Synthesis of a Five-Fold-Differentiated 1,3,5,7,9-Pentasubstituted Corannulene: A Maximal Labeling Problem in the Context of Corannulene

Article abstract of DOI:10.1055/s-0035-1562845

This work defines a maximally labeled isomer problem in the context of 1,3,5,7,9-pentasubstituted corannulenes and explores two new synthetic strategies for the construction of key C-C bonds in the corannulene nucleus: a) a Diels-Alder cycloaddition of thiophene dioxide and acenaphthene fragments; b) a manganese-mediated reductive coupling of benzylic halides, which tolerates carboxy ester functionality. It advances the area of curved aromatics based on corannulene by setting a new family of targets for chemical synthesis and providing additional general synthetic tools.

Full text of DOI:10.1055/s-0035-1562845

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2016, 27, A–F
A
cluster
Synlett
R. Maag, J. Siegel
Cluster
Synthesis of a Five-Fold-Differentiated 1,3,5,7,9-Pentasubstituted
Corannulene: A Maximal Labeling Problem in the Context of Cor-
annulene
R5
X
Roman Maaga
Jay S. Siegel*a,b
R4
X
X = Cl [ICl]
R1
X
X = B(OR)2
[cat. CH activation]
a
???
Department of Chemistry, University of Zurich, Winterthurerstrasse
R3
X
1
90, 8057 Zurich, Switzerland
R2
5
X
b
School of Pharmaceutical Science and Technology, Tianjin University,
2 Weijin Road, Nankai District, Tianjin, 300072, P. R. of China
9
5
4
5
3
4
3
5
4
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3
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4
2
5
dean_spst@tju.edu.cn
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Received: 12.07.2016
Accepted after revision: 28.07.2016
Published online: 05.08.2016
bowl inversion. Thus, there are 48 maximally labeled iso-
mers, each asymmetric (i.e., of C symmetry) as static bowl
1
DOI: 10.1055/s-0035-1562845; Art ID: st-2016-w0452-c
structures, and inversion interconverts the enantiomeric
pairs to yield 24 possible time-averaged C -symmetry iso-
s
Abstract This work defines a maximally labeled isomer problem in the
context of 1,3,5,7,9-pentasubstituted corannulenes and explores two
new synthetic strategies for the construction of key C–C bonds in the
corannulene nucleus: a) a Diels–Alder cycloaddition of thiophene diox-
ide and acenaphthene fragments; b) a manganese-mediated reductive
coupling of benzylic halides, which tolerates carboxy ester functionality.
It advances the area of curved aromatics based on corannulene by set-
ting a new family of targets for chemical synthesis and providing addi-
tional general synthetic tools.
mers. In the present work, selective preparation of one such
isomer serves as a reduction to practice of the idea; howev-
er, a future goal would be to address each isomer by a gen-
eral synthetic methodology. Indeed, if five-fold chemical or-
10
thogonality could be achieved, then in principle any one
of these permutation isomers can serve as the key interme-
diate to prepare a library of derivatives comprising a full set
of 24 pentafunctional derivatives selectively (Scheme 1);
but how to reach that goal?
Key words 1,3,5,7,9-pentasubstituted corannulene, Diels–Alder cyclo-
addition, reductive coupling
Starting from corannulene and step-by-step replacing
CH bonds seems a Herculean task even with modern meth-
1
11
With access to corannulene on kilogram scale, and the
ods in selective directed multi-CH activation. In contrast,
existence of convenient methods to make 1,3,5,7,9-pentaX-
an approach through a convergent synthesis of the coran-
nulene nucleus would reduce the problem to the selective
control of the substitution pattern on the converging frag-
ments (Scheme 2). Following the most common disconnec-
tion, one would combine a tetrasubstituted diene with a
monosubstituted dieneophile (Scheme 2, left). Alternative-
ly, one could imagine combining a trisubstituted dieneo-
phile with a disubstituted diene (Scheme 2, right).
The latter strategy, which happens to balance the num-
ber of substituents in each fragment better, has been given
much less attention in previous corannulene syntheses.
Thus, Diels–Alder chemistry between a disubstituted thio-
phene dioxide and a trisubstituted acenaphthene would
provide an opportunity to explore another general convergent
method toward the corannulene nucleus as well as address
the isomer selectivity problem,12 even if it required separa-
tion of an undesired cycloaddition isomer (Scheme 3).
2
3
corannulene (X = Cl; X = B(OR) ), a diverse spectrum of
2
sym-pentasubstituted forms lie well within the grasp of
4
even the avocational synthetic chemist. In contrast, syn-
thesis of a fivefold differentiated 1,3,5,7,9-pentasubstituted
corannulene remains an open challenge. The issue of selec-
tivity requires the ability to on one hand restrict substitu-
tion to all the pro-R (respectively all pro-S) hydrogen atom
sites, yet replace each such hydrogen by a different ligand
1
2
3
4
5
(
R , R , R , R , R ). Such problems in isomerism fall into the
5
class of maximally labeled ‘symmetric’ scaffolds, for exam-
ple, the classic maximally labeled tetrahedra of van't Hoff,
and LeBel, for which there are two permutational iso-
mers, or the maximally labeled octahedra of Werner, for
6
7
8
9
which there are 30 permutational isomers. In the present
case, the five potential sites of substitution present a field
of C -static symmetry, with the possibility of a dynamic
5
mirror operation perpendicular to the five-fold axis upon
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

B
Synlett
R. Maag, J. Siegel
Cluster
R5
X
R4
X
X = Cl [ICl]
R1
X
X = B(OR)2
[cat. CH activation]
?
??
R3
X
R2
X
5
4
5
3
4
3
5
4
4
3
5
3
4
5
3
4
4
2
5
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
3
4
5
5
2
2
2
4
2
2
2
2
2
2
3
2
3
2
5
5
5
2
4
2
3
2
2
3
3
4
3
4
3
4
5
5
5
3
2
3
2
4
3
4
3
5
4
3
5
3
4
3
4
5
5
2
4
2
4
2
5
2
3
3
2
3
4
5
2
4
3
5
4
5
4
5
5
Scheme 1 Maximally labeled sym-pentasubstituted corannulene
R5
R5
R5
R4
produced carbinol 2. Acidic treatment with HBr induced
a cyclization rearomatization to form 1-tert-butyl-3-ethyl-
6-methylnaphthylene (3) as a clean product.14
R4
R4
R1
R1
R1
OH
R3
R3
R2
Cl
R2
R3
O
c
a
b
O
R2
Scheme 2 Disconnection strategies
1
2
3
Scheme 4 Synthesis of 3. Reagents and conditions: (a) Mg (Et O) ca. –10 °C,
2
R5
R5
R5
3-methylbenzyl chloride (Et O), 2–3 h, ca. –10 °C, propionitrile (Et O),
2
2
R4
R4
R4
48 h, –10 °C to r.t. (84%); (b) i-Pr NH (Et O), 0 °C, n-BuLi (n-hexane), 30
2
2
S
min at 0 °C, 3,3-dimethylbutan-2-one, 1.5 h, at –78 °C, 1, 8 h at –78 °C
(73%); (c) 2 (AcOH), 48% aq HBr, r.t., to 90 °C, 4 h (77%).
O
O
R1
R1
R3
R1
R3
Elaboration of 3 to the acenaphthene took two circu-
itous routes; the shorter reported here and the longer is ar-
chived in the supplementary material as compounds Alt-
Ia/b – Alt-IVa/b. Initially, diacylation of 3 with oxalyl chlo-
R2
R2
R3
R2
undesired
desired
Scheme 3 Diels–Alder strategy from acenaphthene and thiophene-
S,S-dioxide fragments
ride and AlBr lead to the acenaphthoquinone 4-H. Bromi-
3
nation of 4-H occurred selectively at the desired position to
form 4-Br. Reduction of 4-Br with sodium borohydride gave
a mixture of diols, which upon treatment with p-toluene-
sulfonic acid produced acenaphthone 5. After carbonyl re-
duction and dehydration of the ensuing alcohol one arrives
at the acenaphthene 6 (Scheme 5).15
The thiophene dioxide fragment was prepared starting
from 2-methylthiophene. Bromination with elemental bro-
mine in acetic acid gave 2,4-dibromo-5-methylthiophene
(7, Scheme 6). Selective lithiation of the 2-bromo group fol-
lowed by coupling with 1-iodopropane produced 3-bromo-
With a strategy in place, construction of the fragments
could begin. Synthesis of the acenaphthene fragment fol-
lowed a modification of the route developed during earlier
corannulene syntheses for preparing acenaphthoquinones.
The Grignard reagent of α-chloro-m-xylene reacted with
propionitrile and after hydrolysis gave 1-(3-methylphenyl)-
2
-butanone 1 (Scheme 4).13 Aldol reaction between 1 and
the enolate of pinacolone, generated at –78 °C with LDA,
2-methyl-5-propylthiophene (8). Subsequent lithiation of 8
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

C
Synlett
R. Maag, J. Siegel
Cluster
O
O
O
O
O
O
O
O
c, d
e, f
a
O
3
S
Br
X
Br
O O
10
a, b
5
6
b
4-H
4-Br
R
R
Scheme 5 Synthesis of 6. Reagents and conditions: (a) CH Cl (N -de-
2
2
2
gassed), AlBr , at –25 °C, oxalyl chloride (CH Cl ), 30 min at –25 °C, to
3
2
2
Br
ca. –10 °C, 8 h (38%); (b) Br , r.t. to 60 °C, 1 h (98%); (c) CH Cl –EtOH
2
2
2
11-Br
11-Ar
12-Br
12-Ar
(
(
5:1), NaBH , r.t. to reflux, 2 h; (d) toluene, TsOH·H O, r.t. to reflux, 3 h
4
2
84%, 2 steps); (e) CH Cl –EtOH (5:3), NaBH , r.t. to reflux, 2 h; (f) tolu-
6
2
2
4
ene, TsOH·H O, r.t. to reflux, 2 h (69%, 2 steps).
2
Scheme 7 Synthesis of 12-Ar. Reagents and conditions: (a) reflux 24 h,
benzene, DDQ, reflux 4 h (56%); (b) 4-methoxyphenylboronic acid,
K CO (toluene–EtOH–H O, 4:4:1), N , r.t., Pd(PPh ) , r.t. to reflux 5 h
2
3
2
2
3 4
(
28% isolated 12-Ar).
and quenching with CO lead to the 2-methyl-5-propylthio-
2
phene-3-carboxylic acid, which could be esterified to the
16
methyl ester 9. Methyl ester 9 was oxidized by peroxytri-
Despite there being several methods for reductive cou-
fluoroacetic acid to complete the thiophene dioxide frag-
ment 10.
pling of benzylic bromides to convert bromoalkylfluoran-
thenes into corannulenes, the manganese-based coupling of
benzylic bromides had not been investigated.20 This meth-
od promised to tolerate the carboxylic ester, as well as the
tert-butyl group and offered an alternative to the nickel-
mediated methods. Indeed, manganese-mediated reductive
cyclization of pentabromide 13 produced a mixture of cy-
clized products 14, which following rearomatization by
DDQ yielded the target compound 15, a 1,3,5,7,9-penta-
substituted corannulene where all substituents are differ-
17
Br
Br
a
b
Br
S
S
S
7
8
c, d
CO2Me
CO2Me
e
S
S
21
ent (Scheme 8).
O
O
All signals for 15 in the proton NMR spectrum could be
assigned (Figure 1). The proton signals for the five hydro-
gens on the corannulene nucleus all appear in the region δ
1
0
9-Me
Scheme 6 Synthesis of 10. Reagents and conditions: (a) AcOH, at 0 °C,
Br (AcOH), 0 °C to r.t., 12 h (90%); (b) THF, at –78 °C, n-BuLi (n-hexane)
5 min, at –78 °C, n-propyl iodide at –78 °C, 10 min to –15 °C 1 h to r.t.,
h (72%); (c) THF, at –78 °C, n-BuLi (n-hexane) 45 min, at –78 °C, CO2
at –78 °C to r.t., 1 h; (d) MeOH, SOCl , r.t. to reflux 20 h (40%, 2 steps);
2
=
7.5–8.8 ppm. Those proton signals for hydrogens adjacent
to alkyl groups bearing benzylic hydrogens showed the ex-
pectedly small J1,4 couplings (ca. 1 Hz); and therefore as-
4
1
2
(
e) H O (35% in H O) at 0 °C, TFAA at 0 °C (slow addition, very exother-
signment could be made from the splitting patterns. Some
baseline impurities notwithstanding, there is no doubt
about the identity of the final product (see Supporting In-
formation).
2
2
2
mic; DANGER: do not exceed 10 °C), another 10 min at 0 °C, 9-Me
(
MeCN; DANGER: do not exceed 30 °C; 36%).
Diels–Alder reaction between fragments 6 and 10 fol-
lowed by rearomatization with DDQ proceeded smoothly
but gave a mixture of two regioisomeric bromofluoranthe-
nes 11-Br/12-Br in roughly equal parts. The isomers could
only be separated by preparative HPLC. Coupling the mix-
ture of bromides with 4-methoxyphenylboronic acid led to
arylfluoranthenes 11-Ar/12-Ar, which could be separated
by normal chromatographic methods. The desired isomer
18
12-Ar was used moving forward (Scheme 7).
Wohl–Ziegler bromination of the separated 12-Ar deliv-
ered a mixture of brominated fluoranthenes, in which the
major contribution came from a mixture of diastereomers
of pentabromide 13. In the course of this work, C -symmet-
s
rical fluoranthene derivatives with comparable substitu-
ents to 12-Ar have shown similar bromination patterns.19
Figure 1 1H NMR support of structure
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

D
Synlett
R. Maag, J. Siegel
Cluster
O
O
O
O
O
O
Br
Br
Br
Br
Br
O
O
O
12-Ar
13 (mixture)
14
a, b, c
O
H
O
H
H
H
H
O
15
Scheme 8 Synthesis of 15. Reagents and conditions: (a) NBS, BPO (CCl ), r.t. to reflux, hν (Osram, 100 W), 7 h; (b) THF–H O (1.5:1), N , r.t., CuCl , r.t.,
4
2
2
2
3
min, Mn powder, r.t., 24 h; (c) benzene, DDQ, r.t. to reflux, 5 h (11%, 3 steps).
The presence of the ethyl group allows the assessment
the barrier can be estimated to be 8.9 kcal/mol, a value con-
sistent with that seen for other pentasubstituted corannu-
lenes (pentaethyl = 9.0 kcal/mol).
Having demonstrated the proof of principle regarding a
single maximally labeled isomer, the task remains to tailor
each of these substituents to a specific further reactivity.
With an olefin, an electron-rich aromatic, an azide or a thi-
ol, an ester, and an alkyl group, one could imagine exploit-
of the barrier to bowl inversion by variable-temperature
NMR (Figure 2). At the static limit the methylene protons
are diastereotopic and give rise to a doublet of doublet
quartets, which upon increasing rate of bowl inversion co-
alesce and then become a simple quartet at the dynamic
limit. From the line shape or temperature of coalescence,
ing metathesis, E , ‘click’, transesterification, and CH acti-
Ar
vation chemistry in selective ways. At that point one might
be able to display in the ‘second sphere’ all 24 distributions
of a set of five differentiable groups after reaction with ap-
propriate reaction partners. At present this is fantasy and
folly, but also fun!
Overall, this work defines a maximally labeled isomer
problem in the context of 1,3,5,7,9-pentasubstituted coran-
nulenes and explores two new synthetic strategies for the
construction of key C–C bonds in the corannulene nucleus:
1
Figure 2 Variable-temperature H NMR spectra of the methylene re-
gion of 15
Figure 3 Star-growth by orthogonal reactivity
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

E
Synlett
R. Maag, J. Siegel
Cluster
(
a) a Diels–Alder cycloaddition of thiophene dioxide and
(14) Bradsher, C. K. J. Am. Chem. Soc. 1940, 62, 486.
(
15) Becker, H.-D.; Hansen, L.; Andersson, K. J. Org. Chem. 1985, 50,
77.
16) (a) Tatsugi, J.; Okumara, S.; Izawa, Y. Bull. Chem. Soc. Jpn. 1986,
acenaphthene fragments; b) a manganese-mediated reduc-
tive coupling of benzylic halides, which tolerates car-
boxyester functionality. It advances the area of curved aro-
matics based on corannulene by setting a new family of tar-
gets for chemical synthesis and providing additional
general synthetic tools (Figure 3).
2
(
59, 3311. (b) Pu, S.; Liu, G.; Li, G.; Wang, R.; Yang, T. J. Mol. Struct.
2007, 833, 23.
(
17) (a) Nenajdenko, V. G.; Gavryushin, A. E.; Balenkova, E. S. Tetra-
hedron Lett. 2001, 42, 4397. (b) Nenajdenko, V. G.; Moiseev, A.
M.; Balenkova, E. S. Russ. Chem. Bull. Int. Ed. 2004, 53, 2144.
18) Cycloaddition
(
Acknowledgment
To an oven-dried 50 mL round-bottom flask, equipped with stir
bar and reflux condenser with N inlet, was added the acenaph-
2
We thank the Swiss National Science Foundation, National Basic Re-
search Program of China (2015CB856500), the Qian Ren Scholar Pro-
gram of China, and the Synergetic Innovation Center of Chemical
Science and Engineering (Tianjin) for supporting this work.
thylene 6 (1.26 g, 3.83 mmol), thiophene-1,1-dioxide 10 (0.89 g,
3.86 mmol), and dry xylene (9 mL). The yellow solution was
degassed three times by pulling vacuum and heated to reflux
for 24 h. After cooling to r.t., the solvent was removed by rotary
evaporation and the crude product was obtained as brown
resin.
Supporting Information
In an oven-dried 100 mL round-bottom flask, equipped with
stir bar and reflux condenser with N inlet, the crude dihydro-
fluoranthene (max. 3.83 mmol) was dissolved in dry benzene
2
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562845.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
(65 mL). DDQ (1.3 g, 5.73 mmol) was added in one step, and the
dark suspension was heated to reflux for 4 h. After cooling to r.t.,
the mixture was filtered through a plug of silica and thoroughly
rinsed with CH Cl . The filtrate was evaporated giving a dark
References and Notes
2
2
residue which was sonicated with n-hexane. The resulting sus-
pension was filtered through Celite giving a yellow solution. The
(
1) Butterfield, A. M.; Gilomen, B.; Siegel, J. S. Org. Process Res. Dev.
012, 16, 664.
2) (a) Cheng, P.-C. PhD Dissertation; Boston College: USA, 1996.
b) Seiders, T. J.; Elliott, E.; Grube, G.; Siegel, J. S. J. Am. Chem.
2
solution was washed with sat. aq NaHCO , the organic phase
(
3
was dried over MgSO and filtered. The solvent was evaporated,
(
4
and the crude product was subjected to flash column chroma-
tography on silica using n-hexane–EtOAc (50:1). The fluoran-
thenes 11-Br/12-Br (mixture of regioisomers) were obtained as
yellow resins (1.05 g, 56%, two steps). Analytical separation of
the two isomers was achieved by HPLC (Waters Spherisorb S5,
Nitrile, 250 × 20mm, 25 mL/min) with n-hexane–EtOAc (200:1).
The solvent mixture was recycled through rotary evaporation.
Methyl 4-tert-Butyl-2-bromo-6-ethyl-1,7-dimethyl-10-pro-
pylfluoranthene-8-carboxylate (12-Br)
Soc. 1999, 121, 7804. (c) Mizyed, S.; Georghiou, P. E.; Bancu, M.;
Cuadra, B.; Rai, A. K.; Cheng, P.; Scott, L. T. J. Am. Chem. Soc.
2001, 123, 12770. (d) Xu, B. K. MS Dissertation; Tianjin Univer-
sity: P. R. of China, 2016.
(
3) (a) Eliseeva, M. N.; Scott, L. T. J. Am. Chem. Soc. 2012, 134, 15169.
(b) Da Ros, S.; Linden, A.; Baldridge, K. K.; Siegel, J. S. Org. Chem.
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(
4) (a) Wu, Y.-T.; Bandera, D.; Maag, R.; Linden, A.; Baldridge, K. K.;
Siegel, J. S. J. Am. Chem. Soc. 2008, 130, 10729. (b) Pappo, D.;
Mejuch, T.; Reany, O.; Solel, E.; Gurram, M.; Keinan, E. Org. Lett.
Rf = 0.3 (silica gel; n-hexane–EtOAc, 10:1). IR (film): 2958 (w),
2
1
1
932 (w), 2872 (w), 1717 (s), 1585 (w), 1458 (m), 1433 (m),
2
2
009, 11, 1063. (c) Mattarella, M.; Siegel, J. S. Org. Biomol. Chem.
012, 10, 5799. (d) Pogoreltsev, A.; Solel, E.; Pappo, D.; Keinan,
378 (w), 1364 (w), 1277 (m), 1255 (m), 1200 (s), 1168 (m),
1
054 (m), 995 (w), 957 (w), 906 (m), 731 (s). H NMR (500 MHz,
E. Chem. Commun. 2012, 48, 5425. (e) Jackson, E. A.; Steinberg,
B. D.; Bancu, M.; Wakamiya, A.; Scott, L. T. J. Am. Chem. Soc.
CDCl ): δ = 8.61 (s, 1 H), 7.81 (s, 1 H), 7.42 (s, 1 H), 3.95 (s, 3 H),
3
3
3
3
.05 (q, J = 7.5 Hz, 2 H), 2.96 (t-like, J = 7.5 Hz, 2 H), 2.81 (s, 3
H), 2.73 (s, 3 H), 1.69 (sext, J = 7.5 Hz, 2 H), 1.64 (s, 9 H), 1.35 (t,
2
007, 129, 484. (f) Hayama, T.; Baldridge, K. K.; Wu, Y.-T.;
Linden, A.; Siegel, J. S. J. Am. Chem. Soc. 2008, 130, 1583.
g) Scott, L. T.; Jackson, E. A.; Zhang, Q.; Steinberg, B. D.; Bancu,
3
3
3
13
1
J = 7.5 Hz, 3 H), 0.90 (t, J = 7.5 Hz, 3 H). C{ H} NMR (125 MHz,
CDCl ): δ = 168.67, 146.31, 142.11, 141.64, 138.96, 136.95,
(
M.; Li, B. J. Am. Chem. Soc. 2012, 134, 107.
3
1
1
2
34.38, 132.05, 131.40, 131.07, 130.81, 130.07, 130.06, 127.25,
(
5) (a) Pólya, G.; Mead, R. C. Combinatorial Enumeration of Groups,
25.86, 125.49, 51.95, 37.32, 36.12, 32.45, 32.43, 29.22, 24.54,
Graphs and Chemical Compounds; Springer: Berlin, 1987.
+
4.35, 21.96, 15.15, 14.16. ESI-HRMS: m/z [M + Na] calcd for
(b) Pólya, G. Acta Math. 1937, 68, 145.
+
C29H33BrNaO2 : 515.1556; found: 515.1551.
(
(
(
6) van’t Hoff, J. H. Bull. Soc. Chim. Fr. 1875, 23, 295.
7) Le Bel, J. A. Bull. Soc. Chim. Fr. 1874, 22, 337.
Methyl 3-tert-Butyl-5-bromo-1-ethyl-6,7-dimethyl-10-pro-
pylfluoranthene-8-carboxylate (11-Br)
8) For a discussion on the importance of permutational isomerism
to the origins of van’t Hoff's ideas ‘asymmetric centers’, see:
Mislow, K.; Siegel, J. J. Am. Chem. Soc. 1984, 106, 3319.
9) Von Zelewsky, A. Stereochemistry of Coordination Compounds;
John Wiley: Chichester, 1995.
10) Wong, C.-H.; Zimmerman, S. C. Chem. Commun. 2013, 49, 1679.
11) Davies, H. M. L.; Morton, D. J. Org. Chem. 2016, 81, 343.
12) Raasch, M. S. J. Org. Chem. 1980, 45, 856.
Rf = 0.3 (silica gel; n-hexane–EtOAc, 10:1). 1H NMR (500 MHz,
CDCl ): δ = 8.60 (s, 1 H), 7.85 (s, 1 H), 7.40 (s, 1 H), 3.95 (s, 3 H),
3
3
3
.13–2.98 (m, 4 H), 2.74 (s, 3 H), 2.69 (s, 3 H), 1.71 (sext, J = 7.5
(
3
3
Hz, 2 H), 1.65 (s, 9 H), 1.34 (t, J = 7.5 Hz, 3 H), 0.96 (t, J = 7.5 Hz,
1
3
1
3
1
1
3
H). C{ H} NMR (125 MHz, CDCl ): δ = 168.67, 147.17, 142.42,
(
(
(
(
3
41.83, 140.21, 137.89, 134.77, 134.59, 132.38, 131.79, 131.58,
31.06, 129.70, 129.54, 128.08, 126.13, 125.86, 52.13, 37.73,
6.34, 32.65, 31.96, 29.80, 25.15, 24.73, 22.59, 16.10, 14.21.
13) Jones, R. L.; Pearson, D. E.; Gordon, M. J. Org. Chem. 1972, 37,
Aryl Coupling
3369.
The isomeric mixture of bromofluoranthenes 11-Br/12-Br (378
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

F
Synlett
R. Maag, J. Siegel
Cluster
mg, 0.766 mmol), 4-methoxyphenylboronic acid (151.5 mg,
.996 mmol), and K CO were dissolved in thoroughly
(20) Ma, J.; Chan, T.-H. Tetrahedron Lett. 1998, 39, 2499.
(21) Bromination
0
a
2
3
degassed solvent mixture of toluene (13 mL), EtOH (13 mL), and
H O (3.3 mL). To the mixture was added Pd(PPh ) , and the solu-
tion was heated to reflux for 5 h. After cooling to r.t., the
mixture was washed with 10% aq HCl (3 × 50 mL) and brine
Fluoranthene 12-Ar (112 mg, 0.215 mmol) was dissolved in CCl4
(5 mL), and NBS (199 mg, 1.12 mmol) and BPO (2 mg) were
added. The mixture was heated to reflux by irradiating with an
incandescent light bulb (Osram, 100 W). After 7 h the suspen-
sion was cooled in an ice bath, and the succinimide was filtered
2
3 4
(
3 × 50 mL), and the organic phase was dried over MgSO . Filter-
4
ing and evaporating the solvent gave the crude product 11-
Ar/12-Ar as a yellow solid which was purified by column chro-
matography on silica with n-hexane–EtOAc (100:1 to 50:1). The
two isomers can be separated by normal gravity column chro-
matography, a first separation delivered the desired isomer as
yellow solid (112 mg, 28%). Typically, collected mixed fractions
were resubmitted.
with a frit. The filtrate was evaporated (recycling of CCl ) and
4
dissolved in CH Cl . The CH Cl solution was thoroughly washed
2
2
2
2
with H O, dried over MgSO , filtered, and evaporated to deliver
2
4
a crude bromide mixture (185 mg).
Ring Closure
To an oven-dried two-necked 50 mL round-bottom flask,
equipped with stir bar, was added the crude mixture of bromo-
Methyl
4-tert-Butyl-2-(4-methoxyphenyl)-6-ethyl-1,7-
fluoranthenes (185 mg) in THF (16 mL), and H O (10 mL) was
2
dimethyl-10-propylfluoranthene-8-carboxylate (12-Ar)
Rf = 0.3 (silica gel; n-hexane–EtOAc, 10:1). IR (film): 2955 (m),
added. The solution was thoroughly degassed and CuCl2 was
added and the now yellow-greenish mixture was stirred at r.t.
for 3 min, prior to the addition of Mn powder in one step. The
reaction mixture was stirred at r.t. for 24 h, and was then
quenched with 10% aq HCl and extracted with MTBE (3 × 60
mL). The organic phase was washed with brine (3 × 50 mL),
dried over MgSO4, filtered, and evaporated to give a crude
cyclized product as an orange-brownish resin (83 mg).
2
1
1
932 (w), 2871 (w), 2835 (w), 1714 (s), 1608 (m), 1513 (m),
462 (m), 1433 (m), 1390 (m), 1364 (m), 1281 (m), 1264 (s),
245 (s), 1200 (s), 1174 (s), 1160 (m), 1055 (m), 1036 (m), 994
1
(w), 958 (w), 894 (m), 835 (m), 737 (s), 705 (m), 580 (m).
H
NMR (500 MHz, CDCl ): δ = 8.25 (s, 1 H), 7.83 (s, 1 H), 7.46 (s, 1
3
3
3
H), 7.43 (d, J = 8.5 Hz, 2 H), 7.04 (d, J = 8.5 Hz, 2 H), 3.96 (s, 3
H), 3.91 (s, 3 H), 3.11 (q, J = 7.5 Hz, 2 H), 3.04 (t-like, J = 7.5 Hz,
H), 2.85 (s, 3 H), 2.52 (s, 3 H), 1.74 (sext, J = 7.5 Hz, 2 H), 1.66
s, 9 H), 1.37 (t, J = 7.5 Hz, 3 H), 0.94 (t, J = 7.5 Hz, 3 H). C{ H}
3
3
Dehydrogenation
3
2
(
The crude cyclized product (42 mg) was dissolved in dry
benzene (4 mL), and DDQ (55.6 mg, 0.245 mmol) was added.
The dark mixture was refluxed for 5 h and was diluted with n-
hexane after cooling to r.t. The suspension was filtered through
a plug of Al O , which was thoroughly rinsed with n-hexane–
3
3
13
1
NMR (125 MHz, CDCl ): δ = 169.07, 159.06, 147.23, 143.00,
3
1
1
1
2
5
42.24, 142.16, 138.67, 136.76, 135.54, 135.16, 134.43, 132.15,
31.31, 131.25, 131.16, 130.99, 129.80, 128.09, 126.95, 125.12,
13.98, 55.58, 52.06, 37.81, 36.44, 32.73, 29.52, 24.39, 23.27,
2
3
EtOAc (20:1). The filtrate was washed with sat. aq NaHCO3,
•+
+
2.26, 15.53, 14.44. ESI-HRMS: m/z [M ] calcd for C36H40NaO3
:
dried over MgSO , filtered, and evaporated to give the crude
4
43.2870; found: 543.2870.
corannulene 15 as a yellow-brownish resin (18 mg). Preparative
TLC with n-hexane–EtOAc (50:1) followed by n-hexane–EtOAc–
toluene (50:1:1) afforded the pentasubstituted corannulene 15
Methyl
3-tert-Butyl-5-(4-methoxyphenyl)-1-ethyl-6,7-
dimethyl-10-propylfluoranthene-8-carboxylate (11-Ar)
Rf = 0.3 (silica gel; n-hexane–EtOAc, 10:1). IR (film): 2959 (m),
as a yellowish resin (5.2 mg, 11%, 3 steps). R = 0.3 (silica gel; n-
f
2
1
1
873 (w), 1718 (m), 1608 (w), 1513 (m), 1461 (m), 1437 (m),
391 (w), 1378 (w), 1365 (w), 1319 (s), 1219 (m), 1175 (m),
hexane–EtOAc, 10:1). IR (film): 2955 (w), 2930 (w), 2871 (w),
1715 (m), 1607 (w), 1514 (m), 1463 (m), 1438 (w), 1394 (w),
1365 (w), 1247s, 1207 (w), 1175 (m), 1137 (w), 1121 (w), 1094
108 (w), 1088 (w), 1058 (w), 1034 (m), 908 (m), 836 (m), 729
1
1
(m). H NMR (500 MHz, CDCl ): δ = 8.23 (s, 1 H), 7.85 (s, 1 H),
(w), 1069 (w), 1035 (w), 988 (w), 882 (w), 835 (w). H NMR
3
3
3
4
7.44 (d, J = 8.5 Hz, 2 H), 7.04 (d, J = 8.5 Hz, 2 H), 3.95 (s, 3 H),
(500 MHz, CDCl ): δ = 8.79 (s, 1 H), 8.30 (q, J = 1.1 Hz, 1 H), 8.25
3
3
3
3
4
3
.90 (s, 3 H), 3.14 (q, J = 7.5 Hz, 2 H), 3.05 (t-like, J = 7.5 Hz, 2
(s, 1 H), 7.84 (s, 1 H), 7.69 (d, J = 8.7 Hz), 7.55 (t, J = 0.9 Hz),
7.12 (d, J = 8.7 Hz), 4.09 (s, 3 H), 3.93 (s, 3 H), 3.15 (dq, J = 7.5
Hz, J = 0.9 Hz, 2 H), 2.85 (d, J = 1.1 Hz, 3 H), 1.74 (s, 9 H), 1.46
(t, J = 7.5 Hz). C{ H} NMR (125 MHz, CDCl ): δ = 167.83,
3
3
3
H), 2.80 (s, 3 H), 2.46 (s, 3 H), 1.73 (sext, J = 7.5 Hz, 2 H), 1.66 (s,
9
NMR (125 MHz, CDCl ): δ = 168.80, 159.07, 147.92, 142.68,
3
3
13
1
4
4
H), 1.35 (t, J = 7.5 Hz, 3 H), 0.96 (t, J = 7.5 Hz, 3 H). C{ H}
3
13
1
3
3
1
1
1
2
42.40, 142.38, 139.75, 137.50, 135.46, 135.28, 134.44, 131.94,
31.64, 131.44, 131.20, 130.73, 129.30, 127.62, 127.45, 125.20,
13.97, 55.58, 52.04, 37.88, 36.45, 32.70, 29.90, 24.71, 23.72,
2.68, 16.27, 14.22.
159.44, 150.54, 144.25, 140.07, 138.26, 137.99, 135.70, 134.36,
134.32, 133.54, 132.57, 131.00, 130.35, 130.32, 130.21, 128.60,
128.57, 127.70, 127.63, 127.56, 126.19, 123.98, 119.74, 114.28,
55.44, 22.24, 37.29, 32.61, 26.43, 19.03, 16.90. ESI-HRMS: m/z
•+
+
(
19) Maag, R. PhD Thesis; University of Zurich: Switzerland, 2012.
[M ] calcd for C36H32NaO3 : 535.2249; found: 535.2241.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F