A R T I C L E S
Dahl and Mills
Scheme 1
several bisfluorenyl spacer-separated diether systems 6a-c were
synthesized (Scheme 1). The corresponding nonadjacent dica-
tions 6a2+ and 6b2+ were generated by Magic acid ionization
and characterized at low temperatures with 1H NMR spectros-
copy. Dication 6c2+ could not be reliably generated. The
1
1
experimental H NMR shifts along with calculated H NMR
shifts of 6a2+ and 6b2+, nucleus independent chemical shift
(NICS) values, and magnetic susceptibility exaltation (Λ)
calculations for 6a2+-c2+ were analyzed to evaluate the relative
antiaromaticity of the dications and compared to that of the well
studied tetrabenzo[5,5]fulvalene dication system.5,9,32–34 The
quality of the calculated NICS values was evaluated by
comparison of H NMR shifts, which could be compared to
experimental values to determine their accuracy, calculated by
the same method.
1
by way of ionization reactions. These superacids could be useful
in generating antiaromatic dications of neutral precursors
containing readily ionizable lone pair containing functionalities
such as alcohols and ethers, thus expanding the library of
compounds capable of being studied. In theory, this approach
to 1,2-dications is thermodynamically more favorable than
alkene oxidation because the bond breaking is partially com-
pensated by the creation of the new protonated bonds. However,
although the presence of such intermediates is often indirectly
supported, experimentally obserVed 1,2-carbodicationic species
from 1,2-diols or diethers is unknown in the literature, presum-
ably due to the propensity for fast cyclization, rearrangement,
or elimination reactions of those intermediates in the superacidic
media.25 In unpublished studies by our group, attempted
preparation of dications such as 3, R ) 3-CH3, resulted in rapid
cyclization when the dications were formed by oxidation with
SbF5/SO2ClF, and would also be predicted to be inaccessible
by superacid ionization of its 1,2-diol analogue. Therefore, in
order to employ superacidic ionization routes for the production
of experimentally obserVable antiaromatic dications, neutral
precursors with ionizable moieties on nonadjacent carbon atoms
must be utilized.
Possible precursors that would be suitable to afford antiaro-
matic carbodications via superacid ionization are neutral di-
methyl ethers with conjugating phenyl, ethynyl, or ethenyl
“spacer” units connecting the ionizable moieties, such as 5a-c.
Conjugated spacer separated dications and dianions of an
aromatic nature have been reported in the literature,26–31but
similar antiaromatic species are thus far unknown. The diether
functionality has been chosen due to the relative ease of
purification for the neutral precursors and the potential for fewer
side reactions upon superacid ionization when compared to the
corresponding diol species. The spacer unit would serve three
purposes: (1) it hinders cyclization of less stable antiaromatic
dications by rendering the products more sterically demanding
in comparison to the cyclized products of dications with no
spacer unit, (2) it avoids the aforementioned rapid decomposition
of 1,2-dications generated with superacids, and (3) it provides
extra stabilization to the cationic species through delocalization.
Results and Discussion
Synthesis of Precursors to Dications. Phenyl bridged dimethyl
ether 6a was synthesized by double lithium-halogen exchange
on p-dibromobenzene and subsequent addition to 9-fluorenone
to achieve diol 7 (Scheme 2). The diol was then methylated
with NaH and MeI resulting in 6a. Ethynyl and ethenyl bridged
dimethyl ethers 6b and 6c were synthesized by the addition of
ethynylmagnesium bromide to 9-fluorenone. Alkyne deproto-
nation of 8 and a second addition of 9-fluorenone gave diol 9.
The diol 9 was methylated with NaH and MeI, resulting in 6b.
Lithium aluminum hydride reduction of 9 resulted in olefin diol
10 which was methylated to produce 6c.
In order to make a direct comparison between olefin oxidation
and methyl ether ionization as routes toward antiaromatic
dications, the syntheses of the corresponding bridged olefins
were examined. Cyclohexadiene-bridged bisfluorene 14, the
neutral olefin precursor that should produce 6a2+ upon oxidation,
proved to be elusive following two independent synthetic routes.
The first route was a stepwise double Peterson olefination of
monoketal protected 1,4-cyclohexadione with fluorene to ulti-
mately achieve 13. Unfortunately, oxidation of 13 with DDQ
under several different conditions produced no desired product
(Scheme 3). SnCl2 reduction of phenyl bridged diol 7 was also
unsuccessful, although the product was observed transiently as
evidenced by the bright purple color that was observed
immediately after the Sn(II) addition. To our disappointment,
the product decomposed immediately upon reaction workup.
In other reports synthetic attempts to achieve 1435 and similar
species21,22 were also unsuccessful via Zn or Hg reduction of
the dibromo analogue of 7. These reports suggest that 14 is
very difficult to isolate due to the formation of a cyclic tetramer
(25) Nenajdenko, V. G.; Shevchenko, N. E.; Balenkova, E. S.; Alabugin,
I. V. Chem. ReV. 2003, 103, 229–282.
(26) Kagayama, A.; Komatsu, K.; Nishinaga, T.; Takeuchi, K.; Kabuto,
C. J. Org. Chem. 1994, 59, 4999–5004.
(27) Eicher, T.; Berneth, H. Tetrahedron Lett. 1973, 2039–42.
(28) Gilbertson, R. D.; Weakley, T. J. R.; Haley, M. M. J. Org. Chem.
2000, 65, 1422–1430.
(29) Eicher, T.; Berneth, H. Tetrahedron Lett. 1973, 14, 2039–2042.
(30) Komatsu, K. A., M.; Arai, M.; Okamoto, K. Tetrahedron Lett. 1982,
23, 91–94.
(31) Komatsu, K.; Arai, M.; Hattori, Y.; Fukuyama, K.; Katsube, Y.;
Okamoto, K. J. Org. Chem. 1987, 52, 2183–2192.
(32) Malandra, J. L.; Mills, N. S.; Kadlecek, D. E.; Lowery, J. A. J. Am.
Chem. Soc. 1994, 116, 11622–11624.
(33) Mills, N. S.; Burns, E. E.; Hodges, J.; Gibbs, J.; Esparza, E.; Malandra,
J. L.; Koch, J. J. Org. Chem. 1998, 63, 3017–3022.
(34) Mills, N. S.; Benish, M. A. J. Org. Chem. 2006, 71, 2207–2213.
(35) Wittig, G.; Dreher, E.; Reuther, W.; Weidinger, H.; Steinmetz, R.
Leibigs Ann. Chem. 1969, 726, 188–200.
In order to establish proof of concept for this novel and
potentially scope-expanding route to antiaromatic carbodications,
9
10180 J. AM. CHEM. SOC. VOL. 130, NO. 31, 2008