Novel synthesis of thioalkoxy-substituted OXA[9]helicenes by the reaction of helical quinones with thiols

Article abstract of DOI:10.3987/COM-12-12640

The reaction of helical quinone with thiols in the presence of acid such as HCl, para-toluene sulfonic acid (pTSA), or Yb(OTf)₃·3H ₂O to form resulted in the formation of thioalkoxy-substituted oxa[9]helicenes in moderate to good yie

Full text of DOI:10.3987/COM-12-12640

HETEROCYCLES, Vol. 87, No. 3, 2013
547
HETEROCYCLES, Vol. 87, No. 3, 2013, pp. 547 - 550. © 2013 The Japan Institute of Heterocyclic Chemistry
Received, 27th November, 2012, Accepted, 21st January, 2013, Published online, 31st January, 2013
DOI: 10.3987/COM-12-12640
NOVEL
SYNTHESIS
OF
THIOALKOXY-SUBSTITUTED
OXA[9]HELICENES BY THE REACTION OF HELICAL QUINONES
WITH THIOLS
Mohammad Salim,a,b Takao Kimura,a and Michinori Karikomi*
a
Department of Material and Environmental Chemistry, Graduate School of
Engineering, Utsunomiya University, Utsunomiya, Tochigi 321-8585, Japan
E-mail: karikomi@cc.utsunomiya-u.ac.jp
b
Department of Chemistry, School of Physical Sciences, Shahjalal University of
Science and Technology, Sylhet 3114, Bangladesh
Abstract – The reaction of helical quinone with thiols in the presence of acid such
as HCl, para-toluene sulfonic acid (pTSA), or Yb(OTf)3·3H2O to form resulted in
the formation of thioalkoxy-substituted oxa[9]helicenes in moderate to good
yields.
Helicenes and other related helical compounds captured the interest of researchers, owing to their
potential for use as effective chiral sources in asymmetric synthesis, chiral materials, and optical materials
as a result of this potential arises from their inherent asymmetric molecular structures. In the past decade,
a large number of helicenes and other related molecules such as aza- and thia-helicenes have been
developed because of their extraordinary and unique properties. Thus, the synthesis of helicene-like
compounds has become a subject of increasing interest to synthetic organic chemists.1 Among the several
synthetic strategy for the helical polycondensed structure, photo cyclization of stilbene derivatives or
styrylheterocycles has emerged as one of the most powerful and attractive methodologies. Oxahelicenes
are also possible to synthesize according to the same methodology. However, only a few examples of
RSH, acid
CHCl3, rt
+
R
S
O
O
O
O
1
3
2
2a: R = Bu, 2b: R = Dodecyl, 2c: R = -Pr, 2d: R = -Bu, 2e: R = cyclohexyl 2f: R = -tetradecyl 2g: R = -tolyl,
n-
i
t
t
p
2h: R = 2-pyridyl
Scheme 1

548
HETEROCYCLES, Vol. 87, No. 3, 2013
oxahelicenes have been reported. In this context, the development of new synthetic approaches to
synthesize oxygen-containing helical molecules represents an important opportunity to develop an
application of these new, potential and useful molecules. We have previously reported the synthesis of the
helical quinones 1 derived from 2-hydroxybenzo[c]phenanthrenes via a stereo- and region-selective
oxidative coupling using CuCl(OH)–TMEDA.2 Furthermore, we studies the synthetic uses of the
quinones 1 for the construction of new helical molecules. Then, we have reported on synthesis of
oxa[9]helicenes from the helical quinones 1 with Lawesson’s reagent or phosphorous pentasulfide.3 We
also have reported on synthesis of alkoxy substituted oxa[9]helicenes by the reaction of the quinone 1
with several alcohols.4 According to the results, the reaction of the quinone with primary alcohols and
secondary alcohols gave alkoxy-substituted oxa[9]helicenes 2 in good yields. However, the cases of
reactions involving tertiary alcohol, such as t-BuOH did not give any products.4 Thus, as an extension of
these results, we wish to report herein the novel synthesis of thioalkoxy oxa[9]helicenes from the helical
quinone with various thiols. We initially examined the reaction of 1 and n-butylthiol as a nucleophile.
Table 1 shows the reaction of helical quinone 1 with series of structurally different thiols in the presence
of acids (HCl, pTSA, Yb(OTf)3·3H2O). Most of cases a mixture of desired 9-thioalkoxy-11-
oxa[9]helicene 2a-h and undesired non-substituted 11-oxa[9]helicene 3 was obtained in good yield.5,6
Similar to the case of n-butylthiol, n-dodecanethiol also gave the corresponding 2b in moderate
selectivity (entry 4). The reaction of secondary thiols such as i-PrSH and cyclohexylthiol afforded the
corresponding thioalkoxy substituted oxa[9]helicene 2c-d more selectively compare to the cases of
primary thiols (entries 5 and 6). Interestingly, the reactions of tertiary thiols such as t-BuSH and
tert-tetradecanethiol gave thioalkoxy substituted 2e-f selectively in good yield. In these cases, the
formation of 3 was not detected (entries 7 and 8). Aryl thiols were also reacted to give the corresponding
aryl thioalkoxy substituted oxa[9]helicene 2g-h with moderate selectivity (entries 9, 10, and 11).
These results would suggest a convincing reaction mechanism for the synthesis of 2 (Scheme 2). The
initial conjugate addition and the following cyclization are catalyzed by Brønsted acid as a common
process for both 2 and 3. The selectivity for the substituted 2 or non-substituted 3 is realized at the final
elimination step; the selectivity is controlled by the steric hindrance of the thiols. The less hindered
primary and secondary thiols are possible to form disulfide as an eliminating species (route b). Thus, the
product selectivity for 2 (route a) is unsatisfactory. On the other hand, in the cases of tertiary thiols are
too hindered to form the corresponding disulfide. Thus, tertiary thioalkoxy substituted oxa[9]helicenes
2e-f were obtained selectively. Perhaps the most important pieces of experimental evidence to support for
this reaction mechanism is the fact that disulfide was detected in the reaction mixture. When
cyclohexylthiol was used, cyclohexyl disulfide was detected in the reaction mixture by the comparison of
its 1H NMR and 13C NMR to the commercially available authentic sample.

HETEROCYCLES, Vol. 87, No. 3, 2013
549
Table 1. Synthesis of thioalkoxy oxa[9]helicene by the reaction of helical quinone 1 with various thiols
Entry Reagent (equiv)
Acid (equiv)
conc. HCl (4)
pTSA (1)
Time (h) Product Ratio 2:3a Yield (%)b
1
n-BuSH (3)
0.5
0.5
2a
2a
2a
2b
2c
2d
2e
2f
60:40
37:63
34:61
58:45
71:29
71:29
100:-
100:-
67:33
60:40
76:24
82 (44)
79
2
n-BuSH (3)
3
n-BuSH (3)
Yb(OTf)3·3H2O (1) 0.5
82
4
Me(CH2)11SH (3)
Me2CHSH (3)
Cyclohexyl-SH (3)
Me3CSH (3)
conc. HCl (4)
conc. HCl (4)
conc. HCl (4)
conc. HCl (4)
1
71 (32)
81 (50)
79 (49)
(79)
5
1
6
1
7
0.5
0.5
1
8
Me(CH2)10C(CH3)2SH (3) conc. HCl (4)
(70)
9
p-MeC6H4SH (2)
p-MeC6H4SH (2)
2-Pyridyl-SH (2)
conc. HCl (4)
pTSA (1)
2g
2g
2h
90 (55)
55
10
11
1
pTSA (1)
0.5
79 (58)
aThe product ratio was determined from 1H NMR spectra.
bTotal yield as a mixture of 2 and 3. The isolated yield of 2 is shown in parentheses.
RSH/H+
H
1
SR
HSR
O
HO
O
HO
H
H
a
a
SR
SR
RSH
H
SR
O
2a-h
-H2O
O
H2O
b
b
H
SR
H
+ RS-SR
O
3
Scheme 2
In conclusion, this paper describes a novel synthetic route for 9-thioalkoxy-substituted 11-oxa[9]helicene
derivatives 2 using Brønsted acids; the synthesis is catalyzed by the nucleophilic addition of various
thiols and subsequent cyclization and dehydration reactions. Unfortunately, there is a competing side

550
HETEROCYCLES, Vol. 87, No. 3, 2013
reaction for non-substituted 11-oxa[9]helicene 3. We then revealed that the selectivity is considerably
controlled by the steric hindrance of thiols. In the cases of tertiary thiols, the completed selectivity for the
thioalkoxy substituted oxa[9]helicenes 2 were obtained was shown. Further studies aimed at obtaining
substituted oxa[9]helicenes by various nucleophiles are currently underway in our laboratory.
ACKNOWLEDGEMENTS
The authors wish to thank Mr. M. Roppongi of the Collaboration Center for Research & Development,
Utsunomiya University, for MS spectral data.
REFERENCES AND NOTES
1. For review (a) A. Urbano, Angew. Chem., Int. Ed., 2003, 42, 3986; (b) Y. Shen and C.-F. Chen,
Chem. Rev., 2012, 112, 1463.
2. M. Karikomi, M. Yamada, Y. Ogawa, H. Houjou, K. Seki, K. Hiratani, K. Haga, and T. Uyehara,
Tetrahedron Lett., 2005, 46, 5867.
3. M. Salim, A. Akutsu, T. Kimura, M. Minabe, and M. Karikomi, Tetrahedron Lett., 2011, 52, 4518.
4. M. Salim, H. Ubukata, T. Kimura, and M. Karikomi, Tetrahedron Lett., 2011, 52, 6591.
5. General procedure for the synthesis of 2: Quinone 1 (0.05 mmol) was added with thiol (2-3 eq) in
chloroform (1 mL) in the presence of conc. HCl (4 eq) at room temperature for 0.5-1 h. The mixture
was neutralized by 5% NaOH, washed with brine and extracted with chloroform (3 × 10 mL). The
organic layer was dried (Na2SO4), filtered, and concentrated under vacuum. The crude product was
purified by column chromatography on silica gel (chloroform) to give a mixture of 2 and 3. The
mixture was separated by recrystallization with ethyl acetate.
6. Compound characterization: 2a. 1H NMR (500 MHz, CDCl3, /ppm): 8.63 (1H, d, J = 8.5 Hz), 8.35
(1H, s), 8.28 (1H, d, J = 8.5 Hz), 8.23 (1H, d, J = 8.0 Hz), 7.98 (1H, d, J = 8.0 Hz), 7.62 (1H, d, J =
8.5 Hz), 7.59 (1H, d, J = 8.5 Hz), 7.58 (1H, d, J = 8.0 Hz), 7.54 (1H, d, J = 8.5 Hz), 7.40 (1H, d, J =
8.5 Hz), 7.38 (1H, d, J = 8.5 Hz), 7.33 (1H, d, J = 7.5 Hz), 7.28 (1H, d, J = 8.0 Hz), 6.79 (1H, t, J =
7.5 Hz), 6.74 (1H, t, J = 7.0 Hz), 6.22 (1H, d, J = 9.0 Hz), 6.18 (1H, d, J = 8.0 Hz), 5.75 (1H, t, J =
8.0 Hz), 5.72 (1H, t, J = 7.0 Hz), 3.19-3.29 (2H, m), 1.79-1.85 (2H, m), 1.55-1.62 (2H, m), 0.98 (3H,
t, J =7.0 Hz), 13C NMR (125 MHz, CDCl3,  /ppm): 154.04, 153.53, 134.24, 129.94, 129.86, 129.56,
129.52, 129.49, 128.97, 127.59, 127.27, 127.25, 127.19, 126.99, 126.54, 126.51, 126.35, 126.24,
126.05, 125.55, 125.37, 125.33, 125.13, 125.04, 124.63, 124.37, 124.18, 124.15, 124.03, 122.85,
122.31, 122.29, 121, 120.03, 112.24, 110.87, 34.94, 31.21, 22.13, 13.76, HRMS (EI) calcd for
C40H28OS [M]+ 556.1861, found 556.1861.