Helical atropisomers of strained phenanthrenes by photochemistry of aromatic Pauson-Khand cycloadducts

Article abstract of DOI:10.1002/ejoc.201200735

Norbornene and norbornadiene Pauson-Khand adducts of bis(3,5- dimethylphenyl)acetylene and bis(3,4,5-trimethylphenyl)acetylene were prepared. These compounds were subjected to a photochemical 6π-electrocyclic oxidative aromatization reaction to give the corresponding phenanthrene compounds in satisfactory yield in the case of norbornene derivatives. The helical twist imposed by the methyl groups at the 3- and 5-positions on the aromatic rings led to two atropisomers as a result of the non-planar helical phenanthrene structure. The molecular structures and conformational stabilities of these atropisomers were examined by X-ray crystallography and variable temperature NMR studies. Norbornene and norbornadiene Pauson-Khand adducts of bis(3,5-dimethylphenyl)acetylene and bis(3,4,5-trimethylphenyl)acetylene were subjected to a photochemical 6π-electrocyclic oxidative aromatization reaction to give the corresponding phenanthrene compounds. The helical twist imposed by the methyl groups at the 3- and 5-positions on the aromatic rings led to two atropisomers as a result of the non-planar helical phenanthrene structure.

Full text of DOI:10.1002/ejoc.201200735

Job/Unit: O20735
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Date: 06-09-12 15:30:19
Pages: 7
FULL PAPER
DOI: 10.1002/ejoc.201200735
Helical Atropisomers of Strained Phenanthrenes by Photochemistry of
Aromatic Pauson–Khand Cycloadducts
Yining Ji,[a] Héléa Khaizourane,[a] Alexander N. Wein,[a] Xavier Verdaguer,*[a] and
Antoni Riera*[a]
Keywords: Photochemistry / Electrocyclic reactions / Chirality / Atropisomerism / Helical structures
Norbornene and norbornadiene Pauson–Khand adducts of
bis(3,5-dimethylphenyl)acetylene and bis(3,4,5-trimeth-
ylphenyl)acetylene were prepared. These compounds were
subjected to a photochemical 6π-electrocyclic oxidative aro-
matization reaction to give the corresponding phenanthrene
compounds in satisfactory yield in the case of norbornene
derivatives. The helical twist imposed by the methyl groups
at the 3- and 5-positions on the aromatic rings led to two
atropisomers as a result of the non-planar helical phen-
anthrene structure. The molecular structures and conforma-
tional stabilities of these atropisomers were examined by X-
ray crystallography and variable temperature NMR studies.
Introduction
Photochemical reactions are among the most convenient
tools for the synthesis of strained compounds. During the
last decade, we have uncovered several photochemical reac-
tions involving cyclopentenones obtained from Pauson–
Khand reactions (PKRs).[1,2] We have recently studied[2] the
photochemistry of aromatic cycloadducts I, which, by
choosing suitable reaction conditions, can selectively pro-
vide either electrocyclized (II) or photorearranged (III)
products (Scheme 1). The starting cyclopentenones are eas-
ily obtained either in racemic or enantioenriched form[3] by
Pauson–Khand cycloaddition of bis-aromatic acetylenes
with norbornadiene.
The straightforward access to phenanthrene compounds
II from diaryl acetylenes led us to study the synthetic appli-
cations of compounds II further. We envisioned that a suit-
able substitution pattern in the 3- and 5-positions or the
3-, 4-, and 5-positions of the aryl groups would result in
conformationally restricted phenanthrene compounds. A
relatively bulky alkyl group (R) would cause severe van der
Waals repulsion between the two closely arranged substitu-
ents in the 3- and 5-positions, and distortion of the aro-
matic plane would be expected in order to relieve such steric
congestion. If this occurred, the molecule would adopt a
helical structure, leading to two possible isomers (VM and
VP; Scheme 2). Thus, if the interconversion barrier between
Scheme 1. Electrocyclization or photorearranged products arising
from aromatic cycloadducts I.
the two conformers, which in turn is dependent on the steric
volume of the alkyl groups, is high enough, the stereoiso-
mers could be separated, thus leading to compounds with
helical chirality.
Helicenes[4,5] have attracted increasing attention because
of their extraordinary optical[6] and electronic proper-
ties,[4c,4d,7] which are closely associated with their helically
chiral structure. Therefore, we addressed whether the chiral-
ity of the bicyclic cyclopentenone skeleton could be trans-
mitted to the putative helicenic chirality of the phenan-
threne, thus allowing atropisomeric compounds VM and VP
to be formed in a stereoselective way (Scheme 2).[8] In other
words, we aimed to determine whether the electrocyclic
[a] Unitat de Recerca en Síntesi Asimètrica (URSA-PCB), Institute
for Research in Biomedicine (IRB Barcelona) and Departament
de Química Orgànica, Universitat de Barcelona,
c/Baldiri Reixac 10, 08028 Barcelona, Spain
Fax: +34-934037095
E-mail: xavier.verdaguer@irbbarcelona.org
antoni.riera@irbbarcelona.org
Homepage: http://www.ursapcb.org
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200735.
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Y. Ji, H. Khaizourane, A. N. Wein, X. Verdaguer, A. Riera
FULL PAPER
photochemical reaction[9] of adducts IV would allow a new
mode of access to helicene-like molecules. In this paper, we
describe the synthesis and structural study of phenanthrene
derivatives V with methyl substituents.
Scheme 4. Reduction of NBD cycloadducts 3a/3b.
NBD derivative 3a in methanol solution at 300 nm in a
Rayonet apparatus (16 lamps) gave phenanthrene com-
pound 5a in a yield of only 33% after 10 d (Table 1, en-
try 1). The presence of the additional methyl groups in com-
pound 3b further hampered the reaction, giving less than a
13% yield of 5b after 6 d of irradiation. Under the same
conditions, compound 4a behaved similarly (Table 1, en-
try 3). All these reactions gave crude product mixtures that
were difficult to purify.
Table 1. Synthesis of phenanthrene compounds 5 and 6.
Scheme 2. Atropisomers VM/VP formed in a photochemical reac-
tion.
Results and Discussion
Bis(3,5-dimethylphenyl)acetylene (2a) and bis(3,4,5-tri-
methylphenyl)acetylene (2b) were prepared in satisfactory
yields from the corresponding aryl iodide or aryl triflate by
modified Sonogashira coupling reactions.[2] The PKRs
using norbornene (NBN) or norbornadiene (NBD) gave the
corresponding cyclization products 3a–b or 4a–b, respec-
tively, in medium to excellent yields (Scheme 3). Products
4a–b were also obtained directly by hydrogenation of NBD
cycloadducts 3a–b (Scheme 4).
Entry Starting
material
R
H
Light
[nm]
Oxidant Time Product Yield
[%]
[a]
1
2
3
4
5
6
7
3a
3b
4a
4a
4b
4a
4b
300
O2
O2
O2
I2
10 d
6 d
12 d
7 d
10 d
36 h
53 h
5a
5b
6a
6a
6b
6a
6b
33
13
22
96
64
96
94
[a]
Me 300
H
H
300[ [a]
365[b]
Me 365[b]
I2
I2
I2
[a]
[a]
H
300
Me 300
[a] 16 lamps. [b] 8 lamps.
To improve the reaction conditions, we added an external
oxidant to the photochemical reaction. We focused on com-
pounds 4a–b derived from NBN, which lacked the olefinic
bond, and thus we avoided addition of iodine to the double
bond. In the presence of iodine, the photochemical reaction
gave much better results. Irradiation of 4a at 365 nm in
methanol with 1 equiv. I2 gave 6a cleanly in 96% yield
(Table 1, entry 4) after 7 d of irradiation. Under the same
conditions, 4b gave 6b in moderate yield after 10 d of irradi-
ation (Table 1, entry 5). The reactions, especially in the case
of 4b, were extremely slow (10 d to completion). This differ-
ence in reactivity is consistent with the fact that the place-
ment of an extra methyl group enhances the steric crowding
by “buttressing” the methyl groups located at the 4- and 5-
positions.[9] Irradiation with 16 lamps at 300 nm, also using
iodine as oxidant, allowed a reduction of the reaction times
Scheme 3. Synthesis of NBN and NBD cycloadducts; DBU = 1,8-
diazabicycloundec-7-ene.
With cyclopentenones 3a–b and 4a–b in hand, we started to 1–2 d, giving compounds 6a and 6b cleanly in excellent
the study of the photochemical reactions. Irradiation of yields (Table 1, entries 5 and 6).
2
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Helical Atropisomers of Strained Phenanthrenes
As expected, photochemical product 6a was found to be
mixture of atropisomers. The isomeric ratio was determined
1
to be 3:1 by H NMR spectroscopy. Crystallization of the
mixture from DMSO allowed us to obtain a single crystal
that was suitable for X-ray diffraction.[10] The molecular
structure of this crystal is shown in Figure 1. The phen-
anthrene fragment was completely distorted, with the
methyl substituents in the 4- and 5-positions being dis-
placed out of the mean plane of the aromatic system as a
result of steric hindrance. The twist (dihedral angle C4–C4a–
C4b–C5) between the mean planes of the aromatic rings was
32.3° (Figure 1). The configuration of this atropisomer was
M. The bond angles C4a–C4–CH3 and C4b–C5–CH3 were
123.0 and 123.6°, respectively. The steric repulsion between
the methyl groups in the 4- and 5-positions was released
not only by the dihedral distortions but also by a widening
of these bond angles from the theoretical 120°. The 1H
NMR spectrum of the crystals showed that a rapid equili-
bration took place in solution. Variable temperature NMR
studies indicated that the coalescence of the two atropiso-
mers 6aM and 6bP took place at 70.15 °C (Figure 2). The
Gibbs free energy of activation (ΔrG϶) was calculated to be
endoergic by +17.4 kcalmol–1.
Figure 2. Variable temperature 1H NMR spectra of 6b, showing the
coalescence temperature of the two atropisomers.
groups not only lowered the rate of the photochemical reac-
tion, but also increased the atropisomeric ratio of the mix-
ture. Both isomers were isolated sequentially by crystalli-
zation from a mixture of CH2Cl2/MeOH, and when ana-
lyzed by 1H NMR spectroscopy, they revealed high purities
of 99 and 98%, respectively (Figure 3).
Figure 1. X-ray diffraction structure[10] of major atropisomer 6aM.
The geometry and energy of the atropisomers 6aM and
6aP were calculated by ab initio DFT molecular orbital cal-
culations (RB3LYP 6-31G*//6-311+G**).[11] The enthalpy
of formation of the major atropisomer 6aM was found to
be 0.5 kcalmol–1 lower than that of 6aP. The optimized ge-
ometry of 6aM was very close to that observed by X-ray
diffraction. The dihedral angle C4–C4a–C4b–C5 between the
mean planes of the aromatic rings was 33.7° (vs. 32.3° in
the X-ray structure). Since the most stable isomer was the
major and crystalline one, we concluded that the atropisom-
eric equilibrium is controlled by the thermodynamic sta-
bility of the two isomers. The transition state of the in-
terconversion between the two atropisomers was also lo-
cated and geometry-optimized. The energy of the transition
state was found to be 17.2 kcalmol–1 higher than that of
6aM. This energy difference perfectly matches the experi-
mental value of the activation energy. The bond angles C4a–
Figure 3. Aromatic region of the 1H NMR spectra of atropisomers
6bM and 6bP.
A crystal of the major isomer was also analyzed by X-
C4–CH3 and C4b–C5–CH3 were 129.9 and 129.5°, respec- ray diffraction. The structure obtained revealed that this
tively, reflecting that the steric repulsion between the methyl was again the M atropisomer (i.e., 6bM), and it revealed a
groups was released by widening the bond angles.
distorted phenanthrene moiety with a significantly larger
In the case of photoadduct 6b, derived from bis(3,4,5- twist angle (35.9° vs. 32.1°) than that seen in 6aM (Figure 4).
trimethylphenyl)acetylene (2b), the 1H NMR spectrum The larger dihedral angle was due to the strain arising from
showed a 6:1 mixture of atropisomers. The extra methyl the extra methyl groups placed between the other two (i.e.,
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FULL PAPER
at positions 3 and 6 of the phenanthrene fragment; 4 and
4’ of the starting acetylene). The main effect of the extra
methyl groups is to prevent the widening of the bond
angles, since the methyl groups at positions 3 and 6, in-
crease the steric repulsion when these bond angles widen.
This effect can be clearly appreciated in the X-ray structure.
The bond angles C4a–C4–CH3 and C4b–C5–CH3 in 6bM are
121.7 and 120.6°, respectively, much closer to the theoreti-
cal 120° than those in 6aM. Therefore, the buttressing effect
is due to the energy penalty paid in any widening of the
methyl bond angles. The repulsion should be much bigger
in the transition state, which should result in a higher en-
ergy barrier for the interconversion between atropisomers
6bM and 6bP.
Conclusions
In summary, in this paper, we report the preparation of
methyl-substituted phenanthrene compounds by photo-
chemical electrocyclization of Pauson–Khand adducts of
bis(3,5-dimethylphenyl)acetylene and bis(3,4,5-trimeth-
ylphenyl)acetylene. These electrocyclized products have
been fully characterized by X-ray crystallography and
NMR spectroscopy. The repulsion between the two methyl
groups in the 4- and 5-positions of the phenanthrene sys-
tems causes a helical distortion of the planar aromatic sys-
tem, thus yielding two atropisomers. The placement of extra
methyl groups in the 3- and 6-positions enhances the steric
crowding by “buttressing” the methyl groups, which results
in more strained and helically distorted phenanthrenes. As
a result, it has been possible to isolate the two atropisomers
of 6b by crystallization. However, the steric repulsion was
not enough to prevent equilibration in solution. Our find-
ings pave the way for the preparation of configurationally
stable helicenic compounds.
Experimental Section
Figure 4. X-ray diffraction structure[10] of atropisomer 6bM.
3,4,5-Trimethylphenyl Trifluoromethansulfonate (1b): Trifluoro-
methanesulfonic anhydride (0.95 mL, 5.56 mmol) was added drop-
wise to a solution of 3,4,5-trimethylphenol (0.5 g, 3.3 mmol) and
triethylamine (1.5 mL) in CH2Cl2 (17 mL) at –15 °C under an inert
atmosphere. The reaction was left overnight and was then
quenched with H2O and brine. The aqueous phase was extracted
with CH2Cl2 (ϫ3). The combined organic extracts were dried with
MgSO4 and concentrated. Purification by flash chromatography
(SiO2, hexanes) gave 1b (0.88 g, 99%) as a colorless oil. IR (film):
The higher conformational rigidity of 6b relative to 6a
was confirmed by variable temperature NMR spectroscopy.
A mixture of the two atropisomers was heated in DMSO
solution up to 125 °C, but a coalescence point could not be
reached. However, on heating up a solution of a pure iso-
mer, it slowly isomerized to give a 2.5:1 thermodynamic
mixture (Figure 5). This observation indicated the need for
bulkier substituents to achieve stable atropisomers. The syn-
thesis of more strained compounds of this type is currently
being pursued in our laboratory. The results will be re-
ported in due course.
ν = 3052, 1420, 1209, 1142, 1014, 956, 842 cm–1. 1H NMR
˜
(400 MHz, CDCl3): δ = 2.15 (s, 3 H, CH3), 2.31 (s, 2 H, 2 CH),
6.91 (s, 6 H, 2 CH3) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.09
(CH3), 20.80 (2 CH3), 117.25 (C), 119.99 (2 CH), 135.58 (C), 138.67
(2 C), 146.77 (C) ppm. MS: m/z = 269.6 [M + H]+.
Bis(3,5-dimethylphenyl)acetylene
(2a):
Pd(PPh3)4
(223 mg,
0.19 mmol), CuI (62 mg, 0.32 mmol) and 3,5-dimethyl-1-iodo-
benzene (0.47 mL, 3.23 mmol) were placed into a Schlenk tube un-
der a nitrogen atmosphere. While stirring, dry toluene (16 mL) was
added to give a solution with a starting material concentration of
0.20 m. Nitrogen-sparged DBU (2.96 mL, 19.4 mmol) was then
added, and then the reaction tube was purged with nitrogen. Dis-
tilled water (24 μL, 1.29 mmol) and ice-chilled trimethylsilylacetyl-
ene (234 μL, 1.6 mmol) were added sequentially, and then the tube
was capped tightly. The mixture, protected from light, was stirred
and heated at 80 °C for 18 h. The reaction mixture was then cooled
to room temperature and partitioned between diethyl ether and
distilled water. The organic phase was washed with 10% HCl (ϫ3)
and brine, dried with MgSO4, and evaporated in vacuo. Product 2a
(451 mg, 75%) was isolated by flash chromatography as a white
solid; m.p. 123 °C. 1H NMR (400 MHz, CDCl3): δ = 2.29 (s, 12 H,
CH3), 6.93 (s, 2 H, CH), 7.14 (s, 4 H, CH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 21.08, 88.02, 123.00, 129.22, 130.00,
137.78 ppm. GC-MS: m/z (%) = 234 (100) [M]+. C28H18 (354.45):
calcd. C 92.26, H 7.74; found C 92.33, H 7.72.
Bis(3,4,5-Trimethylphenyl)acetylene (2b): The procedure described
for the synthesis of 2a was followed using: Pd(PPh3)4 (141 mg,
0.12 mmol), CuI (38 mg, 0.2 mmol), (3,4,5-trimethylphenyl)triflate
Figure 5. Isomerization of atropisomer 6bM.
4
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Helical Atropisomers of Strained Phenanthrenes
(540 mg, 2.0 mmol), DBU (1.83 mL, 12 mmol), distilled water C28H30O·0.25H2O: calcd. C 86.89, H 7.94; found C 86.83, H 8.08.
(15 μL, 0.81 mmol), ice-chilled (trimethylsilyl)acetylene (145 μL,
1.0 mmol), and toluene (10 mL). The reaction mixture was heated
at 65 °C for 18 h. Product 2b (110 mg, 42%) was isolated as a white
ESI-HRMS: calcd. for C28H31O [M + H]+ 383.2375; found
383.2372; calcd. for C56H60O2Na [2M + Na]+ 787.4491; found
787.4506.
solid by trituration with methanol. IR (film): ν = 2923, 1460 1377,
˜
(1S*,2S*,6R*,7R*)-4,5-Bis(3,5-dimethylphenyl)tricyclo[5,2,1,02,6]-
deca-4-en-3-one (4a): Pd/C (10%; 29 mg, 0.03 mmol) was added to
a solution of Pauson–Khand adduct 3a (191 mg, 0.54 mmol) in
ethanol (5 mL)) under nitrogen. The flask was flushed with hydro-
gen, and the mixture was stirred under a hydrogen atmosphere until
the total disappearance of the starting material was observed. The
solution was filtered through a Celite pad and rinsed with meth-
anol. Concentration of the filtrate under reduced pressure gave 4a
(166 mg, 87%) as a white solid. The product was also obtained by
PKR of 2a with norbornene following the general procedure
1
1211, 1144, 960 cm–1. H NMR (400 MHz, CDCl3): δ = 2.18 (s, 6
H, CH3), 2.27 (s, 12 H, CH3), 7.18 (s, 4 H, CH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 15.38 (2 CH3), 20.37 (4 CH3), 97.13 (2 C),
119.23 (2 C), 130.39 (4 CH), 136.40 (2 C), 137.28 (4 C) ppm. ESI-
HRMS: calcd. for C20H23 [M + H]+ 263.1794; found 263.1795;
calcd. for C40H45 [2M + H]+ 525.3515; found 525.3519.
General Procedure for the Thermal PKRs: Octacarbonyldicobalt
(1.1 equiv.) was added to a solution of alkyne (1 equiv.) in hexane
or toluene (with the alkyne at a concentration of 0.02 m). The reac-
tion mixture was stirred, and evolution of CO was monitored by a
bubbler connected to an outlet. After 1 h of stirring, the alkene
(10 equiv.) was added, the mixture was then heated, and the reac-
tion was monitored by TLC. When no remaining starting complex
was observed, the reaction mixture was allowed to cool and the
flask was opened to air and stirred for 30 minutes. The crude prod-
uct was filtered through a SiO2 pad, evaporated, and purified by
flash chromatography to give the corresponding cyclopentenone.
(78%); m.p. 162 °C (methanol/CH Cl ). IR (film): ν = 2956, 1693,
˜
2
2
1601, 1352, 1249, 852 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.00
(d, J = 10 Hz, 1 H, CH2), 1.24 (d, J = 10 Hz, 1 H, CH2), 1.36–1.46
(m, 2 H, CH2), 1.62–1.70 (m, 2 H, CH2), 2.13 (s, 1 H, CH), 2.21
(s, 6 H, CH3), 2.23 (s, 6 H, CH3), 2.46 (d, J = 5 Hz, 1 H, CH), 2.58
(s, 1 H, CH), 3.17 (d, J = 6 Hz, 1 H, CH), 6.78 (s, 2 H, CH), 6.90
(s, 1 H, CH), 6.91 (s, 2 H, CH), 6.94 (s, 1 H, CH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 21.4 (2 CH3), 21.4 (2 CH3), 29.1 (CH2),
29.2 (CH2), 31.8 (CH2), 38.6 (CH), 39.7 (CH), 50.8 (CH), 54.1
(CH), 126.5 (2 CH), 127.0 (2 CH), 129.5 (CH), 131.3 (CH), 132.5
(C), 135.2 (C), 137.8 (2 C), 137.8 (2 C), 143.0 (C), 170.0 (C), 209.2
(C=O) ppm. C26H28O (356.51): calcd. C 87.60, H 7.92; found C
87.73, H 8.02.
(1S*,2S*,6R*,7R*)-4,5-Bis(3,5-dimethylphenyl)tricyclo[5,2,1,02,6]-
deca-4,8-dien-3-one (3a): Following the general procedure, bis(3,5-
dimethylphenyl)acetylene (0.27 mL, 1.14 mmol), dicobalt octacarb-
onyl (429 mg, 1.25 mmol), and norbornadiene (0.95 mL,
11.39 mmol) were used. The reaction mixture was stirred overnight
at 80 °C. Purification by flash chromatography on SiO2 (Combi-
flash®, hexanes/EtOAc gradient) gave 3a (309 mg, 76%) as a white
(1S*,2S*,6R*,7R*)-4,5-Bis(3,4,5-Trimethylphenyl)tricyclo[5,2,1,02,6]-
deca-4-en-3-one (4b): Compound 4b was obtained following the
procedure described for 4a, but starting from 3b (153 mg,
0.42 mmol) and Pd/C (10%; 22 mg, 0.02 mmol). After stirring at
room temperature for 2 d, 4b (149 mg, 97%) was obtained as a
white solid. It was also prepared by PKR of 2b following the gene-
solid; m.p. 187 °C. IR (film): ν = 2916, 1694, 1601, 1351, 1243,
˜
1
685 cm–1. H NMR (400 MHz, CDCl3): δ = 1.44 (AB, J = 9 Hz, 1
H, CH2), 1.48 (AB, J = 9 Hz, 1 H, CH2), 2.22 (s, 6 H, CH3), 2.24
(s, 6 H, CH3), 2.57 (d, J = 5 Hz, 1 H, CH), 2.63 (s, 1 H, CH), 3.10
(s, 1 H, CH), 3.31 (d, J = 5 Hz, 1 H, CH), 6.31 (AB, J = 5, 3 Hz,,
1 H, CH), 6.34 (AB, J = 5, 3 Hz, 1 H, CH), 6.79 (s, 2 H, CH), 6.90
(s, 1 H, CH), 6.92 (s, 2 H, CH), 6.96 (s, 1 H, CH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 21.4 (2 CH3), 21.4 (2 CH3), 42.0 (CH2),
43.6 (CH), 44.3 (CH), 50.3 (CH), 52.8 (CH), 126.4 (2 CH), 127.0
(2 CH), 130.0 (CH), 131.4 (CH), 132.3 (C), 135.0 (C), 137.8 (2 C),
137.8 (2 C), 138.0 (CH), 138.5 (CH), 144.1 (C), 169.9 (C), 207.8
(C=O) ppm. C30H34O·0.25H2O: calcd. C 86.99, H 7.44; found C
86.88, H 7.47. ESI-HRMS: calcd. for C26H27O [M + H]+ 355.2062;
found 355.2064; calcd. for C52H52O2Na [2M + Na]+ 731.3865;
found 731.3882.
ral procedure (40%); m.p. 207 °C (methanol/CH Cl ). IR (film): ν
˜
2
2
= 2955, 1691, 1453, 1352, 1199, 1015 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 0.99 (d, J = 10 Hz, 1 H, CH2), 1.23 (d, J = 10 Hz, 1
H, CH2), 1.36–1.47 (m, 2 H, CH2), 1.61–1.69 (m, 2 H, CH2), 2.15
(s, 1 H, CH), 2.15 (s, 6 H, CH3), 2.17 (s, 6 H, CH3), 2.21 (s, 6 H,
CH3), 2.44 (d, J = 5 Hz, 1 H, CH), 2.57 (s, 1 H, CH), 3.17 (d, J =
6 Hz, 1 H, CH), 6.82 (s, 2 H, CH), 6.97 (s, 2 H, CH) ppm. 13C
NMR (100 MHz, CDCl3): δ = 15.4 (CH3), 15.7 (CH3), 20.7 (2
CH3), 20.8 (2 CH3), 29.1 (CH2), 29.3 (CH2), 31.8 (CH2), 38.9 (CH),
39.6 (CH), 50.4 (CH), 54.0 (CH), 128.1 (2 CH), 128.3 (2 CH), 129.8
(C), 132.0 (C), 134.6 (C), 136.3 (2 C), 136.4 (2 C), 137.2, (C) 142.4
(C), 169.2 (C), 209.4 (C=O) ppm. C28H32O (384.56): calcd. C 87.45,
H 8.39; found C 87.27, H 8.61.
(1S*,2S*,6R*,7R*)-4,5-Bis(3,4,5-Trimethylphenyl)tricyclo[5,2,1,02,6]-
deca-4,8-dien-3-one (3b): Following the general procedure,
bis(3,4,5-trimethylphenyl)acetylene (110 mg, 0.42 mmol), dicobalt
octacarbonyl (175 mg, 0.46 mmol), and norbornadiene (0.45 mL,
4.20 mmol) were used. The reaction mixture was stirred for 24 h at
80 °C. Purification by flash chromatography on SiO2 (hexanes/
General Procedure for the Photochemical Reactions: A solution of
PK adducts (1 equiv.) and I2 (1 equiv.) in methanol (with the PK
adduct at a concentration of 0.018 m) was placed into a flask pro-
vided with magnetic stirring. The solution was irradiated at 300 nm
in a Rayonet reactor equipped with 8 or 16 lamps, in the presence
of oxygen at room temperature. The reaction was monitored by
TLC. After completion of the reaction, a solution of Na2S2O3 was
added, and the aqueous phase was extracted with CH2Cl2 (ϫ2).
The combined organic extracts were dried (MgSO4), filtered, and
concentrated under reduced pressure. The crude reaction product
was purified by flash chromatography on SiO2 (Combiflash®, hex-
anes/EtOAc gradient).
EtOAc gradient) gave 3b (153 mg, 87 %) as a white solid; m.p.
1
188 °C. IR (film): ν = 2916, 1692, 1502, 1245, 731 cm–1. H NMR
˜
(400 MHz, CDCl3): δ = 1.42 (AB, J = 9 Hz, 1 H, CH2), 1.47 (AB,
J = 9 Hz, 1 H, CH2), 2.16 (s, 3 H, CH3), 2.16 (s, 3 H, CH3), 2.18
(s, 6 H, CH3), 2.21 (s, 6 H, CH3), 2.56 (d, J = 5 Hz, 1 H, CH), 2.65
(s, 1 H, CH), 3.09 (s, 1 H, CH), 3.31 (d, J = 5 Hz, 1 H, CH), 6.30
(AB, J = 5, 3 Hz, 1 H, CH), 6.34 (AB, J = 5, 3 Hz, 1 H, CH), 6.83
(s, 2 H, CH), 7.01 (s, 2 H, CH) ppm. 13C NMR (100 MHz, CDCl3):
δ = 15.4 (CH3), 15.7 (CH3), 20.7 (2 CH3), 20.8 (2 CH3), 42.1 (CH2),
(8cR*,9S*,12R*,12aS*)-8c,9,10,11,12,12a-Hexahydro-9,12-meth-
43.8 (CH), 44.2 (CH), 50.0 (CH), 52.6 (CH), 127.9 (2 CH), 128.3 ano-2,4,5,7-tetramethyl-13H-indeno[1,2-l]phenanthren-13-one (6a):
(2 CH), 129.6 (C), 131.9 (C), 134.7 (C), 136.4 (4 C), 137.3 (C), Following the general procedure, compound 4a (50 mg, 0.14 mmol)
138.0 (CH), 138.5 (CH), 143.5 (C), 169.1 (C), 208.3 (C=O) ppm. and I2 (50 mg, 0.24 mmol) were used. The reaction was irradiated
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O20735
/KAP1
Date: 06-09-12 15:30:19
Pages: 7
Y. Ji, H. Khaizourane, A. N. Wein, X. Verdaguer, A. Riera
FULL PAPER
in the presence of oxygen for 36 h. Flash chromatography on SiO2
40.1 (maj., CH), 41.1 (min., CH), 45.9 (maj., CH), 46.5 (min., CH),
59.8 (maj., CH), 59.2 (min., CH), 121.7 (maj., 2 CH), 121.8 (min.,
2 CH), 122.9 (maj., 2 CH), 123.3 (min., 2 CH), 126.2 (maj., C),
127.7 (min., C), 128.3 (maj., C), 129.3 (maj., C), 131.3 (maj., C),
133.1 (maj., C), 133.4 (min., C), 134.0 (maj., C), 134.7 (maj., C),
135.1 (min., C), 135.2 (maj., C), 135.3 (maj., C), 136.1 (maj., C),
(Combiflash®, hexanes/EtOAc gradient) gave 6a (48 mg, 96%) as
a white solid; m.p. 206 °C. IR (film): ν = 2955, 1686, 1609, 1451,
˜
1247, 731 cm–1. 1H NMR (400 MHz, CDCl3) (mixture of atropiso-
mers): δ = 0.98 (br. s, 2 H, CH2, maj. + min.), 1.44–1.52 (m, 1 H,
CH2, min. + maj.), 1.62–1.69 (m, 1 H, CH2, min. + maj.), 1.70–
1.85 (m, 2 H, CH2, min. + maj.), 2.51 (s, 3 H, CH3, min.), 2.53 (s, 137.8 (min., C), 138.0 (maj., C), 159.4 (min., C), 159.6 (maj., C),
3 H, CH3, maj.), 2.53 (s, 3 H, CH3, maj.), 2.54 (s, 3 H, CH3, maj.
+ min.), 2.55 (s, 3 H, CH3, min.), 2.58 (s, 3 H, CH3, maj. + min.),
2.60–2.70 (m, 3 H, CH, maj. + min.), 3.35 (d, J = 6 Hz, 1 H, CH,
min.), 3.41 (d, J = 6 Hz, 1 H, CH, maj.), 7.26 (s, 1 H, CH, maj.),
7.26 (s, 1 H, CH, min.), 7.39 (br. s, 1 H, CH, maj. + min.), 7.74 (s,
1 H, CH, maj.), 7.79 (s, 1 H, CH, min.), 8.90 (s, 1 H, CH, maj.),
8.91 (s, 1 H, CH, min.) ppm. 13C NMR (100 MHz, CDCl3): δ =
21.4 (min., CH3), 21.5 (maj., CH3), 21.5 (min., CH3), 21.6 (maj.,
CH3), 21.7 (maj., CH3), 21.8 (maj., CH3), 21.8 (min., CH3), 21.8
(min., CH3), 28.7 (min., CH2), 29.0 (maj., CH2), 29.7 (maj., CH2),
29.8 (min., CH2), 32.5 (CH2), 39.2 (min., CH), 39.9 (maj., CH),
40.1 (maj., CH), 41.1 (min., CH), 46.0 (maj., CH), 46.6 (min., CH),
56.6 (maj., CH), 57.1 (min., CH), 121.0 (maj., CH), 121.2 (min.,
CH), 122.3 (maj., CH), 122.6 (min., CH), 128.4 (C), 128.6 (maj.,
C), 128.6 (min., C), 130.1 (min., C), 130.6 (maj., C), 130.6 (CH),
132.0 (maj., C), 132.2 (min., C), 132.4 (maj., C), 132.6 (min., C),
133.1 (min., CH), 133.3 (maj., CH), 135.3 (maj., C), 135.3 (min.,
C), 135.9 (C), 136.4 (min., C), 136.5 (maj., C), 136.9 (maj., C),
136.9 (min., C), 160.2 (min., C), 160.3 (maj., C), 208.8 (min., C=O)
208.9 (maj., C=O) ppm. C26H26O·1/3H2O: calcd. C 86.63, H 7.46;
found C 86.61, H 7.43. ESI-HRMS: calcd. for C26H27O [M + H]+
355.2062; found 355.2068; calcd. for C52H53O2 [2M + H]+
709.4046; found 709.4033.
208.9 (maj., C=O) ppm. C28H30O·0.2H2O: calcd. C 87.09, H 7.94;
found C 87.31, H 7.97. ESI-HRMS: calcd. for C28H31O [M + H]+
383.2375; found 383.2369.
Supporting Information (see footnote on the first page of this arti-
1
cle): H and 13C NMR spectra for all new compounds. Calculated
geometries of both atropisomers of 6a and 6b and the transition
state of the interconversion between 6aM and 6aP. X-ray diffraction
data for 6aM and 6bM.
Acknowledgments
We thank the Spanish Ministerio de Economia y Competitividad
(CTQ2011-23620), the Generalitat de Catalunya (2009SGR 00901)
and IRB Barcelona for financial support. Y. J. thanks the Minis-
terio de Ciencia e Innovación (MCINN) for a fellowship.
[1] a) I. Marchueta, S. Olivella, L. Sola, A. Moyano, M. A. Per-
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2007, 46, 5943–5946.
[2] Y. Ji, X. Verdaguer, A. Riera, Chem. Eur. J. 2011, 17, 3942–
3948.
[3] Y. Ji, A. Riera, X. Verdaguer, Org. Lett. 2009, 11, 4346–4349.
[4] For reviews on helicenes, see: a) H. Hopf, Classics in Hydro-
carbon Chemistry, Wiley-VCH, Weinheim, Germany, 2000, pp.
321–330; b) F. Vögtle, Fascinating molecules in Organic Chemis-
try, Wiley, New York, 1992, pp. 156–180; c) K. P. Meurer, F.
Voegtle, Top. Curr. Chem. 1985, 127, 1–76; d) W. H. Laarhoven,
W. J. C. Prinsen, Top. Curr. Chem. 1984, 125, 63–130; e) R. H.
Martin, Angew. Chem. 1974, 20, 727–738.
[5] For highlights on related topics, see: a) C. Schmuck, Angew.
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2448–2452; b) A. Urbano, Angew. Chem. 2003, 115, 4116–4119;
Angew. Chem. Int. Ed. 2003, 42, 3986–3989.
[6] T. J. Katz, Angew. Chem. 2000, 112, 1997–1999; Angew. Chem.
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[7] a) L. Liu, B. Yang, T. J. Katz, M. K. Poindexter, J. Org. Chem.
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[9] R. N. Armstrong, H. L. Ammon, J. N. Darnow, J. Am. Chem.
Soc. 1987, 109, 2077–2082.
[10] CCDC-884571 (for 6a) and -884572 (for 6b) contain the sup-
plementary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[11] Spartan 06, Wavefunction, Inc., Irvine, CA.
(8cR*,9S*,12R*,12aS*)-8c,9,10,11,12,12a-Hexahydro-9,12-meth-
ano-2,3,4,5,6,7-tetramethyl-13H-indeno[1,2-l]phenanthren-13-one
(6b): Following the general procedure, compound 4b (50 mg,
0.13 mmol) was irradiated in the presence of I2 (33 mg, 0.13 mmol).
After 54 h, the crude product was purified by flash chromatography
on SiO2 (Combiflash®, hexanes/EtOAc gradient) to give 6b (45 mg,
93%) as a mixture of atropisomers; m.p. 219 °C. IR (film): ν =
˜
2915, 1681, 1649, 1443, 1380, 733 cm–1. 1H NMR (400 MHz,
CDCl3) 6bM: δ = 0.96 (s, 2 H, CH2), 1.43–1.50 (m, 1 H, CH2), 1.72
(dt, J = 12, 4 Hz, 1 H, CH2), 1.76–1.85 (m, 2 H, CH2), 2.38 (s, 3
H, CH3), 2.41 (s, 3 H, CH3), 2.42 (s, 3 H, CH3), 2.43 (s, 3 H, CH3),
2.52 (s, 3 H, CH3), 2.56 (s, 3 H, CH3), 2.60 (br. s, 1 H, CH), 2.61
(br. s, 1 H, CH), 2.64 (d, J = 3 Hz, 1 H, CH), 3.39 (d, J = 6 Hz, 1
H, CH), 7.76 (s, 1 H, CH), 8.90 (s, 1 H, CH) ppm. 1H NMR
(400 MHz, CDCl3) 6bP: δ = 0.95 (s, 2 H, CH2), 1.43–1.50 (m, 1 H,
CH2), 1.59–1.66 (m, 1 H, CH2), 1.67–1.83 (m, 2 H, CH2), 2.38 (s,
3 H, CH3), 2.39 (s, 3 H, CH3), 2.43 (s, 6 H, CH3), 2.52 (s, 3 H,
CH3), 2.56 (s, 3 H, CH3), 2.63 (d, J = 6 Hz, 1 H, CH), 2.66 (d, J
= 3 Hz, 1 H, CH), 2.69 (d, J = 4 Hz, 1 H, CH), 3.35 (d, J = 6 Hz,
1 H, CH), 7.81 (s, 1 H, CH), 8.92 (s, 1 H, CH) ppm. 13C NMR
(100 MHz, CDCl3) mixture 6bM (major)/6bP (minor): δ = 16.5
(maj., CH3), 16.8 (min., CH3), 16.9 (maj., CH3), 21.2 (maj., CH3),
21.2 (maj., CH3), 21.3 (maj., CH3), 21.4 (maj., CH3), 21.5 (min.,
CH3), 28.8 (min., CH2), 29.0 (maj., CH2), 29.7 (maj., CH2), 29.8
(min., CH2), 32.5 (maj., CH2), 39.1 (min., CH), 39.8 (maj., CH),
Received: May 31, 2012
Published Online: ᭿
6
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20735
/KAP1
Date: 06-09-12 15:30:19
Pages: 7
Helical Atropisomers of Strained Phenanthrenes
Photochemical Atropisomer Formation
Y. Ji, H. Khaizourane, A. Wein,
X. Verdaguer,* A. Riera* .................. 1–7
Helical Atropisomers of Strained Phen-
anthrenes by Photochemistry of Aromatic
Pauson–Khand Cycloadducts
Norbornene and norbornadiene Pauson–
Khand adducts of bis(3,5-dimethylphenyl)-
acetylene and bis(3,4,5-trimethylphenyl)-
acetylene were subjected to a photochem-
ical 6π-electrocyclic oxidative aromatiza-
tion reaction to give the corresponding
phenanthrene compounds. The helical
twist imposed by the methyl groups at the
3- and 5-positions on the aromatic rings led
to two atropisomers as a result of the non-
planar helical phenanthrene structure.
Keywords: Photochemistry / Electrocyclic
reactions / Chirality / Atropisomerism /
Helical structures
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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