Novel annulene dications from methylated [2.2]metacyclophane monoenes and [e]-ring benzannelated dimethyldihydropyrene

Article abstract of DOI:10.1021/jo0100594

Tetramethyl- and hexamethyl-substituted [2.2]metacyclophane monoenes (10 and 11) are transformed into their corresponding trans-dimethyldihydroethanophenanthrenium dications (14²⁺ and 15²⁺) in FSO₃H·SbF₅ (4:1) and FSO₃H·SbF₅ (1:1) with SO₂ClF or SO₂ as the solvent; these 10π-dications are equivalent to the C-4/C-5 diprotonated dications of the 2,7-dimethyl derivative of trans-DMDHP, 3a. The trans-12c,12d-dimethyl-12c,12d-dihydrobenzo[e]pyrene (6) reacts with FSO₃H/SO₂ClF under surprisingly mild conditions to give initially a persistent diprotonated dication (6H₂²⁺) and, subsequently, the oxidation dication (6²⁺); the 6²⁺:6H₂²⁺ ratio reaches 4:1 after 1 week at low temperature. Protonation of the anti-metacyclophane (13) was also examined. Charge delocalization mode and tropicity in the resulting dications are gauged via detailed NMR studies at 500 MHz.

Full text of DOI:10.1021/jo0100594

J . Org. Chem. 2001, 66, 5329-5332
5329
Novel An n u len e Dica tion s fr om Meth yla ted [2.2]Meta cyclop h a n e
Mon oen es a n d [e]-Rin g Ben za n n ela ted Dim eth yld ih yd r op yr en e
Kenneth K. Laali* and Takao Okazaki
Department of Chemistry, Kent State University, Kent, Ohio 44242
Reginald H. Mitchell and Timothy R. Ward
Department of Chemistry, University of Victoria, Victoria, British Columbia, V8W 3V6 Canada
klaali@kent.edu
Received J anuary 18, 2001
Tetramethyl- and hexamethyl-substituted [2.2]metacyclophane monoenes (10 and 11) are trans-
formed into their corresponding trans-dimethyldihydroethanophenanthrenium dications (142+ and
152+) in FSO3H‚SbF5 (4:1) and FSO3H‚SbF5 (1:1) with SO2ClF or SO2 as the solvent; these 10π-
dications are equivalent to the C-4/C-5 diprotonated dications of the 2,7-dimethyl derivative of
trans-DMDHP, 3a . The trans-12c,12d-dimethyl-12c,12d-dihydrobenzo[e]pyrene (6) reacts with
FSO3H/SO2ClF under surprisingly mild conditions to give initially a persistent diprotonated dication
(6H22+) and, subsequently, the oxidation dication (62+); the 62+:6H22+ ratio reaches 4:1 after 1 week
at low temperature. Protonation of the anti-metacyclophane (13) was also examined. Charge
delocalization mode and tropicity in the resulting dications are gauged via detailed NMR studies
at 500 MHz.
In tr od u ction
Cyclophane dienes are important intermediates in the
synthesis of dihydropyrenes via the Stevens rearrange-
ment-Hoffmann elimination sequence.1 Whereas, the
anti-8,16-dimethyl derivative (1) (Figure 1) spontane-
ously converts thermally at rt to trans-dimethyldihydro-
pyrene (DMDHP, 3), the parent diene (2) is stable,
though it isomerizes when it is warmed.1 Compound 3
has developed into a sensitive probe of ring-current
effects because the methyl groups, dangling in the center,
respond to variations in bond alternation and locali-
zation.2-5 Synthesis and relative diatropicity of the
substituted, benzannelated, and ring-fused derivatives
of 3 continue to receive attention,2-5 as does the interplay
between cyclophane dienes and dimethyldihydropyrenes
via valence isomerism.6
* Corresponding author tel: 330-672-2988; fax: 330-672-3816.
(1) (a) Mitchell, R. H.; Boekelheide, V. J . Am. Chem. Soc. 1974, 96,
1547. (b) Vo¨gtle, F. Cyclophane Chemistry; Wiley: New York, 1995;
Chapter 2.
(2) (a) Mitchell, R. H.; Carruthers, R. J .; Mazuch, L.; Dingle, T. W.
J . Am. Chem. Soc. 1982, 104, 2544. (b) Mitchell, R. H.; Williams, R.
V.; Dingle, T. W. J . Am. Chem. Soc. 1982, 104, 2560. (c) Mitchell, R.
H.; Williams, R. V.; Mahadevan, R.; Lai, Y.-H.; Dingle, T. W. J . Am.
Chem. Soc. 1982, 104, 2571. (d) Mitchell, R. H.; Yan, J . S. H.; Dingle,
T. W. J . Am. Chem. Soc. 1982, 104, 2551.
(3) Lai, Y. H.; Chen, P.; Peck, T.-G. Pure Appl. Chem. 1993, 65, 81.
(4) (a) Mitchell, R. H.; Iyer, Y. S.; Khalifa, M.; Mahadevan, R.;
Venugopalan, S.; Weerawarna, S.; Zhou, P. J . Am. Chem. Soc. 1995,
117, 1514. (b) Mitchell, R. H.; Lau, D. Y. K. Tetrahedron Lett. 1995,
36, 9281.
F igu r e 1. Compound sheet.
(5) (a) Phillips, J . B.; Molyneux, R. J .; Sturm, E.; Boekelheide, V. J .
J . Am. Chem. Soc. 1967, 89, 1704. (b) Lai, Y.-H.; J iang, J . J . J . Org.
Benzannelation (as in 5-7) (Figure 1) reduces the
diatropicity in the macrocycle because of bond localiza-
tion, whereas fusion with conjugated carbocycles (such
as in 8 and 9) does not significantly alter the ring
Chem. 1979, 44, 4733. (c) Mitchell, R. H. In Advances in Theoretically
Interesting Molecules; Halton, B., Ed.; J AI Press: Stanford, CT, 1989;
Vol. 1, p 135.
(6) Mitchell, R. H.; Iyer, Y.S.; Mahadevan, R.; Venugopalan, S.;
Zhou, P. J . Org. Chem. 1996, 61, 5116.
10.1021/jo0100594 CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/11/2001

5330 J . Org. Chem., Vol. 66, No. 16, 2001
Laali et al.
readily, [2.2]metacyclophane monoenes with internal
methyls (i.e., 10 and 11) are kinetically stable, and their
chemistry is just beginning to unravel.7 Instead of the
expected addition to the alkene double bond, dihydropy-
rene was rapidly formed on addition of bromine.7 Metal
π-complexation, however, allowed bromination at the
alkene double bond.7
In parent 3, electrophilic attack is directed to C-2/C-7
positions, and ipso attack occurs in superacids when
these sites are substituted.8 This led to the generation
of several [12]annulenium monocations (see Figure 2).8
With the formyl derivative (12) and with the cyclohex-
enone- and cyclopentenone-fused DMDHP (8 and 9),
persistent oxonium-annulenium dications were gener-
ated (Figure 2), and their tropicities were examined via
NMR.9 Whereas the 16π-dianion of parent DMDHP is a
textbook example of ring-current effects in action,10
a
persistent 12π-oxidation dication remains elusive.11
F igu r e 2. [12]Annulenium monocations and oxonium-an-
nulenium dications from DMDHP and its derivatives.
We report here on remarkably facile generation of
dications: 142+and 152+ (Scheme 1) from 10 and 11 and
the first generation of both the protonation dication
current.4 Substitution in 1 exerts a minor influence on
the ring-current effects.5 Unlike 1, which isomerizes
Sch em e 1. F or m a tion of Dip r oton a ted Dica tion s fr om 10, 11, 13, a n d 6 a n d Oxid a tion Dica tion fr om 6

Novel Annulene Dications
J . Org. Chem., Vol. 66, No. 16, 2001 5331
(6H22+) and the oxidation dication (62+) from the 2,7-di-
tert-butyl-substituted benz[e]annelated 6 under surpris-
ingly mild conditions at low temperature in superacid
media. Charge delocalization mode and tropicity in the
resulting dications are gauged via NMR studies at 500
MHz. The outcome of protonation of 5,13-dimethyl-anti-
[2.2]metacyclophane (13) is also reported.
Resu lts a n d Discu ssion
Sta ble Ion Stu d ies of Cyclop h a n e Mon oen es 10
a n d 11 a n d [2.2]Meta cyclop h a n e 13. Reaction of 10
with FSO3H‚SbF5 (4:1)/SO2 at dry ice/acetone tempera-
ture gave a clear red solution whose NMR spectral data
are fully consistent with near quantitative formation of
1
142+ (Scheme 1 and Figure 3). Its H NMR spectrum is a
“deshielded version” of the monoene precursor, whereby
the center of gravity of the three macrocycle ring proton
singlets move from δ 6.67 in 10 to δ 8.42 in the dication.
The internal methyls appear at δ 0.43, with the other
methyl moving from δ 2.23 in 10 to δ 3.25 in 142+
.
Relative NMR assignments for the C-4/C-5 methylene
protons are unambiguous because the pseudoaxial pro-
tons (δ 3.54) gave NOE with the internal methyls,
whereas the pseudoequatorial ones (δ 4.06) exhibited
NOE with the H-3 ring protons (δ 8.34). The character-
istic quaternary carbon bearing the internal methyl is
at δ 65.2 in the 13C NMR.
Positive charge is highly localized into the two cyclo-
hexadienyl rings giving remarkably large ∆δ13C values
for C-2/C-7, C-3a/C-6a, and C-8a/C-10a (∆δ between 61
and 47 ppm). The sample was practically unchanged
when stored for 1 week at dry ice/acetone temperature.
Quenching gave a 3:1 mixture of 10 and 3a . Dication 142+
was also cleanly generated in FSO3H‚SbF5 (4:1)/SO2
(essentially the same spectra; studied at -50 °C). Pro-
tonation with FSO3H‚SbF5 (1:1)/SO2ClF was less selec-
tive; it gave a dark-orange solution consisting of 90% 142+
and 10% side products.12
Low-temperature reaction of 11 with FSO3H‚SbF5 (1:
1)/SO2ClF gave a dark red-orange solution whose NMR
spectral data are best interpreted as 152+ (90%).12 The
distinction between 152+ and the uncyclized version 15a 2+
(shown in Scheme 1), based on the combined NMR data,
had to rely on the fact that the δ 57.5 resonance bears
no hydrogen (HMQC).13 The center of gravity of two
macrocycle ring proton singlets moves from δ 6.67 in 11
to δ 8.39 in the dication, and the internal methyls appear
at δ 1.64. Relative NMR assignments for the C-4/C-5
methylene protons are based on NOE and are unambigu-
ous.
F igu r e 3. Complete 1H and 13C NMR assignments for 10,
142+; 11, 152+; and 6, 6H22+, and 62+
.
A noteworthy feature is the observed differences in the
chemical shifts of the ethano bridge and of the internal
methyls for 142+ and 152+. They also differ in their
charge-delocalization mode, since in 152+ the charge is
highly localized on the four methyl-bearing macrocycle
ring carbons (1, 3, 6, and 8) and to some extent at C-3a/
C-8a. Dication 152+ remained persistent when stored for
1 week at -75 °C.
For comparison, low-temperature protonation of anti-
13 was examined in several superacid media. With
FSO3H‚SbF5 (1:1)/SO2ClF and FSO3H‚SbF5 (4:1)/SO2ClF,
selectivity was poor, resulting in complex mixtures.
Optimal selectivity was reached in FSO3H/SO2ClF. NMR
data support the presence of a ring-closed symmetrical
dication, most likely 132+, as a major component in a
mixture [aromatic singlet at δ 7.35 and internal hydro-
(7) Mitchell, R. H.; Zhang, L. J . Org. Chem. 1999, 64, 7140.
(8) Laali, K. K.; Bolvig, S.; Raeker, T. J .; Mitchell, R. H. J . Chem.
Soc., Perkin Trans. 2 1996, 2635.
(9) Laali, K. K.; Tanaka, M.; Mitchell, R. H.; Lau, D. Y. K. J . Org.
Chem. 1998, 63, 3059.
(10) Gu¨nther, H. NMR Spectroscopy, 2nd ed.; Wiley: New York,
1995; p 91.
(11) There is NMR evidence that the 2,7-dinitro-DMDHP is doubly
ipso protonated, but the assignment was tentative (see ref 9).
(12) (a) These charged side products exhibited very low field
aromatic signals at δ 10.70 (d), 10.50 (t), 9.66 (d), and 8.94 (d). (b) Local
overheating in the higher acidity superacid could be responsible for
side product formation.
(13) To get to 16a 2+, just switch δ 155.2 and δ 57.5 in Figure 3 and
remove the transannular bond and the ipso double protonate at the
ethano bridge.

5332 J . Org. Chem., Vol. 66, No. 16, 2001
Laali et al.
gens as a broad singlet at δ 3.60; corroboratory 13C NMR
evidence, in particular low field resonances at δ 228.3
(C), 174.2 (C), and 132.1 (CH)]. Quenching gave a mixture
of 2,7-dimethyl-4,5,9,10-tetrahydropyrene (13a ); 2,7-di-
methyl-4,5-dihydropyrene (13b); and 2,7-dimethylpyrene
(13c) in variable amounts in different reactions but with
13a always predominating.14
15a 2+ is especially appealing since the methyls are in the
correct position to stabilize the charge.16,17
Under surprisingly mild conditions, the [e]-ring benz-
annelated derivative of Boekelheide’s DMDHP is dipro-
2+
tonated at the adjacent C-4/C-5 positions to give 6H2
and subsequently undergoes slow two-electron oxidation
to give 62+. The observed double protonation (6H22+) on
adjacent positions (C-4/C-5) in the DMDHP skeleton is
Sta ble Ion Stu d y of th e [e]-Rin g Ben za n n ela ted
Der iva tive 6 a n d Com p a r ison w ith 5. Annulene 6
reacted with FSO3H/SO2ClF at dry ice/acetone temper-
ature to produce a dark-red solution whose NMR spectral
data are fully consistent with the formation of the
2+
unprecedented. Dication 6H2
may be viewed as a
dimethyldihydrotriphenylene dication with an ethano
bridge and represents a benzannelated analogue of 142+
.
Although the direction of shielding and deshielding in
62+ is similar to the dianion 32-, its magnitude is
significantly less.
2+
symmetrical diprotonation dication 6H2 as the major
component (ca. 90%),15a with double protonation occurring
at the adjacent C-4/C-5 positions (Scheme 1, Figure 3).
Relative NMR assignments for the C-4/C-5 methylene
protons is unambiguous because the pseudoaxial protons
gave NOE with the internal methyls, whereas the pseu-
doequatorial ones exhibited NOE with the H-3 ring
protons. The internal methyls move from -1.56 ppm in
the precursor to 0.69 ppm in 6H22+ and show deshielded
ring protons (at δ 9.06 and 8.41) (Figure 3). Positive
charge is highly localized into the two cyclohexadienyl
rings, giving remarkably large ∆δ13C values for C-2/C-7,
C-3a/C-5a, and C-8a/C-12b carbons (between 68 and 40
ppm), with relatively minor delocalization into the an-
nelated [e]-ring. Storing the sample at dry ice/acetone
temperature led to the formation of 62+ at the expense
of 6H22+, such that their ratio reached 4:1 after 1 week.15b
The two-electron oxidation dication 62+ exhibits three
shielded annulene proton singlets with strongly deshield-
ed internal methyls (by 6.32 ppm) (Figure 3). The charge
Mode of benzannelation coupled to the inductively
stabilizing effect of the But groups appear to have a sig-
nificant influence on the ability of the annulene core to
become doubly charged (via diprotonation or two-electron
oxidation), since 5 behaved very differently under the
same set of conditions. A significant feature is reversal
of the ring-current effects between the 14π- (4n + 2)
dication, 6H22+, and the 16π- (4n) oxidation dication, 62+
.
Exp er im en ta l Section
The [2.2]metacyclophane monoenes and benzannelated di-
methyldihydropyrenes were available from previous studies
(in R.H.M.’s laboratory).2,18FSO3H (Allied and Aldrich) and
SbF5 (Fluorochem and Aldrich) were distilled in an all-glass
distillation unit under a dry nitrogen atmosphere and stored
in Nalgene bottles with Teflon caps. Standard procedures were
used for the preparation of superacid solutions and for
synthesis and purification of SO2ClF.19
NMR spectra were recorded at 500 MHz between -70 and
-50 °C. Complete assignments were achieved using 1H, 13C,
H/H COSY, HMQC, and HMBC aided by NOED spectra.
Gen er a l P r oced u r e for Sta ble Ion Gen er a tion . SO2ClF
(ca. 0.4 mL) was distilled into a 5-mm NMR tube containing
the substrate (10 mg) cooled to dry ice/acetone temperature.
To the resulting cold suspension, precooled superacid was
carefully added (2-3 drops) with efficient (vortex) mixing.
Then 2 drops of cold CD2Cl2 was added on top of the solution,
and the mixture was thoroughly mixed until homogeneous.
Qu en ch in g Exp er im en ts. The superacid solution was
carefully poured into ice/bicarbonate, and the mixture was
extracted with CH2Cl2. The organic layer was washed (10%
NaCl) and dried (MgSO4). The solvent was removed under
reduced pressure, and the residue was analyzed by NMR.
2+
delocalization mode in 62+ and 6H2 is rather similar,
with the three carbon resonances due to C-2/C-7, C-3a/
C-5a, and C-8a/C-12a being the most deshielded. Quench-
ing of 62+ returned the skeletally intact 6. Interestingly,
protonation of the unsubstituted benz[e]annelated de-
rivative 5 under a similar set of conditions gave a mixture
of at least three monoprotonated [12]annulenium cations
(a green solution) with no evidence for diprotonation or
dication formation.
Mech a n istic In sigh t. The hitherto unknown 10π-
dications 142+ and 152+ were generated from methylated
[2.2]metacyclophane monoenes 10 and 11 and character-
ized by NMR. These anti-dimethyldihydroethanophenan-
threnium dications are equivalent to C-4/C-5 diprotonat-
ed trans-dimethyldihydropyrenes. A process involving
ene protonation, transannular ring closure, and oxidation
(loss of hydride) is envisioned for their formation. Alter-
natively, doubly ipso-protonated dications 15a 2+ and
14a 2+ (Scheme 1) may be the initially formed species that
rapidly convert to 142+ and 152+ by oxidation (H2 loss)
and transannular bond formation. Initial formation of
Ack n ow led gm en t. This work was supported in part
by the NCI of NIH (R15 CA78235-01A1).
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra for 142+; H/H COSY and 13C NMR spectra for
6H22+; and 1H and 13C NMR spectra for 62+. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O0100594
(16) AM1 predicts however that 10f142+ and 11f152+ conversions
have lower ∆∆Hf than the corresponding 10f14a 2+ and 11f15a 2+
conversions.
(14) (a) Maxfield, M.; Bloch, A. N.; Cowan, D. O. J . Org. Chem. 1985,
50, 1789. (b) Mehta, G.; Shah, S. R. Indian J . Chem. 1990, 29B, 101.
(c) Reynders, P.; Kuhnle, W.; Zachariasse, K. A. J . Am. Chem. Soc.
1990, 112, 3929.
(17) One of the reviewers suggested an alternative mechanism for
consideration involving initial “hydride abstraction” at the ethano
bridge, followed by transannular cyclization and protonation. Although
there is precedent for generation of certain carbocations by hydride
abstraction (i.e., trityl and tropylium using NO+ salts; see, for
example: Olah, G. A.; Laali, K. K.; Wang, X.; Prakash, G. K. S. Onium
Ions; Wiley: New York, 1998; p 42), it is difficult to visualize hydride
abstraction here as the “first step” for reactive substrates, such as 10
and 11, in protic superacids (instead of initial rapid protonation).
(18) (a) Mitchell, R. H.; Ward, T. R.; Wang, Y.; Dibble, P. W. J . Am.
Chem. Soc. 1999, 121, 2601. (b) Mitchell, R. H.; Ward, T. R. Tetrahe-
dron 2001, 57, 3689.
(15) (a) Unidentified byproducts account for the remaining ∼10%.
(b) Formation of 6H2 and 62+ are envisaged in the following way:
2+
[formation of 62+ is a slower process whose contribution to the mixture
increases over time at the expense of 6H22+; competing oxidation is
probably due to minor equilibrium formation of 6 on prolonged storage].
(19) Laali, K. K.; Okazaki, T.; Coombs, M. M. J . Org. Chem. 2000,
65, 7399.