Building with cubane-1,4-diyl. Synthesis of aryl-substituted cubanes, p- [n]cubyls, and cubane-separated bis(arenes)

Article abstract of DOI:10.1021/ja983441f

On treatment with an organolithium 1,4-diiodocubane generates cubane- 1,4-diyl, a highly reactive species, shown here to be a versatile precursor to numerous aryl substituted cubanes, available now for the first time in high yield. The diyl is demonstrated to provide a good route to bicubyl and its derivatives. A kind of 'living polymerization' of the diyl is developed to give the p-[n]cubyls. These oligomers are rigid rods made up to cubanes linked together at the 1 and 4 positions, each cubane adding ~4.15 ? to the length. The properties of these rods, some more than 15 ? long, are discussed; as are methods for modifying their solubility. X-ray crystallographic analyses of some of these compounds are presented, with emphasis on packing parameters.

Full text of DOI:10.1021/ja983441f

J. Am. Chem. Soc. 1999, 121, 4111-4123
4111
Building with Cubane-1,4-diyl. Synthesis of Aryl-Substituted
Cubanes, p-[n]Cubyls, and Cubane-Separated Bis(arenes)1
Philip E. Eaton,*,† Kakumanu Pramod,† Todd Emrick,† and Richard Gilardi‡
Contribution from the Department of Chemistry, The UniVersity of Chicago, Chicago, Illinois 60637, and
Laboratory for the Structure of Matter, NaVal Research Laboratory, Washington, D.C. 20375
ReceiVed September 28, 1998
Abstract: On treatment with an organolithium 1,4-diiodocubane generates cubane-1,4-diyl, a highly reactive
species, shown here to be a versatile precursor to numerous aryl substituted cubanes, available now for the
first time in high yield. The diyl is demonstrated to provide a good route to bicubyl and its derivatives. A kind
of “living polymerization” of the diyl is developed to give the p-[n]cubyls. These oligomers are rigid rods
made up of cubanes linked together at the 1 and 4 positions, each cubane adding ∼4.15 Å to the length. The
properties of these rods, some more than 15 Å long, are discussed, as are methods for modifying their solubility.
X-ray crystallographic analyses of some of these compounds are presented, with emphasis on packing parameters.
Background. In 1990 Eaton and Tsanaktsidis reported that
reaction of 1,4-diiodocubane (1) with phenyllithium in diethyl
ether at room temperature gave a good yield of 4-phenylcubyl
iodide (5).2 The reaction path, as outlined in Scheme 1, involves
rapid iodine-metal exchange between 1 and phenyllithium to
give (at equilibrium) a small concentration of 4-iodocubyl
lithium (2). Loss of lithium iodide therefrom gives a halogen-
free intermediate, demonstrated to be symmetric,2 and dubbed
1,4-dehydrocubane (3). Addition of phenyllithium produces
4-phenylcubyl lithium (4). Finally, reverse lithium-for-iodine
exchange with the iodobenzene generated in the initial step
forms the observed product.
Scheme 1
Both the initial and final iodine/lithium exchanges in Scheme
1 are equilibrium reactions that can be expected to favor
phenyllithium over the cubyllithium. The former is better
stabilized as there is higher s character in an exocyclic aromatic
orbital (33%) than in an exocyclic cubane orbital (31%).3,4
Benzene has been shown to be ∼1000 times more acidic than
cubane kinetically,5 and probably a similar difference pertains
thermodynamically. In accord, we have found experimentally
that there is little “net” reaction between equimolar amounts of
cubyl iodide and phenyllithium; only a trace amount of cubane
is found when the mixture is quenched with water. On the other
hand, and appropriately, equimolar amounts of cubyllithium and
phenyl iodide react to give cubyl iodide in high yield.
Michl6 and Borden7 groups on a number of possible candidate
structures have led to the postulate that 1,4-dehydrocubane is
cubane-1,4-diyl singlet. Michl’s matrix isolation infrared spec-
troscopic studies are in accord with this theory.6 The calculations
place the singlet state of the diyl below the triplet by more than
10 kcal/mol, suggesting substantial through-bond interaction of
the nonbonded electrons.
1,4-Diiodocubane, the precursor of cubanediyl, can be
prepared easily from cubane-1,4-diacid, the now well-known
entry compound into the cubane system.3,8,9 Full details have
been published already of our application of Barton iodinative
decarboxylation of the diacid via its N-hydroxypyridine-2-thione
(PTOC) ester.10 Moriarty’s more direct procedure, in which the
diacid itself is reacted with phenyliodonium diacetate and iodine,
has proven to be much easier.11 and provides the 1,4-diiodide
The critical intermediate 3 in Scheme 1, 1,4-dehydrocubane,
is very reactive and cannot be isolated and characterized in the
usual sense. Its structure, therefore, cannot be taken as fully
established.2 Nonetheless, detailed ab initio calculations by the
† The University of Chicago.
‡ Naval Research Laboratory.
(1) Some of this paper is taken from the Ph.D. Thesis of Todd Emrick,
The University of Chicago, 1997.
(2) Eaton, P. E.; Tsanaktsidis, J. J. Am. Chem. Soc. 1990, 112, 876.
(3) Eaton, P. E.; Cole, T. W., Jr. J. Am. Chem. Soc. 1964, 86, 962.
(4) Della, E. W.; Hine, P. T.; Patney, H. K. J. Org. Chem. 1977, 42,
2940.
(7) Hrovat, D. A.; Borden, W. T. J. Am. Chem. Soc. 1990, 112, 875.
(8) (a) Eaton, P. E. Angew. Chem. Int. Ed. Engl. 1992, 31, 1421. (b)
Chapman, N. B.; Key, J. M.; Toyne, K. J. J. Org. Chem. 1970, 35, 3860.
(c) Luh, T.-Y.; Stock, L. M. J. Org.Chem. 1972, 37, 338.
(9) The 1,4-dimethyl ester is available commercially from Aldrich
Chemical and from SynQuest, Ltd.
(5) Dixon, R. E.; Streitwieser, A.; Williams, P. G.; Eaton, P. E. J. Am.
Chem. Soc. 1991, 113, 357.
(6) Hassenru¨ck, H.-D.; Radziszewski, J. G.; Balaji, V.; Murthy, G. S.;
McKinley, A. J.; David, D. E.; Lynch, V. M.; Martin, J-D.; Michl, J. J.
Am. Chem. Soc. 1990, 112, 873.
(10) Tsanaktsidis, J.; Eaton, P. E. Tetrahedron Lett. 1989, 30, 6967.
(11) (a) Moriarty, R. M., private communication. (b) Moriarty, R. M.;
Khosrowshahi, J. S.; Dalecki, T. M. J. Chem. Soc., Chem. Commun. 1987,
9, 675. (c) Concepcio´n, J. I.; Francisco, C. G.; Freire, R.; Herna´ndez, R.;
Salazar, J. A.; Sua´rez, E. J. Org. Chem. 1986, 51, 402.
10.1021/ja983441f CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/20/1999

4112 J. Am. Chem. Soc., Vol. 121, No. 17, 1999
Eaton et al.
reproducibly on a multigram scale in 85+% yield. Details of
our version are given in the Experimental Section.
(p-biphenyl)cubane (11), (2-naphthyl)cubane (12), p-(dicubyl)-
benzene (13), and m-(dicubyl)benzene (14), respectively.
Aryl Cyclooctatetraenes (COTs) from Arylcubanes. One
use of these compounds is the preparation of novel COTs.
Research in this Laboratory with Cassar and Halpern years ago
showed that rhodium(I) catalysts trigger ring opening of cubane
to syn-tricyclooctadiene, which in turn undergoes ready (un-
catalyzed by the metal) Cope ring opening at 60 °C to
cyclooctatetraene.14 The same holds true for many substituted
cubanes. This offers a novel approach to substituted COTs; for
example, treatment of p-(dicubyl)benzene (13) and m-(dicubyl)-
Synthesis of 4-Arylcubyl Iodides. The generation of cubane-
1,4-diyl from 1 under conditions that permit its effective use in
synthetic schemes depends critically on experimental conditions
and on the organolithium employed. In this section we focus
on the use of aryllithiums. Later, we will consider the use of
cubyllithiums.
1,4-Diiodocubane is very poorly soluble in diethyl ether, the
solvent that routinely gave the cleanest overall results in these
reactions.12 Thus, we could do little more experimentally, on
the small scale we were working, than to add the diiodide as a
well-powdered solid to the aryllithium already in solution. It
was apparent from color changes that reaction of the diiodide
occurred (rapidly) as it dissolved (slowly). Thus, the aryllithium
was always present and available in excess.
When phenyllithium was used, the yield of 4-phenylcubyl
iodide (5), isolated pure, was 80-90%. Similar yields of the
benzene (14) with Rh2(1,5-cyclooctadiene)2Cl2 provides p-
(dicyclooctatetraenyl)benzene (15) and m-(dicyclooctatetraenyl)-
benzene (16), respectively, each in better than 85% yield. This
approach is entirely different from previous modes of access to
these compounds.15
Cubane Couplings. 4,4′-Diiodobicubyl (18)16a was always
observed as a byproduct (∼5%) of the reactions of aryllithiums
with 1,4-diiodocubane. It is formed as shown in Scheme 2 by
the unavoidable in situ combination of the intermediates 2 and
Scheme 2
corresponding 4-arylcubyl iodides were achieved when p-
biphenyllithium (f 6) and 2-naphthyllithium (f 7) were
employed. Use of the doubly lithiated aromatic 1,4-dilithioben-
zene, prepared by halogen-metal exchange between p-dibro-
mobenzene and excess t-BuLi,13 gave p-bis(4-iodocubyl)benzene
(8) in 70% isolated yield. Similarly, reaction of diiodocubane
with 1,3-dilithiobenzene13 gave the meta isomer 9.
Synthesis of Arylcubanes. In all these cases, the iodine
substituents on the cubane skeleton are the result of iodine-for-
lithium exchange equilibria as shown in Scheme 1. Initially each
of the 4-arylcubyl iodides 5-9 is formed as the corresponding
arylcubyllithium. It is simple enough to remake these by reaction
of 5-9 with at least 2 equiv of t-BuLi. Under this condition,
the cubyllithiums are certainly favored. Not only is the negative
charge put in an orbital far more s-rich than that of tert-butyl
anion, but the equilibrium is “pulled” entirely to the right by
t-BuLi-induced elimination of HI from t-BuI.
Cubyllithiums appear to be somewhat less reactive than
common tertiary alkyllithiums. Perhaps this is related to the
increased s character in the exocyclic carbon orbital already
referred to. Qualitatively, cubyllithium lasts longer in ether and
THF than does t-BuLi. Cubyllithiums readily undergo the usual
reactions of organolithiums. This is convenient and provides,
for example, easy methodology for taking cubyliodides to the
corresponding hydrocarbons. Thus, 5-9 were converted by
protonation of their lithium derivatives to phenylcubane (10),
(14) (a) Cassar, L.; Eaton, P. E.; Halpern, J. J. Am. Chem. Soc. 1970,
92, 3515. (b) Eaton, P. E.; Galoppini, E.; Gilardi, R. J. Am. Chem. Soc.
1994, 116, 7588.
(15) (a) Siesel, D. A.; Staley, S. W. J. Org. Chem. 1993, 58, 7870. (b)
Grimm, R. A. Ph.D. Thesis, Carnegie Mellon University, 1997. Prof. S.
Staley has informed us privately that the spectroscopic properties of our
materials compare reasonably to his considering that different solvents were
employed.
(16) (a) This nomenclature is taken from that of the biphenyls and is
convenient for simple, symmetric bicubyls. It is not useful for more complex
molecules. (b) The p(ara)-[n]cubyls are rigid rods made of n cubanes
attached directly to one another at opposite corners. The designation 4* is
used generically to refer to the most distant cubyl position from a substituent
on C1 of a p-[n]cubyl. The numbering of a specific p-[n]cubyl follows by
extension from the following example.
(12) THF is a better solvent for 1,4-diiodocubane, but it is too reactive
toward the intermediate cubyllithiums.
(13) (a) Honrath, U.; Shu-Tang, L.; Vahrenkamp, H. Chem. Ber. 1985,
118, 132. (b) Trepka, W. J.; Sonnenfeld, R. J. J. Organomet. Chem. 1969,
16, 317.

Building with Cubane-1,4-diyl
J. Am. Chem. Soc., Vol. 121, No. 17, 1999 4113
3 (cf. Scheme 1) to give 17, followed by lithium-for-iodine
exchange with iodobenzene.
Scheme 3
Diiodobicubyl 18 is potentially very useful. It is easy enough
to imagine reductive couplings (vide infra) providing for the
preparation of the rigid rod p-[n]cubyls.16b But its yield by this
method is far too low; a better synthesis is necessary. In the
combined milieu of Schemes 1 and 2, most of diyl 3 is usually
trapped by the aryllithium, present in excess. As the concentra-
tion of 4-iodocubyllithium is much lower, it competes poorly.
This (now desired) path can be enhanced by employing steric
effects to diminish the ability of the aryllithium to add to the
diyl. Changing from phenyllithium to o-ethylphenyl lithium
increased the yield of 18 from 5 to 30%. Use of the yet more
hindered mesityllithium increased the yield of 18 to ∼50%.
Unfortunately, this was not improved when the much more
congested 2,4,6-triisopropylphenyl lithium was employed.
Reaction of 18 with t-Buli gave 4,4′-dilithiobicubyl (19). This
is a broadly useful compound as it reacts in standard fashion
with simple electrophiles and gives access to a host of bicubyl
diiodide dissolution. Thus, the concentration of the intermediate
4-iodocubyl lithium is always low, and the diyl as it is formed
is trapped, not by 4-iodocubyl lithium but by 4-phenylcubyl
lithium or by the growing 4*-phenyl-p-[n]cubyllithium rod16b
(Scheme 3).
The process in Scheme 3 is reproducible and reasonably
efficient. Most of the 4-phenyliodocubane (the precursor of
4-phenylcubyl lithium) generated can be recovered and reused.
About 70% of the 1,4-diiodocubane introduced can be accounted
for, mostly incorporated into 23-25, a little is recovered
unchanged. The rest must be mostly in higher oligomers, “lost”
because of their exceedingly low solubility.
When the ratio of phenylcubyllithium (the initiator) to 1,4-
diiodocubane (the monomer precursor) was high (g4:1), the
degree of oligomerization was low; mainly dimers were
produced. When the ratio was lowered, somewhat more of each
of the higher oligomers 23-25 was produced (Table 1). These
compounds were separated crudely by trituration and then
further purified by column chromatography on silica gel, usually
using large amounts of pentane as eluent.
derivatives.2 Quenching with methanol provides the most
convenient access to bicubyl itself (20). Treatment of 18 with
methyllithium at room temperature gave, in part, 4,4′-dimeth-
ylbicubyl (22) and the half-methylated compound, 4′-methyl-
p-[2]cubyl iodide (21), both by way of iodine-for-lithium
exchange, and then reaction of the cubyllithium so made with
connate methyl iodide.
Oligomerization via Cubane-1,4-diyl. The iodobicubyl-
lithium 17 in Scheme 2 arises from reaction of a cubyllithium
(2) with cubane-1,4-diyl (3). It too is a cubyllithium, and were
conditions of rate and concentration appropriate, it too could
react with diyl 3, thus giving a new cubyllithium, this one with
three cubanes in a row. Hypothetically, continuation of this
scheme would lead to an oligomerization with cubane-1,4-diyl
serving as the “monomer”. Indeed, it was clear early on that
small amounts of higher molecular weight materials were being
formed in these reactions. In practice, the oligomerization does
not proceed effectively for the concentration of any cubyllithium
formed within this scheme is small, kept that way by rapid
iodine-for-lithium exchange with the aryl iodide formed inci-
dentally in the first step of Scheme 1. As noted earlier, these
exchanges favor the aryllithium strongly.
Such reasoning led us to use premade 4-phenylcubyl lithium
(4) both to generate and to trap cubanediyl. Its precursor,
4-phenylcubyl iodide (5), is easily prepared, as already shown
in Scheme 1, and it can be isolated pure in 80-85% yield
without difficulty. Iodine-metal exchange at -78 °C in diethyl
ether using 2 equiv of t-BuLi (the “extra” equivalent to destroy
t-BuI) gave 4 essentially quantitatively.
4-Phenylcubyl lithium is reasonably soluble (∼0.10 M) in
ether, but 1,4-diiodocubane is not, even at 0 °C where the
reaction between the two was best run. The metal-halogen
exchange between them is limited therefore by the slow rate of
Table 1. p-[n]Cubyl Oligomer Distribution (% Isolated Yields
Based on Incorporated 1) as a Function of the 4-Phenylcubyllithium
(4):1,4-Diiodocubane (1) Ratio
molar ratio
23
n ) 2
24
n ) 3
25
n ) 4
4:1
4:1
3:1
2:1
1:1
66
47
40
38
12
15
19
24
3
6
Of course, each of the iodides 23-25 can be converted to
the corresponding lithium derivative by reaction with t-BuLi
and thence to numerous derivatives. The conversions of 23 and
24 to the parent hydrocarbons 1-phenyl-p-[2]cubyl (26) and
1-phenyl-p-[3]cubyl (27), respectively, and of 25 to its car-
bomethoxy derivative 28 are given in the Experimental Section
as examples.
Arylcubyl iodides other than 4-phenylcubyl iodide, e.g., 4-(p-
biphenyl)cubyl iodide (6) and 4-(2-naphthyl)cubyl iodide (7),
were used in the process of Scheme 3 with similar results. It is
important to have a sense of the utility of this reaction. For
example, a run employing 1.528 g of 6 and 1.78 g of
1,4-diiodocubane gave 520 mg of recovered 6, 930 mg of

4114 J. Am. Chem. Soc., Vol. 121, No. 17, 1999
Eaton et al.
1-iodo-4′-(p-biphenyl)-p-[2]cubyl (29), 210 mg of 1-iodo-4′′-
(p-biphenyl)-p-[3]cubyl (30), and 64 mg of 1-iodo-4′′′-(p-biphen-
yl)-p-[4]cubyl (31).
staffanes,18 paraphenylenes,19 rodanes,20 [n]carboranes,21 or the
p-[n]cubyls of interest here. This presents very frustrating
experimental difficulties. Various approaches to alleviating the
problem have been tried, here and elsewhere,22 to more or less
effect.
As it is usually the case that less symmetric compounds are
more soluble than their symmetric relatives,22a Scheme 3 was
repeated using 4-(m-ethylphenyl)cubyllithium (32b) instead of
4-phenylcubyllithium, the idea being to break the full axial
symmetry of the developing rod. The starting material, (4-(m-
ethylphenyl)cubyl iodide (32a), was prepared in good yield
(70%) by appropriately modifying Scheme 1 (see Experimental
Section). As hoped for, the oligomerization triggered by 32b
did give a better ratio (1:2) of the 4′′-aryl-p-[3]cubyl (34, aryl
) m-ethylphenyl) to 4′-aryl-p-[2]cubyl (33) than that obtained
(1:3) when 4-phenylcubyllithium was used. An isolable amount
of the cubylog p-[4]cubyl 35 was produced, and for first time
we observed (albeit only by mass spectroscopy) the formation
of a p-[5]cubyl, 36. The solubilities of the purified (m-
ethylphenyl)-p-[2]cubyl and -p-[3]cubyl oligomers are better
than those of their desethyl, more symmetrical analogues. The
[2]cubyl has reasonable solubility in pentane; the [3]cubyl is
somewhat soluble in ether and has good solubility in CH2Cl2.
Nonetheless, the [4]cubyl 35 is not sufficiently soluble to be
useful for elaboration.
It is useful to know (vide infra) as one inspects these rodlike
structures that the distance between the para positions of benzene
(∼2.8 Å) and that along the body diagonal between the 1 and
4 positions of cubane (∼2.7 Å) are almost the same. So too are
the C-C bond lengths between two phenyl rings (∼1.49 Å),
between a phenyl ring and a cubane nucleus (∼1.49 Å), and
between two cubanes (∼1.49 Å). Thus, the straight-line, tip-
to-tip carbon distance in 31 is almost 20 Å.
Cubyl iodide itself, open at the 4 position, can also be used
in Scheme 3, as can 4,4′-diiodobicubyl. This provides access
to unsubstituted p-[n]cubyl rigid rods, the subject of a future
paper.17
The yields of p-[n]cubyls with n g 3 are not good. There are
problems with the dissolution kinetics of 1,4-diiodocubane and
with the insolubility of the growing chains. More fundamentally,
as careful inspection of Scheme 3 shows, the lithium-for-iodine
exchange, which can occur easily among the reaction compo-
nents, provide a termination mechanism for what otherwise
could have been a “living” polymerization.
The effect on solubilities induced by a “floppy” substituent22b
in the para position of the phenyl group of the 4*-phenyl-p-[n]-
cubyls was investigated briefly. 4-(p-Octylphenyl)cubyl iodide
was prepared via Scheme 1 by employing 4-octylphenyllithium.
Lithiation followed by reaction with 1,4-diodocubane afforded
a set of 1-iodo-4*-(p-octylphenyl)-p-[n]cubyls with n ) 2-4.
Although these were certainly more soluble than their unsub-
stituted analogues, no substantial improvement in solubility over
the m-ethyl compounds 33-35 was obseved.
In another approach to solubilization,22c substituents are
distributed along the rigid rod. To this end, we prepared the
diyl precursors 38 and 39 (Scheme 4) taking advantage of our
earlier discoveries relating to systematic substitution on the
cubane nucleus by way of ortho-metalation,23 in this case ortho-
magnesiation of amide 37.23c
Scheme 4
For the reason above, preparation of higher “cubylogs” is
best undertaken by isolating an individual iodo-p-[n]cubyl from
one or another version of Scheme 3 and then using it, now as
starting material, for another round. Thus, for example, 1-iodo-
4′-phenyl-p-[2]cubyl (23), formed as shown in Scheme 3 (Table
1, entry 1, 66% isolated yield), was reacted with t-BuLi in cold
ether. Reaction of an excess (4:1) of the lithio compound so
obtained with 1,4-diiodocubane 1 (ratio 23:1 ) 4:1) gave 1-iodo-
4′′-phenyl-p-[3]cubyl (24) in 50% isolated yield.
Solubilized Cubyl Rods. Unelaborated rigid rods of even
nominal molecular weight are difficulty soluble, be they
(17) Eaton, P. E.; Virtuani, M.; Xiong, Y.; Pramod, K., in preparation.
(18) (a) Hassenru¨ck, K.; Murthy, G. S.; Lynch, V. M.; Michl, J. J. Org.
Chem. 1990, 55, 1013. (b) Mazal, C.; Paraskos, A. J.; Michl, J. J. Org.
Chem. 1998, 63, 2116 and references therein.
(19) For examples: (a) Percec, V.; Zhao, M.; Bae, J.; Hill, D. H.
Macromolecules 1996, 25, 3727. (b) Baker, K. N.; Fratini, A. V.; Resch,
T.; Knachel, H. C.; Adams, W. W.; Socci, E. P.; Farmer, B. L. Polymer
1993, 34, 1571. (c) John, J. A.; Tour, J. M. J. Am. Chem. Soc. 1994, 116,
5011.
(20) Zimmerman, H. E.; King, R. K.; Meinhardt, M. B. J. Org. Chem.
1992, 57, 5484.
(21) For example: (a) Yang, X.; Jiang, W.; Knobler, C. B.; Mortimer,
M. D.; Hawthorne, M. F. Inorg. Chim. Acta 1995, 240, 371. (b) Mu¨ller, J.;
Base, K.; Magnera, T. F.; Michl, J. J. Am. Chem. Soc. 1992, 114, 9721.
Diiodides 38 and 39 are quite soluble in ether, unlike 1,4-
diiodocubane itself. Reaction of each with excess phenyllithium
(22) (a) For example: Lassale, I.; Schmidt, M.; Schlu¨ter, A. D. Acta
Polym. 1994, 45, 389. (b) For example: Tour, J. M. AdV. Mater. 1994, 6,
190. (c) For example: Rehahn, M.; Schlu¨ter, A.-D.; Wegner, G. Makromol.
Chem. 1990, 91, 1991.

Building with Cubane-1,4-diyl
J. Am. Chem. Soc., Vol. 121, No. 17, 1999 4115
proceeds along the path outlined in Scheme 1 via the intermedi-
ate diyls. The product 2,7-disubstituted 4-phenylcubyl iodides
40 and 41, respectively, are formed in reasonable yields.24
Nonetheless, we were not able to obtain oligomerization by
approaches such as that in Scheme 3. We suspect that the
heteroatoms (N or O) in the substituents so alter the properties
of the intermediate cubyllithiums that suitable concentrations
of the required intermediates cannot be obtained (cf. footnote
24), or perhaps such cubyllithiums are incapable of adding to a
cubane diyl.
Solubilization of rigid rods can sometimes be achieved by
having flexible alkyl chains along the rod.23c As alkyl groups
would be expected to be relatively innocuous chemically, this
seemed an attractive choice. To this end, we prepared 1,4-diiodo-
2,7-dihexylcubane (42, Scheme 5, 40% overall), a compound
with quite good solubility in both hydrocarbon and ethereal
solvents.
Cubane-Separated Biaryls. The rate of electron transfer
between donor and acceptor as a function (for example) of the
energy differences between their respective radical anions and
the distance separating them is an area of considerable interest.25
The most studied electron donor-acceptor pairs are aromatics,
whose oxidation-reduction potentials are well-established, for
example, biphenyl and naphthyl. We have already reported on
the use of p-[n]cubyls as well-defined “spacers” between such
electroactive groups.26 The syntheses of these compounds are
described in the present paper. Each cubane unit adds 4.15 Å
to the rod length. There is easy free rotation about each cubane-
to-cubane bond, as the closest approach of hydrogens on
adjacent cubes is ∼2.7 Å. Even 2-tert-butylcubylcubane is freely
rotating at room temperature on the NMR time scale.2 Rotation
about the cubane-to-cubane bond does not change rod length.
Bending at this bond does change rod length, but such bending
is energetically difficult. About 8 kcal/mol is required for the
first 10° excursion; this increases steeply thereafter. Thus, the
p-[n]cubyl oligomers behave as rigid rods of fairly much exactly
calculable length.
Scheme 5
How can cubyl rods be made with different aryl groups at
either end? As shown above, addition of an aryllithium to
cubane-1,4-diyl easily puts an aryl group on one end of a
developing rod; examples of phenyl-, biphenyl-, and 2-naphthyl-
substituted rods of various lengths have been given. The problem
is the introduction of a second (and different) aryl group on the
opposite end of the rod. We have found that it is possible to
couple aryl-substituted cubyl iodide, e.g., the synthesis of 4,4′-
biphenylbicubyl (47), by oxidation of a cuprate. However, such
reactions have proven to be irreproducible and low-yielding.
Hence, cross-coupling variants are bound to be both inelegant
and unrewarding.
If metal-mediated cross coupling between a cubyl-Y (e.g.,
cubyl cuprate, stannate, triflate, etc.) and Ar-X (e.g., aryl halide,
boronate, etc.) could be brought about, the problem of making
cubane-separated mixed biaryls would be simple. However, after
much effort we have been forced to conclude that such reactions
are inoperable (or nearly so) in the cubane series.27
The successful use of 42 in the preparation of high-molecular-
weight p-[n]cubyl rigid rods solubilized by floppy hexyl chain
“fur” all along their substantial length will be reported in a later
paper. Here we are interested in whether alkyl chain substitution
effectively solubilizes 4*-aryl-p-[n]cubyls. Using the methods
already outlined, now through the intermediacy of 2,7-dihexyl-
cubane-1,4-diyl, we have prepared and characterized 43-46.
We have developed instead effective protocols, widely
extensible, for introduction of aromatic units, viz., p-biphenyl,
2-naphthyl, and 9-phenanthryl, built on the reactions of ap-
propriate electrophiles with organolithiums, here aryl[n]cubyl-
lithiums. For example, the biphenyl subunit in 1-phenyl-4-(p-
biphenyl)cubane (48) can be introduced smoothly by reaction
of 4-phenylcubyllithium (4) with 4-phenylcyclohexane-1,2-
epoxide, followed by POCl3/pyridine-induced dehydration and
DDQ dehydrogenation. As numerous variants on 4 are easily
available (e.g., from 6-9, 23-25, and 43a-46a), this scheme
provides for the synthesis of many arylbiphenyl[n]cubyls.
(23) (a) Eaton, P. E.; Castaldi, G. J. Am. Chem. Soc. 1985, 107, 724. (b)
Bashir-Hashemi, A. J. Am. Chem. Soc. 1988, 110, 7234. (c) Eaton, P. E.;
Lee, C.-H.; Xiong, Y. J. Am. Chem. Soc. 1989, 111, 8016.
(24) Interestingly, the diiodo-diamido precursor of 38 did not form a
diyl on reaction with excess phenyllithium. Apparently, the adjacent amide
group so stabilizes23a the cubyllithium formed on iodine-for-metal exchange
that elimination of LiI does not occur competitively with the second
exchange.
(25) For example: (a) Closs, G. L.; Calcaterra, L. T.; Green, N. J.;
Penfield, K. W.; Miller, J. R.; J. Phys. Chem. 1986, 90, 3673. (b) Paddon-
Row, M. N. Acc. Chem. Res. 1994, 27, 18.
(26) Paulson, B.; Pramod, K.; Eaton, P. E.; Closs, G.; Miller, J. R. J.
Phys. Chem. 1993, 97, 13042.
(27) This seems to us to mean that the very successful couplings of
“standard” systems (aromatic, vinyl, allyl) really require participation of
the π-unit. However, see: Charette, A. B.; Giroux, A. J. Org. Chem. 1996,
61, 8718.
These are all compounds that can be eluted fairly readily from
silica gel chromatography columns with pentane. As desired,
they are all hydrocarbon soluble, viscous oils at room temper-
ature, quite unlike their counterparts without the hexyl substit-
uents.
(28) (a) Gilman, H.; Gorisch, R. D. J. Am. Chem. Soc. 1957, 79, 2625.
(b) Caple, R.; Chen, G. M.-S.; Nelson, J. D. J. Org. Chem. 1971, 36, 2874.

4116 J. Am. Chem. Soc., Vol. 121, No. 17, 1999
Eaton et al.
cubyls introduced in this paper are all quite stable kinetically.
None has ever shown shock sensitivity under usual laboratory
conditions. Thermal decomposition does not set in until above
200 °C. Air, light, and moisture, as well as most common
reagents, are without effect. Melting points quickly increase with
increasing rod length: cubane, 130-131 °C; p-[2]cubyl, 169-
171 °C; p-[3]cubyl, ∼200 °C (dec). Phenylcubane, although
essentially the same length as bicubyl, is a liquid at room
temperature. The more rodlike 4′-phenyl-p-[2]cubyl melts at
163-164 °C. In the 1-iodo-4*-phenyl-p-[n]cubyl series, the
melting points of n ) 1-4 are, respectively, 85-86, 144-146,
215-217 (dec), and 225-228 °C (dec). As expected (cf. the
[n]staffanes18a and the p-[n]phenyls19b), the solubility of these
compounds falls off rapidly with increasing rod length. Cubane
is miscible with pentane; the solubility of [2]cubyl is ∼10 mg/
mL, but p-[3]cubyl is essentially insoluble. The solubility of
most 4*-phenyl-p-[n]cubyls is very similar to that of the
corresponding desphenyl-p-[n]cubyl. The phenyl group, unlike
an additional cubane, lengthens the rod without lowering its
solubility.
The oxide bridge in naphthalene-1,4-oxide is strained and
labile. We expected, considering the literature,28 that Lewis acid-
catalyzed reaction with a cubyllithium would open the oxa ring
and lead ultimately to introduction of a â-naphthyl substituent.
As it turned out, no catalyst was required. As shown in Scheme
6, for example, the cubyllithiums derived from1-iodo-4-(p-
biphenyl)cubyl (6) and 1-iodo-4′-(p-biphenyl)-p-[2]cubyl (29)
with naphthalene-1,4-oxide in THF at -70 °C to room tem-
perature gave good yields of the corresponding dihydronaphthols
49 and 50. These were dehydrated nearly quantitatively to 1-(p-
1
NMR Comparisons. The H NMR spectrum of cubane in
Scheme 6
deuteriochloroform is a single, very sharp resonance at δ 4.03
ppm. The spectra of the p-[n]cubyls are far more complex, but
a clear trend is apparent. The resonance for the protons at each
end of the rod (H1 and H4*) becomes a multiplet spread
symmetrically over ∼4.00-4.08 ppm (typical cubane coupling
constants are roughly Jortho ∼ 5 Hz, Jmeta ∼ 3 Hz, Jpara ∼ 1
Hz).29 The resonance for the other cubyl protons are shifted
significantly upfield. In bicubyl, these produce a broad multiplet
extending over δ ∼ 3.81-3.91 ppm (400 MHz). In p-[3]cubyl,
the six identical protons on the central, internal cubane give
rise to a new upfield, slightly broadened singlet at δ 3.68 ppm,
while the chemical shift spread of the nonterminal protons of
the outer cubanes is quite similar to that in bicubyl. The
appearance of new upfield resonances ends with p-[4]cubyl. The
12 protons on its two inner cubanes appear as a somewhat
broadened singlet at δ 3.68 ppm, just as in tricubyl. It is this
signal that would likely continue to grow in weight with
increasing rod length. However, due to solubility difficulties,
the 1H NMR spectrum of a [5]cubyl has not yet been recorded.
Alkyl substituents on a cubane, like a cubyl substituent, shift
the ortho and meta hydrogen resonances upfield from that of
cubane itself.30 Most other substituents result in downfield shifts
for the ortho hydrogen resonance. For example, in cubyl iodide
the ortho proton resonance is at δ 4.32 ppm; in phenylcubane
it is at δ 4.17 ppm. The meta shifts due to these substituents
are smaller, but not necessarily downfield. In cubyl iodide, the
resonance for the protons meta to the substituent is at δ 4.18
ppm; in phenylcubane, at δ 4.01 ppm.
biphenyl)-4-(2-naphthyl)cubane (51) and 1-(p-biphenyl)-4′-(2-
naphthyl)-p-[2]cubyl (52), respectively, on treatment with a bit
of methanesulfonic acid. Again, numerous variations are pos-
sible, including the use of alkyl-substituted cubanes to make
rods of greater length, but still with reasonable solubility, e.g.,
the tricubyl 53, 4′′-(p-biphenyl)-1-(2-naphthyl)-2,7-dihexyl-p-
[3]cubyl.
In 1-iodo-p-[2]cubyl, the resonance for protons ortho to iodine
is at δ 4.17 ppm, an upfield shift of 0.15 ppm from the ortho
protons in iodocubane. This is the result of the meta effect of
the additional cubane. Substitution in the 4′ (para) position of
this cubyl substituent does not change this; the resonance
remains at δ 4.17 ppm in 1-iodo-p-[3]cubyl, 1-iodo-4′-phenyl-
p-[2]cubyl, and 4,4′-diiodobicubyl.
Cubyl-separated biaryls in which one aryl group is 9-phenan-
threne, the best electron acceptor of the aromatics considered
here, were made via reaction of various arylcubyllithiums with
phenanthrene-9,10-epoxide instead of the naphthalene oxide (cf.
Scheme 6). For example, 54, 1-(p-biphenyl)-4′-(9-phenanthryl)-
Table 2 shows the observed difference in chemical shift (∆δ)
in ppm from cubane (4.03 ppm) for the ortho, meta, and para
protons in the X-substituted cubanes central to the work reported
here.
(29) Edward, J. T.; Farrell, P. G.; Langford, G. E. J. Am. Chem. Soc.
1976, 98, 3075.
(30) The ortho, meta, and para ∆δ effects on the chemical shift of cubyl
hydrogens in methylcubane are, respectively, -0.39, -0.19, and +0.02 ppm.
See: Eaton, P. E.; Li, J.; Upadhyaya, S. P. J. Org. Chem. 1995, 60, 966.
p-[2]cubyl, was prepared in 70% overall isolated yield.
Physical and Spectroscopic Properties. Although highly
strained and energy-rich, cubane, the arylcubanes, and the p-[n]-

Building with Cubane-1,4-diyl
J. Am. Chem. Soc., Vol. 121, No. 17, 1999 4117
Table 2. Chemical Shift Difference (∆δ ppm) from Cubane for
Substituted Cubanesa
X
Hortho
Hmeta
Hpara
iodine
phenyl
cubyl
+0.29
+0.14
-0.15
+0.15
-0.02
-0.15
+0.17
+0.09
+0.02
a Downfield shifts are given as positive.
1
Table 3. Calculated vs Experimental H NMR Chemical Shifts
(ppm) of Some 1,4-Disubstituted Cubanes
X
Y
Ha(calc)
Ha(exp)
Hb(calc)
Hb(exp)
iodine
phenyl
cubyl
iodine
iodine
phenyl
cubyl
cubyl
cubyl
iodine
4.30
4.02
3.73
4.17
4.47
4.32
4.05
3.68
4.17
4.40
4.32
3.86
3.73
4.03
4.47
4.32
3.88
3.68
4.03
4.40
Figure 1. Some cubyl-cubyl, cubyl-phenyl, and phenyl-phenyl bond
lengths (Å) from X-ray crystallographic analyses. When there is more
than one molecule in the unit cell, the length given is the average.
Substituent effects on 1H NMR chemical shifts of cubyl
hydrogens are additive, as first shown by Farrell and co-
workers.29 This observation can now be extended to include
cubyl, phenyl, and iodo substituents. So, for example, the
chemical shifts of the 1,4-disubstituted cubanes in Table 3 can
be calculated successfully from the values in Table 2. 4-Phe-
nylcubyl iodide provides an interesting example. The combina-
tion of the ortho effect of iodine with the meta effect of the
phenyl substituent results in a predicted chemical shift of [4.03
+ (0.29 - 0.02)] ) 4.30 ppm for one set of equivalent protons
(Ha). The combination of the ortho effect of the phenyl
substituent and the meta effect of iodine predicts [4.03 + (0.14
+ 0.15)] ) 4.32 ppm for the other set (Hb). What is seen is a
singlet (Wh/2 ) 0.6 Hz) at 4.32 ppm. This is in contrast to nearly
all other unsymmetrical 1,4-disubstituted cubanes, where the
two sets of ortho protons give rise to separate multiplets.
Crystal Structures. Growing crystals of p-[n]cubyls suitable
for X-ray analysis has proved to be very difficult. Most form
powders or glasses from solution rather than providing well-
formed single crystals. Nonetheless, we have obtained good data
for the p-[n]cubyls and the phenyl-p-[n]cubyls shown in Figure
1. Sufficient data are now available to make some general
comments.
In general, when one cubane is attached to another by one
bond, the cage units are perfectly staggered, or very nearly so.
Both carbons making the cubane-to-cubane bond are fully
substituted; nonetheless, the bond is short (∼1.48 Å) relative
to the “standard” C-C bond length of 1.54 Å and even shorter
than that between typical tetrasubstituted carbons, e.g., 1.578
Å in 1,1′-bis(adamantyl).31 This is as expected32 for the
exocyclic bonding orbital of a cubyl carbon is s rich (31%).33
For similar reasons, the bond between a phenyl group and a
cubane unit is short. So, of course, is the bond between two
phenyl units as in biphenyl. The hybridization of the exocyclic
phenyl orbital is 33% s. Figure 1 gives the cubyl-cubyl and
cubyl-phenyl bond lengths now available.34
The average distance along the body diagonal in a cubane
nucleus is 2.70. The “rod” formed by linking two or more
cubanes together at opposite corners, i.e., in the p-[n]cubyls, is
lengthened by ∼4.2 Å for each cubane nucleus added. As the
2.8-Å distance between the para positions of a benzene in a
biphenyl (average of 480 biphenyls listed in the Cambridge
Database) is almost the same as that between C1 and C4 in
cubane and the length of phenyl-to-cubyl and phenyl-to-phenyl
bonds are much like those of cubyl-to-cubyl bonds, appropriate
substitution of a benzene nucleus for a cubane unit into or onto
a cubyl rod does not much change its length. Thus, the calculated
length, carbon tip to carbon tip, of p-[4]cubyl is 15.3 Å and
that of 4′′-phenyl-p-[3]cubyl is 15.4 Å. The actual experimental
value (single-crystal X-ray analysis) for the latter is 15.3 Å.
Within a few standard deviations, most of the cubyl and
phenyl-cubyl rods we have been able to crystallize and analyze
are linear. Save in one case, the maximum departure from a
straight line through any three sequential carbons on the long
axis of the rod is less than 4° and usually less than 2°. In no
instance do we see a coordinated accumulation of deviations.
In 4′′-phenyl-p-[3]cubyl, there is perhaps a more significant
deviation from linearity; the phenyl group is cocked ∼7° in one
molecule of the unit cell and 8.7° in the other. However the
precision of the data in this case is less than that in all the others
because the best crystal that could be obtained was too thin to
scatter strongly.
The rod length of bicubyl, from H-to-H, is 8.7 Å. A view
down the z axis of the unit cell (Figure 2) shows a sheet of
(31) Alden, R. A.; Kraut, J.; Traylor, T. G. J. Am. Chem. Soc. 1968, 90,
74.
(32) (a) Gilardi, R.; Maggini, M.; Eaton, P. E. J. Am. Chem. Soc. 1988,
110, 7232. (b) Ermer, O.; Lex, J. Angew. Chem., Int. Ed. Engl. 1987, 26,
447.
(33) (a) Eaton, P. E.; Cole, T. W., Jr. J. Am. Chem. Soc. 1964, 86, 3157.
(b) Della, E. W.; Hine, T. W.; Patney, H. K. J. Org. Chem. 1977, 42, 2940.
(34) (a) The value for 2-tert-butylbicubyl comes from ref 32a. Note the
length quoted in the text differs from that in the illustration; the latter is
correct. (b) The cubyl-cubyl bond length for bicubyl is from the analysis
reported herein of a pure crystal; another value, 1.45 Å, occurs in a co-
crystal with 2-tert-butylcubylcubane; see: ref 32a. (c) For biphenyl, see:
Charbonneau, G. T.; Delugeard, Y. Acta Crystallogr. 1977, B33, 1586.

4118 J. Am. Chem. Soc., Vol. 121, No. 17, 1999
Eaton et al.
Figure 2. View showing a single layer of bicubyl (20) molecules in the ab plane with their centers at z ) 0.5. Individual molecular axes are tipped
slightly (16°) out of this plane. Identical layers occur at z ) 0 and z ) 1, laterally displaced so that molecules lie over and under the gaps between
those in the layer illustrated.
Figure 3. View down the trigonal (c) axis of the unit cell showing the stacking in 4,4′-diiodobicubyl (18). Each molecule is surrounded by a
hexagonal array of close neighbors. These are alternately displaced, relative to the central molecule, by c/3 (5.12 Å) toward or away from the
viewer; this is about a half-molecule length.
molecules packing in horizontal rows which lie, on average, in
the same plane.
of molecules shown in the “end-on” view of Figure 3.
Crystals of p-dicubylbenzene (13) were grown by slow
evaporation from a methylene chloride solution. The rod is 13.16
Å from tip to tip (H to H). The rod is almost straight; the C1′-
C2-C1A angle is 178.1°, and C1-C1A-C4A is 178.6°.
Molecules of 13 pack in parallel layers, as shown in Figure 4,
but the steric bulk of the cubane core prevents the close
approaches between phenyl groups seen in p-[n]phenyls.36 The
4,4′-Diiodobicubyl (18) was crystallized from benzene. The
molecule is of such high symmetry that only four carbon atoms
(C1-4) are unique; the rest can be generated by symmetry
transformations. As in bicubyl, the molecules pack in planar
sheets; the sheets are packed to give the hexagonal arrangement
(35) For references and enlightening discussions, see: (a) Brock, C. P.
Acta Crystallogr. 1980, B36, 968. (b) Brock C. P.; Minton, R. P. J. Am.
Chem. Soc. 1989, 111, 4586.
(36) Baudour, P. J. L.; Delugeard, Y.; Cailleau, H. Acta Crystallogr.
1976, B32, 150.

Building with Cubane-1,4-diyl
J. Am. Chem. Soc., Vol. 121, No. 17, 1999 4119
Figure 4. Triclinic crystal packing in p-dicubylbenzene (13). This low symmetry leads to an arrangement in which all molecular axes are parallel;
the central benzene units are well separated from one another, while the cubyl units pack with many close (near vdW) contacts.
Figure 5. View of one layer of (p-biphenyl)cubane (11) that lies at the x ) 0.75 level in the unit cell. Here all of the axes are approximately
parallel, but the phenyl groups rotate relative to their phenyl neighbors, to make a perpendicular approach. This is very similar to the type of
herringbone packing seen in the polyphenyls.36
molecules slide by one another along their long axes so that
the bulky cubane portions can avoid one another. This brings a
cubyl hydrogen into close contact (2.86 Å) with the center of a
benzene ring of an adjacent molecule, perhaps in weak
hydrogen-bonding interaction with the π-system. The interaction
occurs on both sides of each benzene ring and is repeated along
an infinite ladder of molecules through the crystal.
the long axis of the cell does not correspond to the long
molecular axis of any member of the cell. The packing is such
that there are layered pairs of stacks in which the cubyl ends of
one stack meet the cubyl ends of another such that their
molecular axes are parallel. The phenyl groups, on the other
hand, interface in herringbone fashion from stack to stack.
There are two independent molecules in the asymmetric unit
of 1-phenyl-p-[3]cubyl (27). Although the symmetry of the
orthorhombic (Pna21) packing scheme is more complex than
in the triclinic packing in 26, the main features are remarkably
similar. The phenyl ends interleave in a herringbone junction
with a large change in axis direction, while the cubyl ends abut
other cubyl ends with parallel molecular axes. The molecules
do not all lie in the same plane. It is tempting to believe that a
pattern of this sort is developing as a common feature as the
rods lengthen, but until more data become available it is too
early to be sure.
(p-Biphenyl)cubane (11) was crystallized from hexane at -20
°C. It is a rod 13.21 Å from tip to tip (H to H). The unit cell is
composed of two not-quite-identical molecules. The phenyl-
phenyl torsional angle in the biphenyl group of each (21° for
one, 29° for the other) is quite different from the room-
temperature arrangement in crystalline biphenyl, p-[3]phenyl,
and p-[4]phenyl, which (oddly) are flat.35 However, these
molecules in low-temperature crystalline phases are twisted,35
as are also most substituted biphenyls. Statistically, the average
twist is ∼21° (237 structures from the Cambridge Database),
similar to what is observed in 11. The packing (Figure 5) in 11
is such that the molecular axes are approximately parallel, but
the molecules undergo cylindrical rotation about their axes so
that adjacent phenyl groups are almost perpendicular to each
other. This is very similar to the packing in p-[3]phenyl.36
Crystals of 1-phenyl-p-[2]cubyl (26) were grown by slow
evaporation of a chloroform solution. The molecule is a rod
13.08 Å long. The packing is complicated. There are four
molecules in the unit cell (Figure 6). Unlike the p-[n]phenyls,
Experimental Section
General Information. NMR spectra were run on samples in solution
in chloroform-d or (when specified) CD2Cl2 at ambient probe temper-
ature: 1H NMR at 400 MHz and referenced to internal tetramethylsi-
lane; 13C NMR spectra at 100.6 MHz and referenced to the central
line of the solvent. Proton chemical shifts are reported to a precision
of (0.01 ppm, carbon chemical shifts to a precision of (0.1 ppm,
sufficient for the purpose at hand. Infrared spectra were taken of

4120 J. Am. Chem. Soc., Vol. 121, No. 17, 1999
Eaton et al.
Figure 6. View down the c axis of the 1-phenyl-p-[2]cubyl (26) packing arrangement. There are two independent molecules in the asymmetric
unit. The two different types stack in double layers which form a phenyl-herringbone interface where the phenyl end groups meet. There is no
change in axis direction when bicubyl units abut those from another layer.
compounds in KBr pellets. Alkyllithium solutions were prepared as
needed or obtained from Aldrich and titrated prior to use.37 The
commercial solutions of t-BuLi used were generally 1.7 M in pentane.
Most reactions, as appropriate, were conducted under argon. Diethyl
ether and tetrahydrofuran were freshly distilled from sodium/benzophe-
none before use. Purifications were normally accomplished by open
column chromatography on Merck silica gel 60 (230-400 mesh) eluting
patiently (!) with pure pentane unless otherwise specified. The mass
spectra are 70-eV electron impact spectra. “Standard workup” means
the following: add the mixture to water; extract with the named solvent;
wash the extract with water followed by brine; dry over Na2SO4 or
MgSO4; remove solvent on a rotary evaporator at about 30-50 Torr
with the bath held near room temperature. Data collection for single-
crystal X-ray diffraction analyses was carried out on an automated
Bruker diffractometer equipped with an incident beam monochromator.
Space group assignments were based on systematic absences present
in the diffraction patterns and were confirmed by structure solution
and refinement. All structures were initially determined by direct
methods, aided by the program XS, and refined with the full-matrix
least-squares program XLS, contained in the SHELXTL collection of
computer programs (Sheldrick, G. M. SHELXTL Crystallographic
Software Version 5. Bruker Analytical Instruments, Madison, WI,
1994). This refinement program does not omit weaker data and refines
only on “observed” data; it uses all data, weighted as to its precision,
and refines on F2, not F values. The weighted F2 R value, wR2, is
directly proportional to the minimized sum of squares and is reported.
The traditional R values based on F are also reported, but values are
somewhat higher when all data are included. In the cases below
involving weaker data sets, traditional R’s based only on “observed”
[I > 2σ(I)] data are given for comparison, but here also, all data were
used to refine the structures.
was refluxed for 6 h. The solution was cooled and washed with aqueous
saturated Na2SO3 (2 × 50 mL) to remove iodine and then with water
(50 mL) and brine (50 mL). The organic portion was dried over MgSO4,
filtered, and the solvent removed to leave a mixture of 1,4-diiodocubane
and iodobenzene. Trituration with cold hexane dissolved away the latter
and left 1 (3.20 g, 85%) as a white solid: mp 225-226 °C (lit.38 mp
226-227 °C).
4-Phenylcubyl Iodide (5). A solution of t-BuLi in pentane (14.7
mL, 25.0 mmol) was added to a stirred solution of bromobenzene (1.88
g, 12.0 mmol) in ether (60 mL) under argon at -78 °C. (Commercial
phenyllithium can be used instead, but its quality must be carefully
checked as it is often contaminated with an appreciable amount of
biphenyl.) The pale yellow solution was allowed to reach room
temperature on its own (∼15 min) and was then cooled to 0 °C. Solid,
powdered 1,4-diiodocubane (1.78 g, 5.00 mmol) was added all at once.
The cooling bath was removed, and the mixture stirred for 40 min at
room temperature. The resulting yellow, homogeneous solution was
cooled to -20 °C and quenched with MeOH (1 mL). Standard workup
(CH2Cl2, 50 mL) and chromatography (hexanes) afforded 5 (1.35 g,
1
88%) as a white solid: mp 85-86 °C; H NMR δ 7.34 (t, 2H), 7.19
(m, 1H), 7.15 (d, 2H), 4.32 ppm (s, 6H); 13C NMR δ 141.5, 128.5,
126.3, 124.7, 60.4 (cubyl, C-phenyl), 54.3 (cubyl, 3C), 51.9 (cubyl,
3C), 39.0 ppm (cubyl, C-I); MS m/e 306 (P+, 100), 180 (5), 179 (20),
178 (50), 152 (10), 102 (5) 89 (15). Anal. Calcd for C14H11I: C, 54.92;
H, 3.61. Found: C, 54.88; H, 3.60.
Phenylcubane (10). A solution of t-BuLi in pentane (1.6 mL, 2.7
mmol) was added to a stirred suspension of 5 (366 mg, 1.20 mmol) in
ether (15 mL) at -78 °C. A pale yellow, homogeneous solution formed.
The dry ice/acetone bath was replaced with an ice/water bath. The
mixture was stirred for 15 min and then quenched carefully with MeOH
(1 mL). Standard workup (ether, 20 mL) and chromatography (hexanes)
afforded 10 (179 mg, 83%) as a colorless liquid: 1H NMR δ 4.01 (m,
Only illustrative procedures/characterizations are given here; the
remainder are available in the Supplemental Material.
3H), 4.12 (m, 1H), 4.17 (m, 3H), 7.20 (m, 3H), 7.38 ppm (t, 2H); 13
C
1,4-Diidodocubane (1). Iodobenzene diacetate (10.0 g, 31.2 mmol)
and iodine (8.50 g, 33.5 mmol) were added as solids to a stirred
suspension of cubane-1,4-dicarboxylic acid (2.00 g, 10.4 mmol) in dry
benzene (200 mL) at room temperature. The purple mixture obtained
NMR δ 44.1 (cubyl, 3C), 48.6 (cubyl, 1C), 51.2 (cubyl, 3C), 59.9
(cubyl, C-phenyl), 124.6, 125.6, 128.3, 143.4 ppm; MS m/e 80 (P+,
15), 179 (90), 178 (100), 165 (75), 152 (40), 115 (25), 102 (60). Anal.
Calcd for C14H12: C, 93.29; H, 6.71; Found: C, 93.34; H, 6.69.
p-Bis(cyclooctatetraenyl)benzene (15). A solution of p-dicubyl-
benzene (13, 282 mg, 1.00 mmol) and [Rh(1,5-cyclooctadiene)Cl]2 (20
mg, 0.04 mmol) in CHCl3 (10 mL) in a tube with a stopcock was
degassed using five freeze-thaw cycles and then heated at 60 °C for
16 h. The crude mixture was filtered through a small column of
(37) Watson, S. C.; Eastham, J. F. J. Organomet. Chem. 1967, 9, 165.
(38) Honegger, E.; Heilbronner, E.; Urbanek, T.; Martin, H.-D. HelV.
Chim. Acta 1985, 68, 23.
(39) Rieke, R. D.; Stack, D. E.; Dawson, B. T.; Wu, T.-C. J. Org.Chem.
1993, 58, 2483.

Building with Cubane-1,4-diyl
J. Am. Chem. Soc., Vol. 121, No. 17, 1999 4121
polymer-bound triphenylphosphine to remove the catalyst. The solvent
was removed in vacuo, and the residue was chromatographed using
5% Et2O in pentane. Cyclooctatetraene 15 (250 mg, 89%) was obtained
as a yellow, crystalline compound:15a UV (Et2O) λmax 224 (16 210),
270 (16 500), 320 nm (7060); IR ν 3009, 2996, 1700, 1684, 1652, 863,
806, 739, 667, 640, 563 cm-1; 1H NMR δ 5.88 (br, 6H), 5.96 (br, 2H),
1-Iodo-4′-phenyl-p-[2]cubyl (23), 1-Iodo-4′′-phenyl-p-[3]cubyl
(24), and 1-Iodo-4′′′-phenyl-p-[4]cubyl (25). A homogeneous solution
of 4-phenylcubyl iodide (5, 612 mg, 2.00 mmol) in stirred diethyl ether
(20 mL) was cooled to -77 °C (internal thermocouple). t-BuLi in
pentane (2.35 mL, 4.00 mmol) was added dropwise; the solution was
allowed to warm to -20 °C. The clear, pale yellow solution was cooled
to -70 °C. Finely powdered, solid 1,4-diiodocubane (712 mg, 2.00
mmol) was added in one portion. The mixture was stirred at -70 °C
for 10 min and then allowed to warm to 0 °C. It was stirred for 30 min
and then cooled to -40 °C. Iodine (500 mg) was added. The mixture
was allowed to come to room temperature and stirred there for 20 min.
The whole was poured into aqueous 5% Na2SO3 (25 mL) sufficient to
remove iodine. The reaction flask was rinsed with ether (30 mL). The
whole was washed with H2O (25 mL) and then brine (25 mL). The
clear, orange ether layer was removed carefully. The remaining ether-
insoluble product on top of the aqueous layer and on the sides of the
funnel were extracted first into CH2Cl2 (3 × 15 mL) and then into
CHCl3 (3 × 15 mL). Separately, the extracts were dried and evaporated
and found to contain 450, 321, and 29 mg of crude product, respectively.
The residue from the CHCl3 fraction was triturated with ether and then
CH2Cl2. It was dried in vacuo to give 25 (24 mg, 6%): mp 225-228
13
6.07 (br, 4H), 6.24 (br, 2H), 7.24 ppm (s, 4H); C NMR δ 126.0,
127.8, 131.5, 131.7, 132.1, 132.2, 132.5, 132.8, 139.2, 141.5 ppm; MS
m/e 282 (P+, 90), 202 (100), 189 (60), 178 (50), 152 (20), 77 (20).
Anal. Calcd for C22H18: C, 93.58; H, 6.41. Found: C, 93.55; H, 6.38.
4,4′-Diiodobicubyl (18, 1,4′-Diiodo-p-[2]cubyl). A solution of
t-BuLi in pentane (2.6 mL, 4.4 mmol) was added to a stirred solution
of mesityl bromide (438 mg, 2.20 mmol) in ether (5 mL) and cooled
in a dry ice/acetone bath. The pale yellow reaction mixture was allowed
to warm to room temperature and was then transferred by cannula to
a cooled (ice/water bath), well-stirred suspension of 1 (356 mg, 1.00
mmol) in ether (10 mL). A yellow suspension formed immediately.
The cooling bath was removed; the reaction mixture was stirred at room
temperature for 1 h. An orange suspension formed. The mixture was
cooled (ice/water bath); MeOH (1 mL) was added. Standard workup
(CH2Cl2, 25 mL) gave a pale orange semisolid. Trituration with hexanes
left 18 (120 mg, 52%) as an off-white powder. It was purified by
chromatography to give 112 mg (49%) of white material. A portion
was crystallized from hot benzene for X-ray analysis: mp 193-196
1
°C (dec); H NMR δ 3.74 (m, 6H), 3.84 (m, 6H), 3.97 (m, 6H), 4.06
(m, 3H), 4.18 (m, 3H), 7.16 (t, 1H), 7.20 (d, 2H), 7.33 ppm (t, 2H);
13C NMR, solubility too poor; MS m/e 612 (P+, 10), 485 (7), 408 (5),
303 (25), 289 (40), 265 (40), 226 (50), 202 (100), 179 (40), 178 (90),
152 (60), 114 (50). Anal. Calcd for C38H29I: C, 74.51; H, 4.76. Found
C, 74.42; H, 4.70. The residue from the CH2Cl2 extract was triturated
several times with ether and then dried in vacuo leaving 24 (124 mg,
24%): mp 215-217 °C (dec); 1H NMR δ 3.73 (m, 6H), 3.86 (m, 3H),
4.00 (m, 3H), 4.05 (m, 3H), 4.18 (m, 3H), 7.15 (t, 1H), 7.20 (d, 2H),
7.34 ppm (t, 2H); 13C NMR δ 40.3, 42.8, 42.9, 43.0, 47.5, 47.7, 54.7,
58.5, 58.68, 58.71, 59.4, 61.3, 124.6, 125.6, 128.3, 143.4 ppm; MS
m/e 510 (P+, 10), 383 (7), 289 (15), 265 (20), 254 (50), 202 (55), 178
(60), 165 (30), 152 (35), 128 (100). Anal. Calcd for C30H23I: C, 70.59;
H, 4.52. Found C, 70.58; H, 4.50. The residue from the ether layer
was subjected to chromatography. Phenylcubane (15 mg) was found
in the early fractions; 1-phenyl-p-[2]cubyl (26, 10 mg) in the later ones.
Further elution gave 5 (220 mg), followed by pure 23 (342 mg, 42%):
1
°C; H NMR δ 4.02 (m, 6H), 4.17 ppm (m, 6H); 13C NMR δ 39.4
(cubyl C-I), 47.4 (cubyl, 6C), 54.4 (cubyl, 6C), 57.9 ppm (cubyl-
cubyl). Anal. Calcd for C16H12I2: C, 41.95; H, 2.64. Found: C, 42.86;
H, 2.76. Crystal data: 18 (FW 458.06) crystallizes in the rhombohedral
space group R(-3)m, with a ) 8.9775(3) Å, b ) 8.9775(3) Å, c )
15.364(1) Å, (R ) â ) 90°, λ ) 120°, volume 1072.40(9) Å3, Z ) 3;
density (X-ray) 2.128 g/cm3. A clear 0.28 × 0.22 × 0.22 mm crystal,
in the shape of an almost-cubic chunk was used, with Mo KR radiation,
λ ) 0.710 73 Å, at T ) 294(2) K. The refinement agreement factors
were R ) 0.0313, wR2 ) 0.0655 for all 373 unique reflections.
Chromatography (hexanes) of the hexanes-soluble material afforded
1
4-mesitylcubyl iodide (21 mg, 10%): mp 127-129 °C; H NMR δ
2.22 (s, 3H), 2.27 (s, 6H), 4.35 (m, 3H), 4.51 (m, 3H), 6.75 ppm (s,
2H); 13C NMR δ 20.5, 21.4, 37.3 (cubyl, C-I), 53.8 (cubyl, 3C), 54.5
(cubyl, 3C), 63.7 (cubyl, C-mesityl), 129.9, 134.4, 135.7, 136.0 ppm;
MS (m/e 348 (P+, 100), 206 (15), 191 (10), 103 (15), 76 (5).
1
mp 143-145 °C; H NMR δ 3.85 (m, 3H), 4.01 (m, 3H), 4.08 (m,
3H), 4.21 (m, 3H), 7.21 (m, 3H), 7.36 ppm (t, 2H); 13C NMR δ 40.0,
42.8, 47.5, 47.6, 54.6, 58.1, 58.4, 61.3, 124.6, 125.7, 128.3, 143.1 ppm;
MS m/e 408 (P+, 2), 281 (15), 265 (65), 202 (100), 178 (75), 127 (25),
77 (30). Anal. Calcd for C22H17I: C, 64.72; H, 4.19. Found: C, 64.66;
H, 4.17.
Bicubyl (20) was prepared as described for 10 using 18 in THF (10
mL) and t-BuLi in pentane (0.65 mL, 1.5 M, 1.0 mmol). Standard
workup (ether) followed by flash chromatography (pentane) afforded
20 (41 mg, 91%) as a white crystalline solid: mp 175 °C; IR ν 2978,
2968, 1210, 865, 833 cm-1; 1H NMR (500 MHz) δ 4.04 (m, 2H) 3.87
ppm (m, 12H); 13C NMR (125 MHz) δ 57.6 (quaternary C), 49.4, 46.4,
44.1 (ppm); MS m/e 206 (P+, 70), 205 (100), 191 (90), 178 (70), 101
(40), 89 (55), 77 (55), 63 (50). Bicubyl (fw ) 206.27) crystallizes in
the monoclinic space group (C2/c, with a ) 16.240(4) Å, b ) 6.216-
(1) Å, c ) 10.289(2) Å, â ) 99.23(2)°, volume 1025.2(4) Å3, Z ) 4;
density (X-ray) 1.336 g/cm3. A clear colorless 0.66 × 0.16 × 0.06
mm crystal, a prism, was used, with Mo KR radiation, λ ) 0.710 73
Å, at T ) 223(2) K. The refinement agreement factors were R ) 0.0675,
wR2 ) 0.1199 for all 917 unique reflections.
4,4′-Dimethylbicubyl (22). Methyllithium (0.505 mmol) in ether
was added dropwise to a suspension of 18 (115 mg, 0.25 mmol) in dry
THF at -78 °C. The mixture was allowed to come to room temperature
and was stirred for 30 min. It was then cooled to -70 °C; a few drops
of methanol were added slowly. Standard workup (CH2Cl2) followed
by chromatography (pentane) gave first 22 (20 mg): 1H NMR δ 3.68
(m, 6H), 3.46 (m, 6H), 126 (s, 6H) ppm; 13C NMR δ 58.7, 57.1, 46.4,
42.5, 20.0 ppm; MS m/e 219 (P+ - CH3), 203 (50), 178 (70), 165
(40), 141 (40), 115 (100), 91 (50). Anal. calcd for C18H18: C, 92.26;
H, 7.73. Found: C, 92.21; H, 7.71. Further elution gave 32 mg of 4′-
methyl-p-[2]cubyl iodide (21): 1H NMR δ 4.17 (m, 3H), 4.02 (m,
3H), 3.68 (m, 3H), 3.48 (m, 3H), 1.27 (s, 3H); 13C NMR δ 58.6, 57.9,
57.2, 54.6, 47.5, 46.3, 42.4, 40.3, 19.8 ppm; MS m/e 219 (P+ - I),
202 (100), 189 (30), 152 (30), 115 (30), 91 (20), 77 (30). Anal. Calcd
for C17H15I: C, 58.98; H, 4.36. Found: C, 59.00, H, 4.33. Further
elution gave 20 mg of “unreacted” starting material.
1-Phenyl-p-[3]cubyl (27). t-BuLi solution (0.15 mL, 0.25 mmol)
was added dropwise to a suspension of 25 (51 mg, 0.10 mmol) in dry
THF (5 mL) at -78 °C. The mixture was allowed to warm to -10 °C
over 30 min and was then quenched with methanol. Standard workup
(CHCl3, 4 × 15 mL) gave a white solid, which was purified by
chromatography to give 36 mg (94%) of the hydrocarbon: IR ν 2970,
1599, 1498, 1444, 1228, 1412, 1189, 1032, 833, 749, 697, 503 cm-1
;
1H NMR δ 3.73 (m, 6H), 3.88 (m, 6H), 3.90 (m, 3H), 4.00 (m, 3H),
4.05 (m, 1H), 7.18 (t, 1H), 7.22 (d, 2H), 7.37 ppm (t, 2H); 13C NMR
δ 42.9, 44.1, 46.4, 47.7, 49.3, 57.7, 58.8, 59.30, 59.34, 61.3, 124.6,
125.6, 128.3, 143.5 ppm. Anal. Calcd for C30H24: C, 93.71; H, 6.28.
Found: C, 93.74; H, 6.29. Crystal data: 27 (fw ) 384.49) crystallizes
in the orthorhombic space group Pna21, with a ) 10.258(2) Å, b )
6.067(2) Å, c ) 62.85(2) Å, volume 3911(2) Å3, Z ) 8; density (X-
ray) 1.306 g/cm3. A colorless 0.60 × 0.20 × 0.01 mm crystal, a very
thin plate, was used, with Cu KR radiation, λ ) 1.541 78 Å, at T )
223(2) K. The refinement agreement factors were quite high, primarily
because the data were very weak; R ) 0.1793; wR2 ) 0.3269 for all
2491 unique reflections, and R ) 0.0900, wR2 ) 0.2133 for 1250
reflections with [I > 2σ(I)].
1,4-Diiodo-2,7-bis(N-methyl-N-tert-butylaminomethyl)cubane (38).
A solution of BH3‚THF (5.5 mL, 5.5 mmol) was added to a stirred
suspension of 1,4-diiodo-2,7-bis(N-methyl-N-tert-butylcarboxamido)-
cubane23c (37, 400 mg, 0.69 mmol) in THF (20 mL) at room
temperature. The mixture was heated to reflux for 4 h, then cooled,
quenched with MeOH (4 mL), and concentrated, leaving a white solid.
This was suspended with stirring in dimethoxyethane (50 mL).

4122 J. Am. Chem. Soc., Vol. 121, No. 17, 1999
Eaton et al.
Hydrochloric acid (2 M, 50 mL) was added, and the mixture was heated
to reflux for 4 h; a clear, colorless solution was obtained. The mixture
was basified using aqueous NaOH, and the product was extracted into
CH2Cl2 (4 × 25 mL). The extract was washed with water (20 mL) and
brine (20 mL), dried over MgSO4, and concentrated to afford 38 (240
4,4′-Diphenylbicubyl (47). Naphthalene (350 mg, 2.73 mmol) was
stirred in dry THF (5 mL). Freshly cut lithium metal (20 mg, 2.8 mmol)
was added. The mixture was sonicated for 2 h using a cleaning bath.
The resulting deep green solution of lithium naphthalenide was cooled
to about -100 °C using a methanol/liquid nitrogen slush. A -78 °C
solution of CuCN (90 mg, 1.0 mmol) and LiBr (175 mg, 2.02 mmol)
in THF (3 mL) was added. A dark red solution of Cu(0) formed.39
Separately, a solution of 5 (80 mg, 0.26 mmol) in THF (2 mL) was
cooled to -40 °C (CH3CN/dry ice bath) and then transferred by cannula
into the Cu(0) solution. The mixture was stirred for 10 min and then
the methanol/liquid nitrogen bath was replaced with a dry ice/acetone
bath. Nitrobenzene (0.35 mL, 3.4 mmol) was added, and the reaction
mixture was allowed to warm to room temperature on its own. Aqueous
saturated NH4Cl (3 mL) was added. Standard workup with ether (3 ×
10 mL) gave a dark semisolid. Column chromatography (hexanes) was
used to separate the desired product from excess naphthalene and
nitrobenzene. A second chromatography (1:1 hexanes/CH2Cl2) afforded
1
mg, 63%): mp 154-156 °C; H NMR δ 4.27 (s, 4H), 2.52 (s, 4H),
2.21 (s, 6H), 1.06 (s, 18H); 13C NMR δ 63.9, 57.3, 54.0, 53.6, 40.2,
36.9, 26.2 ppm; HRMS calcd 554.0655, found 554.0625. Anal. Calcd
for C20H32N2I2: C, 43.34; H, 5.82; N, 5.05. Found C, 43.28; H, 5.88;
N, 4.98.
1,4-Diiodo-2,7-bis(methoxymethyl)cubane (39). Hydrochloric acid
(25 mL, 5 M) was added over 15 min to a stirred suspension of 1,4-
diiodo-2,7-bis(N-methyl-N-tert-butylcarboxamido)cubane (750 mg, 1.29
mmol) in dimethoxyethane (30 mL). The mixture was heated to reflux
for 24 h. DME was removed in vacuo. The residual aqueous suspension
was filtered. The solid was rinsed with cold water and dried to give
crude 1,4-diiodo-2,7-bis(hydroxycarbonyl)cubane (350 mg, 61%): 1H
NMR (DMSO-d6) δ 13.03 (br, 2H), 4.52 ppm (s, 4H). A solution of
BH3‚THF (4.5 mL, 4.5 mmol) was added slowly to a stirred suspension
of this crude diacid (0.25 g, 0.56 mmol) in THF (15 mL) at 0 °C under
nitrogen. The cloudy, white suspension was stirred at room temperature
for 8 h. The reaction was then quenched with MeOH (4 mL). The
solvent and borates were removed in vacuo to afford 1,4-diiodo-2,7-
bis(hydroxymethyl)cubane (230 mg, 98%): mp 190-195 °C (dec);
1H NMR (DMSO-d6) δ 4.72 (t, 2H, OH, J ) 5 Hz), 4.21 (s, 4H), 3.48
ppm (d, 4H, J ) 5 Hz); 13C NMR (DMSO-d6) δ 64.3, 62.0, 54.4, 36.7
ppm. Powdered NaH (100 mg, 4.2 mmol) was added in one portion to
a stirred solution of this crude diol (150 mg, 0.36 mmol) in DME (12
mL) at room temperature under nitrogen. The gray suspension obtained
was stirred for 5 h, CH3I (0.50 mL, 8.0 mmol) was added, and the
suspension was stirred overnight. The mixture was quenched cautiously
with H2O. Standard workup (CH2Cl2, 30 mL) afforded the title diether
39 (150 mg, 94%) as a white solid: mp 115-117 °C; 1H NMR δ 4.26
(s, cubyl, 4H), 3.52 (s, 4H), 3.41 ppm (s, 6H); 13C NMR δ 72.9, 62.8,
59.3, 55.1, 36.1 ppm; MS m/z 444 (P+, <1), 399 (P+ - CH2OCH3, 5),
241 (40), 159 (70), 145 (85), 115 (100). Anal. Calcd for C12H14I2O2:
C, 32.46; H, 3.18. Found: C, 32.54; H, 3.15.
1
47 (9.7 mg, 21%): mp 180-182 °C; H NMR δ 3.91 (m, 6H), 4.03
(m, 6H), 7.24 (m, 6H), 7.38 ppm (t, 4H); 13C NMR δ 43.0, 47.8, 58.8,
61.5, 124.7, 125.7, 128.4, 143.4 ppm; MS m/e 358 (P+, 2), 341, (15),
265 (40), 239 (50), 202 (100), 154 (50), 102 (40). Anal. Calcd for
C28H22: C, 93.82; H, 6.17. Found: C, 93.76; H, 6.15.
1-Phenyl-4-(p-biphenyl)cubane (48). t-BuLi in pentane (2.35 mL,
4.00 mmol) was added dropwise to a homogeneous solution of 5 (612
mg, 2.00 mmol) in dry ether (20 mL) cooled in dry ice/acetone bath.
The resulting solution was allowed to warm to 0 °C and was then cooled
to -70 °C. 4-Phenyl-1,2-epoxycyclohexane40 (400 mg, 2.40 mmol) was
added dropwise. The mixture was allowed to come to room temperature
and then stirred for 4 h. Methanol was added dropwise. Standard workup
(CH2Cl2, 3 × 10 mL) gave a slightly colored oil that was purifed by
chromatography (3:1 pentane/ether). A late fraction (300 mg) was a
viscous oil taken to be the expected alcohol (OH in IR). It was dissolved
in dry pyridine (3 mL). The solution was cooled to 0 °C. Phosphorus
oxychloride (650 µL) was added dropwise. The mixture was stirred at
room temperature for 14 h, cooled in an ice bath, and carefully quenched
by dropwise addition of water. Standard workup (ether, 3 × 10 mL)
gave an oil (320 mg). This was cleaned somewhat by quick passage
through a small column of silica gel. The IR spectrum then showed no
hydroxyl absorption. The material was dissolved in benzene (5 mL);
DDQ (900 mg) was added. The solution was heated at 60 °C for 12 h,
then cooled, and added to water. The CH2Cl2 (3 × 10 mL) extract was
washed twice with dilute aqueous NaOH, water, and brine. Removal
of solvent left a yellowish solid. Chromatography (pentane) gave 200
mg of a 92:8 mixture (by NMR) favoring 48, the desired isomer,
contaminated with some of the meta biphenyl isomer. 48: 1H NMR δ
4.19 (s, 6H), 7.61-7.20 (14H) ppm; 13C NMR δ 47.7, 47.8, 60.6, 60.8,
124.7, 125.2, 125.8, 127.0, 127.0, 127.1, 128.4, 128.7, 138.7, 141.0,
142.1, 143.0 ppm; MS m/e 332 (P+), 230 (100), 178 (80), 152 (50),
115, (20), 102 (20), 77 (20). Anal. Calcd for C26H20: C, 93.94; H,
6.05. Found: C, 93.88; H, 6.06.
1-(p-Biphenyl)-4-(2-naphthyl)cubane (51). t-BuLi solution (0.59
mL, 1.0 mmol) was added dropwise to a stirred solution of 6 (191 mg,
0.500 mmol) in ether (10 mL) and the resultant mixture was cooled in
dry ice/acetone. The mixture was warmed to -10 °C and then cooled
to -70 °C. Solid naphthalene-1,4-oxide28 (75 mg, 0.60 mmol) was
added, and the whole stirred at -70 °C for 10 min. The mixture slowly
acquired an orange color. The cooling bath was removed, and the
mixture was allowed to warm to room temperature. It was cooled to
-30 °C and quenched with methanol. Standard workup (Et2O, 3 × 10
mL) and chromatography (10% Et2O in pentane) gave the dihydro-
naphthol 49 (176 mg, 88%): 1H NMR δ 2.80 (m, 1H), 3.97 (m, 3H),
4.15 (m, 3H), 4.84 (br, 1H), 5.95 (dd, 1H), 6.54 (dd, 1H), 7.16 (d,
1H), 7.24-7.37 (6H), 7.43 (t, 2H), 7.59 ppm (d, 4H); 13C NMR δ 42.7,
45.0, 48.5, 59.5, 60.3, 70.1, 125.2, 125.8, 126.6, 126.9, 127.1, 127.6,
127.8, 128.0, 128.6, 128.7, 132.5, 136.2, 138.6, 141.1, 142.4 ppm. It
was dissolved without further purification in CH2Cl2 (10 mL). A drop
of methanesulfonic acid was added, and the solution was stirred at room
1,4-Diiodo-2,7-dihexylcubane (42). A solution of t-BuLi in pentane
(1.9 mL, 3.2 mmol) was added slowly over ∼5 min to a stirred
suspension of 1,4-diiodo-2,7-bis(N-methyl-N-tert-butylcarboxamido)-
cubane (410 mg, 0.704 mmol) in THF (70 mL) at -77 °C. A yellow
suspension formed; the temperature rose to -60 °C. Hexyl iodide
(Aldrich, 0.85 mL, 5.6 mmol) was added, and the mixture was allowed
to warm to room temperature. Standard workup (CH2Cl2) and chro-
matography (4:1 hexanes/EtOAc) afforded 1,4-bis(N-methyl-N-tert-
butylcarboxamido)-2,7-dihexylcubane (190 mg, 54%) as a pale yellow
solid: 1H NMR δ 3.87 (s, 4H), 2.80 (s, 6H), 1.62 (br, 4H), 1.41 (s,
18H), 1.24 (br, 16H), 0.87 ppm (t, 6H). The procedure was repeated to
accumulate more material. Part of the crude product (260 mg, 0.520
mmol) was dissolved in stirred THF (20 mL). Lithium aluminum
hydride (120 mg, 3.16 mmol) was added in one portion. The mixture
was heated to reflux for 4.5 h, cooled to 0 °C, and quenched carefully
with water (3 mL). Standard workup (CH2Cl2) gave 1,4-bis(N-methyl-
N-tert-butylaminomethyl)-2,7-dihexylcubane (190 mg, 80%) as a
yellow oil: 1H NMR δ 3.36 (s, 4H), 2.58 (s, 6H), 1.57 (br, 4H), 1.24
(br, 16H), 1.01 (s, 18H), 0.87 ppm (t, 6H). It was used as it was directly;
220 mg (0.44 mmol) in a little acetone was added to a stirred solution
of dimethyldioxirane (125 mL, ∼0.10 M) in acetone at 0 °C. The
solution was stirred overnight at room temperature. The solvent was
removed in vacuo; trituration of the residue with CH2Cl2 left 1,4-bis-
(hydroxycarbonyl)-2,7-dihexylcubane (100 mg, 63%) as a white
solid: 1H NMR (acetone-d6) δ 3.82 (s, 4H), 1.70 (br, 4H), 1.29 (br,
16H), 0.86 ppm (br, 6H). Barton iododecarboxylation10 using 50 mg
(0.14 mmol) of the crude diacid, oxalyl chloride (5 mL), anhydrous
sodium salt of 2-thiopyridone N-oxide (52 mg, 0.35 mmol), 4-(N,N-
dimethylamino)pyridine (2 mg), CF3CH2I (0.07 mL, 0.7 mmol), and
dry benzene (4 mL) gave, after standard workup and chromatography
(pentane), 42 (40 mg, 55%) as a white solid: mp 76-77 °C; 1H NMR
δ 4.08 (s, 4H), 1.57 (br, 4H), 1.38 (br, 16H), 0.89 ppm (t, 6H); 13C
NMR δ 65.9, 56.2, 40.4, 32.9, 31.7, 29.3, 23.0, 22.6, 14.1 ppm; Anal.
Calcd for C20H30I2: C, 45.82; H, 5.77. Found C, 45.88; H, 5.82.
(40) Curtin, D. Y.; Harder, R. J. J. Am. Chem. Soc. 1960, 82, 2357.
(41) (a) Krishnan, S.; Kuhn, D. G.; Hamilton, G. A. J. Am. Chem. Soc.
1977, 99, 8121. (b) Murray, R. W.; Jeyaraman, R. J. Org. Chem. 1985, 50,
2847.

Building with Cubane-1,4-diyl
J. Am. Chem. Soc., Vol. 121, No. 17, 1999 4123
temperature for 4 h. Standard workup (including a wash with aqueous
NaHCO3) followed by chromatography gave 51 (165 mg, 86% overall)
as a white solid. Crystallization from ether/pentane gave white
needles: 1H NMR δ 4.26 (m, 6H), 7.37 (m, 3H), 7.45 (m, 5H), 7.62
(m, 5H), 7.82, (d, 2H), 7.86 ppm (d, 1H); 13C NMR δ 47.7, 47.8, 60.7,
61.1, 122.8, 123.5, 125.2, 125.3, 126.0, 127.0, 127.1, 127.5, 127.6,
128.2, 128.7, 131.9, 133.5, 138.8, 140.3, 141.1, 142.1 ppm; MS m/e
382 (P+, 40), 230 (60), 204 (65), 152 (60), 97 (60), 77 (70). Anal.
Calcd for C30H22: C, 94.20; H, 5.79. Found: C, 94.14; H, 5.77.
Acknowledgment. We are grateful to Mario Vituani, Elena
Galoppini, Yusheng Xiong, and Takashi Ishizone for their help
in the development of some of the experimental procedures.
The crystal of bicubyl for X-ray analysis was grown by J.
Tsanaktsidis. This work was supported financially by the
National Science Foundation, the U.S. Army Armament Re-
search, Development and Engineering Center (via Geo-Centers,
Inc.), and the Office of Naval Research. T.E. held a GAANN
Fellowship.
1-(p-Biphenyl)-4′-(9-phenanthryl)-p-[2]cubyl (54) was prepared in
a similar way using 29 (242 mg, 0.500 mmol) suspended in ether (20
mL), t-BuLi in pentane (0.62 mL, 1.05 mmol), and phenanthrene-9,10-
oxide 41 (100 mg, 0.600 mmol). The intermediate dihydrophenanthrol
was chromatographed (10% ether in pentane) to give a clean sample
(233 mg, 80%), which was directly dehydrated. Chromatography (10%
ether in pentane) afforded 54 (206 mg, 77% overall) as a pale yellow
solid: 1H NMR δ 4.00 (m, 3H)), 4.22 (m, 6H), 4.32 (m, 3H), 7.34-
7.88 (16H), 8.66 (d, 1H), 8.78 ppm (d, 1H); 13C NMR δ 43.0, 43.2,
47.5, 47.9, 57.2, 58.4, 61.2, 62.6, 122.4, 123.2, 123.4, 125.2, 125.6,
126.0, 126.2, 126.3, 126.6, 127.0, 127.1, 128.3, 128.7, 129.5, 130.3,
130.9, 131.7, 136.8, 138.6, 141.1, 142.5 ppm. HRMS calcd for
C42H30: m/e 534.2347; found 534.2349.
Supporting Information Available: Drawings of com-
pounds 10-14, 26-28, 32-36, 40, 41, and 47; experimental
procedures for 6-9, 11-14, 16, 26, 28-35, 40, 41, 43-46,
50, 52, and 53; tables of crystal data and structure refinement,
atomic coordinates, bond lengths and angles, anisotropic
displacement parameters and views of the X-ray structures of
11, 13, 18, 20, 26, and 27 with numbering systems used and
thermal ellipsoids; view of the molecular packing in a crystal
of 27 (PDF). This material is available for free on the Internet
at http://pubs.acs.org.
JA983441F