Expeditive syntheses of functionalized pentahelicenes and NC-AFM on ag(001)

Article abstract of DOI:10.1021/ol9014255

One of the shortest and most efficient routes toward a series of functionalized pentahelicenes is reported. Benzylic (dibromo)methine coupling is an important entry into functional helicene chemistry. It allowed a mono- or a double functionalization by so

Full text of DOI:10.1021/ol9014255

ORGANIC
LETTERS
2009
Vol. 11, No. 17
3846-3849
Expeditive Syntheses of Functionalized
Pentahelicenes and NC-AFM on Ag(001)
Sarah Goretta,† Christelle Tasciotti,† Simon Mathieu,| Mario Smet,‡
Wouter Maes,‡ Yoann M. Chabre,† Wim Dehaen,‡ Richard Giasson,|
Jean-Manuel Raimundo,§ Claude R. Henry,§ Clemens Barth,§ and Marc Gingras*,§
CNRS, Aix-Marseille UniVersity, CINAM UPR 3118, AVenue de Luminy,
Case 913, 13288 Marseille Cedex 09, France, De´partement de Chimie, UniVersite´ de
Montre´al, C.P. 6128, succ. Centre-Ville, Montre´al, Que´bec, Canada H3C 3J7, and
Department of Chemistry, Katholieke UniVersiteit LeuVen, Celestijnenlaan 200F,
3001 HeVerlee, Belgium
marc.gingras@uniVmed.fr
Received June 23, 2009
ABSTRACT
One of the shortest and most efficient routes toward a series of functionalized pentahelicenes is reported. Benzylic (dibromo)methine coupling
is an important entry into functional helicene chemistry. It allowed a mono- or a double functionalization by some metal-catalyzed Ar-C,
Ar-S, Ar-CN, and Ar-I bond formations. Those functions offer new avenues for further applications. For instance, helicene (4) can be
supported on a Ag(001) surface, which was characterized by high-resolution NC-AFM imaging.
Helicenes are intriguing helicoidal polyaromatic compounds
with a distorted π-system. They have become the centerpiece
of several developments in the fields of asymmetric cataly-
sis,1 advanced materials,2 (dendrimers, polymers, liquid
crystals, self-assembled monolayers, etc.), molecular opto-
electronics,3 and nanosciences.4
Concerning their synthesis, the photocyclodehydrogenation
of some stilbene-like derivatives has been the method of
choice for several decades,5 but not for pentahelicenes.
Competitive transformation to benzo[g,h,i]perylene lowered
the yield.6 This method usually provides a small amount of
product by using high dilution techniques (10-3 M) in order
to avoid a [2π + 2π] dimerization (typically, 100 mg/L of
solvent). The need for a larger scale production with simple
equipment and a better functionalization of helicenes is a
| Universite´ de Montre´al.
‡ Katholieke Universiteit Leuven.
§ CNRS, Aix-Marseille University.
† Previous address: Institut de chimie de Nice, Faculty of Sciences,
University of Nice-Sophia Antipolis, 06108 Nice, France.
(1) (a) Dreher, S. D.; Katz, T. J.; Lam, K.-C.; Rheingold, A. L. J. Org.
Chem. 2000, 65, 815–822. (b) Terfort, A.; Go¨rls, H.; Brunner, H. Synthesis
1997, 79–86. (c) Reetz, M. T.; Beuttenmu¨ller, E. W.; Goddard, R.
Tetrahedron Lett. 1997, 38, 3211–3214.
(3) (a) Morrison, D. J.; Trefz, T. K.; Piers, W. E.; McDonald, R.; Parvez,
M. J. Org. Chem. 2005, 70, 5309–5312. (b) Verbiest, T.; Sioncke, S.;
Persoons, A.; Vyklicky´, L.; Katz, T. J. Angew. Chem., Int. Ed. 2002, 41,
3882–3884.
(2) Dendrimers: (a) Bender, T. P.; Qi, Y.; Desjardins, P.; Wang, Z. Y.
Can. J. Chem. 1999, 77, 1444–1452. Liquid crystals: (b) Vyklicky´, L.;
Eichhorn, S. H.; Katz, T. J. Chem. Mater. 2003, 15, 3594–3601. Fibers:
(c) Lovinger, A. J.; Nuckolls, C.; Katz, T. J. J. Am. Chem. Soc. 1998, 120,
264–268. (d) Nuckolls, C.; Katz, T. J.; Castellanos, L. J. Am. Chem. Soc.
1996, 118, 3767–3768. Polymers: (e) Bender, T. P.; Wang, Z. Y.
Macromolecules 2000, 33, 9477–9479. (f) Nuckolls, C.; Katz, T. J.; Katz,
G.; Collings, P. J.; Castellan˜os, L. J. Am. Chem. Soc. 1999, 121, 79–88.
(g) Fox, J. M.; Lin, D.; Itagaki, Y.; Fujita, T. J. Org. Chem. 1998, 63,
2031–2038.
(4) For [7]helicene: (a) Parschau, M.; Fasel, R.; Ernst, K.-H. Cryst.
Growth Des. 2008, 8, 1890–1896. (b) Fasel, R.; Parschau, M.; Ernst, K.-H.
Nature 2006, 439, 449–452. (c) Fasel, R.; Parschau, M.; Ernst, K.-H. Angew.
Chem., Int. Ed. 2003, 42, 5178–5181. (d) Ernst, K.-H.; Kuster, Y.; Fasel,
R.; Mu¨ller, M.; Ellerbeck, U. Chirality 2001, 13, 675–678.
(5) (a) Flammand-Barbieux, M.; Nasielski, J.; Martin, R. H. Tetrahedron
Lett. 1967, 743–744. (b) Collet, C.; Gingras, M. Synlett 2005, 2337–2341.
(6) Liu, L.; Katz, T. J. Tetrahedron Lett. 1991, 32, 6831–6834.
(7) (a) Gingras, M.; Dubois, F. Tetrahedron Lett. 1999, 40, 1309–1312.
(b) Dubois, F.; Gingras, M. Tetrahedron Lett. 1998, 39, 5039–5040.
10.1021/ol9014255 CCC: $40.75
Published on Web 08/11/2009
 2009 American Chemical Society

recent quest toward further applications.7,8 We addressed this
goal and describe here a UHV (ultrahigh vacuum) deposition
of a functionalized carbohelicene on a Ag (001) surface,
characterized by non-contact atomic force microscopy imag-
ing (NC-AFM) with a high resolution.
One of us reported some benzylic bromomethylene
(ArCH2Br)-type couplings for making phenanthrene, and
penta- and heptahelicenes.7 However, they suffered from
modest yields, and toxic HMPA and a strong base (LiH-
MDS). 2,2′-Bis(bromomethyl)-1,1′-naphthalene as a precur-
sor to [5]helicene also suffered from a problematic dibro-
mination and purification (50% yield). Only one benzylic
(dibromo)methine (ArCHBr2) coupling was previously at-
tempted but in a mediocre yield of 3 (29%), still contami-
nated by some byproducts. Those results completely dis-
couraged the pursuit of this method, the functionalization
of 3, and further pentahelicene applications.
rationale for our procedure was to use a weaker base than
NaNH2 or LiHMDS. An excess of tBuOK in DMF smoothly
provided an excellent yield of 7,8-dibromo[5]helicene 3
(92-96% yield, 0-3 °C for 10-15 min). The molar ratio
of t-BuOK/2 was optimized to 5:1. At first, we avoided
refluxing in dioxane/aqueous NaOH conditions because of
some reported hydrolytic byproducts,9 but for the sake of a
comparison, a gradual heating from 35 to 100 °C for several
hours in dioxane/NaOH 1 M was ineffective (mostly unre-
acted substrate). In a similar trend, anhydrous K2CO3 in DMF
at 100 °C also left substrate 2 unreacted.
Having produced 3, we achieved a monodebromination
with zinc powder in refluxing acetic acid, which is one of
the simplest reductive methods (Scheme 1). After controlling
the amount of zinc and reaction time, we obtained
7-bromo[5]helicene 4 in a 96% yield after a crystallization
from the reaction mixture, the main byproduct being [5]he-
licene (<3%). Helicenes 3 and 4 were thus produced on a
large scale and in high yields, with cheap reagents and
without a chromatographic separation.
To circumvent all of those difficulties, we now disclose
our strategy for quickly preparing functionalized pentaheli-
cenes on a larger scale (>10 g, Scheme 1). We devised an
The reactivity of 3 and 4 was then verified on such a
distorded π system of a carbohelicene. It is relatively
underexplored in helicene chemistry. In the first set of
reactions, some metal-catalyzed couplings with 4 were tested
(Schemes 2 and 3). A Sonogashira reaction was successful
Scheme 1
.
Expeditive Route to Functionalized Helicenes via a
Benzylic Gem(dibromo)methine Coupling
Scheme 2. Functionalization of 7-Bromo[5]helicene 4
efficient radical tetrabromination of commercial 1 with
benzoyl peroxide and an excess of NBS (96% yield). The
synthesis of 2 previously required two steps with an overall
yield of less than 40%. Finally, a mild and spontaneous ring-
closing step propelled this underdeveloped benzylic dibro-
momethine coupling to among the best methods in helicene
synthesis (96% yield) and in the literature.9
Because a benzylic (dibromo)methine (ArCHBr2) function
is more acidic than a bromomethylene one (ArCH2Br), a
(8) Among some syntheses of carbohelicenes: (a) Urban˜o, A. Angew.
Chem., Int. Ed. 2003, 42, 3986–3989. (b) Collins, S. K.; Grandbois, A.;
Vachon, M. P.; Coˆte´, J. Angew. Chem., Int. Ed. 2006, 45, 2923–2926. (c)
Harrowen, D. C.; Guy, I. L.; Nanson, L. Angew. Chem., Int. Ed. 2006, 45,
2242–2245. (d) Carren˜o, M. C.; Gonza´lez-Lo´pez, A. U. Chem. Commun.
2005, 611–613. (e) K. Paruch, L.; Vylicky´, M.; Wang, E. Z.; Katz, T. J.;
Incarvito, C.; Zakharov, L.; Rheingold, A. L. J. Org. Chem. 2003, 68, 8539–
with trimethylsilylacetylene in the presence of triethylamine,
CuI, and PdCl2(PPh3)2 (Scheme 2). It provided a quantitative
yield of 7-(trimethylsilylacetylene)[5]helicene 5. Removal
of the TMS group at 20 °C in a methanolic solution of K2CO3
produced a quantitative yield of 7-ethynyl[5]helicene 6.
Another acetylenic reagent, such as phenylacetylene,
was tested with Pd(PPh3)4 under classic conditions, but 7
was obtained in a low yield. Similarly, a Pd-catalyzed
Miyaura-Suzuki coupling with phenylboronic acid and
4 led to 7-phenyl[5]helicene in a low yield (26%).
ˇ
8544. (f) Teply´, F.; Stara´, I. G.; Stary´, I.; Kollarovicˇ, A.; Saman, D.;
ˇ
Vyskocˇil, S.; Fiedler, P. J. Org. Chem. 2003, 68, 5193–5197. (g) Pena, D.;
Cobas, A.; Perez, D.; Guitian, E.; Castedo, L. Org. Lett. 2003, 5, 1863–
1866
.
(9) (a) Sygula, A.; Karlen, S. D.; Sygula, R.; Rabideau, P. W. Org. Lett.
2002, 4, 3135–3137. (b) Marcinow, Z.; Grove, D. I.; Rabideau, P. W. J.
Org. Chem. 2002, 67, 3537–3539. (c) Sygula, A.; Xu, G.; Marcinow, Z.;
Rabideau, P. W. Tetrahedron 2001, 57, 3637–3644. (d) Sygula, A.;
Rabideau, P. W. J. Am. Chem. Soc. 2000, 122, 6323–6324
.
Org. Lett., Vol. 11, No. 17, 2009
3847

Scheme 3
.
Pd-Catalyzed Sulfuration of 7-Bromo[5]helicene 4
Scheme 4. Functionalization of 7,8-Dibromo[5]helicene 3
Because iodinated compounds are often good candidates
for generating carbanions by lithium-halogen exchange, we
converted 4 into iodide 8 in an 87% yield in the presence of
KI, CuI in refluxing DMF (Scheme 2).
Having in mind a chiral self-assembly of helicenes on a
gold surface, we focused on the synthesis of 7-sulfanyl[5]-
helicene 10 (Scheme 3). We emphasize the importance and
the originality of this work toward sulfanylated or sulfurated
carbohelicenes, which are particularly rare in the literature.
We first tried a classic thiol formation from elemental sulfur
and t-BuLi. Insolubility in THF at low temperature possibly
prevented a generation of the corresponding anion. Using
our methodology for making thiols from thiomethylated
precursors, it would bring us on familiar grounds.10 We
succeeded in preparing 9 in a 78% yield under Pd-catalyzed
conditions (Scheme 3).11 Nucleophilic deprotection of 9 with
t-BuSNa (freshly prepared from t-BuSH and NaH) in dry
DMF at 160 °C provided the expected thiol 10 in a 99%
yield. We also prepared 7-(tert-butylthio)[5]helicene 11 as
an alternative precursor to 10 because of a known depro-
tection with CF3SO3H. The later was unexpectedly difficult
and most substrate was left unreacted, along with some
byproducts.
dicyano[5]helicene 13 was produced in a 80% yield along
with 7-cyano-8-bromo[5]helicene as a byproduct. Helicene
13 could be reduced to a chiral bidentate diamine or used
for making phtalocyanines.12 A double thiomethylation of
3 to 14 was achieved in a 85% yield from a Pd-catalyzed
reaction with CH3SNa in DMSO/n-BuOH at 100 °C.11
Phenylacetylene reacted with 3 in the presence of Pd(PPh3)4
to afford 15a in 34% yield, along with 7 (23%) and 7-bromo-
8-(2-phenylethynyl)[5]helicene 15b (7%). As for 4, the
reactivity was problematic.
Having in hand a variety of [5]helicene derivatives, we
first demonstrated that they could be supported under
ultrahigh vacuum (UHV at 10-10 mbar) on a metallic surface
for noncontact AFM studies (NC-AFM) at molecular resolu-
tion. Only a few reports dealt with nonfunctionalized
[7]helicene, mostly on a Cu(111) or Ni(111) surface.4
Deposition of functionalized carbohelicenes or [5]helicenes
for AFM or STM studies were never reported. We anticipated
a strong interaction on a single silver crystal as a support
such as Ag(001) and a polarizable and halogenated 4. The
latter molecule was chosen in order to better control its
sublimation, its molecular deposition and its self-assembly.
For the detection of helicenes on a surface, a standard
analytic technique like LEED13 (low-energy electron dif-
fraction) in combination with NC-AFM were used. LEED
yields an average information about the lateral order of nano-
objects on surfaces, wheras NC-AFM is a suitable technique
to locally image the topography of molecules on metal
surfaces at a molecular resolution.14
In a second set of reactions with dibromide 3, 7,8-
diodo[5]helicene 12 (Scheme 4) was produced in a similar
manner as for 8. It should help for other metal-catalyzed
couplings. Due to the importance of helicene amination and
phthalocyanines and chiral diamines as bidentate ligands, we
tried a Rosenmund-von Braun reaction with CuCN in
1-methyl-2-pyrrolidinone at 150-180 °C. The expected 7,8-
(10) (a) Pinchart, A.; Dallaire, C.; Van Bierbeek, A.; Gingras, M.
Tetrahedron Lett. 1999, 40, 5479–5482. (b) Pinchart, A.; Dallaire, C.;
Gingras, M. Tetrahedron Lett. 1998, 39, 543–546.
(11) Among other sulfurated carbohelicenes: (a) F. Teply, I. G.; Stara,
I.; Stary, A.; Kollarovic, D.; Saman, S.; Vyskocil, P.; Fiedler, J. Org. Chem.
2003, 68, 5193–5197. (b) For Pd catalysis: Migita, T.; Shimizu, T.; Asami,
Y.; Shiobara, J.-I.; Kato, Y.; Kosugi, M. Bull. Chem. Soc. Jpn. 1980, 53,
1385–1389.
(12) Sooksimuang, T.; Mandal, B. K. J. Org. Chem. 2003, 68, 652–
655.
(13) Heinz, K. Low-Energy Electron Diffraction (LEED) in Textbook
on Surface Science; Wandelt, K., Ed.; Wiley-VCH: Verlag Berlin GmbH,
December 2008).
(14) Zerweck, U.; Loppacher, Ch.; Otto, T.; Grafstro¨m, S.; Eng, L. M.
Nanotechnology 2007, 18, 084006.
3848
Org. Lett., Vol. 11, No. 17, 2009

silver surface in UHV, the surface exhibited atomically flat
terraces which were intersected by some steps (Figure 1a).
Helicene 4 was then evaporated onto the Ag(001) surface
in the UHV chamber. NC-AFM images obtained in situ
exhibited a granular structure on the surface which cor-
responded to one monolayer of 4 (Figure 1b). The height
differences (profile in Figure 1b) allowed for concluding that
the nano-objects had a size similar to that of 7-bromo-5-
helicene. An additional annealing of the sample at 130 °C
for 1 h did not allow a sufficient molecular mobility on the
surface for self-assembly. It might be due to a strong
molecular interaction with Ag(001) (Figure 1c). Heating at
250 °C finally led to a complete removal of the molecular
layer (Figure 1d).
In summary, an expeditive synthesis of pentahelicene 3
was demonstrated in two steps from 1 (88-92%) or in only
one step from 2 (96%). A mono-debromination of 3 afforded
4 in a 96% yield (85-88% from 1). This synthetic route is
an important entry into mono- or disubstituted carbohelicene
chemistry after highlighting an important benzylic dibro-
momethine coupling (92-96%). All steps proceeded on a
gram scale with inexpensive reagents and facilitated purifica-
tions. Exploration of Ar-S, Ar-I, Ar-C, and Ar-CN metal-
catalyzed bond formation was achieved and quickly led to a
series of useful functionalized pentahelicenes. We further
demonstrated that such helicenes can be supported and
stabilized on a metallic surface like Ag(001). We believe
that this work is a promising step toward new investigations
in the nanoscience of functionalized helicenes supported on
surfaces as well as for further studies in chiral materials
chemistry.
Figure 1. (a) NC-AFM images of 4 representing the topography
Acknowledgment. M.G., J.M.R., and Y.M.C. acknowl-
edge Egide Tournesol Grant No. PAI 03791XM from the
French Government, CNRS, the University of Nice-Sophia
Antipolis, the France-Canada Funds, and a scholarship to
S.M. from the French Ambassy in Canada.
of the Ag(001) surface directly after the preparation of the silver
surface; (b) after deposition of 4 at 20 °C; (c) after an annealing at
130 °C for 1 h; and (d) after a second annealing at 250 °C for 1 h.
For a better comparison, the profiles have the same scale. All
images: 100 × 100 nm2, (a) ∆f ) -21 Hz, (b) ∆f ) -30 Hz, (c)
∆f ) -45 Hz, (d) ∆f ) -23 Hz.
Supporting Information Available: Experimental pro-
cedures and characterization data. This material is available
free of charge via the Internet at http://pubs.acs.org.
After 4 was heated at 150 °C for 12 h at reduced pressure
(0.1 mmHg) to remove any volatiles, no decomposition of
1
4 was observed by H NMR. After the preparation of the
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