1,3,6,9,12,14,17,20-Octaethynyltetrabenz-[a,b,f,j,k,o]-4,5,10,11,15,16,2 1, 22-octadehydro[18]annulene: A carbon-rich hydrocarbon

Article abstract of DOI:10.1021/ol051572x

(Chemical Equation Presented) Dodecaynes 1a-d have been prepared via a convergent strategy that employs Sonogashira couplings as the carbon-carbon bond-forming tool. Due to the steric bulk of the DMTS groups, 1c adopts a nonplanar conformation, the dynami

Full text of DOI:10.1021/ol051572x

ORGANIC
LETTERS
2005
Vol. 7, No. 18
4001-4004
1,3,6,9,12,14,17,20-Octaethynyltetrabenz-
[a,b,f,j,k,o]-4,5,10,11,15,16,21,22-
octadehydro[18]annulene:
A Carbon-Rich Hydrocarbon
Ognjen Sˇ. Miljanic´, Daniel Holmes, and K. Peter C. Vollhardt*
Center for New Directions in Organic Synthesis, Department of Chemistry, UniVersity
of California at Berkeley, and the Chemical Sciences DiVision, Lawrence Berkeley
National Laboratory, Berkeley, California 94720-1460
kpcV@berkeley.edu
Received July 5, 2005
ABSTRACT
Dodecaynes 1a−d have been prepared via a convergent strategy that employs Sonogashira couplings as the carbon−carbon bond-forming
tool. Due to the steric bulk of the DMTS groups, 1c adopts a nonplanar conformation, the dynamics of which have been probed by VT-NMR.
The cobalt-catalyzed isomerization of 1a,b produced the new conjugated phenylenes 2a,b and 3a,b, respectively.
Dehydrobenzannulenes have been subject to intense scrutiny
because of their potential applications as optoelectronic,
liquid crystalline, conducting, and sensing materials, as
building blocks in the construction of allotropes of carbon,
as scaffolds for supramolecular assemblies, and as monomers
in topochemical and other polymerizations.1 In this connec-
tion, the title compound and its derivatives 1 constitute a
new topology combining the 1,2,3,4- with the 1,2,4,5-tetra-
ethynylbenzene motifs in an elaborated octaethynylated
tetrabenz[a,b,f,j,k,o]-4,5,10,11,15,16,21,22-octadehydro[18]-
annulene,2 endowed with internal hydrogens that can serve
as probes for the effect of peripheral alteration on the
aromaticity of the central core. Parent 1d is also the only
second hydrocarbon of composition C48H16 to be made.3
Apart from its intrinsic interest, system 1 is an attractive
substrate for an unprecedented4 4-fold CpCo-catalyzed
isomerization to circular [8]phenylene 4 (Scheme 1). Cyclic
(1) For a highlight, see: (a) Ho¨ger, S. Angew. Chem., Int. Ed. 2005, 44,
3806. For recent reviews, see: (b) Tobe, Y.; Sonoda, M. In Modern
Cyclophane Chemistry; Gleiter, R., Hopf, H., Eds.; Wiley-VCH: Weinheim,
2004; pp 1-40. (c) Marsden, J. A.; Palmer, G. J.; Haley, M. M. Eur. J.
Org. Chem. 2003, 2355. (d) Youngs, W. J.; Tessier, C. A.; Bradshaw, J. D.
Chem. ReV. 1999, 99, 3153. (e) Haley, M. M. Synlett 1998, 557. For very
recent work, see, inter alia: (f) Marsden, J. A.; Miller, J. J.; Shirtcliff, L.
D.; Haley, M. M. J. Am. Chem. Soc. 2005, 127, 2464. (g) Johnson, C. A.;
Haley, M. M.; Rather, E.; Han, F.; Weakley, T. J. R. Organometallics 2005,
24, 1161. (h) Baxter, P. N. W.; Dali-Youcef, R. J. Org. Chem. 2005, 70,
4935. (i) Hisaki, I.; Eda, T.; Sonoda, M.; Niino, H.; Sato, T.; Wakabayashi,
T.; Tobe, Y. J. Org. Chem. 2005, 70, 1853.
(2) (a) For the parent annulene, made by alkyne metathesis, see:
Miljanic´, O. Sˇ.; Vollhardt, K. P. C.; Whitener, G. D. Synlett 2003, 29. (b)
For a di-tert-butylderivative of the parent annulene, made by a stepwise
protocol, see: Zhang, J.; Pesak, D. J.; Ludwick, J. L.; Moore, J. S. J. Am.
Chem. Soc. 1994, 116, 4227.
(3) For an isomeric dehydrotetrabenz[32]annulene, see: Haley, M. M.;
Bell, M. L.; Brand, S. C.; Kimball, D. B.; Pak, J. J.; Wan, W. B. Tetrahedron
Lett. 1997, 43, 7483.
10.1021/ol051572x CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/11/2005

Scheme 1
Scheme 2
phenylenes of this type are important because bond alterna-
tion induced by the cyclobutadienoid rings, as pictured in
the structural drawing and supported by a calculated structure
(B3LYP/6-31G*) of 4d (for this and other calculations, see
Supporting Information), is expected to enable superdelo-
calization.5 In 4, such an effect would involve the Hu¨ckel-
aromatic 18 and 30 electron supercircuits, respectively, of
the inner and outer periphery of the polycycle.
12 created 13, possessing all the carbon atoms of 1. Finally,
bromine-iodine exchange, followed by TMS deprotection
and an intramolecular Sonogashira coupling, afforded 1. A
topological alternative to the above scheme is presented by
the approach to 1b and proceeded with comparable ef-
ficiency. Overall, the yields from 5 are 33% to 1a, 7.6% to
1b, and 16% to 1c, a rather satisfactory outcome.
We report on the synthesis of 1d and its derivatives 1a-c
and on partly successful attempts to reach 4.
The preparative strategy to 12b entailed the independent
formation of 1,2,4,5- and 1,2,3,4-substituted arene fragments
that translate into the “blue” and “red” arene units of 1
(Scheme 1), respectively. Synthesis of the “blue” building
blocks 7 and 8 (Scheme 2) commenced with a Sonogashira6
reaction (PdCl2(PPh3)2, CuI, NEt3) that targeted the more
reactive iodinated positions in 1,5-dibromo-2,4-diiodoben-
zene 5.7 The ensuing bromine-iodine exchange produced 6
in high yields, which was functionalized via a second
Sonogashira reaction, this time with TMSA, to give 7. The
final replacement of bromine with iodine furnished 8, ready
to be coupled with the “red” component.
Dodecaynes 1a-c are yellow-brown waxy solids that are
stable to air, both neat and in solution. On the other hand,
parent 1d decomposed quickly, even in solution, thus
precluding its isolation and full characterization. The elec-
tronic spectra are characterized by a lowest-energy band (λmax
) 369-377 nm) that is significantly shifted bathochromically
relative to that of the parent dehydrobenz[18]annulene (λmax
) 341 nm), a reflection of the extensive alkynyl substitution.
The NMR spectra feature the characteristically deshielded
intracyclic hydrogen signals at δ ∼7.8 ppm2 and the
1
appropriate number of H and 13C peaks. An exception is
The triynes 9, reported previously,5c,8 were chosen as the
precursors for the “red” moieties of 1 (Scheme 3). Selective
TMS removal from 9 generated the corresponding terminal
alkynes, which were coupled with iodides 8 to give the highly
functionalized diarylacetylenes 10. Compounds 10 were the
source of both pieces needed to assemble 13. Protodetri-
methylsilylation provided 11; alternatively, another bromine-
iodine exchange led to 12. Sonogashira coupling of 11 and
1c, in which the DMTS spectral regions revealed not two
but four sets of resonances for each of the three methyl
groups, illustrated for the silylmethyls on top of Figure 1.
DFT calculations predict a nonplanar configuration for 1c,
rendering these groups diastereotopic in the NMR experiment
at slow exchange. Enantiomerization, tantamount to rotation
around the core diarylalkyne bonds,9 and hence coalescence,
appears to be remarkably sluggish, as measured by VT-NMR
at 62 and 90 °C, respectively (Figure 1, bottom). Peak-shape
analysis10 provided an activation barrier of 19.4 ((0.4) kcal
mol-1. In contrast, neither acyclic precursor analogues nor
a related hexaethynyldehydrobenz[12]annulene5c were mobile
conformationally at temperatures as low as -80 °C.11
With systems 1a-d available, experiments were executed
aimed at accessing circular [8]phenylene 4. Since 1c proved
(4) For triple cyclizations of this type, see: Bruns, D.; Miura, H.;
Vollhardt, K. P. C.; Stanger, A. Org. Lett. 2003, 5, 54 and references therein.
(5) For reviews of the phenylenes, see: (a) Miljanic´, O. Sˇ.; Vollhardt,
K. P. C. In Carbon-Rich Compounds: Molecules to Materials; Haley, M.
M., Tykwinsky, R. R., Eds.; Wiley-VCH: Weinheim, 2005; in press. (b)
Vollhardt, K. P. C.; Mohler, D. L. In AdVances in Strain in Organic
Chemistry; Halton, B., Ed.; JAI: London, 1996; pp 121-160. For a related
approach to circular [6]phenylene, “antikekulene”, see: (c) Eickmeier, C.;
Junga, H.; Matzger, A. J.; Scherhag, F.; Shim, M.; Vollhardt, K. P. C.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2103.
(6) Sonogashira, K. In Handbook of Organopalladium Chemistry for
Organic Synthesis; Negishi, E.-i., Ed.; Wiley: New York, 2002; Vol. 1, pp
493 and references therein.
(7) Goldfinger, M. B.; Crawford, K. B.; Swager, T. M. J. Am. Chem.
Soc. 1997, 119, 4578.
(8) While 9a was not known prior to this work, it was readily prepared
using the procedure described for 9b,c (see Supporting Information).
(9) For the observation of hindered rotation in 2,2′,6,6′-tetrakis(alkynyl)-
diphenylacetylenes, see: Miljanic´, O. Sˇ.; Han, S.; Holmes, D.; Schaller,
G. R.; Vollhardt, K. P. C. Chem. Commun. 2005, 2606.
(10) (a) Oˆ ki, M. Applications of Dynamic NMR Spectroscopy to Organic
Chemistry; VCH: Weinheim, 1985. (b) Gasparro, F. P.; Kolodny, N. H. J.
Chem. Educ. 1977, 54, 258.
(11) Hisaki, I.; Vollhardt, K. P. C. Unpublished results.
4002
Org. Lett., Vol. 7, No. 18, 2005

Scheme 3
to be inert and 1d decomposed in the presence of CpCoL2,
conversion of 2b or 3b in the presence of CpCo(CO)2 in
boiling 1,2-dichlorobenzene led to recovery of the respective
starting materials, while switching the solvent to boiling
1,2,4-trichlorobenzene led to decomposition.
even using in situ deprotection protocols,1b,c,e most efforts
focused on the isomerizations of 1a and 1b (Scheme 4).
Disappointingly, only double cyclizations were achieved to
the deep-red doubly bent [5]- and yellow angular [3]-
phenylene derivatives 2 and 3, respectively. DFT calculations
of all possible cyclization intermediates of 1d, either in their
most stable or in a constrained planar conformation, indicate
that, as the quite exothermic cycloisomerization sequence
progresses, the remaining triple bonds in the product of each
step become increasingly separated, thus likely retarding the
normally facile cobaltacyclopentadiene(alkyne) formation.12
A similar phenomenon had frustrated an approach to circular
[6]phenylene.5c It is noteworthy that the third possible
isomeric product of biscyclization (the angular [5]phenylene
version of 2) was not observed. Attempts to induce further
This failure notwithstanding, systems 2 and 3 represent
only the third and fourth examples of phenylenocyclynes in
which the terminal rings of a phenylene are linked by a
conjugating bridge, and the changes in their properties as a
result of this feature are of interest. Indeed, the molecules
appear to be more air sensitive than their component
phenylenes,5a-c and solutions (CHCl3) of, e.g., 2a in air
decomposed within hours. In this case, the mass spectra of
the complex product mixture revealed molecular ions
consistent with the addition of one and two molecules of
oxygen, and the IR spectrum exhibited a strong band at 1645
cm-1, suggesting oxidation via initial single and double
endoperoxidation, as observed for angular [3]- and zigzag
[5]phenylene.5a,13 The electronic spectra, e.g., of 3a and 3b,
(12) Diercks, R.; Eaton, B. E.; Gu¨rtzgen, S.; Jalisatgi, S.; Matzger, A.
J.; Radde, R. H.; Vollhardt, K. P. C. J. Am. Chem. Soc. 1998, 120, 8247.
Org. Lett., Vol. 7, No. 18, 2005
4003

Scheme 4a
a Inseparable mixture with 2a. Isomer 2a was the only product
(11%) when 6 equiv of CpCo(CO)2 was employed.
corresponding signals in 1a: δ ) 7.81 and 7.43 ppm. The
more coupled15 central phenylene hydrogens at δ ) 6.67
(inner H) and 6.47 ppm (outer H) have counterparts in the
parent [5]phenylene at δ ) 6.73 and 6.58 ppm. The
assignments in 2a (inner vs outer H) were corroborated by
NOE experiments.
In summary, a convergent and robust synthetic route to
the octaalkynylated dehydrobenz[18]annulenes 1 has been
developed. These macrocycles appear to adopt a nonplanar
conformation, the dynamics of which can be probed by NMR
with suitable diastereotopic probes. The derivatives 1a and
1b were partly cyclized to the cyclically delocalized phen-
ylenes 2 and 3, in which the remaining alkyne units seem
too distant to undergo CpCo-catalyzed cyclotrimerization to
circular [8]phenylene 4. Future work will aim to modify
chemically the phenylene skeletons of 2 and 3 to circumvent
this problem.
1
Figure 1. Silylmethyl H NMR spectra (dioxane-d8) of 1c at 22
(top) and 99 °C (bottom). The colored spheres represent the
(potentially) diastereotopic methyl substituents; A ) DMTS-Ct
C-, B ) (CH3)2CH(CH3)2C-.
provide a quantitative measure of increased delocalization
in longest wavelength maxima, which are shifted to lower
energies when compared to the parent phenylene substruc-
tures, e.g., ∆λmax ) 35 nm for 2b and ∆λmax ∼ 84 nm for
3b.5a-c,14 A similar comparison of the 1H NMR spectra of 2
and 3 with those of their component phenylenes and of 1
illustrates the absence of any significant “super ring current”
effects. For example, the two relatively sharp singlets at δ
) 7.69 (inner H) and 7.49 ppm (outer H) of the tetraalkynyl-
benzene ring hydrogens in 2a compare well with the
Acknowledgment. The NSF (CHE-0451241) funded this
work. The Center for New Directions in Organic Synthesis
is supported by Bristol-Myers Squibb as a Sponsoring
Member and Novartis as a Supporting Member.
Supporting Information Available: Experimental and
calculational procedures, characterization of all new com-
pounds, and .pdb files of the calculated structures. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(13) (a) Kumaraswamy, S.; Jalisatgi, S. S.; Matzger, A. J.; Miljanic´, O.
Sˇ.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. 2004, 43, 3771. (b) Eickmeier,
C.; Holmes, D.; Junga, H.; Matzger, A. J.; Scherhag, F.; Shim, M.; Vollhardt,
K. P. C. Angew. Chem., Int. Ed. 1999, 38, 800.
OL051572X
(14) Bong, D. T.-Y.; Chan, E. W. L.; Diercks, R.; Dosa, P. I.; Haley,
M. M.; Matzger, A. J.; Miljanic´, O. Sˇ.; Vollhardt, K. P. C.; Bond, A. D.;
Teat, S. J.; Stanger, A. Org. Lett. 2004, 6, 2249.
(15) Strained ring fusion increases Jpara in arenes. For a review, see:
Frank, N. L.; Siegel, J. S. In AdVances in Theoretically Interesting
Molecules; Thummel, R. P., Ed.; JAI: London, 1995; Vol. 3, pp 209-260.
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