (m, 4H), 6.88 ± 6.85 (m, 2H), 3.34
(dd, J ˆ 3.3, 13.2 Hz, 2H), 2.75 (dq, J ˆ 3.7, 13.2 Hz, 2H), 2.21 (dt, J ˆ 3.3,
13.4 Hz, 1H), 1.84 (dq, J ˆ 3.3, 13.4 Hz, 2H), 1.76 (dt, J ˆ 3.7, 13.1 Hz, 1H);
13C NMR (125.8 MHz, CDCl3): d ˆ 203.9, 203.8, 142.9, 141.8, 140.5, 134.7,
134.5, 128.4, 127.9, 126.7, 121.9, 121.7, 63.3, 49.5, 27.3, 26.3; IR (KBr): nÄ ˆ
2926, 1733, 1698, 1254, 766, 701 cm 1; MS (EI, 70 eV): m/z (%): 366 (65)
(4ba,7aa,11ba,15bb)-5,6,7,7a,11b,15b-Hexahydro-4bH-dibenzo-
[2,3:4,5]pentaleno[1,6-jk]fluorene (4)
‡
a) By reduction of tosylate 17: A suspension of 17 (0.60 g, 1.19 mmol) and
lithium aluminum hydride (150 mg, 3.95 mmol) in dry tetrahydrofuran
(90 mL) was heated at reflux for 15 h. The mixture was cooled in ice/water,
carefully hydrolyzed by adding aqueous ammonium chloride, and then
extracted several times with diethyl ether. The combined organic layers
were washed with aqueous sodium thiosulfate (10%) and dried with
sodium sulfate. The solvent was distilled off and the residue was recrystal-
lized from n-hexane/ethyl acetate 3:1 to yield a colorless solid (337 mg, ca.
85%) which, according to 1H NMR spectroscopy, consisted of a mixture of
hydrocarbons 4 (ca. 85%) and olefins (ca. 15%). The mixture (260 mg,
0.78 mmol) was dissolved in dry ethyl acetate/tetrahydrofuran 3:2 (50 mL),
palladium on charcoal (10%, 20 mg, Merck) was added, and the mixture
was shaken under hydrogen at normal pressure and ambient temperature
for 2 d. The catalyst was removed by filtration, the solvent was evaporated,
and the oily residue was crystallized from ethanol to give 4 (217 mg, 83%)
as colorless needles, m.p. 220 ± 2228C (see below).
[M] , 275 (100), 235 (96), 91 (58); exact mass measurement (EI-MS): m/z:
‡
calcd for [M] 366.1620; found: 366.1626.
cis-2,6-Diphenylspiro[cyclohexane-1,2'-[2H]indene]-1',3'-diol (28): cis-Di-
phenylspirodione 27 (880 mg, 2.40 mmol) was dissolved in dry tetrahydro-
furan (20 mL) and the solution was added to a suspension of lithium
aluminum hydride (0.40 g, 10.5 mmol) in dry THF (20 mL) and heated to
reflux for 24 h. The major part of the solvent was distilled off and replaced
with diethyl ether (15 mL). The mixture was carefully hydrolyzed by adding
ice/water and extracted several times with diethyl ether. The combined
organic layers were dried over sodium sulfate and the solvent was removed.
The oily residue was crystallized from ethanol to give spirodiol 28 (471 mg,
53%) as colorless crystals. M.p. 204 ± 2058C; 1H NMR (500 MHz, CDCl3):
d ˆ 7.54 ± 7.52 (m, 2H), 7.22 ± 7.19 (m, 2H), 7.13 ± 7.08 (m, 2H), 6.97 ± 6.95
(m, 1H), 6.90 ± 6.87 (m, 3H), 6.84 ± 6.73 (m, 4H), 5.64 (s, 1H), 5.52 (s, 1H),
3.28 (dt, J ˆ 13.8, 13.0 Hz, 2H), 2.69 (dq, J ˆ 3.8, 13.0 Hz, 1H), 2.33 (dq, J ˆ
4.2, 13.2 Hz, 1H), 2.12 ± 2.07 (m, 2H), 1.79 (d, J ˆ 14.2 Hz, 1H), 1.77 ± 1.68
(m, 1H); 13C NMR (125.8 MHz, CDCl3): d ˆ 144.6, 144.4, 143.6, 141.8,
131.0, 128.9, 128.7, 127.73, 127.68, 127.4, 126.1, 126.1, 125.7, 124.5, 121.8,
78.2, 78.0, 58.4, 51.0, 49.7, 31.3, 28.8, 27.6; IR (KBr): nÄ ˆ 3564, 3443,
2929, 1491, 1453, 1101, 1028, 1010, 759, 747 cm 1; MS (EI, 70 eV): m/z (%):
b) By reduction of dithiolane 15 with Bu3SnH: A solution of 15 (130 mg,
307 mmol) was treated according to the procedure described above for the
case of 16. Workup furnished ccct-fenestrane 4 (89 mg, 87%), m.p. 219 ±
2218C (see below).
‡
370 (1) [M] , 352 (74), 334 (4), 237 (58), 147 (100), 117 (37), 91 (62); exact
c) By Clemmensen reduction of 12: Conc. hydrochloric acid (0.4 mL) and
water (12 mL) were added to zinc (8.00 g, 122.4 mmol) and mercury(ii)
chloride (0.80 g, 2.95 mmol). This mixture was stirred for 5 min and the
‡
mass measurement (EI-MS): m/z: calcd for [M] 370.1933; found:
370.1926.
3398
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Chem. Eur. J. 2001, 7, No. 15

Fenestranes
3387±3400
excess solution was removed. Conc. hydrochloric acid (8 mL) and ketone
12 (0.4 g, 1.15 mmol), suspended in 1,4-dioxane (50 mL), were then added
and the solution was heated at reflux for 48 h (more reducing agent and a
longer reaction time were sometimes necessary). The solution was cooled
to ambient temperature, poured into water (400 mL) and extracted several
times with diethyl ether. The organic layer was dried with sodium sulfate,
the solvent was distilled off, and the crude product was recrystallized from
ethanol to yield 4 (327 mg, 85%), m.p. 220 ± 2218C (see below).
7.32 (AA'BB' system, 4H), 7.22 ± 7.15 (m, 8H), 4.37 (s, 2H), 3.17 (t, J ˆ
6.5 Hz, 1H), 1.90 ± 1.85 (m, 2H), 1.73 ± 1.69 (m, 2H), 1.46 ± 1.43 (m, 2H).
Crystal structure determination of 4:[32] Diffraction data were collected on a
Bruker AXS P4 diffractometer at 203 K with w scan, using graphite
monochromated MoKa radiation. Pertinent crystallographic data are
summarized in Table 2. Three standard reflections were periodically
monitored, showing only random deviations. Lp corrections were applied.
A total of 4718 reflections were collected in the range Vˆ 2.08 ± 26.998,
with h ˆ 1 to 11, k ˆ 25 to 1, and l ˆ 12 to 12, of which 3755
independent reflections (Rint ˆ 0.015) were used for structure determina-
tion. The structure was solved by direct and Fourier methods and refined by
full-matrix, least-squares based on F2 and 236 parameters. All non-
hydrogen atoms were refined anisotropically, hydrogen atoms were placed
at geometrically calculated positions with U(H)iso ˆ 1.2 (C)iso. Refinement
converged smoothly at R1(I > 2sI) ˆ 0.045, wR2 (all data) ˆ 0.133, S ˆ
d) By cyclodehydration of cis-diphenylspirodiol 28: In a reaction vessel
equipped with
a water separator, spirodiol 28 (300 mg, 811 mmol),
orthophosphoric acid (85%, 1.5 g) and toluene (40 mL) were heated at
reflux for 24 h. The organic layer was decanted carefully from the oily
residue, the solvent was removed in vacuo, and the solid residue was
recrystallized from ethanol to give fenestrane 4 (222 mg, 82%) as colorless
needles. M.p. 222 ± 2238C; 1H NMR (500 MHz, CDCl3): d ˆ 7.45 ± 7.41 (m,
2H), 7.20 ± 7.00 (m, 10H), 4.458 (s, 1H), 4.451 (s, 1H), 3.81 (s, 1H), 3.80 (dd,
J ˆ 4.5 Hz, 1H), 2.37 ± 2.32 (m, 1H), 2.24 ± 2.21 (m, 1H), 1.71 ± 1.68 (m,
1.056, max.(D/s) ˆ 0.000, min/max height in final DF map
0.18/
0.25 eŠ 3. Programs used: SHELXTL NT V5.1.[35]
1
1H), 1.59 ± 1.53 (m, 2H), 1.09 ± 1.00 (m, 1H); H NMR (500 MHz, C6D6):
d ˆ 7.30 (d, J ˆ 7.4 Hz, 1H), 7.18 ± 7.16 (m, 1H), 7.08 ± 6.99 (m, 8H), 6.93 ±
6.88 (m, 2H), 4.30 (s, 1H), 4.13 (s, 1H), 3.50 (d, J ˆ 4.1 Hz, 1H), 3.49 (dd,
J ˆ 13.2, 4.7 Hz, 1H), 2.03 ± 1.93 (m, 2H), 1.48 ± 1.40 (m, 2H), 1.35 ± 1.27 (m,
1H), 1.08 ± 0.98 (m, 1H); 13C NMR (125.8 MHz, CDCl3): d ˆ 146.6, 146.3,
145.9, 144.8, 144.7, 143.8, 126.9, 126.8, 126.7, 126.6, 126.4, 126.2, 125.1, 124.6,
124.5, 123.2, 122.8, 120.9, 66.8, 59.7, 56.4, 47.0, 45.3, 28.1, 18.3, 15.4; IR
(KBr): nÄ ˆ 2922, 1468, 1453, 754, 741 cm 1; MS (EI, 70 eV): m/z (%): 334
Acknowledgements
We are grateful to Mr. Dieter Barth for his skillful technical assistance.
Support of this work by the Fonds der Chemischen Industrie and the
Deutsche Forschungsgemeinschaft (DFG) is also gratefully acknowledged.
‡
(100) [M] , 305 (34), 291 (34), 257 (24); exact mass measurement (EI-MS):
‡
m/z: calcd for [M] 334.1722; found: 334.1722; elemental analysis calcd
[1] P. Gund, T. M. Gund, J. Am. Chem. Soc. 1981, 103, 4458 ± 4465.
[2] W. L. Luef, R. Keese, Helv. Chim. Acta 1987, 70, 543 ± 553.
[3] Reviews on fenestrane chemistry: a) D. Kuck in Advances in
Theoretically Interesting Molecules, Vol. 4 (Ed.: R. P. Thummel), JAI
Press, Greenwich, London, 1998, pp. 81 ± 155; b) H. Hopf, Classics in
Hydrocarbon Chemistry, Wiley-VCH, Weinheim, 2000, pp. 81 ± 102;
c) M. Thommen, R. Keese, Synlett 1997, 231 ± 240; d) W. Luef, R.
Keese, Advances in Strain in Organic Chemistry, Vol. 3 (Ed.: B.
Halton), JAI Press, Greenwich, CT, 1993, pp. 229 ± 267; e) W. C.
Agosta in The Chemistry of Alkanes and Cycloalkanes (Eds.: S. Patai,
Z. Rappoport), Wiley, New York, 1992, pp. 927 ± 962; f) A. K. Gupta,
X. Fu, J. P. Snyder, J. M. Cook, Tetrahedron 1991, 47, 3665 ± 3710; g) K.
Krohn in Organic Synthesis Highlights (Eds.: J. Mulzer, H.-J.
Altenbach, M. Braun, K. Krohn, H.-U. Reissig), VCH, Weinheim,
1991, pp. 121 ± 125; h) B. R. Venepalli, W. C. Agosta, Chem. Rev. 1987,
87, 399 ± 410; i) R. Keese in Organic Synthesis: Modern Trends (Ed.:
O. Chizhov), Blackwell, Oxford, 1987, pp. 43 ± 52; j) R. Keese, Nach.
Chem. Tech. Lab. 1982, 30, 844 ± 849.
(%) for C26H22 (334.47): C 93.37, H 6.63; found: C 93.26, H 6.54.
Base-induced epimerization of fenestranone 12: A solution of ketone 12
(1.00 g, 2.87 mmol) and potassium tert-butoxide (5.0 g) was stirred in
DMSO (80 mL) at 208C for 15 h. The brownish liquid was then poured into
water (500 mL), acidified with 2n hydrochloric acid, and extracted with
trichloromethane. The organic extract was washed with water, saturated
aqueous sodium bicarbonate, and again with water, dried over sodium
sulfate, and concentrated to dryness. The crude product was recrystallized
from EtOH/THF to give the all-cis-fenestranone 7 (739 mg, 74%) as a
1
colorless solid, m.p. 283 ± 2858C. The H NMR spectrum was found to be
identical with that of an authentic sample.
H/D exchange experiments
(4ba,7ab,11ba,15bb)-11b,15b-Dideutero-5,6,7,7a,11b,15b-hexahydro-
4bH-dibenzo[2,3:4,5]pentaleno[1,6-jk]fluorene (3a): A mixture of all-cis-
fenestrane
3 (20 mg, 60 mmol), KOtBu (100 mg, 1.04 mmol), and
[D6]DMSO (3 mL) was stirred under argon for 24 h at 208C. The reaction
mixture was then poured into water (50 mL) and extracted with dichloro-
methane. The organic layer was dried with sodium sulfate and the solvent
was removed. The product was purified by column chromatography (n-
hexane/ethyl acetate 3:1) to yield 3a (18.4 mg, 90%) as a colorless solid.
1H NMR (500 MHz, CDCl3): d ˆ 7.37 ± 7.32 (AA'BB' system, 4H), 7.22 ±
7.15 (m, 8H), 3.17 (t, J ˆ 6.5 Hz, 1H), 1.90 ± 1.85 (m, 2H), 1.73 ± 1.69 (m,
[4] J. Tellenbröker, D. Kuck, Eur. J. Org. Chem. 2001, 1483 ± 1489.
[5] a) R. Keese, Angew. Chem., 1992, 104, 307 ± 309; Angew. Chem. Int.
Ed. Engl. 1992, 31, 344 ± 345; b) D. Hirschi, W. Luef, P. Gerber, R.
Keese, Helv. Chim. Acta 1992, 75, 1897 ± 1908; c) J. Wang, M.
Thommen, R. Keese, Acta Crystallogr. Sect. C 1996, 52, 2311 ± 2313;
d) M. Thommen, R. Keese, M. Förtsch, Acta Crystallogr. Sect. C 1996,
52, 2051 ± 2053.
‡
2H), 1.46 ± 1.43 (m, 2H); MS (EI, 70 eV): m/z (%): 337 (100) [M] , 338
(42), 339 (8).
[6] P. A. Grieco, E. B. Brandes, S. McCann, J. D. Clark, J. Org. Chem.
1989, 54, 5849 ± 5851.
[7] W. A. Smit, S. M. Buhanjuk, S. O. Simonyan, A. S. Shashkov, Tetrahe-
dron Lett. 1991, 32, 2105 ± 2108.
[8] a) P. A. Wender, T. M. Dore, M. A. DeLong, Tetrahedron Lett. 1996,
37, 7687 ± 7690; b) P. A. Wender, M. A. DeLong, F. C. Wireko, Acta
Crystallogr. Sect. C 1997, 53, 954 ± 956.
[9] For attempts to prepare cis,cis,cis,trans-[5.5.5.5]fenestranes, see
ref. [3c] (in particular ref. [25] cited therein).
[10] S. Chang, D. McNally, S. Shary-Tehrany, S. M. J. Hickey, R. H. Boyd, J.
Am. Chem. Soc. 1970, 92, 3109 ± 3118; b) N. L. Allinger, Y. H. Yuh, J.-
H. Lii, J. Am. Chem. Soc. 1989, 111, 8551 ± 8566; c) J. W. Barrett, R. P.
Linstead, J. Chem. Soc. 1936, 611 ± 616.
[11] For a discussion of the relative stabilities of the stereoisomeric
hydrindanes, see: E. L. Eliel, S. H. Wilen, Stereochemistry of Organic
Compounds, Wiley, New York, 1994, pp. 774Ð776, and references
therein.
(4ba,7ab,11ba,15bb)-7a,11b,15b-Trideutero-5,6,7,7a,11b,15b-hexa-
hydro-4bH-dibenzo[2,3:4,5]pentaleno[1,6-jk]fluorene (3b): This com-
pound was obtained by treating the cis,cis,cis,trans-fenestrane 4 with
KOtBu and [D6]DMSO exactly as described above, to yield 3b (18.3 mg,
90%). 1H NMR (500 MHz, CDCl3): d ˆ 7.38 ± 7.32 (AA'BB' system, 4H),
7.21 ± 7.16 (m, 8H), 3.17 (t, J ˆ 6.5 Hz, 1H), 1.91 ± 1.87 (m, 2H), 1.74 ± 1.71
‡
(m, 2H), 1.46 ± 1.44 (m, 2H); MS (EI, 70 eV): m/z (%): 337 (100) [M] , 338
(55), 339 (13).
(4ba,7ab,11ba,15bb)-7a-Deutero-5,6,7,7a,11b,15b-hexahydro-4bH-di-
benzo[2,3:4,5]pentaleno[1,6-jk]fluorene (3c):
A mixture of 4 (20 mg,
60 mmol), KOD (100 mg, 1.75 mmol), and [O,O'-D2]-diethylene glycol
(4.0 mL) was stirred under argon and heated at 1808C for 3 h. The reaction
mixture was allowed to cool, then poured into water (50 mL) and extracted
with dichloromethane. The organic layer was dried with sodium sulfate and
the solvent was removed. The product was purified by column chromatog-
raphy (n-hexane/ethyl acetate 3:1), yielding a mixture (19 mg, 90%) of
unreacted 4 and the monodeuterated product 3c in the ratio of 1.2:1.4 (by
1H NMR) as a colorless solid. 1H NMR of 3c (500 MHz, CDCl3): d ˆ 7.37 ±
[12] a) H. J. Monkhorst, J. Chem. Soc. Chem. Commun. 1968, 1111 ± 1112;
b) R. Hoffmann, R. W. Alder, C. F. Wilcox, Jr., J. Am. Chem. Soc.
1970, 92, 4992 ± 4993; c) R. Hoffmann, Pure Appl. Chem. 1971, 28,
Chem. Eur. J. 2001, 7, No. 15
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0947-6539/01/0715-3399 $ 17.50+.50/0
3399

D. Kuck et al.
FULL PAPER
181 ± 194; d) K. B. Wiberg, G. B. Ellison, J. J. Wendelowski, J. Am.
Chem. Soc. 1976, 98, 1212 ± 1218; e) J. B. Collins, J. D. Hill, E. D.
Jemmis, Y. Apeloig, P. v. R. Schleyer, J. A. Pople, J. Am. Chem. Soc.
1976, 98, 5419 ± 5427.
[24] D. J. Cram, M. R. V. Sahyun, G. R. Knox, J. Am. Chem. Soc. 1962, 85,
1734 ± 1735.
[25] a) The Raney nickel used was thoroughly washed until apparent
neutrality (pH 7.0); thus, only catalytic amounts of base, if any, fixed
on the surface of the catalyst may have effected epimerization.
[13] For the most recent work concerning this topic, see ref. [3] and: a) J. E.
Lyons, D. R. Rasmussen, M. P. McGrath, R. H. Nobes, L. Radom,
Angew. Chem. 1994, 106, 1722 ± 1724; Angew. Chem. Int. Ed. Engl.
1994, 33, 1667 ± 1668; b) D. R. Rasmussen, L. Radom, Angew. Chem.
1999, 111, 3051 ± 3054; Angew. Chem. Int. Ed. 1999, 38, 2875 ± 2878;
c) D. Röttger, G. Erker, Angew. Chem. 1997, 109, 840 ± 856; Angew.
Chem. Int. Ed. Engl. 1997, 36, 812 ± 827; d) P. v. R. Schleyer, J. Mol.
Struct. Theochem. 1995, 338, 317 ± 346; e) W. Siebert, A. Gunale,
Chem. Soc. Rev. 1999, 28, 367 ± 371.
[14] a) D. Kuck, A. Schuster, D. Gestmann, F. Posteher, H. Pritzkow,
Chem. Eur. J. 1996, 2, 58 ± 67; b) C. Fusco, M. Fiorentino, A. Dinoi, R.
Curci, R. A. Krause, D. Kuck, J. Org. Chem. 1996, 61, 8681 ± 8684;
c) D. Kuck, A. Schuster, R. A. Krause, J. Org. Chem. 1991, 56, 3472 ±
3475; d) D. Kuck, H. Bögge, J. Am. Chem. Soc. 1986, 108, 8107 ± 8109.
[15] For general reviews including this topic, see: a) D. Kuck, Top. Curr.
Chem. 1998, 196, 167 ± 231; b) D. Kuck, Liebigs Ann./Recueil 1997,
1043 ± 1057; c) D. Kuck, Synlett 1996, 949 ± 965.
.
b) Metal-catalyzed epimerization by H abstraction by the Raney Ni
cannot be ruled out, but Pd/C catalyst at ambient temperature does
not induce this process (cf. Scheme 6).
[26] a) C. G. Gutierrez, R. A. Stringham, T. Nitasaka, K. G. Glasscock, J.
Org. Chem. 1980, 45, 3393 ± 3395; b) for a review, see: W. P. Neumann,
Synthesis 1987, 665 ± 683.
[27] a) W. Ten Hoeve, H. Wynberg, J. Org. Chem. 1980, 45, 2925 ± 2930;
b) W. Ten Hoeve, Proefschrift, Rijksuniversiteit te Groningen, 1979.
[28] The presence of p-toluenesulfonic acid during the conversion 5 ! 26
and/or shorter reaction times did not suppress the epimerization.
[29] a) R. O. Hutchins, C. A. Milewski, B. E. Maryanoff, J. Am. Chem. Soc.
1973, 95, 3662 ± 3668; for a review, see: b) C. F. Lane, Synthesis 1975,
135 ± 146.
[30] B. Bredenkötter, Dissertation, Universität Bielefeld, 2000.
[31] a) This reaction was accompanied by considerable decomposition.
b) It should also be noted that a related benzodithieno-annelated
cis,cis,cis,trans-[5.5.5.6]fenestrane reacted by exclusive H/D exchange
at the benzhydrylic bridgeheads without epimerization to the all-cis
stereoisomer; B. Bredenkötter, D. Kuck, unpublished results.
[32] Crystallographic data (excluding structure factors) for the structure
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-135141. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK
(fax: (‡44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk)..
[33] The apical atoms of the boat, C5, and C7a, respectively, were found to
be 63.4(2) and 66.1(2) pm above its basal mean plane, the four
associated C atoms deviating by only Æ5.0(2) pm from that plane.
[34] D. Kuck, A. Schuster, W. Saak. S. Pohl, unpublished results.
[35] SHELXTL NT, Version 5.10. Bruker AXS, Inc. Madison, Wisconsin,
USA.
[16] B. Bredenkötter, D. Barth, D. Kuck, J. Chem. Soc. Chem. Commun.
1999, 847 ± 848.
[17] D. Kuck, Chem. Ber. 1994, 127, 409 ± 425.
[18] M. Seifert, D. Kuck, Tetrahedron 1996, 52, 13167 ± 13180.
[19] W. Hoeve, H. Wynberg, J. Org. Chem. 1979, 44, 1508 ± 1514.
[20] a) Ya. Shternberga, Ya. F. Freimanis, Zh. Organ. Khim. 1968, 4, 1081 ±
1086; Ya. Shternberga, Ya. F. Freimanis, J. Org. Chem. USSR 1968, 4,
1044 ± 1048; b) Yu. Yu. Popelis, V. A. Pestunovich, I. Ya. Shternberga,
Ya. F. Freimanis, Zh. Organ. Khim. 1972, 8, 1860 ± 1864; Yu. Yu.
Popelis, V. A. Pestunovich, I. Ya. Shternberga, Ya. F. Freimanis, J.
Org. Chem. USSR 1972, 8, 1907 ± 1910.
[21] For further examples, see ref. [3a] and D. Kuck, B. Bredenkötter, D.
Barth, Seifert, M. unpublished results.
[22] The MM ‡ , AM1 and PM3 calculations were performed using the
software package Hyperchem, Release 5.02 for Windows, Hypercube
Inc., Gainesville, FL, USA.
[23] The AM1 calculations suggest the axial (14b) alcohol is only ca.
1.7 kJmol 1 less stable than the quasi-equatorial (14a) alcohol.
Received: December 28, 2000 [F2974]
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