Radical cascade transformations of tris(o-aryleneethynylenes) into substituted benzo[a]indeno[2,1-c]fluorenes

Article abstract of DOI:10.1021/ja8038213

Oligomeric o-aryleneethynylenes with three triple bonds undergo cascade radical transformations in reaction with a Bu₃SnH/AIBN system. These cascades involve three consecutive cycle closures with the formation of substituted benzo[a]indeno[2,1-c]fluorene or benzo[1,2]fluoreno[4,3-b]silole derivatives. The success of this sequence depends on regioselectivity of the initial attack of the Bu₃Sn radical at the central triple bond of the o-aryleneethynylene moiety. The cascade is propagated through the sequence of 5-exo-dig and 6-exo-dig cyclizations which is followed by either a radical attack at the terminal Ar substituent or radical transposition which involves H-abstraction from the terminal TMS group and 5-endo-trig cyclization. Overall, the transformation has potential to be developed into an approach to a new type of graphite ribbons.

Full text of DOI:10.1021/ja8038213

Published on Web 08/02/2008
Radical Cascade Transformations of
Tris(o-aryleneethynylenes) into Substituted
Benzo[a]indeno[2,1-c]fluorenes
Igor V. Alabugin,*,† Kerry Gilmore,† Satish Patil,† Mariappan Manoharan,†
Serguei V. Kovalenko,† Ronald J. Clark,† and Ion Ghiviriga‡
Department of Chemistry and Biochemistry, Florida State UniVersity, Tallahassee, Florida
32306-4390 and Department of Chemistry, UniVersity of Florida,
GainesVille, Florida, 32611-7200
Received May 21, 2008; E-mail: alabugin@chem.fsu.edu
Abstract: Oligomeric o-aryleneethynylenes with three triple bonds undergo cascade radical transformations
in reaction with a Bu3SnH/AIBN system. These cascades involve three consecutive cycle closures with the
formation of substituted benzo[a]indeno[2,1-c]fluorene or benzo[1,2]fluoreno[4,3-b]silole derivatives. The
success of this sequence depends on regioselectivity of the initial attack of the Bu3Sn radical at the central
triple bond of the o-aryleneethynylene moiety. The cascade is propagated through the sequence of 5-exo-
dig and 6-exo-dig cyclizations which is followed by either a radical attack at the terminal Ar substituent or
radical transposition which involves H-abstraction from the terminal TMS group and 5-endo-trig cyclization.
Overall, the transformation has potential to be developed into an approach to a new type of graphite ribbons.
1. Introduction
The rich potential of alkyne functionality is manifested
particularly well in cascade cyclizations. Such transformations
allow for the efficient and atom-economical preparation of
polycyclic frameworks1 found in natural products,2 carbon
nanostructures, and other useful molecules.3 Since each alkyne
carbon has the ability to form more than one new bond without
the involvement of heteroatom containing functional groups,
alkynes lend themselves particularly well to the preparation of
carbon-rich materials.4
Figure 1. o-, m-, and p-Phenyleneethynylenes
Oligomeric and polymeric aryleneethynylenes (Figure 1)
represent a particularly interesting class of alkyne-containing
compounds which have found applications in the design of many
other electronic and photonic devices5 including TNT chemosen-
sory materials,6 molecular nanowires bridging gold nanoelec-
trodes,7 and jacketed blue-emitting rods.8 Although para-
aryleneethynylenes are used most often, recent work of Moore9
and Schanze10 on meta-aryleneethynylenes clearly demonstrated
new opportunities presented by the different substitution pat-
terns. In this context, it is interesting that ortho-aryleneethy-
nylenes, the final member of the family, remain scarcely
studied11 even though the chemistry and structures of the
simplest members of this family which are benzannelated
analogues12 of enediyne natural antibiotics13 continue to be of
great interest. An understanding of reactivity of ortho-arylene-
† Florida State University.
‡ University of Florida.
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Alabugin et al.
Figure 2. Selected possible radical cyclization cascades triggered by the addition of a radical to a substituted (Z,Z)-deca-3,7-diene-1,5,9-triyne. “Unknown”
refers to the processes triggered by the addition of an external radical species. For specific examples of related radical cascades developed by Bergman,
Vollhard, and Wu, see Figure 3.
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A R T I C L E S
Figure 3. Thermal cascade cyclizations of triynes and tetraynes.
Figure 2). Vollhardt and Matzger found that the Bergman
cyclization of benzannelated enediynes can also be followed
by the 5-exo-dig cyclization18 and that, in some cases, the 5-exo
path predominates (Figure 3, cyclic system III in Figure 2).
Wu et al.19 triggered analogous cyclization cascades utilizing
the σ-radical from the σ,π-diradical generated through a
Myers-Saito cyclization (Figure 3). Competition between
5-exo- and 6-endo cyclizations in these systems has been
analyzed computationally by Alabugin and Manoharan who
dissected the contributions of stereoelectronic, strain, and
thermodynamic effects to the selectivity and explained the
observed experimental differences in the above systems.20
Finally, Wang described an interesting example where a
cyclization cascade21 (bottom of Figure 3) is initiated by the
Schmittel cyclization.22
Figure 4. PtCl2/n-H2O catalyzed cyclization of unsymmetrical 2,2′-
bis(ethynyl)diphenylacetylene.
undocumented. In a few known examples, which have provided
structures analogous to those resulting from cascades III and
IV in Figure 2, formation of the reactive radical was achieved
through a different approach (either the Bergman or the Myers-
Saito cyclization). In particular, Bergman himself was the first
to explore initiation of a radical cascade transformation in (Z-
Z)-deca-3,7-diene-1,5,9-triyne16 with the thermal Bergman cy-
clization of enediynes17 and discovered that the intermediate
p-benzyne diradical can be trapped through a 6-endo-dig
cyclization to give naphthalene (Figure 3, cyclic system IV in
Transition metal catalyzed cascade transformations of such
systems have started to attract attention as well. Apart from
numerous examples of ruthenium, rhodium, palladium, and
cobalt catalyzed [2 + 2 + 2] cyclizations of unconjugated
Figure 5. Bu3SnH-promoted 5-exo-dig radical cyclization of enediynes.
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This transformation is initiated by the attack of a Bu3Sn
radical at the internal carbon of one of the triple bonds, resulting
in the formation of an intermediate vinyl radical 2. This radical
undergoes a 5-exo-dig radical cyclization resulting in the fulvene
radical 3, which is subsequently quenched by H-abstraction from
Bu3SnH. The present study aimed to determine whether a 5-exo-
cyclization can be followed by another C-C bond forming step
through an intramolecular reaction of radical 3 with an ap-
propriately positioned alkyne π-system in a radical cyclization
cascade.
The requisite substrates were first prepared and investigated
by Grubbs and Kratz,11,29 who studied the thermolysis of
oligomeric o-aryleneethynylenes and reported evidence of an
exothermic reaction, yet isolated no structurally defined prod-
ucts. Other interesting and potentially relevant examples of
cascade radical transformations of alkynes include selective
6-endo-dig cyclizations in constrained systems by Anthony and
co-workers30,31 and Matzger et al. (Figure 6).32
Although the literature data suggest a significant diversity of
radical cascade cyclizations involving several triple bonds, none
of the above examples affords the same type of polycyclic
skeleton as structures potentially available through a cascade
initiated by the 5-exo-dig cyclizations of the central “enediyne”
moiety. Research described below was undertaken to fill this
gap and to test the feasibility of this chemistry for the rapid
construction of polycyclic systems.
Figure 6. Radical cascade cyclizations of alkynes in constrained systems.
Scheme 1. Synthetic Route A to Substituted Triynes from the
Kowalik-Tolbert Intermediate 10
2. Results
2.1. Synthesis of Starting Materials. The target oligomeric
o-aryleneethynylenes were synthesized by two methods. In the
first approach, the key intermediate is prepared from diphenyl
acetylene (tolane) through a sequence outlined earlier by
Kowalik and Tolbert.33 This sequence involves directed meta-
lation with the LICKOR superbase, quenching of the resulting
dianionic species with TMSCl, and exchange of TMS for iodine
(Scheme 1). Although this method requires both anhydrous and
oxygen-free conditions, it provides a very convenient diiodide
precursor 10 which yields the requisite triynes though Sono-
gashira coupling with 2 mol of an appropriate terminal acetylene.
In the second approach, four sequential Sonogashira reactions
transform ortho-bromoiodobenzene into the key bis(2-ethy-
nylphenyl)acetylene intermediate (Scheme 2).34 These Sono-
gashira reactions are more amenable to scaleup than reactions
of tolane dianion, but overall the two methods are complemen-
tary. Although the second sequence is one step longer, the
average overall yield for the triynes produced through the two
sequences are comparable (∼30%). The first method is par-
triynes,23 a particularly interesting cascade reaction promoted
by PtCl2/n-H2O was recently reported by Liu et al. (Figure
4).24,25 This mechanistically different transformation proceeds
through hydration of a triple bond and sequential cyclizations
of ketone intermediates, leading to the formation of a type IX
polycyclic system from Figure 2.
In this work, we have chosen a different strategy for initiating
the cyclization cascades. This strategy is based on Bu3SnH-
mediated radical 5-exo-dig cyclization of the enediyne moiety
- a process that we developed recently26 for mechanistic studies
of photochemical C1C5 cyclization of enediynes.27 The utility
of this radical cyclization for the preparation of polysubstituted
fulvenes and indenes is illustrated in Figure 5.28
Scheme 2. Synthetic Route B to Substituted Triynes
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A R T I C L E S
Scheme 3. Preparation of Tribenzocyclyne
and tetrakis(triphenylphosphine)palladium copper(I) iodide
catalyst under phase-transfer conditions in 36% yield (Scheme
3).36
2.2. Cyclizations. Radical reactions of the triynes were
initiated by slow addition of Bu3SnH and AIBN using a
syringe pump. The products are shown in Figure 7, whereas
the reaction yields are summarized in Table 1. X-ray structure
of the cyclic product 17c along with that for the starting tris-
alkyne 11c is given in Figure 8. Comparison of the two
structures illustrates the remarkable change in the molecular
structure as the result of this one-pot transformation where
all three triple bonds are involved and three new cycles are
formed in the cascade process.
The efficiency of radical cascades of triynes 11a-c exceeds
those of thermal reactions initiated by cycloaromatizations16
and approaches that of transition metal catalyzed cycliza-
tions.23 Greater efficiency compared to the Bergman cycliza-
tion is not surprising because the formation of the Bergman
six-membered diradical (p-benzyne) is reversible.37 The
diradical can open back up to the enediyne (retro-Bergman
ring opening) or abstract a hydrogen atom before it attacks
ticularly convenient when appropriate terminal alkynes are
readily available. The second method takes better advantage of
the potentially larger pool of iodo/bromo substituted aromatics.
The cyclic version of tris(o-aryleneethynylenes) (tribenzo-
hexadehydro[12]annulene or tribenzocyclyne)35 involves cy-
clooligomerization of an appropriate o-haloethynylbenzene
Figure 7. Products of reaction of substituted triynes 11, 15 with Bu3SnH and AIBN.
Figure 8. X-ray geometries of tris-alkyne 11c (on the left) and cyclized product 17c.
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Alabugin et al.
Figure 9. Regioselective deuterium incorporation in the acyclic product (left, R ) OCH3) and convergent incorporation of deuterium in the cyclization
cascade through two alternative pathways (right, R ) CH3). Contrasting regioselectivity for D-incorporation in the analogous cyclization of enediynes from
ref 28 is shown for comparison below.
Table 1. Yields in the Bu3SnH/AIBN-Promoted Cyclizations and
Reductions of Substituted Triynes
triyne
R
cyclized
monoreduced
direduced
11a
11b
11c
11d
15
trimethylsilyl
phenyl
p-Me-phenyl
p-OMe-phenyl
H
17a 73%a
17b 65%
17c 70%
17d 10%
18 9%b
19 50%
complex mixture
0%
20 42%
16b
p-(CO2Me)-phenyl
a The structure was elucidated from the 1H and 13C NMR one-bond
and long-range couplings revealed by the GHMQC and GHMBC spectra
discussed in detail in the Supporting Information. b Presence of
byproduct with similar Rf values complicated separation, which is
reflected in the low yield of the pure isolated product. NMR analysis of
the crude reaction mixture suggests the yield of ∼35%.
Figure 10. Bu3SnH-promoted cascade cyclization of tribenzocyclane.
the remaining triple bond. Even though Myers-Saito cy-
clization is exothermic and its reversibility is less important,
the cyclized products are still formed in relatively low
(<20%) yields (Figure 3). Increased efficiency of cascades
initiated by the 5-exo-dig radical cyclization suggests that
the side processes are less important for the transformations
discussed in this paper.
Most interestingly, the products of Bu3SnH-mediated cy-
clizations 17a-d differ from the products of thermal and
transition metal catalyzed reactions (Figures 3-6). The cycliza-
tion proceeds through a sequence of the 5-exo-dig and 6-exo-
dig cyclizations which is terminated by a reaction of a vinyl
radical with a substituent (an Ar or TMS group) at the terminal
triple bond (Figures 11, 12). Aromatization through a H-atom
shift completes the transformation (Vide infra). Note that unless
the starting material is symmetric tribenzocyclane 21, directing
the initial Sn radical attack at the central triple bond is essential
for the success of this cascade process. As a result, the
cyclization success depends on the nature of terminal substit-
uents: only reduction of the terminal alkynes is observed for R
) H, while mixture of reduction and cyclization products is
formed for R ) p-OMePh. The presence of an ester group (R
) CO2Me) leads to a complex mixture of unidentified products
(Table 1). NMR analysis of this mixture suggests that the ester
functionality is reactive under these conditions.
As destannylation can be achieved with a source of either
protons or deuterons (HCl/DCl), the position of the tributyltin
moiety in the products can be shown unequivocally, thus
revealing the chemo- and regioselectivity of the first step and
confirming addition of the tributyltin radical to the internal triple
bond. The termination point of the radical cascade can also be
determined through an alternative deuteration process with
Bu3SnD as the reactant (Figure 9). Interestingly, the location
of the deuterium shows that the initiation and termination of
the radical cascade cyclization occur at the same carbon!38 This
observation contrasts the observation of the different location
for the deuterium in the respective cyclizations of enediynes
(bottom part of Figure 9).28
Radical cyclization of symmetric molecule tribenzocyclane
21 proceeded without complications to yield 65% of 1,6-
dihydrobenzo[a]indeno[2,1-c]fluorene 22 (Figure 10). Spectro-
scopic data for this product are identical to the data reported
earlier by Youngs and co-workers who achieved the same
transformation through a lithium-induced cyclization.35b
3. Discussion
Initial attack of the tris-aryleneethynylenes system by the
tributyltin radical is sensitive to substitution at the terminal triple
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A R T I C L E S
Figure 11. Competing pathways with calculated activation barriers and reaction energies (kcal mol-1) of the radical cascade cyclization at the UB3LYP/
6-31G**//UB3LYP/3-21G* level.
Figure 12. Transition state structures involved in the cascade reactions shown in Figure 11 calculated at the UB3LYP/3-21G* level along with the incipient
distances for the forming bonds.
bond and can occur at only three positions: the internal triple
bond and either the internal or external carbon of the terminal
alkyne moieties. Only attack at the internal triple bond will lead
to the 5-exo, 6-endo cascade reported in this paper. In alkyne
15, the attack proceeds at the terminal carbon where the
approaching radical species encounter no steric hindrance.
Attack at the internal carbon of the external triple bond of 15
would produce a radical which is not stabilized by the benzylic
resonance. The directing effect of TMS group in 11a is not
surprising since this moiety kinetically deactivates the terminal
alkyne. As a result, the Bu3Sn radical attack proceeds at the
internal triple bond. Much more interesting is the selectivity in
(16) Bharucha, K.; Marsh, R.; Minto, R.; Bergman, R. J. Am. Chem. Soc.
1992, 114, 3120.
(17) (a) Jones, R. R.; Bergman, R. G. J. Am. Chem. Soc. 1972, 94, 660.
(b) Bergman, R. G. Acc. Chem. Res. 1973, 6, 25.
(18) Matzger, A.; Vollhardt, P. Chem. Commun. 1997, 1415.
(19) Lin, C.-F.; Wu, M.-J. J. Org. Chem. 1997, 62, 4546.
(20) Alabugin, I. V.; Manoharan, M. J. Am. Chem. Soc. 2005, 127, 12583.
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(b) Wang, K. K. Chem. ReV. 1996, 96, 207.
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A R T I C L E S
Alabugin et al.
the aryl-substituted triynes where all triple bonds have similar
properties and, thus, attack at the terminal alkyne moiety should
be possible as well. Here the balance is quite subtle, since phenyl
and p-tolyl groups favor Bu3Sn radical attack at the center alkyne
moiety (Figure 7), whereas the p-OMe-Ph substituted tris-alkyne
11d shows a lack of selectivity.
similar steric interactions depopulate the near-attack conforma-
tion of the reactant.
The experimentally observed “internal” preference (path c
of Scheme 4) for the radical attack in tris-alkynes 11b,c may
be explained by reversibility of the Bu3Sn radical addition to
the triple bond and lack of cyclization pathways with comparable
activation energies for the cyclization of vinyl radicals formed
from the two alternative addition paths a and b (Scheme 4).
Note also that cyclizations of a nonconjugated vinyl radical to
an unsaturated system where breaking of a π-bond leads to the
formation of a carbon-carbon σ-bond are exothermic by 20-30
kcal/mol unless the reacting vinyl radical is deactivated by
benzylic or allylic conjugation.20 Thus, the alternative cyclization
steps should be essentially irreversible under the reaction
conditions, and competition between the alternative cyclization
pathways of each of the isomeric vinyl radicals should be under
kinetic control. In this scenario, the effect of the different
stabilities of isomeric radicals on the selectivity should be
described by the Curtin-Hammett principle. The 5-endo and
4-exo-dig cyclizations of the vinyl radical formed through path
b were shown to have a high barrier because the radical orbital
has to rotate out of conjugation with the aromatic system in
order to attack the in-plane π-bond of the alkyne moiety.
Such loss of benzylic conjugation strongly increases the
cyclization barriers as shown in the earlier computational
work and illustrated by the lack of such cyclizations in the
literature.20,40
Although formation of significant amounts of acyclic products
for R ) OMe is surprising especially in contrast with the
efficient cyclization for R ) Me, the regioselectivity of Bu3Sn
addition to the tris-alkyne 11d offers some insight into the
possible origin of this difference. A possible explanation
(consistent with the results of DFT computations) is that the
p-OMe group provides additional stabilization to the radical at
the benzylic position.39 In agreement with such stabilization,
the attack proceeds at the internal carbon of the triple bond. It
is not clear why we do not observe any cyclization products
from the radical in the above step because both 5-exo-dig and
6-endo-dig closure are usually favorable.26 Since the geometry
of aryl substituted vinyl radicals is not far from linear,26a it is
conceivable that destabilizing steric interactions may occur in
the cyclization transition state due to the presence of an aryl
group at the terminal carbon (Scheme 4). It is also possible that
(22) (a) Schmittel, M.; Strittmatter, M.; Kiau, S. Angew. Chem. 1996, 108,
1952. (b) Schmittel, M.; Kiau, S.; Siebert, T.; Strittmatter, M.
Tetrahedron Lett. 1996, 37, 7691. (c) Schreiner, P. R.; Prall, M. J. Am.
Chem. Soc. 1999, 121, 8615.
(23) (a) Ru: Hoven, G. B.; Efskind, J.; Rømming, C.; Undheim, K. J. Org.
Chem., 2002, 67, 2459. (b) Peters, J.-U.; Blechert, S. Chem. Commun.
1997, 1983. Rh: Kinoshita, H.; Shinokubo, H.; Oshima, K. J. Am.
Chem. Soc, 2003, 125, 7784. (d) Pd: Yamamoto, Y.; Nagata, A,
Nagata, H.; Ando, Y.; Arikawa, Y.; Tatsumi, K.; Itoh, K. Chem.sEur.
J. 2003, 9, 2469. (e) Co: Stara, I. G.; Stary, I.; Kollarovic, A.; Teply,
F.; Saman, D.; Tichy, M. J. Org. Chem. 1998, 63, 4046.
(24) Chang, H.-K.; Datta, S.; Das, A.; Odedra, A.; Liu, R.-S. Angew. Chem.,
Int. Ed. 2007, 46, 4744.
(25) Chang, H.-K.; Liao, Y.-C.; Liu, R.-S. J. Org. Chem. 2007, 72, 8139.
(26) (a) Kovalenko, S. V; Peabody, S; Manoharan, M; Clark, R. J; Alabugin,
I. V. Org. Lett. 2004, 6, 2457. (b) For an earlier report of a 5-exo-dig
radical cyclization of enediynes promoted by nitroxyl radicals, see:
Ko¨nig.; B.; Pitsch, W.; Klein, M.; Vasold, R.; Prall, M. Schreiner,
P. R. J. Org. Chem. 2001, 66, 1742. (c) Schreiner, P.; Prall, M.; Lutz,
V. Angew. Chem., Int. Ed. 2003, 42, 5757.
Computational analysis was carried out (at the UB3LYP/6-
31G**//UB3LYP/3-21G* level of theory41,42) in order to gain
better insight into the nature of the potential energy surface for
the proposed radical cascade mechanism and to distinguish
between mechanistic alternatives (Scheme 4, Figures 11, 13).
The first two 5-exo and 6-exo (Figure 11: A f B, B f C)
cyclizations are predicted to be both fast and essentially
irreversible with the respective activation barriers of ∼3 and 6
kcal/mol and exothermicity of ∼30 kcal/mol. The only mecha-
(39) Such electronic effects on radical reactivity and stability are a topic
of resurging interest:(a) Beeson, T. D.; Mastracchio, A.; Hong, J.-B.;
Ashton, K.; MacMillan, D. W. C Science 2007, 316, 582.
(27) (a) Alabugin, I. V.; Kovalenko, S. V. J. Am. Chem. Soc. 2002, 124,
9052. (b) Alabugin, I. V.; Manoharan, M. J. Am. Chem. Soc. 2003,
125, 4495. (c) For a photochemical transformation of enediynes to
fulvenes and indenes, see also: Ramkumar, D.; Kalpana, M.; Varghese,
B.; Sankararaman, S, Jagadeesh, M. N.; Chandrasekhar, J. J. Org.
Chem. 1996, 61, 2247. (d) See also: Whitlock, H. W.; Sandvick, P. E.;
Overman, L. E.; Reichard, P. B. J. Org. Chem. 1969, 34, 879.
(28) Peabody, S.; Breiner, B.; Kovalenko, S. V.; Patil, S.; Alabugin, I. V.
Org. Biomol. Chem. 2005, 3, 218.
(40) Alabugin, I. V.; Manoharan, M. J. Am. Chem. Soc. 2005, 127, 9534.
(41) B3LYP has been shown to provide reaction barriers which agree well
with the experimental values for a number of radical reaction:(a)
Fischer, H.; Radom, L Angew. Chem., Int. Ed 2001, 40, 1340. (b)
Schreiner, P. R.; Navarro-Vazquez, A.; Prall, M. Acc. Chem. Res. 2005,
38, 29. (c) See also: Hrovat, D. A.; Beno, B. R.; Lange, H.; Yoo,
H.-Y.; Houk, K. N.; Borden, W. T. J. Am. Chem. Soc. 1999, 121,
10529. (d) Saettel, N. J.; Wiest, O.; Singleton, D. A.; Meyer, M. P.
J. Am. Chem. Soc. 2002, 124, 11552. (e) Pickard, F. C.; Shepherd,
R. L.; Gillis, A. E.; Dunn, M. E.; Feldgus, S.; Kirschner, K. N.; Shields,
G C.; Manoharan, M.; Alabugin, I. V. J. Phys. Chem. A 2006, 517.
(f) We have reported previously (refs 20, 40) that computational results
for the related radical cyclizations of alkynes at this level are similar
to those obtained with the higher level BD(T)/cc-pVDZ calculations
(BD(T) ) Brueckner Doubles calculation with a triples contribution).
See also: Prall, M.; Wittkopp, A.; Schreiner, P. R. J. Phys. Chem. A
2001, 105, 9265. (g) Schreiner, P. R.; Navarro-Vazquez, A.; Prall,
M. Acc. Chem. Res. 2005, 38, 29. (h) Crawford, T. D.; Kraka, E.;
Stanton, J. F.; Cremer, D. J. Chem. Phys. 2001, 114, 10638. (i) Cramer,
C. J. J. Am. Chem. Soc. 1998, 120, 6261.
(29) See also: Wudl, F.; Bitler, S. P. J. Am. Chem. Soc. 1986, 108, 4685.
(30) Bowles, D. M.; Palmer, G. J.; Landis, C. A.; Scott, J. L.; Anthony,
J. E. Tetrahedron 2001, 57, 3753.
(31) Scott, J. L.; Parkin, S. R.; Anthony, J. E. Synlett 2004, 161.
(32) Lewis, K. D.; Rowe, M. P.; Matzger, A. J. Tetrahedron 2004, 60,
7191.
(33) Kowalik, J.; Tolbert, L. M. J. Org. Chem. 2001, 66, 3229–3231.
(34) Guo, L.; Bradshaw, J. D.; McConville, D. B.; Tessier, C. A.; Youngs,
W. J. Organometallics 1997, 16, 1685.
(35) (a) Youngs, W. J.; Tessier, C. A.; Bradshaw, J. D. Chem. ReV. 1999,
99, 3153. (b) Malaba, D.; Djebli, A.; Chen, L.; Zarate, E. A.; Tessier,
C. A.; Youngs, W. J. Organometallics 1993, 12, 1266.
(36) Huynh, C.; Linstrumelle, G. Tetrahedron 1988, 44, 6337.
(37) (a) Kaneko, T.; Takahashi, M.; Hirama, M. Tetrahedron Lett. 1999,
40, 2015. (b) Semmelhack, M. F.; Sarpong, R. J. Phys. Org. Chem.
2004, 17, 807. (c) Pickard, F. C.; Shepherd, R. L.; Gillis, A. E.; Dunn,
M. E.; Feldgus, S.; Kirschner, K. N.; Shields, G C.; Manoharan, M.;
Alabugin, I. V. J. Phys. Chem. A 2006, 110, 2517. (d) Zeidan, T.;
Kovalenko, S. V.; Manoharan, M.; Alabugin, I. V. J. Org. Chem. 2006,
71, 962.
(42) (a) This level of theory was shown to provide a good compromise
between accuracy and cost in computational analysis of radical
reactions of alkynes: Ahlstro¨m, B, Kraka, E.; Cremer, D. Chem. Phys.
Lett., 2002, 361, 129. (b) For a detailed comparison of results at the
UB3LYP/6-31G**//UB3LYP/3-21G* level with results of full opti-
mization at the UB3LYP/6-31G** level, see Table S1 in the
Supporting Information.
(43) For a detailed analysis of thermodynamic effects at the activation
barriers in this type of reactions, see:(a) Alabugin, I. V.; Manoharan,
M.; Breiner, B.; Lewis, F. J. Am. Chem. Soc. 2003, 125, 9329.
(38) For another “boomerang” radical cascade involving arylsubstituted
alkynes, see ref 3c.
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A R T I C L E S
Scheme 4. Possible and Observed Cascade Cyclization Pathways Resulting from the Three Directions of the Radical Attack at the Three
Triple Bonds
nistic ambiguity arises after the 6-exo cyclization step. At this
point, the vinyl radical can react through one of two alternative
pathways: (a) 1,5 hydrogen abstraction followed by a 5-endo
cyclization (C f E f F) or b) cyclization at a terminal aryl
ring followed by a 1,5 hydrogen shift which rearomatizes the
ring (C f D f F). The former process is endothermic by ∼16
kcal/mol and proceeds via an unconjugated radical, E, through
a relatively high activation barrier (∼25 kcal/mol). In contrast,
the latter (A f B f C f D f F) pathway is much more
favorable energetically. Even taking into account the quantitative
uncertainty of the computational method, the ∼12 kcal/mol
barrier for the formation of D is certainly lower than that for
the formation of E. The 1,5-hydrogen shift producing F is highly
exothermic and has a relatively low barrier because it is assisted
by aromatization.43
Trimethylsilyl substituted tris-alkynes follow the same 5-exo,
6-exo sequence of steps at the initial stage of the radical cascade.
The differences are minor: the cyclizations have slightly higher
activation barriers and are not quite as exothermic because the
R-effect of Si in H and I is less effective in radical stabilization
than benzylic conjugation in B and C (Figure 13). Since, unlike
the intermediate C in Figure 11, the resulting vinyl radical I has
no available cyclization choices, it abstracts a hydrogen from the
TMS group. 5-Endo-trig cyclization of the resulting radical J has
a remarkably low barrier and is highly exothermic because it is
accompanied by aromatization. The last two steps represent the
classic 1,5-radical translocation/cyclization sequence of Curran.44
3.1. Relation to the Preparation of New Graphite
Ribbons. The efficiency of cascade transformations of tris-
alkynes described in this paper suggests that similar cascades
may prove to be useful for the preparation of interesting
conjugated carbon-rich materials such as, in particular, graphite
ribbons. Graphite ribbons are predicted to have very interesting
electronic properties which combine the relatively small band
gap with high switching speeds and carrier mobility.45 Not
surprisingly, a number of synthetic approaches to such ribbons
illustrated in Figure 14 have been developed in recent years.46
However, not all possible types of the ribbons have been
prepared so far, and thus, it is interesting to envision “zipping
up” the sequence of alkyne bonds into a new system shown at
the bottom right corner of Figure 14. Cascades described in
this paper represent the first steps in the proposed approach. In
the present paper, these cascades are terminated through addition
to the terminal aryl group or by H-abstraction only because of
the absence of another triple bond which would provide a much
more favorable 6-exo-cyclization pathway. Comparison of
activation barriers for the 6-exo-dig cyclization and cyclization
at the aromatic ring (5.8 vs 12.3 kcal mol for steps B f C and
C f D respectively in Figure 11) strongly supports that 6-exo-
(44) (a) Curran, D. P.; Xu, J. J. Am. Chem. Soc. 1988, 110, 5900. (b) Curran,
D. P.; Kim, D.; Liu, H. T; Shen, W. J. Am. Chem. Soc. 1988, 110,
5900. (c) See also:, Robertson, J.; Pillai, J.; Lush, R. Chem. Soc. ReV.
2001, 94. (d) Gross, A.; Fensterbank, L.; Bogen, S.; Thouvenot, R.;
Malacria, M. Tetrahedron 1997, 53, 13797. (e) Capella, L.; Mon-
tevecchi, P. C.; Navacchia, M. L. J. Org. Chem. 1996, 61, 6783.
(45) Li, X.; Wang, X; Li, Z.; Lee, S.; Dai, H. Science 2008, 319, 1229.
(46) (a) Goldfinger, M. B.; Swager, T. M. J. Am. Chem. Soc. 1994, 116,
7895. (b) Scherf, U. J. Mater. Chem. 1999, 9, 1853. (c) Berresheim,
A. J.; Mueller, M.; Muellen, K. Chem. ReV. 1999, 99, 1747. (d)
Mallory, F. B.; Butler, K. E.; Berube, A.; Luzik, E. D.; Mallory, C. W.;
Brondyke, E. J.; Hiremath, R.; Ngo, P.; Carroll, P. J. Tetrahedron
2001, 57, 3715.
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A R T I C L E S
Alabugin et al.
Figure 13. Proposed mechanism for the radical cyclization of 2,2′-bis(trimethylsilylethynyl) diphenylacetylene along with the calculated activation barriers
and reaction energies (kcal mol-1) at the UB3LYP/6-31G**//UB3LYP/3-21G* level.
Figure 14. Comparison of known approaches to graphite ribbons with cascade cyclizations of phenyleneethynylenes.
dig cyclization should be much faster than the alternatives and,
thus, the growth of the polycyclic system should continue as
long as the triple bonds at the appropriate position are available.
It is possible that the presence of the additional triple bonds
will require careful control of the chemoselectivity of the initial
radical attack which must occur at the central triple bond in
order for the cascade to involve all alkyne moieties of the
reactant. If necessary, such control can be achieved if a “weak
link”, a chemically orthogonal functional group for selective
radical formation, is introduced near the central alkyne moiety
of the reactant (Figure 14). Formation of a radical center at the
“weak link” will transform the initial cascade initiation step from
an intermolecular to an intramolecular process, thus, solving
the problem of chemoselective initiation of this cascade. The
final bonds between the “outside” phenyl rings can be formed
through the Mallory reaction.47 One can speculate that the length
of the linker should provide us with control of the shape of the
molecule. For example, a five-membered ring in the product
can be used to introduce additional curvature48 reminiscent of
that at the tip of carbon nanotubes (Figure 14). Our research in
identifying and synthesizing such systems is under way.
(47) Mallory, F. B.; Rudolf, M. J.; Oh, S. M. J. Org. Chem. 1989, 54,
4619.
(48) (a) Scott, L. T. Angew. Chem., Int. Ed. Engl. 2004, 43, 4994. (b) See
also: Scott, L. T.; Cheng, P-. C.; Hashemi, M. M. Bratcher, M. S.;
Meyer, D. T.; Warren, H. B. J. Am. Chem. Soc. 1997, 119, 10963. (c)
Necula, A.; Scott, L. T. J. Am. Chem. Soc. 2000, 122, 1548. (d)
Zimmermann, G.; Nuechter, U.; Hagen, S.; Nuechter, M. Tetrahedron
Lett. 1994, 35, 4747. (e) Liu, C. Z.; Rabideau, P. W. Tetrahedron
Lett. 1996, 37, 3437. (f) Seiders, T. J.; Baldridge, K. K.; Siegel, J. S.
J. Am. Chem. Soc. 1996, 118, 2754.
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A R T I C L E S
4. Conclusions
Research Fund, administered by the American Chemical Society
(Award No. 47590-AC4) for partial support of this research.
In summary, we have developed a new mild, chemo- and
regioselective transformation of conjugated acyclic triynes to
polycyclic systems via a radical cascade process which involves
formation of four new σ-bonds. The products can be either
destannylated with the relatively mild conditions described
above or, potentially, utilized in further reactions such as Stille
cross-coupling.
Supporting Information Available: Detailed comparison of
computational data for 5-exo-dig and 6-endo-dig radical cy-
clizations of vinyl and aryl radicals at the UB3LYP/6-31G**
and UB3LYP/6-31G**//3-21G* levels. Full experimental pro-
1
cedures, spectral data including H and 13C NMR, MS, and
X-ray crystallography data. This material is available free of
charge via the Internet at http://pubs.acs.org.
Acknowledgment. I.A. is grateful to the National Science
Foundation (CHE-0316598) and to the donors of Petroleum
JA8038213
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