A step toward polytwistane: Synthesis and characterization of C 2-symmetric tritwistane

Article abstract of DOI:10.1039/c3ob42152j

Twistane is a classic hydrocarbon with fascinating stereochemical properties. Herein we describe a series of oligomers of twistane that converges on a chiral nanorod, which we term polytwistane. A member of this series, C ₂-symmetric tritwistane, has been synthesized for the first time. This journal is The Royal Society of Chemistry.

Full text of DOI:10.1039/c3ob42152j

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A step toward polytwistane: synthesis and
characterization of C2-symmetric tritwistane†
Cite this: Org. Biomol. Chem., 2014,
12, 108
Martin Olbrich, Peter Mayer and Dirk Trauner*
Received 13th August 2013,
Accepted 31st October 2013
Twistane is a classic hydrocarbon with fascinating stereochemical properties. Herein we describe a series
of oligomers of twistane that converges on a chiral nanorod, which we term polytwistane. A member of
this series, C2-symmetric tritwistane, has been synthesized for the first time.
DOI: 10.1039/c3ob42152j
www.rsc.org/obc
Twistane (tricyclo[4.4.0.03,8]decane) (1) is a tricyclic hydro-
carbon that has played an important role in the development
of organic stereochemistry.1 The D2-symmetrical molecule con-
sists of three interwoven twist boat rings, all of which have
approximate D2-symmetry with identical handedness. It can be
formed, conceptually, through bridging of a cis-decalin with a
single bond or by adding an ethano (ethane-1,2-diyl) bridge to
a bicyclo[2.2.2]octane. In reality, twistane (1) has been syn-
thesized numerous times, in both enantiomeric forms1,2 and
as a racemate,3 starting with Howard Whitlock’s seminal work
in 1962.4 A large variety of substituted twistanes, including
unsaturated derivatives, are now known.5
In a “Gedankenexperiment”, twistane (1) can be further
extended by bridging its six-membered rings with additional
ethano bridges mounted in a 1,4-fashion (Scheme 1). Due to
geometrical constraints, the newly formed six-membered rings
continue to adopt a twist boat conformation with the same
handedness as the existing rings. Provided quaternary carbons
are avoided, the first substitution can only proceed in one way
to yield the C2-symmetrical ditwistane (2). Further addition of
Scheme 1 Twistane (1), oligotwistanes and polytwistane (8).
an ethano bridge to ditwistane in a linear fashion produces environment. It is a chiral nanorod of high rigidity since none
C2-symmetric tritwistane (3). Linear extension of C2-tritwistane of its C,C-bonds can rotate freely and it can exist in two enantio-
(3) affords tetratwistane (4), pentatwistane (5), hexatwistane morphic forms, i.e. as a P or M helix. A more detailed descrip-
(6), heptatwistane (7), and so on. All of these helical com- tion of polytwistane as a geometrical object and a prediction of
pounds are chiral molecules with C2 symmetry.
its physical properties will be described elsewhere.6
Further extension of these oligotwistanes in a linear
Among the hydrocarbons shown in Scheme 1, only twistane
fashion, ideally to infinity, affords a polymer with fascinating (1) and ditwistane (2) are known compounds. Both enantio-
geometrical properties, which we propose to call “polytwistane” mers of ditwistane (2) have been synthesized8 and dozens of
(8) (Fig. 1). Ideal polytwistane has the same molecular formula, compounds that incorporate the ditwistane skeleton have been
CnHn, as polyacetylene but it is fully saturated with all of its sp3 described.8 Structures containing the carbon skeleton of C2-
hybridized carbons and hydrogens in an identical chemical tritwistane9 and C2-hexatwistane10 have also been reported.
None of these compounds, however, have been identified as
oligotwistanes, and polytwistane (8) does not seem to have
Department of Chemistry, Ludwig-Maximilians-Universität München, and Munich
been mentioned in the literature so far.
We now report our studies on linear oligotwistanes, which
were undertaken to extend the series of known oligotwistanes
Center for Integrated Protein Science, Butenandtstrasse 5-13, 81377 München,
Germany. E-mail: dirk.trauner@lmu.de
†Electronic supplementary information (ESI) available. CCDC 948941–948947,
and obtain spectral data that might help in the identification
949955 and 949956. For ESI and crystallographic data in CIF or other electronic
of polytwistane. Our initial studies were based on additions to
format see DOI: 10.1039/c3ob42152j
108 | Org. Biomol. Chem., 2014, 12, 108–112
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Fig. 1 Aspects of polytwistane (8). Top: M helical polytwistane (8)
drawn in a manner that emphasizes the structural unit of twistane.
Middle: M helical polytwistane (8) drawn in a manner that emphasizes
the incorporated bicyclo[2.2.2]-octane units. Bottom: side view (left)
and top view (right) of a C52H58-fragment of M helical polytwistane cal-
culated at the B3LYP/6-31 g(d) level.7
Scheme 3 Initial attempts to synthesize tritwistane via epoxidation of
10 and 11.
Epoxidation of diene 11 with m-CPBA yielded the analogous
ketone 19 as the only isolable product, due to the instability of
the intermediary epoxide 17 under the conditions. The X-ray
structures of ketones 16 and 19, which bear a novel carbon
skeleton, as well as epoxide 14 are shown in the ESI.†
Our attempts to access the tritwistane skeleton, via halogen
addition, using conditions reported by Chou and coworkers9
were more successful (Scheme 4). Exposure of tetrachloro
diene 10 to bromine in chloroform gave the halogenated trit-
wistanes 22a,b together with the interesting syn-adduct 24.
The former presumably stem from an “N-type” nucleophilic
attack onto bromonium ion 20, followed by quenching of the
intermediary carbocation 21 by bromide, which yielded a
7 : 3 mixture of diastereomers 22a and b, respectively. The for-
mation of 24 can be rationalized by a “U-type” nucleophilic
attack, followed by an SN2-type displacement with overall
double inversion. The X-ray structures of the major diastereo-
mer 22a and the syn-dibromide 24 are shown in Fig. 2. We next
investigated the bromination on laticyclic hydrocarbon 11,
which gave the dibromo tritwistane 27 as a single diastereo-
mer, together with the unusual dibromide 30. The former is
again the product of an “N-type” cyclization, whereas the latter
Scheme 2 Synthesis of the laticyclic conjugated precursors.
laticyclic polyenes, which are known to yield twistane motifs.10
To this end, we synthesized the diene 11 and the triene 13
following a strategy developed by Gleiter and colleagues
(Scheme 2).11
Addition of ethylene to triene 9 at high pressure gave tetra-
cyclic tetrachloro diene 10, which was dechlorinated to afford
11. Similarly, Diels–Alder addition of dihydrobarrelene12 to 9
gave 12, the dechlorination of which yielded the hexacyclic
triene 13.
Our first attempts to synthesize tritwistane from dienes 10
or 11 are shown in Scheme 3. Epoxidation of tetrachloro diene
10 gave 14. Treatment of 14 with a Lewis acid in the presence
of a hydride source, however, did not yield a twistane but
exclusively gave 16. Presumably, this compound is the product
of a “U-type” (instead of “N-type”) nucleophilic attack, yielding
intermediate 15, followed by an intramolecular hydride shift,
as evidenced by the stereochemistry of the product 16.13
presumably arises from
a
twofold Wagner–Meerwein
rearrangement of the initial “U-type” cation 28, followed by
nucleophilic interception by bromide. The X-ray structures of
27 and the rearranged 30 are also shown in Fig. 2.
Attempts to synthesize hexatwistane derivatives via bromi-
nation of laticyclic triene 13 were less successful and gave
complex mixtures. So far, we have been unable to separate and
cleanly characterize the major components of this mixture.
Global dehalogenation of tetrachloro dibromo tritwistane 22
also failed under
a
variety of conditions. By contrast,
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Fig. 2 X-ray structures of 22a, 24, 27 and 30.
Scheme 5 Synthesis of tritwistane (3).
N-type additions across laticyclic polyenes are not a viable way
to access longer oligotwistanes or polytwistane (8) due to a
variety of possible side reactions and difficulties associated
with the procurement of precursors. Attempts to synthesize
polytwistane in a more direct fashion from acetylene itself are
ongoing in our laboratory and will be reported in due course.
The relationship of polytwistane to recently reported diamond
nanowires15 and ultra-small carbon nanotubes16 is also under
investigation.
Experimental section
Pentacyclo[6.2.2.23,6.02,7.05,9]tetradecan-4-one (19)
To
a solution of tetracyclotetradecadiene 11 (30.0 mg,
0.161 mmol, 1.00 eq.) in CH2Cl2 (2.50 mL) at 0 °C was added
m-CPBA (70–75 wt%, 37.5 mg, 0.161 mmol, 1.00 eq.). The reac-
tion mixture was stirred at 0 °C for 1 h, was then allowed to
warm to room temperature and stirred at room temperature
for an additional 2 h. After dilution with CH2Cl2 (15 mL) the
reaction mixture was poured into 10% aqueous NaOH (10 mL)
and the organic layer was washed with H2O (2 × 7.5 mL), brine
(7.5 mL), dried (Na2SO4) and concentrated in vacuo. Purifi-
cation of the residue by flash column chromatography
(hexanes–EtOAc = 9 : 1) afforded ketone 19 (20.0 mg, 61%) as a
colorless solid. Recrystallization from hexanes afforded crystals
suitable for X-ray analysis.
Scheme 4 Synthesis of tritwistanes 22a, b and 27 via bromination of 10
and 11.
dehalogenation of dibromo tritwistane 27 using Chatgilialo-
glu’s reagent14 was more successful and gave the parent hydro-
carbon 3 (Scheme 5). C2-Symmetric tritwistane (3) was easy to
identify due to its simplified 1H- and 13C-NMR spectra (see
ESI†).
Rf 0.36 (hexanes–EtOAc = 9 : 1); mp 95–97 °C; 1H NMR
(300 MHz, CDCl3) δ 2.80–2.71 (m, 1H), 2.40–2.29 (m, 1H),
2.27–2.19 (m, 1H), 2.17–2.10 (m, 1H), 2.07–2.01 (m, 1H),
2.00–1.88 (m, 2H), 1.85–1.72 (m, 4H), 1.67–1.53 (m, 5H),
In summary, we have described the first synthesis of
racemic tritwistane (3), which also yielded a variety of interest-
ing byproducts. Several of these, such as compounds 16, 19
and 30, bear a novel carbon skeleton. Our results indicate that
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1.52–1.37 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 222.7, 58.9, column and the solvent was removed in vacuo to afford tritwis-
47.1, 42.5, 40.6, 39.1, 38.3, 37.4, 29.5, 28.6, 28.3, 27.2, 19.8, tane (3) (6 mg, 32%) as a waxy amorphous solid.
19.8; IR νmax 2925, 2859, 1721, 1260, 1090, 1063, 1025, 994,
Rf 0.92 (hexanes); 1H NMR (600 MHz, CDCl3) δ 1.72
909, 886, 858, 812, 798, 732; HRMS (EI) m/z: [M]+ calcd for (m, 2H), 1.70–1.63 (m, 6H), 1.52–1.44 (m, 10H), 1.36 (dd, J =
C14H18O+ 202.1352; found: 202.1348.
12.1, 5.0 Hz, 2H); 13C NMR (150 MHz, CDCl3) δ 35.4, 33.6,
29.1, 28.6, 27.3, 24.8, 22.8; IR νmax 2921, 2908, 2871, 2860;
HRMS (EI) m/z: [M]+ calcd for C14H20+ 188.1560; found: 188.1549.
Bromination of syn-3,4,5,6-tetracyclo[6.2.2.23,6.02,7]tetradeca-4,9-
diene (11)
To a solution of diene 11 (49.9 mg, 268 µmol, 1.00 eq.) in
CHCl3 (3.00 mL) at 0 °C was added a solution of bromine in
CHCl3 (1.253 mL of a 1.37 vol% solution, 335 µmol, 1.25 eq.).
Acknowledgements
The reaction mixture was stirred at 0 °C for 1 h and the reac- We thank the Deutsche Forschungsgemeinschaft (SFB 749) for
tion was then quenched by addition of diluted aqueous financial support. We thank Prof. Benjamin List and Lars
Na2S2O3. The organic layer was separated and the aqueous Winkel (MPI für Kohlenforschung, Mülheim) for assistance
layer was extracted with CHCl3 (3 × 15 mL). The combined with high-pressure ethylene Diels–Alder reactions.
organic layer was washed with NaHCO3 (30 mL), brine
(30 mL), dried (Na2SO4) and concentrated in vacuo. Purifi-
cation of the residue by flash column chromatography
(hexanes–Et2O = 95 : 5) afforded rearranged dibromide 30
Notes and references
(15 mg, 14%) and dibromotritwistane 27 (35 mg, 38%) as col-
orless solids. Recrystallization from hexanes afforded crystals
suitable for X-ray diffraction experiments for both compounds.
5,10-Dibromopentacyclo[6.2.2.23,6.02,7.04,9]tetradecane (27).
Rf 0.25 (hexanes); 1H NMR (600 MHz, CDCl3) δ 4.63 (d, J =
5.9 Hz, 1H), 4.49 (d, J = 5.4 Hz, 1H), 2.67–2.63 (m, 1H),
2.50–2.46 (m, 1H), 2.43–2.38 (m, 1H), 2.33–2.26 (m, 1H),
2.18–2.12 (m, 2H), 2.02–1.95 (m, 2H), 1.82–1.76 (m, 2H),
1.73–1.66 (m, 2H), 1.61–1.52 (m, 2H), 1.48–1.38 (m, 2H);
13C NMR (150 MHz, CDCl3) δ 56.0, 54.9, 42.3, 39.8, 37.8, 37.7,
36.1, 35.6, 32.3, 27.5, 25.9, 21.5, 21.4, 21.2; IR νmax 2939, 2868,
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+
745; HRMS (EI) m/z: [M]+ calcd for C14H18Br2 345.9750;
found: 345.9568.
9,13-Dibromopentacyclo[6.2.2.12,7.13,6.010,14]tetradecane (30).
1
Rf 0.35 (hexanes); mp 130–136 °C; H NMR (600 MHz, CDCl3)
δ 5.12 (m, 1H), 4.78 (ddd, J = 5.4, 5.4, 1.3 Hz, 1H), 2.82–2.79
(m, 1H), 2.79–2.74 (ddd, J = 13.5, 9.6, 4.4 Hz, 1H), 2.52–2.46
(m, 2H), 2.43–2.38 (m, 2H), 2.38–2.31 (m, 4H), 2.27 (dddd,
J = 14.4, 11.4, 4.7, 1.9 Hz, 1H), 2.11 (dddd, J = 14.9, 11.4, 6.0,
6.0 Hz, 1H), 1.83–1.76 (m, 2H), 1.75–1.68 (m, 1H), 1.56–1.53
(m, 1H); 13C NMR (150 MHz, CDCl3) δ 56.3, 53.2, 52.9, 51.9,
47.3, 47.0, 43.1, 41.5, 38.0, 37.2, 28.9, 26.9, 24.0, 18.8; IR νmax
2933, 823, 803, 770, 741, 719; HRMS (EI) m/z: [M − Br]+ calcd
for C14H18Br+ 265.0586; found: 265.0594.
C2-Tritwistane (3)
To a solution of dibromide 27 (34.6 mg, 0.100 mmol, 1.00 eq.)
in toluene (3.00 mL) was added TTMSS (0.075 mL, 59.7 mg,
0.240 mmol, 2.40 eq.) and one crystal of AIBN (2.50 mg,
0.015 mmol, 0.150 eq.). The resulting mixture was heated to
90 °C for 3 h and was then allowed to cool to room tempera-
ture and was concentrated in vacuo. The residue was purified
by flash column chromatography (2 × 20 cm, n-pentane, 8 mL)
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