Accessing [ g]-Face π-Expanded Fluorescent Coumarins by Scholl Cyclization

Article abstract of DOI:10.1021/acs.joc.9b01223

[g]-Face π-expanded coumarins are synthesized by employing the Scholl cyclization method. These new arene-annulated dipolar coumarins display interesting absorption and fluorescent properties. The large Stokes shifts, tuneable fluorescent quantum yields, and high photostability reveal promise in bioimaging application.

Full text of DOI:10.1021/acs.joc.9b01223

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Article
Accessing [g]-Face #-Expanded Fluorescent
Coumarins by Scholl Cyclization
Nitisha ., and Parthasarathy Venkatakrishnan
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01223 • Publication Date (Web): 05 Aug 2019
Downloaded from pubs.acs.org on August 11, 2019
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Accessing [g]-Face π-Expanded Fluorescent Coumarins by Scholl Cyclization
Nitisha and Parthasarathy Venkatakrishnan*
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Department of Chemistry, Indian Institute of Technology Madras, Chennai - 600036,
Tamil Nadu, India.
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pvenkat@iitm.ac.in
Abstract
O
O
400
500
600
700
λ (nm)
[g]-Face π-expanded coumarins are synthesized employing Scholl cyclization method. These
new arene-annulated dipolar coumarins display interesting absorption and fluorescent
properties. The large Stokes-shifts, tuneable fluorescent quantum yields and high photostability
reveal promise in bioimaging application.
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INTRODUCTION
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Coumarins1 are a celebrated class of heterocyclic compounds because of their renowned
application as laser dyes,2 fluorescent probes,3 optical brighteners,4 biomedical imaging
agents,5 and their potential use as light emitters in OLEDs,6 therapeutic agents,7 etc. To
tap their potential, and extract beneficial properties to the fullest extent, various
synthetic efforts are being consistently attempted on coumarins. The recent
development by Gryko and others on the discovery of new π-expanded coumarin
analogues8 has indeed opened-up a budding area of promising research for several
research laboratories, for reasons due to the significant variations observed in their
photophysical properties. For example, benzocoumarins (Figure 1) possessing
elongated conjugation of π-molecular orbitals, with appropriate substituent, reveal
several advantageous features, viz., red-shifted absorption, emission and improved
fluorescence quantum yields, over simple coumarins.9 It is understood that the extended
linear conjugation (rigid) and the substituent contributing to ICT (intramolecular charge
transfer) are essentially the key factors for achieving coumarins with more promising
characteristics; coumarin-314 is one such example. Extending the conjugation linearly,
thereby ICT, in coumarins is known to shift the emission, but fails to improve the
photoluminescence quantum yields (PLQE, Φf), due to their accompanied severe non-
radiative decay pathways.10 In order to improve the PL characteristics, it is of course
important to minimize the above-said pathway by functional rigidification. With this
aim, we started out to synthesize a set of arene-annulated benzocoumarins (rigid
conjugation, Figure 1) via π-expansion strategy, and examine the optical characteristics.
Various classical methods have been employed on to 1-/2-naphthols,11 1-/2-
hydroxyanthracenes,12 phenanthrenes,13 etc. to obtain various annulated π-expanded
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coumarins, but with harsh conditions, low yields and poor regioselectivity.14 On the other hand,
photochemical oxidative cyclization have also been demonstrated as a powerful tool for
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h
f
c
c
6
g
3
3
i
j
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2
O
O
O
O
O
h
O
Benzo[g]coumarin
Coumarin
12
Phenanthro[9,10-g]coumarin
Figure 1. Lateral growth of π-expanded coumarins.
expanding the π-system of coumarins against various faces (regioisomers).15 Along these lines,
Scholl cyclization – a popular reaction utilized for the construction of small to large polycyclic
aromatic hydrocarbons – has been scarcely employed to construct π-expanded coumarins.16 In
1942, Dilthey and coworkers reported the first synthesis of green emitting coumarins with 6-
fused benzene rings via dehydrogenative Scholl coupling.17 Recently, Gryko et al. synthesized
blue-green emitting 1-oxaperylene-2-one by a two-step method involving the classical
Pechmann reaction followed by Scholl reaction.18 Very recently, the same group expanded the
above method further for the preparation of 1,7-dioxaperylene-2,8-diones (yellow emitter);19
the isolated π-expanded coumarins were not very fluorescent in solution.8 While all the above
three approaches benefited from the aryl substituents at 3- or 4- or both positions, there are no
reports employing Scholl methods on the π-expansion at the [g]-face of coumarin by utilizing
the aryl substituents at 6- or (and) 7-positions (Figure 2). This could possibly be because of the
strong dipolar nature of coumarins,20 which reduces the reactivity at the arene part of coumarin
towards Scholl oxidative cyclodehydrogenation. In principle, annulation at the [g]-face must
result in coumarins with larger transition dipole moments than the coumarins annulated at other
faces.5a,8
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3
Scholl
7
O
-expansion
This report
O
O
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Cyclization
-expansion
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Earlier reports
Figure 2. Strategies for the π-expansion of coumarins using Scholl cyclization.
In continuation of our on-going research on coumarins21 and Scholl oxidative
cyclization reactions,21 we have attempted to π-expand coumarins at its 6,7-face ([g]-
face) exploiting intramolecular Scholl reaction, and evaluated their photophysical
properties. Herein we report the syntheses, characterization and photophysical
properties of various [g]-face arene-annulated coumarins. The [g]-face annulated
coumarins demonstrate greater photostability, considerable improvement in their
absorption and emission properties as well as appreciable fluorescence quantum yields
as compared to benzocoumarins.
RESULTS AND DISCUSSION
Initially, we endeavoured our synthesis starting with 7-bromo-4-methylcoumarin 1 (Scheme
1). The bromide 1 was converted using Miyaura borylation to the corresponding boronate ester
2, which upon Pd(II)-mediated Suzuki cross-coupling reaction with 2-bromobiphenyl (3)
afforded 7-(biphen-2'-yl)-4-methylcoumarin 4. As may be seen, the biphenyl unit in 4 is
appropriately situated to undergo oxidative cyclization reaction via C–C bond formation at
either C-6 or C-8 positions of coumarin, involving the benzene ring, to offer either 12a or 5a,
respectively. Thus, we next proceeded for the oxidative cyclodehydrogenation step with
coumarin 4. Our initial efforts to oxidatively (I2/O2 and hv) photocyclize 4 was not fruitful.
While various oxidative coupling reagents are available in the literature,16 we tried the most
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common ones, such as, FeCl3, AlCl3, DDQ/MeSO3H, etc. Unfortunately, none of the tested
conditions yielded the expected cyclized product(s) (5a/12a, Scheme 1 and Table S1), and the
starting material was recovered quantitatively. Similar results were also observed when 6-
(biphen-2'-yl)-4-methylcoumarin 4' was subjected to the above Scholl conditions; neither of
the possible products 5b nor 12a was obtained. At this point, we hypothesized that the failure
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Scheme 1. Scholl cyclization of 7-/6-(biphen-2-yl)coumarin 4/4'.
O
O
6
7
a
B
Br
b
O
O
O
O
1
1'
2
2'
7-Br:
6-Br:
7-B-ester:
6-B-ester:
6
c X
O
O
O
7
O
4
4'
O
12a
7-BiPh:
6-BiPh:
O
5a
5b
O
O
Reagents and conditions: a) Bis(pinacolatodiboron), PdCl2(PPh3)2, KOAc, toluene, 70 °C, 9 h,
82–83%. b) 2-Bromobiphenyl 3, Pd(PPh3)2Cl2, K2CO3, Toluene:EtOH (3:1), 90 °C, 12 h, 71–
98%. c) Oxidative Scholl cyclization or photocyclization conditions.
in the above cases (4 and 4') were due to the electron deficient benzene ring present in
coumarin,22 which probably would have led to a highly unstable radical/arenium cation during
oxidative Scholl cyclization.23 To verify this point, Scheme 2 was taken up. The idea was to
first reduce the double bond at 3,4-positions of the pyranone ring of coumarin, and then to see
if the cyclization could be achieved. Accordingly, the double bond of 6-/7-(biphen-2'-yl)-4-
methylcoumarin at 3-position was reduced using 10 wt% Pd/C. Further, the oxidative
cyclization of 7-/6-(biphenyl-2'-yl)-4-methyl-3,4-dihydrochromen-2-one 6/6' were conducted
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under FeCl3 conditions, which provided compound 7 regioselectively. The formation of C–C
bonds in 7 (as in Scheme 2), after successful oxidative cyclization of 6/6', not only verifies the
electron deficient nature of the benzene ring present in coumarin, but also suggests that the
electron deficient nature is essentially provided by the fused-pyranone unit.22 The compound 7
then upon oxidation led to the [g]-face annulated coumarin, 12a.
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Scheme 2. Scholl cyclization of 7-/6-(biphen-2'-yl)-4-methyl-3,4-dihydrocoumarin 6/6'.
a
b
c
6
7
12a
4 4'
/
O
O
O
O
6 6'
/
7
Reagents and conditions: a) H2, 10 wt% Pd/C, EtOAc, rt, 20 h, 88%. b) FeCl3, DCM, rt, 28 h,
28–50%. c) DDQ, benzene, reflux, 24 h, 99%.
In order to accomplish the target molecule, i.e., [g]-face annulated coumarin, without involving
the coumarin benzene ring, a new synthetic route as shown in Scheme 3 was adapted.
Accordingly, 6,7-dihydroxy-4-methylcoumarin 8 was converted to its corresponding
bis(triflate) 9, which was then subjected to Pd(II)-mediated two-fold Suzuki cross-coupling
reaction with various arylboronic acids (10a-h) to afford the corresponding 6,7-diarylcoumarin
derivatives (11a-h, Scheme 3 and Table 1). While photochemical oxidative cyclization was
successful for 11f, it was unsuccessful for substrates 11a-e,g-h. Subsequently, in an attempt
to realize the cyclodehydrogenated products (12a-h), Scholl oxidative cyclization
reaction conditions were once again explored on 11a-h. The best optimized conditions
and the suitable reagents for the oxidative cyclization of various diarylcoumarins are
consolidated in Tables 1 and S2. As may be noticed, while the oxidative
cyclodehydrogenation of coumarin 11g was accomplished only using DDQ/H+ as the
oxidant, the other precursors 11a-f underwent smooth oxidative Scholl cyclization in
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presence of FeCl3 (2.0 equiv.) to afford the corresponding [g]-face arene-annulated
products 12a-f in good to excellent yields (up to 91%), highlighting the effectiveness of
FeCl3 as oxidant in Scholl cyclization. However, exchanging the reaction condition
yielded discouraging results (see, Table S2). Notably, carbazole-incorporated coumarin
11h underwent cyclization effectively (ca. 1 min.) under DDQ/H+ conditions to furnish
12h in good (85%) yields.16c All the newly synthesized [g]-face annulated coumarins 12a-h
are unprecedented, and their synthesis using von Pechmann reaction from corresponding
phenols is not easy as the latter are not readily available. In view of this, the method
demonstrated herein is advantageous in accessing myriad of π-expanded coumarins, and the
synthetic attempts described herein would certainly pave the way for better understanding of
the Scholl reaction. Beneficially, these coumarins are highly soluble in common organic
solvents, such as, chloroform, dichloromethane, ethyl acetate, etc.
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Scheme 3. Scholl cyclization of 6,7-(diaryl)coumarins 11a-h.
HO
HO
TfO
TfO
a
O
O
O
O
b
10a-h
8
9
R2
R2
R3
R1
R3
R1
6
R4
R4
R4
R4
c
7
O
O
O
O
12a-h
11a-h
R3
R1
R3
R1
R2
R2
Reagents and conditions: a) Tf2O (2.0 equiv.), Et3N, DCM, rt, 3 h, 75%. b) arylboronic
acids (10a-h), Pd(PPh3)2Cl2, K2CO3, Toluene:EtOH (3:1), 90 °C, 12 h, 74–96%. c)
FeCl3 or DDQ/H+, DCM, 0 C to rt, 1 min–16 h.
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Table 1. Optimized Scholl cyclization condition for 11a-h to access 12a-h.
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SM Aryl Substituent
Condition
Product, % yield
12a, 40
11a R1 = R2 = R3 = R4 = H
11b R2 = Me; R1 = R3 = R4 = H
11c R1 = R2 = R4 = H; R3 = t-Bu
FeCl3, DCM, rt, 16 h
FeCl3, DCM, rt, 1.5 h
FeCl3, DCM, rt, 10 h
12b, 50
12c, 47
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11d R2 = OMe; R1 = R3 = R4 = H FeCl3, DCM, rt, 2 h
11e R2 = R3 = OMe; R1 = R4 = H FeCl3, DCM, rt, 1 h
11f R2 = R4 = OMe; R1 = R3 = H FeCl3, DCM, rt, 1 h
12d, 73
12e, 91
12f, 91
12g, 78
11g R1–R2 = CH=CH–CH=CH;
DDQ/MeSO3H, DCM,
R3–R4 = CH=CH–CH=CH
0 C to rt, 1 h
R3
11h
DDQ/MeSO3H, DCM,
0 C to rt, 1 min
12h, 85
R2
N
C6H13
R1, R4 = H;
Fortunately, the single crystals of 11d and 12d were grown by the slow evaporation of
their solutions from chloroform and ethyl acetate, respectively. In 11d, the 3-
methoxyphenyl rings at 6- and 7-positions are tilted to 55.16 and 51.85, respectively,
considering the mean plane of coumarin (Figure 3). After Scholl cyclization, 12d
exhibited a near-planar structure, with a mild twist (ca. 3.05) at the bay regions of the
pyranone-fused triphenylene (Figure 3). While the molecular packing diagram of 11d
reveals a centrosymmetric π-π dimer (3.70 Å), 12d exhibits a strong π-π stacking
interaction (d = 3.67–3.70 Å) between the neighbouring triphenylene units, as expected,
in a non-centrosymmetric fashion (Figure S10). Triphenylenes are known to form one-
dimensional stacking arrangements due to favourable overlap of π-orbitals of the
conjugated system — the behavior which is responsible for their popular liquid
crystalline properties.24 Modified or annulated triphenylene-based liquid crystalline
materials are recently gaining attention.24 Most excitingly, the solid-state arrangement
of 12d reveals that the dipoles of π-expanded coumarins are aligned in the same
direction (Figure S10) leading to a polar crystal (space group: Pna21). Molecules
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crystallize in polar space groups are shown to exhibit interesting pyro-/piezo-
/ferroelectric properties as reported in certain cases.25 Systems possessing polarized
behaviour in the solid-state are attractive for their induced-changes associated with the
dielectric properties;26 for example, ferroelectric liquid crystals gained importance due
to their fast electro-optic response in modern photonics.26 Investigation of such
properties is presently underway in our laboratories.
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OMe
12e
MeO
Me
O
O
MeO
11d
12d
μg = 5.94 D
μe = 8.31 D
OMe
Figure 3. X-ray molecular structures of 11d and 12d (thermal ellipsoids are drawn at 50%
probablility level), and the ICT possible for 12e and the calculated dipole moments.
These novel π-expanded coumarins are highly photostable; no photoreaction or decomposition
was noticed upon photoirradiation at λexc = 350/254 nm under oxygen for more than 48 h. The
effect of structural variation, i.e., π-expansion and substituents, on the photophysical properties
of π-enlarged coumarins 12a-h were examined in dilute chloroform solutions (ca. 10-6 M, Table
2). The absorption bands for all the π-expanded coumarins were located between 300 and 450
nm (Figure 4a and SI). The strong intense band (high ε) in this region may be attributed to the
typical π→π* transition.27 The accompanying less intense (low ε) weak band at longer
wavelength region could be assigned probably to the n→π* transition.27 As expected, all the
π-expanded coumarins 12a-h significantly displayed red-shifted, near-visible absorptions
when compared to the corresponding uncyclized 11 or simple linear/bent benzocoumarins
attesting to their π-extended nature.8 For example, absorption maximum of 12a is red-shifted
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to ca. 32 nm (Table 2), when compared to parent benzo[g]coumarin (λmaxabs, CH3CN = 321
nm). The substituted coumarins 12b-h possess higher molar extinction coefficient (ε) than
unsubstituted 12a. Particularly, the large molar extinction coefficient of 12g/12h is more likely
due to its large π-system. The emission spectrum of 12a-e,g were featureless resembling other
heteroarenes,28 and their emission maximum was found to be in the range 410 to 590 nm, which
covers the blue to cyan to yellow emission region (Figure 4b and SI). The featured emission
profile in 12f and 12h, despite having ICT, may presumably be attributed to the coupling of
locally excited (LE) states with the CT states.29 Noticeably, 12g displays two emission bands
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12a
12b
12c
12d
12e
12f
12a
12b
12c
12d
12e
12f
1.0
0.5
0.0
1.0
0.5
0.0
b)
a)
12g
12h
12g
12h
300
400
Wavelength (nm)
400
500
600
Wavelength (nm)
Figure 4. Absorption (a) and emission spectrum (b) of the coumarins (12a-h) in CHCl3. Inset
shows the photographs of 12a-h (left to right) in CHCl3 under UV irradiation (λex = 365 nm).
Table 2. Optical properties of coumarins 12a-h.
Entry
λmax(abs)a
εa
λmax(em)b
(nm)
415
∆ʋ
Φfc
(%)
12
11
14
17
8
10
12
10
(nm)
(M-1cm-1)
13810
14380
14160
14520
20580
15740
42490
64380
(cm-1)
3500
5100
5400
9000
9600
12a 310, 338, 362, 380 (sh)
12b 313, 327, 347, 386 (sh)
12c
12d
12e
12f
422
423
475
314, 344, 387 (sh)
318, 333, 365 (sh)
322, 333, 368 (sh)
329, 344, 390 (sh)
332, 343, 393(sh)
310, 334, 386 (sh)
491
538, 585 (sh) 10500
415, 478 8200
536, 583 (sh) 11300
12g
12h
a Measured in CHCl3 solutions (ca. 10−6 M) at room temperature. b Recorded at λex = 333 nm.
c Measured using quinine sulfate in H2SO4 (0.1 M) as a standard.30
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at 415 and 478 nm (Figure 4b), originating probably from π-π* (LE) and CT transitions (vide
infra), respectively, besides aggregation (due to its large π-system) at concentrations higher
than 10-4 M in CHCl3 (1H NMR spectrum, Figure S2). As may be inferred from Tables 2 and
S3, the absorption and emission maximum of coumarins 12d-f bearing electron donating
groups (–OMe) are relatively red-shifted (as compared to 12a), which is in analogy to the
common trend observed with similarly substituted coumarins/benzocoumarins, due to the
activation of ICT (as shown in Figure 3).31 Incidentally, the extent of ICT provided by two
methoxy groups in 12f is found to be nearly equivalent to that by one carbazole nitrogen atom
in 12h. The stronger the ICT, the larger is the red-shift in the absorption and emission maxima.
This fact is further supported by the interesting positive emission solvatochromism (less
pronounced in absorption) in 12e (Figure 5a) and subsequent reduction in its PLQE (Φf CHCl3
to MeOH = 0.08 to 0.02), which otherwise are less significant in 12a. This result, along with
the DFT calculated μg = 5.94 and μe = 8.31 D for 12e, hint to the increase of dipole moment
(∆μ, ca. 2.37 D) upon photoexcitation. Thus, these coumarins reveal large Stokes-shifts (up to
ca. 11,300 cm-1) in solvents of varying polarity. In addition, the fluorescence quantum yields
for 12a-h in CHCl3 were determined to be in the range 0.06 to 0.17, which is relatively higher
than that of the simple coumarins (Φf = 0.002) or close to linearly π-expanded coumarins, such
as, 8-methoxy- or 8-hydroxy-benzo[g]coumarin (Φf = 0.12–0.07), reported earlier (for
comparison, see Table S3).8 In principle, such advantageous properties (long wavelength
emission, efficient ICT, good Φf) associated with these skeletons can be further enhanced by
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grafting strong donor groups (such as, –NEt2) at suitable positions and acceptor units at C3
em
position, as has been demonstrated with 7-diethylaminocoumarin-3-carboxylate (λmax
,
CH2Cl2 = 529 nm, Φf = 0.81) or 8-dimethylamino-3-cyanobenzo[g]coumarin (λmaxem, EtOH =
607 nm, Φf = 0.67) in the literature.8 Indeed, dipolar coumarin dyes with large Stokes-shifts
and improved emission characteristics can be excited at longer wavelengths under two-photon
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conditions (as autofluorescence from biological samples is reduced), enabling deep-tissue
imaging.6 These aspects are presently being investigated. The fluorescent lifetime
measurements (Figure 5b) reveal that the coumarin derivatives 12a-c follow mono-
exponential, and the other coumarins 12d-h display bi-exponential decays. The bi-exponential
decay unveils the existence of two emissive excited states; probably the locally excited state
(LE) and the charge transfer states (CT), as described earlier.32 The emission spectrum of 12e
in solvents of varying polarity is also suggestive of this behaviour. The derived lifetimes (ns,
in all cases) indicate the origin of emission is S1→S0.32
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prompt
12 a
12 b
12 c
12 d
12 e
12 f
10000
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MeOH
DMSO
CHCl3
a)
b)
1.0
0.5
0.0
THF
Toluene
12 g
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400
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Time (ns)
Wavelength (nm)
Figure 5. a) Emission solvatochromism for coumarin 12e (λexc = 330 nm), b) fluorescence
lifetime decay profiles of coumarins 12a–g (λexc = 295 nm).
CONCLUSIONS
In summary, it is shown that the Scholl cyclization methods can be accomplished successfully
on 6,7-diarylcoumarins to achieve [g]-face annulated coumarins, whose absorption and
emission characteristics are better than those of simple coumarins or benzocoumarins reported
in the literature. These dipolar coumarins exhibit substituent- as well as solvent-dependent
emission behaviour with very large Stokes shifts proving such coumarins when appropriately
designed may serve as potential candidates for two-photon bioimaging applications.
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EXPERIMENTAL SECTION
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General Information. All the reagents were commercially purchased and used without further
purification. Spectroscopic grade solvents were used for recording UV-vis absorption and
emission spectra. The compound 4-methyl-6,7-dihydroxycoumarin is commercially purchased
and the compounds 6- or 7-bromo-4-methylcoumarin,33 and 4-methyl-6,7-coumarin ditriflate34
were synthesized by following the literature procedures.
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General procedure for the synthesis of 2/2':
To a 50 mL reaction tube, 18 mL dry toluene was added and purged with nitrogen gas for 20
minutes. To this, compound 1/1' (500 mg, 2.1 mmol, 1.0 eq.), bis(pinacolato)diboron (639 mg,
2.5 mmol, 1.2 eq.), PdCl2(PPh3)2 (3 mol %) and potassium acetate (309 mg, 3.15 mmol, 1.5
eq.) were added, and the mixture was heated in an oil bath at 70 oC for 9 h. After completion
of the reaction, water (10 mL) was added and the organic contents were extracted with ethyl
acetate (10 mL × 3). The combined organic portions were dried over anhydrous sodium
sulphate, and the solvent was evaporated to dryness under rotary evaporator. The crude
compound thus obtained was further purified by a short pad silica-gel column chromatography
using hexane/ethyl acetate (8:2) mixtures to afford a white solid with 82–83% yield.
4-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-chromen-2-one, 2’
O
B
O
O
O
2'
Yield: 495 mg, 82%; Mp: 102–108 ºC; Rf = 0.53 (30% ethyl acetate in hexane); 1H NMR (400
MHz, CDCl3) δ 8.0 (d, J = 1.2 Hz, 1H), 7.93 ( dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 7.29 (d, J =
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8.4 Hz, 1H), 6.27 (d, J = 1.6 Hz, 1H), 2.47 (d, J = 1.6 Hz, 3H), 1.34 (s, 12H); 13C{1H} NMR
(100 MHz, CDCl3) δ 160.7, 155.7, 152.9, 138.2, 137.7, 119.5, 116.5, 115.0, 84.3, 24.9, 18.9;
IR (KBr, cm-1): 2979, 2926, 1737, 1604, 1455, 1367, 1340, 1273, 1144, 1093, 853, 677; HRMS
(ESI–TOF) m/z: [M + H]+ Calcd. for C16H20BO4, 287.1455; found, 287.1468.
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4-Methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-chromen-2-one, 2
O
B
O
O
2
O
Yield: 520 mg, 83%; Mp: 159–161 ºC; Rf = 0.53 (30% ethyl acetate in hexane); 1H NMR (400
MHz, CDCl3) δ 7.73 (d, J = 1.2 Hz, 1H), 7.68 (d, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.57 (d, J = 8.0
Hz, 1H), 6.32 (d, J = 1.2 Hz, 1H), 2.44 (d, J = 1.2 Hz, 3H), 1.36 (s, 12H); 13C{1H} NMR (100
MHz, CDCl3) δ 160.9, 153.0, 152.2, 130.1, 123.8, 123.2, 122.1, 116.2, 84.5, 25.0, 18.7; IR
(KBr, cm-1): 2978, 2930, 1725, 1619, 1508, 1402, 1394, 1239, 1143, 970, 854, 686; HRMS
(ESI–TOF) m/z: [M + H]+ Calcd. for C16H20BO4, 287.1455; found, 287.1479.
General procedure for the synthesis of 4/4':
To a 50 mL schlenk tube, solution of 2/2’ (100 mg, 0.35 mmol) in toluene:ethanol (3:1), was
added 2-bromobiphenyl (122 mg, 0.52 mmol), potassium carbonate (121 mg, 0.87 mmol). The
solution was purged with nitrogen gas for a period of 20 mins, and then Pd(PPh3)2Cl2 (101 mg,
7 mol%) was added into the solution. The reaction mixture was kept for stirring and heated in
an oil bath at 80 °C for overnight under nitrogen gas atmosphere. The reaction was monitored
by TLC. After the completion of the reaction, the reaction mixture was diluted with water and
extracted with ethyl acetate (3 × 15 mL). The combined organic layers were dried over
anhydrous sodium sulphate, filtered and the filtrate was concentrated in vacuo. The crude
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product thus obtained was purified by silica-gel column chromatography using hexane-ethyl
acetate mixtures (10% ethyl acetate in hexanes) as the eluent.
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7-([1,1'-Biphenyl]-2-yl)-4-methyl-2H-chromen-2-one, 4
O
O
4
Yield: 78 mg, 71%; white solid; Mp: 126–128 °C; Rf = 0.31 (20% ethyl acetate in hexanes); 1H
NMR (400 MHz, CDCl3) δ 7.43–7.47 (m, 4H), 7.41 (d, J = 8.4 Hz, 1H), 7.21–7.24 (m, 3H),
7.18 (d, J = 1.6 Hz, 1H), 7.13–7.15 (m, 2H), 7.03 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 6.25 (d,
1H, J = 1.2 Hz), 2.39 (d, J = 1.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 161.1, 153.4,
152.3, 145.9, 140.9, 140.8, 138.7, 131.0, 130.6, 129.9, 128.5, 128.3, 127.8, 127.0, 126.2, 124.0,
118.4, 118.2, 114.8, 18.7; IR (KBr, cm-1): 3059, 1725, 1616, 1442, 1394, 1260, 1223, 1162,
947, 862, 830; HRMS (ESI–TOF) m/z: [M + H]+ Calcd. for C22H17O2, 313.1229; found,
313.1240.
6-([1,1'-Biphenyl]-2-yl)-4-methyl-2H-chromen-2-one, 4’
O
O
4'
Yield: 107 mg, 98%; white solid; Mp: 143–145 °C; Rf = 0.37 (20% ethyl acetate in hexanes);
1H NMR (400 MHz, CDCl3): δ 7.47 (bs, 4H), 7.37 (d, J = 8.4 Hz, 1H), 7.18–7.29 (m, 5H),
7.10–7.16 (m, 2H), 6.23 (s, 1H), 2.15 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3):δ 160.9, 152.5,
152.3, 150.5, 141.3, 138.9, 137.5, 133.3, 130.9, 130.4, 130.0, 128.3, 128.2, 128.0, 126.9, 126.3,
119.5, 116.8, 115.2, 18.5; IR (KBr, cm-1): 3055, 3016, 1724, 1619, 1570, 1480, 1443, 1422,
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1373, 1265, 1178, 925; HRMS (ESI–TOF) m/z: [M + H]+ Calcd. for C22H17O2, 313.1229;
5
6
found, 313.1239.
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General procedure for the synthesis of 6/6':
To a solution of 4/4’ (50 mg, 0.32 mmol) in a two-necked 25 mL round bottom flask equipped
with hydrogen gas bladder, was added dry ethyl acetate (3 mL), hydrogen gas was flushed
followed by the addition of 10 wt% Pd/C. The reaction mixture was stirred at room temperature
in the presence of hydrogen gas and the progress of the reaction was monitored by TLC. After
20 h, the reaction mixture was poured into the celite pad to remove the Pd/C and filterate was
evaporated to dryness to obtain the crude product which was further purified by silica-gel
column chromatography using hexane-ethyl acetate mixtures (10% ethyl acetate in hexane).
7-([1,1'-Biphenyl]-2-yl)-4-methyl-3,4-dihydro-2H-chromen-2-one, 6
O
O
6
1
Yield: 88 mg, 88%; white gummy solid; Rf = 0.41 (20% ethyl acetate in hexanes); H NMR
(500 MHz, CDCl3): δ 7.40–7.43 (m, 4H), 7.22 (m, 3H), 7.13–7.15 (m, 2H), 7.04–7.07 (m, 1H),
6.86–6.88 (m, 2H), 3.10–3.20 (m, 1H), 2.79–2.86 (m, 1H), 2.51–2.61 (m, 1H), 1.32 (d, J = 6.8
Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 168.6, 151.0, 142.2, 141.2, 140.7, 139.2, 130.6,
129.9, 128.1, 128.0, 127.7, 126.8, 126.3, 126.0, 125.9, 118.3, 37.0, 29.2, 19.8; IR (KBr, cm-1):
1767, 1616, 1571, 1474, 1410, 1235, 1151, 1077, 1005, 832; HRMS (ESI–TOF) m/z: [M + H]+
Calcd. for C22H19O2, 315.1385; found, 315.1381.
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6-([1,1'-Biphenyl]-2-yl)-4-methyl-3,4-dihydro-2H-chromen-2-one, 6’
5
6
7
8
9
O
O
6'
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Yield: 88 mg, 88%; white solid; Mp: 149–151°C; Rf = 0.47 (20% ethyl acetate in hexanes); IR
1
(KBr, cm-1): 1765, 1495, 1482, 1469, 1218, 1152, 902, 753; H NMR (400 MHz, CDCl3): δ
7.43 (bs, 4H), 7.22 (m, 3H), 7.11–7.13 (m, 3H), 6.95 (d, J = 8.0 Hz, 1H), 6.86 (s, 1H), 2.91–
3.01 (m, 1 H), 2.72–2.80 (m, 1H), 2.45–2.52 (m, 1H), 1.07 (d, J = 7.2 Hz, 3H); 13C{1H} NMR
(100 MHz, CDCl3): δ 168.4, 150.0, 141.6, 140.8, 139.5, 137.9, 130.8, 130.3, 130.0, 129.6,
128.5, 128.1, 127.83, 127.80, 127.2, 126.7, 116.7, 36.9, 29.4, 19.8. HRMS (ESI–TOF) m/z: [M
+ H]+ Calcd. for C22H19O2, 315.1385; found, 315.1376.
Procedure for the oxidative cyclization of 6 to yield 7:
O
O
7
To a solution of 6 (50 mg, 0.16 mmol) in dry dichloromethane (10 mL), FeCl3 (129 mg, 0.80
mmol) was added under nitrogen gas atmosphere and the reaction was kept for stirring at room
temperature. The progress of the reaction was monitored by TLC. After 7.5 h of the reaction,
another portion of FeCl3 (0.80 mmol) was added to the reaction mixture. After 28 h, the reaction
was quenched by addition of water. The organic contents were extracted using chloroform (3
 5 mL). The organic layer was combined, washed with brine, dried over anhydrous Na2SO4,
filtered and evaporated to dryness. The obtained crude product was purified by silica-gel
column chromatography using hexane-ethyl acetate mixtures (10% ethyl acetate in hexane) as
the eluent. A white solid in 28% yield (14 mg) was isolated. Characterization details of 7 are
given below.
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Procedure for the oxidative cyclization of 6' to yield 7:
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O
O
7
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To a solution of 6’ (50 mg, 0.16 mmol) in dry dichloromethane (5 mL), FeCl3 (52 mg, 0.32
mmol) was added under nitrogen gas atmosphere and the reaction was allowed to stir at room
temperature. The progress of the reaction was monitored by TLC. After 24 h of stirring, the
reaction was quenched by addition of water. The extraction of the organic contents was done
by using chloroform (3  5 mL). The organic layer was combined, washed with brine, dried
over anhydrous Na2SO4, filtered and evaporated to dryness. The crude product thus obtained
was purified by silica-gel column chromatography using hexane-ethyl acetate mixtures (10%
ethyl acetate in hexane) as the eluent to obtain a white solid in 50% yield (25 mg).
3,4-Dihydro-4-methyl-phenanthro[9,10-g]-2H-chromen-2-one, 7: White solid; Mp: 128–
130 °C; Rf = 0.39 (20% ethyl acetate in hexanes); IR (KBr, cm-1): 1767, 1731, 1634, 1149, 756,
719; 1H NMR (400 MHz, CDCl3): δ 8.65 (m, 2H), 8.60 (m, 1H), 8.49–8.52 (m, 2H), 8.27 (s,
1H), 7.67–7.68 (m, 4H), 3.43–3.47 (m, 1H), 2.96–3.02 (m, 1H), 2.70–2.76 (m, 1H), 1.26 (d, J
= 7.2 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3): δ 168.4, 150.8, 130.5, 130.1, 129.7, 129.3,
129.1, 127.93, 127.89, 127.6, 127.5, 127.3, 126.8, 123.63, 123.57, 123.5, 123.2, 121.6, 110.8,
37.2, 30.1, 20.3; HRMS (ESI–TOF) m/z: [M + H]+ Calcd. for C22H17O2, 313.1229; found,
313.1236.
Procedure for the synthesis of 12a from 7:
DDQ (2.9 mg, 0.013 mmol) was added into a solution of 7 (4 mg, 0.013 mmol) in benzene (1.0
mL) and kept for stirring at 80 ˚C in an oil bath for 24 h. Upon completion, the reaction was
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quenched by NaHCO3 solution. The product was extracted into ethyl acetate (2 × 3 mL),
washed with brine solution. The organic layers were combined together and dried over
anhydrous Na2SO4, filtered and evaporated to dryness. The crude product was passed through
a short-pad filter column using hexane-ethyl acetate mixtures (10% ethyl acetate in hexane) as
the eluent and the product was isolated in quantitative yield. Please see below for the
characterization details.
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General procedure for the preparation of 6,7-bis(aryl)-4-methyl-2H-chromen-2-ones
11a-h:
To a toluene:ethanol (3:1) solution of bis(triflate) analogue 5 (500 mg, 1.09 mmol) and the
corresponding arylboronic acid (3.29 mmol) was added K2CO3 (603 mg, 4.36 mmol). The
nitrogen gas was purged into the solution for 20 min and Pd(PPh3)2Cl2 (61 mg, 8 mol%) was
added to the solution. The mixture was heated in an oil bath at 80 °C under nitrogen gas
atmosphere and kept for stirring overnight. The reaction was monitored by TLC. After the
completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl
acetate (3 × 25 mL). The combined organic layers were dried over anhydrous sodium sulphate,
filtered and the filtrate was concentrated in vacuo. The crude product thus obtained was purified
by silica-gel column chromatography using hexane-ethyl acetate mixtures (10% ethyl acetate
in hexane).
4-Methyl-6,7-diphenyl-2H-chromen-2-one, 11a
O
O
11a
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Yield: 279 mg, 82%; white solid; Mp: 168–170 °C [lit., 163-165 °C]34; Rf = 0.65 (20% ethyl
acetate in hexane); IR (KBr, cm-1): 3058, 3025, 1727, 1618, 1545, 1480, 1443, 1406, 1383,
1292, 1271, 1223, 1164, 1075; 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.41 (s, 1H), 7.23–
7.26 (m, 6H), 7.12–7.16 (m, 4H), 6.34 (d, J = 1.2 Hz, 1H), 2.48 (d, J = 1.2 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 161.0, 152.8, 152.3, 144.6, 140.3, 139.8, 137.3, 129.97, 129.8,
128.3, 127.6, 127.2, 126.6, 119.2, 118.7, 115.4,18.8; HRMS (ESI–TOF) m/z: [M + H]+ Calcd.
for C22H17O2, 313.1229; found, 313.1212.
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6,7-Bis(3-methylphenyl)-4-methyl-2H-chromen-2-one, 11b
O
O
11b
Yield: 356 mg, 96%; white solid; Mp: 140–142 °C; Rf = 0.83 (20% ethyl acetate in hexane);
IR (KBr, cm-1): 3019, 2921, 2862, 1724, 1618, 1546, 1435, 1402, 1382, 1294, 1272, 1220,
1
1163; H NMR (400 MHz, CDCl3) δ 7.59 (s, 1H), 7.39 (s, 1H), 7.04–7.14 (m, 4H), 7.01 (s,
2H), 6.88–6.89 (m, 2H), 6.33 (d, J= 1.2 Hz, 1H), 2.48 (d, J= 1.2 Hz, 3H), 2.29 (s, 3H), 2.27 (s,
3H); 13C{1H} NMR(100 MHz, CDCl3) δ 161.1, 152.7, 152.4, 144.8, 140.3, 139.7, 137.9, 137.4,
130.6, 130.4, 128.3, 128.0, 127.8, 127.1, 127.0, 126.5, 119.0, 118.5, 115.2, 21.5, 18.8; HRMS
(ESI–TOF) m/z: [M + H]+ Calcd. for C24H21O2, 341.1542; found, 341.1527.
6,7-Bis(4-tert-butylphenyl)-4-methyl-2H-chromen-2-one, 11c
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O
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60
Yield: 389 mg, 84%; white solid; Mp: 133–136 °C; Rf = 0.72 (20% ethyl acetate in hexane);
IR (KBr, cm-1): 3019, 2962, 2905, 2869, 1729, 1617, 1541, 1515, 1482, 1413, 1396, 1385,
1363, 1293, 1269, 1221, 1165, 1113, 1074, 1011; 1H NMR (500 MHz, CDCl3): δ 7.60 (s, 1H),
7.40 (s, 1H), 7.23–7.26 (m, 4H), 7.06 (m, 4H), 6.32 (s, 1H), 2.46 (s, 1H), 1.31 (s, 9H), 1.30 (s,
13
9H); C{1H} NMR (125 MHz, CDCl3): δ 161.2, 152.8, 152.4, 150.6, 150.1, 144.8, 137.5,
137.3, 136.9, 129.6, 129.4, 126.5, 125.1, 118.9, 118.5, 115.1, 114.9, 34.6, 31.7, 31.46, 31.4,
18.8; HRMS (ESI–TOF) m/z: [M + Na]+ Calcd. for C30H32NaO2, 447.2300; found, 447.2284.
6,7-Bis(3-methoxyphenyl)-4-methyl-2H-chromen-2-one, 11d
OMe
O
O
11d
OMe
Yield: 300 mg, 74%; white solid; Mp: 138–140 °C; Rf = 0.8 (20% ethyl acetate in hexane); IR
(KBr, cm-1): 3008, 2954, 2834, 2361, 2337, 1726, 1603, 1472, 1430, 1402, 1383, 1284, 1213,
1169, 1039, 1012; 1H NMR (400 MHz, CDCl3): δ 7.62 (s, 1H), 7.41(s, 1H), 7.15–7.20 (m, 2H),
6.75–6.81 (m, 4H), 6.67 (s, 2H), 6.33 (d, J = 1.2 Hz, 1H), 3.65 (s, 3H), 3.63 (s, 3H), 2.47 (d,
J= 1.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3): δ 161.0, 159.4, 159.3, 152.8, 152.3, 144.4,
141.7, 141.1, 137.1, 129.3, 126.4, 122.3, 122.1, 119.2, 118.5, 115.5, 115.4, 115.0, 113.7, 113.0,
55.30, 55.29, 18.8; HRMS (ESI–TOF) m/z: [M + Na]+ Calcd. for C24H20NaO4, 395.1259;
found, 395.1265.
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6,7-Bis(3,4-dimethoxyphenyl)-4-methyl-2H-chromen-2-one, 11e
5
6
7
O
O
8
9
10
11
12
13
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47
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57
58
59
60
O
O
O
11e
O
Yield: 396 mg, 84%; white solid; Mp: 116–119 °C; Rf = 0.42 (20% ethyl acetate in hexane);
IR (KBr, cm-1): 3015, 2933, 2837, 1726, 1609, 1585, 1518, 1486, 1462, 1406, 1358, 1323,
1251, 1164, 1141, 1025; 1H NMR (500 MHz, CDCl3): δ 7.59 (s, 1H), 7.41 (s, 1H), 6.80–6.82
(m, 4H), 6.60 (s, 1H), 6.58 (s, 1H), 6.33 (s, 1H), 3.88 (s, 3H), 3.87 (s, 3H), 3.62 (s, 3H), 3.61
(s, 3H), 2.48 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3): δ 160.9, 152.8, 152.2, 148.8, 148.5,
144.3, 136.9, 133.3, 132.5, 126.3, 122.1, 122.0, 118.9, 118.3, 115.2, 113.7, 113.4, 111.3, 111.2,
56.1, 56.0, 55.97, 55.9, 18.7; HRMS (ESI–TOF) m/z: [M + H]+ Calcd. for C26H25O6, 433.1651;
found, 433.1681.
6,7-Bis(3,5-dimethoxyphenyl)-4-methyl-2H-chromen-2-one, 11f
OMe
MeO
MeO
O
O
11f
OMe
Yield: 396 mg, 84%; white solid; Mp: 172–174 °C; Rf = 0.42 (20% ethyl acetate in hexane);
IR (KBr, cm-1): 3000, 2951, 2839, 1726, 1595, 1548, 1457, 1425, 1403, 1382, 1362, 1206,
1
1154, 1060, 1017; H NMR (400 MHz, CDCl3): δ 7.61 (s, 1H), 7.42 (s, 1H), 6.36–6.38 (m,
2H), 6.32–6.35 (m, 5H), 3.65 (s, 6H,), 3.64 (s, 6H), 2.47 (d, J= 1.2 Hz, 3H); C{1H} NMR
13
(125 MHz, CDCl3): δ 161.0, 160.6, 160.5, 152.8, 152.3, 144.4, 142.3, 141.7, 137.1, 126.2,
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119.2, 118.4, 115.4, 108.1, 107.8, 100.1, 99.3, 55.5, 18.8; HRMS (ESI–TOF) m/z: [M + H]+
5
6
Calcd. for C26H25O6, 433.1651; found, 433.1662.
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4-Methyl-6,7-di(phenanthren-9-yl)-2H-chromen-2-one, 11g
O
O
11g
Yield: 449 mg, 79%; white solid; Mp: >260 °C; Rf = 0.53 (20% ethyl acetate in hexane); IR
(KBr, cm-1): 3061, 3016, 1725, 1620, 1491, 1448, 1406, 1378, 1292, 1267, 1219, 1178, 1159,
1054 cm-1;1H NMR (400 MHz, CDCl3): δ 8.54–8.59 (m, 1H), 8.44–8.50 (m, 3H), 7.69–7.92
(m, 4H), 7.58–7.66 (m, 3.4H), 7.55 (s, 0.6H), 7.40–7.54 (m, 4H), 7.32–7.40 (m, 4H), 6.42-6.43
(m, 1H), 2.48 (d, J = 1.2 Hz, 1.2H), 2.46 (d, J = 1.2 Hz, 1.8H); C{1H} NMR (100 MHz,
13
CDCl3): δ 161.0, 152.6, 152.4, 144.9, 137.2, 136.0, 132.0, 130.9, 130.3, 130.0, 129.6, 129.4,
128.71, 128.67, 128.6, 128.0, 127.9, 127.6, 127.3, 127.0, 126.9, 126.8, 126.74, 126.69, 126.6,
126.54, 126.48, 126.4, 126.3, 126.2, 122.99, 122.95, 122.8, 122.5, 122.4, 120.2, 119.9, 119.4,
115.7, 18.9; HRMS (ESI–TOF) m/z: [M + Na]+ Calcd. for C38H24NaO2, 535.1674; found,
535.1665.
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6,7-Bis(9-hexyl-9H-carbazol-2-yl)-4-methyl-2H-chromen-2-one, 11h
5
6
7
C6H13
N
8
9
10
11
12
13
14
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59
60
O
O
11h
N
C6H13
Yield: 128 mg, 89%; white solid; Mp: 158–161 °C; Rf = 0.69 (20% ethyl acetate in hexane);
IR (KBr, cm-1): 3057, 2930, 2864, 1726, 1610, 1459, 1333, 1231, 1168, 1004, 902, 863; H
1
NMR (400 MHz, CDCl3): δ 8.02 (d, J = 7.6 Hz, 1H), 8.01 (d, J = 7.2 Hz, 1H), 7.99 (d, J = 6.8
Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.79 (s, 1H), 7.61 (s, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.38 (d,
J = 7.6 Hz, 1H), 7.22–7.26 (m, 2H), 7.14–7.22 (m, 4H), 7.11 (s, 1H), 7.04 (s, 1H), 6.37 (s, 1H),
3.97 (t, J = 6.8 Hz, 2H), 3.95 (t, J = 6.8 Hz, 2H), 2.54 (s, 3H), 1.25–1.33 (m, 4H), 0.86–1.11
(m, 12 H), 0.76 (t, J = 7.2 Hz, 3H), 0.72 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3):
δ 161.0, 151.9, 151.5, 142.4, 142.1, 139.7, 139.5, 133.7, 127.0, 126.7, 126.5, 125.8, 124.8,
124.3, 123.8, 123.4, 122.8, 122.7, 121.1, 121.0, 119.1, 118.3, 114.6, 114.0, 113.8, 109.8, 108.9,
108.7, 101.7, 100.5, 43.0, 42.7, 31.7, 31.6, 28.9, 28.7, 27.2, 27.0, 22.73, 22.71, 18.5,14.2;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C46H47N2O2, 659.3638; found, 659.3628.
General procedure for the Scholl oxidative cyclization
General procedure for the oxidative cyclization of 11a-f,h under FeCl3
To a solution of 11a-f (100 mg, 1.0 equiv.) in 20 mL dichloromethane, was added FeCl3 (2.0
equiv.). The reaction mixture was stirred at room temperature from 1-16 h. TLC was used to
analyze the progress of the reaction. After completion, the reaction was quenched with
methanol. The organic contents were extracted using chloroform, washed with water followed
by brine solution. The combined organic layers were dried over anhydrous sodium sulfate,
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filtered and the solvent was evaporated in vacuo. The crude product thus obtained was purified
using silica gel column chromatography using hexane-ethyl acetate mixtures.
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4-Methyl-phenanthro[9,10-g]-2H-chromen-2-one, 12a
O
O
12a
Yield: 40 mg, 90%; white solid; Mp: 250 °C; Rf = 0.56 (2:8, ethyl acetate:hexane); IR (KBr,
cm-1): 2939, 2900, 1713, 1622, 1540, 1412, 1381, 1307, 1227, 1178;1H NMR (400 MHz,
CDCl3): δ 8.69 (s, 1H), 8.60–8.63 (m, 2H), 8.53–8.55 (m, 1H), 8.50 (d, J= 6.4 Hz, 1H), 8.38
13
(s, 1H), 7.66–7.73 (m, 4H), 6.37 (s, 1H), 2.61 (s, 3H); C{1H} NMR (100 MHz, CDCl3): δ
160.9, 152.1, 133.1, 130.7, 129.7, 129.1, 128.8, 128.6, 127.8, 126.4, 124.1, 123.7, 123.6, 123.1,
119.7, 119.5, 115.8, 110.4, 18.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C22H14O2,
311.1072; found, 311.1091.
4,7,12-Trimethyl-phenanthro[9,10-g]-2H-chromen-2-one, 12b
O
O
12b
Yield: 49 mg, 50%; white solid; Mp: >240 °C; Rf = 0.51 (2:8, ethyl acetate:hexane); IR (KBr,
cm-1): 3015, 2965, 1722, 1622, 1415, 1380, 1260, 1176, 1078, 1024; H NMR (500 MHz,
1
CDCl3): δ 8.63 (s, 1H), 8.45 (d, J1 = 8.5 Hz, 1H), 8.44 (d, J1 = 8.5 Hz, 1H), 8.26 (s, 1H), 8.25
(s, 1H), 7.49 (dd, J1 = 8.5 Hz, J2 = 1.0 Hz, 1H), 7.47 (dd, J1 = 8.5 Hz, J2 = 1.0 Hz, 1H), 6.35 (d,
J = 1.0 Hz, 1H), 2.62 (s, 3H), 2.60 (s, 6H); 13C{1H} NMR (125 MHz, CDCl3) δ 161.0, 152.1,
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152.0, 137.1, 133.2, 130.2, 129.1, 128.7, 128.5, 128.2, 127.5, 126.4, 124.1, 123.4, 123.3, 123.0,
119.5, 119.3, 115.6, 110.3, 22.0, 21.9, 18.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C24H19O2, 339.1385; found, 339.1360.
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8,11-Di-tert-butyl-4-methyl-phenanthro[9,10-g]-2H-chromen-2-one, 12c
O
O
12c
Yield: 47 mg, 47%; white solid; Mp: 226–229 °C; Rf = 0.43 (10% ethyl acetate in hexanes); IR
(KBr, cm-1): 3014, 2961, 2905, 2869, 1727, 1622, 1476, 1421, 1384, 1365, 1311, 1265, 1226,
1178, 1074; 1H NMR (500 MHz, CDCl3): δ 8.77 (s, 1H), 8.66 (s, 2H), 8.55 (d, J = 8.5 Hz, 1H),
8.51 (d, J = 8.5 Hz, 1H), 8.45 (s, 1H), 7.74–7.78 (m, 2H), 6.39 (d, J = 1.0 Hz, 1H), 2.66 (d, J
= 1.0 Hz, 3H), 1.57 (s, 18H); 13C{1H} NMR (125 MHz, CDCl3): δ 161.0, 152.2, 152.0, 151.7,
150.5, 133.1, 130.7, 129.6, 127.0, 126.6, 126.3, 125.7, 125.6, 124.1, 123.1, 119.4, 119.3, 119.2,
115.5, 110.2, 35.4, 35.2, 31.6, 31.5, 18.8; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd. for
C30H30NaO2, 445.2143; found, 445.2159.
7,12-Dimethoxy-4-methyl-phenanthro[9,10-g]-2H-chromen-2-one, 12d
OMe
O
O
12d
OMe
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9
Yield: 73 mg, 73%; white solid; Mp: 230–232 °C; Rf = 0.56 (20% ethyl acetate in hexane); IR
(KBr, cm-1): 2908, 2857, 1707, 1611, 1458, 1411, 1378, 1235, 1174, 1034; 1H NMR (400 MHz,
CDCl3): δ 8.64 (s, 1H), 8.45 (d, J = 8.8 Hz, 1H), 8.43 (d, J = 8.8 Hz, 1H), 8.35 (s, 1H), 7.95 (d,
J = 2.8 Hz, 1H), 7.87 (d, J = 2.8 Hz, 1H), 7.31 (d, J1 = 9.6 Hz, J2 = 2.6 Hz, 1H), 7.28 (d, J1 =
9.6 Hz, J2 = 2.6 Hz, 1H), 7.27–7.32 (m, 2H), 6.39 (d, J = 1.2 Hz, 1H), 4.04 (s, 3H), 4.03 (s,
3H), 2.63 (d, J = 1.2 Hz, 1H); 13C{1H} NMR (125 MHz, CDCl3): δ 160.9, 158.6, 158.5, 152.1,
152.0, 133.2, 129.6, 129.3, 128.9, 126.4, 124.8, 124.7, 123.8, 119.8, 119.4, 117.8, 115.7, 115.1,
110.4, 106.9, 106.1, 55.7, 55.6, 18.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C24H18O4,
371.1283; found, 371.1301.
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7,8,11,12-Tetramethoxy-4-methyl-phenanthro[9,10-g]-2H-chromen-2-one, 12e
O
O
O
O
O
12e
O
Yield: 90 mg, 91%; pale yellow solid; Mp: 236–238 °C; Rf = 0.39 (50% ethyl acetate in
hexanes); IR (KBr, cm-1): 2923, 2852, 1719, 1617, 1540, 1514, 1459, 1422, 1389, 1264, 1217,
1196, 1152, 1045; 1H NMR (500 MHz, CDCl3): δ 8.22 (s, 1H), 7.83 (s, 1H), 7.67 (s, 1H), 7.59
(s, 1H), 7.54 (s, 1H), 7.48 (s, 1H), 6.28 (s, 1H), 4.11 (s, 3H), 4.09 (s, 6H), 4.00 (s, 3H), 2.51 (s,
13
3H); C{1H} NMR (125 MHz, CDCl3): δ 160.9, 152.1, 151.0, 150.5, 149.8, 149.2, 149.1,
131.8, 125.2, 124.9, 123.8, 122.7, 122.1, 118.6, 118.3, 115.1, 109.2, 104.99, 104.7, 104.6,
104.1, 56.3, 56.2, 56.18, 56.0, 18.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C26H23O6,
431.1495; found, 431.1476.
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7,9,10,12-Tetramethoxy-4-methyl-phenanthro[9,10-g]-2H-chromen-2-one, 12f
5
6
OMe
7
8
9
MeO
MeO
10
11
12
13
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46
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60
O
O
12f
OMe
Yield: 90 mg, 90%; white solid; Mp: 206–208 °C; Rf = 0.40 (30% ethyl acetate in hexanes); IR
(KBr, cm-1): 3003, 2939, 2835, 1725, 1605, 1571, 1459, 1425, 1401, 1383, 1365, 1328, 1303,
1280, 1231, 1203, 1182, 1163, 1118, 1065, 1037, 1019; 1H NMR (400 MHz, CDCl3): δ 8.56
(s, 1H), 8.28 (s, 1H), 7.50 (s, 1H), 7.44 (s, 1H), 6.76 (s, 1H), 6.74 (s, 1H), 6.37 (s, 1H), 4.02 (s,
3H), 4.01 (s, 3H), 4.00 (s, 3H), 3.99 (s, 3H), 2.62 (s, 1H); 13C{1H} NMR (125 MHz, CDCl3):
δ 160.9, 159.2, 152.23, 152.18, 131.6, 127.2, 119.9, 119.5, 115.6, 110.7, 100.0, 98.0, 97.9,
97.4, 77.4, 77.1, 76.9, 56.0, 55.8, 55.7, 18.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C26H23O6, 431.1495; found, 431.1462. This compound was also obtained by photochemical
means whose procedure is provided below.
1’,1’’-Dihexyl-1’H,1’’H-indolo[2’,3’:2,3;2”,3”:6,7]-4-methyl-phenanthro[9,10-g]-2H-
chromen-2-one, 12h
C6H13
N
O
O
12h
N
C6H13
Yield: 54 mg, 54%; yellow solid; Mp: 242–244 °C; Rf = 0.56 (20% ethyl acetate in hexane);
IR (KBr, cm-1): 3023, 2942, 2871, 1724, 1618, 1432, 1372, 1221, 1042, 932; H NMR (400
1
MHz, CDCl3): δ 9.27 (s, 1H), 9.25 (s, 1H), 8.60 (s, 1H), 8.41 (s,1H), 8.36 (d, J = 7.2 Hz), 8.35
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(d, J = 7.2 Hz, 1H), 8.19 (s, 1H), 8.17 (s, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.58 (t, J = 7.6 Hz, 1H),
7.45 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.36 (t, J = 7.2 Hz, 2H), 6.22 (s, 1H), 4.30
(t, J = 7.2 Hz, 2H), 4.28 (t, J = 7.6 Hz, 2H), 2.59 (s, 3H), 1.90–1.99 (m, 4H), 1.44–1.49 (m, 4
H), 1.30–1.39 (m, 8 H), 0.88 (t, J = 6.8 Hz, 6H); 13C{1H} NMR (125 MHz, CDCl3): δ 161.0,
152.0, 151.8, 142.6, 142.3, 139.9, 139.7, 134.0, 127.1, 127.0, 126.8, 126.0, 124.5, 124.0, 123.6,
122.9, 122.8, 121.1, 121.0, 119.3, 119.2, 114.9, 114.2, 114.1, 110.1, 109.0, 108.8, 101.9, 100.7,
43.2, 42.9, 31.7, 31.6, 29.8, 29.0, 28.8, 27.2, 27.1, 22.7, 18.6, 14.2; HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd. for C46H45N2O2, 657.3481; found, 657.3467. This compound 12h was also
synthesized in 85% yields by following the DDQ/H+ conditions described below.
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General procedure for the Scholl oxidative cyclization of 11g under DDQ/H+ conditions
A representative procedure for the synthesis of 12g from 11g is given below.
To a solution of 11g (100 mg, 0.19 mmol, 1.0 equiv.) in 20 mL dichloromethane, was added
methanesulphonic acid (20.0 equiv.) dropwise at 0 °C followed by the addition of DDQ (2.0
equiv.). The reaction was kept at room temperature for stirring. The reaction progress was
monitored by TLC. The reaction was quenched by NaHCO3 solution. The organic components
of the reaction were extracted into chloroform, washed with water and washed with brine
solution. The combined organic layers were dried over anhydrous sodium sulfate, filtered and
the solvent was evaporated under vacuo. The crude product thus obtained was purified by
silica-gel column chromatography using hexane-ethyl acetate mixtures as eluent.
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