Synthesis of [5]-, [6]-, and [7]helicene via Ni(0)- or Co(I)-catalyzed isomerization of aromatic cis,cis-dienetriynes

Article abstract of DOI:10.1021/ja0259584

An original approach to helicene frameworks exploiting atom economic isomerization of appropriate energy-rich aromatic cis,cis-dienetriynes has been developed. The new paradigm provides nonphotochemical syntheses of helicenes based on the easy, convergent, and modular assembly of key cis,cis-dienetriynes and their nickel(0)-catalyzed [2+2+2] cycloisomerization. The potential of the methodology is underlined by the syntheses of the parent [5]helicene (2), 7,8-dibutyl[5]helicene (23), [6]helicene (24), and [7]helicene (25). The approach can be adapted to prepare functionalized helicenes as exemplified by the eight-step synthesis of 7,8-dibutyl-2,3-dimethoxy[6]helicene (34). Density functional theory (DFT) calculations showed that bis[2-((1Z)-1-buten-3- ynyl)phenyl]acetylene (1) and isomeric [5]helicene (2) differ enormously in the Gibbs energy content (ΔG= -136.6 kcal.mol^-1) to favor highly the devised intramolecular simultaneous construction of three aromatic rings.

Full text of DOI:10.1021/ja0259584

Published on Web 07/13/2002
Synthesis of [5]-, [6]-, and [7]Helicene via Ni(0)- or
Co(I)-Catalyzed Isomerization of Aromatic cis,cis-Dienetriynes
Filip Teply´, Irena G. Stara´,* Ivo Stary´,* Adrian Kolla´rovicˇ, David Sˇ aman,
Lubom´ır Rul´ısˇek,† and Pavel Fiedler
Contribution from the Institute of Organic Chemistry and Biochemistry and Center for Complex
Molecular Systems and Biomolecules, Academy of Sciences of the Czech Republic,
FlemingoVo na´m. 2, 166 10 Prague 6, Czech Republic
Received February 18, 2002
Abstract: An original approach to helicene frameworks exploiting atom economic isomerization of
appropriate energy-rich aromatic cis,cis-dienetriynes has been developed. The new paradigm provides
nonphotochemical syntheses of helicenes based on the easy, convergent, and modular assembly of key
cis,cis-dienetriynes and their nickel(0)-catalyzed [2+2+2] cycloisomerization. The potential of the methodol-
ogy is underlined by the syntheses of the parent [5]helicene (2), 7,8-dibutyl[5]helicene (23), [6]helicene
(24), and [7]helicene (25). The approach can be adapted to prepare functionalized helicenes as exemplified
by the eight-step synthesis of 7,8-dibutyl-2,3-dimethoxy[6]helicene (34). Density functional theory (DFT)
calculations showed that bis[2-((1Z)-1-buten-3-ynyl)phenyl]acetylene (1) and isomeric [5]helicene (2) differ
enormously in the Gibbs energy content (∆G ) -136.6 kcal.mol-1) to favor highly the devised intramolecular
simultaneous construction of three aromatic rings.
Introduction
on pure atom economic isomerization of appropriate energy-
rich aromatic cis,cis-dienetriynes under transition metal catalysis.
Isomerizations, besides ultimate addition reactions, perfectly
fulfill criteria of atom economy1 and, when cleverly used,2
reflect art in organic synthesis. The simple, photochemically
mediated isomerization of stilbene-like precursors to ortho fused
aromatics3 is almost in full harmony with this concept, but it
has been hampered by fundamental drawbacks to evolve into a
really convenient method for preparing helicenes.4 Despite
further remarkable progress in helicene chemistry that has been
recorded in the past decade,5 namely due to the revolutionary
Diels-Alder approach invented and exploited by Katz,6 the task
of developing novel strategies for the preparation of helicenes
remains a challenge to state-of-the-art synthesis. In this paper,
we report an original approach to helicene frameworks based
Results and Discussion
Devising Helicene Precursors. Being inspired by photode-
hydrocyclization of cis/trans-1,2-diaryl ethenes relying on the
UV-mediated six-electron electrocyclization followed by in situ
oxidation, we sought a similar but more efficient alternative
pathway based on a simple isomerization of a suitable precursor
under transition metal catalysis to build up a helicene frame-
work. As the preparation of [5]helicene 2 (Scheme 1) might be
called a “benchmark process” in helicene chemistry to test the
(5) For recent nonphotochemical syntheses, see: (a) Carreno, M. C.; Garcia-
Cerrada, S.; Urbano, A. J. Am. Chem. Soc. 2001, 123, 7929. (b) Carreno,
M. C.; Garcia-Cerrada, S.; Sanz-Cuesta, M. J.; Urbano, A. Chem. Commun.
2001, 1452. (c) Okubo, H.; Nakano, D.; Anzai, S.; Yamaguchi, M. J. Org.
Chem. 2001, 66, 557. (d) Eskildsen, J.; Krebs, F. C.; Faldt, A.; Sommer-
Larsen, P.; Bechgaard, K. J. Org. Chem. 2001, 66, 200. (e) Murguly, E.;
McDonald, R.; Branda, N. R. Org. Lett. 2000, 2, 3169. (f) Okubo, H.;
Nakano, D.; Yamaguchi, M.; Kabuto, C. Chem. Lett. 2000, 1316. (g)
Modlerspreitzer, A.; Fritsch, R.; Mannschreck, A. Collect. Czech Chem.
Commun. 2000, 65, 555. (h) Minuti, L.; Taticchi, A.; Marrocchi, A.; Gacs-
Baitz, E.; Galeazzi, R. Eur. J. Org. Chem. 1999, 3155. (i) Carreno, M. C.;
Herna´ndez-Sa´nchez, R.; Mahugo, J.; Urbano, A. J. Org. Chem. 1999, 64,
1387. (j) Stara´, I. G.; Stary´, I.; Kolla´rovicˇ, A.; Teply´, F.; Vyskocˇil, Sˇ.;
Sˇaman, D. Tetrahedron Lett. 1999, 40, 1993. (k) Gingras, M.; Dubois, F.
Tetrahedron Lett. 1999, 40, 1309. (l) Dubois, F.; Gingras, M. Tetrahedron
Lett. 1998, 39, 5039. (m) Okubo, H.; Yamaguchi, M.; Kabuto, C. J. Org.
Chem. 1998, 63, 9500. (n) Minuti, L.; Taticchi, A.; Marrocchi, A. Synth.
Commun. 1998, 28, 2181. (o) Tanaka, K.; Suzuki, H.; Osuga, H. J. Org.
Chem. 1997, 62, 4465. (p) Tanaka, K.; Suzuki, H.; Osuga, H. Tetrahedron
Lett. 1997, 38, 457. (q) Minuti, L.; Taticchi, A.; Marrocchi, A.; Gacs-
Baitz, E. Tetrahedron 1997, 53, 6873. (r) Cossu, S.; De Lucchi, O.; Fabbri,
D.; Valle, G.; Painter, G. F.; Smith, A. J. Tetrahedron 1997, 53, 6073. (s)
Pischel, I.; Grimme, S.; Kotila, S.; Nieger, M.; Vo¨gtle, F. Tetrahedron:
Asymmetry 1996, 7, 109. (t) Larsen, J.; Bechgaard, K. J. Org. Chem. 1996,
61, 1151. (u) Yamaguchi, M.; Okubo, H.; Hirama, M. Chem. Commun.
1996, 1771. (v) Dore, A.; Fabbri, D.; Gladiali, S.; Valle, G. Tetrahedron:
Asymmetry 1995, 6, 779. (w) Stara´, I. G.; Stary´, I.; Tichy´, M.; Za´vada, J.;
Hanusˇ, V. J. Am. Chem. Soc. 1994, 116, 5084.
* Corresponding author. E-mail: stary@uochb.cas.cz.
† Center for Complex Molecular Systems and Biomolecules.
(1) (a) Sheldon, R. A. Chem. Ind. 1997, 12. (b) Trost, B. M. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 259. (c) Sheldon, R. A. CHEMTECH 1994, 24,
38. (d) Trost, B. M. Science 1991, 254, 1471.
(2) Akutagawa, S.; Tani, K. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima,
I., Ed.; Wiley-VCH: New York, 2000; Chapter 3, p 145.
(3) For reviews, see: (a) Laarhoven, W. H. In Organic Photochemistry; Padwa,
A., Ed.; Marcel Dekker: New York, 1989; Vol. 10, p 163. (b) Mallory, F.
B.; Mallory, C. W. Org. React. 1984, 30, 1. (c) Floyd, A. J.; Dyke, S. F.;
Ward, S. E. Chem. ReV. 1976, 76, 509. For pioneering and pivotal papers,
see: (d) Liu, L.; Yang, B.; Katz, T. J.; Poindexter, M. K. J. Org. Chem.
1991, 56, 3769. (e) Flammang-Barbieux, M.; Nasielski, J.; Martin, R. H.
Tetrahedron Lett. 1967, 743. (f) Mallory, F. B.; Wood, C. S.; Gordon, J.
T.; Lindquist, L. C.; Savitz, M. L. J. Am. Chem. Soc. 1962, 84, 4361. (g)
Parker, C. O.; Spoerri, P. E. Nature 1950, 166, 603.
(4) For reviews, see: (a) Katz, T. J. Angew. Chem., Int. Ed. Engl. 2000, 39,
1921. (b) Osuga, H.; Suzuki, H. J. Synth. Org. Chem., Jpn. 1994, 52, 1020.
(c) Oremek, G.; Seiffert, U.; Janecka, A. Chem.-Ztg. 1987, 111, 69. (d)
Vo¨gtle, F. Fascinating Molecules in Organic Chemistry; Wiley: New York,
1992; p 156. (e) Meurer, K. P.; Vo¨gtle, F. Top. Curr. Chem. 1985, 127, 1.
(f) Laarhoven, W. H.; Prinsen, W. J. C. Top. Curr. Chem. 1984, 125, 63.
(g) Martin, R. H. Angew. Chem. 1974, 86, 727. (h) Wynberg, H. Acc. Chem.
Res. 1971, 4, 65.
9
10.1021/ja0259584 CCC: $22.00 © 2002 American Chemical Society
J. AM. CHEM. SOC. 2002, 124, 9175-9180
9175

A R T I C L E S
Teply´ et al.
Scheme 1. Calculated Gibbs Energy Content of
cis,cis-Dienetriyne 1 and [5]Helicene 2
Scheme 2. Preparation of cis,cis-Dienetriynes 1 and 9a
feasibility of a synthetic strategy,7 we proposed the model
isomeric cis,cis-dienetriyne 1 as a potential precursor of [5]-
helicene 2.
Computational Study. For the reaction 1 f 2 in tetrahy-
drofuran, the value of ∆G0298(THF) ) -136.6 kcal‚mol-1 has
been calculated (for details, see the Experimental Section). It
can be decomposed into three significant contributions: ∆E )
-148.0 kcal‚mol-1 (difference between potential energies of
reactant and product), ∆G0298(gas phase) - ∆E ) 14.3
kcal‚mol-1 (difference in the gas-phase corrections to Gibbs
energy), and ∆Gsolv ) -2.9 kcal‚mol-1 (difference in the
solvation energies of reactant and product in tetrahydrofuran).
It can be seen that dominant energy contribution comes from
the decay of three triple bonds and the formation of three
aromatic rings.8 The calculations support the idea of “energy-
rich” intermediate 1 and demonstrate that its conversion into
[5]helicene 2 is thermodynamically highly favored.9
a Conditions: (a) TIPS-CtCH (1.0 equiv), Pd(PPh3)4 (5%), CuI (10%),
iPr2NH, 0 °C to room temperature, 2 h, 99%. (b) nBu-CtCH (2.1 equiv),
i
Pd(PPh
3)4 (5%), CuI (10%), Pr2NH, 0 °C to room temperature, 12 h, 99%.
t
(c) BuLi (2.0 equiv), ether, -90 °C, 10 min, then I2 (1.7 equiv), -90 °C,
10 min, 98%. (d) BuLi (2.0 equiv), ether, -90 °C, 10 min, then I2 (1.7
t
equiv), -90 °C, 10 min, 97%. (e) HCtCH (gaseous), Pd(PPh3)4 (5%), CuI
(10%), piperidine, room temperature, 3 h, 79%. (f) HCtCH (gaseous),
Pd(PPh3)4 (5%), CuI (10%), piperidine, room temperature, 1 h, 78%. (g)
nBu4NF (2.4 equiv), THF, room temperature, 5 min, 71%. (h) TMS-CtCH
(1.1 equiv), Pd(PPh3)4 (5%), CuI (10%), iPr2NH, room temperature, 50 min,
99%. (i) CH3ONa (2.4 equiv), methanol, room temperature, 2 h, 98%.
(6) For the syntheses of helicenes and heterohelicenes based on Diels-Alder
approach, see: (a) Phillips, K. E. S.; Katz, T. J.; Jockusch, S.; Lovinger,
A. J.; Turro, N. J. J. Am. Chem. Soc. 2001, 123, 11899. (b) Weix, D. J.;
Dreher, S. D.; Katz, T. J. J. Am. Chem. Soc. 2000, 122, 10027. (c) Paruch,
K.; Vyklicky´, L.; Katz, T. J.; Incarvito, C. D.; Rheingold, A. L. J. Org.
Chem. 2000, 65, 8774. (d) Paruch, K.; Katz, T. J.; Incarvito, C.; Lam, K.
C.; Rhatigan, B.; Rheingold, A. L. J. Org. Chem. 2000, 65, 7602. (e)
Thongpanchang, T.; Paruch, K.; Katz, T. J.; Rheingold, A. L.; Lam, K. C.;
Liablesands, L. J. Org. Chem. 2000, 65, 1850. (f) Dreher, S. D.; Katz, T.
J.; Lam, K. C.; Rheingold, A. L. J. Org. Chem. 2000, 65, 815. (g) Dreher,
S. D.; Paruch, K.; Katz, T. J. J. Org. Chem. 2000, 65, 806. (h) Fox, J. M.;
Katz, T. J.; Van Elshocht, S.; Verbiest, T.; Kauranen, M.; Persoons, A.;
Thongpanchang, T.; Krauss, T.; Brus, L. J. Am. Chem. Soc. 1999, 121,
3453. (i) Nuckolls, C.; Katz, T. J.; Katz, G.; Collings, P. J.; Castellanos,
L. J. Am. Chem. Soc. 1999, 121, 79. (j) Dreher, S. D.; Weix, D. J.; Katz,
T. J. J. Org. Chem. 1999, 64, 3671. (k) Fox, J. M.; Katz, T. J. J. Org.
Chem. 1999, 64, 302. (l) Nuckolls, C.; Katz, T. J. J. Am. Chem. Soc. 1998,
120, 9541. (m) Fox, J. M.; Goldberg, N. R.; Katz, T. J. J. Org. Chem.
1998, 63, 7456. (n) Katz, T. J.; Liu, L. B.; Willmore, N. D.; Fox, J. M.;
Rheingold, A. L.; Shi, S. H.; Nuckolls, C.; Rickman, B. H. J. Am. Chem.
Soc. 1997, 119, 10054. (o) Dai, Y. J.; Katz, T. J. J. Org. Chem. 1997, 62,
1274. (p) Nuckolls, C.; Katz, T. J.; Castellanos, L. J. Am. Chem. Soc. 1996,
118, 3767. (q) Dai, Y. J.; Katz, T. J.; Nichols, D. A. Angew. Chem., Int.
Ed. Engl. 1996, 35, 2109. (r) Shi, S.; Katz, T. J.; Yang, B. V.; Liu, L. J.
Org. Chem. 1995, 60, 1285. (s) Willmore, N. D.; Hoic, D. A.; Katz, T. J.
J. Org. Chem. 1994, 59, 1889. (t) Willmore, N. D.; Liu, L. B.; Katz, T. J.
Angew. Chem., Int. Ed. Engl. 1992, 31, 1093. (u) Liu, L.; Katz, T. J.
Tetrahedron Lett. 1990, 31, 3983.
Despite the encouraging fact that thermodynamic factors stood
on our side, the basic questions about synthetic availability/
stability of energy-rich, fully unsaturated cis,cis-dienetriynes and,
most importantly, about kinetics of the key isomerization to
helicenes under transition metal catalysis primarily still has to
be answered.
Synthesis of cis,cis-Dienetriynes. The synthesis of cis,cis-
dienetriynes 1 and 9 began from known cis-dibromide 3
(Scheme 2).10 Sonogashira coupling with TIPS-CtCH or
nBu-CtCH proceeded smoothly under Pd0/CuI catalysis with
excellent regioselectivity at the vinyl part of 3 to deliver cis-
enyne 4 and 6, respectively. To ensure further clean Sonogashira
coupling with acetylene or TMS-CtCH without participation
of the ortho enyne moiety, we converted bromide 4 and 6 to
t
iodide 5 and 7, respectively, by routine lithiation with BuLi
and subsequent quenching aryllithiums with iodine. Then, on
reaction with gaseous acetylene under Pd0/CuI catalysis, we
obtained the symmetrical cis,cis-dienetriynes 8 and 9. Smooth
desilylation of 8 with nBu4NF ensued to provide cis,cis-
dienetriyne 1. In addition, iodide 5 was treated with TMS-Ct
CH under Pd0/CuI catalysis to afford cis-endiyne 10. The
(7) Synthesis of parent pentahelicene 2 by photocyclization of stilbene-type
precursors is difficult without using a bromine auxiliaries trick, see: (a)
Liu, L.; Katz, T. J. Tetrahedron Lett. 1991, 32, 6831. For other preparations
of pentahelicene 2, see refs 5j-l,w and: (b) Bestmann, H. J.; Both, W.
Chem. Ber. 1974, 107, 2923. (c) Bestmann, H. J.; Both, W. Angew. Chem.
1972, 84, 293. (d) Mukharji, P. C.; Ray, S. B.; Ghosh, A. Indian J. Chem.
1971, 408. (e) Bestmann, H. J.; Armsen, R.; Wagner, H. Chem. Ber. 1969,
102, 2259. (f) Altman, Y.; Ginsburg, D. J. Chem. Soc. 1959, 466.
(8) The studied reaction is anisodesmic. The local electronic environments of
most of the atoms change significantly in the course of the reaction.
Therefore we carried out model calculations for the simple reaction (3C2H2
f C6H6) to ascertain the accuracy of the calculated data. It was found that
the ∆E value calculated at B3LYP/6-311++G(d,p) level (∆E ) -151.7
kcal‚mol-1) was in a very good agreement with reference CCSD(T)/6-
311++G(d,p) values (∆E ) -148.6 kcal‚mol-1). The B3LYP method
performed even better than MP2/6-311++G(d,p), which yielded ∆E )
-153.6 kcal‚mol-1. In this respect, we consider the adopted computational
scheme as reasonably accurate and estimate the error in the calculated value
(9) The difference between the potential energy ∆E ) -148.0 kcal‚mol-1 for
the simultaneous formation of three aromatic rings in 2 and the enthalpy
value ∆H ) -143.1 kcal‚mol-1 (calculated from tabulated data, see ref
24) for the formation of benzene from three acetylenes is not so significant
as expected. This incongruity may be attributed to the presence of a torsional
strain in pentahelicene 2. Its value calculated at the B3LYP/6-31+G(d)
level as the difference in thermodynamic stability of 2 and picene is 11.9
kcal‚mol-1, in agreement with the previous findings of Schulman for [n]-
helicenes and [n]phenacenes (ref 25).
(10) cis-Bromide 3 was readily available from commercial trans-2-bromocin-
namic acid in two steps, see: (a) Yasuike, S.; Shiratori, S.-I.; Kurita, J.;
Tsuchiya, T. Chem. Pharm. Bull. 1999, 47, 1108. (b) Tietze, L. F.; Noebel,
T.; Spescha, M. J. Am. Chem. Soc. 1998, 120, 8971.
of ∆G0298(THF) for reaction 1 f 2 to be 5-10 kcal‚mol-1
.
9
9176 J. AM. CHEM. SOC. VOL. 124, NO. 31, 2002

Synthesis of [5]-, [6]-, and [7]Helicene
A R T I C L E S
Scheme 3. Preparation of cis,cis-Dienetriynes 20 and 22a
leaving the bromine atom at naphthalene untouched. Then the
regioselective Pd0/CuI-catalyzed Sonogashira coupling with
TIPS-CtCH gave cis-enyne 15. The synthesis of its more
reactive iodo analogue 16 was accomplished by routine halogene
exchange with use of the tBuLi-metalation/iodination protocol.
Similarly, cis-vinyl bromide 14 was regioselectively coupled
with nBu-CtCH to give cis-enyne 17 and the following
bromine-to-iodine displacement delivered cis-enyne 18 that was
further utilized in the synthesis of functionalized [6]helicene
34, vide infra.
Having prepared the suitable building blocks 11 and 16, vide
supra, we could assemble the model cis,cis-dienetriynes 20 and
22. Starting from the same cis-enyne 16, the Pd0/CuI-catalyzed
reaction with cis-endiyne 11 provided the cross-coupled cis,cis-
dienetriyne 19 while the reaction with gaseous acetylene led to
the homo-coupled cis,cis-dienetriyne 21. Finally, deprotection
of terminal acetylene units at 19 and 21 with nBu4NF delivered
the free cis,cis-dienetriyne 20 and 22, respectively.
Isomerization of cis,cis-Dienetriynes to Helicenes. The
[2+2+2] cycloisomerization of alkynes under transition metal
catalysis to deliver benzene derivatives is a well-established
synthetic tool.14 As the isomerization of cis,cis-dienetriynes to
helicenes was proposed to follow this mechanistic pathway, we
focused on Co(I) and Ni(0) catalysis like that recently applied
to the synthesis of helicene-like15 and tetrahydrohelicene5j
molecules.
Initial attempts to isomerize 1 with Co2(CO)8 provided only
tiny amounts of pentahelicene 2 (Table 1, entry 1) because an
undesirable polymerization of the starting material occurred.
Changing the catalyst to CpCo(CO)2/PPh3 improved the yield
slightly (Table 1, entry 2). Stoichiometric amounts of CpCo-
(CO)2 gave only a moderate yield of 2 (Table 1, entry 3).
Accordingly, we turned our attention to nickel(0) catalysis,
which is usually swifter than cobalt catalysis when six-
membered rings are closed.5j Indeed, adding an equimolar
amount of Ni(cod)2 to 1 gave an instantaneous reaction and led
to pentahelicene 2 in high yield (Table 1, entry 4). Gratifyingly,
catalytic amounts of Ni(cod)2 also produced 2 in good yield
(Table 1, entry 5). The results with nonterminal cis,cis-
dienetriyne 9 were similar. It was smoothly cycloisomerized to
bisalkylated pentahelicene 23 (Table 1, entry 6).
a Conditions: (a) CBr4 (2.0 equiv), PPh3 (2.0 equiv), Zn (2.0 equiv),
CH2Cl2, room temperature, 14 h, 85%. (b) nBu3SnH (1.5 equiv), Pd(PPh3)4
(5%), toluene, room temperature, 3 h, 80%. (c) TIPS-CtCH (1.1 equiv),
i
Pd(PPh3)4 (5%), CuI (10%), Pr2NH, 0 °C to room temperature, 25 min,
n
i
99%. (d) Bu-CtCH (1.1 equiv), Pd(PPh3)4 (5%), CuI (10%), Pr2NH, 0
°C to room temperature, 1.5 h, 86%. (e) tBuLi (2.0 equiv), ether, -90 °C,
t
5 min, then I2 (1.7 equiv), -90 °C, 10 min, 96%. (f) BuLi (2.0 equiv),
ether, -90 °C, 5 min, then I2 (1.7 equiv), -90 °C, 10 min, 94%. (g) 11
i
(1.0 equiv), Pd(PPh3)4 (5%), CuI (10%), Pr2NH, room temperature, 2 h,
99%. (h) nBu4NF (2.4 equiv), THF, room temperature, 5 min, 87%. (i)
HCtCH (gaseous), Pd(PPh3)4 (2.5%), CuI (5%), piperidine, 80 °C, 0.5 h,
n
57%. (j) Bu4NF (2.4 equiv), THF, room temperature 5 min, 63%.
selective removal of the TMS group by CH3ONa accomplished
the preparation of the building block 11 that was further used
in the synthesis of cis,cis-dienetriyne 20, vide infra.
Encouraged by the easy formation of the pentahelicene
backbone, we focused our attention on the synthesis of higher
homologues. In the presence of a stoichiometric amount of
Ni(0) complex, a smooth cycloisomerization of both 20 and 22
proceeded to deliver hexahelicene 24 (ref 16) and heptahelicene
The synthesis of cis,cis-dienetriynes 20 and 22 relied on a
very similar strategy. Starting from known bromo aldehyde 12
(ref 11), we had to install the cis-enyne moiety (Scheme 3).
The Corey-Fuchs olefination12 led to tribromide 13 that was
subjected to regio- and stereoselective hydrogenolysis on
(14) For reviews, see: (a) Saito, S.; Yamamoto, Y. Chem. ReV. 2000, 100, 2901.
(b) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49. (c) Grotjahn,
D. B. In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone,
F. G. A., Wilkinson, G., Eds.; Hegedus, L. S., Volume Ed.; Elsevier
Science: Oxford, 1995; Vol. 12, Chapter 7.3, p 741. (d) Schore N. E. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L.
A., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, Chapter 9.4, p 1129. (e)
Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539.
n
treatment with Bu3SnH under Pd0 catalysis according to the
Uenishi-Tsuji procedure13 to furnish cis-vinyl bromide 14,
(11) For preparation of 12, see: (a) Clayden, J.; McCarthy, C.; Westlund, N.;
Frampton, C. S. J. Chem. Soc., Perkin Trans. 1 2000, 1363. (b) Grissom,
J. W.; Klingberg, D.; Meyenburg, S.; Stallman, B. L. J. Org. Chem. 1994,
59, 7876. (c) Rawal, V. H.; Florjancic, A. S.; Singh, S. P. Tetrahedron
Lett. 1994, 35, 8985. (d) Smith, J. G.; Dibble, P. W.; Sandborn, R. E. J.
Org. Chem. 1986, 51, 3762. (e) Weber, E.; Csoregh, I.; Stensland, B.;
Czugler, M. J. Am. Chem. Soc. 1984, 106, 3297. (f) Trost, B. M.; Liu,
G.-J. J. Org. Chem. 1981, 46, 4617.
(12) (a) Scott, L. T.; Cooney, M. J.; Otte, C.; Puls, C.; Haumann, T.; Boese, R.;
Carroll, P. J.; Smith, A. B., III; de Meijere, A. J. Am. Chem. Soc. 1994,
116, 10275. (b) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769.
(13) Uenishi, J.; Kawahama, R.; Yonemitsu, O.; Tsuji, J. J. Org. Chem. 1998,
63, 8965.
(15) (a) Stara´, I. G.; Stary´, I.; Kolla´rovicˇ, A.; Teply´, F.; Sˇaman, D.; Tichy´, M.
J. Org. Chem. 1998, 63, 4046. (b) Stara´, I. G.; Stary´, I.; Kolla´rovicˇ, A.;
Teply´, F.; Sˇaman, D.; Tichy´, M. Chimia 1997, 51, 378.
(16) For preparation of parent hexahelicene 24, see: (a) Brown, J. M.; Field, I.
P.; Sidebottom, P. J. Tetrahedron Lett. 1981, 22, 4867. (b) Borkent, J. H.;
Diesveld, J. W.; Laarhoven, W. H. Recl.: J. R. Neth. Chem. Soc. 1981,
100, 114. (c) Hibert, M.; Solladie, G. J. Org. Chem. 1980, 45, 5393. (d)
Newman, M. S.; Lednicer, D. J. Am. Chem. Soc. 1956, 78, 4765.
(17) For preparation of parent heptahelicene 25, see ref 5k and: (a) Sudhakar,
A.; Katz, T. J. Tetrahedron Lett. 1986, 27, 2231. (b) Corsane, M.; Defay,
N.; Martin, R. H. Bull. Soc. Chim. Belg. 1985, 94, 215. (c) Martin, R. H.;
Schurter, J. J. Tetrahedron 1972, 28, 1749. (d) Laarhoven, W. H.; Cuppen,
T. J. H. M.; Nivard, R. J. F. Tetrahedron 1970, 26, 4865.
9
J. AM. CHEM. SOC. VOL. 124, NO. 31, 2002 9177

A R T I C L E S
Teply´ et al.
Table 1. [2+2+2] Cycloisomerization of cis,cis-Dienetriynes
Scheme 4. Synthesis of Substituted [6]Helicene 34a
a Conditions: (a) CBr4 (2.0 equiv), PPh3 (2.0 equiv), Zn (2.0 equiv),
CH2Cl2, room temperature, 17 h, 99%. (b) nBu3SnH (1.2 equiv), Pd(PPh3)4
(5%), toluene, room temperature, 10 h, 72%. (c) nBu-CtCH (1.5 equiv),
a The reactions mediated by Co complexes were run in dioxane at 80-
90 °C (entries 1 and 2) or in decane at 140 °C (entry 3) until the educt
disappeared (1-22 h). When CpCo(CO)2 was used, the reaction mixture
was irradiated by a halogen lamp. b The reactions mediated by Ni(cod)2
were run in THF at room temperature until the educt disappeared (5-15
min). c Isolated.
i
t
Pd(PPh3)4 (5%), CuI (10%), Pr2NH, 40 °C, 15 min, 95%. (d) BuLi (2.0
equiv), ether, -90 °C, 5 min, then I2 (1.7 equiv), -90 °C, 30 min, 81%.
i
(e) TMS-CtCH (1.4 equiv), Pd(PPh3)4 (5%), CuI (10%), Pr2NH, room
temperature 30 min, 77%. (f) CH3ONa (2.4 equiv), methanol, room
temperature, 4.5 h, 99%. (g) 18 (0.98 equiv), Pd(PPh3)4 (5%), CuI (10%),
iPr2NH, room temperature, 1 h, 91%. (h) Ni(cod)2 (20%), PPh3 (40%), THF,
room temperature, 15 min, 61%.
25 (ref 17), respectively, in excellent or good yield (Table 1,
entries 7 and 9). Under catalytic conditions, the yields of 24
and 25 were also reasonable (Table 1, entries 8 and 10). Note,
in all cases helicenes were formed as the only low molecular
weight products and they were easily separable from the reaction
mixture by flash chromatography.
digm for the nonphotochemical preparation of parent [5]-, [6]-,
and [7]helicenes. Its bases are the easy, convergent, and modular
assembly of energy-rich cis,cis-dienetriynes and the high
susceptibility of these materials to cyclize to helicenes. It can
be applied to synthesize functionalized helicenes. Further studies
are therefore underway to extend the syntheses so they give
helicenes that are substituted in other ways and helicenes that
are nonracemic.
Synthesis of Functionalized Helicenes. To establish the
scope of this new approach to helicenes, we embarked on a
synthesis of the functionalized [6]helicene 34 (Scheme 4).
Starting from commercially available aldehyde 26, we followed
the modular approach developed for the unsubstituted cis,cis-
dienetriynes 1, 9, 20, and 22. Dibromoolefination led smoothly
to 27, which was stereoselectively dehalogenated to provide cis-
vinyl bromide 28. Regioselective coupling with 1-hexyne
afforded cis-enyne 29, which has a nonterminal acetylene unit.
Accordingly, after a halogene exchange, iodide 30 could be
coupled with TMS-CtCH to give endiyne 31. In this reaction,
the pendant butyl-substituted acetylene unit participated in
undesirable Heck addition to a very low extent, and so pure 31
could be isolated by flash chromatography in good yield.
Removal of the TMS group furnished 32, which was coupled
with naphthyl iodide 18 to deliver the key cis,cis-dienetriyne
33. No significant Heck addition interfered. In the final step,
Ni(0)/PPh3 catalyst instantaneously cyclized dienetriyne 33 to
substituted [6]helicene 34 in 61% yield.
Experimental Section
Computational Details. The calculations were performed with a
Gaussian 98 program package18 in the framework of density functional
theory (B3LYP functional).19 Two standard basis sets have been used
throughout the calculations: 6-31+G(d) (ref 20) and 6-311++G(2p,d)
(ref 21). The optimizations of molecular geometries and vibrational
analyses have been carried out at the B3LYP/6-31+G(d) and single
point electronic energies computed at the B3LYP/6-311++G(p,d) level.
The computed vibrational frequencies have been used for the subsequent
thermochemistry calculations, preformed according to the standard
(18) Frisch, M. J. et al. Gaussian 98, Revision A.7; Gaussian, Inc.: Pittsburgh,
PA, 1998.
(19) (a) Becke, A. D. Phys. ReV. A 1988, 38, 3098. (b) Lee, C.; Yang, W.; Parr,
R. G. Phys. ReV. B 1988, 37, 785. (c) Vosko, S. H.; Wilk, L.; Nusair, M.
Can. J. Phys. 1980, 58, 1200.
(20) (a) Hehre, W. J.; Ditchfield, R.; Pople, J. A. J. Chem. Phys. 1972, 56,
2257. (b) Gordon, M. S. Chem. Phys. Lett. 1980, 76, 163.
(21) (a) McLean, A. D.; Chandler, G. S. J. Chem. Phys. 1980, 72, 5639. (b)
Krishnan, R.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980,
72, 650.
Conclusions
In summary, the nickel(0)-catalyzed [2+2+2] cycloisomer-
ization of aromatic cis,cis-dienetriynes represents a new para-
9
9178 J. AM. CHEM. SOC. VOL. 124, NO. 31, 2002

Synthesis of [5]-, [6]-, and [7]Helicene
A R T I C L E S
formulas of statistical thermodynamics in the ideal gas approximation.
In this way, ∆G0gas values have been obtained. Solvation Gibbs energies,
∆Gsolv, for reactant and product have been computed in the framework
of the PCM reaction field model of Tomasi.22 The standard dielectric
constant for tetrahydrofuran has been used (ꢀr ) 7.58). The reference
calculations of a simple model reaction described in ref 8 were carried
out by using a very accurate CCSD(T) method.23
Procedure for Corey-Fuchs Olefination of 12 and 26. Triph-
enylphosphine (525 mg, 2.0 mmol, 2.0 equiv) in dichloromethane (5
mL) was added to a mixture of tetrabromomethane (663 mg, 2.0 mmol,
2.0 equiv) and zinc powder (131 mg, 2.0 mmol, 2.0 equiv) in
dichloromethane (3 mL) under argon. After the mixture was stirred at
room temperature for 30 min, aldehyde (1.0 mmol) in dichloromethane
(5 mL) was added and the suspension was stirred at room temperature
for 14-17 h. The crude reaction mixture was passed through a short
pad of silica gel using dichloromethane, the solution was evaporated
in vacuo to dryness, and the residue was chromatographed on silica
gel to get the product.
Procedure for Sonogashira Coupling of Aryl Iodides 5, 16, 18,
and 30 or Vinyl Bromides 3, 14, and 28 with nBu-, TMS-, or
TIPS-CtCH or Aryl Acetylenes 11 and 32. A Schlenk flask was
charged with aryl or vinyl halide (1.0 mmol), Pd(PPh3)4 (58 mg, 0.050
mmol, 5 mol %), and CuI (19 mg, 0.100 mmol, 10 mol %) and flushed
with argon. Diisopropylamine (10-15 mL) was added and the reaction
mixture was briefly heated under stirring to 40-50 °C and then cooled
Procedure for Stereoselective Hydrogenolysis of 13 and 27. A
Schlenk flask was charged with dibromovinyl derivative (0.800 mmol)
and Pd(PPh3)4 (46.2 mg, 0.040 mmol, 5 mol %) and flushed with argon.
Toluene (8 mL) was added and the solution was treated with tributyltin
hydride (254 µL, 0.958 mmol, 1.2 equiv) under stirring at room
temperature for 0.2-3 h until the reaction composition did not change
(monitored by TLC). The reaction mixture was diluted with brine and
extracted with dichloromethane (3×). The combined fractions were
dried over anhydrous Na2SO4, the solvents were evaporated in vacuo,
and the residue was chromatographed on silica gel to obtain the product.
n
to 0 °C or room temperature. Bu-, TMS-, or TIPS-CtCH or aryl
acetylene (1.0-2.4 mmol, 1.0-2.4 equiv) was added and the reaction
mixture was stirred at 0 °C or room temperature or 40 °C for 0.25-14
h until the reaction composition did not change (monitored by TLC).
The precipitate was filtered off and washed with petroleum ether (5 ×
2 mL). The combined fractions were evaporated to dryness in vacuo
and the residue was chromatographed on silica gel to obtain the product.
Procedure for Sonogashira Coupling or Aryl Iodides 5, 7, and
16 with Gaseous Acetylene. A Schlenk flask was charged with aryl
iodide (1.0 mmol), Pd(PPh3)4 (58 mg, 0.050 mmol, 5 mol %), and CuI
(19 mg, 0.100 mmol, 10 mol %) and flushed with argon. Piperidine
(10-15 mL) was added and the reaction mixture was briefly heated
under stirring to 40-50 °C and then cooled to room temperature. A
rubber balloon filled with acetylene was attached to the Schlenk flask
and the reaction mixture was stirred at room temperature or 80 °C for
0.5-3 h until the reaction composition did not change (monitored by
TLC). The precipitate was filtered off and washed with petroleum ether
(5 × 2 mL). The combined fractions were evaporated to dryness in
vacuo and the residue was chromatographed on silica gel to obtain the
product.
Procedure for Conversion of Bromides 4, 6, 15, 17, and 29 to
Corresponding Iodides. tert-Butyllithium (1.7 M solution in pentane,
940 µL, 1.60 mmol, 2.0 equiv) was added dropwise (trickling along a
cooled flask surface) to a vigorously stirred solution of aryl bromide
(0.800 mmol) in ether (4 mL) at -90 °C under argon. After the mixture
was stirred at -90 °C for 5-10 min, iodine (345 mg, 1.36 mmol, 1.7
equiv) in ether (3 mL) was added dropwise. The mixture was stirred
at -90 °C for 10-30 min and then warmed to room temperature. The
reaction mixture was diluted with dichloromethane (4-fold to the amount
of ether), washed with Na2S2O3 (2×) and water (1×), and dried over
anhydrous Na2SO4. The solvents were removed in vacuo and the residue
was chromatographed on silica gel to afford the product.
Procedure for Nickel-Mediated [2+2+2] Cycloisomerization of
cis,cis-Dienetriynes 1, 9, 20, 22, and 33: Stoichiometric Method. A
Schlenk flask was charged with cis,cis-dienetriyne (0.100 mmol) and
flushed with argon. The substrate was dissolved in THF (2 mL), a stock
solution of Ni(cod)2 in THF (0.06 M, 1.70 mL, 100 mol %) was added,
and the mixture was stirred at room temperature for 15 min. The solvent
was evaporated in vacuo and the residue was chromatographed on silica
gel to obtain the product. Catalytic Method. In a Schlenk flask,
triphenylphosphine (10.5 mg, 0.040 mmol, 20 mol %) was dissolved
in THF (1 mL) under argon, a stock solution of Ni(cod)2 in THF (0.06
M, 330 µL, 10 mol %) was added, and the mixture was stirred at room
temperature for 5 min. cis,cis-Dienetriyne (0.200 mmol) in THF (2
mL) was added and the mixture was stirred at room temperature for
5-15 min. The solvent was evaporated in vacuo and the residue was
chromatographed on silica gel to obtain the product.
Procedure for Cobalt-Mediated [2+2+2] Cycloisomerization of
cis,cis-Dienetriyne 1: Cycloisomerization with Co2(CO)8. A Schlenk
flask was charged with 1 (52 mg, 0.187 mmol) and flushed with argon.
The substrate was dissolved in dioxane (1 mL), a solution of Co2(CO)8
(9.6 mg, 0.028 mmol, 15 mol %) in dioxane (1 mL) was added, and
the mixture was stirred at 80 °C for 40 min. The solvent was evaporated
in vacuo and the residue was chromatographed on silica gel (petroleum
ether-ether 99:1) to obtain 2 (ref 7) (4.4 mg, 8%) as an amorphous
solid.
Cycloisomerization with CpCo(CO)2: Stoichiometric Method.
A Schlenk flask was charged with 1 (23 mg, 0.083 mmol) and flushed
with argon. The substrate was dissolved in decane (5 mL), a solution
of triphenylphosphine (43.3 mg, 0.165 mmol, 200 mol %) in decane
(1 mL) and CpCo(CO)2 (11 µL, 0.083 mmol, 100 mol %) were added,
and the mixture was stirred at 140 °C for 1.2 h under concomitant
irradiation with a halogen lamp. The solvent was evaporated in vacuo
and the residue was chromatographed on silica gel (petroleum ether-
ether 100:0 to 99:1) to obtain 2 (10 mg, 43%) as an amorphous solid.
Catalytic Method. A Schlenk flask was charged with 1 (52 mg, 0.187
mmol) and flushed with argon. The substrate was dissolved in dioxane
(3 mL), a solution of triphenylphosphine (19.6 mg, 0.075 mmol, 40
mol %) in dioxane (1 mL) and CpCo(CO)2 (5 µL, 0.038 mmol, 20
mol %) were added, and the mixture was stirred at 90 °C for 22 h
under concomitant irradiation with a halogen lamp. The solvent was
evaporated in vacuo and the residue was chromatographed on silica
gel (petroleum ether-ether 99:1) to obtain 2 (15.8 mg, 30%) as an
amorphous solid.
Procedure for Selective TMS-Deprotection of 10 and 31. Sodium
methanolate (0.5 M solution in methanol, 4.80 mL, 2.40 mmol, 2.4
equiv) was added to TMS derivative (1.0 mmol) in methanol (4 mL)
under argon and the mixture was stirred at room temperature for 2-4.5
h. The solution was evaporated in vacuo to dryness and the residue
was chromatographed on silica gel to obtain the product.
Procedure for TIPS-Deprotection of 8, 19, and 21. Tetrabutyl-
ammonium fluoride (1.0 M solution in THF, 720 µL, 0.720 mmol, 2.4
equiv) was added to silylated cis,cis-dienetriyne (0.300 mmol) in THF
(4 mL) under argon and the mixture was stirred at room temperature
for 5 min. The solution was evaporated in vacuo to dryness and the
residue was chromatographed on silica gel to obtain the product.
(22) (a) Miertus, S.; Scrocco, E.; Tomasi, J. Chem. Phys. 1981, 55, 117. (b)
Cossi, M.; Barone, V.; Cammi, R.; Tomasi, J. Chem. Phys. Lett. 1996,
255, 327.
(23) (a) Cˇ izˇek, J. J. Chem. Phys. 1966, 45, 4256. (b) Raghavachari, K.; Trucks,
G. W.; Pople, J. A.; Head-Gordon, M. Chem. Phys. Lett. 1989, 157, 479.
(24) For standard molar enthalpies ∆fH° of acetylene and benzene in the gas
phase at 298.15 K, see: CRC Handbook of Chemistry and Physics, 77th
ed.; Lide, D. R., Frederikse, H. P. R., Eds.; CRC Press: Boca Raton, FL,
1996; pp 5-29 and 5-43.
Acknowledgment. The financial support by the Grant Agency
of the Czech Republic (Reg. No. 203/99/1448 and 203/02/0248),
(25) Schulman, J. M.; Disch, R. L. J. Phys. Chem. A 1999, 103, 6669.
9
J. AM. CHEM. SOC. VOL. 124, NO. 31, 2002 9179

A R T I C L E S
Teply´ et al.
the Center for Complex Molecular Systems and Biomolecules
(Project LN00A032), and the Institute of Organic Chemistry
and Biochemistry, Academy of Sciences of the Czech Republic
(Research Project Z4 055 905) is gratefully acknowledged. We
are very indebted to Dr. J. Za´vada of this Institute for valuable
and stimulating discussions.
Supporting Information Available: Experimental details,
characterization data, and 1H NMR spectra for 1, 2, 4-11, 13-
25, and 27-34 (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
JA0259584
9
9180 J. AM. CHEM. SOC. VOL. 124, NO. 31, 2002