A new rotane family: Synthesis, structure, conformation, and dynamics of [3.4]-, [4.4]-, [5.4]-, and [6.4]rotane

Article abstract of DOI:10.1021/ja973118x

The synthesis, structure, conformation, and dynamics of a new rotane family consisting of four-membered rings are described. All syntheses are based on bicyclobutylidene (9): [2+1] cycloaddition of cyclobutylidene yields [3.4]rotane (5) (9-5), [2+2] cyclo

Full text of DOI:10.1021/ja973118x

J. Am. Chem. Soc. 1998, 120, 317-328
317
A New Rotane Family: Synthesis, Structure, Conformation, and
Dynamics of [3.4]-, [4.4]-, [5.4]-, and [6.4]Rotane1
Lutz Fitjer,*,† Christoph Steeneck,† Said Gaini-Rahimi,† Ulrike Schro1der,† Karl Justus,†
Peter Puder,† Martin Dittmer,† Carla Hassler,† Jo1rg Weiser,† Mathias Noltemeyer,‡ and
Markus Teichert‡
Contribution from the Institut fu¨r Organische Chemie der UniVersita¨t Go¨ttingen, Tammannstrasse 2,
D-37077 Go¨ttingen, Germany, and Institut fu¨r Anorganische Chemie der UniVersita¨t Go¨ttingen,
Tammannstrasse 4, D-37077 Go¨ttingen, Germany
ReceiVed September 4, 1997X
Abstract: The synthesis, structure, conformation, and dynamics of a new rotane family consisting of four-
membered rings are described. All syntheses are based on bicyclobutylidene (9): [2+1] cycloaddition of
cyclobutylidene yields [3.4]rotane (5) (9-5), [2+2] cycloaddition of trimethyleneketene followed by
spiroalkylation of the resulting trispiroketone 10 yields [4.4]rotane (6) (9-10-13-14-6), homologization of
10 via â-hydroxy selenides gives access to tetraspiroketone 11 and pentaspiroketone 12 (10-15-11-16-
12), and further elaboration directed toward a cyclopropylcarbene-cyclobutene rearrangement yields [5.4]-
rotane (7) and [6.4]rotane (8) [11(12)-18(24)-19(25)-20(26)-21(27)-22(28)-23(29)-7(8)]. The structures
of 6, 7, and 8 were determined by high-precision low-temperature X-ray analyses and by force field calculations
using the search routine HUNTER in connection with MM3(92). The following special features were
observed: From 5 to 8, the bond angles of the central ring increase while the bond angles at the spiro center
of the spiroannelated cyclobutane rings decrease. As a consequence, the cyclobutane rings change their geometry
from a regular trapezoid in 6 to a kite with the smallest angle at the spiro center in 7 and 8. At the same time
their folding decreases, until in 8 they are close to planar. At room temperature, all hexaspiranes (8, 25-29)
are conformationally stable. This phenomenon allowed a stereoselective synthesis of axially labeled [1-13C]-
8’ and, via a high-temperature equilibration with equatorially labeled [1-13C]8, a determination of the free
energy of activation for the chair to chair interconversion as ∆Gq487 ) 156.8 ( 1.1 kJ/mol. This is the highest
barrier of inversion ever reported for a cyclohexane. Promising candidates for even higher barriers are [6.5]-
rotane (32) and [6.6]rotane (33).
Introduction
rotane family was complete with the synthesis of [6.3]rotane
(4)6 in 1976 (Chart 1). [6.3]Rotane (4) was the first per(cyclo)-
alkylated cyclohexane existing at room temperature in solution
[m.n]Rotanes are composed of an m-membered central ring
(m ) 3, 4, 5, ...) and m n-membered peripheral rings (n ) 3, 4,
5, ...) such that each atom of the central ring is at the same
time part of a peripheral ring.2 Originally denominated as [n]-
rotanes3 and restricted to polyspiranes of three-membered rings,
they have attracted considerable interest. Beginning with the
synthesis of [5.3]rotane (3)3 and [4.3]rotane (2)4 in 1969, and
followed by the synthesis of [3.3]rotane (1)5 in 1973, the first
in a fixed chair conformation.7 Its barrier of inversion (G*
298
) 89.4 ( 1.0 kJ/mol)6,7a was the highest of a cyclohexane
known at the time. During the years which followed, the
physical-chemical properties8 and structural parameters9 of 1-4
(6) (a) Fitjer, L. Angew. Chem. 1976, 88, 804-805; Angew. Chem., Int.
Ed. Engl. 1976, 15, 763-764. (b) Proksch, E.; de Meijere, A. Tetrahedron
Lett. 1976, 4851-4854. (c) Fitjer, L. Chem. Ber. 1982, 115, 1047-1060.
(7) For other examples including cases of conformational isomerism
see: (a) Fitjer, L.; Klages, U.; Ku¨hn, W.; Stephenson, D. S.; Binsch, G.;
Noltemeyer, M.; Egert, E.; Sheldrick, G. M. Tetrahedron 1984, 40, 4337-
4349. (b) Wehle, D.; Fitjer, L. Tetrahedron Lett. 1986, 27, 5843-5846. (c)
Fitjer, L.; Giersig, M.; Wehle, D.; Dittmer, M.; Koltermann, G.-W.;
Schormann, N.; Egert, E. Tetrahedron 1988, 44, 393-404. (d) Fitjer, L.;
Klages, U.; Wehle, D.; Giersig, M.; Schormann, N.; Clegg, W.; Stephenson,
D. S.; Binsch, G. Tetrahedron 1988, 44, 405-416.
† Institut fu¨r Organische Chemie.
‡ Institut fu¨r Anorganische Chemie.
X Abstract published in AdVance ACS Abstracts, December 15, 1997.
(1) Polyspiranes, Part 26. Part 25: Fitjer, L.; Majewski, M.; Monzo´-
Oltra, H. Tetrahedron 1995, 51, 8835-8852. Preliminary communica-
tions: (a) Fitjer, L.; Quabeck, U. Angew. Chem. 1987, 99, 1054-1056;
Angew. Chem., Int. Ed. Engl. 1987, 26, 1023-1025. (b) Fitjer, L.; Justus,
K.; Puder, P.; Dittmer, M.; Hassler, C.; Noltemeyer, M. Angew. Chem. 1991,
103, 431-433; Angew. Chem., Int. Ed. Engl. 1991, 30, 436-438.
(2) Giersig, M.; Wehle, D.; Fitjer, L.; Schormann, N.; Clegg, W. Chem.
Ber. 1988, 121, 525-531.
(8) Gleiter, R.; Haider, R.; Conia, J. M.; Barnier, J. P.; de Meijere, A.;
Weber, W. J. Chem. Soc., Chem. Commun. 1979, 130-132.
(9) Crystal structures: (a) Pascard, C.; Prange, T.; de Meijere, A.; Weber,
W.; Barnier, J. P.; Conia, J. M. J. Chem. Soc., Chem. Commun. 1979, 425-
426. (b) Prange, T.; Pascard, C.; de Meijere, A.; Behrens, U.; Barnier, J.
P.; Conia, J. M. NouV. J. Chim. 1980, 4, 321-327. (c) Boese, R.; Miebach,
T.; de Meijere, A. J. Am. Chem. Soc. 1991, 113, 1743-1748. Calcula-
tions: (d) Randic, M.; Jakab, L. Croat. Chem. Acta 1970, 42, 425-432.
(e) Kovacevic, K.; Maksic, Z. B.; Mogus, A. Croat. Chem. Acta 1979, 52,
249-263. (f) Ioffe, A. I.; Svyatkin, V. A.; Nefedov, O. M. IzV. Akad. Nauk
SSSR, Ser. Khim. 1987, 801-807; Bull. Acad. Sci. USSR, DiV. Chem. Sci.
(Engl. Transl.) 1987, 727-733. (g) Aped, P.; Allinger, N. L. J. Am. Chem.
Soc. 1992, 114, 1-16.
(3) (a) Ripoll, J. L.; Conia, J. M. Tetrahedron Lett. 1969, 979-980. (b)
Ripoll, J. L.; Limasset, J. C.; Conia, J. M. Tetrahedron 1971, 27, 2431-
2452.
(4) (a) Conia, J. M.; Denis, J. M. Tetrahedron Lett. 1969, 3545-3546.
(b) Le Perchec, P.; Conia, J. M. Tetrahedron Lett. 1970, 1587-1588. (c)
Denis, J. M.; Le Perchec, P.; Conia, J. M. Tetrahedron 1977, 33, 399-
408.
(5) (a) Fitjer, L.; Conia, J. M. Angew. Chem. 1973, 85, 349-350; Angew.
Chem. Int. Ed. Engl. 1973, 12, 334-335. (b) Fitjer, L. Angew. Chem. 1973,
85, 832-833; Angew. Chem., Int. Ed. Engl. 1973, 12, 761-762.
S0002-7863(97)03118-1 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/06/1998

318 J. Am. Chem. Soc., Vol. 120, No. 2, 1998
Fitjer et al.
Chart 1
Chart 2
Scheme 1
were studied, and incomplete rotanes derived from 4 were
rearranged, yielding incomplete [6.4]coronanes.10 Today, the
chemistry of rotanes composed of three-membered rings is very
well known, and papers on more elaborate structures containing
spiroannelated three-membered rings ([n]triangulanes,11 [n]-
cyclotriangulanes,11 “exploding” rotanes12) are beginning to
appear.
For several reasons 5-8 (Chart 1) and hence rotanes of four-
membered rings are attractive synthetic goals: first, the complete
lack of knowledge of how to construct, homologize, and
spiroalkylate functionalized polyspiranes of four-membered
rings, second, an early report13 on an unsuccessful synthesis of
[3.4]rotane (5), and third, the definitive expectation that [6.4]-
rotane (8) would exhibit conformational isomerism14 at room
temperature and a barrier of inversion (160 kJ/mol)7d far beyond
that of 4. In the following, we give a full account of the
synthesis, structure, conformation, and dynamics of the complete
series 5-8.
reported13 that cyclobutylidene, as generated from cyclobutanone
tosyl hydrazone, does not add to bicyclobutylidene (9). We
therefore adopted the protocol of Brinker16 and generated the
cyclobutylidene at -70 °C by slow addition of methyllithium
to a solution of dibromocyclobutane17 in ether. In the presence
of an excess of bicyclobutylidene (9) we obtained the desired
[3.4]rotane (5) (symmetry D3h) in 30% yield, easily recognized
by the appearance of only three resonances in the 13C NMR
spectrum [15.39 (d), 22.11 (d), 30.64 (s)].
For the synthesis of [4.4]rotane (6) we reacted trimethyl-
eneketene18 with bicyclobutylidene (9) and spiroalkylated the
resulting trispiroketone 10 using the procedure of Trost.19 (See
Scheme 1.) For the experimental realization, cyclobutanecar-
boxylic acid chloride (0.10 mol) was added to a solution of
triethylamine (0.15 mol) in a large excess of bicyclobutylidene
(9) (100 mL) and the resulting mixture heated for 5 h to 120
°C. After acidic workup, 10 (bp 76 °C/0.6 Torr; yield 54%)
was isolated by distillation. Unchanged 9 (bp 145-148 °C)15
could be recovered as the first fraction. At lower temperatures
and with a less pronounced excess of bicyclobutylidene the
yields were distinctly lower. To achieve the spiroalkylation,
10 was reacted with 1-lithiocyclopropyl phenyl sulfide19a and
the resulting â-hydroxy sulfide 13 ring enlarged and hydrolyzed
to cyclobutanone 14 by treatment with p-toluenesulfonic acid
monohydrate in benzene.19b Wolff-Kishner reduction then
Results and Discussion
Our approach to 5-8 was based on the idea that the readily
available bicyclobutylidene (9)15 could open the way to all
compounds desired: [2+1] cycloaddition of cyclobutylidene
could deliver 5, and [2+2] cycloaddition of trimethyleneketene
followed by 2-fold homologization could lead to 10-12 (Chart
2) and, by subsequent spiroalkylation, to 6-8.
Synthesis of [3.4]Rotane (5) and [4.4]Rotane (6). For the
synthesis of [3.4]rotane (5) and [4.4]rotane (6) we envisaged
an addition of cyclobutylidene to bicyclobutylidene (9) and a
spiroalkylation of trispiroketone 10, respectively. It has been
(10) (a) Fitjer, L.; Wehle, D. Angew. Chem. 1979, 91, 927-928; Angew.
Chem., Int. Ed. Engl. 1979, 18, 868-869. (b) Fitjer, L.; Wehle, D.;
Noltemeyer, M.; Egert, E.; Sheldrick, G. M. Chem. Ber. 1984, 117, 203-
221.
(11) Nomenclature: (a) Zefirov, N. S.; Kozhushkov, S. I.; Kuznetsova,
T. S.; Kokoreva, O. V.; Lukin, K. A.; Ugrak, B. I.; Trach, S. S. J. Am.
Chem. Soc. 1990, 112, 7702-7707. (b) Zefirov, N. S.; Kutznetsova, T. S.;
Eremenko, O. V.; Kokoreva, O. V.; Zatonsky, G.; Ugrak, B. I. J. Org.
Chem. 1994, 59, 4087-4089. Recent reviews: (c) Zefirov, N. S.; Kuz-
netsova, T. S.; Zefirov, A. N. IzV. Akad. Nauk, Ser. Khim. 1995, 44, 1613-
1621; Russ. Chem. Bull. 1995, 44, 1543-1552. (d) de Meijere, A.;
Kozhushkov, S. In AdVances in Strain in Organic Chemistry; Halton, B.,
Ed.; JAI Press Ltd.: London 1995; Vol. 4, pp 225-282.
(12) (a) de Meijere, A.; Kozhushkov, S.; Puls, C.; Haumann, T.; Boese,
R.; Cooney, M. J.; Scott, L. T. Angew. Chem. 1994, 106, 934-936; Angew.
Chem., Int. Ed. Engl. 1994, 33, 869-871. (b) de Meijere, A.; Kozhushkov,
S.; Haumann, T.; Boese, R.; Puls, C.; Cooney, M. J.; Scott, L. T. Chem.
Eur. J. 1995, 1, 124-131.
(13) Bee, L. K.; Everett, J. W.; Garratt, P. J. Tetrahedron 1977, 33,
2143-2150.
(16) Brinker, U. H.; Boxberger, M. Angew. Chem. 1984, 96, 971-972;
Angew. Chem., Int. Ed. Engl. 1984, 23, 974-975.
(17) Blankenship, C.; Paquette, L. A. Synth. Commun. 1984, 14, 983-
987.
(18) Cycloadditions of trimethyleneketene to other compounds were not
known. Its dimerization has been described: Erickson, J. L. E.; Collins,
Jr., F. E.; Owen, B. L. J. Org. Chem. 1966, 31, 480-484.
(19) (a) Trost, B. M.; Keeley, D. E.; Arndt, H. C.; Rigby, J. H.;
Bagdanowicz, M. J. J. Am. Chem. Soc. 1977, 99, 3080-3087. (b) Trost, B.
M.; Keeley, D. E.; Arndt, H. C.; Bogdanowicz, M. J. J. Am. Chem. Soc.
1977, 99, 3088-3100.
(14) We use the term “conformational isomerism” in the sense defined
by Dale (Dale, J. Stereochemie und Konformationsanalyse; Verlag Che-
mie: Weinheim, 1978). For this and other definitions, see also: Ernst, L.
Chem. Unserer Zeit 1983, 17, 21.
(15) Fitjer, L.; Quabeck, U. Synthesis 1987, 299-300.

A New Rotane Family
J. Am. Chem. Soc., Vol. 120, No. 2, 1998 319
Scheme 2
experimental determination through dynamic NMR could be
excluded and the necessity to synthesize stereospecifically
labeled material for a classical equilibration study became
obvious. Clearly, the spiroalkylation used for the synthesis of
[4.4]rotane (6) was unsuitable, but a synthesis via a cyclopro-
pylcarbene-cyclobutene rearrangement24 seemed promising. In
this case, specific labeling with carbon-13 could be introduced
in the first step, and specific labeling with deuterium in the first
or the last step of a sequence beginning with a methylenation
(12-24) and ending with a hydrogenation (29-8). All inter-
mediates (25-28) were expected to be conformationally stable
while the regiochemistry of the cyclopropylcarbene to cy-
clobutene rearrangement (28-29) was recognized as of no
influence on the stereochemical result. (See Scheme 3.)
For the synthesis of unlabeled [5.4]rotane (7) and [6.4]rotane
(8) the ketones 11 and 12 were subjected to high-temperature
methylenations25 and the products 18 and 24 converted by
copper-catalyzed decomposition of methyl diazoacetate into the
pentaspirane 19 (mp 65 °C), and the conformationally isomeric
hexaspiranes 25 (mp 130-134 °C) and 25’ (mp 147-151 °C),
respectively. The stereochemistry of the hexaspiranes was
secured by an X-ray analysis of the minor isomer 25’,26 while
the major isomer 28 was used for further elaboration. Reduction
of 19 and 25 with lithium aluminium hydride afforded the
alcohols 20 (mp 49 °C) and 26 (mp 135-185 °C), respectively,
and Swern oxidation27 yielded the aldehydes 21 and 27,
respectively. Reaction of 21 and 27 with tosyl hydrazide in
dichloromethane/triethylamine28 and heating of the resulting
hydrazones 22 and 28 with sodium methoxide in diethylene
glycol dimethyl ether yielded the cyclobutenes 23 (mp 105 °C)
and 29 (mp 175-188 °C), respectively, which were hydroge-
nated over palladium on carbon in pentane to afford the desired
[5.4]rotane (7) (mp 70-110 °C) and [6.4]rotane (8) (mp 274
°C), respectively. Deuteration of 29 yielded [1,2-D2]8. As with
4 and 5, the structures of the new rotanes followed from their
13C NMR spectra. At room temperature, 7 [16.78 (d), 27.40
(d), 55.30 (s)] shows three resonances for a planar or rapidly
inverting species (effective symmetry D5h), while 8 [16.76 (d),
25.65 (d), 28.53 (d), 49.79 (s)] shows four resonances for a
fixed chair conformation (symmetry D3d).
yielded [4.4]rotane (6) (effective symmetry D4h), and once again
the appearance of only three resonances in the 13C NMR
spectrum [16.58 (d), 25.20 (d), 50.19 (s)] indicated the final
success.
Homologization of Trispiroketone 10. For the synthesis
of [5.4]rotane (7) and [6.4]rotane (8) we needed the tetra- and
pentaspiroketones 11 and 12, respectively. We therefore
explored the possibility of a ring enlargement of 10 via
â-hydroxy selenides20 using 1-lithio-1-(methylseleno)-21 and
1-lithio-1-(phenylseleno)cyclobutane.21 Indeed, both reagents
added to trispiroketone 10 to give the desired â-hydroxy
selenides 15a and 15b, respectively, which could be ring
enlarged to tetraspiroketone 11 by treatment with silver tet-
rafluoroborate on aluminium oxide or 3-chloroperoxybenzoic
acid. (See Scheme 2.)
Attempts to repeat the homologization with 1-lithio-1-
(phenylseleno)cyclobutane failed. However, 1-lithio-1-(meth-
ylseleno)cyclobutane reacted smoothly, and ring enlargement
of the resulting â-hydroxy selenide 16a using silver tetrafluo-
roborate on aluminium oxide completed the synthesis of 12.22
With 3-chloroperoxybenzoic acid a considerable amount of
epoxide 17 was formed. The successful homologization 10-
11-12 represents a further example for the usefulness of
selenium-stabilized carbanions for sterically demanding addition
reactions otherwise difficult to achieve.23
Crystal Structures and Force Field Calculations. Suitable
crystals for high-precision low-temperature X-ray analyses could
be obtained from [4.4]rotane (6), [5.4]rotane (7), and [6.4]rotane
(8). As several unusual structural features emerged, 6-8 were
also subjected to force field calculations using the conforma-
(24) Review: Shapiro, R. H. Org. React. (N.Y.) 1976, 23, 405-507.
(25) Fitjer, L.; Quabeck, U. Synth. Commun. 1985, 15, 855-864.
(26) The X-ray crystal structure data of 25’ are available as Supporting
Information.
Synthesis of [5.4]Rotane (7) and [6.4]Rotane (8). As
already pointed out, the expected barrier of inversion of [6.4]-
rotane (8) was so extremely high (160 kJ/mol)7d that an
(27) Review: Mancuso, A. J.; Swern, D. Synthesis 1981, 165-185. 21
and 27 were used as crude products and contained small amounts of
triethylamine. Upon attempting a chromatographic purification on silica gel
in dichloromethane 21 rearranged to a mixture of two stereoisomeric
aldehydes, 30 and 31.1b
(20) Ring expansions via â-hydroxy selenides are known: (a) Labar,
D.; Krief, A. J. Chem. Soc., Chem. Commun. 1982, 564-566. (b) Labar,
D.; Laboureur, J. L.; Krief, A. Tetrahedron Lett. 1982, 23, 983-986. (c)
Laboureur, J. L.; Krief, A. Tetrahedron Lett. 1984, 25 2713-2716. The
insertion of a cyclobutane is new.
(21) Synthesis of selenoketals: (a) Krief, A.; Clarembeau, M.; Cravador,
A.; Dumont, W.; Hevesi, L.; Luchetti, J.; van Ende, D. Tetrahedron 1985,
41, 4793-4812. Reductive metalations: (b) Krief, A. Tetrahedron 1980,
36, 2531-2640.
(22) For an alternative synthesis, see: (a) Fitjer, L.; Giersig, M.; Clegg,
W.; Schormann, N.; Sheldrick, G. M. Tetrahedron Lett. 1983, 24, 5351-
5354. (b) Giersig, M.; Wehle, D.; Fitjer, L.; Schormann, N.; Clegg, W.
Chem. Ber. 1988, 121, 525-531.
(23) 1-Lithiocyclobutyl phenyl sulfide and cyclopropylidene triph-
enylphosphorane did not react with 11.
(28) By treatment with tosyl hydrazide in aqueous methanol (Wiberg,
K. B.; Lavanish, J. M. J. Am. Chem. Soc. 1966, 88, 5272-5275) 21
rearranged to a single tosylhydrazone derived from one of the two
stereoisomeric aldehydes obtained during attempted chromatographic
purification of 21.

320 J. Am. Chem. Soc., Vol. 120, No. 2, 1998
Fitjer et al.
Scheme 3
Table 1. Averaged Values for Selected Bond Lengths, Bond Angles, and Puckering Angles in 6-8 As Determined by Force Field
Calculations and by X-ray Analysis
rotane
a (Å)
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
δ (deg)
φ (deg)
method
6
1.544
1.543
1.549
1.537
1.545
1.545
1.547
1.546
1.563
1.570
1.572
1.582
1.547
1.561
1.539
1.557
1.541
1.556
87.5
87.4
103.6
104.0
112.6
113.2
88.6
90.4
87.5
86.7
88.0
87.2
88.7
86.1
89.8
89.5
90.9
91.9
88.6
89.2
89.2
87.6
90.2
89.0
24.8
31.0
17.5
26.7
3.0
X-ray
MM3
X-ray
MM3
X-ray
MM3
7
8
0.0
tional search routine HUNTER29 in connection with MM3(92).30
ORTEP plots of the X-ray crystal structures are given in Figure
1, and selected experimental and calculated structural data are
collected in Table 1.
proximal and the distal bonds are identical (b ) c ) 1.547 Å),
but in 7 and 8, the proximal bonds are elongated (b ) 1.563
(7) and 1.572 (8) Å) and the distal bonds are shortened (c )
1.539 (7) and 1.541 (8) Å). A similar course follows for the
corresponding bond angles â and δ: These angles are identical
in 6 (â ) δ ) 88.6°), but in going to 7 and 8, â decreases (â
) 87.5° (7), and 88.0°) and δ increases (δ ) 89.2° (7) and
90.2° (8)). Obviously, the increase in R (R ) 87.5° (6), 103.6°
(7), and 112.6° (8)) translates to a decrease in â and an increase
in δ with concomitant lengthening of b and shortening of c.
(See Chart 3.) As a result, the spiroannelated cyclobutane rings
change their geometry from a regular trapezoid in 6 to a kite
with the smallest angle at the spiro center in 7 and 8. In [3.4]-
rotane (5) the situation should be inverse.31
Due to a lack of parameters, [3.4]rotane (5) was not accepted
by MM3(92). The parameters for all other rotanes were
available. Within 3 kcal above the global minimum the search
routine HUNTER located four conformers for 6, five conformers
for 7, and a single conformer for 8. All conformers of 6 and 8
and the four lowest in energy of 7 are shown in Figure 2.
In [4.4]rotane (6), the calculated global minimum conforma-
tion represents the conformation in the crystal state. In [5.4]-
rotane (7), none of the four conformations lowest in energy
In the crystal state, the cyclobutane rings in [4.4]rotane (6)
are systematically folded (φ ) 33.4° (central ring) and 24.9
and 24.7° (peripheral rings)). In [5.4]rotane (7), the cyclopen-
tane ring adopts a slightly distorted envelope conformation:
C(1), C(5), C(9), and C(17) form an almost perfect plane (mean
deviation 0.021 Å), while the flap atom C(13) is located 0.684
Å above this plane. The cyclobutane rings at C(13) and C(9)
are nearly planar (φ ) 9.7°) and planar (φ ) 0.2°), respectively.
The remaining three cyclobutane rings are moderately puckered
(φ ) 23.1, 26.5, and 28.2°). In [6.4]rotane (8), the cyclohexane
ring adopts a slightly flattened chair conformation (∑|θ| )
308.4°). All cyclobutane rings are close to planar (φ ) 1.0,
3.8, and 4.2°), and all proximal cyclobutane bonds are perfectly
staggered (|θ| ) 48.6-50.0°).
Interesting anomalies are observed in the spiroannelated
cyclobutane rings (Table 1): In 6, the averaged lengths of the
(29) Weiser, J.; Holthausen, M. C.; Fitjer, L. J. Comput. Chem. 1997,
18, 1264-1281. A Unix version of HUNTER connected with MM3(92)
(QCPE #674) may be obtained from the Quantum Chemistry Program
Exchange (QCPE), University of Indiana, Bloomington, IN 47405.
(30) Allinger, N. L.; Yuh, Y. H.; Lii, J.-H. J. Am. Chem. Soc. 1989,
111, 8551-8556.
(31) For an experimental study on the closely related [3.3]rotane (1),
see ref 9c.

A New Rotane Family
J. Am. Chem. Soc., Vol. 120, No. 2, 1998 321
Figure 3. Least-squares fit of the X-ray crystal structures (continuous)
and the calculated global minimum structures (dotted) of 6, 7, and 8.
Chart 3
is planar in the crystal, but folded according to MM3(92).
Interestingly, this cyclobutane ring is the only one where the
anisotropic displacement parameters of the peripheral carbon
atom (C(11)) even at -140 °C are large. In contrast to 6 and
7, only a single low-energy conformer exists for [6.4]rotane
(8). The geometry of this conformer is governed by strong
nonbonding interactions and matches the crystal structure
closely. A least-squares fit of the X-ray crystal structures and
the calculated global minimum structures of 6, 7, and 8 is shown
in Figure 3. In all cases, the mean deviations are small (6,
0.0632 Å; 7, 0.0957 Å; 8, 0.0395 Å). This indicates that MM3-
(92) delivers reliable results.
Dynamics of [6.4]Rotane (8). [6.4]Rotane (8) is very
sparingly soluble, and all attempts to determine its inversion
barrier 2H NMR spectroscopically via a high temperature
equilibration of [1,2-D2]8 failed because of the large line widths
and the poor solubility. To increase the sensitivity toward an
NMR analysis, stereospecifically 13C-labeled material had to
be prepared. Therefore, 12 was methylenated with ([13C]-
methylene)triphenylphosphorane and subsequently converted to
[1-13C]8’ as described for unlabeled 8 ([methylene-13C]-24 f
[2-13C]25 f [2-13C]26 f [2-13C]27 f [2-13C]28 f [3-13C]29
f [1-13C]8’).
Figure 1. ORTEP plots of the X-ray crystal structures of 6, 7, and 8
(50% probability ellipsoids, hydrogen atoms omitted) in side view and
top view.
Preliminary measurements revealed that the equilibration of
[1-13C]8’ could best be followed by 13C NMR spectroscopy
(125.9 MHz, 1,3-bis([D3]methoxy)benzene) at 214 °C using the
resonances of the axial (26.01) and equatorial carbon atoms
(28.82) of the cyclobutane rings. For the kinetic analysis, the
spectra were taken at appropriate times and the intensities of
the resonances of the axial (I′) and equatorial (I) carbon atoms
measured by careful integration (Figure 4). As could have been
expected, the equilibration followed first-order kinetics (Figure
5) and led to k([1-13C]8’) ) k([1-13C]8) ) (1.547 ( 0.019) ×
10-4 s-1 at 214 ( 3 °C. Insertion of these data into the Eyring
equation yielded the free energy of activation as ∆Gq487 ) 156.8
( 1.1 kJ/mol and thereby the highest barrier of inversion ever
reported for a cyclohexane.
In view of the unusual properties of [6.4]rotane (8) it is
tempting to speculate that cyclohexanes with even more
pronounced anomalies could exist. In a search for possible
candidates, we performed MM3 calculations on [6.5]rotane (32)
and [6.6]rotane (33). Within 3 kcal above the global minimum
the search routine HUNTER located more than 40 minima for
32 and more than 100 minima for 33. In all cases, the central
ring adopts a chair, while the peripheral rings exist in a large
number of different combinations of envelope conformations
in 32 and chair and/or boat conformations in 33. Surprisingly,
none of the high-symmetry conformations 32b and 33b-d,
Figure 2. Low-energy conformations and corresponding heats of
formation (strain energies) (kcal/mol) of 6, 7, and 8 as determined with
HUNTER in connection with MM3(92).
matches the crystal structure exactly. However, the global
minimum conformation fits best: Four of the five cyclobutane
rings are folded as in the crystal, and only one cyclobutane ring

322 J. Am. Chem. Soc., Vol. 120, No. 2, 1998
Fitjer et al.
Figure 4. 13C NMR spectra (125.9 MHz, 1,3-bis([D3]methoxy)benzene
(x), 50 °C) of [1-13C]8’: (a) before and (b) after equilibration. Spectral
parameters and details concerning the kinetic analysis are given in the
Experimental Section.
Figure 6. Selected low-energy conformations and corresponding heats
of formation (strain energies) (kcal/mol) of 32 and 33 as determined
with HUNTER in connection with MM3(92).
Figure 7. Heats of formation (strain energies/reduced strain energies)
of 34-37 and 8 as determined with HUNTER in connection with MM3-
(92), and experimental free energies of activation for the chair-to-chair
interconversions (kcal/mol).
Figure 5. Time course of the intensity of the resonance lines for the
axial (I’) and equatorial (I) carbon atoms of the cyclobutane rings in
[1-13C]8’ at 214 °C, and least-squares approximation of -ln(K1 - K2-
[I/(I + I’)]) ) [k([1-13C]8’) + k([1-13C]8)]t with K1 ) 1 + 12p/(m -
p) and K2 ) 2(11p + m)/(m - p). The rate law includes corrections
for the observed superposition of the resonance lines for magnetically
equivalent labeled (m ) 99) and unlabeled (p ) 1) positions. Details
are given in the Experimental Section.
in 8 (87.0 kcal/mol) and 32 (90.9 kcal/mol) are indeed strong,
but only half as strong as in 33 (170.3 kcal/mol). We therefore
believe that a synthesis and investigation of the structure,
conformation, and dynamics of the unknown rotanes 32 and
33 could lead to new frontiers.
A last note concerns the origin of the extraordinary barrier
of [6.4]rotane (8) and its relation to the barriers of the
hexaspiranes 34,7a 357c, and 36,7c and the topologically simpler
permethylcyclohexane (37)32 (Figure 7). In the ground state,
all compounds adopt a chair and the reduced strain energy,
quantifying the nonbonding interactions and calculated as before,
first strongly increases (45.7 (34), 53.4 (35), 67.2 (36), 87.0
respectively, represent a global minimum. According to MM3-
(92), the global minima are the low-symmetry conformations
32a and 33a (Figure 6).
Clearly, the conformation and dynamics of [6.4]rotane (8),
[6.5]rotane (32), and [6.6]rotane (33) must be governed by
strong nonbonding interactions. A rough estimate for such
interactions results if the calculated total strain energies (245.7
(8), 135.2 (32), 182.1 (33) kcal/mol) are reduced by the sum of
the calculated strain energies of all individual rings (26.2
(cyclobutane), 7.1 (cyclopentane), 1.7 (cyclohexane) kcal/mol).
The values obtained indicate that the nonbonding interactions
(32) (a) Fitjer, L.; Scheuermann, H.-J.; Wehle, D. Tetrahedron Lett. 1984,
25, 2329-2332. (b) Wehle, D.; Scheuermann, H.-J.; Fitjer, L. Chem. Ber.
1986, 119, 3127-3140.

A New Rotane Family
J. Am. Chem. Soc., Vol. 120, No. 2, 1998 323
or a Bruker AMX 300 spectrometer. For standards other than TMS
the following chemical shifts were used: δH(CHDCl2) ) 5.32 ppm,
δH(CHCl3) ) 7.24 ppm, δH(C6HD5) ) 7.28 ppm, δC(CD2Cl2) ) 53.80
ppm, δC(CDCl3) ) 77.00 ppm, δC(C6D6) ) 128.00 ppm, and δC[1,3-
(CD3O)2C6H4, hept] ) 54.05 ppm. Some of the 13C NMR spectra were
studied by APT (attached proton test) to determine the number of
protons attached to each carbon. Mass spectra were determined with
a Varian MAT 311 A, Varian MAT 731, or a Finnigan MAT 95
instrument operated at 70 eV. Preparative GC was carried out on an
Intersmat IGC 16, Carlo Erba FTV 2450, or Delsi IGC 121 MLR
instrument employing a thermal conductivity detector and hydrogen
as the carrier gas. Product ratios were not corrected for relative
response. Rf values are quoted for Macherey & Nagel Polygram SIL
G/UV254 plates. Colorless substances were detected by oxidation with
3.5% alcoholic molybdophosphoric acid (Merck) and subsequent
warming. Melting points were observed on a Reichert microhotstage
or a Bu¨chi melting point apparatus and are not corrected. Microana-
lytical determinations were done at the Microanalytical Laboratory of
the Institute of Organic Chemistry, Go¨ttingen.
(8) kcal/mol), and then slightly decreases (76.7 kcal/mol (37)).
In the transition state, the additional strain, quantified by the
experimental free energies of activation,33 first strongly increases
(22.0 (34), 26.8 (35), 32.5 (36), 37.5 (8) kcal/mol), and then
sharply decreases (17.3 kcal/mol (37)). Given the fact that
cyclopropanes and cyclobutanes, as compared to a geminal
dimethyl group, are well defined structural entities with a
restricted motional freedom, the pronounced energetical response
of the hexaspiranes 34, 35, 36, and 8 to the inevitable approach
of parts of the molecule during inversion was to be expected.
However, a detailed analysis must await for a study of the
conformational energy surface of all molecules in question. Such
a study already exists for 37.34
Summary and Conclusions
We report on the synthesis, structure, conformation, and
dynamics of a new rotane family consisting of four-membered
rings. The most important features of the synthetic part are a
[2+1] cycloaddition of cyclobutylidene to bicyclobutylidene for
the synthesis of [3.4]rotane (5) (9-5), a [2+2] cycloaddition
of trimethyleneketene to bicyclobutylidene with subsequent
spiroalkylation of the resulting trispiroketone 10 for the synthesis
of [4.4]rotane (6) (9-10-13-14-6), a ring enlargement of 10
via â-hydroxy selenides for the synthesis of tetraspiroketone
11 and pentaspiroketone 12 (10-15-11-16-12), and a further
elaboration directed to a cyclopropylcarbene-cyclobutene rear-
rangement for the synthesis of [5.4]rotane (7) and [6.4]rotane
(8) [11(12)-18(24)-19(25)-20(26)-21(27)-22(28)-23(29)-
7(8)].
The structures of 6, 7, and 8 were determined by high-
precision low temperature X-ray analyses and by force field
calculations using the search routine HUNTER in connection
with MM3(92). The following special features were ob-
served: From 5 to 8, the bond angles within the central ring
increase while the bond angles at the spiro center of the
peripheral cyclobutane rings decrease. As a consequence, the
peripheral cyclobutane rings change their geometry from a
regular trapezoid in 6 to a kite with the smallest angle at the
spiro center in 7 and 8. At the same time, the cyclobutane rings
become less folded, until in [6.4]rotane (8) they are nearly
planar. This documents increasingly strong nonbonding interac-
tions, leading to an extremely well-defined ground state
geometry in 8.
The most important result concerns the dynamics of [6.4]-
rotane (8). All hexaspiranes (8, 25-29) exist at room temper-
ature in a fixed chair conformation and preserve their stereo-
chemistry through sufficiently high barriers of inversion. For
the determination of the inversion barrier of 8, we synthesized
axially labeled [1-13C]8’ and followed its equilibration with
equatorially labeled [1-13C]8 by 13C NMR spectroscopy at 214
°C. The equilibration followed first-order kinetics and yielded
the free energy of activation for the chair to chair interconversion
as ∆Gq487 ) 156.8 ( 1.1 kJ/mol. This is the highest barrier of
inversion ever reported for a cyclohexane. Promising candidates
for even higher barriers are [6.5]rotane (32) and [6.6]rotane (33).
Trispiro[3.0.3.0.3.0]dodecane ([3.4]Rotane) (5). To a stirred
solution of 1,1-dibromocyclobutane17 (10.7 g, purity 94%, 50 mmol)
and bicyclobutylidene (9)15 (21.6 g, 200 mmol) in anhydrous ether (50
mL) under nitrogen at -70 °C was added over a period of 20 min a
1.1 M solution of methyllithium in ether (68 mL, 75 mmol). Stirring
was continued at -70 °C until GC analysis [3 m × 1/4 in. all glass
system, 15% OV 210 on Chromosorb W AW/DMCS 60-80 mesh,
100 °C; relative retention times: 1.00 (9), 2.82 (1,1-dibromocyclobu-
tane), 4.08 (5)] indicated that 1,1-dibromocyclobutane had been
consumed (1.5 h). The mixture was warmed to 0 °C over a period of
3 h hydrolyzed with water (50 mL), the layers were separated, the
aqueous phase was extracted with ether (3 × 20 mL), and the combined
organic phases were dried (MgSO4). The solvent was evaporated (bath
temperature 30 °C, 15 Torr) and the yellow, liquid residue (23.4 g)
chromatographed on silica gel (0.05-0.20 mm) in pentane [column
50 × 6 cm; Rf ) 0.65 (5), 0.55 (9)], yielding 2.40 g (30%) of 5 as a
colorless liquid: 1H NMR (200 MHz, CDCl3, CHCl3 int) 1.66-1.76
(m, 12), 1.86-2.20 (m, 6); 13C NMR (50.3 MHz, CDCl3, CDCl3 int)
15.35 (t), 22.11 (t), 30.64 (s); MS m/z 162 (2, M+), 91 (100). Anal.
Calcd for C12H18: C, 88.89; H, 11.11. Found: C, 88.91; H, 11.08.
Trispiro[3.0.3.0.3.1]tridecan-13-one (10). To a stirred solution of
anhydrous triethylamine (15.2 g, 150 mmol) in bicyclobutylidene (9)15
(100 mL, 87.8 g, 812 mmol) under nitrogen at 80 °C was added
cyclobutanecarboxylic acid chloride (11.9 g, 100 mmol) and the
resulting mixture heated for 5 h to 120 °C. After dilution with ether
(200 mL) the salts were dissolved in water (20 mL), and the organic
phase was washed with 2 N HCl (20 mL) and a saturated solution of
sodium bicarbonate (20 mL) and dried (MgSO4). Distillation over a
20 cm Vigreux column yielded first ether, then unchanged bicyclobu-
tylidene (9) (70.8 g, bp 51 °C, 12 Torr), then dispiro[3.1.3.1]decan-
5,10-one18 (1.3 g, bp 70 °C, 2 Torr; mp 84-86 °C), and finally 10 as
a colorless oil (10.3 g, 54%, bp 75-85 °C, 1 Torr): IR (neat) (CdO)
1760 cm-1; 1H NMR (100 MHz, CDCl3, CHCl3 int) 1.5-2.2 (m); 13
C
NMR (20 MHz, CDCl3, CDCl3 int) 15.54, 15.78, 23.80, 25.58, 44.80,
64.34, 216.01; MS m/z 190 (5, M+), 80 (100). Anal. Calcd for
C13H18O: C, 82.06; H, 9.54. Found: C, 81.85; H, 9.45.
13-[1’-(Phenylsulfanyl)cyclopropyl]trispiro[3.0.3.0.3.1]tridecan-
13-ol (13). To a stirred solution of cyclopropyl phenyl sulfide19a (3.16
g, 21.0 mmol) in anhydrous tetrahydrofuran (50 mL) under nitrogen at
0 °C was added within 15 min a 1.48 M solution of n-butyllithium in
hexane (14.2 mL, 21.0 mmol). After 1 h at 0 °C, 10 (4.00 g, 21.0
mmol) was added within 15 min and the mixture stirred at 0 °C until
TLC [pentane/ether, 9:1; Rf ) 0.92, 0.53 (10), 0.48 (13), 0.25] indicated
that 10 had been consumed (1.5 h). The mixture was diluted with
ether (50 mL), washed with brine (25 mL), and dried (MgSO4). The
solvents were evaporated (bath temperature 50 °C, 12 Torr), and the
red to yellow, liquid residue (7.00 g) was chromatographed on silica
gel (0.05-0.20 mm) in pentane/ether (9:1; column 120 × 4 cm),
yielding 3.84 g (54%) of 13 as a colorless solid: mp 67 °C; IR (neat)
Experimental Section
IR spectra were recorded on a Perkin-Elmer 298 or a Bruker IFS 25
spectrophotometer. 1H and 13C NMR spectra were obtained with a
Varian EM 360, FT 80 A, AH 100, XL 200, VXR 200, or VXR 500
(33) Enthalpies of activation only exist for 34 (∆Hq ) 21.1 kcal/mol)7a
and 37 (∆Hq ) 15.6 kcal/mol).32
(34) Ermer, O.; Ivanov, P. M.; Osawa, E. J. Comput. Chem. 1985, 6,
401-428.
1
(O-Hass) 3600-3200 cm-1; H NMR (300 MHz, CDCl3, CHCl3 int)
0.91-0.99 (AA’-part of an AA’BB’ system, 2), 1.25-1.33 (BB’-part
of an AA’BB’ system, 2), 1.72-2.05 (m, 10), 2.11-2.35 (m, 9), 7.13-

324 J. Am. Chem. Soc., Vol. 120, No. 2, 1998
Fitjer et al.
7.21 (m, 3), 7.49-7.57 (m, 2); 13C NMR (75 MHz, CDCl3, CDCl3 int)
14.52 (t), 15.74 (t), 16.58 (t), 25.81 (t), 26.25 (t), 26.80 (t), 26.83 (t),
33.14 (s), 50.77 (s), 53.26 (s), 78.90 (s), 125.71 (d), 128.57 (d), 129.17
(d), 137.24 (s); MS m/z 340 (10, M+), 232 (100). Anal. Calcd for
C22H28OS: C, 77.60; H, 8.29; S, 9.42. Found: C, 77.57; H, 8.38; S,
9.47.
9:1; Rf ) 0.53 (10), 0.40 (15b)) indicated that 10 had been consumed
(12 h). The mixture was hydrolyzed with water (5 mL), the organic
phase was washed with saturated sodium bicarbonate (2 × 80 mL),
the combined aqueous phases were extracted with ether (2 × 80 mL),
and the combined organic phases were dried (MgSO4). The solvents
were evaporated (bath temperature 50 °C, 12 Torr), and the orange,
oily residue (60.5 g) was chromatographed on silica gel (0.05-0.20
mm) in pentane/ether (9:1; column 130 × 7 cm), yielding 21.7 g (68%)
Tetraspiro[3.0.3.0.3.0.3.0]hexadecan-1-one (14). Benzene (60 mL)
was saturated with water, 13 (3.84 g, 11.3 mmol) and p-toluenesulfonic
acid monohydrate (1.95 g, 11.3 mmol) were added, and the mixture
was heated to reflux until TLC [pentane/ether, 95:5; Rf ) 0.47 (13),
0.38 (14)] indicated that 13 had been consumed (1.5 h). The mixture
was washed with water (10 mL), saturated sodium bicarbonate (30 mL),
and brine (30 mL) and dried (MgSO4). The solvent was evaporated
(bath temperature 25 °C, 15 Torr) and the red, liquid residue (3.11 g)
chromatographed on silica gel (0.05-0.20 mm) in pentane/ether (95:
5; column 70 × 4 cm), yielding 1.52 g (58%) of 42 as a colorless
of 15a as a light yellow solid: mp 72 °C; IR (KBr) (O-H) 3380 cm-1
;
1H NMR (300 MHz, CDCl3, TMS int) 1.63-2.10 (m, 13), 2.12-2.27
(m, 6), 2.29-2.48 (m, 4), 2.65-2.80 (m, 2), 7.30-7.40 (m, 3), 7.71-
7.80 (m, 2); 13C NMR (75 MHz, CDCl3, CDCl3 int) 15.73 (t), 15.84
(t), 16.90 (t), 25.69 (s), 26.38 (t), 26.45 (t), 26.97 (t), 27.13 (t), 32.98
(t), 50.69 (s), 52.85 (s), 79.64 (s), 128.48 (d), 128.82 (d), 128.90 (s),
137.67 (d); MS m/z 402 (1, M+), 137 (100). Anal. Calcd for C23H30-
OSe: C, 68.81; H, 7.53. Found: C, 68.95; H, 7.54.
1
solid: mp 76 °C; IR (KBr) (CdO) 1770 cm-1; H NMR (300 MHz,
Tetraspiro[3.0.3.0.3.0.3.1]heptadecan-17-one (11). A. From 15a
with Silver Tetrafluoroborate. Protected from light, dry neutral
aluminum oxide (153 g, 1.50 mol) and silver tetrafluoroborate (32.6 g,
167 mmol) were added to dry acetone (100 mL) (exothermic effect).
After 5 min of stirring the solvent was evaporated und the residue dried
(6 h, 100 °C, 0.01 Torr). The coated material was suspended in dry
carbon tetrachloride (500 mL), and within 15 min at -20 °C under
nitrogen with stirring, a solution of crude 15a (49.6 g, 146 mmol) was
added. After 21 h at -20 °C TLC (pentane/ether, 96:4; Rf ) 0.67,
0.29 (11), 0.22, 0.11 (15a)) indicated that the reaction was complete.
The yellow mixture was filtered through Celite and the Celite eluated
with ether (6.0 L, control by TLC). The filtrate was washed with
saturated sodium bicarbonate (3 × 500 mL), the aqueous phases were
extracted with ether (100 mL), and the combined organic phases were
dried (CaCl2). The solvents were evaporated (bath temperature 30 °C,
20 Torr), and the residual yellow oil (31.6 g) was chromatograped on
silica gel (0.1-0.2 mm) in pentane/ether (96:4; column 50 × 8 cm),
yielding 18.6 g (52%) of 11 as a colorless solid: mp 78 °C. According
to GC (2.5 m × 1/4 in. all glass system, 15% SE 30 on Chromosorb
W AW/DMCS 60-80 mesh, 3 min 160 °C, 20 °C/min to 250 °C;
relative retention times: 1.00 (11), 1.79 (15a)) the material was 98%
pure: IR (KBr) (CdO) 1725 cm-1; 1H NMR (80 MHz, CDCl3, CHCl3
int) 1.5-2.4 (m); 13C NMR (20 MHz, CDCl3, CDCl3 int) 15.63, 15.92,
23.36, 26.99, 50.71, 56.53, 224.25; MS m/z 244 (14, M+), 134 (100).
Anal. Calcd for C17H24O: C, 83.55; H, 9.90. Found: C, 83.39; H,
9.73.
B. From 15a with m-Chloroperoxybenzoic Acid. To a stirred
suspension of 70% m-chloroperoxybenzoic acid (64.0 g, 260 mmol)
in dichloromethane (600 mL) was added within 30 min a solution of
15a (16.0 g, 47 mmol) in ether (18 mL) (exothermic effect). After 5
min TLC (pentane/ether, 95:5; Rf ) 0.61, 0.35 (11), 0.24, 0.15 (15a),
0.09, 0.05) indicated that the reaction was complete. The mixture was
washed with 1 N NaOH (1 × 280 mL, 2 × 50 mL) and dried (MgSO4).
The solvent was evaporated (bath temperature 50 °C, 15 Torr) and the
yellow, solid residue (17.9 g) chromatographed on silica gel (0.05-
0.20 mm) in pentane/ether (97:3; column 18 × 8 cm), yielding 10.6 g
(84%) of 11 (purity 92%, GC) as a light yellow solid: mp 48-62 °C.
C. From 15b with m-Chloroperoxybenzoic Acid. To a stirred
suspension of 70% m-chloroperoxybenzoic acid (61.5 g, 250 mmol)
in dichloromethane (800 mL) at 0 °C was added a solution of 15b
(20.0 g, 50 mmol) in dichloromethane (200 mL) such that the
temperature did not exceed 5 °C. Stirring was continued at 0-5 °C
until TLC [pentane/ether, 9:1; Rf ) 0.59 (11), 0.40 (15b)] indicated
that 15b had been consumed (2 h). The mixture was washed with 1 N
NaOH (4 × 200 mL) and dried (MgSO4). The solvent was evaporated
(bath temperature 50 °C, 15 Torr) and the residual yellow oil (11.4 g)
chromatographed on silica gel (0.05-0.20 mm) in pentane/ether (9:1;
column 130 × 7 cm), yielding 8.3 g (68%) of 11 (purity 98%, GC) as
a colorless solid: mp 78 °C.
CDCl3, CHCl3 int) 1.63-2.07 (m, 20), 2.78 (t, 2, J ) 8.5 Hz); 13C
NMR (75 MHz, CDCl3, CDCl3 int) 15.93 (t), 16.16 (t), 16.73 (t), 24.11
(t), 24.54 (t), 26.18 (t), 26.34 (t), 43.77 (t), 49.92 (s), 50.51 (s), 75.34
(s), 212.20 (s); MS m/z 230 (1, M+), 131 (100). Anal. Calcd for
C16H22O: C, 83.43; H, 9.63. Found: C, 83.14; H, 9.47.
Tetraspiro[3.0.3.0.3.0.3.0]hexadecane ([4.4]Rotane) (6). A stirred
solution of 80% aqueous hydrazine hydrate (1.13 g, 18.0 mmol), grinded
potassium hydroxide (1.35 g, 24.0 mmol), and 14 (1.38 g, 6.0 mmol)
in diethylene glycol (12 mL) under nitrogen was heated to 160 °C until
TLC [pentane/ether, 95:5; Rf ) 0.95 (6), 0.38 (14), 0.04, 0.00
(hydrazone)] indicated that 14 had been consumed (2 h). The
temperature was raised to 195 °C, a vigorous gas evolution occurred,
and after 2 h at 195 °C the reaction was complete. The mixture was
diluted with water (12 mL) and extracted with pentane (5 × 25 mL).
The combined extracts were washed with water (3 × 30 mL), dried
(MgSO4), and concentrated on a rotary evaporator (bath temperature
25 °C, 12 Torr). Chromatography of the oily residue (886 mg) on
silica gel (0.05-0.20 mm) in pentane (column 30 × 3 cm; Rf ) 0.75)
1
yielded 581 mg (45%) of 6 as a colorless solid: mp 92 °C; H NMR
(300 MHz, CDCl3, CHCl3 int) 1.56-1.86 (m); 13C NMR (75 MHz,
CDCl3, CDCl3 int) 16.58 (t), 25.20 (t), 50.19 (s); MS m/z 216 (2, M+),
131 (100). Anal. Calcd for C16H24: C, 88.82; H, 11.18. Found: C,
88.82; H, 11.26.
13-[(1’-Methylselanyl)cyclobutyl]trispiro[3.0.3.0.3.1]tridecan-13-
ol (15a). To a stirred solution of 1,1-bis(methylselanyl)cyclobutane21
(36.3 g, 150 mmol) in anhydrous ether (150 mL) at -78 °C under
nitrogen was added a 1.4 M solution of tert-butyllithium in pentane
(107 mL, 150 mmol) such that the temperature did not exceed -60 °C
(30 min). After 1 h, 10 (28.5 g, 150 mmol) was added within 30 min
and stirring at -78 °C continued until GC analysis [2.5 m × 1/4 in. all
glass system, 15% SE 30 on Chromosorb W AW/DMCS 60-80 mesh,
10 min 170 °C, 20 °C/min to 250 °C; relative retention times: 1.00
(10), 3.30 (15a)] indicated that 10 had been consumed (2 h). The still
cold mixture was washed with saturated ammonium chloride (3 × 75
mL), the combined aqueous phases were extracted with ether (30 mL),
and the combined organic phases were dried (CaCl2). The solvents
were evaporated (bath temperature 50 °C, 20 Torr), yielding 49.7 g
(98%) of crude 15a (purity 90%, GC) as a yellow, vile-smelling liquid.
A 100 mg sample was chromatographed on silica gel (0.1-0.2 mm)
in pentane/ether [9:1; column 20 × 1 cm; Rf ) 0.58, 0.32, 0.22 (15a)],
yielding 57 mg of pure 15a as a colorless, vile-smelling liquid: 1H
NMR (80 MHz, CDCl3, TMS int) 1.5-2.9 (m, 25), 2.14 (s, 3); 13C
NMR (50.3 MHz, CDCl3, TMS int) 4.68 (q), 15.82 (t), 16.25 (t), 16.91
(t), 26.24 (t), 26.36 (t), 27.05 (2 t), 31.77 (t), 50.92 (s), 52.79 (s), 55.98
(s), 79.90 (s).
13-[1’-(Phenylselanyl)cyclobutyl]trispiro[3.0.3.0.3.1]tridecan-13-
ol (15b). To a stirred solution of 1,1-bis(phenylselanyl)cyclobutane21
(43.9 g, 120 mmol) in anhydrous tetrahydrofuran (120 mL) at -78 °C
under nitrogen was added a 1.6 M solution of n-butyllithium in n-hexane
(75 mL, 120 mmol) such that the temperature did not exceed -70 °C
(1.5 h). After 1 h at -78 °C the mixture was warmed to -40 °C and
treated with a solution of 10 (15.0 g, 79 mmol) in anhydrous
tetrahydrofuran (80 mL) such that the temperature did not exceed -35
°C (1 h). This temperature was maintained until TLC (pentane/ether,
17-[1-(Methylselanyl)cyclobutyl]tetraspiro[3.0.3.0.3.0.3.1]hep-
tadecan-17-ol (16a). To a stirred solution of 11 (18.6 g, 76.1 mmol)
and 1,1-bis(methylselanyl)cyclobutane21 (18.4 g, 76.1 mmol) in anhy-
drous ether (50 mL) at -30 °C under nitrogen was added over a period
of 5 h a 1.4 M solution of tert-butyllithium in pentane (54.3 mL, 76.1
mmol) and the reaction progress monitored by TLC [pentane/ether,

A New Rotane Family
J. Am. Chem. Soc., Vol. 120, No. 2, 1998 325
97:3; Rf ) 0.25 (16a), 0.15 (11)]. After 15 h at -30 °C, more 1,1-
bis(methylseleno)cyclobutane (3.7 g, 15.2 mmol) and, over a period
of 1 h, more of a 1.4 M solution of tert-butyllithium in pentane (10
mL, 14.0 mmol) were added. After an additional 18 h at -30 °C the
reaction was complete. The still cold mixture was hydrolyzed with
saturated ammonium chloride (30 mL) and washed with brine (30 mL).
The combined aqueous phases were extracted with ether (30 mL) and
the combined organic phases dried (CaCl2). The solvents were
evaporated (bath temperature 25 °C, 20 Torr), and the yellow, oily
residue (35.0 g) was chromatographed on silica gel (0.05-0.20 mm)
in pentane/ether (97:3; column 50 × 8 cm), yielding 21.1 g (70%) of
pure 16a as a colorless liquid: IR (neat) (O-H) 3620 cm-1; 1H NMR
(80 MHz, CDCl3, CHCl3 int) 1.50-2.70 (m, 30), 1.55 (s, 1, D2O
exchange), 2.18 (s, 3); 13C NMR (50.3 MHz, CDCl3, TMS int) 6.24
(q), 15.39 (t), 15.61 (t), 16.43 (t), 18.47 (t), 24.98 (t), 25.12 (t), 25.50
(t), 27.83 (t), 28.83 (t), 33.12 (t), 54.05 (s), 55.44 (s), 55.93 (s), 58.67
(s), 61.54 (s), 86.95 (s), all other signals were not visible due to
coalescence phenomena; MS m/z 394, 392 (2, 1, M+), 67 (100). Anal.
Calcd for C22H34OSe: C, 67.16; H, 8.71. Found: C, 66.16; H, 8.49.
Pentaspiro[3.0.3.0.3.0.3.0.3.1]heneicosan-21-one (12). A. From
16a with Silver Tetrafluoroborate. Protected from light, neutral
aluminum oxide (62.9 g, 617 mmol) was coated with silver tetrafluo-
roborate (12.0 g, 61.7 mmol) as described for 11. The material was
suspended in dry tetrachloromethane (200 mL), and then, within 1 h
at -20 °C under nitrogen with stirring, a solution of 16a (20.2 g, 51.4
mmol) in dry tetrachloromethane (100 mL) was added. Stirring was
continued for 1 d at -10 °C and then at 0 °C while the reaction progress
was monitored by TLC [pentane/ether, 98:2; Rf ) 0.70, 0.28 (12), 0.22
(16a)]. After 5 d more silver tetrafluoroborate (3.0 g, 15.4 mmol) was
added, and after an additional 2 d the reaction was complete. The now
black reaction mixture was filtered through Celite, and the celite was
eluated with ether (3 L, control by TLC). The filtrate was washed
with saturated sodium bicarbonate (3 × 200 mL), the aqueous phases
were extracted with ether (50 mL), and the combined organic phases
were dried (CaCl2). The solvents were evaporated (bath temperature
30 °C, 20 Torr), and the yellow, solid residue (12.9 g) was chromato-
graphed twice on silica gel (0.05-0.20 mm) in pentane/ether (98:2;
columns 50 × 8 cm, 120 × 4 cm), yielding 7.02 g (46%) of 12 as a
colorless solid: mp 137-138 °C (lit.22 mp 137-138 °C). The 13C
NMR data were in accord with literature data.22
indicated that the reaction was complete (20 h). The mixture was
diluted with pentane (55 mL) and hydrolyzed with water (3.5 mL).
The organic phase was decanted and the residue extracted with pentane
(3 × 30 mL). The combined organic phases were washed with water
(3 × 25 mL) and dried (MgSO4). The solvent was evaporated (bath
temperature 20 °C, 15 Torr) and the residue (4.56 g) chromatographed
on silica gel (0.1-0.2 mm) in pentane (column 15 × 5 cm; Rf ) 0.61),
yielding 2.14 g (84%) of pure 18 as a colorless liquid: IR (neat) (CdC)
1
1640 cm-1; H NMR (200 MHz, CDCl3, CHCl3 int) 0.80-2.20 (m,
24), 5.33 (s, 2); 13C NMR (126 MHz, CDCl3, CDCl3 int) 15.46 (t),
15.92 (t), 23.55 (t), 31.56 (t), 53.54 (s), 53.60 (s), 101.76 (t), 171.60
(s); MS m/z 242 (1, M+), 171 (100). Anal. Calcd for C18H26: C, 89.19;
H, 10.81. Found: C, 89.10; H, 10.71.
Pentaspiro[2.0.3.0.3.0.3.0.3.0]nonadecane-1-carboxylic Acid Meth-
yl Ester (19). To a stirred solution of 11 (738 mg, 3.04 mmol) in
cyclohexane (1.5 mL) under nitrogen was added electrolyte copper (190
mg, 2.99 mmol) and the mixture heated to 110 °C. Dropwise addition
of diazoacetic acid methyl ester (1.22 g, 12.2 mmol) caused a
concomitant gas evolution which subsided until the addition was
complete. The mixture was filtered, the filtrate concentrated (bath
temperature 20 °C, 15 Torr), and the yellow, oily residue (640 mg)
chromatographed on silica gel (0.05-0.20 mm) in pentane/ether [95:
5; column 30 × 3 cm; Rf ) 0.66 (11), 0.26 (19)], yielding 225 mg
(31%) of unchanged 11 and 211 mg (22%) of pure 19 as a colorless
1
solid: mp 65 °C; IR (KBr) (CdO) 1730 cm-1; H NMR (500 MHz,
CDCl3, TMS int) 1.18 (dd, 1, J ) 9, 5 Hz), 1.37-1.86 (m, 15), 1.97
(dd, 1, J ) 9, 8 Hz), 2.01-2.32 (m, 10), 3.72 (s, 3); 13C NMR (50.3
MHz, CDCl3, TMS int) 15.92 (t), 15.94 (t), 16.05 (t), 16.53 (t), 16.84
(t), 23.61 (d), 24.53 (t), 24.96 (t), 25.07 (t), 25.16 (t), 27.48 (t), 28.57
(t), 29.15 (t), 29.42 (t), 48.27 (s), 51.62 (s), 51.78 (q), 53.87 (s), 54.40
(s), 55.39 (s), 173.68 (s); MS m/z 200 (100), 157 (70). Anal. Calcd
for C21H30O2: C, 80.21; H, 9.61. Found: C, 80.14; H, 9.57.
Pentaspiro[2.0.3.0.3.0.3.0.3.0]nonadecane-1-methanol (20). To a
stirred suspension of lithium aluminum hydride (55 mg, 1.25 mmol)
in anhydrous ether (1 mL) at room temperature under nitrogen was
added within 5 min a solution of 19 (266 mg, 0.85 mmol) in anhydrous
ether (1 mL). After 10 min TLC [dichloromethane; Rf ) 0.67 (19),
0.47, 0.29 (20)] indicated that the reaction was complete. The mixture
was treated with water (50 µL), a 15% aqueous solution of sodium
hydroxide (50 µL), and water (160 µL), the organic phase was decanted,
and the residue was extracted with ether (10 × 1.5 mL, control by
TLC). The combined organic phases were concentrated (bath temper-
ature 25 °C, 15 Torr), and the colorless, solid residue was chromato-
graphed on silica gel (0.05-0.20 mm) in dichloromethane (column 17
× 1.3 cm), yielding 284 mg (99%) of pure 20 as a colorless solid: mp
49 °C; IR (KBr) (O-H) 3340 cm-1; 1H NMR (200 MHz, CDCl3, CHCl3
int) 0.60-0.93 (m, 2), 1.50 (s, 1, D2O exchange), 1.20-2.30 (m, 25),
3.75-4.10 (m, 2); 13C NMR (20 MHz, CDCl3, CDCl3 int) 14.01, 15.40,
15.64, 16.08, 16.47, 24.15, 24.32, 24.95, 25.29, 25.51, 27.95, 28.24,
29.22, 29.65, 41.73, 51.95, 53.12, 54.55, 55.58, 63.22; MS m/z 286 (2,
M+), 200 (100). Anal. Calcd for C20H30O: C, 83.86; H, 10.56.
Found: C, 83.65; H, 10.47.
Pentaspiro[2.0.3.0.3.0.3.0.3.0]nonadecane-1-carbaldehyde (21).
To a stirred solution of oxalyl chloride (140 mg, 1.10 mmol) in
anhydrous dichloromethane (2.5 mL) at -60 °C under nitrogen was
added a solution of dimethyl sulfoxide (44 mg, 0.56 mmol) in anhydrous
dichloromethane (0.5 mL). After 2 and 15 min, respectively, a solution
of 20 (284 mg, 0.99 mmol) in anhydrous dichloromethane (1.0 mL)
and triethylamine (507 mg, 5.01 mmol) were added. After a further
10 min at -60 °C the colorless suspension was warmed to room
temperature and hydrolyzed with water (5 mL). The layers were
separated, the aqueous phase was extracted with dichloromethane (5
mL), and the combined organic phases were washed with brine (10
mL) and dried (molecular sieves 4 Å). Evaporation of the solvent (bath
temperature 20 °C, 15-0.5 Torr) yielded 284 mg (100%) of crude 21
as a yellow liquid. This material was used as such as an attempt of a
chromatographic purification on silica gel in dichloromethane led to a
mixture of rearranged aldehydes: IR (neat) (CdO) 1690 cm-1; 1H NMR
(60 MHz, CDCl3, CHCl3 int) 0.50-2.50 (m, 27), 9.45 (d, 1, J ) 7
Hz); 13C NMR (20 MHz, CDCl3, CDCl3 int) 14.87 (t), 15.54 (t), 15.76
(t), 16.29 (t), 18.84 (t), 24.37 (t), 24.63 (t), 24.86 (t), 24.97 (t), 27.19
B. From 16b with m-Chloroperoxybenzoic Acid. Con-
current Formation of 17-(5-Oxabicyclo[2.1.0]pent-1-yl)tetraspiro-
[3.0.3.0.3.0.3.1]heptadecan-17-ol (17). To a stirred suspension of 70%
m-chloroperoxybenzoic acid (23.0 g, 93.3 mmol) in dichloromethane
(150 mL) was added within 30 min a solution of 16b (5.91 g, 15.0
mmol) in dichloromethane (12 mL) (exothermic effect). After 5 min
TLC [pentane/ether, 95:5; Rf ) 0.42 (12), 0.17 (17)] indicated that the
reaction was complete. The mixture was washed with 1 N NaOH (1
× 100 mL, 2 × 50 mL) and dried (CaCl2). The solvents were
evaporated (bath temperature 50 °C, 15 Torr), and the yellow, oily
residue (5.1 g) was chromatographed on silica gel (0.05-0.20 mm) in
pentane/ether (95:5; column 30 × 4 cm), yielding 1.59 g (36%) of 12
as a colorless solid, mp 127-129 °C, and 1.53 g (32%) of 17 as a
light yellow, slowly crystallizing oil. Analytically pure 17 was obtained
by 2-fold crystallization from acetone as a colorless solid: mp 71-76
1
°C; IR (KBr) (O-H) 3510 cm-1; H NMR (80 MHz, CDCl3, CHCl3
int) 1.4-2.7 (m, 28), 2.3 (s, H, D2O exchange), 3.9-4.0 (m, 1); 13C
NMR (20 MHz, CDCl3, CDCl3 int) 15.85, 16.38, 16.56, 17.29, 24.28,
24.94, 25.17, 25.35, 25.56 (coincidence of two lines), 26.35, 26.66,
28.69, 31.44, 54.72, 54.75, 56.41, 57.23, 58.06, 69.45, 80.18; MS m/z
314 (0.02, M+), 91 (100). Anal. Calcd for C21H30O2: C, 80.21; H,
9.62. Found: C, 80.37; H, 9.64.
17-Methylentetraspiro[3.0.3.0.3.0.3.1]heptadecane (18). To a
stirred suspension of potassium tert-butoxide (5.88 g, 52.5 mmol) in
anhydrous benzene (120 mL) under nitrogen was added methyltriph-
enylphosphonium bromide (18.8 g, 52.5 mmol) and the mixture heated
to reflux. After 2 h, 11 (2.57 g, 10.5 mmol) was added and most of
the solvent distilled off under nitrogen until the bath temperature reached
130 °C. This temperature was maintained until GC analysis [1.2 m ×
1/4 in. all glass system, 15% OV 210 on Chromosorb W AW/DMCS
60-80 mesh, 190 °C; relative retention times: 1.00 (18), 2.79 (11)]

326 J. Am. Chem. Soc., Vol. 120, No. 2, 1998
Fitjer et al.
(t), 28.66 (t), 28.71 (t), 32.07 (t), 35.03 (d), 51.33 (s), 51.75 (s), 53.67
(s), 54.23 (s), 54.99 (s), 200.68 (d); MS m/z 284 (33, M+), 227 (100).
HRMS m/z (M+) calcd 284.2140, obsd 284.2140.
(200 MHz, CDCl3, CHCl3 int) 1.08-2.58 (m, 30), 5.20 (d, 2, J ) 154
Hz); 13C NMR (50.3 MHz, CDCl3, CDCl3 int) 108.53.
Hexaspiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosane-1eq-carboxylic Acid Meth-
yl Ester (25) and Hexaspiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosane-1ax-
carboxylic Acid Methyl Ester (25’). To a stirred solution of 24 (540
mg, 1.82 mmol) in cyclohexane (0.9 mL) under nitrogen was added
electrolyte copper (200 mg, 3.15 mmol) and the mixture heated to 110
°C. Dropwise addition of diazoacetic acid methyl ester (1.85 g, 18.5
mmol) caused a concomitant gas evolution which subsided until the
addition was complete (2.5 h). TLC [pentane/ether, 98:2; Rf ) 0.64
(24), 0.16 (25’), 0.11 (25)] indicated the formation of two products.
The mixture was diluted with ether (12 mL), filtered, and concentrated
(bath temperature 20 °C, 15 Torr) and the residue chromatographed
on silica gel (0.1-0.2 mm) in pentane/ether (98:2; column 22 × 2 cm)
yielding 320 mg (59%) of unchanged 24, 132 mg (20%) of a mixture
of 25 and 25’, and 109 mg (16%) of pure 25. Chromatography of the
mixture of 25 and 25’ yielded 46 mg (7%) of 25, mp 130-134 °C,
and 36 mg (5%) of 25’, mp 147-151 °C, as colorless solids. Data for
Pentaspiro[3.0.3.0.3.0.3.0.3.0]eicos-1-ene (23) via N-Pentaspiro-
[2.0.3.0.3.0.3.0.3.0]nonadec-1-ylidene-N’-(p-tosyl)hydrazine (22). Con-
current Formation of 17-Methylenetetraspiro[3.0.3.0.3.0.3.1]-
heptadecane (18). To a stirred solution of crude 21 (170 mg, 0.60
mmol) in anhydrous dichloromethane (1.0 mL) at 0 °C were added
anhydrous triethylamine (61 mg, 0.60 mmol) and tosyl hydrazide (112
mg, 0.60 mmol). The reaction was monitored by TLC [ether; Rf )
0.66 (21), 0.58 (22), 0.41, 0.33 (tosyl hydrazide)], and after 21 and 30
h at 0 °C, more tosyl hydrazide (45 mg, 0.24 mmol) and triethylamine
(31 mg, 0.30 mmol) were added. After 42 h at 0 °C, all 21 had been
consumed. The mixture was warmed to room temperature, dried
(molecular sieves 4 Å), and concentrated (bath temperature 20 °C, 15-
0.5 Torr), yielding 370 mg of crude 22 as a viscous yellow liquid. The
crude 22 was dissolved in anhydrous diethylene glycol dimethyl ether
(2.0 mL) and the solution treated with sodium methoxide (162 mg,
3.00 mmol) under nitrogen at 130 °C. A gas evolution was observed,
and after 5 min TLC [ether; 0.69 (23, 18), 0.58 (22), 0.36] indicated
that the reaction was complete. The mixture was filtered through silica
gel (0.05-0.20 mm) in pentane and concentrated (bath temperature
20 °C, 15 Torr) and the yellow, oily residue (130 mg) chromatographed
on silica gel (0.05-0.20 mm) in pentane [column 30 × 1.5 cm; Rf )
0.62 (23), 0.57 (18)], yielding 57 mg of a 3:1 mixture of 23 and 18 as
a colorless solid (mp 105 °C). This material was used for the
preparation of 7. Nearly pure 23 was obtained by repeated chroma-
tography on silica gel in pentane: 1H NMR (80 MHz, CDCl3, CHCl3
int) 0.65-2.45 (m, 24; 0.65-1.40 pentane), 2.30 (d, 2, J ) 0.95 Hz),
6.07 (d, 1, J ) 2.85 Hz), 6.28 (td, 1, J ) 2.85, 0.95 Hz).
1
25: IR (KBr) (CdO) 1730 cm-1; H NMR (80 MHz, CDCl3, CHCl3
int) 0.8-2.9 (m, 33), 3.78 (s, 3); 13C NMR (20 MHz, CDCl3, CDCl3
int) 11.90, 15.65, 16.25, 16.43, 16.51, 16.75, 18.80, 25.27, 25.34, 25.38,
25.88, 26.34, 26.56, 27.89, 28.61 (coincidence of two lines), 28.77,
34.06, 47.95, 49.16, 49.78, 50.72, 51.16, 51.90, 173.39; MS m/z 240
1
(66), 91 (100). Data for 25’: IR (KBr) (CdO) 1735 cm-1; H NMR
(80 MHz, CDCl3, CHCl3 int) 1.0-3.0 (m, 33), 3.50 (s, 3); 13C NMR
(20 MHz, CDCl3, CDCl3 int) 9.16, 16.18, 16.30, 16.49, 16.77, 16.80,
25.11, 25.33 (coincidence of two lines), 26.00, 26.15, 26.34, 27.20
(coincidence of two lines), 28.75 (coincidence of two lines), 31.27,
36.68, 49.41, 50.02, 50.23, 50.39, 50.59, 51.55, 174.14; MS m/z 240
(59), 197 (100). Anal. Calcd for C25H36O2: C, 81.47; H, 9.85.
Found: C, 81.57; H, 9.95.
Pentaspiro[3.0.3.0.3.0.3.0.3.0]eicosane ([5.4]Rotane) (7). A stirred
solution of a 3:1 mixture of 23 and 18 (56 mg) in pentane (1.5 mL) at
20 °C was hydrogenated at 1.1 atm of H2 over 10% Pd/C (50 mg)
until TLC [pentane; Rf ) 0.64 (7), 0.62 (23), 0.57 (18)] indicated that
23 had been consumed (1 h). Chromatography on silica gel (0.05-
0.20 mm) in pentane (column 7.0 × 0.6 cm) yielded 54 mg of a viscous,
colorless liquid. Preparative GC [1.2 m × 1/4 in. all glass system,
15% OV 210 on Chromosorb W AW/DMCS 60-80 mesh, 180 °C;
relative retention times: 0.27, 0.38, 0.63, 0.76, 1.00 (7)] gave 11.4 mg
(27%) of 7 as a colorless solid, mp 70-110 °C. Recrystallization from
methanol gave colorless crystals: 1H NMR (200 MHz, CD2Cl2, CHDCl2
int) 1.66-1.88 (m, 10, 1.96-2.10 (m, 20); 13C NMR (50.3 MHz, CD2-
Cl2, CD2Cl2 int) 16.78, 27.40, 55.30; MS m/z 270 (14, M+), 147 (100);
HRMS m/z (M+) calcd 270.2348, obsd 270.2348.
[2-13C]-Hexaspiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosane-1eq-carboxyl-
ic Acid Methyl Ester ([2-13C]25) and [2-13C]Hexaspiro-
[2.0.3.0.3.0.3.0.3.0.3.0]tricosane-1ax-carboxylic Acid Methyl Ester
([2-13C]25’). Under the conditions described for the preparation of 25
and 25’, [methylene-13C]24 (316 mg, 1.10 mmol) yielded 162 mg (51%)
of unchanged [methylene-13C]24, 81 mg (30%) of [2-13C]25, and 31
mg (12%) of [2-13C]25’. Data for [2-13C]25: 1H NMR (200 MHz,
CDCl3, CHCl3 int) 0.48-2.74 (m, 33), 3.80 (s, 3); 13C NMR (50.3
MHz, CDCl3, CDCl3 int) 11.95. Data for [2-13C]25’: 1H NMR (200
MHz, CDCl3, CHCl3 int) 0.74-2.78 (m, 33), 3.53 (s, 3); 13C NMR
(50.3 MHz, CDCl3, CDCl3 int) 9.17.
Hexaspiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosane-1eq-methanol (26). To
a stirred suspension of lithium aluminum hydride (31 mg, 0.82 mmol)
in anhydrous ether (1.0 mL) at room temperature under nitrogen was
added within 2 min a solution of 25 (109 mg, 0.30 mmol) in anhydrous
ether (1.5 mL). Stirring was continued until TLC [dichloromethane;
Rf ) 0.62 (25), 0.31, 0.22 (26)] indicated that the reaction was complete
(50 min). The mixture was treated with water (31 µL), a 10% aqueous
solution of sodium hydroxide (46 µL), and water (72 µL), the organic
phase was separated, and the residue was extracted with ether (10 × 1
mL, control by TLC). The combined organic phases were concentrated
(bath temperature 25 °C, 15 Torr), and the colorless, solid residue (95
mg) was chromatographed on silica gel (0.05-0.20 mm) in dichlo-
romethane (column 16 × 1.3 cm), yielding 85 mg (83%) of pure 26 as
21-Methylenepentaspiro[3.0.3.0.3.0.3.0.3.1]heneicosane (24). To
a stirred suspension of potassium tert-butoxide (3.77 g, 33.6 mmol) in
anhydrous benzene (70 mL) at room temperature under nitrogen was
added methyltriphenylphosphonium bromide (12.00 g, 33.6 mmol) and
the mixture heated to reflux. After 2 h, a solution of 12 (980 mg, 3.29
mmol) in anhydrous benzene (6 mL) was added and most of the solvent
distilled off under nitrogen until the bath temperature reached 130 °C.
This temperature was maintained until TLC [pentane/ether, 99:1; Rf )
0.64 (24), 0.33, 0.24 (12)] indicated that the reaction was complete
(63 h). The reaction mixture was diluted with pentane (70 mL) and
hydrolyzed with water (7 mL) and the organic phase decanted. The
residue was extracted with pentane (3 × 20 mL), and the combined
organic phases were washed with water (3 × 20 mL), dried (MgSO4),
and concentrated (bath temperature 50 °C, 50 Torr). The residue (5.9
g) was chromatographed on silica gel (0.05-0.20 mm) in pentane
(column 35 × 3 cm), yielding 540 mg (55%) of 24 as a colorless solid,
mp 165-181 °C (lit.7c mp 192-195 °C).
1
a colorless solid: mp 136-185 °C; IR (KBr) (O-H) 3400 cm-1; H
NMR (80 MHz, CDCl3, CHCl3 int) 0.6-2.9 (m, 34), 1.4 (dd, 1, J ) 5
Hz, D2O exchange), 4.2-4.4 (m, 2); 13C NMR (20 MHz, CDCl3, CDCl3
int) 11.15, 15.29, 16.54 (coincidence of three lines), 16.83, 18.53, 25.22,
25.47, 25.62, 25.67, 26.50, 28.00, 28.27, 28.76, 28.91, 29.00, 29.62,
47.47, 49.17, 49.77, 50.61, 51.28, 61.37; MS m/z 91 (100).
[2-13C]Hexaspiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosane-1eq-methanol ([2-
13C]26). Under the conditions described for the preparation of 26,
reduction of [2-13C]-25 (79 mg, 0.21 mmol) with lithium aluminum
hydride (28 mg, 0.74 mmol) yielded 62 mg (86%) of [2-13C]26: 1H
NMR (500 MHz, CDCl3, CHCl3 int) 0.71 (ddd, 1, J ) 154, 9, 5.5 Hz),
0.72 (ddd, 1, J ) 159, 12, 5.5 Hz), 1.80-2.36 (m, 32), 4.28 (ddd, 1,
J ) 11, 8, 2.5 Hz), 4.40 (ddd, 1, J ) 11, 6, 5 Hz); 13C NMR (126
MHz, CDCl3, CDCl3 int) 11.17.
[21-methylene-13C]Pentaspiro[3.0.3.0.3.0.3.0.3.1]heneicosane ([me-
thylene-13C]-24). Methylenation of 12 (0.50 g, 1.7 mmol) with ([13C]-
methyl)triphenylphosphonium iodide35 (9.50 g, 23.5 mmol, 99% 13C)
and potassium tert-butoxide (2.63 g, 23.5 mmol), analogous to the
preparation of 24, gave 216 mg (43%) of [methylene-13C]24: 1H NMR
(35) ([13C]Methyl)triphenylphosphonium iodide (99 atom % 13C, mp 176
°C) was obtained by reacting triphenylphosphine (70 mmol) in dry benzene
(60 mL) with [13C]methyl iodide (70 mmol, 99 atom % 13C) for 72 h at
room temperature (yield 98%).
Hexaspiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosane-1eq-carbaldehyde (27).
To a stirred solution of oxalyl chloride (40 mg, 0.31 mmol) in anhydrous

A New Rotane Family
J. Am. Chem. Soc., Vol. 120, No. 2, 1998 327
Table 2. Crystal Data and Structure Refinement Details for 6-8
6
7
8
formula
C16H24
216.35
monoclinic
C2/c
colorless
0.60 × 0.50 × 0.45
13.619(3)
8.230(2)
12.452(3)
90
115.24(3)
90
1262.4(5)
4
1.138
0.063
480
133(2)
6.0-66.4
13610
2401
0.0201
2401
C20H30
270.44
monoclinic
C2/c
colorless
0.60 × 0.50 × 0.35
22.859(5)
9.513(2)
14.725(3)
90
102.96(3)
90
3120.5(11)
8
1.151
0.064
C24H36
324.53
triclinic
P1h
molecular weight
crystal system
space group
color of crystal
crystal size (mm)
a (Å)
colorless
0.60 × 0.50 × 0.20
7.666(2)
7.983(1)
8.208(2)
69.08(1)
74.08(1)
76.60(1)
446.17(17)
1
1.208
0.067
180
133(2)
5.4-59.6
5947
2320
0.0231
2320
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
V (Å3)
Z
D
calcd (g/cm3)
µ (mm-1
F(000)
T (K)
)
1200
133(2)
4.7-55.9
19601
3722
0.0284
3722
2θ range (deg)
no. of rflns colld
no. of indep rflns
R(int)
no. of data
no. of params
no. of restraints
goodness of fit
R1 [I > 2(I)]
wR2 (all data)
extinction coefficient
g1
122
27
1.074
0.0393
0.1064
303
135
1.055
0.0496
0.1228
0.0016(3)
0.0454
3.1424
0.339
183
54
1.047
0.0409
0.1149
0.073(15)
0.0617
0.1330
0.321
0.0581
0.4277
0.370
g2
largest diff peak
largest diff hole (e Å-3
)
-0.185
-0.192
-0.215
dichloromethane (650 µL) at -60 °C under nitrogen was added a
solution of dimethyl sulfoxide (48 mg, 0.62 mmol) in anhydrous
dichloromethane (130 µL). After 2 and 20 min, respectively, a solution
of 26 (79 mg, 0.23 mmol) in anhydrous dichloromethane (2 mL) and
triethylamine (131 mg, 1.29 mmol) were added. After a further 15
min at -60 °C the colorless suspension was warmed to room
temperature and hydrolyzed with water (1.5 mL). The layers were
separated, the aqueous phase was extracted with dichloromethane (2
× 1.5 mL), and the combined organic phases were washed with brine
(3 mL) and dried (molecular sieves 4 Å). Evaporation of the solvent
(bath temperature 20 °C, 15 Torr) yielded 55 mg (71%) of 27 as a
colorless solid: IR (KBr) (CdO) 1730, 1695 cm-1; 1H NMR (80 MHz,
CDCl3, CHCl3 int) 1.1-3.0 (m, 33), 10.0 (d, 1, J ) 5 Hz); 13C NMR
(20 MHz, CDCl3, CDCl3 int) 14.52, 15.41, 16.10, 16.43 (coincidence
of two lines), 16.57, 25.09, 25.31 (coincidence of two lines), 26.01,
27.00, 27.87, 28.66, 29.01 (coincidence of two lines), 29.16, 29.52,
40.62, 48.13, 48.93, 50.29, 50.79, 51.20, 201.59; MS m/z 338 (1, M+),
86 (100). HRMS m/z (M+) calcd 338.2610, obsd 338.2610.
gas evolution was observed, and after 5 min TLC [ether; 0.76 (29),
0.64 (28)] indicated that 28 had been consumed. The mixture was
cooled and chromatographed on silica gel (0.05-0.20 mm) in pentane
[column 22 × 1.8 cm; Rf ) 0.58 (29), 0.53, 0.47], yielding 22 mg of
a colorless, partially crystallized oil. Crystallization from dichlo-
romethane yielded 10 mg (19%) of 29 as a colorless solid: mp 175-
1
188 °C; H NMR (80 MHz, CDCl3, CHCl3 int) 1.35-2.90 (m, 32),
6.20 (dt, 1, J ) 3, 1 Hz), 6.57 (d, 1, J ) 3 Hz); 13C NMR (20 MHz,
CDCl3, CDCl3 int) 16.10, 16.46, 16.57, 24.91, 25.16, 26.96, 27.15,
27.88, 28.03, 35.22, 47.99, 49.25, 49.69, 57.45, 135.39, 140.91; MS
m/z 322 (2, M+), 75 (100); HRMS m/z (M+) calcd 322.2661, obsd
322.2661.
[3-13C]Hexaspiro[3.0.3.0.3.0.3.0.3.0.3.0]tetracos-1eq-ene ([3-13C]-
29) via [2-13C]-N-Hexaspiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosan-1eq-
ylidene-N’-(p-tosyl)hydrazine ([2-13C]28). To a solution of crude
[2-13C]27 (51 mg, 0.15 mmol) in anhydrous dichloromethane (0.4 mL)
was added anhydrous tosyl hydrazide (58 mg, 0.32 mmol) and the
mixture stirred at room temperature until TLC [ether; Rf ) 0.76, 0.70
([2-13C]27), 0.64 ([2-13C]28), 0.55, 0.47, 0.32] indicated that [2-13C]-
27 had been consumed (40 h). The mixture was concentrated (bath
temperature 25 °C, 15-0.01 Torr), yielding 87 mg of crude [2-13C]28
which was dissolved in diethylene glycol dimethyl ether (0.5 mL) and
converted with sodium methoxide (80 mg, 1.10 mmol) to [3-13C]29 as
described for 29. Low-temperature crystallization of the crude material
(25 mg) from dichloromethane yielded 5 mg (10%) of pure [3-13C]29
as a colorless solid: 1H NMR (500 MHz, CDCl3, CHCl3 int) 1.48-
2.66 (m, 30), 2.11 (dd, 2, J ) 137, 1 Hz), 6.25 (ddt, 1, J ) 5, 3, 1 Hz),
6.61 (dd, 1 J ) 12.5, 3 Hz); 13C NMR (126 MHz, CDCl3, CDCl3 int)
35.21.
Hexaspiro[3.0.3.0.3.0.3.0.3.0.3.0]tetracosane ([6.4]Rotane) (8). To
a stirred solution of 29 (9 mg, 0.025 mmol; purity 90%, GC) in
anhydrous pentane (2 mL) was added 10% Pd/C (50 mg) and the
mixture hydrogenated at 1.1 atm of H2 until GC analysis [1.8 m × 1/4
in. all glass system, 2% SE 30 on Chromosorb W AW/DMCS 60-80
mesh, 205 °C; relative retention times: 1.0, 1.7 (29), 2.2 (8)] indicated
that 29 had been consumed (60 min). Filtration through silica gel
[2-13C]Hexaspiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosane-1eq-carbalde-
hyde ([2-13C]27). Under the conditions described for the preparation
of 27, oxidation of [2-13C]26 (58 mg, 0.17 mmol) with oxalyl chloride
(28 mg, 0.22 mmol), dimethyl sulfoxide (34 mg, 0.44 mmol), and
triethylamine (91 mg, 0.90 mmol) yielded 53 mg (92%) of [2-13C]27:
1H NMR (500 MHz, CDCl3, CHCl3 int) 1.04-2.70 (m, 33), 10.04 (dd,
1, J ) 5, 0.6 Hz); 13C NMR (126 MHz, CDCl3, CDCl3 int) 15.54.
Hexaspiro[3.0.3.0.3.0.3.0.3.0.3.0]tetracos-1-ene (29) via N-Hexa-
spiro[2.0.3.0.3.0.3.0.3.0.3.0]tricosan-1-ylidene-N’-(p-tosyl)hydra-
zine (28). To a solution of crude 27 (55 mg, 0.16 mmol) in anhydrous
dichloromethane (0.5 mL) were added anhydrous triethylamine (12 mg,
0.12 mmol) and tosyl hydrazide (60 mg, 0.32 mmol), and the mixture
1
was stirred at room temperature until H NMR analysis revealed that
the resonance of the aldehyde proton of 27 had disappeared (44 h).
The mixture was concentrated (bath temperature 20 °C, 15 Torr), the
residue (114 mg) containing the crude 28 dissolved in anhydrous
diethylene glycol dimethyl ether (0.7 mL), and the solution treated with
sodium methoxide (57 mg, 1.06 mmol) under nitrogen at 130 °C. A

328 J. Am. Chem. Soc., Vol. 120, No. 2, 1998
Fitjer et al.
(0.05-0.20 mm) in pentane and evaporation of the solvent yielded 9
mg (99%) of crude 8 (purity 90%, GC) as a colorless solid. Analytically
pure 8 was obtained by recrystallization from trichloromethane as a
colorless solid: mp 274 °C (closed capillary); 1H NMR (80 MHz,
CDCl3, CHCl3 int) 1.5-2.2 (m, 24), 2.9-3.3 (m, 12); 13C NMR (20
MHz, CDCl3, CDCl3 int) 16.76, 25.65, 28.53, 49.79; MS m/z 91 (100).
[1eq,2-D2]Hexaspiro[3.0.3.0.3.0.3.0.3.0.3.0]tetracosane ([1eq,2-D2]-
[6.4]Rotane) ([1,2-D2]8). Under the conditions described for the
preparation of 8, deuteration of 29 (6 mg, 0.019 mmol, purity 80%,
GC) yielded 4 mg (83%) of pure [1,2-D2]8. 2H NMR (30.7 MHz,
CDCl3, CDCl3 int) 1.70 (br s, 1), 2.52 (br s, 1).
omitted) are shown in Figure 1. Crystal data and structure refinement
details are listed in Table 2.
Rate Law of the Equilibration of [1-13C]8’. The rate law for a
reversible, energetically degenerate first-order reaction like the equili-
bration of [1-13C]8’ is given by -ln(A - Ae)/(Ao - Ae) ) 2kt (1), where
Ao, A, and Ae refer to the initial, actual, and equilibrium concentrations,
respectively.38 In the case of [1-13C]8’ the initial and equilibrium
concentrations are Ao ) 100% ) 1 (2) and Ae ) Ao/2 ) 1/2 (3),
respectively. Insertion of (2) and (3) into (1) yields -ln(2A - 1) )
2kt (4). In many cases, the integrals of appropriate resonance lines
are a direct measure for A and Ao. However, because of the presence
of magnetically equivalent labeled und unlabeled positions, the situation
in [1-13C]8’ is different. If the equilibration of [1-13C]8’ has reached
a degree x (0 e x e 1), the integrals I’ and I for the resonance lines of
the axial and equatorial carbon atoms, respectively, are composed as
follows: I’ ) (m + 5p)(1 - x) + 6px (5) and I ) (m + 5p)x + 6p(1
- x) (6), with m ) 0.99 and p ) 0.01, where m and p denominate the
degree of 13C in the labeled and unlabeled positions, respectively. The
sum of the integrals is I + I’) 11p + m (7), and by dividing (6) by
(7), it follows that x ) [(11p + m)I/(I + I’) - 6p]/(m - p) (8). Taking
into account that A ) Ao - x ) 1 - x, it follows from (4) that -ln[2(1
- x) - 1] ) 2kt (9). Insertion of (8) into (9) yields -ln(K1 - K2[I/(I
+ I’)]) ) 2kt (10) with K1 ) 1 + 12p/(m - p) and K2 ) 2(11p +
m)/(m - p). This is the rate law of the equilibration of [1-13C]8’.
Kinetic Measurements. A precision 5 mm o.d. NMR tube (No.
507 PP, Wilmad Glass Co.) was filled with a solution of 2.0 mg of
[1-13C]8’ in 400 L of 1,3-bis([D3]methoxy)benzene and heated in a
thermostated silicone bath (Haake Thermosistor TP 24) to 214 ( 3
°C. At intervals of 22 (three measurements), 32 (two measurements),
and 62 min (one measurement) the probe was chilled to 50 °C and a
13C NMR spectrum taken (125.9 MHz, 256 transients, acquisition time
1.193 s, pulse width 41°). After additional 17 h at 214 ( 3 °C the
equilibration was complete while a final spectrum indicated an intensity
ratio I/I’ ) 1.02. Supposing an incomplete relaxation of one or both
nuclei, the acquisition time was set to 60 s and indeed, the intensity
ratio changed to I/I’) 1.00. Therefore, all intensities I were corrected
by a factor of 0.98 until they were used in the kinetic analysis according
to (10). The least-squares adjustment of the rate data was done with
the program ACTPAR.39
[1-13Cax]Hexaspiro[3.0.3.0.3.0.3.0.3.0.3.0]tetracosane([1-13Cax][6.4]-
Rotane) ([1-13C]8’). Under the conditions described for the preparation
of 8, hydrogenation of [3-13C]29 (5 mg, 15 µmol) yielded 4 mg (78%)
of pure [1-13C]8’: 1H NMR (500 MHz, CDCl3, CHCl3 int) 1.77-2.09
(m, 24), 2.63-2.69 (m, 12); 13C NMR (126 MHz, CDCl3, CDCl3 int)
16.76 (t), 25.64 (t), 28.52 (t), 49.76 (s); 13C NMR (126 MHz, 1,3-bis-
([D3]methoxy)benzene, 1,3-bis([D3]methoxy)benzene int) 17.08, 26.01
(C-1), 28.82, 50.18.
1,3-Bis([D3]methoxy)benzene (30). To a solution of sodium
ethoxide in ethanol, prepared from sodium (4.00 g, 170 mmol) and
ethanol (190 mL), were added under nitrogen with stirring a solution
of 1,3-dihydroxybenzene (9.4 g, 85 mmol) in ethanol (40 mL) and [D3]-
methyl iodide (25 g, 170 mmol). After 5 h of reflux most of the ethanol
(200 mL) was distilled off and the residue poured into a 50% aqueous
solution of sodium hydroxide (70 mL). The mixture was extracted
with ether (3 × 200 mL), and the combined extracts were washed with
water (4 × 50 mL) and dried (CaCl2). The solvent was evaporated
and the residue fractionated, yielding 3.4 g of a colorless liquid (bp
105-116 °C, 16 Torr) which was chromatographed on silica gel (0.1-
0.2 mm) in pentane/ether [9:1; column 30 × 3 cm; Rf ) 0.48, 0.39
(30), 0.24, 0.17, 0.12, 0.05], yielding 3.0 g of crude 30. Preparative
GC of 2.4 g of crude 30 [2 m × 1/4 in. all glass system, 15% FFAP
on Chromosorb W AW/DMCS 60-80 mesh, 140 °C; relative retention
times: 1.00 (30), 1.14, 1.20] gave 0.9 g (7%) of pure 30: 1H NMR
(60 MHz, CDCl3, TMS int) 6.3-7.7 (m, 4); 13C NMR (126 MHz,
CDCl3, CDCl3 int) 54.05 (hept), 100.29, 105.92, 129.68, 160.76.
X-ray Structure Determinations for 6-8. Data were collected at
140 °C on a Stoe-Siemens-Huber diffractometer with monochromated
Mo K radiation ()0.710 73 Å) by using a SMART-CCD area detector.
Acknowledgment. This work was supported by the Deutsche
Forschungsgemeinschaft and the Fonds der Chemischen Indus-
trie.
For the integration of intensities the program SAINT was used.
A
semiempirical absorption correction was employed for structures 6-8.
The structures were solved by direct methods using SHELXS-97.36 All
non-hydrogen atoms were refined anisotropically. All hydrogen atoms
were refined freely with isotropic displacement parameters. CH
distances and HH 1,3-distances were restrained to be equal. The
Supporting Information Available: Tables of X-ray crystal
data, non-hydrogen atomic coordinates and their anisotropic
displacement parameters, bond lengths, bond angles, torsion
angles, and hydrogen coordinates and their isotropic displace-
ment parameters for 6-8 and 25’ (32 pages). See any current
masthead page for ordering and Internet access instructions.
structures were refined against F2 with a weighting scheme of w-1
)
σ2(Fo ) + (g1P)2 + g2P with P ) (Fo + 2Fc2)/3 using SHELXL-97,
2
2
including the isotropic extinction correction.37 The R values are defined
as R1 ) ∑||Fo| - |Fc||/∑|Fo| and wR2 ) [∑w(Fo - Fc2)2/∑wFo ]0.5
.
2
4
ORTEP plots (50% probability displacement ellipsoids, hydrogen atoms
JA973118X
(36) Sheldrick, G. M. SHELXS-90/96, a program for solving crystal
structures, University of Go¨ttingen, 1990; Acta Crystallogr., Sect. A 1990,
46, 467-473.
(37) Sheldrick, G. M. SHELXL-96, a program for crystal structure
refinement, University of Go¨ttingen, 1997.
(38) Sandstro¨m, J. Dynamic NMR Spectroscopy; Academic Press:
London, 1982; p 143.
(39) Binsch, G.; Kessler, H. Angew. Chem. 1980, 92, 445-463; Angew.
Chem., Int. Ed. Engl. 1980, 19, 411-428.