(3) were then treated with methanesulfonic acid in
dichloromethane at room temperature to afford the doubly
bridged p-terphenyls via two facile intramolecular Friedel-
Crafts cyclizations8 (Scheme 2).
cyclization also produced significant amounts of bisindano
products (i.e., 5a, 5d, and 5f) where the cyclization occurred
at the central aromatic ring (see Scheme 3 and Table 1).
Furthermore, the structure of a representative bisindano
product (i.e., 5d) was confirmed by X-ray crystallography
(see Scheme 3).
With the use of the protocol developed in Scheme 2, a
variety of doubly bridged p-terphenyls were prepared in
excellent overall yields (see Table 1) and their structures were
To further confirm that the preferential formation of doubly
bridged p-terphenyls (4), containing seven-membered car-
bocycles in Scheme 3, did not occur via an acid-catalyzed
rearrangement of 5 to 4 or vice versa, samples of both 4a
and 5a were subjected to the same acidic conditions
employed for the Friedel-Crafts intramolecular cyclizations,
1
established by H/13C NMR spectroscopy and further con-
firmed by X-ray crystallography (see Table 1).
It is noteworthy that the use of 1-ethynyl-1-cyclohexanol
instead of 2-methyl-3-butyn-2-ol (in Scheme 1) easily allows
for the preparation of a biscyclohexyl derivative 4h instead
of the corresponding tetramethyl derivative 4e (see Table 1
and Supporting Information for additional details). As such,
the preparation of 4h also demonstrates that the bridge
substituents (i.e., dimethyl and cylohexyl in 4e and 4h,
respectively) can be easily varied by employing an appropri-
ate acetylenic tertiary alcohol, which, in turn, can be readily
prepared by a reaction of the acetylene monoanion with the
corresponding ketone, e.g., eq 1.
1
and the course of the reactions was monitored by H NMR
spectroscopy over several days. Under these conditions, both
4 and 5 showed no signs of interconversion as judged by
1
the H NMR spectroscopic analysis of the aliquots after 3
and 6 days.
The DFT calculations at the B3LYP/6-31G* level10 showed
that two atropisomers of the doubly bridged p-terphenyls, i.e.,
the chiral syn atropoisomer (C2) or the achiral anti (meso)
astropoisomer (Ci), are almost isoenergentic (see Figure 2).
As shown in Scheme 3, the final step of the synthesis of
the doubly bridged p-terphenyls (4) required that the
Figure 2. Structures of the two almost isoenergetic atropisomers
Scheme 3. Intramolecular Friedel-Crafts Cyclizations Leading
of the doubly bridged p-terphenyl 4a as obtained by DFT calcula-
to Seven-Membered vs Five-Membered Isomers
tions at the B3LYP/6-31G* level.10
Interestingly, however, in the solid state almost all doubly
bridged p-terphenyls showed the presence of only the
centrosymmetric anti (meso) conformer with the dihedral
angles between the central and peripheral aryl rings varying
only in a very narrow range, i.e., 45.6-49.5°, as determined
by X-ray crystallography (see Table 1). The exception is the
fluoranyl-containing 4g which contained a 1:1 mixture of
both syn and anti atropisomers in a single crystal, i.e., the
meso and chiral atropisomers (see Figure 3). The cocrystal-
lization of both syn and anti conformers may, in part, arise
owing to the fact that each half of the syn-4g was structurally
identical to that of the anti-4g (see Figure 3) with the dihedral
angles of 47.6 and 46.9° between the central aryl and
fluoranyl rings.
Friedel-Crafts cyclization must occur at the terminal aryls
producing a pair of entropically less accessible seven-
membered carbocycles. Indeed, the substrates which con-
tained an activating para-substituent (i.e., at carbon 3) on
the terminal aryls (i.e., 3b, 3c, 3e, 3g, and 3h) exclusively
produced the doubly bridged p-terphenyls (4), without
contamination from the products (i.e., 5, Scheme 3) formed
via an alternative Friedel-Crafts cyclization onto the central
aromatic ring producing the entropically favored five-
membered carbocycles (i.e., Scheme 3).
The low activation barriers for the interconversion between
the (isoenergetic) syn and anti conformers of the various doubly
bridged p-terphenyls was apparent by the presence of broadened
methyl signals in their 1H NMR spectra at ambient temperatures
(see Supporting Information and Figure 4).
Expectedly, in the case of p-terphenyl substrates (i.e., 3a,
3d, and 3f), which do not contain an activating substituent
at carbon 3 of the terminal aryl groups, the Friedel-Crafts
1
Variable-temperature H NMR spectroscopy of a repre-
sentative doubly bridged p-terphenyl (4e) in dichloromethane-
d2 over a temperature range of +20 to -90 °C showed that
(8) Compare: Rathore, R.; Abdelwahed, S. H.; Guzei, I. A. J. Am. Chem.
Soc. 2003, 125, 8712.
(9) Rathore, R.; Burns, C. L. J. Org. Chem. 2003, 68, 4071–4074.
(10) The DFT calculations were performed using Spartan 10.
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Org. Lett., Vol. 11, No. 20, 2009