An efficient one-pot approach to phenanthrene derivatives using a catalyzed tandem Ullmann-pinacol coupling reaction

Article abstract of DOI:10.1016/j.tet.2008.08.004

In the presence of catalyst (Ph₃P)₂NiCl₂ and reductant Zn, the Ullmann reactions of ortho-halo aryl aldehydes generate biaryl-dialdehydes and zinc halides. Subsequently, ZnX₂ can catalyze the intramolecular pinacol coupling reaction of biaryl-dialdehydes to form 9,10-dihydrophenanthrene-9,10-diols. One-pot synthesis of 9-phenanthrols can be achieved using this strategy.

Full text of DOI:10.1016/j.tet.2008.08.004

Tetrahedron 64 (2008) 9906–9910
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient one-pot approach to phenanthrene derivatives using a catalyzed
tandem Ullmann-pinacol coupling reaction
Shuang-zheng Lin, Tian-pa You *
Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 April 2008
Received in revised form 24 July 2008
Accepted 5 August 2008
Available online 8 August 2008
In the presence of catalyst (Ph P) NiCl and reductant Zn, the Ullmann reactions of ortho-halo aryl al-
3
2
2
dehydes generate biaryl-dialdehydes and zinc halides. Subsequently, ZnX
2
can catalyze the intra-
molecular pinacol coupling reaction of biaryl-dialdehydes to form 9,10-dihydrophenanthrene-9,10-diols.
One-pot synthesis of 9-phenanthrols can be achieved using this strategy.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Tandem catalysis
Ullmann-pinacol reaction
9
9
,10-Dihydrophenanthrene-9,10-diols
-Phenanthrols
1. Introduction
powder as a reductant, but this tandem sequence failed when the
18a
benzaldehydes bearing electron-donating substituents.
It is
The phenanthrenes constitute a significant class of organic
meaningful to overcome this shortcoming, because most of the
natural phenanthrenes are electron-rich. In this paper, we present
our continuous research on this tandem Ullmann-pinacol coupling
and its applications to the reactions of electron-rich benzaldehydes.
We also constructed 9-phenanthrols using this one-pot method.
1
compounds abundantly distributed in nature. They are useful in-
2
termediates for natural product synthesis and exhibit a broad
3
4
spectrum of biological activities such as antimalarial, anticancer,
5
1f,6
7
anti-HIV, antimicrobial, and emetic activity. These compounds
also serve as a common structural motif in materials science based
on their photochemical, photoconducting, optoelectrical, and
2. Results and discussion
8
electroluminescent properties. For the last several decades, nu-
merous methods have been developed for the construction of
Numerous Lewis acids, served as catalyst in many chemical
2
phenanthrene derivatives, such as the photochemical cyclizations
transformations, are metal salts. However, these salts generated in
reactions are usually discarded as wastes and in fact they can be
reused into a lot of synthetic reactions. Can the salt engendered in
the reaction in situ catalyze a subsequent reaction? To the best of
our knowledge, there is no example on this strategy although other
types of ‘one-pot’ reactions have been reported extensively in the
of stilbenes,9 the radical cyclizations, the Pd-catalyzed cocycli-
10
11
zations of arynes with alkenes or alkynes, the metal-catalyzed
0
12
cycloaddition of 2,2 -dihalobiphenyl with alkynes, and the car-
13
bocyclization of alkynylated biaryl derivatives, a o-metalation
followed by a catalyzed cyclization, the McMurry coupling,14 the
1
d
ring-closing metathesis,1 and the base-mediated condensations.
5
16
19
literature. We noted that the metal halides produced from the
Besides these, facile one-pot approaches have been realized via
2
0
Ullmann reactions of aryl halides are promoters for the pinacol
17
a Suzuki–Miyaura coupling/aldol condensation cascade reaction,
or the tandem Ullmann-pinacol couplings developed by our group
21
couplings (Scheme 1), which we have focused on for a long
2
2
time.
18
and Scherf’s group independently. In the preliminary letter, we
have reported that o-carbonyl aryl halides can be coupled to form
trans-9,10-dihydrophenanthrene-9,10-diols (phenanthrenediols)
Envisioning a tandem Ullmann-pinacol could be achieved, the
homocoupling experiment of o-bromobenzaldehyde (1a) was
firstly investigated under the classical Ullmann reaction condi-
3 2 2
by a one-pot method, using (Ph P) NiCl as a catalyst and zinc
2
3
tions with some modifications (Table 1).
3 2 2
As expected, the reaction of 1a catalyzed by (Ph P) NiCl led to
phenanthrenediol 3a in good yield (Table 1, entry 1). The influences
of the amount of zinc power and reaction temperature were then
investigated. As shown above, more reductant and higher reaction
*
Corresponding author. Tel.: þ086 551 3606944.
E-mail address: lins@mail.ustc.edu.cn (S.-zheng Lin).
0
040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.08.004

S.-zheng Lin, T.-pa You / Tetrahedron 64 (2008) 9906–9910
9907
X
Table 2
Scope of the (Ph
Cat.
M
+
MXn
3
P)
2
NiCl
2
-catalyzed tandem Ullmann-pinacol couplinga
R1
N
R2 Ar
Ar
OH
Ar
R2 Ar
OH
OH
OH
OH
MXn
O
(Ph3P)2NiCl2
ArCHO
M
R1
Zn
DMF
HO
X
R2 Ar R1
1
N
n
Scheme 1. MX produced from Ullmann reaction is a promoter for pinacol coupling.
3
3i
CHO
Br
Substrates:
CHO
Br
temperature were not beneficial, but less zinc powder and lower
temperature seriously retarded the reaction (Table 1, entries 2–5).
The stoichiometry of triphenylphosphine was also investigated. The
results suggested that this ligand had few influence on this tandem
reaction although the reaction time should be prolonged to 7 h if no
additional ligand was added (Table 1, entry 6). Finally, the reaction
catalyzed by palladium complex was examined, but the yield of 3a
was inferior to that done by zinc salt (Table 1, entry 7).
CHO
Cl
CHO
Cl
1a
1a'
1b
1c
F
CHO
CHO
Cl
Me
CHO
Cl
Me
Br
F
Table 1
a
1d
1e
1f
Coupling reactions of o-bromobenzaldehyde
O
CHO
Br
COMe
Cl
1h
CHO
Cl
Cat.
CHO
Br
OH
OH
(
0.05 equiv)
CHO
CHO
O
N
+
Ph P
3
Zn
DMF
1g
1i
1a
2
3a
ꢀ
Yieldb (%)
Entry
Substrate
Time (h)
Temp ( C)
Product
ꢀ
b
Entry PPh
3
(equiv) Zn (equiv) Temp ( C) Time (h) Yield of 2 (%) Yield of 3ab (%)
1
2
3
4
5
6
7
8
9
1a
1a
7
10
12
9
12
12
12
15
24
12
60
60
60
60
60
70
70
70
60
60
3a
3a
3b
3c
3d
3e
3f
3g
3h
3i
81
76
71
63
73
79
70
77
19
45
0
dc
dc
1
2
3
4
5
6
7
0.28
3
3
3
2
4
3
3
60
70
50
60
60
60
60
5
5
10
10
5
81
81
34
62
84
81
59
1b
1c
1d
1e
1f
1g
1h
1i
0.28
0.28
0.28
0.28
d
38
25
c
d
c
c
c
7
7
d
d
c
d
d
d
a
Reaction conditions: (Ph
P)
3 2
NiCl
2
(0.05 equiv), PPh
3
,
Zn and o-bromo-
10
benzaldehyde were stirred in dry DMF (0.15 ml) under N
2
atmosphere.
a
b
3 2 2
Reaction conditions: (Ph P) NiCl (0.05 equiv), Zn (3 equiv), and aldehyde
Isolated yield.
Not obtained.
c
(0.3 mmol) were stirred in dry DMF (0.15 ml) under N
2
atmosphere.
b
d
Isolated yield.
3 4 3 2 2
Pd(PPh ) was used instead of (Ph P) NiCl , benzaldehyde was isolated with 38%
c
(
Ph
3
P)
2
NiCl
2
(0.1 equiv) was used.
yield.
d
0
0
The main product was 1,1 -(biphenyl-2,2 -diyl)diethanone (54% yield).
To support our hypothesis of the reaction mechanism, the
reaction of biphenyl-2,2 -dialdehyde (2) was conducted under the
0
ꢀ
reaction temperature should be raised to 70 C if there were elec-
similar conditions to 2-bromobenzaldehyde. But dialdehyde 2 was
recovered completely and no diol product was obtained. On the
tron-donating groups on the phenyl group (Table 2, entries 6–8).
The necessity of raising the reaction temperature might result from
the low reactivities of the electron-rich benzaldehydes in the
pinacol couplings. For example, if the reaction of 1g was conducted
other hand, the dialdehyde
2 was smoothly converted to
phenanthrenediol 3a catalyzed by ZnCl
2
(Scheme 2).
ꢀ
at 60 C, no diol 3g was obtained even the reaction time was pro-
longed to 24 h; the main product was the dialdehyde intermediate.
When the reaction temperature was raised to 70 C, the reactivity
O
O
ꢀ
ZnCl2 (>0.4 equiv)
Zn (2.5 equiv)
HO
OH
of this dialdehyde intermediate was greatly increased, which led to
diol product 3g with a good yield. For ketone 1h, the yield of diol 3h
was low (Table 2. entry 9), presumably because of the lower re-
activity of ketone and the increased steric hindrance of the methyl
groups that was an obstacle to the subsequent pinacol reaction.
When heterocyclic 1i was examined, a consecutive Ullmann re-
action/reduction occurred instead of an Ullmann-pinacol coupling
(Table 2, entry 10).
DMF, 60 °C, 4h
81%
2
3a
Scheme 2.
We then investigated the reactions of many ortho-carbonyl-
substituted aryl halides (Table 2).
Comparable yield of phenanthrenediol was obtained when the
bromide 1a was replaced with the less reactive chloride 1a though
Interestingly, all the phenanthrenediols were obtained stereo-
selectively. A trans-structure of 3a was further determined by its
monoacetate (Scheme 3).
0
the reaction time was longer (Table 2. entries 1 and 2). In the case of
naphthalene derivatives 1b and 1c, the cascade reaction also pro-
ceeded smoothly (Table 2. entries 3 and 4). Other substituted
o-halobenzaldehyes were also investigated. For electron-poor 1d,
the reaction was carried out smoothly (Table 2, entry 5). The
The coupling constant of the two benzylic hydrogens in the
central ring is 8.1 Hz for our product 4, trans-10-hydroxy-9,10-
dihydrophenanthren-9-yl acetate, and 3.8 Hz for its cis-
2
4
counterpart.

9908
S.-zheng Lin, T.-pa You / Tetrahedron 64 (2008) 9906–9910
As an application, the one-pot approach to 9-phenanthrols can
9
0
be easily achieved using this tandem reaction followed by de-
hydration under acidic conditions (Table 3).
Ac O
2
EtOAc
rt, 20h
OAc
OH
2
OAc
OAc
Na CO
3
3a
+
9-Phenanthrols are key intermediates in the synthesis of some
1
1d
25
natural products, such as gymnopusin and steganone. But te-
2
6
dious steps are usually required to prepare these compounds.
Apparently, phenanthrenediols can be dehydrated to furnish
-phenanthrols under acidic conditions. We added hydrochloric
17%
J
= 8.1Hz
-H,10-H
9
4
79%
9
acid to the mixtures when the conversions to diols were completed.
After preliminary investigation, we found that 6 M HCl was suit-
able, because less concentrated hydrochloric acid leads to in-
complete reaction and higher concentration of acid makes the
reaction too drastic. In this way, 9-phenanthrols were easily syn-
thesized from the o-halobenzaldehydes in one-pot.
Scheme 3. Monoacetate phenanthrenediol 3a.
H
C
H
O
Zn2+
O
C
H
HO
OH
H
3. Conclusion
5
3a
3 2 2
In summary, we have developed a tandem (Ph P) NiCl -cata-
lyzed Ullmann reaction/ZnX -mediated pinacol coupling. This is
2
an unprecedented tandem catalysis, in which the catalyst of the
sequential step is a salt produced in situ in the previous step.
Phenanthrenediols and 9-phenanthrols can be conveniently con-
structed by this one-pot method using this cascade coupling. These
facile approaches to phenanthrenes would be expected to provide
important references to synthetic chemistry, pharmaceutical, and
materials science.
H
H
6'
6
2
+
Zn
O
O
C
2'
2
C
HO
OH
H
H
6
3a'
Scheme 4. Possible reaction mechanism about the trans-selectivity.
4
4
. Experimental section
.1. General
A possible reaction mechanism of this trans-selectivity is illus-
trated in Scheme 4.
We assumed that both the carbonyls should coordinate to Zn2þ
All reactions were conducted in oven-dried glassware. NMR
spectra were measured on a Bruker 300 MHz spectrometer.
Chemical shifts were reported in parts per million relative to in-
ternal tetramethylsilane. High resolution mass spectroscopy
(HRMS) was performed on a Micromass GCT mass spectrometer.
Column chromatography was carried out on silica gel (200–400
to form an intermediate like 5 or 6 in the reaction. This coordination
would bring the two carbonyls together and lead to a subsequent
intramolecular coupling. However, in the reaction of heterocyclic
2
þ
1
i, the co-coordination of Zn with both carbonyls might be dis-
turbed by the nitrogen atoms on the heterocycles, and no pinacol
product was obtained. Among two transition states, 5 would be
more favorable. Because the two phenyls would have to be nearly
coplanar to form the alternative intermediate 6, in which severe
ꢀ
mesh) using petroleum ether (60–90 C) and EtOAc as eluents.
27
28
Compounds 1b and 1c were prepared according to the pro-
cedures described in the literature. All solvents were purified be-
fore use. Other reagents were purchased from vendors and used
0
steric hindrance between the hydrogens at the 6- and 6 -position
without further purification.
purification.
2
N was used without further
would be present. Therefore a diastereoselective reaction to 3a was
achieved.
Table 3
a
One-pot syntheses of 9-phenanthrols
4.2. Synthesis of phenanthrenediols (3a–i): general
procedures
1
2
) (Ph P) NiCl
R
R
Ar
Ar
3
2
2
OH
R
Ar
X
O
Zn (3 equiv)
) 6 M HCl
(Ph
3
P)
2
NiCl
2
(10 mg, 0.015 mmol), zinc powder (59 mg,
0
.90 mmol), and the aldehyde (0.3 mmol) were stirred in DMF
H
ꢀ
ꢀ
(
0.15 ml) at 60 C or 70 C under N
dicated in Table 2. The reaction was quenched with ice bath; the
mixture was diluted with 2 ml 1 M HCl and 5 ml CH Cl . The
2
atmosphere for the time in-
1
7
2
2
Entry
Substrate
Product
Yieldb (%)
mixture was stirred for several minutes, and then filtered to remove
the unreacted zinc powder. The phases were separated and the
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
7a
7b
7c
7d
7e
7f
56
63
c
aqueous phase was extracted twice with CH
2 2
Cl . The combined
d
organic extracts were dried over MgSO and concentrated. Purifi-
4
70
90
50
32
cation of the residue by column chromatography gave the products.
1g
7g
29
4
.2.1. 9,10-Dihydrophenanthrene-9,10-diol (3a)
a
1
Reaction conditions: after the reactions of Ullmann-pinacol couplings were
completed (Table 2, footnote a), the mixtures were cooled with ice bath following
addition of 1.2 ml of 6 M HCl, then the reactions were heated at 100 C for 2 h under
Yield: 81%. H NMR (300 MHz, CDCl
):
d
7.76 (dd, J¼6.2, 2.8 Hz,
3
2
H), 7.67 (dd, J¼9.4, 3.1 Hz, 2H), 7.42–7.36 (m, 4H), 4.76 (s, 2H), 1.65
ꢀ
13
(br, 2H). C NMR (75 MHz, CDCl
3
):
d
136.2, 132.6, 128.6, 128.5,
N
2
atmosphere.
þ
b
125.3, 123.9, 74.2. HRMS calcd for C14
212.0838.
H
O
(M ) 212.0837, found
Isolated yield.
12
2
c
Pure product was not obtained.

S.-zheng Lin, T.-pa You / Tetrahedron 64 (2008) 9906–9910
9909
4
.2.2. 13,14-Dihydropicene-13,14-diol (3b)
Yield: 71%. H NMR (300 MHz, acetone-d
were separated. The aqueous phase was extracted with EtOAc. The
combined organic extracts were dried and concentrated. Purifica-
1
6
):
d
8.41 (d, J¼8.4 Hz,
2
2
H), 8.21 (d, J¼8.7 Hz, 2H), 8.02 (d, J¼8.7 Hz, 2H), 7.95 (d, J¼7.8 Hz,
tion of the residue by flash chromatography gave 4 (10 mg,
1
3
1
H), 7.64–7.51 (m, 4H), 5.69 (s, 2H), 3.13 (s, 2H). C NMR (75 MHz,
0.04 mmol, 79% yield) as white solid. H NMR (300 MHz, CDCl
3
):
acetone-d
6
):
d
134.3, 133.9, 132.1, 131.5, 129.8, 129.2, 127.5, 126.6,
d
7.75 (m, 2H), 7.55 (d, J¼7.2 Hz, 1H), 7.41–7.22 (m, 5H), 6.02 (d,
þ
13
124.8, 123.5, 67.9. HRMS calcd for C22
H
16
O
2
(M ) 312.1150, found
J¼8.1 Hz, 1H), 4.82 (d, J¼8.1 Hz, 1H), 2.48 (s, 1H), 2.11 (s, 3H).
C
312.1148.
3
NMR (75 MHz, CDCl ): d 171.3,135.5,133.1,132.3,132.0,129.2,128.9,
1
28.5, 128.1, 127.6, 127.1, 123.9, 123.8, 74.5, 71.1, 21.1. HRMS calcd for
þ
4
.2.3. 3,4-Dihydro-dibenzo[c,g]phenanthrene-3,4-diol30 (3c)
16 14 3
C H O
(M ) 254.0943, found 254.0949.
1
Yield: 63%. H NMR (300 MHz, CDCl
3
):
d
8.00 (d, J¼8.4 Hz, 2H),
7
.95–7.91 (m, 4H), 7.56 (d, J¼8.4 Hz, 2H), 7.46 (t, J¼7.5 Hz, 2H), 7.27
4.4. Synthesis of 9-phenanthrols (7a–g): general procedure
13
(
t, J¼6.6 Hz, 2H), 4.73 (s, 2H), 2.61 (br, 2H). C NMR (75 MHz,
CDCl
3
):
d
136.2, 133.8, 130.2, 129.1, 129.1, 128.5, 127.6, 125.6, 125.4,
(Ph
3
P)
2
NiCl
2
(10 mg, 0.015 mmol), zinc powder (59 mg,
þ
121.4, 75.0. HRMS calcd for C22
H
16
O
2
(M ) 312.1150, found 312.1157.
0.90 mmol), and the aldehyde (0.3 mmol) were stirred in DMF
ꢀ ꢀ
2
0.15 ml) at 60 C or 70 C under N atmosphere for the time in-
(
4
.2.4. 3,6-Difluoro-9,10-dihydrophenanthrene-9,10-diol (3d)
dicated in Table 2. The mixture was quenched by an ice bath, 1.2 ml
6 M HCl was added. The reaction was then continued at 100 C
1
ꢀ
Yield: 73%. H NMR (300 MHz, acetone-d
.0 Hz, 2H), 7.60 (dd, J¼10.3, 2.5 Hz, 2H), 7.13 (td, J¼8.6, 2.5 Hz, 2H),
6
):
d
7.71 (dd, J¼8.4,
6
4
for 2 h under N
9-phenanthrols.
2
atmosphere. Conventional work-up led to the
13
.60 (s, 2H), 3.12 (s, 2H). C NMR (75 MHz, acetone-d ): 163.7 (d,
6
d
J¼241.0 Hz), 135.1 (d, J¼2.9 Hz), 134.7 (dd, J¼8.0, 2.3 Hz), 129.0 (d,
3
1
J¼8.4 Hz), 115.6 (d, J¼21.5 Hz), 111.2 (d, J¼23.1 Hz), 73.4. HRMS
4.4.1. Phenanthren-9-ol (7a)
þ
1
calcd for C14H
10
O
F
2 2
(M ) 248.0649, found 248.0654.
Yield: 56%. H NMR (300 MHz, CDCl
3
):
d
8.68 (d, J¼7.8 Hz, 1H),
8
.61 (dd, J¼7.8, 1.8 Hz, 1H), 8.32 (d, J¼8.4 Hz, 1H), 7.73–7.63 (m, 3H),
13
4
9
.2.5. 1,8-Difluoro-2,7-dimethyl-9,10-dihydrophenanthrene-
,10-diol (3e)
7.56–7.48 (m, 2H), 7.03 (s, 1H), 5.28 (br, 1H). C NMR (75 MHz,
CDCl
3
):
d
149.9, 132.8, 130.3, 128.8, 128.7, 127.2, 127.0, 126.9, 126.4,
1
þ
Yield: 79%. H NMR (300 MHz, acetone-d
H), 7.24 (t, J¼7.8 Hz, 2H), 5.04 (s, 2H), 3.04 (s, 2H), 2.27 (s, 6H).
):
6
):
d
7.51 (d, J¼8.1 Hz,
124.2, 122.8, 122.7, 122.6, 106.2. HRMS calcd for C14
194.0732, found 194.0728.
H10O (M )
1
3
2
C
NMR (75 MHz, acetone-d
6
d
160.9 (d, J¼244.2 Hz), 133.6, 131.8 (d,
J¼5.6 Hz), 125.7 (d, J¼18.6 Hz), 123.3 (d, J¼13.7 Hz), 120.2 (d,
4.4.2. Picen-13-ol (7b)
þ
1
J¼2.9 Hz), 67.4, 14.6 (d, J¼4.2 Hz). HRMS calcd for C16
H
14
O
2
F
2
(M )
Yield: 63%. H NMR (300 MHz, acetone-d
6
):
d
10.07 (d, J¼8.4 Hz,
2
76.0962, found 276.0966.
1H), 8.90 (d, J¼9.0 Hz, 1H), 8.80–8.75 (m, 2H), 8.54 (s, 1H), 8.10–7.99
13
(
m, 3H), 7.88 (d, J¼9.0 Hz, 1H), 7.73–7.62 (m, 4H). C NMR (75 MHz,
4.2.6. 3,6-Dimethyl-9,10-dihydrophenanthrene-9,10-diol (3f)
acetone-d ): 156.3, 154.6, 133.5, 133.3, 132.2, 131.7, 130.7, 130.1,
6
d
1
Yield: 63%. H NMR (300 MHz, acetone-d
6
):
d
7.62 (s, 2H), 7.56
130.0, 129.4, 129.2, 128.9, 127.5, 127.2, 126.9, 125.2, 124.0, 123.7,
122.7, 122.6, 121.2, 106.3. HRMS calcd for C22
found 294.1048.
þ
(
(
d, J¼7.8 Hz, 2H), 7.14 (d, J¼7.2 Hz, 2H), 4.55 (s, 2H), 3.03 (s, 2H), 2.37
H
14O (M ) 294.1045,
s, 6H). 13C NMR (75 MHz, acetone-d
):
d
137.9, 136.0, 133.4, 129.2,
6
þ
126.5, 124.7, 74.1, 21.3. HRMS calcd for C16
H
16
O
2
(M ) 240.1150,
found 240.1152.
4.4.3. 3,6-Difluorophenanthren-9-ol (7d)
1
Yield: 70%. H NMR (300 MHz, acetone-d
6
):
d
8.44–8.36 (m, 2H),
4
.2.7. 11,12-Dihydro-1,3,8,10-tetraoxa-dicyclopenta-
8.30 (dd, J¼11.1, 2.1 Hz, 1H), 7.79–7.72 (m, 1H), 7.48 (td, J¼8.6,
13
[a,i]phenanthrene-11,12-diol (3g)
2.2 Hz, 1H), 7.35 (td, J¼8.6, 2.4 Hz, 1H), 7.15 (s, 1H), 3.41 (br, 1H).
NMR (75 MHz, acetone-d ):
C
1
Yield: 77%. H NMR (300 MHz, acetone-d
6
):
d
7.30 (d, J¼8.4 Hz,
6
d
162.1 (d, J¼242.8 Hz), 159.9 (d,
13
2
H), 6.82 (d, J¼8.1 Hz, 2H), 6.03 (s, 4H), 4.99 (s, 2H), 3.04 (s, 2H).
C
J¼238.7 Hz), 150.6, 132.8 (d, J¼8.2 Hz), 130.9, 128.8 (d, J¼8.2 Hz),
126.6, 125.7 (d, J¼8.9 Hz), 123.7, 117.1 (d, J¼22.4 Hz), 116.3 (d,
NMR (75 MHz, acetone-d
6
):
d
148.1, 147.6, 128.5, 118.4, 117.6, 108.7,
þ
102.3, 65.4. HRMS calcd for C16
H
12
O
6
(M ) 300.0634, found
J¼23.7 Hz), 115.5 (d, J¼23.7 Hz), 111.6 (d, J¼25.1 Hz), 108.1 (dd,
þ
3
00.0640.
J¼22.4, 9.1 Hz), 104.2. HRMS calcd for C14
H
8
OF
2
(M ) 230.0543,
found 230.0545.
4
.2.8. 9,10-Dimethyl-9,10-dihydrophenanthrene-9,10-diol (3h)
1
Yield: 19%. H NMR (300 MHz, acetone-d
6
):
d
7.78–7.72 (m, 4H),
4.4.4. 1,8-Difluoro-2,7-dimethylphenanthren-9-ol (7e)
1
3
1
7.34–7.29 (m, 4H), 3.04 (s, 2H), 1.24 (s, 6H). C NMR (75 MHz, ac-
Yield: 90%. H NMR (300 MHz, CDCl
3
):
d
8.17 (d, J¼8.4 Hz, 1H),
etone-d
calcd for C16
6
):
d
144.8, 132.7, 128.8, 128.0, 125.1, 124.0, 77.3, 25.0. HRMS
8.01 (d, J¼8.4 Hz, 1H), 7.35–7.30 (m, 2H), 7.22–7.11 (m, 1H), 7.01 (s,
þ
13
H
16
O
2
(M ) 240.1150, found 240.1153.
1H), 2.40 (s, 3H), 2.39 (s, 3H). C NMR (75 MHz, CDCl ): 157.7 (d,
3
d
J¼237.5 Hz), 156.0 (d, J¼245.2 Hz), 149.2, 133.9 (d, J¼19.4 Hz), 132.0,
129.9 (d, J¼6.8 Hz), 128.6 (d, J¼6.8 Hz), 126.9 (d, J¼5.0 Hz), 122.7 (d,
J¼16.4 Hz), 121.4 (dd, J¼33.2, 17.8 Hz), 119.4 (d, J¼3.2 Hz), 117.8 (d,
0
0
4
.2.9. 3,3 -Bipyridine-4,4 -diyldimethanol (3i)
1
Yield: 45%. H NMR (300 MHz, CDCl
3
):
d
8.48 (s, 4H), 7.55 (d,
):
1
3
J¼4.5 Hz, 2H), 4.81 (s, 4H), 2.96 (br, 2H). C NMR (75 MHz, CDCl
3
J¼3.7 Hz), 114.0 (d, J¼6.3 Hz), 101.4 (d, J¼6.2 Hz), 14.5 (d, J¼3.3 Hz),
þ
d
148.7, 148.1, 147.8, 129.8, 122.1, 61.3. HRMS calcd for C12
H
12
N
2
O
2
14.3 (d, J¼6.2 Hz). HRMS calcd for C16
H12OF
2
(M ) 258.0856, found
þ
(
M ) 216.0899, found 216.0897.
258.0862.
4
9
.3. Synthesis of trans-10-hydroxy-9,10-dihydrophenanthren-
-yl acetate (4)
4.4.5. 3,6-Dimethylphenanthren-9-ol (7f)
1
Yield: 50%. H NMR (300 MHz, CDCl
.16 (d, J¼8.4 Hz, 1H), 7.53 (d, J¼8.1 Hz, 1H), 7.43 (d, J¼8.1 Hz, 1H),
7.32 (d, J¼7.8 Hz, 1H), 6.86 (s, 1H), 5.44 (s, 1H), 2.60 (s, 3H), 2.56 (s,
3
): d 8.42 (s, 1H), 8.35 (s, 1H),
8
2 3
To a suspension of 3a (11 mg, 0.05 mmol) and Na CO (16 mg,
13
0
.15 mmol) in EtOAc (0.5 ml), Ac O (14 l, 0.15 mmol) was added at
2
m
3
3H). C NMR (75 MHz, CDCl ): d 149.1, 136.8, 133.6, 131.5, 130.9,
room temperature. After the reaction was completed (monitored by
TLC), the mixture was poured into 2 ml of cold H O and the phases
129.8, 129.8, 128.6, 128.1, 126.7, 123.8, 122.6, 122.5, 122.3, 22.2, 22.0.
þ
2
HRMS calcd for C16
H14O (M ) 222.1045, found 222.1046.

9910
S.-zheng Lin, T.-pa You / Tetrahedron 64 (2008) 9906–9910
4
.4.6. 1,3,8,10-Tetraoxa-dicyclopenta[a,i]phenanthren-11-ol (7g)
7280–7286; (c) Pe n˜ a, D.; P e´ rez, D.; Guiti a´ n, E.; Castedo, L. J. Org. Chem. 2000, 65,
6944–6950.
2. (a) Kanno, K.-i.; Liu, Y.-H.; Lesato, A.; Nakajima, K.; Takahashi, T. Org. Lett. 2005,
, 5453–5456; (b) Catellani, M.; Motti, E.; Baratta, S. Org. Lett. 2001, 3, 3611–
3614; (c) Mandal, A. B.; Lee, G.-H.; Liu, Y.-H.; Peng, S.-M.; Leung, M.-K. J. Org.
Chem. 2000, 65, 332–336.
1
Yield: 32%. H NMR (300 MHz, CDCl
3
):
d
8.08 (d, J¼9.0 Hz, 1H),
1
7
.94 (d, J¼8.7 Hz, 1H), 7.21 (d, J¼8.7 Hz, 1H), 7.05–6.98 (m, 2H), 6.20
7
13
(
s, 2H), 6.13 (s, 2H), 6.00 (br, 1H). C NMR (75 MHz, CDCl ): 149.0,
3
d
1
1
44.8, 144.4, 142.0, 141.2, 128.2, 122.2, 118.3, 117.5, 116.5, 116.2, 110.2,
1
3. (a) Shen, H.-C.; Tang, J.-M.; Chang, H.-K.; Yang, C.-W.; Liu, R.-S. J. Org. Chem.
005, 70, 10113–10116; (b) Mamane, V.; Hannen, P.; F u¨ rstner, A. Chem.dEur. J.
2004, 10, 4556–4575; (c) F u¨ rstner, A.; Mamane, V. J. Org. Chem. 2002, 67, 6264–
267.
4. (a) Some, S.; Dutta, B.; Ray, J. K. Tetrahedron Lett. 2006, 47, 1221–1224; (b) Gies,
A.-E.; Pfeffer, M. J. Org. Chem. 1999, 64, 3650–3654.
þ
10 5
07.0, 102.1, 101.7, 99.7. HRMS calcd for C16H O (M ) 282.0528,
2
found 282.0528.
6
1
References and notes
1
5. Luliano, A.; Piccioli, P.; Fabbri, D. Org. Lett. 2004, 6, 3711–3714.
16. (a) Wang, Y.; Xu, J.-J.; Burton, D. J. J. Org. Chem. 2006, 71, 7780–7784; (b)
Monsieurs, K.; Rombouts, G.; Tapolcs a´ nyi, P.; M a´ tyus, P.; Maes, B. U. W. Synlett
2006, 3225–3230; (c) Kraus, G. A.; Hoover, K.; Zhang, N. Tetrahedron Lett. 2002,
43, 5319–5321.
1
. (a) Kov a´ cs, A.; Vasas, A.; Hohmann, J. Phytochemistry 2008, 69, 1084–1110; (b)
Jones, S. B.; He, L.-W.; Castle, S. L. Org. Lett. 2006, 8, 3757–3760; (c) Kumar, V.;
Poonam; Prasad, A. K.; Parmar, V. S. Nat. Prod. Rep. 2003, 20, 565–583; (d)
Wang, X.; Snieckus, V. Tetrahedron Lett. 1991, 32, 4879–4882; (e) Guinaudeau,
H.; Leboeuf, M.; Cav e´ , F. J. Nat. Prod. 1988, 51, 389–474; (f) Boger, D. L.; Mullican,
M. D. J. Org. Chem. 1984, 49, 4045–4050.
17. Kim, Y. H.; Lee, H.; Kim, Y. J.; Kim, B. T.; Heo, J.-N. J. Org. Chem. 2008, 73,
495–501.
2
3
. Floyd, A. J.; Dyke, S. F.; Ward, S. E. Chem. Rev. 1976, 76, 509–562.
. (a) Dey, A. S.; Neumeyer, J. L. J. Med. Chem. 1974, 17, 1095–1110; (b) Huffmann, C.
W.; Traxler, J. T.; Krbechek, L. O.; Riter, R. R.; Wagner, R. G. J. Med. Chem. 1971, 14,
18. (a) Lin, S.-Z.; Chen, Q.-A.; You, T.-P. Synlett 2007, 2101–2105; (b) Reisch, H. A.;
Enkelmann, V.; Scherf, U. J. Org. Chem. 1999, 64, 655–658.
19. (a) Enders, D.; Grondal, C.; H u¨ ttl, M. R. M. Angew. Chem., Int. Ed. 2007, 46, 1570–
1581; (b) Wasilke, J.-C.; Obrey, S.-J.; Baker, R. T.; Bazan, G. C. Chem. Rev. 2005,
105, 1001–1020; (c) Bruggink, A.; Schoevaart, R.; Kieboom, T. Org. Process Res.
Dev. 2003, 7, 622–640.
20. (a) Bringmann, G.; Mortimer, A. J. P.; Keller, P. A.; Gresser, M. J.; Garner, J.;
Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384–5427; (b) Hassan, J.; S e´ v-
ignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102, 1359–1469.
21. (a) Chatterjee, A.; Joshi, N. N. Tetrahedron 2006, 62, 12137–12158; (b) Tanaka, K.;
Kishigami, S.; Toda, F. J. Org. Chem. 1990, 55, 2981–2983.
90–94.
4
5
6
. (a) Wei, L.-Y.; Shi, Q.; Bastow, K. F.; Brossi, A.; Morris-Natschke, S. L.; Nakagawa-
Goto, K.; Wu, T.-S.; Pan, S.-L.; Teng, C.-M.; Lee, K.-H. J. Med. Chem. 2007, 50,
3674–3680; (b) Wilson, S.; Ruenitz, P. C. J. Pharm. Sci. 1993, 82, 571–574.
. (a) Hoshino, H.; Seki, J.-I.; Takeuchi, T. J. Antibiot. 1989, 42, 344–346; (b) Tanabe,
A.; Nakashima, H.; Yoshida, O.; Yamamoto, N.; Tenmyo, O.; Oki, T. J. Antibiot.
1988, 41, 1708–1710.
. Hattori, T.; Shimazumi, Y.; Goto, H.; Yamabe, O.; Morohashi, N.; Kawai, W.;
Miyano, S. J. Org. Chem. 2003, 68, 2099–2108.
22. (a) Wen, J.-W.; Zhao, J.; You, T.-P. J. Mol. Catal. A: Chem. 2006, 245, 278–280; (b)
Li, Y.-G.; Tian, Q.-S.; Zhao, J.; Feng, Y.; Li, M.-J.; You, T.-P. Tetrahedron: Asymmetry
2004, 15, 1707–1710.
23. Colon, I.; Kelsey, D. R. J. Org. Chem. 1986, 51, 2627–2637.
24. Jerina, D. M.; Selander, H.; Yagi, H.; Wells, M. C.; Davey, J. F.; Mahadevan, V.;
Gilbson, D. T. J. Am. Chem. Soc. 1976, 98, 5988–5996.
7
8
. Cannon, J. G.; Khonji, R. R. J. Med. Chem. 1975, 18, 110–112.
. (a) He, B.; Tian, H.-K.; Geng, Y.-H.; Wang, F.-S.; M u¨ llen, K. Org. Lett. 2008, 10,
73–776; (b) Yamamoto, T.; Koizumi, T.-a Polymer 2007, 48, 5449–5472; (c)
Grisorio, R.; Suranna, G. P.; Mastrorilli, P.; Nobile, C. F. Org. Lett. 2007, 9, 3149–
152; (d) Boden, B. N.; Jardine, K. J.; Leung, A. C. W.; MacLachlan, M. J. Org. Lett.
006, 8, 1855–1858; (e) Yang, C.; Scheiber, H.; List, E. J. W.; Jacob, J.; M u¨ llen, K.
7
3
2
25. Narasimhan, N. S.; Aidhen, I. S. Tetrahedron Lett. 1988, 29, 2987–2988.
26. Fu, J.-M.; Snieckus, V. Can. J. Chem. 2000, 78, 905–919.
Macromolecules 2006, 39, 5213–5221; (f) Tanaka, F.; Mase, N.; Barbas, C. F., III.
J. Am. Chem. Soc. 2004, 126, 3692–3693.
. Almeida, J. F.; Castedo, L.; Fern a´ ndez, D.; Neo, A. G.; Romero, V.; Tojo, G. Org.
27. (a) Russell, A.; Lockhart, L. B. Org. Synth. Coll. Vol. 3; Wiley & Sons: New York, NY,
1955; p. 463–465; (b) Shoesmith, J. B.; Mackie, A. J. Chem. Soc. 1930, 1584–1586.
28. (a) Oi, S.; Matsunaga, K.-i.; Hattori, T.; Miyano, S. Synthesis 1993, 895–898; (b)
Smith, J. G.; Dibble, P. W.; Sandborn, R. E. J. Org. Chem. 1986, 51, 3762–3768.
29. Taniguchi, N.; Hata, T.; Uemura, M. Angew. Chem., Int. Ed. 1999, 38, 1232–1235.
30. Ohmori, K.; Kitamura, M.; Suzuki, K. Angew. Chem., Int. Ed. 1999, 38, 1226–1229.
31. Raddo, P. D.; Chan, T. H. J. Org. Chem. 1982, 47, 1427–1431.
9
Lett. 2003, 5, 4939–4941.
1
0. Est e´ vez, J. C.; Villaverde, M. C.; Est e´ vez, R. J.; Castedo, L. Tetrahedron 1995, 51,
075–4082.
1. (a) Yoshikawa, E.; Yamamoto, Y. Angew. Chem., Int. Ed. 2000, 39, 173–175; (b)
Yoshikawa, E.; Radhakrishnan, K. V.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122,
4
1