Synthesis of 3-hexahelicenol and its transformation to 3-hexahelicenylamines, diphenylphosphine, methyl carboxylate, and dimethylthiocarbamate

Article abstract of DOI:10.1021/jo034369t

A nonphotochemical synthetic route to 3-hexahelicenol is reported. It involves a key [2+2+2] cycloisomerization of CH₃O-substituted triyne that is readily available from 1-methoxy-3-methylbenzene and 1-bromo-2-(bromomethyl)naphthalene. Further

Full text of DOI:10.1021/jo034369t

Syn th esis of 3-Hexa h elicen ol a n d Its Tr a n sfor m a tion to
3-Hexa h elicen yla m in es, Dip h en ylp h osp h in e, Meth yl Ca r boxyla te,
a n d Dim eth ylth ioca r ba m a te
Filip Teply´,† Irena G. Stara´,*,† Ivo Stary´,*,† Adrian Kolla´rovicˇ,† David Sˇaman,†
Sˇteˇpa´n Vyskocˇil,‡ and Pavel Fiedler†
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
Flemingovo na´m 2, 166 10 Prague 6, Czech Republic, and Department of Organic Chemistry,
Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
stara@uochb.cas.cz; stary@uochb.cas.cz
Received March 20, 2003
A nonphotochemical synthetic route to 3-hexahelicenol is reported. It involves a key [2+2+2]
cycloisomerization of CH3O-substituted triyne that is readily available from 1-methoxy-3-methyl-
benzene and 1-bromo-2-(bromomethyl)naphthalene. Further functional group transformations led
to 3-CO2CH3, 3-NH2, 3-PPh2, and 3-SC(O)N(CH3)2 substituted hexahelicenes.
In tr od u ction
From a synthesis point of view, two different strategies
may be considered to introduce substituents: function-
alizing bare helicene skeletons or assembling helicenes
from functionalized building blocks. While the former
approach based on aromatic electrophilic substitution is
rare in the literature8 and usually suffers from low
regioselectivity, the latter approach is waiting for an
effective and modular method for the helicene synthesis
to be developed.9
Recently, we have revealed a new paradigm for the
nonphotochemical synthesis of tetrahydrohelicenes/heli-
cenes that is based on a key intramolecular [2+2+2]
cycloisomerization of aromatic triynes/cis,cis-dienetriynes
under Co(I) or Ni(0) catalysis.10 Herein, we disclose this
flexible methodology can easily be adapted to the syn-
Carbohelicenes are stable nonplanar aromatic systems
being inherently chiral.1 The indispensable prerequisite
to a wide exploitation of these molecules is availability
of their derivatives. Although much effort has so far been
devoted to the synthesis of carbohelicenes,2 in the hexa-
helicene series the functional group variety is limited to
OH or CO2H and their congeners.3,4 To the best of our
knowledge, only one monodentate phosphine,5 one bi-
dentate phosphine,5,6 one amine,7 and no thiol derivative
have been up to now described in the hexahelicene series.
† Academy of Sciences of the Czech Republic.
‡ Charles University.
(1) For reviews, see: (a) Katz, T. J . Angew. Chem., Int. Ed. 2000,
39, 1921. (b) Osuga, H.; Suzuki, H. J . Synth. Org. Chem., J pn. 1994,
52, 1020. (c) Oremek, G.; Seiffert, U.; J anecka, 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. 1970, 4, 65.
(4) For carboxylic acids and their derivatives, see: (a) Fox, J . M.;
Lin, D.; Itagaki, Y.; Fujita, T. J . Org. Chem. 1998, 63, 2031. (b) J anke,
R.; Haufe, G. Zh. Org. Khim. 1994, 30, 1365. (c) Hassine, B. B.;
Gorsane, M.; Geerts-Evrard, F.; Pecher, J .; Martin, R. H.; Castelet, D.
Bull. Soc. Chim. Belg. 1986, 95, 557. (d) Hassine, B. B.; Gorsane, M.;
Geerts-Evrard, F.; Pecher, J .; Martin, R. H.; Castelet, D. Bull. Soc.
Chim. Belg. 1986, 95, 547. (e) Gorsane, M.; Defay, N.; Martin, R. H.
Bull. Soc. Chim. Belg. 1985, 94, 215. (f) Kim, Y. H.; Balan, A.; Tishbee,
A.; Gil-Av, E. J . Chem. Soc., Chem. Commun. 1982, 1336. (g) Balan,
A.; Gottlieb, H. E. J . Chem. Soc., Perkin Trans. 2 1981, 350. (h) Martin,
R. H.; Libert, V. J . Chem. Res. Miniprint 1980, 4, 1940. (i) Cochez, Y.;
Martin, R. H.; J espers, J . Isr. J . Chem. 1976, 15, 29. (j) J utz, C.;
Loebering, H.-G. Angew. Chem. 1975, 87, 415. (k) Martin, R. H. Chimia
1975, 29, 137. (l) Martin, R. H.; Cosyn, J . P. Synth. Commun. 1971, 1,
257.
(5) For monophosphine, see: Terfort, A.; Gorls, H.; Brunner, H.
Synthesis 1997, 79.
(6) For bisphosphine, see refs 3a and 5 and the following: (a) Reetz,
M. T.; Sostmann, S. J . Organomet. Chem. 2000, 603, 105. (b) Reetz,
M. T.; Beuttenmuller, E. W.; Goddard, R. Tetrahedron Lett. 1997, 38,
3211.
(2) According to the CrossFire Beilstein database, more than 480
carbohelicenes are known within the [5]- to [14]helicene series.
(3) For alcohols and their derivatives, see: (a) Ogawa, Y.; Toyama,
M.; Karikomi, M.; Seki, K.; Haga, K.; Uyehara, T. Tetrahedron Lett.
2003, 44, 2167. (b) Ogawa, Y.; Ueno, T.; Karikomi, M.; Seki, K.; Haga,
K.; Uyehara, T. Tetrahedron Lett. 2002, 43, 7827. (c) Reetz, M. T.;
Sostmann, S. Tetrahedron 2001, 57, 2515. (d) Paruch, K.; Vyklicky´,
L.; Katz, T. J .; Incarvito, C. D.; Rheingold, A. L. J . Org. Chem. 2000,
65, 8774. (e) Thongpanchang, T.; Paruch, K.; Katz, T. J .; Rheingold,
A. L.; Lam, K.-C.; Liable-Sands, L. J . Org. Chem. 2000, 65, 1850. (f)
Dreher, S. D.; Paruch, K.; Katz, T. J . J . Org. Chem. 2000, 65, 806. (g)
Meier, H.; Schwertel, M.; Schollmeyer, D. Acta Crystallogr. Sect. C:
Cryst. Struct. Commun. 2000, 56, 684. (h) Nuckolls, C.; Katz, T. J .;
Katz, G.; Collings, P. J .; Castellanos, L. J . Am. Chem. Soc. 1999, 121,
79. (i) Meier, H.; Schwertel, M.; Schollmeyer, D. Angew. Chem., Int.
Ed. 1998, 37, 2110. (j) Katz, T. J .; Liu, L.; Willmore, N. D.; Fox, J . M.;
Rheingold, A. L.; Shi, S.; Nuckolls, C.; Rickman, B. H. J . Am. Chem.
Soc. 1997, 119, 10054. (k) Dai, Y.; Katz, T. J . J . Org. Chem. 1997, 62,
1274. (l) Nuckolls, C.; Katz, T. J .; Castellanos, L. J . Am. Chem. Soc.
1996, 118, 3767. (m) Dai, Y.; Katz, T. J .; Nichols, D. A. Angew. Chem.
1996, 108, 2230. (n) Yang, B.; Liu, L.; Katz, T. J .; Liberko, C. A.; Miller,
L. L. J . Am. Chem. Soc. 1991, 113, 8993. (o) Hassine, B. B.; Gorsane,
M.; Geerts-Evrard, F.; Pecher, J .; Martin, R. H.; Castelet, D. Bull. Soc.
Chim. Belg. 1986, 95, 557. (p) Brown, J . M.; Field, I. P.; Sidebottom,
P. J . Tetrahedron Lett. 1981, 22, 4867.
(7) For amine, see: op den Brouw, P. M.; Laarhoven, W. H. Recl.
Trav. Chim. Pays-Bas 1978, 97, 265.
(8) For electrophilic substitution of parent hexahelicene, see ref 7.
(9) Most of the functionalized helicenes mentioned in refs 3-7 were
prepared from substituted stilbene-type precursors via impractical UV
light-mediated photodehydrocyclization or, in the case of hydroxy
derivatives, by benzoquinone cycloaddition to (bis)vinyl aromatics.
Although the latter approach published by Katz is quite general in
regard to the helicene skeleton, a substitution portfolio is very limited.
10.1021/jo034369t CCC: $25.00 © 2003 American Chemical Society
Published on Web 05/24/2003
J . Org. Chem. 2003, 68, 5193-5197
5193

Teply´ et al.
SCHEME 2. Syn th esis of th e Bu ild in g Block 9a
F IGURE 1. 3-Functionalized hexahelicenes.
SCHEME 1. Syn th esis of th e Bu ild in g Block 4a
a
Reagents and conditions: (a) LiCH2C≡CTIPS (1.04 equiv),
THF, -78 °C, 1 h, 92%. (b) nBuLi (1.04 equiv), THF, -78 °C, 15
min, then I2 (1.1 equiv), -78 °C, 20 min, 98%. (c) TMS-C≡CH
i
(1.2 equiv), Pd(PPh3)4 (1%), CuI (2%), Pr2NH, autoclave, 80 °C,
1.5 h, 99%. (d) CH3ONa (1.7 equiv), methanol, rt, 16 h, 99%.
SCHEME 3. Con str u ction of 3-Hexa h elicen ol 15
a n d Its Tetr a h yd r oa n a logu e 13a
a
Reagents and conditions: (a) NBS (2.1 equiv), CH2Cl2, IR
lamp, 4 h, reflux, 99%. (b) LiCH2C≡CTIPS (1.05 equiv), THF, -78
°C, 15 min, 95%. (c) nBuLi (1.05 equiv), THF, -78 °C, 10 min,
then I2 (1.1 equiv), -78 °C, 20 min, 96%.
thesis of various substituted carbohelicenes. Starting
from simple building blocks, an array of 3-functionalized
hexahelicenes is now attainable (Figure 1).
Resu lts a n d Discu ssion
Syn th esis of Bu ild in g Block s. 3-Methyl anisole 1,
whose methoxy group appears as a useful functionality
in a desired position at the hexahelicene scaffold, vide
infra, was brominated with N-bromosuccinimide accord-
ing to the literature procedure11 to obtain dibromide 2
(Scheme 1). On treatment with LiCH2C≡CTIPS (gener-
ated in situ from CH3C≡CTIPS and n-butyllithium),
bromide 3 was produced bearing a protected alkyne unit
in the sidearm. To avoid the tethered alkyne unit
participating in the planned Sonogashira coupling, bro-
mide 3 was converted to iodide 4 by lithiation/iodination.
The synthesis of the unsubstituted naphthalene build-
ing block 9 starts from dibromide 5 (Scheme 2). After the
attachment of the sidearm with the alkyne unit, bromide
6 was transformed to the known iodide 712 to ensure a
clean Sonogashira coupling with HC≡CTMS providing
diyne 8. The selective removal of the TMS group com-
pleted the synthesis of 9. The easy preparation of 4 and
9 was carried out on a multigram scale and high yields
were throughout both the synthesis schemes.
a
Reagents and conditions: (a) 4 (1.0 equiv), 9 (1.0 equiv),
Pd(PPh3)4 (2%), CuI (4%), iPr2NH, 80 °C, 15 min, 90%. (b) nBu4NF
(2.4 equiv), THF, rt, 15 min, 74%. (c) CpCo(CO)2 (20%), PPh3 (40%),
decane, halogen lamp, 140 °C, 2.5 h, 68%. (d) BBr3 (4.6 equiv),
CH2Cl2, rt, 20-40 min, 89% (13) or 83% (15). (e) Ph3CBF4 (3.4
equiv), 1,2-dichloroethane, 80 °C, 2 h, 99%.
Sonogashira coupling of the building blocks 4 and 9 led
to the silylated triyne 10 (Scheme 3). Deprotection of the
terminal alkyne units afforded the key triyne 11 in
reasonable yield.
To achieve the desired [2+2+2] cycloisomerization and,
accordingly, to build up the helix, triyne 11 was exposed
to various transition metal catalysts. Initial attempts
with Grubbs catalyst recently used in this context13 were
unsuccessful (Table 1, entry 1). In the case of Co2(CO)8
(ref 13), the desired cyclization took place and substituted
tetrahydrohexahelicene 12 was formed in moderate yield
(Table 1, entry 2). By changing the catalyst to CpCo(CO)2
Con str u ction of 3-Hexa h elicen ol 15. Having pre-
pared the suitable building blocks, we could approach
assembling the hexahelicene scaffold. Smooth and clean
(10) (a) Teply´, F.; Stara´, I. G.; Stary´, I.; Kolla´rovicˇ, A.; Sˇaman, D.;
Rul´ısˇek, L.; Fiedler, P. J . Am. Chem. Soc. 2002, 124, 9175. (b) Stara´,
I. G.; Stary´, I.; Kolla´rovicˇ, A.; Teply´, F.; Vyskocˇil, Sˇ.; Sˇaman, D.
Tetrahedron Lett. 1999, 40, 1993.
(11) Hoye, T. R.; Mi, L. J . Org. Chem. 1997, 62, 8596.
(12) Stara´, I. G.; Kolla´rovicˇ, A.; Teply´, F.; Stary´, I.; Sˇaman, D.;
Fiedler, P. Collect. Czech. Chem. Commun. 2000, 65, 577.
(13) Das, S. K.; Roy, R. Tetrahedron Lett. 1999, 40, 4015.
5194 J . Org. Chem., Vol. 68, No. 13, 2003

3-Hexahelicenol
TABLE 1. [2+2+2] Cycloisom er iza tion of 11
TABLE 2. Ar om a tiza tion of 12
reagent
(equiv)
temp, °C yield of
entry
solvent
(time, h) 14, %a
Pd/Cb
MnO2 (10)
DDQ (10)
Ph3COH (3.3) TFA
Ph3CBF4 (3.4) 1,2-dichloroethane
1-methylnaphthalene 360 (5)
no rxn
temp, °C yield of
1
2
3
4
5
entry
1
MLn (mol %)
ligand (mol %)
PPh3 (40)
(time, h) 12, %a
C6H6
C6H6
80 (20) no rxn
100c (7)
72 (2)
6
51
99
(Cy3P)2Cl2-
rt (24)b no rxn
RudCHPh (40)
Co2(CO)8 (40)
CpCo(CO)2 (20)
Ni(cod)2 (20)
80 (2)
2
3
4
100 (1)c
140 (2.5)d 68
54
a
b
Isolated. 10% Pd/C, 100 mg/mmol of 12. c In a sealed tube.
(S)-(-)-BOP (40) -20 (0.1)e 74
42% eef
SCHEME 4. Meth oxyca r bon yla tion of
P er flu or oa lk ylsu lfon a tes 16 a n d 17a
a
d
Isolated. b In CH2Cl2. c In dioxane. In decane, irradiated with
a halogen lamp. e In THF. f (+)-Enantiomer prevails; determined
by HPLC on a Chiracel OD-H column (n-heptane:2-propanol
99:1).
(ref 14), a better yield was achieved (Table 1, entry 3).
Halogen lamp irradiation and triphenylphosphine addi-
tion were not essential but the former promoted the
reaction via the catalyst activation and the latter kept
the active catalyst alive for a longer period although
slightly decreasing the cyclization rate. Most notably,
nickel(0) catalysts10 have proven to be very active and
by employing chiral ligands absolute stereochemistry
could be controlled at the helix formation. By using
Ni(cod)2 with the Hayashi’s monophosphine ligand,15
triyne 11 was cyclized to 12 in reasonable yield and with
moderate enantioselectivity (Table 1, entry 4).16
To transform tetrahydrohexahelicene 12 to hexaheli-
cene 14, several attempts at aromatization17 were un-
dertaken. Both dehydrogenation of 12 by treatment with
palladium on charcoal under severe conditions18 and
oxidation of 12 with manganese dioxide19 were totally
ineffective, leaving the starting material unreacted (Table
2, entries 1 and 2). Even reaction with DDQ commonly
used as a dehydrogenating agent20 afforded 14 in very
low yield (Table 2, entry 3) and the bulk of the educt was
a
Reagents and conditions: (a) nBuLi (1.04 equiv), THF, -78
°C, 10 min, then Tf2O (1.4 equiv), -78 °C, 20 min, 50%. (b) NaH
(2.2 equiv), DMF, rt, 20 min, then NfF (2.0 equiv), 0 °C to room
temperature, 30 min, 85%. (c) CO (atm. pressure), Pd(OAc)2 (10%),
dppp (10%), Et3N (3.0 equiv), DMSO-methanol (3:2), 70 °C, 1.5-2
h, 59% (from 16) or 89% (from 17).
recovered. Fortunately, the trityl cation as a hydride-
abstracting species has been found to aromatize 12
efficiently. Being generated in situ from triphenylmetha-
nol in trifluoroacetic acid,21 fully aromatic 14 was pro-
duced in reasonable yield (Table 2, entry 4). Further
optimization and the use of the trityl cation as a
substance22 resulted in a quantitative yield of 14 (Table
2, entry 5).23
The synthesis of 3-hexahelicenol 15 was accomplished
by demethylation of 14 with boron tribromide.24 Under
the same conditions, the methoxy derivative 12 also could
be converted to alcohol 13 in comparable yield.
Con ver sion of 3-Hexah elicen ol to th e Cor r espon d-
in g C-, N-, P -, a n d S-An a logu es. To displace the
3-hydroxy group in 15 with other functionalities, reactive
triflate 16 or nonaflate 17 had to be prepared first
(Scheme 4). Reaction of alcohol 15 with triflic anhydride
in pyridine15 failed but treatment of lithium alkoxide
generated from 15 with triflic anhydride furnished tri-
(14) (a) Stara´, I. G.; Stary´, I.; Kolla´rovicˇ, A.; Teply´, F.; Sˇaman, D.;
Tichy´, M. J . Org. Chem. 1998, 68, 4046. For review, see: (b) Vollhardt,
K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539.
(15) Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J . Org. Chem.
1993, 58, 1945.
(16) To the best of our knowledge, this is the first example of
enantioselective transition metal catalysis applied to the synthesis of
substituted helicenes. Enantioselectivity achieved is not sufficient for
the practical synthesis of nonracemic 12 and further search for a more
effective chiral ligand is under way.
(21) Fu, P. P.; Harvey, R. G. Tetrahedron Lett. 1974, 36, 3217.
(22) Lindow, D. F.; Harvey, R. G. J . Am. Chem. Soc. 1971, 93, 3786.
(23) 3-Methoxyhexahelicene 14 can be resolved into enantiomers on
an inexpensive triacetylcellulose column. Unfortunately, its solubility
in ethanol is too poor for the preparative HPLC separation.
(24) 3-Hexahelicenol 15 was converted to the corresponding non-
racemic camphor sulfonate, menthyl carbonate, and camphanate. No
separation of diastereomers was observed in TLC (silica gel) or HPLC
(Whelk O1) analyses.
(17) For review, see: Fu, P. P.; Harvey, R. G. Chem. Rev. 1978, 78,
317.
(18) Yamamoto, K.; Sonobe, H.; Matsubara, H.; Sato, H.; Okamoto,
S.; Kitaura, K. Angew. Chem., Int. Ed. Engl. 1996, 35, 69.
(19) Mashraqui, S.; Keehn, P. Synth. Commun. 1982, 12, 637.
(20) (a) Tashiro, M.; Yamato, T.; Kobayashi, K.; Arimura, T. J . Org.
Chem. 1987, 52, 3196. (b) Hayakawa, K.; Takewaki, M.; Fujimoto, I.;
Kanematsu, K. J . Org. Chem. 1986, 51, 5100.
J . Org. Chem, Vol. 68, No. 13, 2003 5195

Teply´ et al.
SCHEME 5. Ha r tw ig-Bu ch w a ld Am in a tion of
SCHEME 7. Tr a n sfor m a tion of Alcoh ol 15 to
Tr ifla te 16a
Th ioca r ba m a te 25a
a
Reagents and conditions: (a) NaH (2.2 equiv), DMF, rt, 20
min, then (CH3)2NC(S)Cl (1.3 equiv), 85 °C, 20 min, 83%. (b) 280
°C, 30 min, 86%.
SCHEME 8. Syn th esis of Alk yla ted Der iva tive 27a
a
Reagents and conditions: (a) PhNH2 (3.1 equiv), Pd(dba)2 (6%),
(R)-(+)-BINAP (7%), Cs2CO3 (2.4 equiv), toluene, 90 °C, 14 h, 69%.
(b) PhC(NH)Ph (1.5 equiv), Pd(OAc)2 (6%), (R)-(+)-BINAP (6%),
Cs2CO3 (1.4 equiv), THF, 65 °C, 40 h, 85%. (c) PhC(NH)Ph (1.2
equiv), Pd(OAc)2 (4%), (R)-(+)-BINAP (6%), Cs2CO3 (1.4 equiv),
THF, 65 °C, 40 h, then HCl (aq, 2 M), rt, 10 min, 57%.
SCHEME 6. Tr a n sfor m a tion of Tr ifla te 16 to
P h osp h in e 23a
a
Reagents and conditions: (a) EtMgBr (2.4 equiv), THF, 50 °C,
1 h, then CuCl (2.0 equiv), CH2dCHCH2Br (4.0 equiv), 70 °C, 45
min, 67%. (b) CpCo(CO)2 (20%), PPh3 (40%), decane, halogen lamp,
140 °C, 3 h, 74%.
or high yield (Scheme 5). Despite the use of chiral (R)-
(+)-BINAP as a ligand for palladium in the reaction of
racemic triflate 16, no significant kinetic resolution was
observed.
a
Reagents and conditions: (a) Ph2P(O)H (2.0 equiv), Pd(OAc)2
(6%), dppb (6%), iPr2NEt (5.5 equiv), DMSO, 100 °C, 1 h, 74%. (b)
HSiCl3 (12.0 equiv), Et3N (9.0 equiv), xylene, 120 °C, 3 h, 73%.
Helicene-based phosphines are envisaged to serve as
unique ligands for transition metals in enantioselective
catalysis.6 Due to the still limited family of effective chiral
monodentate phosphines and the lasting quest for them,
we decided to explore the synthetic route to the novel
3-hexahelicenyl diphenylphosphine 23 (Scheme 6). Ex-
ploiting the methodology used by Hayashi in the binaph-
thyl series,15 triflate 16 was converted to diphenylphos-
phine oxide 22 on reaction with diphenylphosphine oxide
under Pd catalysis. The following reduction with trichloro-
silane led to the desired monophosphine 23. Both steps
provided good yields.
Aiming to anchor helicene-based components to the
gold surface, we needed to develop the synthetic access
to unprecedented helicene thiol derivatives. Therefore,
the sodium salt of 3-hexahelicenol 15 was reacted with
dimethylthiocarbamoyl chloride to give the corresponding
O-hexahelicenyl thiocarbamate 24 (Scheme 7). The sub-
sequent Newman-Kwart rearrangement28 proceeded
smoothly to provide isomeric S-hexahelicenyl thiocar-
flate 16 in acceptable yield. Analogously, sodium salt
derived from 15 reacted smoothly with perfluoro-1-
butanesulfonyl fluoride to provide nonaflate 17 in high
yield. Both triflate 16 and nonaflate 17 were subjected
to methoxycarbonylation reaction under palladium ca-
talysis25 to afford the methyl ester of 3-hexahelicene-
carboxylic acid 18 in reasonable or excellent yield,
respectively.
Moreover, we have demonstrated that triflate 16 could
serve also as a common starting point for introducing
other substituents. Being inspired by the breakthrough
discovery of Pd-catalyzed aryl halide amination by Hartwig
and Buchwald,26 we applied their chemistries to the
helicene series. Accordingly, on treatment of 16 with
aniline or benzophenone imine under the standard reac-
tion conditions,27 derivatives 19 and 20 along with the
parent 3-hexahelicenylamine 21 were prepared in good
(25) Dolle, R. E.; Schmidt, S. J .; Kruse, L. I. J . Chem. Soc., Chem.
Commun. 1987, 904.
(26) For reviews, see: (a) Hartwig, J . F. In Modern Amination
Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim, Germany, 2000. (b)
Yang, B. H.; Buchwald, S. L. J . Organomet. Chem. 1999, 576, 125. (c)
Hartwig, J . F. Angew. Chem., Int. Ed. 1998, 37, 2046. (d) Wolfe, J . P.;
Wagaw, S.; Marcoux, J .-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31,
805.
(27) (a) Wolfe, J . P.; Åhman, J .; Sadighi, J . P.; Singer, R. A.;
Buchwald, S. L. Tetrahedron Lett. 1997, 38, 6367. (b) Vyskocˇil, Sˇ.
Private communication.
(28) Cossu, S.; De Lucchi, O.; Fabbri, D.; Valle, G.; Painter, G. F.;
Smith, R. A. J . Tetrahedron 1997, 53, 6073.
5196 J . Org. Chem., Vol. 68, No. 13, 2003

3-Hexahelicenol
bamate 25. Throughout the sequence high yields were
achieved.29
crossroads, 3-hexahelicenol 15 could be easily trans-
formed to a series of C-, N-, P-, and S-substituted
analogues in a divergent way. Thus, the carbohelicene-
based primary amine, monodentate phosphine, and thiol
derivative were prepared. The key helicity-forming cy-
clization was shown to proceed enantioselectively when
making use of nickel(0) catalysis in the presence of chiral
ligands. Further studies on the practical nonracemic
synthesis of subtituted carbohelicenes are in progress.
In tr od u cin g Alk yl Su bstitu en ts. The methodology
described also allows introduction of alkyl substituents
into desired positions. Starting from triyne 11, in situ
generated bisacetylide was alkylated with allyl bromide
to furnish 26 in reasonable yield (Scheme 8). Then, under
CpCo(CO)2/PPh3 catalysis, triyne 26 was cyclized to
bisallylated tetrahydrohexahelicene 27 in good yield.
Con clu sion
Ack n ow led gm en t. The financial support by the
Grant Agency of the Czech Republic (Reg. No. 203/99/
1448 and 203/02/0248) 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.
In summary, a synthetic sequence relying on the Co(I)-
and Ni(0)-catalyzed intramolecular [2+2+2] cycloisomer-
ization of aromatic triynes provided a reliable route to
novel substituted hexahelicenes. By using simple building
blocks, 3-hexahelicenol 15 was synthesized in a conver-
gent way allowing most of the synthetic steps to be
carried out on a multigram scale. Standing on the
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails and characterization data for all synthesized compounds
and 1H NMR spectra for 3, 4, 6, and 8-27. This material is
available free of charge via the Internet at http://pubs.acs.org.
(29) On treatment of 25 with lithium aluminium hydride in tetra-
hydrofuran, free corresponding thiol was produced in nearly quantita-
tive yield after flash chromatography. Its structure was confirmed only
by HR EI MS (calculated for C26H16S 360.097272, found 360.095867)
as 1H NMR and IR provided complex spectra due to the partial
formation of diastereomeric disulfides.
J O034369T
J . Org. Chem, Vol. 68, No. 13, 2003 5197