Triptycenediols by rhodium-catalyzed [2 + 2 + 2] cycloaddition

Article abstract of DOI:10.1021/ol701642j

An efficient, modular synthesis of triptycene derivatives is presented, in which the triptycene ring system is constructed from readily available anthraquinone and alkyne starting materials. A rhodium-catalyzed alkyne cyclotrimerization reaction serves as

Full text of DOI:10.1021/ol701642j

ORGANIC
LETTERS
2007
Vol. 9, No. 18
3695-3697
Triptycenediols by Rhodium-Catalyzed
[2 2] Cycloaddition
+
2 +
Mark S. Taylor and Timothy M. Swager*
Department of Chemistry and Institute for Soldier Nanotechnologies,
Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
tswager@mit.edu
Received July 12, 2007
ABSTRACT
An efficient, modular synthesis of triptycene derivatives is presented, in which the triptycene ring system is constructed from readily available
anthraquinone and alkyne starting materials. A rhodium-catalyzed alkyne cyclotrimerization reaction serves as the key step in this new method
for the preparation of these useful unnatural products.
The rigid hydrocarbon triptycene (1, Scheme 1) was first
prepared in 1942, in order to test the hypothesis that a radical
at the bridgehead position of this ring system would be
significantly less stable than the geometrically unconstrained
triphenylmethyl radical.1 Since these initial studies, the
triptycene scaffold has been applied creatively in a number
of settings, including studies of atropisomerism2 and host-
guest chemistry,3 ligand design, and as a component of
“molecular machines”.4 Synthetic studies have expanded this
family of unnatural products to include a wide range of
related structures, known collectively as iptycenes.5 Our
group has demonstrated that the “free volume” of iptycenes
can be exploited to increase the thin-film quantum yield of
fluorescent polymers,6 to improve the porosity7 and mechan-
ical properties8 of polymers, and to favor the alignment of
fluorophores in liquid crystalline matrices.9
Diels-Alder reactions of anthracene with benzyne or with
p-benzoquinone (followed by aromatization) have served as
the dominant synthetic strategy for the preparation of
iptycenes, both historically and in recent applications. While
(1) Bartlett, P. D.; Ryan, M. J.; Cohen, S. G. J. Am. Chem. Soc. 1942,
64, 2649.
(2) Oki, M. Topics in Stereochemistry; Allinger, N. L., Eliel, E. L., Wilen,
S. H., Eds.; Wiley: New York, 1983; Vol. 14, p 1.
(3) (a) Rathore, R.; Kochi, J. K. J. Org. Chem. 1998, 63, 8630. (b) Veen,
E. M.; Postma, P. M.; Jonkman, H. T.; Spek, A. L.; Feringa, B. L. Chem.
Commun. 1999, 1709.
Scheme 1. Structure of Triptycene and [2 + 2 + 2] Approach
to Substituted Triptycenediols
(4) (a) Godinez, C. E.; Zepeda, G.; Mortko, C. J.; Dang, H.; Garcia-
Garibay, M. A. J. Org. Chem. 2004, 69, 1652-1662. (b) Kelly, T. R.; Cai,
X.; Damkaci, F.; Panicker, S. B.; Tu, B.; Bushell, S. M.; Cornella, I.; Pigott,
M. J.; Salives, R.; Cavero, M.; Zhao, Y.; Jasmin, S. J. Am. Chem. Soc.
2007, 129, 376-386 and references therein.
(5) Hart, H. Pure Appl. Chem. 1993, 65, 27-34.
(6) Yang, J.-S.; Swager, T. M. J. Am. Chem. Soc. 1998, 120, 11864-
11873.
(7) Long, T. M.; Swager, T. M. J. Am. Chem. Soc. 2003, 125, 14113-
14119.
(8) Tsui, N. T.; Paraskos, A. J.; Torun, L.; Swager, T. M.; Thomas, E.
L. Macromolecules 2006, 39, 3350-3358.
(9) Long, T. M.; Swager, T. M. J. Am. Chem. Soc. 2002, 124, 3826-
3827.
10.1021/ol701642j CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/08/2007

Scheme 2. Cis-Selective Acetylide Additions to
Table 2. Preparation of Substituted Triptycenediols by
Rhodium-Catalyzed [2 + 2 + 2] Cycloadditiona
Anthraquinones
these reactions are clearly well suited to this class of targets,
limitations of this approach have become evident. In
particular, the preparation of iptycenes bearing multiple side
chains at defined positions often necessitates multistep,
moderate-yielding syntheses. Since the presence of such
substituents improves the solubility of iptycene-based poly-
mers,10 and may provide “handles” for the introduction of
new functional components to iptycene derivatives, we have
become interested in developing new, modular methods for
the construction of substituted iptycenes. Herein, we describe
a new application of metal-catalyzed alkyne cyclotrimeriza-
tion reactions ([2 + 2 + 2] cycloadditions) that provides
access to substituted 9,10-triptycenediols in 2-3 steps from
readily available anthraquinones and alkynes.
Metal-catalyzed [2 + 2 + 2] cycloadditions have become
a powerful synthetic tool for the construction of benzene
rings, advancing at a rapid pace since the pioneering studies
of Vollhardt and co-workers.11 A range of transition metal
catalysts have been identified for these reactions, including
Table 1. Optimization of [2 + 2 + 2] Cycloaddition Reaction
a General conditions: 5 mol % of Rh(PPh3)3Cl, 2.5 equiv of alkyne,
toluene, 100 °C. b Isolated yield, 0.25 mmol scale. c 2.5 mol % of
[Rh(cod)Cl]2, 5 equiv of norbornadiene, toluene, 100 °C.
complexes of cobalt, nickel, ruthenium, rhodium and pal-
ladium.12 We envisioned that a [2 + 2 + 2] cycloaddition
of diyne 3 with substituted alkynes could generate the
triptycene ring system (Scheme 1). In turn, diyne 3 would
be prepared by a cis-selective addition of two equivalents
of metal acetylide to an anthraquinone (2), an attractive
starting point since many anthracene derivatives employed
in Diels-Alder preparations of triptycenes are themselves
derived from anthraquinones. The identification of a suitable
catalyst for the proposed [2 + 2 + 2] cycloaddition, and of
reaction conditions for the diastereoselective preparation of
entry
substrate
catalyst
yieldc (%)
1
2
3
4
6a
6b
6a
6b
Cp*Ru(cod)Cla
Cp*Ru(cod)Cla
Rh(PPh3)3Clb
Rh(PPh3)3Clb
10
40
90
40
a Conditions: 70 °C in 1,2-dichloroethane, 14 h. b Conditions: 100 °C
in toluene, 14 h. c Isolated yield on 0.1 mmol scale.
3696
Org. Lett., Vol. 9, No. 18, 2007

cis-diol 3 were challenges to be addressed in order to
implement this synthetic plan.
and the diyne components. A variety of terminal alkynes,
including aliphatic, aromatic, and functionalized derivatives,
reacted smoothly with 6a, yielding triptycenediols 7a-h
(Table 2). Alkoxy-substituted 7f was obtained in 81% yield
by reaction of 6c with 1-hexyne. Internal alkynes, such as
4-octyne, diphenylacetylene, and bis(trimethylsilyl)acetylene,
did not react with 6a under the optimized conditions. In
contrast, phenylacetylene adduct 6d readily underwent [2 +
2 + 2] cycloaddition with 1-hexyne to provide the desired
product 7g. Furthermore, 7h, the product of formal cyclo-
addition of acetylene with 6d, was obtained by reaction with
norbornadiene in the presence of [Rh(cod)Cl]2, a precedented
reaction that is postulated to proceed by [2 + 2 + 2]
cycloaddition followed by retro-Diels-Alder reaction and
expulsion of cyclopentadiene.14
We studied the addition of lithium (trimethysilyl)acetylide
to anthraquinone (Scheme 2) and found that the diastereo-
selectivity of this reaction is solvent dependent. Whereas the
addition is highly trans-selective (>9:1 trans/cis) when
carried out in tetrahydrofuran, moderate selectivity for the
cis isomer was observed when toluene was used as solvent.
Separation of the diastereomers was achieved by column
chromatography, resulting in the isolation of diastereomeri-
cally pure 5 in 64% yield.13 Desilylation (KOH, THF/
CH3OH, 80%) provided terminal diyne 6a, which served as
the test substrate for the optimization of conditions for the
metal-catalyzed [2 + 2 + 2] cyloaddition, along with methyl
ether 6b. Alkoxy-substituted 6c and internal alkyne 6d were
prepared by similar protocols.
Ruthenium- and rhodium-based catalysts were evaluated
for the reaction of 6a and 6b with 1-hexyne (Table 1).
Although reactions of 6b were sluggish, presumably a result
of the steric influence of the methyl ether groups, 6a reacted
smoothly in the presence of Wilkinson’s catalyst, yielding
triptycenediol 7a in 90% yield. The catalytic activity of
Ru(Cp*)(cod)Cl (cod ) cyclooctadiene) was significantly
lower than that of Wilkinson’s catalyst for this combination
of substrates.
The synthetic approach to triptycenediols presented herein
thus represents an attractive alternative to Diels-Alder-based
approaches, rapidly providing access to multi-substituted
derivatives suitable for further functionalization. Continued
investigations of the scope of this method, and applications
in materials science, are attractive avenues for future studies.
Acknowledgment. This work was supported by the U.S.
Army through the Institute for Soldier Nanotechnologies,
under contracts DAAD-19-02-0002 and W911NF-07-D-004
with the US Army Research Office. The content does not
necessarily reflect the position of the Government, and no
official endorsement should be inferred.
The scope of the rhodium-catalyzed [2 + 2 + 2]
cycloaddition was evaluated with respect to both the alkyne
(10) For example: Zhao, D.; Swager, T. M. Org. Lett. 2005, 7, 4357-
4360.
(11) Vollhardt, K. P. C. Acc. Chem. Res. 1977, 10, 1-8.
(12) For reviews: (a) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996,
96, 49-92. (b) Sato, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901-
2915. (c) Chopade, P. R.; Louie, J. AdV. Synth. Catal. 2006, 348, 2307-
2327.
Supporting Information Available: Experimental pro-
cedures and characterization data (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
OL701642J
(13) X-ray crystallography of 6b served to elucidate the configuration
of 6a and 6b. Diols 6c and 6d are assigned by analogy, an assignment that
1
is supported by diagnostic chemical shifts in the H NMR spectrum (see
(14) Wu, Y.-T.; Hayama, T.; Baldridge, K. K.; Linden, A.; Siegel, J. S.
the Supporting Information).
J. Am. Chem. Soc. 2006, 128, 6870-6884.
Org. Lett., Vol. 9, No. 18, 2007
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