Synthesis and First Molecular Structure of a Bis-2-spiro-1-boraadamantane Derivative

Article abstract of DOI:10.1021/ol035661q

(Matrix presented) A new method for synthesizing the 2-spiro- boraadamantane pyridine complex (2) from 1-ethynylcyclohexylmethyl ether has been developed. The chemistry has been applied to the synthesis of bis-2-spiro-1-boraadamantane-pyridine (1) from tr

Full text of DOI:10.1021/ol035661q

ORGANIC
LETTERS
2004
Vol. 6, No. 3
313-316
Synthesis and First Molecular Structure
of a Bis-2-spiro-1-boraadamantane
Derivative
Carl E. Wagner and Kenneth J. Shea*
Department of Chemistry, UniVersity of California, IrVine, California 92697
kjshea@uci.edu
Received August 31, 2003 (Revised Manuscript Received January 2, 2004)
ABSTRACT
A new method for synthesizing the 2-spiro-boraadamantane pyridine complex (2) from 1-ethynylcyclohexylmethyl ether has been developed.
The chemistry has been applied to the synthesis of bis-2-spiro-1-boraadamantane‚pyridine (1) from trans-1,4-diethynyl-1,4-dimethoxycyclohexane
(8). This bis-Lewis acid serves as a self-assembling molecular building block with difunctional Lewis bases.
The allylboron condensation reaction of triallylborane with
alkynes permits the efficient construction of 1-boraadaman-
tane derivatives.1 1-Boraadamantane forms air-stable solid
adducts with primary amines2 and pyridine,3 and 1-boraada-
mantane derivatives can be converted to 1-adamantane,4
1-homoadamantane,5 and 1-aza-adamantane6 derivatives. Our
studies of the allylboron condensation reaction with alkynes
have focused on developing a suitable dialkyne substrate that
would lead to a bis-2-spiro-1-boraadamantane framework,
as exemplified in the dipyridine adduct 1. The bis-Lewis acid
can be used as a building block to direct the self-assembly
of nitrogen-containing Lewis bases.
The use of metals such as copper, palladium, zinc, and
cobalt to direct the self-assembly of rationally designed Lewis
bases to form supramolecular networks has been demon-
strated.7 Additionally, the use of boron to form supramo-
lecular structures8 and boron-containing polymers9 with
Lewis bases has also been achieved. The framework of the
bis-2-spiro-1-boraadamantane could potentially be applied
as a self-assembling molecular building block upon the
addition of an appropriate difunctional Lewis base, such as
pyrazine, to give an extended supramolecular network (4)
(Figure 1).
(1) (a) Mikhailov, B. M.; Baryshnikova, T. K.; Kiselev, V. G.; Shashkov,
A. S. IzV. Akad. Nauk SSSR, Ser. Khim 1979, 28, 2544. (b) Mikhailov, B.
M.; Baryshnikova, T. K. IzV. Akad. Nauk SSSR, Ser. Khim. 1979, 28, 2541.
(2) (a) Lagutkin, N. A.; Mitin, N. I.; Zubairov, M. M.; Arkhipova, T.
N.; Petracheva, T. K.; Mikhailov, B. M.; Smirnov, V. N.; Baryshnikova,
T. K.; Govorov, N. N. Khimiko-Farm. Zh. 1983, 17, 1077. (b) Mikhailov,
B. M.; Smirnov, V. N.; Smirnova, O. D.; Kasparov, V. A.; Lagutkin, N.
A.; Mitin, N. I.; Zubairov, M. M. Khimiko-Farm. Zh. 1979, 13, 35.
(3) Vorontsova, L. G.; Chizhov, O. S.; Smirnov, V. N.; Mikhailov, B.
M. IzV. Akad. Nauk SSSR, Ser. Khim. 1981, 30, 595.
(4) Gurskii, M. E.; Potapova, T. V.; Bubnov, Yu. N. MendeleeV Commun.
1993, 56.
(5) Mikhailov, B. M.; Govorov, N. N.; Angelyuk, Y. A.; Kiselev, V.
G.; Struchkova, M. I. IzV. Akad. Nauk SSSR, Ser. Khim. 1980, 29, 1621.
(6) Bubnov, Y. N.; Gurskii, M. E.; Pershin, D. G. MendeleeV Commun.
1994, 2, 43.
The inspiration for constructing such a framework arose
from the reported synthesis of the 2-spiro-1-boraadamantane‚
(7) (a) Noveron, J. C.; Lah, M. S.; Del Sesto, R. E.; Arif, A. M.; Miller,
J. S.; Stang, P. J. J. Am. Chem. Soc. 2002, 124, 6613. (b) Seidel, S. R.;
Stang, P. J. Acc. Chem. Res. 2002, 35, 972.
(8) (a) Wakabayashi, S.; Sugihara, Y.; Takakura, K.; Murata, S.;
Tomioka, H.; Ohnishi, S.; Tatsumi, K. J. Org. Chem. 1999, 64, 6999. (b)
Wies, N.; Pritzkow, H.; Siebert, W. Eur. J. Inorg. Chem. 1999, 393.
(9) (a) Grosche, M.; Herdtweck, E.; Peters, F.; Wagner, M. Organome-
tallics 1999, 18, 4669. (b) Matsumoto, F.; Chujo, Y. Macromolecules 2003,
36, 5516.
10.1021/ol035661q CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/14/2004

Scheme 1
Figure 1. Targets of the allylboron condensation reaction.
The pyridine molecule in 2 coordinates to the 2-spiro-1-
boraadamantane core in a plane parallel to the plane formed
by the proximal axial hydrogen atoms and C10 or C14. This
led directly to the speculation that the structure of a bis-2-
spiro-1-boraadamantane‚pyridine complex (1), with the boron
atoms oriented trans on the central cyclohexane ring, would
be predisposed to affix the coordinated pyridine molecules
in opposite directions.
The rigidity imposed by the spirocyclohexane moiety could
prove to be a favorable characteristic for supramolecular self-
assembly. In contrast to the rigid molecular structure of 1,
the crystal structure of 3 shows that the ethylene bridge
permits a skewed orientation of the bridged boraadamantane
cores and thus a skewed orientation of the coordinated
pyridine molecules.13
Since 1-ethynylcyclohexyl methyl ether (5) led to the
successful assembly of 2, trans-1,4-diethynyl-1,4-dimethy-
oxycyclohexane (8) was selected as the appropriate substrate
in our synthetic approach to 1. Prior to the synthesis of 8
and 1, a modeling study at the HF/3-21g* level of theory
was performed to estimate the relative stabilities of the
isomeric bis-2-spiro-1-boraadamantane frameworks (Figure
2).
The modeling study suggests that the trans orientation (III)
of the boron atoms in a bis-2-spiro-1-boraadamantane
framework is favored over the cis orientation (I) by 2.5 kcal/
mol. Furthermore, the trans-diaxial III is preferred over the
trans-diequatorial II by 5.0 kcal/mol. As expected, the axial-
equatorial structure 1 is intermediate in energy between II
and III. However, this modeling study does not take into
account the subsequent coordination of Lewis basic ligands
such as THF or pyridine to the Lewis acidic boron centers
in the frameworks of I, II, and III. The subsequent
coordination of pyridine to both boron centers in III could
alter the equilibrium to favor the trans-diequatorial orienta-
tion of the boron centers in II.
pyridine (2)10 and the 2,2′-ethylenedi-1-boraadamantane‚
pyridine complex (3).11 Mikhailov and co-workers reported
the synthesis of 2 in 59% overall yield from 1-ethynylcy-
clohexene. Thus, a reasonable synthetic approach to the bis-
2-spiro-1-boraadamantane framework in (1) could potentially
follow from 1,4-diethynyl-1,4-cyclohexadiene. However, the
availability of hydrocarbon precursors limits the generality
of this approach. Since there is ample precedent for the
synthesis of 1-boraadamantane derivatives from propargyl
ether substrates, 1-ethynylcyclohexyl methyl ether (5) was
selected as a model substrate for allylboron condensation in
our synthetic approach to 2. In this approach, the condensa-
tion of triallylborane with 5 should give borabicylc 6, and
the hydroboration of 6 followed by the addition of pyridine
should yield the pyridine adduct 2. Furthermore, if the
substitution of ether 5 for 1-ethynylcyclohexene succeeds
in this approach to 2, then the readily available substrate,
trans-1,4-diethynyl-1,4-dimethoxy-cyclohexane (8), could
lead to the synthesis of 1.
The Williamson ether synthesis was used to prepare ether
5 in 75% yield.12 Condensation of 5 with triallylborane
followed by methanolysis provides the borabicycle 6 as a
yellow viscous liquid in 74% yield after purification by
vacuum distillation (108 °C, 0.05 mmHg). The hydroboration
of 6 by borane‚THF followed by the removal of THF results
in a crude white residue. Addition of benzene to the residue
forms a suspension, and the addition of pyridine to this
suspension provides the 2-spiro-1-boraadamantane complex
(2) in 56% yield after precipitation and filtration (Scheme
1). Recrystallization of 2 from a 1:1 solution of acetone/2-
propanol affords air-stable crystals of 2 suitable for X-ray
diffraction (Scheme 1).
(10) (a) Mikhailov, B. M.; Cherkasova, K. L. Zh. Obshch. Khim. 1972,
42, 138. (b) Mikhailov, B. M.; Cherkasova, K. L. Zh. Obshch. Khim. 1972,
42, 1744. (c) Bubnov, Yu. N.; Grandberg, A. I. IzV. Akad. Nauk SSSR, Ser.
Khim. 1986, 35, 1451.
With the results of the modeling study in hand, we
proceeded with the synthesis of diyne 8. Thus, diol 7 was
(11) Gursky, M. E.; Potapova, T. V.; Bubnov, Yu. N. Russ. Chem. Bull.
1998, 47, 749.
(12) Mamedov, S.; Ismiev, I. I.; Gadzhizade, F. S. Zh. Org. Khim. 1965,
1, 2131.
(13) Gurskii, M. E.; Pershin, D. G.; Potapova, T. V.; Ponomarev, V. A.;
Antipin, M. Yu.; Starikova, Z. A.; Bubnov, Yu. N. Russ. Chem. Bull. 2000,
49, 501.
314
Org. Lett., Vol. 6, No. 3, 2004

Scheme 3
by vacuum distillation. Thus, THF and excess methanol were
simply removed under high vacuum (0.01 mmHg, 1 d)
following methanolysis, and the crude mixture of products
was carried into the hydroboration reaction.
The crude, dried methanolysis products were dissolved in
THF, and following hydroboration, excess THF was removed
by distillation under atmospheric pressure. The resulting
crude white foam was dissolved in benzene. Upon the
addition of pyridine (2.2 equiv) the solution became orange
and mildly exothermed and a fine off-white precipitate
formed. The precipitate was filtered, washed with cold
benzene, and dried under high vacuum to give the bis-2-
spiro-1-boraadamantane‚pyridine (1) in 16% yield.
A small portion of the fine powder of complex 1 was
dissolved in benzene and further purified by chromatography
(SiO2, Hex/benzene 1:1). Crystals of 1 formed incorporating
two molecules of benzene from the chromatography solvent
for every molecule of 1. An X-ray diffraction study
confirmed the presence of benzene and the structure of 1
(Figure 3).
Figure 2. Computational study of the relative stabilities of the
isomeric bis-2-spiro-1-boraadamantane frameworks.
prepared according to a modified procedure of Bilton and
co-workers (Scheme 2).14 Diyne 8 is conveniently obtained
by the methylation of trans-1,4-diethynylcyclohexane-1,4-
diol (7) by treatment with NaH followed by MeI.
Scheme 2
The stereochemistry of the trans-isomer was ultimately
confirmed by an X-ray diffraction study on a single crystal
of 8 (Scheme 2).
With diyne 8 in hand, we proceeded with the allylboron
condensation reaction, followed by methanolysis and hydro-
boration to assemble the bis-2-spiro-1-boraadamantane core
of 1 (Scheme 3). Triallylborane was added to solid diyne 8
and immediately heated to 140 °C with stirring. The reaction
solution changed from colorless to yellow. After being stirred
for 1 h at 140 °C, the solution was cooled to 50 °C, and
THF was added to keep the reaction solution liquid upon
further cooling to room temperature. Methanol was added
(2.7 equiv). The mixture of products could not be purified
Figure 3. X-ray crystal structure of 1.
The framework of the bis-2-spiro-1-boraadamantane di-
pyridine adduct (1) is the trans-diequatorial II isomer (Figure
2). While other isomeric products of the condensation of
(14) Bilton, C.; Howard, J. A. K.; Madhavi, N. N. L.; Nangia, A.;
Desiraju, G. R.; Allen, F. H.; Wilson, C. C. Chem. Commun. 1999, 1675.
Org. Lett., Vol. 6, No. 3, 2004
315

pyrazine adduct was isolated by precipitation and filtration
as a bright vermillion solid. Elemental analysis showed the
correct percentages of carbon, hydrogen, and nitrogen.
Interestingly, the 1H NMR spectrum of this compound
included two roughly equivalent pyrazine signals and
multiple peaks for the boraadamantane fragment. The two
pyrazine peaks coalesced at approximately 60 °C (CDCl3).
On the basis of this information, the structures are tentatively
assigned as a 1:1 mixture of rotamers 9 and 10.
Scheme 4
In conclusion, we have synthesized the known 2-spiro-1-
boraadamantane (2) from 1-ethynylcyclohexyl methyl ether
(5) in comparable yield (41%) to the reported synthesis. This
methodology was extended to the synthesis of the novel bis-
2-spiro-1-boraadamantane‚pyridine (1) from trans-1,4-di-
ethynyl-1,4-dimethyoxycyclohexane (8) and determined its
molecular structure. Efforts are in progress to utilize the bis-
2-spiro-1-boraadamantane framework in supramolecular as-
semblies.
triallylborane with diyne 8 may have been produced in the
reaction, they were not observed by the procedure used to
isolate 1.
The benzene incorporated into the crystals of 1 evaporates
over the course of a few days under atmospheric pressure
or a few minutes under high vacuum. However, the remain-
ing off-white solid of 1 is air-stable. While the overall yield
of 1 is only 16%, it represents an average yield of 60% per
step, and this methodology provides access to a quantity of
1 that can be used for further experimentation.
As a prelude to the use of 1 for the formation of
supramolecular assemblies, pyrazine was examined as a di-
functional Lewis base for the 2-spiro-1-boraadamantane
system (Scheme 4). Following a similar procedure used to
synthesize 2, except substituting pyrazine (0.5 equiv) for
pyridine (1 equiv), the bis(2-spiro-1-boraadamantane)‚
Acknowledgment. This research was supported by a
grant from the National Science Foundation (Grant No. CHE-
9617475). C.E.W. wishes to thank Allergan, Inc., for a
graduate fellowship.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for compounds 1, 2, 5-8,
and 10. X-ray crystallographic data in CIF format. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL035661Q
316
Org. Lett., Vol. 6, No. 3, 2004