Synthesis, crystal structure, and circular dichroism spectra of (1S)- 4,8-diphenylbarbaralane-2,6-dicarbonitrile - Chiroptical properties of the transition state of a degenerate cope rearrangement

Article abstract of DOI:10.1002/(sici)1099-0690(199908)1999:8<1811::aid-ejoc1811>3.0.co;2-v

Diphenylbicyclo[3.3.1]nonane-2,6-dione rac-3 is resolved in 57 % overall yield by chromatographic separation of the diastereomeric (R)-N-(1- phenylethyl)carbamates 9 which are obtained from (R)-(1-phenylethyl) isocyanate (8) and the 6-hydroxydiphenylbicyclo[3.3.1]nonan-2-ones endo- and exo-4. The enantiomers (1R)- (e.r. = 98:2) and (1S)-3 (e.r. = 97:3) are regenerated from 9 by reduction with lithium aluminium hydride followed by Swern oxidation of the resulting diols 5. The title compound (1S)-1 is synthesised in three steps from (1S)-3 in improved yield on the route that had led to rac-1. The absolute configurations are established by X-ray diffraction analyses of the carbamates endo-(1R)-9 and exo(1S)-9. X-ray diffraction analyses were also performed of the camphanoate (1R)-7, the intermediates rac-endo-4 and (1S)-3, and the title compound (1S)-1. Hydroxy ketone rac-endo-4 adopts similar conformations in the solid state and in solution as shown by a comparison of vicinal ¹H,¹H coupling constants from proton spectra with those calculated from torsional angles in the crystal. The molecular structures of (1S)-1 and (1S)-3 closely resemble those of the corresponding racemates investigated previously. These results show (i) that intermolecular interactions in the solid state are of minor importance and (ii) that the unusually long C2-C8 distance of (1S)-1 and rac-1 (168 pm) is a molecular but not an averaged property due to a non-degenerate Cope rearrangement in the crystal. CD spectra are reported for (1R)- and (1S)-3, the unsaturated dicarbonitrile (1S)-13, and (1S)-1. The CD spectrum of (1S)- 1 exhibits a weak positive band at 459 nm where rac-1 shows a temperature- dependent absorption which has been assigned to the higher, vibronic state represented by rac-1*. The intensity of the weak CD band depends on the temperature and the solvents in the same way as the UV/Vis absorption of rac- 1. This supports the conclusion that both bands originate from the same source, viz. the transition state 1* of the degenerate Cope rearrangement 1 ? 1'.

Full text of DOI:10.1002/(sici)1099-0690(199908)1999:8<1811::aid-ejoc1811>3.0.co;2-v

FULL PAPER
Synthesis, Crystal Structure, and Circular Dichroism Spectra of
(1S)-4,8-Diphenylbarbaralane-2,6-dicarbonitrile – Chiroptical Properties of
the Transition State of a Degenerate Cope Rearrangement[1]
Helmut Quast,*[a] Maximilian Seefelder,[a] Eva-Maria Peters,[b] and Karl Peters[b]
Keywords: Asymmetric synthesis / Automerisation / Circular dichroism / Conformation analysis / Enantiomeric
resolution / Polycycles / Solid-state structures / Solvent effects / Thermochromism / Transition states
Diphenylbicyclo[3.3.1]nonane-2,6-dione rac-3 is resolved in
torsional angles in the crystal. The molecular structures of
57 % overall yield by chromatographic separation of the
(1S)-1 and (1S)-3 closely resemble those of the corresponding
diastereomeric (R)-N-(1-phenylethyl)carbamates 9 which are racemates investigated previously. These results show (i) that
obtained from (R)-(1-phenylethyl) isocyanate (8) and the 6-
hydroxydiphenylbicyclo[3.3.1]nonan-2-ones endo- and exo-
4. The enantiomers (1R)- (e.r. = 98:2) and (1S)-3 (e.r. = 97:3)
are regenerated from 9 by reduction with lithium aluminium
hydride followed by Swern oxidation of the resulting diols 5.
The title compound (1S)-1 is synthesised in three steps from
(1S)-3 in improved yield on the route that had led to rac-1.
intermolecular interactions in the solid state are of minor
importance and (ii) that the unusually long C2–C8 distance of
(1S)-1 and rac-1 (168 pm) is a molecular but not an averaged
property due to a non-degenerate Cope rearrangement in
the crystal. CD spectra are reported for (1R)- and (1S)-3, the
unsaturated dicarbonitrile (1S)-13, and (1S)-1. The CD
spectrum of (1S)-1 exhibits a weak positive band at 459 nm
The absolute configurations are established by X-ray where rac-1 shows a temperature-dependent absorption
diffraction analyses of the carbamates endo-(1R)-9 and exo-
(1S)-9. X-ray diffraction analyses were also performed of the
camphanoate (1R)-7, the intermediates rac-endo-4 and (1S)-
3, and the title compound (1S)-1. Hydroxy ketone rac-endo-
4 adopts similar conformations in the solid state and in
which has been assigned to the higher, vibronic state
represented by rac-1*. The intensity of the weak CD band
depends on the temperature and the solvents in the same
way as the UV/Vis absorption of rac-1. This supports the
conclusion that both bands originate from the same source,
viz. the transition state 1* of the degenerate Cope
rearrangement 1 o 1Ј.
1
solution as shown by a comparison of vicinal H,1H coupling
constants from proton spectra with those calculated from
sorption around 450 nm.[4] The increase of this band with
temperature has been ascribed to an equilibrium between
the two degenerate localised ground states 1, 1Ј and a long
wavelengths absorbing, delocalised state, which is located
just above the flat potential energy maximum between the
ground states; that is, in an area of the energy hypersurface
where vibronic interaction is strong. The latter state is to be
considered as the transition state of the degenerate Cope
rearrangement 1 o 1Ј and may be represented by the bisho-
moaromatic C2 structure 1*.[5] This simple model applies
only to the gas-phase and solutions in nonpolar or weakly
polar solvents, however, because, in strongly dipolar, aprotic
solvents, solvations terms predominate over the gas-phase
enthalpy difference between 1, 1Ј and 1* thus rendering the
solvated delocalised structure 1* more stable than the sol-
vated localised structures 1, 1Ј.[6] A nonracemic barbaral-
anedicarbonitrile (1R)- or (1S)-1 would offer the unique op-
portunity to investigate the chiroptical properties of the
transition structure (1R)- or (1S)-1*. The circular dichroism
spectra are expected to be characterised by the same effects
of temperature and solvents that have been documented for
the near-UV/Vis spectra of the equilibrating racemic species
1 o 1* o 1Ј.[6] This is indeed the case.
Introduction
Barbaralanes and semibullvalenes may be chiral by virtue
of their substitution pattern. Such chiral systems that un-
dergo rapid degenerate Cope rearrangements may be iso-
lated in nonracemic form provided that chirality is retained
in the Cope transition state, which hence must possess C2
symmetry. Degenerate Cope rearrangements via transition
states of CS symmetry lead to enantiomerisation, of co-
urse.[2] No nonracemic degenerate barbaralane or semi-
bullvalene has yet been prepared. Almost two decades ago,
Paquette and coworkers have synthesised a single nonra-
cemic semibullvalene, viz. (ϩ)-2(4)-methylsemibullvalene,
which is not however, degenerate.[3] Here we report syn-
thesis, X-ray diffraction analysis and circular dichroism
spectra of the title compound (1S)-1, which is the first non-
racemic degenerate Cope system. Two intriguing problems
induced us to embark on the present project.
(i) The racemic barbaralanedicarbonitrile rac-1 is ther-
mochromic owing to a temperature-dependent UV/Vis ab-
[a]
Institut für Organische Chemie, Universität Würzburg
Am Hubland, D-97074 Würzburg, Germany
Fax: (internat.) ϩ 49-931/888-4606
E-mail: seefelde@chemie.uni-wuerzburg.de
[b]
Max-Planck-Institut für Festkörperforschung,
(ii) The racemic barbaralanedicarbonitrile rac-1 forms a
racemate in the solid state.[4] Because the nonracemic com-
pound must crystallise in a different space group, a com-
Heisenbergstraße 1, D-70569 Stuttgart, Germany
Fax: (internat.) ϩ 49-711/689-1599
E-mail: karpet@vsibm1.mpi-stuttgart.mpg.de
Eur. J. Org. Chem. 1999, 1811Ϫ1823
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0808Ϫ1811 $ 17.50ϩ.50/0
1811

H. Quast, M. Seefelder, E.-M. Peters, K. Peters
FULL PAPER
parison of the molecules embedded in two different crystal ethanol).[16] Unfortunately, a preparative column packed
lattices promised to demonstrate their importance for the with the latter adsorbent was unavailable. Therefore, we set
apparent molecular geometry. In the case of rac-1 and other out to resolve rac-3 via diastereomeric derivatives. This
degenerate barbaralanes and semibullvalenes, unusual strategy appeared particularly promising since efficient pre-
atomic distances have been interpreted in terms of average parative high-resolution chromatography (MPLC) was at
values associated with the Cope rearrangement of two va- hand.[17] A host of procedures have been documented for
lence tautomers whose degeneracy is lifted in the solid state the resolution of enantiomeric ketones in this way.[18] One
owing to the particular crystal lattice of each system.[7]
of the most versatile and reliable involves reduction to the
We report our results in several sections. First, we detail racemic secondary alcohols and reoxidation after separ-
the enantiomer resolution of 4,8-diphenylbicyclo- ation and hydrolysis of their diastereomeric derivatives.[9]
[3.3.1]nonane-2,6-dione (rac-3) which is the crucial inter-
mediate on the route to the the racemic barbaralanedicar-
bonitrile rac-1.[4] Subsequently, we give a brief description
of the synthesis of (1S)-1 from (1S)-3 on that route. Exper-
imental procedures were simplified and improved yields ob-
tained in each step. In the next section, solid state structures
of racemates are compared to those of the corresponding
enantiomers. Finally, we investigate chiroptical properties
of the barbaralanedicarbonitrile (1S)-1 and intermediates
of its synthesis.
While the reduction of the diketone rac-2 with complex
hydrides is highly diastereoselective, affording the endo,
endo-diol,[19] sodium borohydride reduced the diphenyl di-
ketone rac-3 to a mixture which was separated into three
components, viz. two hydroxy ketones, rac-endo-4 (56%)
Results and Discussion
and rac-exo-4 (25%) and a mixture of diastereomeric diols
rac-5 (19%). The latter could be recycled almost quantitat-
Enantiomer Resolution of exo,exo-4,8-
Diphenylbicyclo[3.3.1]nonane-2,6-dione
ively by Swern oxidation[20] to the starting diketone rac-3.
Attempts to separate the racemic barbaralanedicarbo- Attempts to improve the poor diastereoselectivity by em-
nitrile rac-1 by analytical HPLC on chiral columns met with ploying other reducing agents[21] met with failure but at-
failure.[8] Because other separation techniques appeared tested to the lower reactivity of rac-3 compared to that of
even less attractive, we resorted to an enantioselective syn- rac-2.
thesis. The racemic compound rac-1 has been obtained in
The assignment of the structures to the two hydroxy ke-
seven steps from MeerweinЈs ester.[4] Of all intermediates tones rac-4 was based on carbon-13- (Table 8) and proton-
on this route, only the 2,6-diketones rac-2 and rac-3 offered NMR spectra which were completely analysed for the pro-
the opportunity of an efficient enantiomer resolution on a tons of the bicyclic skeletons (Tables 5 and 6). The relative
preparative scale. In fact, Gerlach has obtained (1S)-2 on a configurations may be deduced from the γ-gauche effect of
gramme scale from the corresponding racemic endo,endo- the 6-hydroxy groups on the chemical shifts of the carbon-
diol by fractionating crystallisation of the diastereomeric 13 atoms C4 which absorb at δ ϭ 35.0 and 42.1. Clearly,
bis[(1S)-camphanoates] followed by hydrolysis and oxi- the former value is indicative of the endo configuration.
dation.[9][10] Various preparations of single enantiomers of
(1S)-Camphanoyl chloride (6) has a longstanding record
2 or corresponding alcohols involving kinetic enantiomer in the resolution of racemic alcohols,[18] including the endo,
resolutions with bakerЈs yeast[11] or enzymes[12] are endo-diol derived from rac-2.[9] Treatment of the hydroxy
rendered unattractive, however, by low reactivity and mod- ketone rac-endo-4 with 6 in the presence of 4-(dimethylami-
est yields,[11] and the necessity of several steps including no)pyridine afforded an almost quantitative yield of the
cumbersome experimental and isolation procedures.[12] On diastereomeric camphanoates 7 which showed base-line
the other hand, the diphenyl diketone rac-3 is readily avail- separation on a high-resolution reversed-phase HPLC col-
able from rac-2 in three steps with an overall yield of umn. Unfortunately, a preparative column of this sort was
50Ϫ60% on a 0.1 mole scale[13][14] and lies already halfway unavailable, and attempts at separation on normal silica-gel
on the route to rac-1. Exploratory experiments with the columns met with failure. Slow crystallisation of the crude
view of resolving rac-3 by enantioselective HPLC gave only product from ethyl acetate afforded fine needles in 52%
unsatisfactory results on microcrystalline triacetylcellulose yield of a single diastereomer whose absolute configuration
(eluent methanol) but a fair, albeit not with base-line separ- (1S)-7[22] was proved by an X-ray diffraction analysis (Fig-
ation, on tris(phenylcarbamoyl)celluloseϪsilica[15] (eluent ure 1). The moderate yield and the lack of an efficient chro-
1812
Eur. J. Org. Chem. 1999, 1811Ϫ1823

Chiroptical Properties of the Transition State of a Degenerate Cope Rearrangement
FULL PAPER
matographic separation of the diastereomers deterred us
from further pursuing this method.
Figure 2. UV trace (λ ϭ 254 nm) recorded during medium-pressure
liquid chromatography (MPLC, five cycles) of the diastereomeric
N-(1-phenylethyl)carbamates endo-9 (2 g) on a (70 ϫ 7)-cm silica
column with petroleum ether/ethyl acetate
Figure 1. Stereographic projection of the camphanoate (1R)-7 with
the numbering of the atoms[22]
Much better results were obtained when (R)-(1-phenyl-
ethyl) isocyanate (8) was employed as resolving agent.[18]
In the presence of 4-(dimethylamino)pyridine, it converted
quantitatively both racemic hydroxy ketones endo- and exo-
4 into the corresponding mixtures of diastereomeric N-(1-
phenylethyl)carbamates 9. Both mixtures could be sepa-
rated by preparative chromatography on silica gel. While
cyclic MPLC was required for the complete separation of
endo-(1R)- and endo-(1S)-9 (Figure 2),[17cϪ17f] flash chro-
matography sufficed for separation of the diastereomers
exo-(1R)- and exo-(1S)-9 to be separated into fractions with
diastereomeric ratios (d.r.) > 97:< 3. MPLC improved these
ratios further.
It was very convenient that one diastereomer of the endo
pair and one of the exo pair, viz. endo-(1R)- and exo-(1S)-
9,[22] formed crystals suitable for X-ray diffraction analyses
which obviated the necessity of establishing the absolute
configurations by other methods (Figure 3).
Cleavage of carbamates is usually carried out with alkali
alkoxides, lithium aluminium hydride,[23] or, under particu-
larly mild conditions, with trichlorosilane in the presence of
triethylamine.[24] Treatment of the N-(1-phenylethyl)carba-
mate endo-(1R)-9 with the latter reagent gave, surprisingly,
only 46% of the hydroxy ketone endo-(1R)-4 besides 22%
of a by-product. On the basis of NMR evidence, we as-
signed the enamine structure 11 to the minor product. En-
amine 11 apparently arises from the major product and the
secondary amine 10 formed by reduction of the N-(1-phen-
Figure 3. Stereographic projections of the diastereomeric N-(1-phe-
nylethyl)carbamates endo-(1R)-9 (above) and exo-(1S)-9 (below)
with the numbering of the atoms[22]
Eur. J. Org. Chem. 1999, 1811Ϫ1823
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H. Quast, M. Seefelder, E.-M. Peters, K. Peters
FULL PAPER
ylethyl)carbamoyl moiety. Attempts to hydrolyse 11 with Synthesis of (1S)-4,8-Diphenylbarbaralane-2,6-
hydrochloric acid in ethanol were frustrated by the forma- dicarbonitrile
tion of three unknown products besides only small amounts
The racemic barbaralanedicarbonitrile rac-1 has been
of endo-(1R)-4. Therefore, endo-(1R)-9 as well as the other
prepared from the diphenyl diketone rac-3 in three or four
steps involving the conversion of rac-3 to the unsaturated
dicarbonitrile rac-13 in the usual way via a mixture of di-
three diastereomers were reduced with an excess of lithium
aluminium hydride to afford the corresponding 2,6-diols 5,
which were not characterised. Instead, the crude products
were converted by Swern oxidation[20] into the enantiomeric
diphenyl diketones (1R)- and (1S)-3 which could be isolated
in yields of 72Ϫ80% based on the single hydroxy ketones 4
(Table 1).
asteromeric bis[(O-trimethylsilyl)cyanohydrins] rac-12. The
crucial cyclisation of rac-13 to rac-1 was performed either
by the N-bromosuccinimide brominationϪzinc-copper cou-
ple debromination sequence or, in a single step, by phase
transfer-catalysed chlorinationϪdehydrochlorination with
hexachloroethane in the presence of concentrated aqueous
sodium hydroxide.[4] For the synthesis of (1S)-1 from (1S)-
3, the second, shorter route was followed and simplified
further by omitting the purification of the intermediate cy-
anohydrins (1S)-12. It was gratifying to obtain improved
yields for each step. Yields and melting points of the nonra-
cemic compounds with the absolute configuration (1S) are
listed in Table 1 together with the data of the racemic com-
pounds for comparison.
Table 1. Starting materials, reagents, yields, melting points and IR
data; yields and melting points of racemic mixtures are given in
brackets for comparison;[4] endo and exo are abbreviated as n and
x, respectively
X-ray Diffraction Analyses of the Bicyclic Ketones
rac-endo-4 and (1S)-3, and Barbaralanedicarbonitrile
(1S)-1
X-ray diffraction analyses of the hydroxy ketone deriva-
tives that were prepared with resolving reagents, viz. endo-
(1R)-7, endo-(1R)-, and exo-(1S)-9, established the absolute
configurations for all nonracemic compounds of this study.
An X-ray diffraction analysis of the racemic hydroxy ketone
rac-endo-4 itself not only confirmed the endo configuration
of the hydroxy group, which was derived on the basis of
NMR evidence, but also allowed a comparison of the con-
formations in the solid state and in solution by means of
1
torsional angles and vicinal H,1H coupling constants. The
molecule adopts the boat-chair conformation in the solid
state (Figure 4). That this conformation is also preferred in
solution is shown by the similarity between the vicinal
coupling constants that were calculated from torsional
angles φ in the crystal according to the Karplus equation
[Equation (1)][25] and those obtained by analysis of the 600-
MHz proton spectrum taken from a solution in [D]tri-
chloromethane (Tables 2 and 5). The same arguments have
led to similar results in previous comparative studies of the
[a]
Recorded for a solution in [D]trichloromethane (1-cm Infrasil
quartz cuvette). Ϫ [b] The crude product obtained by flash chroma-
tography was recycled by Swern[20] oxidation to rac-3. Ϫ Based
[c]
on the enantiomer in the racemic starting material. Ϫ [d] Tempera-
[e]
ture range of softening of the semi-solid material. Ϫ
Mixture
of endo,endo-, endo,exo- and exo,exo-(1S)-12 [41:45:14, RP-HPLC;
endo and exo refer to the (O-trimethylsilyl)oxy groups].
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Chiroptical Properties of the Transition State of a Degenerate Cope Rearrangement
FULL PAPER
conformations adopted by other bicyclo[3.3.1]nonanes, in- nonane system. This becomes evident by a comparison of
cluding rac-3,[4] in the solid state and in solution.[26][27] Sur- no less than six structures, viz. rac-[4] and (1S)-3, rac-endo-
prisingly, large vicinal coupling constants are missing in the 4, (1R)-7, endo-(1R)- and exo-(1S)-9 (Figures 5, 4, 1, and 3,
high-field proton spectrum of the exo-hydroxy ketone rac- respectively). In the case of exo-(1S)-9, even two large exo
exo-4 (Table 6). This shows that there are no antiperiplanar groups occupy the 1,3 diaxial conformation at the chair
1H,1H relationships that exist long enough for detection on cyclohexane ring rather than invert the conformations at
the NMR time scale. Therefore, the molecule rac-exo-4 ad- both sides.
opts either a single, very flattened configuration or two
boat-chair conformations that rapidly equilibrate.
Figure 4. Stereographic projections with the numbering of the
atoms of the (1R) enantiomer in the crystal of the racemic hydroxy
ketone rac-endo-4
Table 2. Torsional angles φ [°] obtained by X-ray diffraction analy-
sis, and calculated (Equation 1) and experimental vicinal 1H,1H
coupling constants (3J [Hz]) for the hydroxy ketone rac-endo-4;
endo and exo are abbreviated as n and x, respectively
Figure 5. Stereographic projections of the diphenyl diketone (1S)-
3 with the numbering of the atoms (above) and angles between the
planes of the bicyclo[3.3.1]nonane skeleton (below)
The (1S) enantiomer in the racemate rac-1[4] and a molecule
of (1S)-1 are almost superimposable. Only small differences
are found for the torsional angles involving the phenyl
3J ϭ 7 Ϫ cos φ ϩ 5 · cos(2 · φ) [Hz]
(1)
Cooperative interactions between molecules in the solid groups (Figure 6) and for the atomic distances of the tri-
state determine space group and crystal system, and may cyclic skeleton. In most cases (Table 3), the differences only
modify conformations of flexible molecules. The synthesis slightly exceed the standard deviations. Very small energy
of nonracemic molecules, i.e. diphenyl diketones (1R)- and barriers for the degenerate Cope rearrangement in solutions
(1S)-3, and barbaralanedicarbonitrile (1S)-1, whose race- of certain barbaralanes and semibullvalenes,[28] and solid-
mates had been studied by X-ray diffraction analyses,[4] of- state NMR evidence[7] support the suggestion that, in prin-
fered the opportunity to probe the effect of those cooperat- ciple, this rearrangement may also occur very rapidly in the
ive interactions in different crystal structures on (i) the con- solid state where it may be nondegenerate, however, because
formations and (ii) the equilibrium associated with a rapid intermolecular interactions render the two valence tauto-
Cope rearrangement of nondegenerate valence tautomers of mers nonequivalent. In these cases, the observed average
1. The racemic diphenyl diketone rac-3 takes the boat-chair lengths of the atomic distances C2ϪC8 and C4···C6 have
conformation with both wings being considerably flat- been considered as a measure for the positions of such equi-
tened.[4] Exactly the same conformation is adopted by the libria, which could be calculated on the basis of nonre-
nonracemic compound (1S)-3 (Figure 5). The molecules of arranging models.[7] Thus, rac-1 was assumed to exist in
rac-3 and (1S)-3 are distinct only by virtue of somewhat the crystal as two valence tautomers in the ratio 9:1.[4] The
different torsional angles involving their phenyl groups. The surprisingly small influence of the different crystal lattices
intramolecular interactions that determine the boat-chair on the molecular geometries of rac-1 and (1S)-1, uncovered
conformation obviously predominate over any intermolecu- in the present work, supports the idea, however, that the
lar interactions. The boat conformation of the β-phenyl- molecules are completely locked in one of the valence-tau-
cyclohexanone moiety appears particularly resistant to tomeric sites. As a result, the observed atomic distances be-
changes at the other cyclohexane ring of the bicyclo[3.3.1]- long to individual molecules and are not average values aris-
Eur. J. Org. Chem. 1999, 1811Ϫ1823
1815

H. Quast, M. Seefelder, E.-M. Peters, K. Peters
FULL PAPER
ing from two nondegenerate valence tautomers. Conse- dicarbonitriles rac-1 and (1S)-1 with those of 2,6-diphenyl-
quently, the length of the cyclopropane bond C2ϪC8 (168 barbaralane,[31] whose phenyl groups rotate without hin-
pm) adds 1 to the growing group of molecules with excep- drance by a neighbouring nitrile group. Accordingly, the
tionally long carbonϪcarbon single bonds.[29][30]
phenyl group at the cyclopropane ring of the latter adopts
an almost perfect bisected conformation. By contrast, the
phenyl groups of the former barbaralanes are twisted
strongly from this conformation, viz. by 63° (rac-1) and 59°
[(1S)-1] (Figure 6). There is little doubt that this deviation
from the most stable (bisected) conformation is caused by
the steric effect of the vicinal nitrile group. The torsional
angles involving the phenyl groups and the double bonds
at the other (“open”) side of the barbaralanes are similar,
however, viz. 22.6° (rac-1), 32.5° ([(1S)-1] (Figure 6) and
26.5° (2,6-diphenylbarbaralane).[31] This shows that there is
no significant steric interaction between the phenyl and the
cyano groups at the “open” side of the barbaralane skel-
eton. While the unfavourable interaction of the phenyl and
the cyano group at the cyclopropane ring destabilises the
ground state of the molecules 1, virtually no such interac-
tion is expected in the transition state 1* of the degenerate
Cope rearrangement. Therefore, we conclude that steric in-
teractions of the substituents at the cyclopropane rings of
barbaralanes and semibullvalenes contribute to the lower-
ing of the activation barriers by substituents. As a result,
these barriers cannot be estimated for 2,4,6,8-substituted
systems by merely adding the effects that were measured
with 2,6-substituted compounds.[28]
Both rac-1 and (1S)-1 are also orange-coloured and
thermochromic in the solid state. These properties attest to
the presence of a certain small fraction of the molecules
that occupy a higher, vibronic state, which corresponds to
the transition state 1* of the degenerate Cope rearrange-
ment in solution.[5] Because the sum of the atomic distances
C2/C4 and C4/C6 of this state is certainly larger than that
of a localised valence tautomer, the occupation of such
higher, vibronic states is one of the reasons for the large
values of this sum measured by X-ray diffraction analyses
of thermochromic barbaralanes[4][26] and semibullval-
enes.[2,7,32] In the absence of precise knowledge of the pro-
portions and the geometry of the higher states, however,
their share in the observed magnitudes of the atomic dis-
tances cannot be assessed.
Figure 6. Stereographic projection of the barbaralanedicarbonitrile
(1S)-1 with the numbering of the atoms (above). Newman projec-
tions along the bonds between the ipso carbon atoms of the phenyl
groups and the carbon atoms C8 (left) and C4 (right) for (1S)-1
(middle) and the racemate rac-1 (below)[4]
Table 3. Atomic distances d [pm] (standard deviations) for the tri-
cyclic skeleton of the racemic (rac-1)[4] and the nonracemic barba-
ralanedicarbonitrile (1S)-1 and differences between the distances
∆ ϭ d(rac-1) Ϫ d[(1S)-1]
Circular Dichroism Spectra[18a,33]
The enantiomeric ratios for (1R)- (98:2) and (1S)-3 (97:3)
and the products of the latter, (1S)-1 and (1S)-13, were cal-
culated from the enantiomeric ratio of the resolving agent
employed, viz. the isocyanate 8 (98:2), and the ratios
achieved in the separation of the diastereomeric carbam-
ates, i.e. 100:0 for endo- and exo-(1R)-9, and 99:1 for endo-
and exo-(1S)-9.
Optical rotations, circular dichroism (CD) and UV/Vis
data are listed in Table 4. The absorption for the barbaral-
anedicarbonitrile (1S)-1 in the visible range precluded the
[a]
The value 237.0(10) pm listed in Table 4 of ref.[4] is in error; the
correct figure (238.1 pm) has been given in the text.
It is enlightening to compare the conformations of the measurement of the optical rotation. CD spectra recorded
phenyl groups in the solid state of the diphenylbarbaralane- for (1R)- and (1S)-3, (1S)-13, and (1S)-1, and UV/Vis spec-
1816
Eur. J. Org. Chem. 1999, 1811Ϫ1823

Chiroptical Properties of the Transition State of a Degenerate Cope Rearrangement
FULL PAPER
tra taken from solutions of the corresponding racemic mix- Table 4. Optical rotations [α]D23, and circular dichroism and UV/
Vis data recorded for solutions in acetonitrile at 20Ϫ25°C
tures are displayed in Figures 7Ϫ9. The CD bands of the
diphenyl diketones (1R)- and (1S)-3, and the unsaturated
dicarbonitrile (1S)-13 are readily correlated with the UV
absorptions of the chromophors present. While circular
dichroism spectra for a number of bicyclic diketones have
been reported,[9,10,34] no data are known for unsaturated ni-
triles comparable to (1S)-13.
[a] The concentration [g/100 mL of the solution] is given in brackets.
Ϫ
[b] UV/Vis spectra were taken from solutions of the racemic mix-
[c]
tures. Ϫ
Measurement of the optical rotation with the light of
a sodium or mercury lamp was precluded by the absorption of
(1S)-1.
Figure 7. Circular dichroism spectra recorded for solutions of the
diphenyl diketones (1R)- and (1S)-3 (∆ε, left axis) and UV/Vis
spectrum taken from a solution of rac-3 (log ε, right axis); solvent
acetonitrile; temperature 20Ϫ25°C
Figure 9. Circular dichroism spectra recorded for a solution of
(1S)-1 (∆ε, left axis) and UV/Vis spectrum taken from a solution
of rac-1 (log ε, right axis); solvent acetonitrile; temperature
20Ϫ25°C; the insert shows the expanded CD spectrum (∆ε ϫ 50)
in the visible range
The most intriguing feature in the CD spectrum of (1S)-
1 is the weak, positive band with a maximum at 459 nm
which emerges after expansion of the ∆ε scale. The band is
neighbouring upon the UV/Vis absorption around 440 nm,
which has been attributed to a higher, vibronic state. In fact,
deconvolution of the UV/Vis spectrum of rac-1 with Gauss
curves has revealed the precise position of the long-wave-
length maximum at 460 nm.[5] Therefore, little room is left
for doubts of the identity of the sources for both, the CD
band and the UV/Vis band at long wavelengths. Convincing
evidence is provided by an investigation of the influence
of temperature and solvents on the former band. Rising
temperatures do indeed increase it (Figure 10) just as they
Figure 8. Circular dichroism spectra recorded for a solution of
(1S)-13 (∆ε, left axis) and UV/Vis spectrum taken from a solution
of rac-13 (log ε, right axis); solvent acetonitrile; temperature
20Ϫ25°C
The relatively strong positive (λmax ϭ 234 nm) and nega- enhance the UV/Vis absorption of rac-1 at long wave-
tive (λmax ϭ 267 nm) bands observed in the CD spectrum lengths.[4][5] More strongly intensifying effects are exerted
of (1S)-1 (Figure 9) may be assigned to the unsaturated ni- by polar, in particular dipolar aprotic solvents (Figure 11),
trile and the styryl chromophor, respectively, as indicated which affect the band of rac-1 in the visible range exactly
by a comparison with the CD spectrum of the unsaturated in the same way.[6] The coincidence of the maximum, and
dinitrile (1S)-13 (Figure 8).
the temperature and solvent dependence of the CD band
Eur. J. Org. Chem. 1999, 1811Ϫ1823
1817

H. Quast, M. Seefelder, E.-M. Peters, K. Peters
FULL PAPER
portant for the molecular geometry, which, therefore, may
be considered as crystal-independent molecular property.
Diphenylbarbaralanedicarbonitrile 1 is characterised by un-
common features, i.e. a very long carbonϪcarbon bond in
the cyclopropane ring, ground-state destabilisation by un-
favourable steric interactions across that bond, an extremely
low barrier towards the degenerate Cope rearrangement,
and a temperature- and solvent-dependent long-wavelength
absorption which is indicative of a sizeable fraction occupy-
ing a higher, vibronic (transition) state. The latter phenom-
enon is also observed in the CD spectra of (1S)-1. Thus
chiral, nonracemic thermochromic barbaralanes and semi-
bullvalenes allow the investigation of the chiroptical proper-
ties of pericyclic transition states.
Experimental Section
General Remarks: Yields, diastereomeric ratios (d.r.), melting
points, and IR: Table 1. Ϫ 1H NMR: Tables 2, 5Ϫ7. Ϫ 13C NMR:
Table 8. Ϫ MS: Table 9. Ϫ [α]D, CD and UV/Vis: Table 4. Ϫ Molec-
ular formulae and masses, and elemental analyses: Table 10. Ϫ
Melting points: Kofler apparatus from Reichert, Vienna, Austria.
Figure 10. Effect of temperature on circular dichroism spectra ta-
ken from a solution of (1S)-1 in butyronitrile; temperature-depen-
dent changes of the volume were taken into account by means of
density data;[6] reference temperature 298 K
1
Ϫ IR: PerkinϪElmer 1420. Ϫ H and 13C NMR: Bruker AC 250
(11) and DMX 600. The signals were assigned on the basis of
1
DEPT spectra, and H,1H and 13C,1H COSY experiments (except
for 11). Ϫ MS (70 eV): Finnigan MAT 8200. Ϫ UV/Vis: Perki-
nϪElmer 330; the data were transferred with the programme MS-
DOS Kermit 3.15 (Trusties of Columbia University), [ε] ϭ L molϪ1
cmϪ1. Ϫ Specific rotations: PerkinϪElmer polarimeter 241 MC. Ϫ
CD: Jobin-Yvon dichrograph CD6; variable-temperature CD spec-
tra were recorded with a 0.1-cm quartz cuvette equipped with a
heating mantel (Hellma, D-79371 Müllheim), which was kept at
constant temperatures with a thermostat (Colora K5, D-73547
Lorch). The temperature was measured in the cuvette (ther-
mometer 16213 with a NiCrϪNi thermoelement, Bioblock Scien-
tific, F-67403 Illkirch-Cedex). Ϫ HPLC: BrukerϪFranzen LC 21-
C equipped with a UV detector Knauer 87.00 (λ ϭ 254 nm), (250
ϫ 4.6) mm stainless-steel column packed with Ultremex 3µ silica
(Phenomenex), 1.5 mL/min petroleum ether (50Ϫ70°C) (PE)/ethyl
acetate (EA), 80:20, retention times tR [min] ϭ 4.7 [(1S)-13], 5.1
(3), 7.1 [(1S)-1], 8.2 (endo-4), 9.8 (exo-4); 7.2 [exo-(1R)-9], 10.0 [exo-
(1S)-9]; (90:10), tR ϭ 17.0 [endo-(1R)-9], 18.8 [endo-(1S)-9]; (250 ϫ
4.6)-mm stainless-steel column packed with reversed-phase silica
Figure 11. Long-wavelength sections of circular-dichroism spectra
recorded for solutions of (1S)-1 in different solvents at 20Ϫ25°C
˚
Prodigy 5µ ODS (3) 100 A (Phenomenex), 1.0 mL/min acetonitrile/
water (62:38), tR ϭ 34.5 [(1R)-7], 36.0 [(1S)-7]; 1.5 mL/min (70:30),
tR ϭ 2.7, 2.8 (5), 3.8 (endo-, exo-4), 5.1 (3), 9.4 [exo-(1S)-9], 9.9
[endo-(1S)-9], 10.5 [endo-(1R)-9], 10.6 [exo-(1R)-9], 28.3 (11);
1.5 mL/min acetonitrile, tR [min] ϭ 3.8 [endo,endo-(1S)-12], 4.3 [en-
with those of the UV/Vis band cannot be fortuitous. There-
fore, the arguments that support the assignment of the UV/
Vis band to the vibronic state, which may be represented by
the delocalised structure 1*, apply to the CD band as do,exo-(1S)-12], 5.2 [exo,exo-(1S)-12]. Ϫ (1S)-Camphanoyl chloride
well.[5][6] Consequently, the present study of chiroptical
properties of 1* complements the recent direct observation
by UV/Vis spectra of the transition state for the degenerate
(6) (> 98%, e.r. ϭ 99.5:0.5) and (R)-(1-phenylethyl) isocyanate (8)
(> 98%, e.r. ϭ 98:2) were purchased from Aldrich. Diphenyl dike-
tone rac-3 was prepared according to the published procedure.[14]
Cope rearrangement 1 o 1Ј, thus providing for novel chal- (1R)- and (1S)-exo-4,exo-8-Diphenylbicyclo[3.3.1]nonane-2,6-dione
[(1R)- and (1S)-3]
lenges to theoretical chemists.
endo- and exo-6-Hydroxy-exo-4,exo-8-diphenylbicyclo[3.3.1]nonan-
2-one [(endo- and exo-4)]: Sodium borohydride (0.17 g, 4.4 mmol)
was added to a stirred solution of rac-3 (3.00 g, 9.9 mmol) in etha-
nol (750 mL) followed by stirring for 16 h at 20Ϫ25°C. The pH of
the clear, yellow solution was adjusted to a value of 5 by addition
of aq. HCl (1 , 5 mL). The solvent was distilled in vacuo. Water
Conclusion
The present study demonstrates for two examples that
differences in the crystal lattices between the racemates (rac-
1, rac-3) and single enantiomers [(1S)-1, (1S)-3] are unim- (200 mL) was added to the residue followed by extraction of the
1818 Eur. J. Org. Chem. 1999, 1811Ϫ1823

Chiroptical Properties of the Transition State of a Degenerate Cope Rearrangement
FULL PAPER
suspension with CH2Cl2 (2 ϫ 50 mL). The combined org. layers
were extracted with water (50 mL) and dried with MgSO4. Distil-
Diastereomeric (1S)-Camphanoates (1R)- and (1S)-7: Under N2, a
solution of endo-4 (91.9 mg, 0.30 mmol), 6 (83.3 mg, 0.38 mmol),
lation of the solvent in vacuo gave a colourless, semi-solid residue and 4-(dimethylamino)pyridine (45.8 mg, 0.38 mmol) in CH2Cl2
which was dissolved in a minimum amount of ethanol. Slow crys- (1.5 mL) was stirred for 16 h at 20Ϫ25°C. The colourless solution
tallisation at Ϫ20°C afforded colourless crystals (endo- and exo-4) was extracted with aq. HCl (1 , 2 ϫ 1 mL). The combined aq.
and a mother liquor, which contained a mixture of endo- and exo- layers were extracted with CH2Cl2. The combined org. layers were
4 (13%) and the diastereomeric diols rac-5 (87%, RP-HPLC). extracted with water and dried with MgSO4. Distillation of the
MPLC of the crystals with PE/EA {73:27, 62 mL/min, 13 bar, tR
[min] ϭ 102 (endo-4), 113 (exo-4)} afforded two fractions. The sol-
vent was distilled in vacuo, and the solid residues were recrystal-
solvent in vacuo gave a colourless semi-solid residue (146 mg, 98%,
d.r. ϭ 1:1, RP-HPLC), which was recrystallised from EA by al-
lowing the solution to cool from 60 to 20Ϫ25°C during 15 h.
lised at Ϫ20°C to yield colourless prisms. The first fraction gave Colourless fine needles (38 mg, 52%, m.p. 204Ϫ206°C) were ob-
endo-4 (1.68 g, 56%), m.p. 139Ϫ141°C. The second fraction yielded tained which consisted exclusively of the faster eluted diastereomer
exo-4 (0.75 g, 25%), m.p. 107Ϫ108°C. Ϫ The solvent of the first
mother liquor was distilled i. vac. The colourless, semi-solid residue
was recycled to rac-3 by Swern oxidation (see below).
(1R)-7. The mother liquor was concentrated in vacuo. Seeding with
a crystal of (1R)-7 yielded a small second crop of colourless
needles, (1R)-/(1S)-7 ϭ 87:13. The mother liquor contained (1R)-
and (1S)-7 in the ratio 29:71.
Diastereomeric N-(1-Phenylethyl)carbamates endo- and exo-9: A
stirred solution of endo- or exo-4 (3.00 g, 9.8 mmol), 8 (1.51 g,
10.3 mmol) and 4-(dimethylamino)pyridine (1.25 g, 10.3 mmol) in
tetrahydrofuran was heated under reflux for 18 h. Distillation of
the solvent in vacuo gave a light-brown oil, which was dissolved in
CH2Cl2 (100 mL). The solution was extracted with aq. HCl (1 ,
50 mL). The aq. layer was extracted with CH2Cl2. The combined
org. layers were extracted with water (50 mL) and dried with
MgSO4. Distillation of the solvent in vacuo yielded light-brown oils
which were purified or separated by flash chromatography with PE/
EA (7:3).
Table 5. Chemical shifts (δ values, diagonal elements) and absolute
values of coupling constants ([Hz], other elements) in the 600-MHz
proton spectrum of the hydroxy ketone endo-4 taken from a solu-
tion in [D]trichloromethane; zigzag couplings (4J) are printed in
italics
endo-(1R)- and endo-(1S)-9: Flash chromatography yielded
a
colourless solid [d.r. ϭ 1:1 (HPLC)]. Cyclic MPLC with PE/EA
{80:20, 80 mL/min, tR [min] ϭ 131 [endo-(1R)-9], 135 [endo-(1S)-9]}
gave two fractions (Figure 2). The first afforded colourless crystals
(2.15 g, 96%), m.p. 163Ϫ164°C [endo-(1R)-9, d.r. ϭ 100:0]. Recrys-
tallisation from ethanol/water (7:3) at 60°C yielded crystals that
were suitable for an X-ray diffraction analysis. Ϫ The second frac-
tion afforded a colourless semi-solid material (2.13 g, 96%), soften-
ing at 62Ϫ69°C, [endo-(1S)-9, d.r. ϭ 99:1]. Attempts at crystallis-
ation from ethanol or EA met with failure.
exo-(1R)- and exo-(1S)-9: Flash chromatography yielded two frac-
tions with d.r. > 97:< 3 (HPLC). The separation was completed for
each fraction by MPLC with PE/EA {73:27, 60 mL/min, 10 bar, tR
[min] ϭ 76 [exo-(1R)-9], 98 [exo-(1S)-9]}. The first fraction afforded
a
colourless, semi-solid material (1.95 g, 88%), softening at
48Ϫ52°C [exo-(1R)-9, d.r. ϭ 100:0]. Attempts at crystallisation
from ethanol or EA met with failure. Ϫ The second fraction af-
forded colourless crystals (1.89 g, 86%), m.p. 118Ϫ119°C [exo-
(1S)-9, d.r. ϭ 99:1]. Recrystallisation from ethanol/water (1:1)
yielded crystals that were suitable for an X-ray diffraction analysis.
Table 6. Chemical shifts (δ values, diagonal elements) and absolute
values of coupling constants ([Hz], other elements) in the 600-MHz
proton spectrum of the hydroxy ketone exo-4 taken from a solution
in [D]trichloromethane; zigzag couplings (4J) are printed in italics
Cleavage of the N-(1-Phenylethyl)carbamate endo-(1R)-9 with Trich-
lorosilane in the Presence of Triethylamine: Under Ar, trichlorosil-
ane (3.72 g, 27.6 mmol) was added to a stirred solution of endo-
(1R)-9 (1.00 g, 2.2 mmol) and triethylamine (5.6 g, 55 mmol) in
CH2Cl2. After stirring for 24 h, endo-(1R)-9 had disappeared al-
most completely (RP-HPLC). The brown mixture was poored cau-
tiously upon ice (25 g). The white solid was removed by filtration
and washed with CH2Cl2 (50 mL). The colourless aq. layer was
extracted with CH2Cl2. The combined org. layers were dried with
MgSO4. Distillation of the solvent i. vac. gave a light-brown solid
which consisted of equal amounts of endo-(1R)-4 and a second
product with a long retention time on RP-HPLC. Flash chroma-
tography with PE/EA (7:3) separated the solid into two fractions.
The first afforded a light-brown solid (0.20 g, 22%, 11), melting
range 182Ϫ187°C, which was almost pure (RP-HPLC). Ϫ 1H
Eur. J. Org. Chem. 1999, 1811Ϫ1823
1819

H. Quast, M. Seefelder, E.-M. Peters, K. Peters
FULL PAPER
NMR (250 MHz, [D]trichloromethane): δ ϭ 1.60 (d, J ϭ 7 Hz),
4.87 (q), 2.47 (s) (H3CϪCHϪNϪCH3), 1.41 (dt, J ϭ 13.3, 2.8 Hz,
9-HЈ), 1.68 (dtd, J ϭ 13.3, 3.2, 0.9 Hz, 9-H), 1.97 (m, 1-H), 2.06
(td, J ϭ 11.9, 6.0 Hz, 3-Hendo), 2.23 (br. s, OH), 2.24 (ddm, J ϭ 12,
5 Hz, 3-Hexo), 2.98 (m, 5-H), 3.38 (dm, J ϭ 6 Hz, 4-H), 3.81 (d,
J ϭ 4.0 Hz, 8-H), 4.21 (dt, J ϭ 12.2, 4.7 Hz, 2-H), 4.73 (d, J ϭ
4.0 Hz, 7-H), 7.13Ϫ7.48 (m, 3 Ph). Ϫ 13C NMR (63 MHz, [D]trich-
loromethane): δ ϭ 16.8, 55.3, 33.0 (H3CϪCHϪNϪCH3), 21.9
(CH2-9), 30.5 (CH2-3), 35.2, 38.1, 42.4, 43.1 (CH), 69.4 (CHOH),
105.6, 149.2 (CHϭCϪN), 125.63, 125.73, 126.76, 127.20, 127.42,
127.57, 128.07, 128.23, 128.39 (ArϪCH), 142.1, 144.0, 147.9 (ipso-
C). Ϫ IR (CCl4): ν˜ ϭ 3590 cmϪ1 (OH). Ϫ The second fraction
yielded pale yellow crystals [0.31 g, 46%, endo-(1R)-4], m.p.
137Ϫ139°C, which were identified by comparison with rac-endo-
4 (HPLC).
Table 7. Chemical shifts (δ values) and absolute values of coupling
constants ([Hz]) in 600-MHz proton spectra recorded for solutions
in [D]trichloromethane; an asterisk (*) indicates that the couplings
can be observed in the 1H,1H-COSY spectrum but the values of
the coupling constants cannot be determined[22]
Reduction of the Diastereomeric N-(1-Phenylethyl)carbamates 9:
Lithium aluminium hydride (0.25 g, 6.6 mmol) was added in por-
tions to a stirred solution of a single diastereomer of 9 (1.00 g,
2.2 mmol) in tetrahydrofuran (5 mL) followed by heating under re-
flux for 6 h. The mixture was allowed to cool to 20Ϫ25°C. Accord-
ing to a recommended procedure,[36] water (0.25 mL), aq. NaOH
(15%, 0.25 mL), and water (0.75 mL) were added. The grey solid
was removed by filtration and washed with tetrahydrofuran.
CH2Cl2 (100 mL) was added to the filtrate, and the mixture was
extracted with aq. HCl (1 , 50 mL). The aq. layer was extracted
with CH2Cl2 (3 ϫ 25 mL). The combined org. layers were dried
with MgSO4. Distillation of the solvent i.vac. yielded a colourless,
semi-solid material (5). The crude product was immediately oxi-
dised according to Swern.[20]
Swern Oxidation of the Diastereomeric Diols 5: Trifluoroacetic an-
hydride (1.73 g, 8.3 mmol) was added dropwise under Ar to a
stirred, cooled (Ϫ75°C) solution of dimethyl sulphoxide (0.85 g,
11.0 mmol) in CH2Cl2 (12 mL) A colourless precipitate formed im-
mediately. After stirring for 10 min at Ϫ75°C, a solution of 5, ob-
tained from 9 (2.2 mmol), in CH2Cl2 (70 mL) was added dropwise
during 20 min. Stirring at Ϫ75°C was continued for 40 min fol-
lowed by dropwise addition of triethylamine (1.61 g, 16.0 mmol).
The stirred mixture was allowed to attain 20Ϫ25°C overnight. The
[a]
The protons 3-Hx, 3-Hn, and 4-H form an ABX system.
Table 8. Chemical shifts (δ values) in 151-MHz carbon-13 spectra recorded for solutions in [D]trichloromethane; figures that are printed
in italics may be exchanged
[a]
The signal has double intensity.
1820
Eur. J. Org. Chem. 1999, 1811Ϫ1823

Chiroptical Properties of the Transition State of a Degenerate Cope Rearrangement
FULL PAPER
10 mL). Crystallisation at Ϫ20°C afforded colourless crystals; re-
sults: Table 1.
Table 9. Masses of molecular ions and fragment ions (m/z), and
relative intensities [% of the base peak ( ϭ 100%)] in 70-eV mass
spectra recorded for the hydroxy ketones 4 and their derivatives
(1S)-4,8-Diphenylbarbaralane-2,6-dicarbonitrile [(1S)-1]
(1S)-exo-4,exo-8-Diphenylbicyclo[3.3.1]nona-2,6-diene-2,6-
dicarbonitrile [(1S)-13]: Trimethylsilyl cyanide (2.92 g, 29.4 mmol)
was added under Ar to a stirred solution of (1S)-3 (2.0 g, 6.6 mmol)
and KCN/18-crown-6 (1.09 g, 3.3 mmol) in CH2Cl2 (25 mL). The
solution, which was pale yellow at the beginning, turned colourless
under warming. After stirring of the solution for 2 h at 20Ϫ25°C,
sat. aq. KH2PO4 (60 mL) was added causing evolution of HCN
(Caution!). The layers were separated, and the aq. layer was ex-
tracted with CH2Cl2 (2 ϫ 30 mL). The combined org. layers were
extracted with a mixture of aq. sat. KH2PO4 (30 mL) and water
(30 mL). The aq. layer was extracted with CH2Cl2 (30 mL). The
combined org. layers were dried with MgSO4. The solvent was dis-
tilled in vacuo until the volume was about 20 mL. The dark yellow
solution was filtered through a short column (5 ϫ 2.5 cm) packed
with silica gel, which was rinsed with CH2Cl2 (100 mL). Distillation
of the solvent in vacuo gave a colourless, semi-solid product (3.0 g,
91%) consisting of endo,endo-, endo,exo-, and exo,exo-(1S)-12
(41:45:14, RP-HPLC).[4] The crude product was dissolved under
Ar in freshly distilled phosphoryl chloride (11 mL, 120 mmol). To
the cooled (0°C), stirred solution, a solution of HF in pyridine
(0.7 mL, 65%, 26 mmol) was added cautiously, followed by stirring
for 1 h at 20Ϫ25°C. Dry pyridine (33 mL, 0.41 mol) was added at
0°C, and the mixture was heated at 85°C for 2.5 h. CH2Cl2
(100 mL) was added at 0°C followed by slow, cautious addition of
cold aq. H2SO4 (1 , 210 mL). The layers were separated, and the
aq. layer was extracted with CH2Cl2 (2 ϫ 50 mL). The combined
[a]
[b]
Molecular ion. Ϫ
Relative intensity of the molecular ion ϭ
[c]
3%. Ϫ Relative intensity of the molecular ion ϭ 0.05%.
Table 10. Molecular formulae and masses, and elemental analyses
pale yellow solution was extracted with aq. HCl (1 , 40 mL), sat. org. layers were extracted with sat. aq. K2CO3 (100 mL) and dried
aq. NaHCO3 (40 mL) and water (40 mL) and dried with MgSO4.
Distillation of the solvent in vacuo gave a light-brown solid which
was dissolved at 20Ϫ25°C in a minimum amount of ethanol (ca.
with MgSO4. Distillation of the solvent in vacuo and flash chroma-
tography of the brown residue with PE/EA (85:15) yielded colour-
less crystals (1.06 g, 51%), m.p. 229Ϫ231°C.
Table 11. Experimental details and results of the X-ray diffraction analyses
[a]
[b]
Maximum and minimum of the remaining electron density in the final differential Fourier synthesis.
Eur. J. Org. Chem. 1999, 1811Ϫ1823
1821

H. Quast, M. Seefelder, E.-M. Peters, K. Peters
FULL PAPER
[14]
H. Quast, C. Becker, E.-M. Peters, K. Peters, H. G. von Schne-
(1S)-4,8-Diphenylbarbaralane-2,6-dicarbonitrile [(1S)-1]: According
to the procedure for rac-1,[4] (1S)-13 (0.98 g, 3.0 mmol) was treated
with hexachloroethane (2.16 g, 9.1 mmol) in a vigorously stirrred
mixture consisting of CH2Cl2 (15 mL), aq. tetrabutylammonium
hydroxide (0.7 mL, 40%) and aq. NaOH (8 mL, 50%). Workup as
described, distillation of the solvent in vacuo, and flash chromatog-
raphy of the dark-red, solid residue with PE/EA (8:2) afforded
brick-red needles (0.64 g, 65%), m.p. 224Ϫ225°C. Recrystallisation
from PE/EA (1:1) yielded crystals that were suitable for an X-ray
diffraction analysis.
ring, Liebigs Ann. 1997, 685Ϫ698.
[15] [15a]
Y. Okamoto, M. Kawashima, K. Hatada, J. Am. Chem.
[15b]
Soc. 1984, 101, 5357Ϫ5359. Ϫ
Review: Y. Okamoto, E.
Yashima, Angew. Chem. 1998, 110, 1072Ϫ1095; Angew. Chem.
Int. Ed. Engl. 1998, 37, 1020Ϫ1043.
[16]
We are indebted to Professor Mannschreck and coworkers, Re-
gensburg, for performing these experiments; c. f.: A. Mann-
schreck, Trends. Anal. Chem. 1993, 12, 220Ϫ225.
[17] [17a] G. Helmchen, B. Glatz, Ein präparativ einfaches System und
Säulen höchster Trennleistung zur präparativen Mitteldruck-
[17b]
Flüssigkeitschromatographie, Universität Stuttgart, 1978. Ϫ
E. Ade, G. Helmchen, G. Heiligenmann, Tetrahedron Lett.
[17c]
1980, 21, 1137Ϫ1140. Ϫ
B. A. Bidlingmeyer, Preparative
X-ray Diffraction Analyses were performed on transparent, colour-
less [rac-endo-4, (1R)-7, endo-(1R)-9, exo-(1S)-9, (1S)-3] or brick-
red [(1S)-1] crystals. The cell parameters were determined on the
basis of 70 reflections. The number of reflections reported in Table
11 were obtained with Mo-Kα radiation and 2 Θmax ϭ 55° [rac-
endo-4, endo-(1R)-9, exo-(1S)-9, (1S)-3, (1S)-1] or Cu-Kα radiation
and 2 Θmax ϭ 110° [(1R)-7] (graphite monochromator, ω scan).
Measurements were carried out with a system Siemens P4. The
programme SHELXTL PLUS[37] was employed. The structure was
solved by direct methods and refined anisotropically by the least-
squares method. The weighting scheme for Rw is 1/σ2. The posi-
tions of the hydrogen atoms were calculated by the riding model
and included with isotropic descriptions.[38]
Liquid Chomatography (Journal of Chromatography Library,
[17d]
vol. 38), 1st ed. Elsevier, Amsterdam 1987. Ϫ
A. Werner,
Kontakte (Darmstadt) 1989, (3), 50. Ϫ [17e] H. Quast, H. Jakobi,
B. Seiferling, Liebigs Ann. Chem. 1991, 41Ϫ46. Ϫ [17f] H. Quast,
J. Carlsen, R. Janiak, Chem. Ber. 1993, 126, 1461Ϫ1463.
[18] [18a]
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Chiroptical Properties of the Transition State of a Degenerate Cope Rearrangement
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Crystallographic data (excluding structure factors) for the struc-
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113999 [endo-(1R)-9], -114000 [exo-(1S)-9], -114001 [(1S)-3 ],
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1823