Direct one-pot synthesis of phenanthrenes via Suzuki-Miyaura coupling/aldol condensation cascade reaction

Article abstract of DOI:10.1021/jo702001n

(Chemical Equation Presented) We have developed an efficient cascade reaction, a Suzuki-Miyaura coupling followed by an aldol condensation, for the construction of phenanthrene derivatives using microwave irradiation. For example, the reaction of methyl 2-bromophenylacetamide with 2- formylphenylboronic acid in the presence of a palladium catalyst and a base provided a biaryl intermediate, which underwent in situ cyclization to afford the corresponding phenanthrene in high yield.

Full text of DOI:10.1021/jo702001n

Direct One-Pot Synthesis of Phenanthrenes via Suzuki-Miyaura
Coupling/Aldol Condensation Cascade Reaction
Young Ha Kim,† Hyuk Lee,‡ Yeong Joon Kim,† Bum Tae Kim,‡ and Jung-Nyoung Heo*,‡
The Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, 100 Jang-dong,
Daejeon 305-600, Korea, and Department of Chemistry, Chungnam National UniVersity, 220 Gung-dong,
Daejeon 305-764, Korea
heojn@krict.re.kr
ReceiVed September 12, 2007
We have developed an efficient cascade reaction, a Suzuki-Miyaura coupling followed by an aldol
condensation, for the construction of phenanthrene derivatives using microwave irradiation. For example,
the reaction of methyl 2-bromophenylacetamide with 2-formylphenylboronic acid in the presence of a
palladium catalyst and a base provided a biaryl intermediate, which underwent in situ cyclization to
afford the corresponding phenanthrene in high yield.
Introduction
photochemical, and electroluminescent properties.5 For the last
several decades, much attention has focused on the development
of synthetic methods for the construction of phenanthrene
derivatives. These strategies can be divided into three classes
that depend upon the order in which the central ring is connected
as shown in Figure 1. First, most classical approaches to
phenanthrenes require the preparation of a stilbene followed by
an intramolecular cyclization via aryl-aryl bond formation such
as photocyclization,6 the Pschorr reaction,7 and oxidative8 and
radical9 reactions (connection B and then A). Second, the reverse
approaches have also been studied considerably (connection A
Phenanthrenes belong to an important skeleton of organic
compounds due to their core structure in natural products1 and
interesting biological activities such as antimalarial,2 anticancer,3
and emetic activity.4 They also serve as a common structural
motif in materials science based on their photoconducting,
* Corresponding author. Fax: +82-42-861-0307.
† Chungnam National University.
‡ Korea Research Institute of Chemical Technology.
(1) (a) Floyd, A. J.; Dyke, S. F.; Ward, S. E. Chem. ReV. 1976, 76, 509-
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10.1021/jo702001n CCC: $40.75 © 2008 American Chemical Society
Published on Web 12/23/2007
J. Org. Chem. 2008, 73, 495-501
495

Kim et al.
SCHEME 1. Two-Step Approach to Phenanthrene
Results and Discussion
Two-Step Sequence for the Synthesis of Phenanthrene.
To verify our synthetic strategy, we carried out the Suzuki-
Miyaura coupling reaction using methods previously developed
in our laboratory.20 Coupling of 2-bromophenylacetamide 1a21
with 2-formylphenylboronic acid (2a) in the presence of a Pd
catalyst provided biaryl 3 in 79% yield (Scheme 1).22 In this
reaction, we observed little or no phenanthrene 4a based on
GC/MS analysis. Then, we attempted the intramolecular aldol-
type cyclization under mild basic conditions (Cs2CO3) at a
higher temperature (150 °C) using microwave heating. This
operation successfully afforded the desired phenanthrene 4a in
excellent yield.
FIGURE 1. Strategy for the construction of phenanthrenes.
then B). Among them, the Suzuki-Miyaura reaction10 is most
frequently utilized in combination with various intramolecular
cyclization methods including directed ortho and remote meta-
lation,11 ring-closing metathesis,12 and DDQ oxidation.13 Other
examples include Ullman coupling/McMurry cyclization,14
a
Fridel-Crafts-type reaction with quinone/base-mediated con-
densation,15 and siloxane coupling/Friedel-Crafts coupling.16
Third, there are more direct approaches to phenanthrenes based
on the metal-induced carbocyclization of alkynylated biaryl
derivatives17 and metal-catalyzed cyclotrimerization of arynes18
(connection A to C). Despite these advances, there is still
demand for methods with improved yields and greater diversity
of substituents for the synthesis of highly functionalized
phenanthrene derivatives. Thus, we have designed a two-step
sequence, Suzuki-Miyaura coupling of III with IV followed
by intramolecular aldol-type condenstion of II, for the rapid
access of phenanthrenes I under microwave irradiation (Figure
1).19 For feasible aldol condensation and aromatization of II,
we thought that nitrile, ketone, ester, amide, and sulfone groups
would be useful as activating partners.
Direct One-Pot Synthesis of Phenanthrenes. Having dem-
onstrated the synthesis of phenanthrene 4a, we envisioned that
a cascade reaction of Suzuki-Miyaura coupling/aldol-type
condensation in one pot might be possible through a suitable
catalyst and base system. The results are illustrated in Table 1.
We initially ran the reaction at higher temperature (150 °C) for
an extended time period (10 min). In this case, we were able to
obtain phenanthrene 4a, although the reaction yield was very
low (entry 1 in Table 1). With the use of Pd(PPh3)4 as a
palladium source, the reaction proceeded in improved 13% yield
(entry 2 in Table 1).
Since aldol condensation with inorganic bases requires polar
reaction media,23 we decided to use a protic solvent environ-
ment. Reaction in dioxane/H2O, however, provided no desired
product as well as a lower coupling yield (entry 3 in Table 1).
We were pleased to find that the reaction in toluene/EtOH (2:1
v/v) provided the phenanthrene 4a in excellent yield with
complete consumption of biphenyl intermediate 3 (entry 4 in
Table 1).24 We next examined temperature and base effects,
but the reaction yields were inferior to those of the previous
reaction (entries 5-8 in Table 1). Additionally, we observed
(11) (a) Cai, X.; Brown, S.; Hodson, P.; Snieckus, V. Can. J. Chem.
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J.-M.; Snieckus, V. Can. J. Chem. 2000, 78, 905-919. (d) Pathak, R.;
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Ma´tyus, P.; Maes, B. U. W.; Riedl, Z.; Hajo´s, G.; Lemie`re, G. L. F.;
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K. J. Org. Chem. 2000, 65, 332-336.
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(21) For preparation of 1a-f, 1k, and 2b, see Supporting Information.
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formylbiphenyl-2-acetate, see: Saha, M.; Das, T. K.; Das, A.; Ghosh, N.
R. Synth. Commun. 1990, 20, 137-151.
496 J. Org. Chem., Vol. 73, No. 2, 2008

Direct One-Pot Synthesis of Phenanthrenes
TABLE 1. Synthesis of Phenanthrene via Suzuki-Miyaura
TABLE 3. Synthesis of Phenanthrene Derivativesa
Coupling/Aldol Condensation Cascade Reactiona
yield (%)b
entry
Pd
base
solvents
temp (°C)
3
4a
1
2
3
4
5
6
7
8
9
Pd(PPh3)2Cl2 Cs2CO3 dioxane
150
150
150
150
130
150
150
150
150e
63
53
27
0
0
0
30
17
0
3
13
0
87
83
75
0
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Cs2CO3 dioxane
Cs2CO3 dioxane/H2Oc
Cs2CO3 toluene/EtOHd
Cs2CO3 toluene/EtOHd
Pd(PPh3)2Cl2 Cs2CO3 toluene/EtOHd
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Na2CO3 toluene/EtOHd
K3PO4
toluene/EtOHd
Cs2CO3 toluene/EtOHd
27
81
a Reaction conditions: aryl bromide 1a (0.5 mmol), boronic acid 2a (0.6
mmol, 1.2 equiv), Pd (4 mol %), base (1.5 mmol), solvents (3 mL), MW,
10 min. b Isolated yield. c Dioxane/H2O ) 9:1. d Toluene/EtOH ) 2:1. e Oil
bath heating, 2 h.
TABLE 2. Solvent Effects: Reaction of 1a with 2aa
GC yields (%)
ratio
entry
(toluene/EtOH)
3
4a
1
2
3
4
9:1
4:1
2:1
1:1
69
0
0
16
84 (71)b
87b
0
73
a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol, 1.2 equiv),
Pd(PPh3)4 (4 mol %), Cs2CO3 (1.5 mmol), solvents (3 mL), MW 150 °C,
10 min. b Isolated yields.
that the thermal reaction in an oil bath for 2 h smoothly
proceeded to furnish the phenanthrene 4a in 81% yield (entry
9 in Table 1).
The ratio of toluene/EtOH is crucial for achieving high yields
of the phenanthrene. As illustrated in Table 2, we examined
various ratios of toluene and ethanol (9:1, 4:1, 2:1, and 1:1).
When a larger proportion of toluene was used, the reaction was
less effective for the aldol condensation (entry 1 in Table 2).
On the contrary, increasing amounts of ethanol equal to toluene
(1:1) resulted in loss of reaction yield (entry 4 in Table 2). We
found that the optimum ratio was 2:1 (entry 3 in Table 2).
To study the scope and limitations of the cascade reaction,
we examined a variety of aryl halides with substituted
2-formylphenylboronic acids (Table 3).25 Reactions of an aryl
bromide possessing an amide or ester moiety with boronic acids
provided the corresponding phenanthrenes in good yields. In
the case of methyl ester 1e, however, transesterification with
ethanol occurred significantly. Decreasing the reaction temper-
ature to 130 °C reduced transesterification (entry 6 in Table 3).
a Reaction conditions: aryl halide (0.5 mmol), boronic acid (0.6 mmol,
1.2 equiv), Pd(PPh3)4 (4 mol %), Cs2CO3 (1.5 mmol), toluene/EtOH (2
mL/1 mL), MW 150 °C, 10 min. b Isolated yield. c MW 130 °C, 10 min,
4g was isolated (18%). d DavePhos (6 mol %) was added, MW 120 °C, 5
min f MW 150 °C, 10 min. e SPhos (6 mol %) was added.
(24) On the basis of GC/MS analysis, we observed that dehalogenated
product was obtained as a major side product (∼5%) and that intramolecular
cyclization product 9 was not detected under these conditions, see: Yang,
B. H.; Buchwald, S. L. Org. Lett. 1999, 1, 35-38.
When ethyl ester 1f was used, the phenanthrene ethyl ester 4g
was obtained in excellent yield (entry 7 in Table 3). The
coupling of 2-bromoacetophenone (1g) with boronic acids
(25) In cases of aryl bromides such as 2-bromobenzyl methyl ether and
N-(2-bromobenzyl)acetamide, we failed to obtain the corresponding phenan-
threnes.
J. Org. Chem, Vol. 73, No. 2, 2008 497

Kim et al.
SCHEME 2. Synthesis of Phenanthrene Using Arylboronate
SCHEME 3. Synthesis of Phenanthrene Using
2-Acetylphenylboronic Acid
provided phenanthrenes in good yields (entries 8-9 in Table
3). Phenyl sulfone 1h also proved to be an excellent coupling
partner in this type of cascade reaction, with 85% yield (entry
10 in Table 3). Additionally, efficient cascade reactions of
phenylacetonitriles 1i-l with 2-formylphenylboronic acid were
achieved (entries 11-14 in Table 3). In the case of aryl bromide
1k,26 having the hindered o-methyl group, we were able to
obtain 5-methylphenanthrene 4m in moderate yield (entry 13
in Table 3). Importantly, 1l having the chloride moiety also
served as a good Suzuki-Miyaura coupling partner, in the
presence of additional SPhos ligand,27 to provide phenanthrene
4n in 80% yield (entry 14).
Reverse Approach Using Boronate Ester. Despite the
successful utilization of the cascade reaction, limitations still
exist. For example, o-formylphenylboronic acids 2 are difficult
to synthesize.28 We recognized that this drawback could be
overcome by the use of boronate ester 529 and 2-haloaryl
carboxaldehyde counterparts 6, which are commercially avail-
able (Scheme 2). The cascade reaction of pinacol boronate ester
5 with 2-bromobenzaldehyde (6a) under the same conditions
afforded the phenanthrene 4k in slightly lower yield than that
of aryl bromide 1i with boronic acid 2a. Additionally, with the
use of 2-bromo-4,5-dimethoxybenzaldehyde (6b) possessing
electron-donating groups, the cascade reaction of 5 proceeded
sluggishly. On the other hand, 2-bromo-5-fluorobenzaldehyde
(6c), which contains an electron-withdrawing group, afforded
the phenanthrene 4p in 73% yield. Furthermore, this strategy
employing a boronate ester allowed the use of heteroaryl
carboxaldehydes such as 2-bromonicotinaldehyde (6d) for the
synthesis of benzoquinoline 4q in good yield.
SCHEME 4. Synthesis of Phenanthrene Lactam
conditions,30 we found that additional DavePhos ligand (6 mol
%) and lower reaction temperature (120 °C) for the Suzuki-
Miyaura coupling step resulted in an improved 71% yield
(method B). In addition, the cascade reactions of 1e, 1f, and 1i
also afforded the corresponding phenanthrenes 8b, 8c, and 8d
in 71, 52, and 56% yields, respectively.
Synthesis of Phenanthrene Excimer. Finally, we utilized
our approach for the synthesis of a fluorescent excimer 11,
which was previously reported by the Lewis group.5a Retrosyn-
thetically, we have envisioned the synthesis starting from 10-
methylphenanthrene ethyl ester 8c. As shown in Scheme 4,
phenanthrene 8c was treated with NBS/AIBN to afford methyl
bromide 10 in 93% yield. Subsequent lactamization of 10 using
methyl amine furnished phenanthrene lactam 11 in excellent
yield. This protocol can be applied to the synthesis of novel
fluorescent phenanthrene excimers.
Conclusion
In summary, we have demonstrated that a one-pot cascade
reaction of Suzuki-Miyaura coupling/aldol condensation can
be a mild, simple, and efficient method for the synthesis of
highly functionalized phenanthrenes. This one-pot method has
also proved to be a robust and rapid route to construct a central
ring of phenanthrenes from readily available ortho substituted
aryl bromides and o-formyl- or o-acetyl-arylboronic acids.
Furthermore, applications of this protocol toward the total
synthesis of natural products and polycyclic aromatic compounds
will be reported in due course.
Synthesis of 10-Methylphenanthrenes. To further challenge
the scope of the cascade reaction, we employed 2-acetylphe-
nylboronic acid 7, which contains a ketone as an aldol acceptor
(Scheme 3). Using the previously optimized conditions (method
A), we obtained the desired product 8a only in 40% yield. In
this result, we believe that the primary factor affecting the
reaction yield of phenanthrene is the efficiency of the Suzuki-
Miyaura coupling. After screening a number of reaction
(26) Baker, R. W.; Foulkes, M. A.; Griggs, M.; Nguyen, B. N.
Tetrahedron Lett. 2002, 43, 9319-9322.
Experimental Section
(27) (a) Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L.
J. Am. Chem. Soc. 2005, 127, 4685-4696. (b) Billingsley, K. Buchwald,
S. L. J. Am. Chem. Soc. 2007, 129, 3358-3366.
2-(2′-Formylbiphenyl-2-yl)-N-methylacetamide (3). To a solu-
tion of aryl bromide 1a (114 mg, 0.5 mmol) in 3 mL of dioxane
was added boronic acid 2a (90 mg, 0.6 mmol), Pd(PPh3)2Cl2 (14
(28) (a) Geen, G. R.; Mann, I. S.; Mullane, M. V.; McKillop, A.
Tetrahedron 1998, 54, 9875-9894. (b) Hall, D. G. Boronic Acids; Wiley-
VCH: Weinheim, Germany, 2005.
(29) Baudoin, O.; Gue´nard, D.; Gue´ritte, F. J. Org. Chem. 2000, 65,
9268-9271.
(30) We have evaluated reaction conditions using a variety of palladium
sources (Pd(PPh3)4, Pd(OAc)2, and PdCl2) and ligands (DavePhos, XPhos,
and SPhos).
498 J. Org. Chem., Vol. 73, No. 2, 2008

Direct One-Pot Synthesis of Phenanthrenes
mg, 4 mol %), and Cs2CO3 (489 mg, 1.5 mmol). The mixture was
irradiated at 120 °C for 5 min using a microwave reactor and cooled
to room temperature. The mixture was diluted with EtOAc and
filtered through a short Celite pad. The solution was concentrated
in vacuo and purified by flash column chromatography (10% f
50% EtOAc/hexanes) to provide biphenyl 3 (101 mg, 79%) as a
colorless oil: 1H NMR (300 MHz, CDCl3) δ 9.76 (s, 1H), 8.00
(dd, 1H, J ) 7.6, 1.2 Hz), 7.63 (td, 1H, J ) 7.4, 1.5 Hz), 7.54 (td,
1H, J ) 7.6, 0.6 Hz), 7.46-7.20 (m, 5H), 5.29 (bs, 1H), 3.43 (d,
A of ABq, 2H, J ) 15.9 Hz), 3.34 (d, B of ABq, 2H, J ) 15.9
Hz), 2.63 (d, 3H, J ) 4.8 Hz); 13C NMR (75 MHz, CDCl3) δ 192.2,
171.0, 143.9, 138.6, 134.2, 133.9, 133.6, 131.2, 131.0, 130.9, 129.1,
129.0, 128.6, 127.4, 41.5, 26.6; IR (neat) 3305, 1691, 1644, 1254
cm-1; MS (EI) m/z 253 (M+, 2), 235 (22), 195 (33), 181 (16), 178
(34), 165 (100), 152 (42), 139 (16), 115 (13); HRMS (EI) calcd
for C16H15NO2 [M+] 253.1103, found 253.1128.
N-Methylphenanthrene-9-carboxamide (4a). To a solution of
biphenyl 3 (100 mg, 0.4 mmol) in toluene/EtOH (2 mL/1 mL) was
added Cs2CO3 (390 mg, 1.2 mmol). The suspension was irradiated
at 150 °C for 10 min using a microwave reactor and cooled to
room temperature. The mixture was diluted with EtOAc and filtered
through a short Celite pad. The solution was concentrated in vacuo,
and the residue was purified by silica gel flash column chroma-
tography (10% f 50% EtOAc/hexanes) to afford phenanthrene 4a
(86 mg, 91%) as a white solid: mp 160 °C (lit.5b 191-192 °C);
1H NMR (300 MHz, CDCl3) δ 8.73-8.67 (m, 2H), 8.35-8.31 (m,
1H), 7.89 (dd, 2H, J ) 3.8, 1.4 Hz), 7.86-7.59 (m, 4H), 6.09 (bs,
1H), 3.13 (d, 1H, J ) 4.9 Hz); 13C NMR (75 MHz, CDCl3) δ 170.5,
133.8, 131.2, 130.8, 130.6, 129.3, 128.8, 128.1, 127.4, 127.3, 127.2,
126.5, 126.4, 123.1, 122.9, 27.7; IR (neat) 3272, 1631, 1548, 1320
cm-1; MS (EI) m/z 235 (M+, 100), 234 (11), 206 (11), 205 (79),
178 (13), 177 (79), 176 (51), 151 (22), 150 (20); HRMS (EI) calcd
for C16H13NO [M+] 235.0997, found 235.0993.
2,7-Dimethoxy-N-methylphenanthrene-9-carboxamide (4d).
1
Yield 58%, white solid, mp 205∼206 °C; H NMR (300 MHz,
CDCl3) δ 8.45 (t, 2H, J ) 8.3 Hz), 7.75 (s, 1H), 7.73 (d, 1H, J )
2.6 Hz), 7.31-7.25 (m, 2H), 7.17 (d, 1H, J ) 2.6 Hz), 6.16 (bs, 1
H), 3.93 (s, 6H), 3.10 (d, 3H, J ) 4.9 Hz); 13C NMR (75 MHz,
DMSO-d6) δ 169.8, 158.2, 157.9, 134.0, 131.3, 129.5, 127.2, 125.4,
125.2, 124.7, 118.9, 117.7, 109.8, 107.7, 55.9, 55.8, 26.8; IR (neat)
3287, 2935, 1618, 1467 cm-1; HRMS (EI) calcd for C18H17NO3
[M+] 295.1208, found 295.1209.
N-Benzylphenanthrene-9-carboxamide (4e). Yield 73%, white
1
solid, mp 154∼156 °C; H NMR (300 MHz, CDCl3) δ 8.67 (t,
2H, J ) 9.5 Hz), 8.35 (dd, 1H, J ) 7.8, 1.1 Hz), 7.86-7.83 (m,
2H), 7.72-7.56 (m, 4H), 7.44-7.29 (m, 5H), 6.46 (bs, 1H), 4.74
(d, 2H, J ) 5.8 Hz); 13C NMR (75 MHz, CDCl3) δ 169.7, 138.4,
133.4, 131.2, 130.8, 130.5, 129.3, 129.1, 128.7, 128.2, 128.1, 127.9,
127.4, 127.3, 127.2, 126.5, 123.1, 122.9, 44.3; IR (neat) 3268, 1631,
1528, 1450, 1261 cm-1; MS (EI) m/z 312 (14), 311 (M+, 61), 205
(78), 87 (100), 151 (26), 104 (26), 91 (37); HRMS (EI) calcd for
C22H17NO [M+] 311.1310, found 311.1310.
Methyl Phenanthrene-9-carboxylate (4f). The reaction mixture
was irradiated for 10 min at 130 °C. Yield 57%, white solid, mp
76∼80 °C (lit.5b 115 °C); 1H NMR (300 MHz, CDCl3) δ 8.91 (m,
1H), 8.71 (t, 2H, J ) 8.4 Hz), 8.47 (d, 1H, J ) 6.3 Hz), 7.97 (d,
1H, J ) 7.8 Hz), 7.75-7.46 (m, 4H), 4.05 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 168.3, 132.7, 132.4, 130.9, 130.3, 130.2, 129.3,
129.2, 127.7, 127.3, 127.1, 126.8, 126.4, 1231, 122.9, 52.5; IR (neat)
1705, 1444, 1432, 1252 cm-1; MS (EI) m/z 237 (19), 236 (M+,
100), 205 (88), 177 (78), 176 (74), 151 (25), 150 (23); HRMS (EI)
calcd for C16H12O2 [M+] 236.0837, found 236.0837.
Ethyl Phenanthrene-9-carboxylate (4g). In addition to the
reagents used in method A, DavePhos (6 mol %) was added. The
reaction mixture was irradiated for 5 min at 120 °C and then for a
further 5 min at 150 °C using a microwave reactor. Yield 87%,
1
Typical Procedure for Direct One-Pot Synthesis of Phenan-
threnes. Method A: to a thick-well borosilicate glass vial (3 mL)
was added aryl bromide (0.5 mmol), boronic acid (0.6 mmol), Pd-
(PPh3)4 (4 mol %), and Cs2CO3 (1.5 mmol) sequentially. The
mixture was suspended in toluene/EtOH (2 mL/1 mL). Then, the
reaction vial was sealed and placed into a microwave reactor and
irradiated at 150 °C for 10 min (Usually, the average microwave
power ranged from 60 to 80 W and the internal pressure was 6-8
bar). After being cooled to room temperature, the mixture was
diluted with EtOAc and filtered through a short Celite pad. The
solution was concentrated in vacuo, and the residue was purified
by silica gel flash column chromatography (EtOAc/hexanes) to
afford a phenanthrene product.
colorless oil, H NMR (300 MHz, CDCl3) δ 8.93-8.89 (m, 1H),
8.75-8.67 (m, 2H), 8.46 (s, 1H), 7.97 (d, 1H, J ) 7.8 Hz), 7.78-
7.61(m, 4H), 4.52 (q, 2H, J ) 7.1 Hz), 1.50 (t, 3H, J ) 7.1 Hz);
13C NMR (75 MHz, CDCl3) δ 167.9, 132.4, 132.3, 130.9, 130.3,
130.1, 129.3, 129.1, 127.6, 127.2, 127.1, 126.9, 126.8, 123.1, 122.9,
61.5, 14.7; IR (neat) 1713, 1448, 1302, 1252, 1186 cm-1; MS (EI)
m/z 251 (20), 250 (M+, 100), 222 (21), 205 (89), 177 (89), 151
(28); HRMS (EI) calcd for C17H14O2 [M+] 250.0994, found
250.1007.
1-(Phenanthren-9-yl)ethanone (4h). Yield 72%, white solid,
mp 62 °C; 1H NMR (300 MHz, CDCl3) δ 8.74-8.67 (m, 3H), 8.21
(s, 1H), 7.96 (d, 1H, J ) 7.8 Hz), 7.79-7.63 (m, 4H), 2.83 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 201.6, 134.3, 131.8, 130.7,
130.6, 129.7, 129.6, 128.8, 128.2, 127.4, 127.0, 126.9, 126.7, 122.6,
122.5, 30.0; IR (neat) 1670, 1527, 1444, 1352, 1293, 1248, 1212,
1156, 1141 cm-1; MS (EI) m/z 221 (11), 220 (M+, 78), 205 (86),
177 (100), 176 (65), 151 (34), 150 (23); HRMS (EI) calcd for
C16H12O [M+] 220.0888, found 220.0729.
2,3-Dimethoxy-N-methylphenanthrene-9-carboxamide (4b).
1
Yield 80%, white solid, mp 198∼200 °C; H NMR (300 MHz,
CDCl3) δ 8.50 (d, 1H, J ) 7.7 Hz), 8.31 (d, 1H, J ) 8.1 Hz), 7.92
(d, 1H, J ) 2.2 Hz), 7.73 (d, 1H, J ) 3.0 Hz), 7.66-7.53 (m, 2H),
7.14 (d, 1H, J ) 3.5 Hz), 6.16 (s, 1H), 4.10 (s, 3H), 3.99 (s, 3H),
3.11 (d, 3H, J ) 4.7 Hz); 13C NMR (75 MHz, CDCl3) δ 170.8,
150.0, 149.3, 131.5, 129.9, 127.9, 126.6, 126.4, 126.1, 125.7, 125.5,
125.3, 122.3, 108.5, 103.0, 56.0, 55.9, 26.9; IR (neat) 3377, 1660,
1504, 1464, 1435, 1249, 1151 cm-1; MS (EI) m/z 296 (22), 295
(M+, 100), 265 (74), 207 (11), 165 (11), 151 (14); HRMS (EI)
calcd for C18H17NO3 [M+] 295.1208, found 295.1214.
1-(2-Methoxyphenanthren-9-yl)ethanone (4i). Yield 66%, white
1
solid, mp 82 °C; H NMR (300 MHz, CDCl3) δ 8.67-8.57 (m,
3H), 8.13 (s, 1H), 7.69-7.58 (m, 2H), 7.38 (dd, 1H, J ) 9.1, 2.6
Hz), 7.32 (d, 1H, J ) 2.6 Hz), 3.99 (s, 3H), 2.82 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 202.2, 158.8, 135.6, 131.6, 131.2, 130.2, 127.5,
127.4, 127.0, 126.8, 126.6, 124.6, 122.5, 119.8, 109.6, 55.7, 30.3;
IR (neat) 2837, 1666, 1572, 1452, 1244 cm-1; MS (EI) m/z 251
(13), 250 (M+, 74), 236 (16), 235 (100), 207 (19), 192 (43), 164
(43), 163 (50); HRMS (EI) calcd for C17H14O [M+] 250.0994, found
250.1009.
6-Methoxy-N-methylphenanthrene-9-carboxamide (4c). Yield
1
86%, white solid, mp 166∼168 °C; H NMR (300 MHz, CDCl3)
δ 8.58 (d, 1H, J ) 8.1 Hz), 8.27 (d, 1H, J ) 9.1 Hz), 8.05 (d, 1H,
J ) 2.5 Hz), 7.85 (dd, 1H, J ) 6.7, 3.7 Hz), 7.71-7.57 (m, 3H),
7.26 (dd, 1H, J ) 9.0, 2.5 Hz), 6.16 (bs, 1H), 4.02 (s, 3H), 3.11 (d,
3H, J ) 4.9 Hz); 13C NMR (75 MHz, CDCl3) δ 170.6, 158.7, 133.4,
132.3, 130.9, 129.2, 128.0, 127.5, 127.4, 127.2, 124.0, 123.3, 122.8,
9-(Phenylsulfonyl)phenanthrene (4j). Yield 85%, white solid,
1
mp 164∼166 °C; H NMR (300 MHz, CDCl3) δ 8.92 (s, 1H),
8.72-8.61 (m, 3H), 8.11 (dd, 1H, J ) 7.8, 1.1 Hz), 8.02-7.99 (m,
2H), 7.85-7.79 (m, 1H), 7.74-7.57 (m, 4H), 7.53-7.44 (m, 3H);
13C NMR (75 MHz, CDCl3) δ 141.8, 134.4, 133.4, 133.3, 133.0,
131.5, 131.1, 131.0, 130.4, 129.5, 129.4, 127.9, 127.8, 127.6, 126.2,
125.6, 123.6, 123.0; IR (neat) 1444, 1290, 1139, 1086 cm-1; MS
116.9, 55.6, 26.9; IR (neat) 3281, 2835, 1620, 1530, 1234 cm-1
;
MS (EI) m/z 265 (M+, 100), 235 (78), 207 (58), 163 (61), 125
(11); HRMS (EI) calcd for C17H15NO2 [M+] 265.1103, found
265.1097.
J. Org. Chem, Vol. 73, No. 2, 2008 499

Kim et al.
(EI) m/z 319 (12), 318 (M+, 43), 253 (47), 176 (60), 165 (100),
151 (24); HRMS (EI) calcd for C20H14O2S [M+] 318.0715, found
318.0714.
7.84 (m, 2H), 7.61 (dd, 1H, J ) 8.1, 4.4 Hz); 13C NMR (75 MHz,
CDCl3) δ 151.9, 147.6, 136.8, 134.2, 131.5, 130.7, 129.9, 128.9,
125.6, 125.2, 124.6, 122.9, 117.6, 110.6; IR (neat) 2221, 1591, 1444,
1230 cm-1; MS (EI) m/z 205 (17), 204 (M+, 100), 176 (10), 150
(10), 102 (11); HRMS (EI) calcd for C14H8N2 [M+] 204.0687, found
204.0704.
Typical Procedure for One-Pot Synthesis of 10-Methylphenan-
threnes. Method B: in addition to the reagents used in method A,
DavePhos (6 mol %) was added. The reaction mixture was irradiated
for 5 min at 120 °C and then for a further 5 min at 150 °C using
a microwave reactor.
N,10-Dimethylphenanthrene-9-carboxamide (8a). Yield 71%,
white solid, mp 136 °C; 1H NMR (300 MHz, CDCl3) δ 8.71-8.64
(m, 2H), 8.09 (dd, 1H, J ) 7.6, 2.0 Hz), 7.83 (dd, 1H, J ) 7.7, 1.7
Hz), 7.72-7.55 (m, 4H), 5.96 (bs, 1H), 3.14 (d, 1H, J ) 4.8 Hz),
2.69 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 171.3, 133.6, 131.3,
130.5, 129.7, 129.3, 128.9, 127.4, 127.3, 127.2, 126.6, 125.8, 125.3,
123.1, 122.9, 26.9, 17.1; IR (neat) 3303, 2924, 1631, 1555, 1276
cm-1; MS (EI) m/z 249 (M+, 100), 219 (81), 191 (39), 189 (30),
165 (49); HRMS (EI) calcd for C17H15NO [M+] 249.1154, found
249.1166.
Phenanthrene-9-carbonitrile (4k). Yield 83%, white solid,
mp 100∼106 °C (lit.31 105-106 °C); 1H NMR (300
MHz, CDCl3) δ 8.74-8.69 (m, 2H), 8.33-8.26 (m, 2H), 7.95 (d,
1H, J ) 7.8 Hz), 7.84-7.66 (m, 4H); 13C NMR (75 MHz,
CDCl3) δ 135.8, 131.9, 130.1, 130.0, 129.9, 129.7, 129.0, 128.4,
128.3, 127.8, 126.2, 1233, 123.0, 118.2, 109.5; IR (neat) 2219,
1527, 1448, 1247 cm-1; MS (EI) m/z 204 (13), 203 (M+, 100),
176 (11); HRMS (EI) calcd for C15H9N [M+] 203.0735, found
203.0740.
6-(Trifluoromethyl)phenanthrene-9-carbonitrile (4l). Yield
1
90%, white solid, mp 148∼150 °C; H NMR (300 MHz, CDCl3)
δ 8.95 (s, 1H), 8.70 (d, 1H, J ) 8.3 Hz), 8.43-8.36 (m, 2H), 8.00-
7.86 (m, 3H), 7.77 (t, 1H, J ) 7.4 Hz); 13C NMR (75 MHz, CDCl3)
δ 137.8, 131.5, 130.8, 130.7, 130.4, 130.2, 129.9, 129.8, 128.7,
127.2, 124.3 (J ) 271.0 Hz), 124.2 (J ) 3.3 Hz), 123.1, 120.8 (J
) 2.8 Hz), 117.4, 109.1; IR (neat) 2222, 1320, 1121, 1080, 747
cm-1; MS (EI) m/z 272 (20), 271 (M+, 100), 252 (14), 221 (15),
201 (10), 175 (7), 136 (8), 110 (9); HRMS (EI) calcd for C16H8F3N
[M+] 271.0609, found 271.0618.
Methyl 10-Methylphenanthrene-9-carboxylate (8b). Yield
5-Methylphenanthrene-9-carbonitrile (4m). In addition to
reagents used in method A, SPhos (6 mol %) was added. Yield
1
71%, yellow oil; H NMR (300 MHz, CDCl3) δ 8.74-8.68 (m,
2H), 8.13 (dd, 1H, J ) 7.6, 1.2 Hz), 7.74-7.57 (m, 5H), 4.09 (s,
3H), 2.70 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 171.1, 131.2,
130.7, 130.4, 130.1, 129.6, 128.4, 127.6, 127.4, 127.3, 126.7, 125.5,
125.4, 123.2, 123.0, 52.7, 17.5; IR (neat) 2949, 1723, 1445, 1205
cm-1; MS (EI) m/z 251 (20), 250 (M+, 100), 219 (62), 189 (69),
178 (11), 165 (39), 109 (8); HRMS (EI) calcd for C17H14O2 [M+]
250.0994, found 250.1004.
1
56%, white solid, mp 120∼122 °C; H NMR (300 MHz, CDCl3)
δ 8.90 (d, 1H, J ) 8.6 Hz), 8.27-8.24 (m, 2H), 7.65 (dd, 1H, J )
7.8, 0.9 Hz), 7.78 (dt, 1H, J ) 7.6, 1.2 Hz), 7.70-7.63 (m, 3H),
3.16 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 136.3, 136.2, 133.2,
133.1, 131.2, 130.4, 130.1, 129.9, 129.0, 127.8, 127.5, 127.0, 124.9,
118.6, 110.3, 27.6; IR (neat) 2216, 1450, 1210, 783 cm-1; HRMS
(EI) calcd for C16H11N{M+] 217.0891, found 217.0896.
Ethyl 10-Methylphenanthrene-9-carboxylate (8c). Yield 52%,
8-Fluorophenanthrene-9-carbonitrile (4n). In addition to re-
agents used in method A, SPhos (6 mol %) was added. Yield 80%,
orange solid, mp 142∼144 °C; 1H NMR (300 MHz, CDCl3) δ 8.63
(d, 1H, J ) 8.4 Hz), 8.48 (d, 1H, J ) 8.4 Hz), 8.27 (s, 1H), 7.92
(d, 1H, J ) 7.9 Hz), 7.85-7.79 (m, 1H), 7.74-7.65 (m, 2H), 7.39
(ddd, 1H, J ) 12.5, 7.9, 0.9 Hz); 13C NMR (75 MHz, CDCl3) δ
158.6 (J ) 252.8 Hz), 138.6, 132,5 (J ) 2.6 Hz), 131.0 (J ) 2.7
Hz), 130.6, 129.9 (J ) 1.0 Hz), 129.7, 128.6 (J ) 8.8 Hz), 128.5,
123.4, 119.3 (J ) 4.1 Hz), 119.1, 118.6 (J ) 11.3 Hz), 113.6 (J )
20.8 Hz), 103.7 (J ) 2.4 Hz); IR (neat) 2223, 1241, 1457, 1378
cm-1; MS (EI) m/z 222 (16), 221 (M+, 100), 194 (4), 110 (10), 97
(9); HRMS (EI) calcd for C15H8FN [M+] 221.0641, found 221.0654.
2,3-Dimethoxyphenanthrene-9-carbonitrile (4o). Yield 32%,
white solid, mp 149∼151 °C; 1H NMR (300 MHz, CDCl3) δ 8.53
(dd, 1H, J ) 6.8, 0.5 Hz), 8.26 (dd, 1H, J ) 6.2, 1.0 Hz), 8.13 (s,
1H), 7.95 (s, 1H), 7.74-7.65 (m, 2H), 7.23 (s, 1H), 4.14 (s, 3H),
4.06 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 152.0, 150.2, 134.4,
129.5, 128.7, 127.8, 127.3, 126.3, 125.2, 122.8, 118.6, 108.8, 107.2,
103.2, 56.3; IR (neat) 2216, 1613, 1506, 1217 cm-1; MS (EI) m/z
264 (18), 263 (M+, 100), 220 (18), 202 (160, 190 (20), 177 (51),
150 (20); HRMS (EI) calcd for C17H13NO2 [M+] 263.0946, found
263.0944.
1
colorless oil; H NMR (300 MHz, CDCl3) δ 8.72-8.66 (m, 2H),
8.12 (dd, 1H, J ) 7.3, 1.9 Hz), 7.76-7.59 (m, 5H), 4.58 (q, 2H, J
) 7.1 Hz), 2.70 (s, 3H), 1.48 (t, 3H, J ) 7.1 Hz); 13C NMR (75
MHz, CDCl3) δ 171.0, 131.2, 130.6, 129.8, 128.4, 127.5, 127.4,
127.3, 126.7, 125.4, 125.3, 123.2, 122.9, 61.7, 17.3, 14.6; IR (neat)
1712, 1446, 1205, 1033 cm-1; MS (EI) m/z 265 (24), 264 (M+,
100), 219 (77), 191 (95), 189 (92), 161 (57); HRMS (EI) calcd for
C18H16O2 [M+] 264.1150, found 264.1147.
10-Methylphenanthrene-9-carbonitrile (8d). Yield 56%, white
solid, mp 154∼158 °C; 1H NMR (300 MHz, CDCl3) δ 8.69-8.61
(m, 2H), 8.25 (m, 1H), 8.11 (dd, 1H, J ) 8.2, 1.3 Hz), 7.81-7.61
(m, 4H), 2.99 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 142.1, 131.2,
130.0, 129.2, 129.0, 128.8, 128.0, 127.4, 127.3, 125.8, 125.7, 123.1,
122.7, 117.5, 109.2, 18.9; IR (neat) 2188, 1609, 1434,
1230 cm-1; MS (EI) m/z 217 (M+, 100), 216 (27), 189 (27), 110
(13); HRMS (EI) calcd for C16H11N [M+] 217.0891, found
217.0896.
Ethyl 10-(Bromomethyl)phenanthrene-9-carboxylate (10). To
a solution of methylphenanthrene 8c (100 mg, 0.38 mmol) in 10
mL of benzene was added NBS (81 mg, 0.45 mmol) and AIBN (6
mg, 0.04 mmol). The resulting solution was stirred at reflux
temperature for 4 h. After cooling to room temperature, the mixture
was filtered while being rinsed with Et2O. The solution was washed
with a 10% aqueous Na2S2O3 solution, H2O, and brine. The organic
solution was dried over MgSO4, filtered, and concentrated in vacuo.
The residue was purified by silica gel flash column chromatography
(10% EtOAc/hexanes) to give (bromomethyl)phenanthrene 10 (121
mg, 93% yield) as a brown solid. mp 108∼110 °C; 1H NMR (300
MHz, CDCl3) δ 8.69-8.59 (m, 2H), 8.22-8.19 (m, 1H), 7.79 (dd,
1H, J ) 7.7, 1.4 Hz), 7.69-7.55 (m, 4H), 4.93 (s, 2H), 4.61 (q,
2H, J ) 7.1 Hz), 1.15 (t, 3H, J ) 7.1 Hz); 13C NMR (75 MHz,
CDCl3) δ 169.3, 132.2, 131.3, 130.8, 128.8, 128.7, 128.1, 128.0,
127.9, 127.7, 127.6, 126.4, 125.3, 123.4, 123.1, 62.3, 27.8, 14.6;
IR (neat) 1722, 1447, 1247, 1206, 1068 cm-1; MS (EI) m/z 344
(23), 342 (M+, 21), 263 (91), 235 (100), 205 (56), 191 (88), 189
(95), 178 (37), 177 (40); HRMS (EI) calcd for C18H15BrO2 [M+]
342.0255, found 342.0268.
2-Fluorophenanthrene-9-carbonitrile (4p). Yield 73%, white
solid, mp 152∼154 °C; 1H NMR (300 MHz, CDCl3) δ 8.72-8.63
(m, 2H), 8.31 (dd, 1H, J ) 3.0 Hz), 8.19 (s, 1H), 7.83-7.73 (m,
2H), 7.60-7.52 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 161.7 (J
) 247.9 Hz), 134.6 (J ) 3.9 Hz), 131.2 (J ) 9.0 Hz), 129.9, 128.8,
128.5 (J ) 1.5 Hz), 128.4, 128.2 (J ) 0.8 Hz), 126.4, 125.5 (J )
8.7 Hz), 123.1 (J ) 0.8 Hz), 119.0 (J ) 23.6 Hz), 117.7, 113.7 (J
) 20.9 Hz), 111.0; IR (neat) 3073, 2221, 1623, 1530, 1454, 1221
cm-1; MS (EI) m/z 222 (17), 221 (M+, 100), 194 (6), 168 (5), 110
(7); HRMS (EI) calcd for C15H8FN [M+] 221.0641, found 221.0646.
Benzo[h]quinoline-6-carbonitrile (4q). Yield 63%, white solid,
1
mp 150∼152 °C; H NMR (300 MHz, CDCl3) δ 9.36-9.32 (m,
1H), 9.11 (dd, 1H, J ) 4.4, 1.7 Hz), 8.31-8.21 (m, 3H), 7.89-
(31) Gore, P. H.; Kamounah, F. S.; Miri, A. Y. Tetrahedron 1979, 35,
2927-2929.
500 J. Org. Chem., Vol. 73, No. 2, 2008

Direct One-Pot Synthesis of Phenanthrenes
Phenanthrene-10-aminomethyl-9-carboxamide Lactam (11).
To a solution of 10 (100 mg, 0.29 mmol) in 8 mL of CH2Cl2 was
added methylamine 0.13 mL (1.46 mmol, 40 wt % in water). The
solution was stirred at room temperature for 2 h. The mix-
ture was quenched with H2O (10 mL) and extracted with CH2Cl2
(3 × 10 mL). The combined organic phases were washed with
brine solution, dried over MgSO4, and concentrated in vacuo. The
residue was purified by silica gel flash column chromato-
graphy (50% EtOAc/hexanes) to provide phenanthrene lactam 11
(62 mg, 86%) as a white solid. mp 142∼146 °C (lit.5a 142-144
1392, 1252 cm-1; MS (EI) m/z 248 (15), 247 (M+, 87), 218 (100),
189 (17), 176 (24), 108 (14); HRMS (EI) calcd for C17H18NO [M+]
247.0997, found 247.0996.
Acknowledgment. We are grateful to the Korea Research
Institute of Chemical Technology for financial support of this
work. Y.J.K. thanks the Ministry of Commerce, Industry and
Energy for financial support.
1
°C); H NMR (300 MHz, CDCl3) δ 9.28 (dd, 2H, J ) 7.0, 2.5
Supporting Information Available: Experimental procedures
and spectroscopic data for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
Hz), 8.57-8.52 (m, 2H), 7.84 (d, 1H, J ) 7.8 Hz), 7.77-7.62 (m,
4H), 4.66 (s, 2H), 3.31 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
170.0, 140.8, 131.6, 130.3, 128.3, 127.6, 127.5, 127.1, 127.0, 126.4,
125.3, 124.6, 123.6, 123.5, 122.7, 50.7, 29.5; IR (neat) 1667, 1448,
JO702001N
J. Org. Chem, Vol. 73, No. 2, 2008 501