Synthesis of 1,3-dehydroadamantanes possessing alkyl, phenyl, and alkoxy substituents by intramolecular wurtz-type coupling reaction of 1,3-dibromoadamantanes

Article abstract of DOI:10.1055/s-0033-1338554

A series of highly strained [3.3.1]propellane derivatives, 1,3-dehydroadamantanes (DHAs) possessing alkyl, phenyl, and alkoxy substituents, such as 5-butyl, 5-hexyl, 5-octyl, 5-phenyl, 5-methoxy, 5-butoxy, 5,7-dimethyl, 5-ethyl-7-hexyl, 5,7-dibutyl-, 5-butyl-7-isobutyl, 5-butyl-7-hexyl, 5-butyl-7-phenyl, 5-butyl-7-methoxy, and 5-butoxy-7-butyl, were synthesized in several gram amounts. The 1,3-dibromoadamantanes carrying alkyl, phenyl, and alkoxy substituents were converted into the corresponding DHAs via the intramolecular Wurtz-type coupling reactions with lithium metal in THF in 21-81% yields. Georg Thieme Verlag Stuttgart . New York.

Full text of DOI:10.1055/s-0033-1338554

3332▌
FEATURE ARTICLE
feature article
Synthesis of 1,3-Dehydroadamantanes Possessing Alkyl, Phenyl, and Alkoxy
Substituents by Intramolecular Wurtz-Type Coupling Reaction of 1,3-Dibro-
moadamantanes
Synthesis of 1,3-Dehydroadamantanes
Sotaro Inomata, Yusuke Harada, Yuya Nakamura, Taisuke Nakamura, Takashi Ishizone*
Department of Organic and Polymeric Materials, Tokyo Institute of Technology , 2-12-1-S1-13 Ohokayama, Meguro-ku, Tokyo 152-8552,
Japan
E-mail: tishizon@polymer.titech.ac.jp
Received: 29.08.2013; Accepted after revision: 10.10.2013
at the bridgehead carbon. The inverted 1,3-carbon–carbon
Abstract: A series of highly strained [3.3.1]propellane derivatives,
σ-bond of 1a readily undergoes electrophilic and free-
1,3-dehydroadamantanes (DHAs) possessing alkyl, phenyl, and
radical ring-opening reactions with acetic acid, bromine,
alkoxy substituents, such as 5-butyl, 5-hexyl, 5-octyl, 5-phenyl, 5-
methoxy, 5-butoxy, 5,7-dimethyl, 5-ethyl-7-hexyl, 5,7-dibutyl-, 5-
and oxygen to form the corresponding 1,3-disubstituted
butyl-7-isobutyl, 5-butyl-7-hexyl, 5-butyl-7-phenyl, 5-butyl-7- adamantanes (Scheme 2),1,2 while no reaction occurred
methoxy, and 5-butoxy-7-butyl, were synthesized in several gram
amounts. The 1,3-dibromoadamantanes carrying alkyl, phenyl, and
with nucleophilic reagents such as n-butyllithium or
phenylmagnesium chloride. These results clearly indicate
alkoxy substituents were converted into the corresponding DHAs
the high electron density of the cyclopropane ring in 1a.
via the intramolecular Wurtz-type coupling reactions with lithium
Interestingly, a thermally stable insoluble polymeric prod-
metal in THF in 21–81% yields.
uct was obtained by heating 1a at 160 °C, indicating its
Key words: 1,3-dehydroadamantanes, 1,3-dibromoadamantanes,
thermal polymerizability.2 On the other hand, the cationic
Wurtz coupling reaction, [3.3.1]propellanes
or radical ring-opening polymerization of 1a also pro-
ceeded with a catalytic amount of trifluoromethanesulfon-
ic acid (TfOH) or α,α′-azobisisobutyronitrile (AIBN) to
give an insoluble polymer in quantitative yield.11,12 More
Introduction
interestingly, we have found the spontaneous copolymer-
1,3-Dehydroadamantane (1a)1–3 is a typical highly izability of 1a with electron-deficient vinyl monomers,
strained [3.3.1]propellane derivative that can be synthe- such as acrylonitrile or methyl acrylate, to give soluble co-
sized by the intramolecular Wurtz-type coupling reaction polymers with predominantly alternating sequences.13
of 1,3-dibromoadamantane (2a) with lithium metal in The resulting copolymers derived from 1a showed a high
THF, as shown in Scheme 1. It is well known that small- thermal stability and high glass transition temperature (Tg)
ring propellanes, such as the [1.1.1]-,4 [2.2.2]-,5 [2.2.1]-,6 due to the introduction of a bulky and rigid adamantane-
and [3.3.1]propellanes,7 show high reactivities toward 1,3-diyl framework into the main chain.
various chemical reagents due to the high strains in their
In order to expand the range of polymerizable cyclic
unique structures.8 Their reactivity, stability, strain, and
monomers and to increase the solubility of the resulting
structure have attracted significant attention not only from
polymers, we have synthesized a series of alkyl-substitut-
organic chemists, but also from polymer chemists, since
ed 1,3-dehydroadamantanes (DHAs) and attempted their
these propellanes often exhibit a ring-opening polymeriz-
homopolymerization under various conditions.11,12,14
ability to form a polymeric product in addition to the sim-
Since the resulting alkyl-substituted polymers showed
sufficient solubility in organic solvents, such as THF or
ple ring-opening reaction.9,10
CHCl3, as well as an excellent thermal stability, various
Br
Br
characterizations, such as NMR and size exclusion chro-
matography (SEC) measurements, were possible to clari-
fy the unique structure of the poly(1,3-adamantane)s
consisting of adamantane-1,3-diyl linkages. Thus, DHAs
including 1a can be positioned as an attractive cyclic
monomer or a rigid building unit that affects the thermal
property or solubility of the resulting polymers. However,
the synthesis of DHA derivatives carrying other substitu-
ents is usually difficult and still challenging, because the
construction of the highly strained cyclopropane ring is
required in the presence of the substituents. In our labora-
tory, several grams of the DHA compounds are needed in
order to examine their ring-opening polymerizability and
to characterize the structures, molecular weights, and
properties of the resulting poly(1,3-adamantane)s. In this
Li
THF, r.t., 24 h
2a
1a
Scheme 1 General synthetic scheme of DHAs via intramolecular
Wurtz-type coupling reaction
Similar to other small-ring propellanes, 1a shows a high
reactivity derived from its inverted tetrahedral geometry
SYNTHESIS 2013, 45, 3332–3340
Advanced online publication: 04.11.2013
DOI: 10.1055/s-0033-1338554; Art ID: SS-2013-Z0562-FA
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

FEATURE ARTICLE
Synthesis of 1,3-Dehydroadamantanes
3333
paper, we report typical synthetic procedures of DHAs
carrying alkyl,11,12,14 phenyl,15 and alkoxy substituents15 in
Scope and Limitations
gram-scale experiments and discuss the practical aspects Pincock and Torupka first succeeded in the synthesis of
of their preparations.
1a by the intramolecular Wurtz-type coupling reaction of
2a using the Na/K alloy in n-heptane under reflux.1 A sim-
ilar reaction of 2a with the Na/K alloy in diethyl ether con-
taining HMPA at room temperature gave 1a in 77%
Biographical Sketches█
Sotaro Inomata was born the synthesis of polymers Professor
Kenneth
B.
in Tokyo, Japan, in 1986. containing adamantane Wagener at the University
He received a bachelor’s de- skeletons in the main chain of Florida as a visiting stu-
gree in polymer chemistry under the supervision of dent for 6 months. He is
from Tokyo Institute of Professor Takashi Ishizone currently
working
in
Technology in 2008 and a in the same institution in FUJIFILM Corporation in
master’s degree from the 2013. In 2011, he performed Kanagawa, Japan.
same institution in 2010. He acyclic diene metathesis po-
obtained a Ph.D. degree on lymerization in the group of
Yusuke Harada was born completed a master’s degree Ishizone in the same institu-
in Miyazaki, Japan, in 1988. on ring-opening polymer- tion in 2012. He is currently
He received a bachelor’s de- ization of 1,3-dehydroada- working in SHOWA DENKO
gree in polymer chemistry mantanes carrying alkoxy K. K. in Hyogo, Japan.
from Tokyo Institute of groups under the supervi-
Technology in 2010. He sion of Professor Takashi
Yuya Nakamura was born Technology in 2012. He is tanes carrying trialkylsilyl
in Saitama, Japan, in 1989. currently conducting his groups under the supervi-
He received a bachelor’s de- master course research on sion of Professor Takashi
gree in polymer chemistry ring-opening polymeriza- Ishizone.
from Tokyo Institute of tion of 1,3-dehydroadaman-
Taisuke Nakamura was tute of Technology in 2013. with
electron-deficient
born in Shizuoka, Japan, in He is currently conducting monomers under the super-
1989. He received a bache- his master research on spon- vision of Professor Takashi
lor’s degree in polymer taneous copolymerization Ishizone.
chemistry from Tokyo Insti- of 1,3-dehydroadamantanes
Takashi Ishizone was born receiving a doctorate degree eas center on the synthesis
in Saitama, Japan, in 1963. in 1994, he studied organic of novel thermally stable
He received a master’s de- chemistry as a visiting sci- polymers possessing ada-
gree in polymer chemistry entist at The University of mantane skeletons and the
from Tokyo Institute of Chicago in the group of Pro- synthesis of novel function-
Technology in 1988 under fessor P. E. Eaton from al polymers showing water-
the supervision of Profes- 1995 to 1996. Since 2000 he solubility and thermore-
sors Seiichi Nakahama and is an Associate Professor in sponsive properties by
Akira Hirao and started his the Department of Organic means of living anionic po-
academic career as an assis- and Polymeric Materials at lymerization.
tant professor in the same Tokyo Institute of Technol-
institution from 1989. After ogy. His main research ar-
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3332–3340

3334
S. Inomata et al.
FEATURE ARTICLE
H
OAc
no reaction
AcOH
R2
Br
R1
X
n-BuLi
Br
Br2
O2
n
CF3SO3H
ring-opening
polymerization
R1
R2
R2
R1
DHAs
R2
R1
CH2=CH
CH2 CH
C
O
O
C
N
n
n
N
spontaneous
copolymerization
R1
R2
R1
R2
Scheme 2 Ring-opening reactions of DHAs
yield.2 Adcock and Clark synthesized 1a in 67% yield by
treating 2a with lithium in diethyl ether under reflux.16 In
these cases of using alkali metals as strong reducing re-
agents, the intramolecular ring-closing reaction of 2a pro-
duced a highly strained cyclopropane ring in the
adamantane framework. When we employed magnesium
to react with 5-butyl-1,3-dibromoadamantane (2b) in
THF, 5-butyl-1,3-dehydroadamantane (1b) was similarly
obtained in 50% yield. It should be noted that a significant
amount (7%) of a reduced by-product, 1-butyladaman-
tane, formed along with 1b in the reaction using magne-
sium. Interestingly, 5-bromo-1,3-dehydroadamantane
could be prepared by the reaction of 1,3,5-tribromoada-
mantane with n-BuLi at –35 °C in a mixture of diethyl
ether and HMPA.17
Table 1 Synthesis of 1,3-Dehydroadamantanesa
Br
Br
Li
THF, r.t., 24 h
R2
R1
R2
R1
2
1
DHA
R1
R2
Yield (%)
1a
1ab
1b
1bc
1c
H
H
H
81
46
79
50
64
73
47
58
57
86
67
38
57
67
54
21
60
62
H
H
Bu
H
Bu
H
C6H13
C8H17
Ph
Among these synthetic procedures for the DHAs, the
Wurtz-type reaction of the 1,3-dibromoadamantanes with
lithium in THF (Scheme 1) is very attractive from the
standpoint of yield and safety, since the lithium metal was
easy to handle compared to the Na/K alloy in the reaction.
This reaction can be performed in hydrocarbons, such as
n-heptane, or ethereal solvents, such as diethyl ether,
THF, and tetra(ethylene glycol) dimethyl ether (tetra-
glyme). In addition, the starting compounds, a series of
1,3-dibromoadamantanes carrying various substituents,
such as alkyl, phenyl, and alkoxy groups, are available via
several synthetic pathways as previously reported.11,12,14
There are several precautions required for the preparation
of DHAs from the 1,3-dibromoadamantanes and lithium
metal in THF. The substituents in the 1,3-dibromoada-
mantanes must be stable to lithium during the formation
of the DHAs. In addition, the substituents must coexist
with the highly reactive DHA frameworks after the reac-
tion.
1d
1e
H
H
1f
H
OMe
OBu
Me
1g
1h
1hb
1i
H
Me
Me
Et
Bu
Bu
Bu
Bu
Bu
Bu
Me
C6H13
Bu
1j
1k
1l
i-Bu
C6H13
Ph
1m
1n
1o
OMe
OBu
A series of 1,3-dibromoadamantanes, 2a–o, were convert-
ed into the corresponding DHAs 1a–o in 21–81% yields
by treating with lithium (3–5 equiv) in THF under argon
at room temperature (Table 1). Under argon, the surface
of lithium showed a metallic luster and the reaction mix-
ture turned black as the reaction proceeded. The starting
compounds, the 1,3-dibromoadamantanes, were always
completely consumed and converted into the DHAs with-
a Unless otherwise indicated, reactions were conducted with Li in
THF at r.t. for 24 h.
b In tetraglyme at 60 °C for 3 d.
c With Mg in THF at reflux for 24 h.
in 24 hours, and even the 1-bromoadamantanes were not
detected in the reaction mixture. The resulting suspen-
sions were transferred to an all-glass apparatus with
Synthesis 2013, 45, 3332–3340
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Synthesis of 1,3-Dehydroadamantanes
3335
H
H
OAc
AcO
O
H
AcOH
THF
O
H
O(CH2)4OAc
AcO
1a
Scheme 3 Reaction of 1a with AcOH in the presence of THF
break-seals on a vacuum line to remove the excess amount 1b–g and 1i–o, the complete removal of THF was attained
of lithium.18 Repeated vacuum distillations of the mixture after repeated vacuum distillations. On the other hand, for
were performed in order to thoroughly remove the lithium the DHAs having relatively low boiling points, 1a and 1h,
bromide and THF from the resulting DHAs. In most cas- tetraglyme (bp 95 °C/3.0 mmHg) was often employed as
es, except for 1e, 1i, and 1m, the DHAs with sufficient pu- the solvent instead of THF for the reactions of 2a and 2h
rity could be isolated in over 50% yield after these workup with lithium (Scheme 4). In these cases, the ether-free
processes. However, it should be noted that the formation DHAs could be isolated by vacuum distillation due to the
of a reduced product, the corresponding strain-free ada- higher boiling point of tetraglyme.
mantane derivative, was confirmed by NMR and GLC
analyses as previously reported by Pincock.1,2 In most cas-
O
2
e
c
es, the adamantanes were formed in 1–3% yields in the re-
action mixture as side products along with the DHAs. The
removal of such adamantanes from the resulting DHAs
was very difficult by fractional distillations, since the mo-
lecular weights of DHAs and the corresponding adaman-
tanes were very similar and both compounds possessed
similar polarities. Therefore, we performed the ring-open-
ing reactions or ring-opening polymerizations of DHAs in
the presence of trace amounts of the reduced adaman-
tanes. As expected, the adamantanes were found to be in-
tact during the ring-opening reactions and ring-opening
polymerizations of the DHAs.
3
1
O
8
b
O
a
f
d
10
4
9
7
5
6
Figure 1 1-(4-Acetoxybutoxy)adamantane
Br
Br
Li
tetraglyme, 60 °C, 72 h
R2
R1
R2
R1
2a: R1, R2 = H
2h: R1, R2 = Me
1a: R1, R2 = H
1h: R1, R2 = Me
On the other hand, the complete removal of THF from the
DHAs was strongly required in selected cases. For exam-
ple, the reaction of 1a with AcOH in the presence of THF
unexpectedly gave a mixture of 1-acetoxyadamantane and
1-(4-acetoxybutoxy)adamantane (Figure 1), as shown in
Scheme 3. Although 1a was intact in THF, the 1-adaman-
tyl cation was readily produced via the protonation of 1a
with AcOH. The resulting 1-adamantyl cation was cap-
tured by the nucleophilic THF to form a cyclic oxonium
species. The subsequent ring-opening reaction of the THF
moiety in the oxonium salt occurred with a nucleophilic
acetate anion resulting in the formation of 1-(4-acetoxy-
butoxy)adamantane.19 For the cationic ring-opening po-
lymerization of DHAs with strong Brønsted acids, such as
TfOH, the trace amount of THF certainly hindered the po-
lymerization by formation of the oxonium ion reacting
with the 1-adamantyl cation. Thus, the removal of nucleo-
philic ethereal solvents, such as THF, is essential for the
following ring-opening reaction of the DHAs under the
cationic conditions. On the other hand, THF did not hin-
der the spontaneous copolymerization of 1a with acrylo-
nitrile to afford the copolymer with alternating
sequences.13 We now consider that this copolymerization
smoothly proceeds in THF via a radical mechanism. In
practice, for most DHAs with high molecular weights,
Scheme 4 Synthesis of 1a and 1h in tetraglyme
Another significant impurity, which hinders the reaction,
is oxygen. Oxygen deactivated the lithium metal during
the ring-closing reaction using the 1,3-dibromoadaman-
tanes, and it spontaneously reacted with the DHAs to form
an alternating polymer, poly(DHA-alt-oxygen), contain-
ing peroxide linkages between the adamantane-1,3-diyl
moieties (Scheme 2), as previously reported.1,2 The for-
mation of such alternating copolymers was confirmed by
the formation of the 1,3-dihydroxyadamantanes by the re-
duction reaction of the copolymer with lithium aluminum
hydride. Therefore, it is necessary to treat the DHAs in an
inert atmosphere, such as argon or nitrogen, not only dur-
ing the formation process, but also when stored. In prac-
tice, the NMR measurements of the DHAs were possible
to characterize the chemical structure, if the isolated
DHAs were diluted with inert deuterated solvents under
an inert atmosphere. On the other hand, elemental analysis
and mass spectroscopic measurement of the DHAs were
difficult using the normal procedures.
It is noteworthy that the isolated DHAs often underwent
spontaneous polymerization in the bulk even under a low
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3332–3340

3336
S. Inomata et al.
FEATURE ARTICLE
temperature condition, indicating their high reactivities. amount of MsOH. These results clearly indicated the high
Therefore, we immediately diluted the isolated DHAs electron density of the cyclopropane rings in the DHAs as
with appropriate inert solvents, such as n-heptane, ben- well as their intolerance toward acidic reagents. Since an
zene, dichloromethane, and THF, to prevent the spontane- adamantane molecule has a pseudotetrahedral symmetry,
ous polymerization. In fact, we could store the DHAs an adamantane derivative possessing four different sub-
without any polymerization and/or degradation under di- stituents on the four bridgehead carbons should have a ste-
luted conditions in the above-mentioned solvents. For ex- reogenic center.20 In fact, the ring-opening reactions of
ample, the DHAs proved to be stable in deuterated DHAs possessing two different substituents on the 5- and
benzene, C6D6, for at least several years in sealed glass 7-positions, 1i and 1k–o, with suitable acidic reagents,
tubes. This stability of the DHAs, [3.3.1]propellane, is such as AcOH, afforded multi-substituted adamantanes
noteworthy when compared to the relatively short half life bearing a stereogenic center.15 Thus, DHAs are regarded
of other propellane derivatives.8 For example, the half life as an attractive precursor of chiral adamantane deriva-
of [2.2.2]propellane was reported to be only 28 minutes at tives.
25 °C.5
The substituent effect in the DHA framework should be
On the other hand, the DHAs readily underwent ring- mentioned for estimating the electronic environment and
opening reactions with acidic reagents, such as AcOH and the relative reactivity. Table 2 summarizes the selected
methanesulfonic acid (MsOH), and the polymers of 13C NMR chemical shifts and JC,H coupling constants of
DHAs were obtained when using the stronger Brønsted the DHAs. For the monosubstituted DHAs, carbon signals
acids, such as TfOH and trifluoromethanesulfonimide for C1, C2, C3, and part of the cyclopropane ring were ob-
[(CF3SO2)2NH].11,12,14 Interestingly, even in methanol, the served in a high-field region compared to the unsubstitut-
DHAs were slowly consumed to give exclusively the ring- ed 1a. In particular, the alkoxy-substituted DHAs 1f and
opening products, 1-methoxyadamantanes. For example, 1g showed significant high-field shifts (ca. 7.0 ppm for C1
the reaction of 1b with methanol proceeded to yield 1-bu- and C3, and ca. 5.0 ppm for C2) compared to 1a, while
tyl-3-methoxyadamantane.15 The conversion of 1b could those DHAs exhibited reactivities similar to 1a. The 5-
be monitored by NMR and GLC measurements as 8, 48, substituted alkoxy groups presumably affect the electron
85, and 100% after 10 minutes, 1.5, 6, and 30 hours, re- density of the cyclopropane ring apart from the alkoxy
spectively. On the other hand, all the DHAs rapidly react- groups through the σ-bond framework without π-conjuga-
ed with methanol to form the corresponding 1- tion. The 13C NMR chemical shifts of the 5,7-disubstitut-
methoxyadamantanes in the presence of a catalytic ed DHAs also tended to shift to a higher field region than
Table 2 13C NMR Chemical Shifts and JC,H Constants of DHAsa
DHA
R1
R2
Position (ppm)
1,3
JC,H (Hz)b
2
5
7
1a
H
H
37.3
36.0
36.1
36.0
35.4
30.3
30.4
36.5
34.7
34.8
34.8
34.3
34.3
28.9
29.1
49.6
48.0
48.1
48.0
47.9
44.2
44.2
46.4
46.4
46.5
46,5
46.4
46.4
42.7
42.7
54.5
64.3
64.4
64.4
67.4
91.6
91.3
59.6
63.5
63.5
63.5
63.6
66.7
91.2
90.9
54.5
53.5
53.5
53.5
53.8
52.9
52.9
59.6
63.9
63.5
63.5
63.6
63.9
63.9
64.0
156
155
157
154
156
160
161
156
159
155
155
156
156
155
154
1b
H
Bu
1c
H
C6H13
C8H17
Ph
1d
H
1e
H
1f
H
OMe
OBu
Me
1g
H
1h
Me
Me
Bu
Bu
Bu
Bu
Bu
Bu
1i
C6H13
Bu
1j
1k
i-Bu
C6H13
Ph
1l
1m
1n
OMe
OBu
1o
a Measured in C6D6.
b JC,H coupling constants of C2 carbon.
Synthesis 2013, 45, 3332–3340
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Synthesis of 1,3-Dehydroadamantanes
3337
1,3-Dibromoadamantane (2a), Li (wire), Na, Mg, AcOH, MsOH,
MeOH, and LiAlH4 were used as received. Other 1,3-dibromoada-
mantanes, 2b–o, were synthesized according to our previous re-
port.15 Tetraglyme was distilled over LiAlH4 in vacuo. THF was
refluxed over sodium wire for 3 h, and distilled over LiAlH4 under
N2.
the corresponding monosubstituted DHAs. We next com-
pared the JC,H coupling constant of the C2 methylene
group in the DHA framework in order to estimate the or-
bital hybridization,21 since no proton was present on the
C1 and C3 carbons. The JC,H values of the DHAs are ob-
served between 154 and 161 Hz, indicating their similar
electronic environments. In fact, these JC,H values are
comparable to the typical compounds showing an sp2 or-
bital hybridization, such as ethylene (156 Hz), cyclopro-
pane (161 Hz), and [1.1.1]propellane (164 Hz), but are
very different when compared to the values of ethane (125
Hz, sp3), adamantane (131 Hz, sp3), and acetylene (249
Hz, sp).
1H NMR and 13C NMR spectra were recorded at 300 MHz and 75
MHz, respectively, either in CDCl3 or C6D6. The chemical shifts
were reported in ppm downfield relative to CHCl3 (δ = 7.26) or
1
C6H6 (δ = 7.16) for H NMR and CDCl3 (δ = 77.1) or C6D6 (δ =
128.0) for 13C NMR as standards. In the 1H NMR spectral data, the
marking of the 5-substituent group of 1 is provided to distinguish
them from the ring CH2 groups, wherever necessary. IR spectra
were recorded on a FT-IR instrument by ATR or NaCl disk method.
High-resolution mass spectra (HRMS) were obtained on an electro-
spray ionization (ESI) mass spectrometer.
Finally, we would like to describe the practical synthetic
aspects. Due to the high reactivity of the DHAs, it is often
difficult to estimate the yields of the produced DHAs in
gravimetric terms, while the conversion of the starting
1,3-dibromoadamantanes could be checked by GLC or
NMR measurements. Therefore, an aliquot of the reaction
mixture was taken under nitrogen to estimate the yields of
Preparation of DHAs in THF; 5-Butyl-1,3-dehydroadamantane
(1b); Typical Procedure A
A mixture of 1,3-dibromo-5-butyladamantane (2b; 11.1 g, 31.7
mmol) and Li (1.00 g, 144 mmol) in anhydrous THF (50 mL) was
reacted at r.t. for 24 h under argon. The resulting suspension was
transferred into a round-bottomed flask equipped with a break-seal
to remove residual Li, and THF was removed from the suspension
the DHAs by gravimetric means and/or by NMR spectros- in vacuo. The residue was sealed off under high vacuum conditions
(10–6 Torr) on a vacuum line.18 After first vacuum distillation in an
all-glass apparatus, 1b was isolated from LiBr. Repeating vacuum
distillations in the all-glass apparatus gave 1b as a colorless liquid
(4.76 g, 25.0 mmol, 79%). For the cationic polymerization, the dis-
copy. The conversion of the 1,3-dibromoadamantanes and
the yield of the DHAs were often estimated by the NMR
measurements after converting the DHAs into the corre-
sponding 1-acetoxyadamantanes by quenching with
tilled DHAs were rapidly diluted with anhydrous CH2Cl2 or anhy-
AcOH. In our laboratory, the preparations of the DHAs
were usually performed using 1,3-dibromoadamantanes
in 3–30 gram amounts. This means that 1–15 grams of the
DHAs will be theoretically obtained after isolation. In
fact, the reaction mixture was transferred to an all-glass
apparatus on the vacuum line to effectively isolate the
DHAs and remove THF and lithium bromide.18 The ex-
periments under high vacuum conditions (10–6 Torr) using
an all-glass hand-made apparatus equipped with break-
seals were very effective for producing reproducible and
reliable results. For the DHAs with high boiling points,
the thermal polymerizations often lowered the isolated
yields of the DHAs during the vacuum distillations, in
particular, for the large-scale preparation.
drous n-heptane in an ampoule equipped with a break-seal, and the
solution was stored at –30 °C. For the NMR measurement, the dis-
tilled DHAs were rapidly diluted with C6D6 and sealed in an NMR
tube.
Marking of the butyl group: CdH2CcH2CbH2CaH3.
1H NMR (300 MHz, C6D6): δ = 0.89 (t, J = 7.1 Hz, CaH3, 3 H),
1.09–1.29 (m, 10 H, CdH2CcH2CbH2, one of C4H2, one of C8H2, one
of C9H2, one of C10H2), 1.63 (s, 2 H, C6H2), 1.73 (d, J = 10 Hz, 2 H,
one of C4H2, one of C9H2), 1.86 (d, J = 10 Hz, 2 H, one of C8H2, one
of C10H2), 1.97–2.05 (m, 2 H, C2H2), 2.81 (s, 1 H, C7H).
13C NMR (75 MHz, C6D6): δ = 14.4 (Ca), 24.2 (Cb), 27.8 (Cc), 36.1
(C1, C3), 37.8 (Cd), 42.6 (C6), 45.3 (C8, C10), 48.1 (C2), 49.8 (C4, C9),
53.5 (C7), 64.4 (C5).
In the large-scale preparation of DHA, the reaction was similarly
conducted using 2b (31.3 g, 89.4 mmol) to yield 13.2 g of 1b (67.9
mmol, 76%). It is also noteworthy that isolation of DHAs was pos-
sible by the vacuum distillation using usual laboratory glassware,
although the experimental procedure using vacuum line seemed
more effective for achieving reproducible and reliable results. For
example, 1b (1 g scale with sufficient purity) was obtained in 60%
yield after vacuum distillation using usual laboratory glassware,
In summary, we have developed practical synthetic proce-
dures for a series of DHAs carrying alkyl, phenyl, and alk-
oxy substituents in several gram amounts. The highly
strained [3.3.1]propellane frameworks in the DHAs can
be constructed in 21–81% yields by the reaction of the
1,3-dibromoadamantane derivatives with lithium in THF. when 1b was carefully treated to prevent contact with air.
The resulting DHAs show similar high ring-opening reac-
tivities and polymerizabilities toward various chemical
reagents, which are not the subjects of this report. The re-
5-Hexyl-1,3-dehydroadamantane (1c)
The reaction was performed following typical procedure A, starting
from 5-hexyl-1,3-dibromoadamantane (2c; 11.7 g, 30.9 mmol) to
sulting asymmetrical 5,7-disubstituted DHAs were re- yield 1c (4.32 g, 19.8 mmol, 64%) as a colorless oil.
Marking of the hexyl group: CfH2CeH2CdH2CcH2CbH2CaH3.
vealed to be precursors of multi-substituted adamantane
derivatives bearing a stereogenic center. From the view-
point of polymer chemists, DHAs are promising novel cy-
clic monomers for constructing a rigid building unit,
adamantane-1,3-diyl, via the ring-opening polymeriza-
tion.
1H NMR (300 MHz, C6D6): δ = 0.89–0.93 (t, J = 6.5 Hz, 3 H, CaH3),
1.10–1.40 (m, 14 H, CbH2, CcH2, CdH2, CeH2, CfH2, one of C4H2,
one of C8H2, one of C9H2, one of C10H2), 1.64 (s, 2 H, C6H2), 1.73–
1.76 (d, J = 10 Hz, 2 H, one of C4H2, one of C9H2), 1.85–1.88 (d,
J = 10 Hz, 2 H, one of C8H2, one of C10H2), 1.98–2.06 (m, 2 H,
C2H2), 2.82 (br s, 1 H, C7H).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3332–3340

3338
S. Inomata et al.
FEATURE ARTICLE
13C NMR (75 MHz, C6D6): δ = 14.5 (Ca), 23.2 (Cb), 25.6 (Cc), 30.8
(Cd), 32.3 (Ce), 36.1 (C1, C3), 38.1 (Cf), 42.6 (C6), 45.3 (C8, C10),
48.1 (C2), 49.9 (C4, C9), 53.5 (C7), 64.4 (C5).
Marking of the ethyl and hexyl groups: CbH2CaH3;
CcH2CdH2CeH2CfH2CgH2ChH3.
1H NMR (300 MHz, C6D6): δ = 0.82–0.87 (t, J = 7.5 Hz, 3 H, CaH3),
0.91–0.95 (t, J = 6.4 Hz, 3 H, ChH3), 1.06–1.14 (m, 4 H, one of
C4H2, one of C8H2, one of C9H2, one of C10H2), 1.26–1.43 (m, 12 H,
CbH2, CcH2, CdH2, CeH2, CfH2, CgH2), 1.59 (s, 2 H, C6H2), 1.64–1.70
(m, 4 H, one of C4H2, one of C8H2, one of C9H2, one of C10H2), 1.93
(s, 2 H, C2H2).
13C NMR (75 MHz, C6D6): δ = 9.8 (Ca), 14.5 (Ch), 23.2, 25.7, 30.0,
30.9, 32.9, and 37.9 (Cb, Cc, Cd, Ce, Cf, Cg), 34.7 (C1, C3), 46.5 (C2),
47.3 (C6), 48.5 and 49.1 (C4, C8, C9, C10), 63.5 and 63.9 (C5, C7).
5-Octyl-1,3-dehydroadamantane (1d)
The reaction was performed following typical procedure A, starting
from 5-octyl-1,3-dibromoadamantane (2d; 4.93 g, 12.1 mmol) to
yield 1d (2.17 g, 8.82 mmol, 73%) as a colorless oil.
Marking of the octyl group: ChH2CgH2CfH2CeH2CdH2CcH2CbH2
CaH3.
1H NMR (300 MHz, C6D6): δ = 0.89–0.93 (t, J = 6.4 Hz, 3 H, CaH3),
1.11–1.40 (m, 18 H, CbH2, CcH2, CdH2, CeH2, CfH2, CgH2, ChH2, one
of C4H2, one of C8H2, one of C9H2, one of C10H2), 1.65 (s, 2 H,
C6H2), 1.73–1.77 (d, J = 10 Hz, 2 H, one of C4H2, one of C9H2),
1.85–1.88 (d, J = 10 Hz, one of C8H2, one of C10H2), 1.95–2.05 (m,
2 H, C2H2), 2.82 (s, 1 H, C7H).
5,7-Dibutyl-1,3-dehydroadamantane (1j)
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5,7-dibutyladamantane (2j; 15.3 g, 37.7 mmol)
to yield 1j (5.30 g, 21.5 mmol, 57%) as a colorless oil.
13C NMR (75 MHz, C6D6): δ = 14.4 (Ca), 23.2 (Cb), 25.6 (Cc), 29.9
and 30.1 (Cd, Ce), 31.2 (Cf), 32.4 (Cg), 36.0 (C1, C3), 38.1 (Ch), 42.6
(C6), 45.3 (C8, C10), 48.0 (C2), 49.8 (C4, C9), 53.5 (C7), 64.4 (C5).
1H NMR (300 MHz, C6D6): δ = 0.92 (t, J = 6.7 Hz, 6 H, CaH3),
1.05–1.08 (d, J = 10 Hz, 4 H, one of C4H2, one of C8H2, one of C9H2,
and one of C10H2), 1.16–1.29 (m, 12 H, CbH2, CcH2, CdH2), 1.57 (s,
2 H, C6H2), 1.65–1.68 (d, J = 10 Hz, 4 H, one of C4H2, one of C8H2,
one of C9H2, one of C10H2), 1.94 (s, 2 H, C2H2).
5-Phenyl-1,3-dehydroadamantane (1e)
The reaction was performed following typical procedure A, starting
from 5-phenyl-1,3-dibromoadamantane (2e; 7.90 g, 21.3 mmol) to
yield 1e (2.10 g, 10.0 mmol, 47%) as a white solid.
13C NMR (75 MHz, C6D6): δ = 14.4 (Ca), 24.2 (Cb), 27.9 (Cc), 34.8
(C1, C3), 37.6 (Cd), 46.5 (C2), 47.8 (C6), 49.1 (C4, C8, C9, C10).
1H NMR (300 MHz, C6D6): δ = 1.10–1.14 (d, J = 11 Hz, 2 H, one
of C8H2, one of C10H2), 1.43–1.47 (d, J = 11 Hz, 2 H, one of C4H2,
one of C9H2), 1.87–2.03 (m, 6 H, C2H2, C6H2, one of C8H2, one of
C10H2), 2.18–2.23 (m, 2 H, one of C4H2, one of C9H), 2.79 (s, 1 H,
C7H), 7.05–7.20 (m, 5 H, C6H5).
13C NMR (75 MHz, C6D6): δ = 35.4 (C1, C3), 44.9 (C8, C10), 45.1
(C6), 47.9 (C2), 50.1 (C4, C9), 53.8 (C7), 67.4 (C5), 126.1 (Cm), 126.5
(Cp), 128.4 (Co), 146.7 (Ci).
5-Butyl-7-isobutyl-1,3-dehydroadamantane (1k)
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5-butyl-7-isobutyladamantane (2k; 8.35 g, 20.6
mmol) to yield 1k (3.41 g, 13.9 mmol, 67%) as a colorless oil.
Marking of the butyl and isobutyl groups: CdH2CcH2CbH2CaH3;
CeH2CfH(CgH3)2.
1H NMR (300 MHz, C6D6): δ = 0.89–0.95 (m, 9 H, CaH3, CgH3),
1.01–1.10 (m, 4 H, one of C4H2, one of C8H2, one of C9H2, one of
C10H2), 1.20–1.29 (m, 8 H, CbH2, CcH2, CdH2, CeH2), 1.58 (s, 2 H,
C6H2), 1.63–1.72 (m, 5 H, one of C4H2, one of C8H2, one of C9H2,
one of C10H2, CfH), 1.93 (br s, 2 H, C2H2).
13C NMR (75 MHz, C6D6): δ = 14.4 (Ca), 24.2 (Cb), 25.0 (Cf), 25.3
(Cg), 27.9 (Cc), 34.8 (C1, C3), 37.6 (Cd), 46.5 (C2), 47.0 (Ce), 48.1
(C6), 49.0 and 50.0 (C4, C8, C9, C10), 63.5 (C5, C7).
5-Methoxy-1,3-dehydroadamantane (1f)
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5-methoxyadamantane (2f; 4.37 g, 13.5 mmol)
to yield 1f (1.28 g, 7.80 mmol, 58%) as a colorless oil.
1H NMR (300 MHz, C6D6): δ = 0.90–0.94 (d, J = 11 Hz, 2 H, one
of C8H2, one of C10H2), 1.39–1.42 (d, J = 10 Hz, 2 H, one of C4H2,
one of C9H2), 1.62–1.67 (m, 3 H, one of C2H2, one of C8H2, one of
C10H2), 1.76–1.78 (m, 1 H, one of C2H2), 1.83–1.88 (m, 4 H, C6H2,
one of C4H2, one of C9H2), 2.69 (br s, 1 H, C7H), 3.09 (s, 3 H,
OCH3).
5-Butyl-7-hexyl-1,3-dehydroadamantane (1l)
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5-butyl-7-hexyladamantane (2l; 4.47 g, 10.3
mmol) to yield 1l (1.52 g, 5.55 mmol, 54%) as a colorless oil.
13C NMR (75 MHz, C6D6): δ = 30.3 (C1, C3), 41.7 (C6), 44.2 (C2),
Marking of the butyl and hexyl groups : CdH2CcH2CbH2CaH3;
44.3 (C8, C10), 46.0 (C4, C9), 51.0 (OCH3), 52.9 (C7), 91.6 (C5).
CeH2CfH2CgH2ChH2CiH2CjH3.
5-Butoxy-1,3-dehydroadamantane (1g)
1H NMR (300 MHz, C6D6): δ = 0.89–0.93 (m, 6 H, CaH3, CjH3),
1.04–1.14 (m, 4 H, one of C4H2, one of C8H2, one of C9H2, one of
C10H2), 1.20–1.35 (m, 16 H, CbH2, CcH2, CdH2, CeH2, CfH2, CgH2,
ChH2, CiH2), 1.60 (s, 2 H, C6H2), 1.66–1.70 (m, 4 H, one of C4H2,
one of C8H2, one of C9H2, one of C10H2), 1.95 (s, 2 H, C2H2).
13C NMR (75 MHz, C6D6): δ = 14.5 (Ca, Cj), 23.2, 24.2, 25.7, and
27.9 (Cb, Cg, Ch, Ci), 31.0 and 32.4 (Cc, Cf), 34.8 (C1, C3), 37.6 and
37.9 (Cd, Ce), 46.6 (C2), 47.9 (C6), 49.2 (C4, C8, C9, C10), 63.6 (C5,
C7).
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5-butoxyadamantane (2g; 7.21 g, 19.7 mmol) to
yield 1g (2.31 g, 11.2 mmol, 57%) as a colorless oil.
Marking of the butoxy group: OCdH2CcH2CbH2CaH3.
1H NMR (300 MHz, C6D6): δ = 0.85–0.96 (m, 5 H, CaH3, one of
C8H2, one of C10H2), 1.36–1.58 (m, 6 H, CbH2, CcH2, one of C4H2,
one of C9H2), 1.66–1.69 (m, 3 H, one of C2H2, one of C8H2, one of
C10H2), 1.78–1.80 (m, 1 H, one of C2H2), 1.90–1.93 (C6H2, one of
C4H2, one of C9H2), 2.72 (br s, 1 H, C7H), 3.28–3.32 (t, J = 6.3 Hz,
2 H, CdH2).
13C NMR (75 MHz, C6D6): δ = 14.2 (Ca), 19.8 (Cb), 30.4 (C1, C3),
33.1 (Cc), 42.1 (C6), 44.2 (C2), 44.3 (C8, C10), 46.8 (C4, C9), 52.9
(C7), 63.0 (Cd), 91.3 (C5).
5-Butyl-7-phenyl-1,3-dehydroadamantane (1m)
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5-butyl-7-phenyladamantane (2m; 6.44 g, 15.1
mmol) to yield 1m (830 mg, 3.12 mmol, 21%) as a colorless oil.
1H NMR (300 MHz, C6D6): δ = 0.87–0.91 (t, J = 6.7 Hz, 3 H, CaH3),
1.06–1.10 (d, J = 10 Hz, 2 H, one of C4H2, one of C9H2), 1.18–1.24
(m, 6 H, CbH2, CcH2, CdH2), 1.40–1.44 (d, J = 10 Hz, 2 H, one of
C8H2, one of C10H2), 1.71 (m, 2 H, one of C4H2, one of C9H2), 1.86
(s, 2 H, C6H2), 1.94 (s, 2 H, C2H2), 2.16 (m, 2 H, one of C8H2, one
of C10H2), 7.10–7.20 (m, 5 H, C6H5).
5-Ethyl-7-hexyl-1,3-dehydroadamantane (1i)
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5-ethyl-7-hexyladamantane (2i; 6.68 g, 16.4
mmol) to yield 1i (1.54 g, 6.26 mmol, 38%) as a colorless oil.
Synthesis 2013, 45, 3332–3340
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Synthesis of 1,3-Dehydroadamantanes
3339
13C NMR (75 MHz, C6D6): δ = 14.4 (Ca), 24.1 (Cb), 27.8 (Cc), 34.3
(C1, C3), 37.4 (Cd), 46.4 (C2), 48.8 (C4, C9), 49.3 (C8, C10), 50.4 (C6),
63.9 (C5), 66.7 (C7), 126.2 (Cm), 126.7 (Cp) 128.4 (Co) 146.8 (Ci).
flask equipped with a break-seal and then sealed off under high vac-
uum conditions. Repeating vacuum distillations in the all-glass ap-
paratus gave 1a as a white solid (7.45 g, 55.5 mmol, 81%). Then, 1a
was diluted with THF (40 mL) and stored in an ampoule equipped
with a break-seal at –30 °C. The resulting THF solution of 1a was
used for the copolymerization reaction with acrylonitrile or methyl
acrylate.13
5-Butyl-7-methoxy-1,3-dehydroadamantane (1n)
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5-butyl-7-methoxyadamantane (2n; 6.51 g, 17.1
mmol) to yield 1n (2.26 g, 10.3 mmol, 60%) as a colorless oil.
1H NMR (300 MHz, C6D6): δ = 0.85–0.94 (m, 5 H, CaH3, one of
C8H2, and one of C10H2), 1.12–1.24 (m, 6 H, CbH2, CcH2, CdH2),
1.36–1.39 (d, J = 10 Hz, one of C4H2, one of C9H2), 1.51–1.57 (m,
3 H, one of C2H2, one of C8H2, one of C10H2) 1.73–1.86 (m, 5 H, one
of C2H2, C6H2, one of C4H2, one of C9H2), 3.14 (s, 3 H, OCH3).
13C NMR (75 MHz, C6D6): δ = 14.4 (Ca), 24.1 (Cb), 27.9 (Cc), 28.9
(C1, C3), 36.6 (Cd), 42.7 (C2), 45.3 (C8, C10), 46.7 (C6), 48.3 (C4, C9),
51.2 (OCH3), 63.9 (C5), 91.2 (C7).
5,7-Dimethyl-1,3-dehydroadamantane (1h)
Similarly following typical procedure C, 1h was obtained in 86%
(4.15 g, 25.6 mmol) yield by the reaction of 2h (9.60 g, 29.8 mmol)
and Li (1.50 g, 217 mmol) in THF (55 mL).
Synthesis of 1b Using Magnesium
A mixture of 2b (2.75 g, 7.86 mmol) and Mg (0.71 g, 29.6 mmol)
in anhydrous THF (28 mL) was refluxed for 24 h under argon. Then,
the resulting black solution was transferred into a distillation flask
to remove residual Mg by vacuum distillation to give 1b (0.75 g,
3.92 mmol, 50%) as a colorless oil. The distilled products contained
7% of reduced 1-butyladamantane along with 1b.
5-Butoxy-7-butyl-1,3-dehydroadamantane (1o)
The reaction was performed following typical procedure A, starting
from 1,3-dibromo-5-butoxy-7-butyladamantane (2o; 2.33 g, 5.52
mmol) to yield 1o (904 mg, 3.45 mmol, 62%) as a colorless oil.
Reaction of 1b with Oxygen in the Bulk
Liquid of 1b (0.70 g, 3.66 mmol) was stirred in the air in the bulk at
r.t. After 24 h, the resulting viscous liquid was diluted with THF (5
mL) and poured into MeOH (100 mL) to afford white powdery solid
(0.38 g, 54%). The resulting powder was identified as an alternating
copolymer of 1b with oxygen, poly(1b-alt-O2), by 1H and 13C NMR
measurements.
1H NMR (300 MHz, CDCl3): δ = 0.87 (br s, 3 H, CaH3), 1.21 (br s,
6 H, CbH2, CcH2, CdH2), 1.27 (br s, 2 H, C6H2), 1.41–1.50 (br m, 4
H, C4H2, C9H2), 1.59–1.72 (br m, 4 H, C8H2, C10H2), 1.78–1.85 (br
m, 2 H, C2H2), 2.31 (br s, 1 H, C7H).
Marking of the butyl and butoxy groups: CdH2CcH2CbH2CaH3;
OChH2CgH2CfH2CeH3.
1H NMR (300 MHz, C6D6): δ = 0.87–0.95 (m, 8 H, CaH3, CeH3, one
of C8H2, one of C10H2), 1.16–1.22 (m, 6 H, CbH2, CcH2, CdH2),
1.36–1.59 (m, 9 H, one of C2H2, one of C4H2, one of C8H2, one of
C9H2, one of C10H2, CfH2, CgH2), 1.74–1.77 (m, 1 H, one of C2H2),
1.83–1.86 (m, 4 H, C6H2, one of C4H2, one of C9H2), 3.31–3.35 (t,
J = 6.3 Hz, 2 H, ChH2).
13C NMR (75 MHz, C6D6): δ = 14.3 (Ce), 14.4 (Ca), 19.9 (Cf), 24.1
(Cb), 28.0 (Cc), 29.1 (C1, C3), 33.2 (Cg), 36.7 (Cd), 42.7 (C2), 46.0
(C4, C9), 47.1 (C6), 48.4 (C8, C10), 63.1 (Ch), 64.0 (C5), 90.9 (C7).
13C NMR (75 MHz, CDCl3): δ = 14.2 (Ca), 23.5 (Cb), 25.2 (Cc), 30.5
(C7), 37.2 (C5), 39.4 (C8, C10), 40.7 (C6), 42.9 (Cd), 43.4 (C2), 44.6
(C4, C9).
Preparation of 1a and 1h in Tetraglyme; 1,3-Dehydroadaman-
tane (1a); Typical Procedure B
The resulting polymer possessed Mn = 6000 g/mol and
Mw/Mn = 2.60, measured by size exclusion chromatography in THF
calibrated with polystyrene standards.
A mixture of 1,3-dibromoadamantane (2a; 9.96 g, 39.1 mmol) and
Li (1.20 g, 173 mmol) in anhydrous tetraglyme (80 mL) was reacted
at 60 °C for 3 days under argon. Complete consumption of 2a was
confirmed by GLC. The resulting suspension was transferred into a
round-bottomed flask equipped with a break-seal and then sealed
off under high vacuum conditions. Vacuum distillations in the all-
glass apparatus gave 1a as a white solid (2.41 g, 18.0 mmol, 46%).
The resulting DHAs were diluted with CH2Cl2 or n-heptane and
used for the cationic polymerization.
Reaction of Poly(1b-alt-O2) with LiAlH4
Poly(1b-alt-O2) [0.12 g, 0.54 mmol (number of repeating units)]
was treated with LiAlH4 (2.18 g, 57.4 mmol) in THF (20 mL) at re-
flux for 72 h. After quenching with i-PrOH (2 mL), MeOH (2 mL),
H2O (5 mL), and aq HCl (10 mL), the resulting mixture was extract-
ed with CHCl3 (4 × 30 mL), and the combined organic layers were
dried (MgSO4). After removal of the solvent in vacuo, the major
product (0.14 g, quant) was identified as 1-butyl-3,5-dihydroxyad-
amantane; viscous liquid.
1H NMR (300 MHz, C6D6): δ = 1.26–1.30 (d, J = 11 Hz, 4 H, C4H2,
C8H2, C9H2, C10H2), 1.84 (br s, 2 H, C6H2), 2.02–2.06 (d, J = 11 Hz,
4 H, C4H2, C8H2, C9H2, C10H2), 2.19 (s, 2 H, C2H2), 2.90 (br s, 2 H,
C5H, C7H).
1H NMR (300 MHz, CDCl3): δ = 0.86–0.91 (t, J = 6.4 Hz, 3 H,
CaH3), 1.22 (br s, 6 H, CbH2, CcH2, CdH2), 1.28 (m, 2 H, C6H2), 1.40
(s, 4 H, C4H2, C9H2), 1.53–1.64 (2 d, J = 12.2 Hz, 4 H, C8H2, C10H2),
1.69 (s, 2 H, C2H2), 2.30 (m, 1 H, C7H), 2.66 (br s, 2 H, OH).
13C NMR (75 MHz, C6D6): δ = 37.8 (C1, C3), 38.1 (C6), 46.6 (C4, C8,
C9, C10), 50.1 (C2), 55.0 (C5, C7).
13C NMR (75 MHz, CDCl3): δ = 14.2 (Ca), 23.5 (Cb), 25.2 (Cc), 30.9
(C7), 37.7 (C1), 39.9 (C8), 42.4 (Cd), 43.5 (C6, C10), 48.9 (C2, C9),
52.4 (C4), 70.9 (C3, C5).
5,7-Dimethyl-1,3-dehydroadamantane (1h)
The reaction was performed following typical procedure B, starting
from 1,3-dibromo-5,7-dimethyladamantane (2h; 11.6 g, 35.9
mmol) to yield 1h (3.90 g, 24.1 mmol, 67%) as a white solid.
1H NMR (300 MHz, C6D6): δ = 0.90 (s, 6 H, CH3), 0.99–1.02 (d,
J = 10 Hz, 4 H, C4H2, C8H2, C9H2, C10H2), 1.47 (br s, 2 H, C6H2),
1.57–1.61 (d, J = 10 Hz, 4 H, C4H2, C8H2, C9H2, C10H2), 1.91 (s, 2
H, C2H2).
Reaction of 1a with MeOH in the Presence of MsOH
A methanolic solution of MsOH (0.145 M, 0.145 mmol, 1 mL) was
added to a solution of 1a (372 mg, 2.77 mmol) in CH2Cl2 (4.5 mL)
and then the mixture was stirred at r.t. under N2 atmosphere for 3.5
h. After removal of solvent in vacuo, 1-methoxyadamantane (383
mg, 2.31 mmol, 83%, bp 37–39 °C/4.0 mmHg) was obtained as a
colorless oil.
13C NMR (75 MHz, C6D6): δ = 22.6 (CH3), 36.5 (C1, C3), 46.4 (C2),
50.9 (C4, C8, C9, C10), 52.1 (C6), 59.6 (C5, C7).
IR (film): 2903, 2850, 1451, 1354, 1177, 1115, 1089, 1051, 893
cm–1.
Preparation of 1,3-Dehydroadamantane (1a) in THF; Typical
Procedure C
A mixture of 2a (17.1 g, 68.5 mmol) and Li (1.70 g, 245 mmol) in
anhydrous THF (50 mL) was reacted at r.t. for 24 h under argon.
The resulting suspension was transferred into a round-bottomed
1H NMR (300 MHz, CDCl3): δ = 1.53–1.66 (m, 6 H, C4H2), 1.71 (s,
6 H, C2H2), 2.13 (s, 3 H, C3H), 3.21 (s, 3 H, OCH3).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3332–3340

3340
S. Inomata et al.
FEATURE ARTICLE
13C NMR (75 MHz, CDCl3): δ = 30.6 (C3), 36.6 (C4), 41.1 (C2), 47.9
References
(OCH3), 72.0 (C1).
(1) Pincock, R. E.; Torupka, E. J. J. Am. Chem. Soc. 1969, 91,
4593.
(2) Pincock, R. E.; Schmidt, J.; Scott, W. B.; Torupka, E. J. Can.
J. Chem. 1972, 50, 3958.
(3) (a) Fokin, A. A.; Schreiner, P. R.; von Schleyer, P. R.;
Gunchenko, P. A. J. Org. Chem. 1998, 63, 6494. (b) The
strain energies of 1a and [3.3.1]propellane were estimated to
be 55.5 and 36.1 kcal·mol–1, which were much higher than
those of cyclopropane (27.2 kcal·mol–1) and cyclobutane
(26.4 kcal·mol–1).
(4) Wiberg, K. B.; Walker, F. H. J. Am. Chem. Soc. 1982, 104,
5239.
(5) Eaton, P. E.; Temme, G. H. III J. Am. Chem. Soc. 1973, 95,
7508.
(6) Wiberg, K. B.; Bailey, W. F.; Jason, M. E. J. Org. Chem.
1976, 41, 2711.
(7) Wiberg, K. B.; Lupton, E. C. Jr.; Burgmaier, G. J. J. Am.
Chem. Soc. 1969, 91, 3372.
Reaction of 1b with MeOH in the Absence of Acid
A mixture of 1b (190 mg, 1.0 mmol), CH2Cl2 (1.6 mL), and MeOH
(1.0 mL) was stirred at r.t. under argon. The substrate 1b was slowly
consumed, and 1-butyl-3-methoxyadamantane was newly formed
in the mixture. The conversion of 1b was monitored by NMR and
GLC measurements as 8, 48, 85, and, 100% after 10 min, 1.5 h, 6 h,
and 30 h, respectively. Finally, 1-butyl-3-methoxyadamantane was
obtained as the only product after 30 h.15
1H NMR (300 MHz, CDCl3): δ = 0.88 (t, J = 6.9 Hz, 3 H, CaH3),
1.13–1.25 (m, 6 H, CbH2, CcH2, CdH2), 1.37 (br s, 4 H, C8H2, C9H2),
1.43 (s, 2 H, C6H2), 1.53 (br s, 2 H, C2H2), 1.64–1.68 (m, 4 H, C4H2,
C10H2), 2.18 (br s, 2 H, C5H, C7H), 3.22 (s, 3 H, OCH3).
13C NMR (75 MHz, CDCl3): δ = 14.3 (Ca), 23.7 (Cb), 25.1 (Cc), 30.7
(C5, C7), 35.8 (C1), 36.3 (C6), 40.7 (C8, C9), 41.6 (C4, C10), 43.8 (C2),
45.9 (Cd), 48.0 (OCH3), 73.0 (C3).
Reaction of 1b with AcOH
AcOH (1 mL, 17.5 mmol) was added to a solution of 1b (698 mg,
3.67 mmol) in CH2Cl2 (7.7 mL) and stirred for 5 min under N2. Af-
ter removal of solvent in vacuo, 1-acetoxy-3-butyladamantane (910
mg, 99%) was obtained as a colorless oil.
(8) (a) Wiberg, K. B. Acc. Chem. Res. 1984, 17, 379.
(b) Wiberg, K. B. Chem. Rev. 1989, 89, 975.
(9) (a) Kaszynski, P.; Michl, J. J. Am. Chem. Soc. 1988, 110,
5225. (b) Friedli, A. C.; Kaszynski, P.; Michl, J.
Tetrahedron Lett. 1989, 30, 455.
(10) (a) Schlüter, A.-D. Angew. Chem., Int. Ed. Engl. 1988, 27,
296. (b) Schlüter, A.-D. Macromolecules 1988, 21, 1208.
(c) Opitz, K.; Schlüter, A.-D. Angew. Chem., Int. Ed. Engl.
1989, 28, 456.
(11) Ishizone, T.; Matsuoka, S.; Sakai, S.; Harada, W.; Tajima, H.
Macromolecules 2004, 37, 7069.
(12) Inomata, S.; Matsuoka, S.; Sakai, S.; Tajima, H.; Ishizone, T.
Macromolecules 2012, 45, 4184.
IR (film): 2960, 2855, 1731, 1455, 1365, 1238, 1139, 1024, 864,
606 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.86–0.90 (t, J = 6.6 Hz, 3 H,
CaH3), 1.12–1.54 (m, 12 H, CbH2, CcH2, CdH2, C4H2, C6H2, C10H2),
1.81 (s, 2 H, C2H2), 1.96 (s, 3 H, COCH3), 2.01–2.09 (m, 4 H, C8H2,
C9H2), 2.18–2.19 (br s, 2 H, C5H, C7H).
13C NMR (75 MHz, CDCl3): δ = 14.2 (Ca), 22.8 (COCH3), 23.6
(Cb), 24.9 (Cc), 30.9 (C5, C7), 35.9 (C6), 36.2 (C3), 40.9 (C8, C9),
41.2 (C4, C10), 43.4 (Cd), 45.9 (C2), 81.3 (C1), 170.4 (C=O).
(13) Matsuoka, S.; Ogiwara, N.; Ishizone, T. J. Am. Chem. Soc.
2006, 128, 8708.
(14) Inomata, S.; Harada, Y.; Nakamura, Y.; Uehara, Y.;
Ishizone, T. J. Polym. Sci. Part A: Polym. Chem. 2013, 51,
4111 .
HRMS (ESI-TOF): m/z calcd for C16H26O2 + Na [M + Na]+:
273.1825; found: 273.1820.
Reaction of 1a with AcOH in THF
AcOH (0.83 mL, 13.2 mmol) was added to a solution of 1a (379 mg,
2.83 mmol) in THF (9.0 mL) and stirred for 15 min under argon. Af-
ter removal of solvent in vacuo, a mixture (760 mg) of 1-acetoxy-
adamantane (~22%) and 1-(4-acetoxybutoxy)adamantane (~78%)
was obtained as a viscous liquid. Column chromatography (SiO2;
hexane–EtOAc, 9:1) of the mixture gave 1-acetoxyadamantane
(119 mg, 0.613 mmol, 22%, colorless oil) and 1-(4-acetoxybut-
oxy)adamantane (496 mg, 1.86 mmol, 66%, colorless oil), respec-
tively.
(15) Inomata, S.; Harada, Y.; Matsuoka, S.; Ishizone, T.
Tetrahedron 2013, 69, 3238.
(16) Adcock, W.; Clark, C. I. J. Org. Chem. 1993, 58, 7341.
(17) Scott, W. B.; Pincock, R. E. J. Am. Chem. Soc. 1973, 95,
2040.
(18) Hirao, A.; Takenaka, K.; Packrisamy, S.; Yamaguchi, K.;
Nakahama, S. Makromol. Chem. 1985, 186, 1157.
(19) If the removal of LiBr is insufficient in addition to THF, a
trace amount of 1-(4-bromobutoxy)adamantane is formed
after the addition of AcOH. In this case, nucleophilic
reaction of bromide ion takes place with the oxonium ion
instead of the acetate ion.
(20) (a) Jasys, V. J.; Lombardo, F.; Appleton, T. A.; Bordner, J.;
Ziliox, M.; Volkmann, R. A. J. Am. Chem. Soc. 2000, 122,
466. (b) Schreiner, P. R.; Fokin, A. A.; Lauenstein, O.;
Okamoto, Y.; Wakita, T.; Rinderspacher, C.; Robinson, G.
H.; Vohs, J. K.; Campana, C. F. J. Am. Chem. Soc. 2002,
124, 13348.
Selected data for 1-(4-acetoxybutoxy)adamantane:
1H NMR (300 MHz, CDCl3): δ = 1.48–1.70 (m, 9 H, C3H, C4H2,
C5H, C6H2, C7H, C10H2), 1.70–1.81 (m, 6 H, C2H2, C8H2, C9H2),
2.01–2.09 (s, 3 H, CaH3), 2.09–2.11 (br, 4 H, CdH2, CeH2), 3.87–
3.48 (t, J = 6.3 Hz, 2 H, CfH2), 4.02–4.13 (t, J = 6.6 Hz, 2 H, CcH2).
13C NMR (75 MHz, CDCl3): δ = 21.1 (Ca), 25.7 (Ce), 27.1 (Cd), 30.6
(C3, C5, C7), 36.6 (C4, C6, C10), 41.7 (C2, C8, C9), 59.2 (Cf), 64.6 (Cc),
71.9 (C1), 171.3 (Cb).
HRMS (ESI-TOF): m/z calcd for C16H26O3 + Na [M + Na]+:
289.1780; found: 289.1778.
(21) (a) Jarret, R. M.; Cusumano, L. Tetrahedron Lett. 1990, 31,
171. (b) Frei, K.; Bernstein, H. J. J. Chem. Phys. 1963, 38,
1216. (c) Eaton, P. E. Angew. Chem., Int. Ed. Engl. 1992, 31,
1421.
Synthesis 2013, 45, 3332–3340
© Georg Thieme Verlag Stuttgart · New York