Synthesis of phenanthrenes through copper-catalyzed cross-Coupling of N-tosylhydrazones with terminal alkynes

Article abstract of DOI:10.1021/jo501489c

A novel protocol for the synthesis of phenanthrenes through the copper-catalyzed reaction of aromatic tosylhydrazones with terminal alkynes is explored. The reaction proceeds via the formation of an allene intermediate and subsequent six-π-electron cyclization-isomerization, affording phenanthrene derivatives in good yields. The transformation can be performed in two ways:(1)with Ntosylhydrazones derived from [1,1'-biphenyl]-2-carbaldehydes and terminal alkynes as the starting materials and(2)with Ntosylhydrazones derived from aromatic aldehydes and 2-alkynyl biphenyls as the starting materials. This new phenanthrene synthesis uses readily available starting materials and a cheap copper catalyst and has a wide range of functional group compatibility.

Full text of DOI:10.1021/jo501489c

Article
pubs.acs.org/joc
Synthesis of Phenanthrenes through Copper-Catalyzed Cross-
Coupling of N‑Tosylhydrazones with Terminal Alkynes
Mohammad Lokman Hossain,†,§ Fei Ye,†,§ Zhenxing Liu,† Ying Xia,† Yi Shi,† Lei Zhou,† Yan Zhang,†
and Jianbo Wang*,†,‡
†Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering
of the Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China
‡State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
S
* Supporting Information
ABSTRACT: A novel protocol for the synthesis of phenan-
threnes through the copper-catalyzed reaction of aromatic
tosylhydrazones with terminal alkynes is explored. The
reaction proceeds via the formation of an allene intermediate
and subsequent six-π-electron cyclization−isomerization,
affording phenanthrene derivatives in good yields. The
transformation can be performed in two ways: (1) with N-
tosylhydrazones derived from [1,1′-biphenyl]-2-carbaldehydes
and terminal alkynes as the starting materials and (2) with N-
tosylhydrazones derived from aromatic aldehydes and 2-alkynyl biphenyls as the starting materials. This new phenanthrene
synthesis uses readily available starting materials and a cheap copper catalyst and has a wide range of functional group
compatibility.
Scheme 1. General Strategies for the Synthesis of
Phenanthrenes
INTRODUCTION
■
Because of their versatile applications in materials science1 and
medicinal chemistry2 as well as their wide presence in natural
products,3 phenanthrenes have attracted great attention over
the years. Consequently, significant efforts have been devoted
to the study of this type of compound, and a series of
methodologies for phenanthrene synthesis have been devel-
oped over the past decades.4 Among the various methods
developed, a general approach is intramolecular aryl−aryl bond
formation from stilbene derivatives (Scheme 1a).5 Carbocyc-
lization−annulation represents another useful and versatile
strategy for the synthesis of phenanthrene derivatives. This
strategy can be divided into two types: (1) using alkynylated
biaryls as the starting materials and (2) using biphenyl
derivatives and alkynes as the starting materials. The former
is represented in many cyclization methods such as Lewis acid-
catalyzed cyclizations, base-catalyzed cyclizations, electrophilic
cyclizations, and transition-metal-catalyzed electrophilic cycliza-
tions (Scheme 1b).6 For the latter, various metal-catalyzed [4 +
2] cycloadditions have been documented for phenanthrene
synthesis (Scheme 1c).7 Other strategies to synthesize
phenanthrenes, such as ring-closing olefin metathesis,8 Ullman
coupling−McMurry cyclization,9 and carbene dimerization,10
have also been reported (Scheme 1d). Despite the significant
advances that have been achieved over the years, the methods
developed to date suffer from at least one of the following
limitations: low efficiency, poor regioselectivity, use of
expensive and/or toxic reagents, poor accessibility of the
starting substrates, and so on. As a result, in view of the
importance of phenanthrenes and the drawbacks of the existing
methods, the development of new approaches for the synthesis
of functionalized phenanthrenes is highly desirable.
We recently reported a method for the synthesis of allenes
through Cu(I)-catalyzed cross-coupling of N-tosylhydrazones
with terminal alkynes.11,12 The reaction is proposed to involve a
copper(I) carbene migratory insertion process (Scheme 2).
Since the allene moiety is also reactive under Cu(I)-catalyzed
Received: July 6, 2014
© XXXX American Chemical Society
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Scheme 2. Cu(I)-Catalyzed Synthesis of Allenes
Scheme 4. Synthesis of N-Tosylhydrazones 2a−i and Alkynes
3a−e
reaction conditions, we further developed a straightforward
synthesis of benzofurans and indoles by introducing nucleo-
philes such as −OH and −NH2 into the substrates.12a To
further explore this coupling reaction, we conceived that the
allene moiety generated from the Cu(I)-catalyzed coupling of
N-tosylhydrazones with terminal alkynes may participate in a
6π cycloaddition−isomerization process to afford phenan-
threnes (Scheme 3). We have previously communicated
additive, and the substrate ratio resulted in the optimized
conditions, which can be summarized as follows: 2:1 substrate
ratio (2a:4a), 10 mol % CuBr2, LiOtBu (4.0 equiv), and 20 mol
% tetrabutylammonium bromide (TBAB) in dioxane at 90 °C
for 4 h and then at 120 °C for 24 h.12b Under such conditions,
5a was isolated in 74% GC yield and 57% isolated yield (eq 1).
Scheme 3. Synthesis of Phenanthrenes through Copper-
Catalyzed Cross-Coupling of N-Tosylhydrazones and
Terminal Alkynes
Subsequently, the scope of the reaction with a series of N-
tosylhydrazones 2b−i and alkynes 4a−i was investigated under
the optimized reaction conditions. As shown in Scheme 5,
substituents on the aromatic ring of the alkyne do not show a
significant effect on the reaction. Both electron-donating and
electron-withdrawing groups, including methoxy, alkyl, halogen,
and trifluoromethyl substituents, are compatible with the
reaction, giving the corresponding phenanthrenes in moder-
ately high yields. In addition, the reaction with a series of N-
tosylhydrazones bearing a substituted phenyl ring or hetero-
aromatic ring also proceeded smoothly, affording the
corresponding phenanthrenes in comparable yields.
Encouraged by the above results, we proceeded to study the
copper-catalyzed coupling reaction using N-tosylhydrazones
derived from aromatic aldehydes and 2-alkynyl biphenyls as the
starting materials. We initially performed the experiment using
CuI as the catalyst and 2-ethynylbiphenyl (3a) and N-
tosylhydrazone 6 as the model substrates in the presence of
LiOtBu (Table 1). The reaction gave the expected phenan-
threne product in 25% yield together with allene 5a′ (15%) and
the recovery of significant amount of alkyne. When the reaction
time was prolonged to 24 h and the temperature was raised to
120 °C, the allene byproduct was not observed, and the desired
phenanthrene 5a was obtained in 40% yield with the recovery
of a small amount of alkyne 3a (Table 1, entry 1). A study of
the solvent effect indicated that toluene gave comparable results
while DMF was less effective (entries 2 and 3).
preliminary results on the synthesis of phenanthrenes by a
CuBr2-catalyzed coupling−cyclization cascade with terminal
alkynes and N-tosylhydrazones derived from o-formyl biphenyls
as the starting materials.12b Herein we report the details of this
reaction and the further expansion of this transformation by
using 2-alkynyl biphenyls and N-tosylhydrazones derived from
aromatic aldehydes as the starting materials.
RESULTS AND DISCUSSION
■
As outlined in Scheme 4, N-tosylhydrazones 2a−i and alkynes
3a−e can be readily synthesized in excellent yields by a two-
step transformation. Suzuki−Miyaura cross-coupling of the
commercially available α-formyl aryl halide and arylboronic acid
starting materials afforded formyl biphenyls 1a−l in good
yields. Treatment of formyl biphenyls 1a−i with TsNHNH2 in
MeOH at 60 °C for 5−30 min afforded the desired N-
tosylhydrazones 2a−i as precipitates that could be readily
separated by simple filtration. On the other hand, submitting
the formyl biphenyls to the Corey−Fuchs reaction gave alkynyl
biphenyls 3a−e in good yields.
To fully convert the alkyne substrate in this reaction, some
ligands were next examined, and phenanthrolines were found to
be effective, affording the product in improved yield (Table 1,
entries 4−7). With 3,4,7,8-tetramethyl-1,10-phenanthroline
(L3) as the optimal ligand, a series of copper catalysts were
The copper-catalyzed phenanthrene synthesis was first
studied by using N-tosylhydrazone 2a and ethynylbenzene
(4a) as the model substrates. Screening of the reaction
conditions by inspection of the copper catalyst, the base, the
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Scheme 5. Substrate Scope with N-Tosylhydrazones 2b−i
Table 1. Optimization of the Reaction Conditions with
a
a
and Alkynes 4a−i
Phenylacetylene 3a and N-Tosylhydrazone 6
yield of 5a
b
entry
catalyst
ligand
base
solvent
(%)
1
2
CuI
CuI
CuI
CuI
CuI
CuI
CuI
none
none
none
PPh3
L1
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
LiOtBu
NaH
dioxane
toluene
DMF
40
42
29
51
48
62
3
4
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
5
6
L2
c
7
L3
64 (55)
8
Cu(MeCN)4PF6
CuBr
L3
52
58
46
25
60
35
47
25
21
9
L3
10
11
12
13
14
15
16
CuCl
L3
CuOTf·C6H6
CuBr2
L3
L3
Cu(OTf)2
CuI
L3
L3
CuI
L3
KOH
CuI
L3
Cs2CO3
a
Reaction conditions: 3a (0.2 mmol), 6 (0.5 mmol), base (4.5 equiv),
copper catalyst (15 mol %), and ligand (30 mol %) in the solvent
b
a
solvents (1.5 mL). Isolated yields by silica gel column chromatog-
Reaction conditions: N-tosylhydrazone 2b−i (0.8 mmol), alkyne 4a−
c
raphy. The yield in the parentheses refers to the scale-up reaction
i (0.4 mmol), CuBr2 (10 mol %), TBAB (20 mol %), and LiOtBu (1.6
mmol) in dioxane (4 mL) at 90 °C for 4 h and then at 120 °C for 24
h. Yields of products isolated by silica gel column chromatography are
shown. The reaction was carried out at 90 °C for 4 h and then at 120
°C for 36 h. 20% of the starting alkyne was recovered.
with 5 mmol alkyne 3a.
b
c
investigated (entries 7−13), and the CuI was found to be the
most effective (entry 7). Notably, CuBr2 also afforded the
product 5a in comparable yield (entry 12), but allene 5a′ was
isolated as a byproduct.
Subsequently, we examined the effect of the base. A series of
bases including NaH, KOH, and Cs2CO3 were examined, but
they were all found to be less efficient than LiOtBu (Table 1,
entries 14−16). We also studied the effects of phase-transfer
catalysts, including TBAB, TBAI (n-Bu4NI), and TBAC (n-
Bu4NCl). The reactions also proceeded in the presence of these
additives; however, no distinguishable effect was noticed.
Finally, under the optimized conditions (entry 7), a gram-
scale experiment was carried out and afforded the product in
55% yield.
Following the optimization of the reaction conditions, the
scope of the reaction was then studied with a series of N-
tosylhydrazones (7a−s) and alkynes (3a−e). The results are
collected in Table 2 and Scheme 6. First of all, the reaction was
not significantly affected by substituents on the aromatic ring of
the N-tosylhydrazone (Table 2). Substrates possessing either
electron-donating groups (entries 1−3, 9, and 12) or electron-
withdrawing groups (entries 4−8, 10, and 11) all reacted
smoothly. The aromatic tosylhydrazones bearing various
substituents, including alkyloxy, allyloxy, alkyl, halogen, and
trifluoromethyl groups, reacted efficiently to afford the
corresponding phenanthrenes in moderately good yields.
Tosylhydrazones possessing heterocycles, including pyridine
and thiophene, also gave the corresponding phenanthrene
products in moderate yields (entries 18 and 19). However, the
reaction of aliphatic tosylhydrazones with alkynes resulted in
mixtures of allenes (as major products) and phenanthrenes (as
minor products).
Next, the scope of alkynes was explored. Under the
optimized reaction conditions, alkynes possessing alkyl, alkoxy,
and thioalkyl substituents on the aromatic ring (3b−e) were
used as the substrates for the reaction with aromatic
tosylhydrazones (Scheme 6). The reactions all proceeded
smoothly, giving the corresponding phenanthrenes in moderate
yields with good functional group tolerance. For the reactions
with 2-ethynyl-3′-methoxy-1,1′-biphenyl (3c) and (2′-ethynyl-
[1,1′-biphenyl]-3-yl)(methyl)sulfane (3d), the cyclization
occurred exclusively at the sterically favored position to give
the corresponding products 9d−f and 9g−i. The structure of
one of the phenanthrene products, 9g, was confirmed by X-ray
crystallography (see the Supporting Information).
Since the transformation of aldehydes to the corresponding
tosylhydrazones is highly efficient, a one-pot process starting
directly from the aldehydes was then carried out. The one-pot
procedure afforded similar results as the stepwise trans-
formation (Scheme 7). This result considerably simplifies the
preparation of phenanthrenes by this coupling reaction.
CONCLUSION
■
A convenient and highly efficient synthetic approach for
phenanthrene derivatives has been developed. The reaction
employs readily available N-tosylhydrazones and terminal
alkynes as the staring materials. Mechanistically, the reaction
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a
a
Table 2. Substrate Scope of N-Tosylhydrazones
Scheme 6. Substrate Scope of Alkynes
b
entry
7, Ar
8, yield (%)
1
2
7a, m-MeC6H4
7b, p-MeC6H4
8a, 62
8b, 74
8c, 65
8d, 59
8e, 70
8f, 65
8g, 67
8h, 61
8i, 71
8j, 80
3
7c, p-tBuC6H4
4
7d, p-BrC6H4
5
7e, m-BrC6H4
6
7f, p-ClC6H4
7
7g, p-FC6H4
8
7h, p-NCC6H4
7i, p-MeOC6H4
7j, p-F3CC6H4
9
10
11
12
13
14
15
16
17
18
19
c
7k, m-O2NC6H4
7l, p-Me2NC6H4
7m, m,p-Cl2C6H3
7n, m,m-(MeO)2C6H3
7o, o-Cl-p-F3CC6H3
7p, o-alloxy-C6H4
7q, m,p-(OCH2O)C6H3
7r, 2-thiophenyl
7s, 3-pyridinyl
8k, 48
8l, 53
8m, 66
8n, 60
d
8o, 69 (59)
8p, 70
8q, 63
8r, 54
8s, 72
a
Reaction conditions: alkyne 3a (0.2 mmol), N-tosylhydrazone 7a−s
(2.5 equiv), CuI (15 mol %), L3 (30 mol %), and LiOtBu (4.5 equiv)
in toluene (1.5 mL) at 120 °C for 24 h. Yields of products isolated by
silica gel column chromatography. The reaction was carried out at
110 °C for 10 h. The yield in parentheses refers to the scaled-up
reaction with 5 mmol of alkyne.
b
c
a
Reaction conditions: alkyne 3b−e (0.2 mmol), N-tosylhydrazone 6,
7d, 7e, or 7m (2.8 equiv), CuI (15 mol %), L3 (30 mol %), and
d
b
LiOtBu (4.5 equiv) in toluene (1.5 mL) at 120 °C for 24 h. Yields of
products isolated by silica gel column chromatography are shown.
involves a cascade of CuI-catalyzed coupling−allenylation−six-
π-electron cyclization−aromatization. This method has the
following advantages: (1) easy preparation of the N-
tosylhydrazone starting materials from the corresponding
readily available aromatic aldehydes; (2) the use of an
inexpensive copper catalyst; (3) easy operation and good
functional group tolerance. With these advantages, we expect
that this new protocol for phenanthrene synthesis will find wide
applications in organic synthesis and related areas.
a
Scheme 7. One-Pot Preparation of Phenanthrenes
EXPERIMENTAL SECTION
■
General Methods. Except for the scale-up experiments, all of the
reactions were performed under a nitrogen atmosphere in a 20 mL
Schlenk tube. For the scale-up experiments, the reactions were carried
out in round-bottom flask. Dioxane was dried over Na before use. For
chromatographic purification, 200−300 mesh silica gel was employed.
1
Chemical shifts for H NMR (400 MHz) and 13C NMR (100 MHz)
spectra are reported relative to the chemical shift of tetramethylsilane
(TMS). IR spectra are reported in wavenumbers (cm−1). For HRMS
measurements, the mass analyzer was an FT-ICR instrument. N-
Tosylhydrazones 2a−i, 6, and 7a−s were prepared according to the
literature procedure.13 Unless otherwise noted, materials purchased
from commercial suppliers were used as received without further
purification.
General Experimental Procedure for the Preparation of 1a−l
by Suzuki−Miyaura Cross-Coupling. Under a nitrogen atmos-
phere, α-formyl aryl halide (10 mmol), arylboronic acid (12 mmol),
K2CO3 (30 mmol), and PdCl2(PPh3)2 (5 mol %, 350 mg) were
suspended in DMF/H2O (15 mL/1.5 mL). The resulting solution was
stirred at 110 °C for 12 h. After cooling to room temperature, the
reaction mixture was filtered through a short path of silica gel. The
a
Reaction conditions: aldehyde (2.5 equiv), TsNHNH2 (2.5 equiv),
alkyne (0.2 mmol), CuI (15 mol %), L3 (30 mol %), and LiOtBu (6.0
equiv) in dioxane (1.5 mL) at 120 °C for 24 h. Yields of products
isolated by silica gel column chromatography are shown.
b
mixture was extracted with EtOAc/Et2O (1:1) several times. The
combined organic layers were washed with saturated NaCl three times
and dried over anhydrous MgSO4. The reaction mixture was then
D
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concentrated under vacuum, and the crude residue was purified by
silica gel column chromatography (petroleum ether/EtOAc) to afford
the coupling product.
8.07 (d, J = 7.6 Hz, 1H), 7.71 (dt, J = 7.6, 1.6 Hz, 1H), 7.59 (t, J = 7.6
Hz, 1H), 7.43 (d, J = 7.6 Hz, 1H), 7.32−7.34 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 191.1, 149.8, 145.8, 142.7, 133.9, 133.4, 130.3, 129.0,
128.4, 124.7.
Biphenyl-2-carbaldehyde (1a).14 Colorless liquid (910 mg, 50%);
Rf = 0.5 (petroleum ether/EtOAc = 30:1); 1H NMR (400 MHz,
CDCl3) δ 9.98 (s, 1H), 8.02 (dd, J = 8.0, 1.2 Hz, 1H), 7.62 (dt, J = 7.6,
1.2 Hz, 1H), 7.42−7.50 (m, 6H), 7.36−7.38 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 192.3, 145.9, 133.7, 133.6, 133.5, 130.7, 130.0, 128.3,
128.0, 127.7, 127.5.
3′-Methoxybiphenyl-2-carbaldehyde (1j).6c Colorless liquid (1.90
g, 90%); Rf = 0.43 (petroleum ether/EtOAc = 100:1); 1H NMR (400
MHz, CDCl3) δ 9.99 (s, 1H), 8.01 (dd, J = 0.9, 7.8 Hz, 1H), 7.62 (dt, J
= 1.3, 7.5 Hz, 1H), 7.44−7.50 (m, 2H), 7.37 (t, J = 7.9 Hz, 1H), 6.92−
6.99 (m, 3H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 192.3,
159.5, 145.8, 139.1, 133.7, 133.4, 130.5, 129.4, 127.8, 127.4, 122.7,
115.6, 113.6, 55.3.
4′-tert-Butylbiphenyl-2-carbaldehyde (1b).15 Colorless liquid
(1.53 g, 64%); Rf = 0.55 (petroleum ether/EtOAc = 30:1); 1H
NMR (400 MHz, CDCl3) δ 9.90 (s, 1H), 7.90 (d, J = 7.6 Hz, 1H),
7.47−7.50 (m, 1H), 7.36−7.38 (m, 2H), 7.31−7.33 (m, 2H), 7.18−
7.20 (m, 2H), 1.26 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 192.5,
151.1, 145.9, 134.6, 133.7, 133.4, 130.7, 129.8, 127.4, 127.4, 125.3,
34.6, 31.2.
3′-(Methylthio)biphenyl-2-carbaldehyde (1k). Colorless liquid
(1.73 g, 76%); Rf = 0.45 (petroleum ether/EtOAc = 100:1); IR
(film) 3052, 2919, 2846, 1692, 1597, 1258, 1195, 1022, 909, 962, 654
1
cm−1; H NMR (400 MHz, CDCl3) δ 9.98 (s, 1H), 8.02 (dd, J = 0.9,
7.8 Hz, 1H), 7.63 (dt, J = 1.3, 7.5 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H),
7.43 (d, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.31 (d, J = 8.1 Hz,
1H), 7.24 (s, 1H), 7.12 (d, J = 7.4 Hz, 1H), 2.50 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 192.1, 145.3, 139.2, 138.4, 133.7, 133.5, 130.6,
128.6, 127.9, 127.5, 127.4, 126.7, 125.8, 15.5; EI-MS m/z (relative
intensity) 228 (M+, 100), 213 (5), 200 (30), 181 (35), 167 (30), 152
(70), 139 (10), 115 (8); HRMS (ESI) calcd for C14H12OSNa [(M +
Na)+] 251.0501, found 251.0500.
2,4-Bis(4′-methoxyphenyl)benzaldehyde (1c). White powder
(1.75 g, 55%); mp 101−102 °C; Rf = 0.35 (petroleum ether/EtOAc
= 10:1); IR (film) 2917, 2848, 1682, 1597, 1517, 1251, 1177, 1028,
1
824, 730, 676 cm−1; H NMR (400 MHz, CDCl3) δ 10.00 (s, 1H),
8.06 (d, J = 8.4 Hz, 1H), 7.60−7.66 (m, 4H), 7.36 (d, J = 8.4 Hz, 2H),
7.01 (t, J = 8.4 Hz, 4H), 3.88 (s, 3H), 3.86 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 192.2, 160.1, 159.7, 146.2, 145.8, 132.0, 131.9, 131.2,
130.2, 128.7, 128.5, 128.3, 125.5, 114.4, 113.9, 55.4, 55.3; EI-MS m/z
(relative intensity) 319 [(M + H)+, 35], 318 (M+, 100), 303 (16), 287
(26), 275 (27), 259 (9), 247 (15), 231 (14), 215 (22), 202 (28), 189
(9), 182 (22), 159 (8), 139 (12), 132 (10), 84 (8), 72 (7), 59 (13), 43
(40); HRMS (ESI) calcd for C21H19O3 [(M + H)+] 319.1329, found
319.1330.
2′-Formylbiphenyl-4-carbonitrile (1l).20 White powder (1.65 g,
80%); mp 98−99 °C; Rf = 0.40 (petroleum ether/EtOAc = 100:1); 1H
NMR (400 MHz, CDCl3) δ 9.95 (s, 1H), 8.05 (d, J = 7.7 Hz, 1H),
7.78 (d, J = 8.1 Hz, 2H), 7.70 (dt, J = 1.2, 7.5 Hz, 1H), 7.59 (t, J = 7.6
Hz, 1H), 7.51 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 7.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ 191.1, 143.4, 142.7, 133.8, 133.5, 132.1, 130.6,
130.5, 128.9, 128.6, 118.4, 112.0.
4′-Methoxybiphenyl-2-carbaldehyde (1d).16 White powder (1.51
g, 71%); mp 51−52 °C; Rf = 0.5 (petroleum ether/EtOAc = 30:1); 1H
NMR (400 MHz, CDCl3) δ 10.0 (s, 1H), 7.99 (d, J = 7.6 Hz, 1H),
7.60 (dt, J = 7.6, 1.2 Hz, 1H), 7.40−7.46 (m, 2H), 7.29 (d, J = 7.6 Hz,
2H), 6.99 (d, J = 8.4 Hz, 2H), 3.85 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 192.5, 159.6, 145.5, 133.6, 133.4, 131.2, 130.7, 129.9, 127.5,
127.2, 113.8, 55.2.
General Procedure for the Preparation of N-Tosylhydra-
zones 2a−i. A solution of TsNHNH2 (5 mmol) in methanol (5 mL)
was stirred and heated to 60 °C until the TsNHNH2 was completely
dissolved. Then the aldehyde 1a−i was dropped into the solution
slowly. After approximately 5−30 min, the crude product was obtained
as a precipitate. The precipitate was washed with petroleum ether and
then dried in vacuo to afford the pure product. The reaction provided
N-tosylhydrazones 2a−i in 70−99% yield.
3-Chloro-4′-methoxybiphenyl-2-carbaldehyde (1e). Greenish
liquid (1.09 g, 44%); Rf = 0.5 (petroleum ether/EtOAc = 10:1); IR
(film) 2961, 2916, 1698, 1607, 1513, 1249, 1179, 1049, 1025, 836,
N′-(Biphenyl-2-ylmethylene)-4-methylbenzenesulfonohydrazide
(2a).21 White powder (1.72 g, 98%); H NMR (400 MHz, CDCl3) δ
1
1
794, 663 cm−1; H NMR (400 MHz, CDCl3) δ 10.0 (s, 1H), 7.45−
7.95 (dd, J = 7.6, 0.8 Hz, 1H), 7.82−7.84 (d, J = 8.4 Hz, 2H), 7.79 (s,
1H), 7.68 (s, 1H), 7.25−7.43 (m, 8H), 7.17−7.20 (m, 2H), 2.41 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 146.9, 144.2, 142.4, 139.1,
135.3, 130.5, 130.1, 129.7, 129.6, 128.3, 127.9, 127.6, 127.6, 126.3,
21.6.
N′-((4′-tert-Butylbiphenyl-2-yl)methylene)-4-methylbenzenesul-
fonohydrazide (2b). White powder (1.95 g, 96%); mp 138−139 °C;
1H NMR (400 MHz, CDCl3) δ 7.93−7.96 (dd, J = 7.6, 0.8 Hz, 1H),
7.46 (m, 2H), 7.31 (dd, J = 6.4, 2.4 Hz, 1H), 7.22−7.26 (m, 3H), 6.97
(d, J = 8.8 Hz, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
190.3, 158.8, 145.3, 133.2, 131.6, 130.9, 129.9, 129.0, 128.7, 128.5,
113.0, 54.3; EI-MS m/z (relative intensity) 248 (M+, 37Cl, 90), 246
(M+, 90), 231 (12), 215 (28), 203 (30), 183 (18), 175 (45), 168 (33),
152 (27), 140 (33), 139 (100), 115 (14), 84 (28), 75 (8), 63 (12), 58
(22), 43 (84); HRMS (ESI) calcd for C14H12ClO2 [(M + H)+]
247.0520, found 247.0514.
2-(Thiophen-2-yl)benzaldehyde (1f).17 Colorless liquid (1.13 g,
60%); Rf = 0.4 (petroleum ether/EtOAc = 10:1); 1H NMR (400 MHz,
CDCl3) δ 10.18 (s, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.61 (d, J = 8.0 Hz,
1H), 7.50−7.55 (m, 3H), 7.14−7.16 (m, 1H), 7.07−7.08 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 192.1, 133.5, 133.4, 131.3, 129.5, 128.8,
128.5, 128.2, 127.8, 127.3.
7.83−7.85 (d, J = 8.4 Hz, 2H), 7.79 (s, 1H), 7.72 (s, 1H), 7.37−7.41
(m, 3H), 7.26−7.35 (m, 4H), 7.12−7.14 (d, J = 8.4 Hz, 2H), 2.41 (s,
3H), 1.35 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 150.6, 147.2,
144.1, 142.3, 136.1, 135.4, 130.5, 130.1, 130.0, 129.6, 129.4, 127.9,
127.4, 126.2, 125.3, 34.6, 31.3, 21.6; IR (film) 3196, 2962, 1703, 1363,
1167, 1049, 945, 813, 678, 667 cm−1; EI-MS m/z (relative intensity)
236 (M+, 6), 222 (28), 207 (78), 179 (36), 165 (64), 152 (12), 139
(16), 124 (12), 107 (10), 91 (75), 65 (36), 57 (100); HRMS (ESI)
calcd for C24H27N2O2S [(M + H)+] 407.1788, found 407.1793.
4-Methyl-N′-(2,4-bis(4′-methoxyphenyl)phenylmethylene)-
benzenesulfonohydrazide (2c). White powder (2.19 g, 90%); mp
112−113 °C; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.4 Hz, 1H),
7.85 (d, J = 8.0 Hz, 3H), 7.73 (s, 1H), 7.51−7.55 (m, 3H), 7.44−7.44
(d, J = 1.6 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H),
6.92−6.97 (m, 4H), 3.84 (s, 6H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 159.6, 159.3, 147.3, 144.1, 142.6, 142.3, 135.4, 132.5, 131.5,
130.8, 129.6, 128.9, 128.2, 128.1, 127.9, 126.8, 125.5, 114.3, 113.8,
60.4, 55.3, 21.6; IR (film) 2923, 1681, 1597, 1517, 1250, 1167, 1029,
824, 704, 661 cm−1; EI-MS m/z (relative intensity) 486 (M+, 8), 320
(6), 303 (100), 287 (38), 272 (14), 259 (12), 228 (14), 215 (24), 189
(8), 165 (6), 156 (16), 139 (22), 108 (8), 91 (78), 65 (42); HRMS
(ESI) calcd for C28H27N2O4S [(M + H)+] 487.1686, found 487.1676.
4′-Chlorobiphenyl-2-carbaldehyde (1g).17 Colorless liquid (1.58
1
g, 73%); Rf = 0.3 (petroleum ether/EtOAc = 60:1); H NMR (400
MHz, CDCl3) δ 9.96 (s, 1H), 8.02 (dd, J = 8.0, 1.2 Hz, 1H), 7.64 (dt, J
= 7.6, 1.2 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.39−7.45 (m, 3H), 7.30−
7.32 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 191.8, 144.4, 136.2,
134.4, 133.6, 133.6, 131.2, 130.6, 128.6, 128.1, 127.8.
4′-(Hydroxymethyl)biphenyl-2-carbaldehyde (1h).18 Colorless
1
liquid (1.28 g, 60%); Rf = 0.2 (petroleum ether/EtOAc = 3:1); H
NMR (400 MHz, CDCl3) δ 9.96 (s, 1H), 8.02 (d, J = 8.0 Hz, 1H),
7.62−7.65 (dt, J = 7.6, 0.8 Hz, 1H), 7.42−7.48 (m, 2H), 7.35−7.37
(m, 2H), 4.78 (s, 2H), 2.34 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
192.4, 145.6, 140.9, 136.9, 133.6, 133.6 (peak overlaps), 130.7, 130.2,
127.7, 127.6 (peak overlaps), 126.9, 64.7.
2-(Pyridin-4-yl)benzaldehyde (1i).19 Solid powder (1.17 g, 64%);
1
mp 67−68 °C; Rf = 0.2 (petroleum ether/EtOAc = 3:1); H NMR
(400 MHz, CDCl3) δ 9.98 (s, 1H), 8.72−8.73 (d, J = 6.0 Hz, 2H),
E
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N′-((4′-Methoxybiphenyl-2-yl)methylene)-4-methylbenzenesulfo-
HRMS (ESI) calcd for C19H18N3O2S [(M + H)+] 352.1114, found
352.1104.
1
nohydrazide (2d). White powder (1.7 g, 89%); mp 144−145 °C; H
NMR (400 MHz, CDCl3) δ 7.92 (d, J = 7.6 Hz, 1H), 7.83−7.86 (m,
3H), 7.71 (s, 1H), 7.24−7.40 (m, 5H), 7.11 (d, J = 8.4 Hz, 2H), 6.90
(d, J = 8.4 Hz, 2H), 3.82 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 159.3, 147.5, 144.3, 142.2, 135.5, 131.6, 131.0, 130.7, 130.3,
130.2, 129.8, 128.1, 127.4, 126.5, 114.0, 55.5, 21.7; IR (film) 3192,
1701, 1514, 1246, 1166, 1036, 943, 883, 764, 664 cm−1; EI-MS m/z
(relative intensity) 380 (M+, 14), 225 (10), 210 (10), 196 (100), 181
(88), 165 (48), 153 (92), 139 (22), 124 (14), 115 (12), 91 (74), 77
(22), 65 (38); HRMS (ESI) calcd for C21H21N2O3S [(M + H)+]
381.1267, found 381.1268.
N′-((3-Chloro-4′-methoxybiphenyl-2-yl)methylene)-4-methylben-
zenesulfonohydrazide (2e). White powder (1.45 g, 70%); mp 53−54
°C; 1H NMR (400 MHz, CDCl3) δ 8.12 (s, 1H), 7.74 (d, J = 8.0 Hz,
2H), 7.64 (s, 1H), 7.26−7.29 (m, 4H), 7.16 (d, J = 7.6 Hz, 1H), 7.08
(d, J = 8.4 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 3.81 (s, 3H), 2.42 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 159.3, 145.3, 144.2, 144.0,
135.6, 133.9, 131.7, 130.9, 129.9, 129.6, 129.4, 129.1, 129.0, 128.2,
113.8, 55.4, 21.7; IR (film) 3196, 2924, 1608, 1514, 1441, 1247, 1155,
1047, 813, 678 cm−1; EI-MS m/z (relative intensity) 414 (M+, 18),
386 (6), 259 (8), 233 (28), 231 (96), 215 (36), 196 (100), 181 (24),
152 (42), 139 (8), 91 (24), 65 (10); HRMS (ESI) calcd for
C21H20ClN2O3S [(M + H)+] 415.0878, found 415.0886.
General Procedure for the Preparation of 3a−e by the
Corey−Fuchs Reaction. First Step. To a solution of aldehyde (1.0
equiv) and CBr4 (1.5 equiv) in anhydrous DCM cooled to 0 °C (ice−
water bath) was added Ph3P (3.0 equiv) as a solid in small portions.
The resultant light-yellow reaction mixture was then stirred at ambient
temperature for 3−5 h. Solvent was removed in vacuo, and the residue
was dissolved in petroleum ether/EtOAc (60:1). Triphenylphosphine
oxide was filtered off by suction. The filtrate was concentrated under
reduced pressure, and the crude gem-dibromide was purified by
chromatography on silica gel using petroleum ether/EtOAc as the
eluent.
Second Step. A well-stirred solution of the gem-dibromide (10
mmol) in anhydrous THF was cooled to −40 °C under an argon
atmosphere. n-BuLi (1.6 M solution in hexanes, 2.05 equiv) was then
added dropwise via syringe. The stirring was continued at −40 °C until
the reaction was complete as monitored by TLC (2−3 h). After
completion of the reaction, the resultant light-yellow/orange mixture
was diluted with distilled water, and the stirring was continued for 0.5
h to allow the mixture to slowly reach room temperature. The layers
were separated, and the aqueous layer was extracted with Et2O. The
combined organic layers were washed with brine, dried over anhydrous
Na2SO4, filtered, and concentrated under reduced pressure. The crude
product was purified by chromatography on silica gel using petroleum
ether/EtOAc as the eluent.
4-Methyl-N′-(2-(thiophen-2-yl)benzylidene)benzenesulfono-
1
hydrazide (2f). White powder (1.51 g, 85%); mp 139−140 °C; H
2-Ethynylbiphenyl (3a).22 Colorless liquid (1.35 g, 76%); Rf = 0.51
NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.90−7.92 (m, 2H), 7.84−
7.86 (d, J = 8.0 Hz, 2H), 7.30−7.38 (m, 6H), 7.03−7.06 (m, 1H),
6.85−6.86 (d, J = 7.2 Hz, 1H), 2.41 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 146.7, 144.2, 140.2, 135.3, 134.6, 131.3, 130.8, 130.0, 129.7,
128.2, 128.1, 127.9, 127.5, 126.7, 126.5, 21.6; IR (film) 3194, 2925,
1596, 1448, 1324, 1166, 943, 762, 665 cm−1; EI-MS m/z (relative
intensity) 355 (M+, 12), 201 (18), 185 (12), 171 (100), 156 (6), 139
(12), 129 (12), 115 (8), 91 (22); HRMS (ESI) calcd for
C18H17N2O2S2 [(M + H)+] 357.0726, found 357.0733.
1
(petroleum ether); H NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 7.5,
13.1 Hz, 1H), 7.36−7.44 (m, 5H), 7.23−7.31 (m, 1H), 3.02 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 144.4, 140.2, 133.8, 129.6, 129.2,
128.9, 128.0, 127.5, 127.0, 120.4, 83.1, 80.1; IR (film) 3064, 2964,
2360, 1595, 1474, 1449, 1432, 1260, 1017, 800, 759, 699, 658 cm−1.
4′-(tert-Butyl)-2-ethynylbiphenyl (3b). Colorless liquid (1.7 g,
1
73%); Rf = 0.55 (petroleum ether); H NMR (400 MHz, CDCl3) δ
7.70 (s, 1H), 7.62 (d, J = 7.6 Hz, 1H), 7.37−7.41 (m, 5H), 7.23−7.31
(m, 1H), 3.03 (s, 1H), 1.36 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
150.5, 144.9, 139.7, 133.9, 129.6, 128.9, 127.8, 126.9, 126.8, 126.1,
124.3, 120.4, 83.4, 80.0, 34.9, 31.3; IR (film) 3078, 2960, 2362, 1595,
1472, 1364, 1240, 910, 758, 707, 688 cm−1; HRMS (ESI) calcd for
C18H19 [(M + H)+] 235.1481, found 235.1478.
N′-((4′-Chlorobiphenyl-2-yl)methylene)-4-methylbenzenesulfo-
nohydrazide (2g). Brown powder (1.5 g, 78%); mp 135−136 °C; 1H
NMR (400 MHz, CDCl3) δ 8.11 (s, 1H), 7.91−7.93 (m, 1H), 7.82 (d,
J = 8.0 Hz, 2H), 7.69 (s, 1H), 7.29−7.41 (m, 6H), 7.21−7.23 (m, 1H),
7.10−7.13 (m, 2H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
146.5, 144.2, 141.0, 137.5, 135.2, 133.8, 130.9, 130.6, 130.1, 129.9,
129.6, 128.5, 128.3, 127.9, 126.4, 21.6; IR (film) 3187, 2924, 1596,
1361, 1317, 1163, 1090, 946, 814, 672 cm−1; EI-MS m/z (relative
intensity) 386 (M+, 37Cl, 4), 384 (M+, 6), 269 (12), 267 (22), 252 (4),
229 (12), 212 (10), 199 (16), 194 (10), 165 (100), 163 (20), 139
(24), 124 (8), 107 (12), 91 (82), 84 (18), 65 (39); HRMS (ESI) calcd
for C20H18ClN2O2S [(M + H)+] 385.0772, found 385.0775.
N′-((4′-(Hydroxymethyl)biphenyl-2-yl)methylene)-4-methylben-
zenesulfonohydrazide (2h). Brown powder (1.65 g, 87%); mp 70−71
°C; 1H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H), 7.94−7.96 (m, 1H),
7.83 (d, J = 8.0 Hz, 2H), 7.67 (s, 1H), 7.25−7.40 (m, 7H), 7.16 (d, J =
8.0 Hz, 2H), 4.68 (d, 2H), 2.40 (s, 3H), 1.80 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 146.9, 144.1, 142.0, 140.1, 138.5, 135.4, 130.7, 130.0,
129.9, 129.6, 128.2, 127.9, 127.7, 127.1, 126.2, 64.8, 21.6; IR (film)
3199, 2922, 1596, 1326, 1165, 1043, 813, 663 cm−1; EI-MS m/z
(relative intensity) 380 (M+, 8), 214 (6), 212 (6), 196 (30), 179 (26),
167 (100), 152 (36), 139 (24), 124 (8), 107 (8), 93 (6), 91 (72), 77
(22), 65 (46); HRMS (ESI) calcd for C21H21N2O3S [(M + H)+]
381.1267, found 381.1275.
2-Ethynyl-3′-methoxybiphenyl (3c).6c Colorless liquid (1.73 g,
1
83%); Rf = 0.41 (petroleum ether/EtOAc = 60:1); H NMR (400
MHz, CDCl3) δ 7.61 (d, J = 7.6 Hz, 1H), 7.27−7.39 (m, 4H), 7.14−
7.16 (m, 2H), 6.92 (dd, J = 1.7, 8.3 Hz, 1H), 3.84 (s, 3H), 3.05 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 159.1, 144.2, 141.6, 133.9,
129.5, 129.0, 128.9, 127.0, 121.7, 120.4, 114.8, 133.3, 83.1, 80.3, 55.3;
IR (film) 3060, 2834, 2367, 1604, 1582, 1219, 910, 669, 657 cm−1.
(2′-Ethynylbiphenyl-3-yl)(methyl)sulfane (3d). Colorless liquid
(1.5 g, 67%); Rf = 0.50 (petroleum ether/EtOAc = 100:1); 1H
NMR (400 MHz, CDCl3) δ 7.61 (d, J = 7.7 Hz, 1H), 7.49 (s, 1H),
7.24−7.40 (m, 6H), 3.05 (s, 1H), 2.51 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 143.9, 140.8, 138.0, 133.9, 129.5, 129.0, 128.4, 127.3, 127.2,
126.0, 125.8, 120.4, 83.0, 80.4, 15.8; IR (film) 3063, 2926, 2364, 1588,
1465, 1438, 1103, 759, 657 cm−1; HRMS (ESI) calcd for C15H13S [(M
+ H)+] 225.0732, found 225.0733.
2′-Ethynylbiphenyl-4-carbonitrile (3e). White powder (1.2 g,
59%); mp 104−105 °C; Rf = 0.48 (petroleum ether/EtOAc =
30:1); 1H NMR (400 MHz, CDCl3) δ 7.70−7.63 (m, 5H), 7.45 (t, J =
7.3 Hz, 1H), 7.39−7.34 (m, 2H), 3.07 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 144.8, 142.3, 134.0, 131.8, 129.9, 129.3, 129.2, 128.1, 120.4,
118.8, 111.3, 82.2, 81.0; IR (film) 3072, 2228, 1608, 1476, 841, 761,
733, 655 cm−1; HRMS (ESI) calcd for C15H10N [(M + H)+] 204.0808,
found 204.0803.
4-Methyl-N′-(2-(pyridin-4-yl)benzylidene)benzenesulfono-
1
hydrazide (2i). White powder (1.69 g, 96%); mp 172−173 °C; H
NMR (400 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.64−8.66 (m, 2H),
7.82−7.84 (m, 2H), 7.73−7.75 (m, 2H), 7.48−7.52 (m, 2H), 7.41−
7.43 (m, 2H), 7.34−7.36 (m, 1H), 7.27−7.28 (m, 2H), 2.37 (s, 3H);
13C NMR (100 MHz, DMSO-d6) δ 149.6, 146.4, 144.9, 143.6, 139.0,
136.1, 130.7, 130.2, 130.0, 129.7, 128.9, 127.2, 125.4, 124.5, 21.0; IR
(film) 3147, 2255, 1655, 1049, 1024, 1003, 824, 761, 666 cm−1; EI-MS
m/z (relative intensity) 351 (M+, 10), 323 (4), 195 (8), 183 (6), 168
(100), 156 (12), 139 (52), 115 (12), 113 (6), 91 (33), 84 (16);
Typical Procedure for the CuBr2-Catalyzed Coupling of N-
Tosylhydrazones 2a−i and Terminal Alkynes 4a−i. CuBr2 (10
mol %, 9 mg), LiOtBu (1.6 mmol, 128 mg), TBAB (20 mol %, 26 mg),
and N-tosylhydrazone 2a (0.8 mmol, 280 mg) were suspended in
dioxane (4 mL) in a 10 mL Schlenk tube under nitrogen.
Phenylacetylene (4a) (0.4 mmol, 41 mg) was added. The resulting
solution was stirred at 90 °C for 4 h, and then the temperature was
F
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raised to 120 °C for another 24 h. After cooling to room temperature,
the resulting mixture was filtered through a short path of silica gel,
eluting with EtOAc. The volatile compounds were removed in vacuo,
and the crude residue was purified by column chromatography (SiO2,
hexane) to afford the phenanthrene product 5a.
HRMS (ESI) calcd for C23H21O [(M + H)+] 313.1587, found
313.1588.
10-(4-tert-Butylbenzyl)-2-methoxyphenanthrene (5g). White
powder (79 mg, 56%); Rf = 0.45 (petroleum ether/EtOAc = 30:1);
1H NMR (400 MHz, CDCl3) δ 8.59 (d, J = 9.2 Hz, 1H), 8.54 (d, J =
8.0 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.49−7.56 (m, 3H), 7.38 (d, J =
2.4 Hz, 1H), 7.28 (m, 2H), 7.18−7.24 (m, 3H), 4.39 (s, 2H), 3.80 (s,
3H), 1.28 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 158.1, 149.0,
137.1, 134.4, 132.8, 130.8, 130.0, 128.4, 128.3, 128.2, 126.2, 125.6,
125.4, 125.1, 124.6, 121.9, 116.1, 106.3, 55.2, 39.5, 34.4, 31.4; IR (film)
2960, 1616, 1466, 1042, 748 cm−1; EI-MS m/z (relative intensity) 354
(M+, 100), 239 (24), 297 (8), 2212 (16), 169 (12), 155 (7), 131 (7);
HRMS (ESI) calcd for C26H27O [(M + H)+] 355.2056, found
355.2059; C26H26NaO [(M + Na)+] 377.1876, found 377.1879.
10-Benzyl-2-methoxyphenanthrene (5h). White powder (67 mg,
56%); Rf = 0.5 (petroleum ether/EtOAc = 30:1); 1H NMR (400 MHz,
CDCl3) δ 8.61 (d, J = 8.8 Hz, 1H), 8.55 (d, J = 8.4 Hz, 1H), 7.79 (d, J
= 7.6 Hz, 1H), 7.60−7.49 (m, 3H), 7.37−7.19 (m, 7H), 4.43 (s, 2H),
3.81 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.1, 140.1, 134.2,
132.7, 130.7, 130.0, 128.7, 128.5, 128.4, 128.2, 126.3, 126.1, 125.6,
125.0, 124.6, 121.9, 116.1, 106.1, 55.2, 40.0; IR (film) 2960, 1616,
1466, 1042, 748 cm−1; EI-MS m/z (relative intensity) 298 (M+, 100),
265 (18), 252 (10), 221 (7), 178 (6), 126 (7); HRMS (ESI) calcd for
C22H19O [(M + H)+] 299.1430, found 299.1434; C22H18NaO [(M +
Na)+] 321.1250, found 321.1254.
9-Benzylphenanthrene (5a).6j White powder (61 mg, 57%); Rf =
1
0.75 (petroleum ether); H NMR (400 MHz, CDCl3) δ 8.73 (d, J =
8.4 Hz, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.81
(d, J = 7.6 Hz, 1H), 7.55−7.63 (m, 4H), 7.32−7.36 (m, 2H), 7.25−
7.28 (m, 4H), 4.49 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 141.2,
140.4, 134.9, 132.0, 131.5, 131.0, 128.7, 128.4, 128.1, 128.1, 126.9,
126.8, 126.4, 126.3, 125.2, 123.3, 122.6, 39.8.
10-(4-(Trifluoromethyl)benzyl)-2-methoxyphenanthrene (5b).
White powder (72 mg, 49%); Rf = 0.45 (petroleum ether/EtOAc =
1
30:1); H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 9.2 Hz, 1H), 8.56
(d, J = 8.4 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.52−7.60 (m, 3H),
7.19−7.32 (m, 4H), 6.94−6.98 (m, 2H), 4.40 (s, 2H), 3.83 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 158.2, 135.8, 135.8, 135.7, 134.0,
132.6, 131.0, 130.6, 130.0, 128.2, 127.7 (q, J = 162.5 Hz), 125.5 (q, J =
5.0 Hz, CF3), 125.1, 124.7, 121.9, 116.1, 115.4, 115.2, 106.2, 55.2,
39.2; IR (film) 2849, 1616, 1508, 1224, 827 cm−1; EI-MS m/z (relative
intensity) 316 (100), 299 (6), 283 (16), 270 (8), 221 (5), 141 (4);
HRMS (ESI) calcd for C23H17F3NaO [(M + Na)+] 389.0760, found
389.0756.
10-(4-Fluorobenzyl)-2-methoxyphenanthrene (5c). White powder
1
10-(3-Methylbenzyl)-2-methoxyphenanthrene (5i). White powder
(86 mg, 68%); Rf = 0.45 (petroleum ether/EtOAc = 30:1); H NMR
1
(70 mg, 56%); Rf = 0.5 (petroleum ether/EtOAc = 30:1); H NMR
(400 MHz, CDCl3) δ 8.61 (d, J = 8.8 Hz, 1H), 8.55 (d, J = 8.4 Hz,
1H), 7.78−7.79 (d, J = 7.6 Hz, 1H), 7.49−7.61 (m, 4H), 7.18−7.30
(m, 4H), 6.94−6.98 (m, 2H), 4.39 (s, 2H), 3.83 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 161.4 (d, J = 243.0 Hz), 158.2, 135.8 (d, J = 3.1
Hz), 134.0, 132.5, 130.6, 130.1 (d, J = 7.1 Hz), 128.5, 128.2, 126.5,
126.4, 125.7, 125.1, 124.7, 121.9, 116.1, 115.3 (d, J = 21.0 Hz), 106.1,
55.2, 39.2; IR (film) 1616, 1508, 1042, 823, 749 cm−1; EI-MS m/z
(relative intensity) 316 (M+, 100), 283 (21), 270 (10), 71 (11), 57
(16), 43 (16); HRMS (ESI) calcd for C22H18FO [(M + H)+]
317.1336, found 317.1340.
(400 MHz, CDCl3) δ 8.61 (d, J = 9.2 Hz, 1H), 8.56 (d, J = 8.4 Hz,
1H), 7.80 (d, J = 8.0 Hz, 1H), 7.59−7.51 (m, 3H), 7.39−7.39 (m,
1H), 7.26−7.00 (m, 5H), 4.40 (s, 2H), 3.83 (s, 3H), 2.28 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 158.1, 140.1, 138.1, 134.4, 132.8, 130.7,
130.0, 129.5, 128.4, 128.4, 128.2, 127.0, 126.3, 125.8, 125.6, 125.1,
124.6, 121.9, 116.1, 106.2, 55.2, 40.0, 21.4; IR (film) 2920, 1615, 1224,
1042, 747 cm−1; EI-MS m/z (relative intensity) 312 (M+, 100), 265
(9), 149 (11), 111 (12), 97 (17), 71 (40), 57 (65); HRMS (ESI) calcd
for C23H21O [(M + H)+] 313.1587, found 313.1589.
5-(4-Fluorobenzyl)benzo[f ]isoquinoline (5j). Slightly yellow pow-
10-(4-Chlorobenzyl)-2-methoxyphenanthrene (5d). White pow-
1
der (70 mg, 61%); Rf = 0.35 (petroleum ether/EtOAc = 3:1); H
1
der (77 mg, 58%); Rf = 0.45 (petroleum ether/EtOAc = 30:1); H
NMR (400 MHz, CDCl3) δ 9.39 (s, 1H), 8.74 (d, J = 2.4 Hz, 1H),
8.66−8.64 (m, 1H), 8.43 (d, J = 5.2 Hz, 1H), 7.87−7.85 (m, 1H),
7.70−7.68 (m, 2H), 7.58−7.57 (m, 1H), 7.23−7.20 (m, 2H), 6.70−
6.96 (m, 2H), 4.52 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 161.6 (d,
J = 243.0 Hz), 149.9, 148.7, 145.0, 135.6, 135.1 (d, J = 3.2 Hz), 134.0,
133.3, 130.2 (d, J = 7.8 Hz), 129.0, 128.9, 128.8, 128.4, 128.1, 126.9,
123.0, 115.5 (d, J = 21.0 Hz), 38.0; IR (film) 1616, 1509, 1224, 829,
750 cm−1; EI-MS m/z (relative intensity) 287 (M+, 100), 257 (6), 192
(7), 142 (11), 109 (10), 57 (9); HRMS (ESI) calcd for C20H15FN
[(M + H)+] 288.1183, found 288.1180.
9-(4-Fluorobenzyl)-1-chloro-7-methoxyphenanthrene (5k). White
powder (97 mg, 69%); Rf = 0.35 (petroleum ether/EtOAc = 30:1); IR
(film) 1614, 1508, 1219, 1043, 790, cm−1; 1H NMR (400 MHz,
CDCl3) δ 8.54 (d, J = 9.2 Hz, 1H), 8.44 (d, J = 8.4 Hz, 1H), 8.06 (s,
1H), 7.59−7.57 (d, J = 8.0 Hz, 1H), 7.46 (d, J = 7.6 Hz, 1H), 7.28−
7.17 (m, 4H), 6.96−6.92 (m, 2H), 4.41 (s, 2H), 3.79 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 161.4 (d, J = 243 Hz), 158.6, 135.6 (d, J =
3.2 Hz), 135.4, 132.5, 132.3, 131.6, 129.9 (d, J = 7.8 Hz), 127.8, 126.2,
126.1, 125.1, 124.8, 124.1, 120.9, 116.7, 115.3 (d, J = 21.0 Hz), 106.1,
55.2, 39.6; EI-MS m/z (relative intensity) 352 (M+, 37Cl, 33), 350
(M+, 35Cl, 100), 283 (19), 230 (24), 195 (14), 152 (12), 135 (10), 57
(14); HRMS (ESI) calcd for C22H17ClFO [(M + H)+] 351.0946,
found 351.0952.
NMR (400 MHz, CDCl3) δ 8.62 (d, J = 8.8 Hz, 1H), 8.56 (d, J = 8.0
Hz, 1H), 7.80−7.78 (d, J = 8.0 Hz, 1H), 7.62−7.58 (m, 1H), 7.54−
7.50 (m, 2H), 7.29−7.17 (m, 6H), 4.39 (s, 2H), 3.83 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 158.2, 138.7, 133.6, 132.5, 131.9, 130.6,
130.1, 130.0, 128.6, 128.3, 126.5, 125.8, 125.1, 124.7, 122.0, 116.1,
106.1, 55.3, 39.3; IR (film) 1599, 1488, 1260, 1048, 778, 749 cm−1; EI-
MS m/z (relative intensity) 334 (M+, 37Cl, 36), 332 (M+, 35Cl, 100),
281 (10), 266 (9), 265 (13), 252 (12), 126 (13); HRMS (ESI) calcd
for C22H18ClO [(M + H)+] 333.1041, found 333.1044.
2-Methoxy-10-(3-methoxybenzyl)phenanthrene (5e). White pow-
1
der (70 mg, 53%); Rf = 0.35 (petroleum ether/EtOAc = 30:1); H
NMR (400 MHz, CDCl3) δ 8.61 (d, J = 9.2 Hz, 1H), 8.55 (d, J = 8.4
Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.60−7.50 (m, 3H), 7.38−7.18 (m,
5H), 6.89−6.73 (m, 3H), 4.40 (s, 2H), 3.83 (s, 3H), 3.72 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 159.8, 158.1, 141.8, 134.1, 132.7, 130.7,
130.0, 129.4, 128.5, 128.3, 126.3, 125.6, 125.1, 124.0, 121.9, 116.1,
114.6, 113.4, 106.2, 55.2, 55.1, 40.1; IR (film) 2971, 1633, 1460, 1058,
762 cm−1; EI-MS m/z (relative intensity) 328 (M+, 100), 262 (62),
252 (8), 213 (11), 176 (6), 126 (10); HRMS (ESI) calcd for
C23H21O2 [(M + H)+] 329.1536, found 329.1540; C23H20NaO2 [(M +
Na)+] 351.1356, found 351.1359.
10-(4-Methylbenzyl)-2-methoxyphenanthrene (5f). White powder
1
(77 mg, 62%); Rf = 0.40 (petroleum ether/EtOAc = 30:1); H NMR
(10-(4-Fluorobenzyl)phenanthren-2-yl)methanol (5l). White pow-
1
(400 MHz, CDCl3) δ 8.61 (d, J = 9.2 Hz, 1H), 8.55 (d, J = 8.4 Hz,
1H), 7.79 (d, J = 7.6 Hz, 1H), 7.48−7.60 (m, 3H), 7.38 (s, 1H), 7.22−
7.25 (m, 1H), 7.15−7.17 (m, 2H), 7.07−7.09 (m, 2H), 4.39 (s, 2H),
3.83 (s, 3H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.1,
137.0, 135.6, 134.5, 132.8, 130.8, 130.0, 129.2, 128.6, 128.3, 128.2,
126.2, 125.6, 125.1, 124.6, 121.9, 116.1, 106.2, 55.2, 39.6, 21.0; IR
(film) 1616, 1466, 1225, 1042, 748 cm−1; EI-MS m/z (relative
intensity) 312 (M+, 100), 281 (14), 265 (14), 126 (12), 57 (25);
der (68 mg, 54%); Rf = 0.25 (petroleum ether/EtOAc = 5:1); H
NMR (400 MHz, CDCl3) δ 8.71 (d, J = 8.4 Hz, 1H), 8.64 (d, J = 8.0
Hz, 1H), 7.97 (s, 1H), 7.81−7.79 (d, J = 7.6 Hz, 1H), 7.64−7.51 (m,
4H), 7.22−7.18 (m, 2H), 6.98−6.94 (m, 2H), 4.84 (s, 2H), 4.44 (s,
2H), 1.76 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 161.4 (d, J = 243
Hz), 139.1, 135.7 (d, J = 3.2 Hz), 134.6, 131.7, 131.2, 130.3, 130.2 (d, J
= 7.7 Hz), 129.8, 128.3, 128.1, 126.7, 126.4, 125.3, 123.6, 122.7, 122.5,
115.3 (d, J = 21 Hz), 65.5, 38.7; IR (film) 1603, 1221, 1039, 822, 749
G
dx.doi.org/10.1021/jo501489c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
cm−1; EI-MS m/z (relative intensity) 316 (M+, 100), 285 (26), 179
(15), 165 (15), 149 (14), 109 (25), 57 (33); HRMS (ESI) calcd for
C22H17FNaO [(M + Na)+] 339.1156, found 339.1157.
added to a mixture of CuI (5.7 mg, 15 mol %, 0.03 mmol), LiOtBu (72
mg, 0.9 mmol), 3,4,7,8-tetramethyl-1,10-phenanthroline (14.2 mg, 30
mol %, 0.06 mmol), and N-tosylhydrazone 6 (137 mg, 0.5 mmol) in
toluene (1.5 mL). The mixture was stirred at 120 °C for 24 h and
monitored by TLC. After cooling to room temperature, the resulting
mixture was filtered through a short path of silica gel using EtOAc as
the eluent. The solvent was then removed in vacuo. The crude product
was purified on a silica gel column using petroleum ether as the eluent
to afford phenanthrene 5a as a white powder (35 mg, 64% based on
3a).
10-(4-Fluorobenzyl)-2-methoxy-6-(4-methoxyphenyl)-
phenanthrene (5m). White powder (96 mg, 57%); Rf = 0.25
1
(petroleum ether/EtOAc = 30:1); H NMR (400 MHz, CDCl3) δ
8.70−8.68 (m, 2H), 7.84−7.82 (m, 1H), 7.73−7.69 (m, 3H), 7.54 (s,
1H), 7.31−6.94 (m, 9H), 4.40 (s, 2H), 3.88 (s, 3H), 3.83 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 161.4 (d, J = 244 Hz), 159.3, 158.3, 138.9,
135.8 (d, J = 3.2 Hz), 134.2, 133.8, 132.8, 130.3, 130.1 (d, J = 7.8 Hz),
129.4, 128.7, 128.5, 128.2, 125.0, 124.7, 119.8, 116.1, 115.3 (d, J = 21
Hz), 114.3, 106.2, 55.4, 55.2, 39.2; IR (film) 1608, 1247, 1221, 1045,
821 cm−1; EI-MS m/z (relative intensity) 422 (M+, 100), 407 (7), 350
(6), 211 (7), 149 (10), 57 (17); HRMS (ESI) calcd for C29H24FO2
[(M + H)+] 423.1755, found 423.1763.
9-(3-Methylbenzyl)phenanthrene (8a). White powder (35 mg,
1
62%); mp 129−130 °C; Rf = 0.48 (petroleum ether); H NMR (400
MHz, CDCl3) δ 8.71 (dd, J = 8.2, 32.9 Hz, 2H), 8.02 (d, J = 8.1 Hz,
1H), 7.72 (d, J = 7.8 Hz, 1H), 7.68−7.51 (m, 4H), 7.28−7.23 (m,
2H), 7.19 (t, J = 7.4 Hz, 1H), 7.09 (t, J = 7.3 Hz, 1H), 6.98 (d, J = 7.5
Hz, 1H), 4.42 (s, 2H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
138.0, 136.6, 134.3, 131.8, 131.5, 130.6, 130.1, 129.7, 129.6, 128.3,
127.0, 126.7, 126.6, 126.5, 126.3, 126.2, 124.5, 123.1, 122.4, 36.6, 19.6;
IR (film) 2917, 1602, 1452, 1260, 1031, 743 cm−1; HRMS (EI) calcd
for C22H19 [(M + H)+] 283.1481, found 283.1484.
4-(4-Chlorobenzyl)naphtho[1,2-b]thiophene (5n). White powder
1
(90 mg, 73%); Rf = 0.45 (petroleum ether/EtOAc = 60:1); H NMR
(400 MHz, CDCl3) δ 8.10 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 7.6 Hz,
1H), 7.54−7.43 (m, 4H), 7.37−7.36 (m, 1H), 7.24−7.22 (m, 2H),
7.15−7.13 (m, 2H), 4.33 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
138.5, 138.0, 137.2, 133.2, 132.0, 131.0, 130.1, 128.6, 128.4, 128.2,
126.2, 125.8, 125.1, 123.5, 123.2, 39.5; IR (film) 1608, 1247, 1221,
1045, 821 cm−1; EI-MS m/z (relative intensity) 310 (M+, 37Cl, 36),
308 (100), 271 (26), 197 (27), 149 (8), 135 (12); HRMS (ESI) calcd
for C19H14ClS [(M + H)+] 309.0499, found 309.0500.
9-(4-Methylbenzyl)phenanthrene (8b).23 White powder (42 mg,
1
74%); mp 123−124 °C; Rf = 0.55 (petroleum ether); H NMR (400
MHz, CDCl3) δ 8.70 (dd, J = 8.1, 23.2 Hz, 2H), 8.04 (d, J = 8.1 Hz,
1H), 7.82 (d, J = 7.6 Hz, 1H), 7.65−7.52 (m, 5H), 7.14 (d, J = 8.0,
2H), 7.08 (d, J = 7.9 Hz, 2H), 4.45 (s, 2H), 2.31 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 137.1, 135.6, 135.0, 131.8, 131.4, 129.9, 129.2,
128.6, 128.2, 127.8, 126.6, 126.2, 126.1, 125.0, 123.1, 122.4, 39.2, 21.0;
IR (film) 3022, 2962, 2913, 2356, 1794, 1493, 1260, 1022, 771 cm−1.
9-(4-(tert-Butyl)benzyl)phenanthrene (8c).23 White powder (42
4-(4-Fluorobenzyl)naphtho[1,2-b]thiophene (5o). White powder
1
(72 mg, 62%); Rf = 0.45 (petroleum ether/EtOAc = 60:1); H NMR
(400 MHz, CDCl3) δ 8.10 (d, J = 7.6 Hz, 1H), 7.83 (d, J = 8.0 Hz,
1H), 7.52−7.38 (m, 5H), 7.22−6.93 (m, 4H), 4.34 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 161.4 (d, J = 243 Hz), 138.0, 137.2, 135.6 (d, J =
3.2 Hz), 133.6, 131.1, 130.2 (d, J = 7.8 Hz), 128.4, 128.1, 126.2, 125.8,
125.1, 125.0, 123.5, 123.2, 115.3 (d, J = 21 Hz), 39.4; IR (film) 1508,
1221, 1157, 811, 748 cm−1; EI-MS m/z (relative intensity) 292 (M+,
100), 259 (7), 197 (33), 149 (30), 57 (11); HRMS (ESI) calcd for
C19H14FS [(M + H)+] 293.0795, found 293.0796.
1
mg, 65%); mp 132−133 °C; Rf = 0.58 (petroleum ether); H NMR
(400 MHz, CDCl3) δ 8.62 (dd, J = 8.1, 24.1 Hz, 2H), 7.98 (d, J = 8.1
Hz, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.55−7.47 (m, 5H), 7.21 (d, J = 7.7
Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 4.38 (s, 2H), 1.21 (s, 9H); 13C
NMR (100 MHz, CDCl3) δ 148.9, 137.1, 134.9, 131.8, 131.4, 130.8,
129.9, 128.4, 128.2, 127.8, 126.6, 126.2, 126.1, 125.4, 125.1, 123.1,
122.4, 39.0, 34.4, 31.4; IR (film) 2960, 1513, 1260, 1019, 803, 724
cm−1.
4-(3-Methoxybenzyl)naphtho[1,2-b]thiophene (5p). White pow-
1
der (85 mg, 70%); Rf = 0.40 (petroleum ether/EtOAc = 30:1); H
NMR (400 MHz, CDCl3) δ 8.09 (d, J = 7.6 Hz, 1H), 7.83 (d, J = 7.6
Hz, 1H), 7.52−7.43 (m, 5H), 7.21−7.17 (m, 1H), 6.84−6.73 (m, 3H),
4.35 (s, 2H), 3.72 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.7,
141.6, 137.7, 137.4, 133.6, 131.1, 129.4, 128.4, 128.1, 126.0, 125.7,
125.1, 124.9, 123.4, 123.4, 121.3, 114.8, 111.3, 55.1, 40.2; IR (film)
1599, 1488, 1260, 1048, 778, 749 cm−1; EI-MS m/z (relative intensity)
304 (M+, 100), 272 (14), 258 (6), 197 (18), 152 (7); HRMS (ESI)
calcd for C20H17OS [(M + H)+] 305.0995, found 305.0999.
10-(4-Methoxybenzyl)-2-tert-butylphenanthrene (5q). White
powder (72 mg, 51%); Rf = 0.45 (petroleum ether/EtOAc = 30:1);
1H NMR (400 MHz, CDCl3) δ 8.63−8.60 (m, 2H), 8.02 (s, 1H), 7.78
(d, J = 8.0 Hz, 1H), 7.69−7.66 (m, 1H), 7.59−7.52 (m, 3H), 7.21−
7.19 (m, 2H), 6.83−6.81 (m, 2H), 4.41 (s, 2H), 3.75 (s, 3H), 1.36 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 157.9, 149.1, 135.5, 132.5,
131.6, 131.0, 129.8, 129.8, 128.6, 128.1, 127.4, 126.2, 126.0, 124.4,
122.8, 122.3, 121.0, 113.9, 55.2, 39.1, 35.0, 31.4; IR (film) 1510, 1246,
1037, 826, 748 cm−1; EI-MS m/z (relative intensity) 354 (M+, 100),
339 (41), 297 (12), 231 (45), 170 (8), 121 (21); HRMS (ESI) calcd
for C26H27O [(M + H)+] 355.2056, found 355.2059.
9-(4-Bromobenzyl)phenanthrene (8d). White powder (41 mg,
59%); mp 152−153 °C; Rf = 0.48 (petroleum ether); H NMR (400
1
MHz, CDCl3) δ 8.70 (dd, J = 8.1, 24.1 Hz, 2H), 7.94 (d, J = 8.2 Hz,
1H), 7.82 (d, J = 7.6 Hz, 1H), 7.65−7.53 (m, 5H), 7.38 (d, J = 8.4 Hz,
2H), 7.11 (d, J = 8.4 Hz, 2H), 4.42 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 139.3, 134.1, 131.9, 131.6, 131.1, 130.9, 130.5, 129.9, 128.3,
128.0, 126.7, 126.6, 126.4, 126.3, 124.8, 123.2, 122.5, 120.0, 39.0; IR
(film) 2928, 2851, 2368, 1618, 1486, 1012, 799, 747 cm−1; HRMS
(EI) calcd for C21H16Br [(M + H)+] 347.0430, found 347.0436.
9-(3-Bromobenzyl)phenanthrene (8e). Colorless powder (49 mg,
1
70%); mp 121−122 °C; Rf = 0.45 (petroleum ether); H NMR (400
MHz, CDCl3) δ 8.70 (dd, J = 8.2, 23.6 Hz, 2H), 7.94 (d, J = 7.6 Hz,
1H), 7.83 (d, J = 7.6 Hz, 1H), 7.65−7.53 (m, 5H), 7.40 (s, 1H), 7.33
(d, J = 7.3 Hz, 1H), 7.16−7.10 (m, 2H), 4.44 (s, 2H); 13C NMR (100
MHz, CDCl3) δ 142.7, 133.8, 131.7, 131.1, 130.9, 130.0, 129.4, 128.3,
128.2, 127.4, 126.7, 126.4, 126.3, 124.8, 123.2, 122.7, 122.5, 39.3; IR
(film) 2965, 1591, 1474, 1260, 1071, 798 cm−1; HRMS (EI) calcd for
C21H16Br [(M + H)+] 347.0430, found 347.0432.
9-(4-Chlorobenzyl)phenanthrene (8f). White powder (39 mg,
1
65%); mp 159−160 °C; Rf = 0.44 (petroleum ether); H NMR (400
10-(4-Methoxybenzyl)-2-chlorophenanthrene (5r). White powder
1
MHz, CDCl3) δ 8.70 (dd, J = 8.2, 24.4 Hz, 2H), 7.95 (d, J = 8.1 Hz,
1H), 7.82 (d, J = 7.5 Hz, 1H), 7.65−7.53 (m, 5H), 7.24 (d, J = 8.3 Hz,
2H), 7.16 (d, J = 8.3 Hz, 2H), 4.44 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 138.8, 134.2, 131.9, 131.7, 131.1, 130.9, 130.1, 128.7, 128.3,
128.0, 126.7, 126.6, 126.4, 126.3, 124.9, 123.2, 122.5, 39.0; IR (film)
2958, 2923, 2851, 2329, 1490, 1259, 702 cm−1; HRMS (EI) calcd for
C21H16Cl [(M + H)+] 303.0935, found 303.0942.
(54 mg, 41%); Rf = 0.45 (petroleum ether/EtOAc = 30:1); H NMR
(400 MHz, CDCl3) δ 8.61 (d, 1H, J = 8.8 Hz), 8.57 (d, 1H, J = 8.4
Hz), 8.00 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.63−7.50 (m, 4H), 7.16−
7.14 (m, 2H), 6.85−6.83 (m, 2H), 4.45 (s, 2H), 3.78 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 158.1, 134.3, 132.6, 132.6, 131.7, 131.5,
129.8, 129.4, 129.1, 128.7, 128.4, 126.6, 124.7, 124.3, 122.3, 114.0,
55.2, 38.4; IR (film) 2922, 1511, 1036, 821, 748 cm−1; EI-MS m/z
(relative intensity) 334 (M+, 37Cl, 38), 332 (M+, 35Cl, 100), 297 (18),
265 (19), 252 (14), 148 (10), 121 (23), 71 (30), 43 (40); HRMS
(ESI) calcd for C22H17ClNaO [(M + Na)+] 355.0860, found 355.0864.
Typical Procedure for the CuI-Catalyzed Reaction of
Terminal Alkynes 3a−e and N-Tosylhydrazones 6 and 7a−s.
Under a nitrogen atmosphere, alkyne 3a (35.6 mg, 0.2 mmol) was
9-(4-Fluorobenzyl)phenanthrene (8g). White powder (38.5 mg,
67%); mp 153−154 °C; Rf = 0.35 (petroleum ether/EtOAc = 100:1);
1H NMR (400 MHz, CDCl3) δ 8.70 (dd, J = 8.2, 24.9 Hz, 2H), 7.98
(d, J = 8.1 Hz, 1H), 7.81 (dd, J = 1.1, 7.8 Hz, 1H), 7.65−7.52 (m, 5H),
7.21−7.17 (m, 2H), 6.96 (t, J = 8.7 Hz, 2H), 4.44 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 162.6, 160.2, 135.9, 135.8, 134.6, 131.7, 131.2,
H
dx.doi.org/10.1021/jo501489c | J. Org. Chem. XXXX, XXX, XXX−XXX

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130.8, 130.1, 130.0, 129.9, 128.3, 127.9, 126.7, 126.6, 126.3, 124.9,
123.2, 122.5, 115.4, 115.2, 38.8; IR (film) 3024, 2923, 2850, 2358,
1602, 1508, 1218, 1014, 743, 661 cm−1; HRMS (EI) calcd for C21H16F
[(M + H)+] 287.1231, found 287.1235.
1461, 1205, 1155, 1067, 747 cm−1; HRMS (EI) calcd for C23H21O2
[(M + H)+] 329.1536, found 329.1538.
9-(2-Chloro-4-(trifluoromethyl)benzyl)phenanthrene (8o). White
powder (51 mg, 69%); mp 119−120 °C; Rf = 0.45 (petroleum ether/
EtOAc = 60:1); 1H NMR (400 MHz, CDCl3) δ 8.72 (dd, J = 8.2, 27.9
Hz, 2H), 7.89 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 7.7 Hz, 1H), 7.69−7.63
(m, 2H), 7.60−7.57 (m, 3H), 7.46 (d, J = 8.3 Hz, 1H), 7.40 (s, 1H),
7.27 (s, 1H), 4.59 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 139.0,
138.0, 132.3, 131.6, 130.9, 130.8, 130.1, 130.0, 128.4, 127.9, 127.5,
127.4, 126.9, 126.8, 126.6, 124.7, 124.6, 124.3, 123.3, 122.5, 36.8; IR
(film) 2928, 2856, 2333, 1612, 1332, 1170, 1083, 742 cm−1; HRMS
(EI) calcd for C22H15ClF3 [(M + H)+] 371.0809, found 371.0808.
9-(2-(Allyloxy)benzyl)phenanthrene (8p). White waxy liquid (45
mg, 70%); Rf = 0.43 (petroleum ether/EtOAc = 60:1); 1H NMR (400
MHz, CDCl3) δ 8.70 (dd, J = 8.1, 23.4 Hz, 2H), 8.05 (d, J = 8.1 Hz,
1H), 7.79 (d, J = 7.6 Hz, 1H), 7.64−7.52 (m, 5H), 7.19−7.15 (m,
1H), 6.92 (d, J = 8.8 Hz, 2H), 6.78 (dd, J = 5.8, 13.4 Hz, 1H), 6.13−
6.03 (m, 1H), 5.44 (dd, J = 1.5, 17.3 Hz, 1H), 5.26 (dd, J = 1.4, 10.5
Hz, 1H), 4.64 (d, J = 5.0 Hz, 2H), 4.50 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 156.1, 134.8, 133.5, 131.9, 131.6, 130.7, 130.1, 129.0, 128.2,
127.7, 127.2, 126.5, 126.1, 126.0, 125.1, 123.0, 122.4, 120.7, 117.1,
111.5, 68.8, 33.1; IR (film) 3033, 2962, 2927, 1726, 1560, 1490, 1451,
1260, 1019, 746 cm−1; HRMS (EI) calcd for C24H21O [(M + H)+]
325.1587, found 325.1595.
5-(Phenanthren-9-ylmethyl)benzo[d][1,3]dioxole (8q). Pale-white
solid (39 mg, 63%); mp 127−129 °C; Rf = 0.42 (petroleum ether/
EtOAc = 60:1); 1H NMR (400 MHz, CDCl3) δ 8.69 (dd, J = 8.1, 23.9
Hz, 2H), 8.02 (d, J = 8.1 Hz, 1H), 7.82 (d, J = 7.4 Hz, 1H), 7.64−7.54
(m, 5H), 7.35−7.12 (m, 3H), 5.89 (s, 2H), 4.39 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 147.7, 145.9, 134.8, 134.1, 131.7, 131.3, 130.8,
129.9 128.8, 128.2, 127.8, 126.6, 126.5, 126.2, 124.9, 123.1, 122.5,
121.6, 109.2, 108.2, 100.8, 39.3; IR (film) 2926, 2855, 2322, 1727,
1502, 1259, 1039, 799 cm−1; HRMS (EI) calcd for C22H17O2 [(M +
H)+] 313.1223, found 313.1228.
9-(4-Cyanobenzyl)phenanthrene (8h). White solid (36 mg, 61%);
1
mp 164−165 °C; Rf = 0.45 (petroleum ether/EtOAc = 30:1); H
NMR (400 MHz, CDCl3) δ 8.71 (dd, J = 8.2, 25.1 Hz, 2H), 7.85 (dd, J
= 7.8, 12.2 Hz, 2H), 7.68−7.52 (m, 7H), 7.33 (d, J = 8.3 Hz, 2H), 4.53
(s, 2H); 13C NMR (100 MHz, CDCl3) δ 146.1, 133.0, 132.3, 131.5,
130.9, 130.8, 130.1, 129.4, 128.4, 128.3, 126.9, 126.8, 126.7, 126.5,
124.7, 123.3, 122.5, 118.9, 110.2, 39.7; IR (film) 2960, 2925, 2854,
2227, 1606, 1260, 1020, 800 cm−1; HRMS (EI) calcd for C22H15NNa
[(M + Na)+] 316.1097, found 316.1103.
9-(4-Methoxybenzyl)phenanthrene (8i). Pale-white powder (42.5
1
mg, 71%); mp 114−115 °C; Rf = 0.32 (hexane/EtOAc = 19:1); H
NMR (400 MHz, CDCl3) δ 8.61 (dd, J = 8.1, 24.2 Hz, 2H), 7.96 (d, J
= 7.8 Hz, 1H), 7.73 (d, J = 7.5 Hz, 1H), 7.57−7.45 (m, 5H), 7.10 (dd,
J = 8.7, 14.8 Hz, 2H), 6.71 (dd, J = 8.7, 23.0 Hz, 2H), 4.34 (s, 2H),
3.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.0, 135.2, 132.2,
131.8, 131.4, 130.8, 130.0, 129.7, 128.2, 127.7, 126.6, 126.5, 126.2,
126.1, 125.0, 123.1, 122.4, 113.9, 55.2, 38.7; IR (film) 3027, 1603,
1410, 1261, 798, 695, 667 cm−1; HRMS (EI) calcd for C22H19O [(M +
H)+] 299.1430, found 299.1432.
9-(4-(Trifluoromethyl)benzyl)phenanthrene (8j). White powder
(54 mg, 80%); mp 126−127 °C; Rf = 0.48 (petroleum ether/EtOAc =
60:1); 1H NMR (400 MHz, CDCl3) δ 8.63 (dd, J = 8.2, 24.6 Hz, 2H),
7.85 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 7.6 Hz, 1H), 7.58−7.43 (m, 7H),
7.28−7.17 (m, 2H), 4.45 (s, 2H); 13C NMR (100 MHz, CDCl3) δ
144.47, 133.64, 131.6, 131.0, 130.9, 130.0, 129.0, 128.3, 128.2, 126.8,
126.7, 126.5, 126.4, 125.4 (q, J = 3.8 Hz, CF3), 124.8, 123.2, 122.5,
39.4; IR (film) 2961, 2926, 2322, 1616, 1326 cm−1; HRMS (EI) calcd
for C22H16F3 [(M + H)+] 337.1199, found 337.1203.
9-(3-Nitrobenzyl)phenanthrene (8k). Pale-white solid (30 mg,
48%); mp 103−104 °C; Rf = 0.30 (EtOAc/petroleum ether = 30:1);
1H NMR (400 MHz, CDCl3) δ 8.71 (dd, J = 8.2, 25.5 Hz, 2H), 8.15
(s, 1H), 8.06 (d, J = 8.1 Hz, 1H), 7.87 (dd, J = 7.9, 25.3 Hz, 2H),
7.68−7.53 (m, 6H), 7.41 (t, J = 7.9 Hz, 1H), 4.57 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 148.5, 142.5, 133.8, 133.0, 131.5, 130.8, 130.1,
129.4, 128.5, 128.3, 126.9, 126.8, 126.7, 126.6, 124.6, 123.5, 123.4,
122.5, 121.5, 39.3; IR (film) 2960, 2923, 2854, 1528, 1348, 1260, 1017,
799 cm−1; HRMS (EI) calcd for C21H16NO2 [(M + H)+] 314.1176,
found 314.1181.
2-(Phenanthren-9-ylmethyl)thiophene (8r). Pale-yellow solid (29
1
mg, 54%); mp 134−135 °C; Rf = 0.48 (petroleum ether); H NMR
(400 MHz, CDCl3) δ 8.70 (dd, J = 8.3, 25.3 Hz, 2H), 8.09 (d, J = 8.1
Hz, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.67−7.56 (m, 4H), 7.25 (s, 1H),
7.14 (dd, J = 1.1, 5.1 Hz, 1H), 6.91 (dd, J = 3.5, 5.1 Hz, 1H), 6.82−
6.81 (m, 1H), 4.65 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 143.4,
134.3, 131.7, 130.9, 130.8, 130.1, 128.4, 127.5, 126.9, 126.7, 126.4,
126.3, 125.4, 124.7, 123.8, 123.2, 122.5, 34.0; IR (film) 2925, 2854,
1453, 1022, 656 cm−1; HRMS (EI) calcd for C19H15S [(M + H)+]
275.0889, found 275.0895.
N,N-Dimethyl-4-(phenanthren-9-ylmethyl)aniline (8l).24 Pale-red
powder (33 mg, 53%); mp 131−132 °C; Rf = 0.32 (petroleum ether/
EtOAc = 40:1); 1H NMR (400 MHz, CDCl3) δ 8.69 (dd, J = 8.1, 23.4
Hz, 2H), 8.08 (d, J = 8.1 Hz, 1H), 7.81 (dd, J = 1.1, 7.8 Hz, 1H),
7.64−7.53 (m, 5H), 7.24−7.11 (m, 2H), 6.69 (d, J = 8.5 Hz, 2H), 4.40
(s, 2H), 2.90 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 135.6, 131.9,
131.5, 130.7, 129.8, 129.4, 128.2, 127.5, 126.5, 126.1, 126.0, 125.1,
123.0, 122.4, 113.0, 40.8, 38.6; IR (film) 2960, 2922, 2850, 1615, 1520,
1260, 1019, 800 cm−1.
3-(Phenanthren-9-ylmethyl)pyridine (8s). Pale-green powder (39
mg, 72%); mp 125−126 °C; Rf = 0.30 (petroleum ether/EtOAc =
1:1); 1H NMR (400 MHz, CDCl3) δ 8.70 (dd, J = 8.2, 26.3 Hz, 2H),
8.64 (s, 1H), 8.47 (d, J = 4.1 Hz, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.81
(d, J = 7.9 Hz, 1H), 7.66−7.56 (m, 4H), 7.54 (s, 1H), 7.46 (d, J = 7.8
Hz, 1H), 7.16 (dd, J = 4.9, 7.7 Hz, 1H), 4.47 (s, 2H); 13C NMR (100
MHz, CDCl3) δ 150.2, 147.7, 136.1, 135.7, 133.4, 131.6, 130.9, 130.0,
128.3, 128.1, 126.8, 126.5, 126.4, 124.7, 123.4, 123.2, 122.5, 36.7; IR
(film) 2925, 1725, 1422, 1260, 1026, 749 cm−1; HRMS (EI) calcd for
C20H16N [(M + H)+] 270.1277, found 270.1280.
9-(3,4-Dichlorobenzyl)phenanthrene (8m). White powder (44.5
mg, 66%); mp 141−142 °C; Rf = 0.42 (petroleum ether/EtOAc =
1
100:1); H NMR (400 MHz, CDCl3) δ 8.70 (dd, J = 8.2, 24.1 Hz,
10-Benzyl-2-(tert-butyl)phenanthrene (9a). White powder (40
mg, 62%); mp 101−102 °C; Rf = 0.44 (petroleum ether/EtOAc =
100:1); 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 1.9 Hz, 1H), 8.70
(d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.79 (dd, J = 0.9, 7.8 Hz,
1H), 7.63−7.53 (m, 3H), 7.49 (s, 1H), 7.27−7.23 (m, 4H), 4.46 (s,
2H), 1.47 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 148.9, 140.4,
134.5, 132.0, 130.5, 130.1, 129.3, 128.8, 128.5, 128.3, 127.8, 127.2,
126.4, 126.1, 126.0, 124.9, 124.7, 122.3, 118.8, 39.6, 35.1, 31.5; IR
(film) 3026, 2962, 1602, 1494, 1260, 1028, 802, 699 cm−1; HRMS
(EI) calcd for C25H25 [(M + H)+] 325.1951, found 325.1958.
10-(4-Bromobenzyl)-2-(tert-butyl)phenanthrene (9b). White pow-
der (53 mg, 66%); mp 122−123 °C; Rf = 0.44 (petroleum ether/
EtOAc = 100:1); 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 10.0 Hz,
2H), 7.88 (8, J = 8.7 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.64−7.54 (m,
3H), 7.48 (s, 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.11 (d, J = 8.3 Hz, 2H),
4.39 (s, 2H), 1.47 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 149.1,
2H), 7.89 (d, J = 7.8 Hz, 1H), 7.83 (dd, J = 1.0, 7.8 Hz, 1H), 7.66−
7.53 (m, 5H), 7.32−7.24 (m, 2H), 7.05 (dd, J = 1.9, 8.2 Hz, 1H), 4.41
(s, 2H); 13C NMR (100 MHz, CDCl3) δ 140.6, 133.4, 132.5, 131.6,
130.9, 130.8, 130.5, 130.4, 130.2, 130.1, 128.3, 128.2, 128.1, 126.8,
126.7, 126.6, 126.5, 124.7, 123.3, 122.5, 38.8; IR (film) 2963, 2927,
2356, 1452, 1325, 1260, 1029, 727 cm−1; HRMS (EI) calcd for
C21H15Cl2 [(M + H)+] 337.0545, found 337.0550.
9-(3,5-Dimethoxybenzyl)phenanthrene (8n). Brown powder (39
mg, 60%); mp 108−109 °C; Rf = 0.35 (petroleum ether/EtOAc =
30:1); 1H NMR (400 MHz, CDCl3) δ 8.69 (dd, J = 8.1, 22.4 Hz, 2H),
8.03 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 7.5 Hz, 1H), 7.64−7.24 (m, 5H),
6.42 (d, J = 2.1 Hz, 2H), 6.32 (t, J = 2.1 Hz, 1H), 4.41 (s, 2H), 3.71 (s,
6H); 13C NMR (100 MHz, CDCl3) δ 160.9, 142.7, 134.4, 131.8,
131.4, 130.8, 130.0, 128.3, 127.9, 126.6, 126.5, 126.2, 125.0, 123.1,
122.4, 107.1, 98.0, 55.2, 39.9; IR (film) 2958, 2927, 2851, 1723, 1595,
I
dx.doi.org/10.1021/jo501489c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
139.4, 133.9, 131.9, 131.5, 130.5, 130.1, 129.0, 128.3, 127.3, 126.5,
126.2, 125.0, 124.6, 122.4, 119.9, 118.9, 39.0, 35.1, 31.5; IR (film)
2959, 1605, 1486, 1260, 790, 697 cm−1; HRMS (EI) calcd for
C25H24Br [(M + H)+] 403.1056, found 403.1066.
(10-(3,4-Dichlorobenzyl)phenanthren-3-yl)(methyl)sulfane (9i).
Pale-white solid (57.5 mg, 75%); mp 107−108 °C; Rf = 0.37
1
(petroleum ether/EtOAc = 60:1); H NMR (400 MHz, CDCl3) δ
8.62 (d, J = 8.1 Hz, 1H), 8.54 (d, J = 1.8 Hz, 1H), 7.82 (d, J = 7.5 Hz,
1H), 7.79 (d, J = 8.7 Hz, 1H), 7.65−7.57 (m, 2H), 7.48 (s, 1H), 7.44
(dd, J = 1.9, 8.6 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H), 7.03 (dd, J = 2.0,
8.2 Hz, 1H), 4.37 (s, 2H), 2.63 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 140.6, 137.0, 133.1, 132.5, 132.0, 131.4, 130.5, 130.4, 129.2, 128.5,
128.3, 128.0, 127.6, 127.1, 126.5, 125.7, 125.2, 122.5, 120.3, 38.7, 16.0;
IR (film) 2961, 2927, 2862, 2368, 1724, 1598, 1470, 1260, 1031, 658
cm−1; HRMS (EI) calcd for C22H17Cl2S [(M + H)+] 383.0423, found
383.0424.
2-(tert-Butyl)-10-(3,4-dichlorobenzyl)phenanthrene (9c). White
powder (47 mg, 60%); mp 99−100 °C; Rf = 0.43 (petroleum ether/
1
EtOAc = 19:1); H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 10.3 Hz,
2H), 7.82 (t, J = 7.1 Hz, 2H), 7.65−7.55 (m, 3H), 7.49 (s, 1H), 7.32
(dd, J = 4.8, 7.3 Hz, 2H), 7.06 (dd, J = 1.3, 8.2 Hz, 1H), 4.39 (s, 2H),
1.47 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 149.2, 140.8, 133.2,
132.4, 131.8, 130.6, 130.5, 130.3, 130.2, 130.1, 128.8, 128.3, 128.1,
127.5, 126.6, 126.3, 125.1, 124.5, 122.4, 118.9, 38.8, 35.1, 31.5; IR
(film) 2962, 1725, 1471, 1260, 1029, 800, 748 cm−1; HRMS (EI) calcd
for C25H23Cl2 [(M + H)+] 393.1171, found 393.1176.
10-Benzyl-3-methoxyphenanthrene (9d). White powder (42 mg,
70%); mp 109−110 °C; Rf = 0.40 (petroleum ether/EtOAc = 60:1);
1H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 7.9 Hz, 1H), 8.09 (d, J =
2.5 Hz, 1H), 7.93 (d, J = 9.0 Hz, 1H), 7.79 (dd, J = 1.4, 7.7 Hz, 1H),
7.57 (dp, J = 1.5, 7.0 Hz, 2H), 7.42 (s, 1H), 7.28−7.22 (m, 4H), 7.18
(dt, J = 2.1, 9.2 Hz, 2H), 4.45 (s, 2H), 3.99 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 158.0, 140.4, 134.6, 132.3, 129.4, 128.7, 128.5, 128.3,
126.7, 126.6, 126.1, 126.0, 125.8, 125.7, 122.5, 116.3, 104.6, 55.4, 39.7;
IR (film) 2961, 2927, 2853, 2350, 1727, 1618, 1453, 1230, 1030, 799,
748, 663 cm−1; HRMS (EI) calcd for C22H19O [(M + H)+] 299.1430,
found 299.1431.
10-Benzylphenanthrene-2-carbonitrile (9j). Reddish powder (34.5
mg, 59%); mp 117−118 °C; Rf = 0.32 (petroleum ether/EtOAc =
1
30:1); H NMR (400 MHz, CDCl3) δ 8.77 (d, J = 8.6 Hz, 1H), 8.64
(d, J = 9.1 Hz, 1H), 8.36 (d, J = 1.3 Hz, 1H), 7.85 (dd, J = 2.1, 7.1 Hz,
1H), 7.80 (dd, J = 1.5, 8.6 Hz, 1H), 7.71−7.67 (m, 2H), 7.64 (s, 1H),
7.30 (d, J = 6.8 Hz, 2H), 7.25−7.22 (m, 3H), 4.47 (s, 2H); 13C NMR
(100 MHz, CDCl3) δ 139.2, 134.1, 133.5, 132.7, 131.0, 130.2, 129.7,
128.9, 128.8, 128.7, 128.6, 128.5, 128.4, 128.2, 127.7, 127.1, 126.6,
124.2, 123.0, 119.4, 109.9, 39.3; IR (film) 2961, 2924, 2852, 2227,
2343, 1725, 1259, 1018, 730, 705 cm−1; HRMS (EI) calcd for
C22H16N [(M + H)+] 294.1277, found 294.1280.
Typical Procedure for Scale-Up Experiments. Under a
nitrogen atmosphere, alkyne 3a (890 mg, 5 mmol) was added to a
mixture of CuI (142.5 mg, 0.75 mmol), 3,4,7,8-tetramethyl-1,10-
phenanthroline (354 mg, 1.5 mmol), LiOtBu (1.8 g, 22.5 mmol), and
N-tosylhydrazone 6 (3.43 g, 12.5 mmol) in dioxane (30 mL). The
solution was stirred at 120 °C for 24 h. Upon completion of the
reaction, the reaction mixture was cooled to room temperature and
filtered through a short silica gel column, eluting with EtOAc. The
solvent was removed in vacuum to leave a crude mixture, which was
purified by silica gel column chromatography using petroleum ether as
an eluting solvent to afford pure 9-benzylphenanthrene (5a) as white
solid powder (735 mg, 55% based on 3a).
Typical Procedure for the One-Pot Reaction. 4-Trifluorome-
thylbenzaldehyde (87 mg, 0.5 mmol) and 4-methylbenzenesulfonohy-
drazide (TsNHNH2) (93 mg, 0.5 mmol) were suspended in dioxane
(1.5 mL) in a 10 mL microwave tube, and the resulting suspension was
stirred at 60 °C for 30 min. Upon completion of the reaction (as
monitored by TLC), CuI (5.7 mg, 0.03 mmol), 3,4,7,8-tetramethyl-
1,10-phenanthroline (14.2 mg, 0.06 mmol), and LiOtBu (96 mg, 1.2
mmol) were added under nitrogen. Then alkyne 3a (35.6 mg, 0.2
mmol) was added. The resulting mixture was stirred at 120 °C for 24
h. After cooling to room temperature, the mixture was filtered through
a short silica gel column, eluting with EtOAc. The solvent was
removed under vacuum, and the crude residue was purified by column
chromatography on silica gel, eluting with PE/EtOAc (60:1), to afford
pure 9-(4-(trifluoromethyl)benzyl)phenanthrene (8j) as a white
powder (50 mg, 74% based on 3a).
10-(4-Bromobenzyl)-3-methoxyphenanthrene (9e). Pale-yellow
powder (56 mg, 74%); mp 138−139 °C; Rf = 0.41 (petroleum
ether/EtOAc = 60:1); 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 6.6
Hz, 1H), 8.08 (d, J = 2.5 Hz, 1H), 7.84 (d, J = 9.0 Hz, 1H), 7.79 (dd, J
= 1.3, 7.7 Hz, 1H), 7.62−7.54 (m, 2H), 7.39−7.23 (m, 3H), 7.16 (dd,
J = 2.6, 9.0 Hz, 1H), 7.08 (d, J = 8.4 Hz, 2H), 4.36 (s, 2H), 3.98 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 158.1, 139.4, 133.9, 133.2,
132.6, 132.4, 132.2, 131.5, 130.4, 129.5, 128.3, 126.8, 126.4, 126.0,
125.8, 125.7, 122.5, 120.0, 116.4, 104.7, 55.4, 39.1; IR (film, cm−1)
2917, 2850, 2229, 1722, 1618, 1486, 1230, 1070, 1011, 748; HRMS
(EI) calcd for C22H18BrO [(M + H)+] 377.0536, found 377.0542.
10-(3,4-Dichlorobenzyl)-3-methoxyphenanthrene (9f). White
powder (53 mg, 72%); mp 99−100 °C; Rf = 0.40 (petroleum ether/
1
EtOAc = 19:1); H NMR (400 MHz, CDCl3) δ 8.58 (d, J = 7.9 Hz,
1H), 8.09 (d, J = 2.5 Hz, 1H), 7.82−7.78 (m, 2H), 7.63−7.56 (m,
2H), 7.40 (s, 1H), 7.30 (dd, J = 3.2, 5.0 Hz, 2H), 7.18 (dd, J = 2.5, 9.0
Hz, 1H), 7.03 (dd, J = 1.8, 8.3 Hz, 1H), 4.36 (s, 2H), 3.99 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 158.2, 140.7, 133.2, 132.4, 132.1, 130.5,
130.3, 130.1, 129.6, 128.3, 128.0, 126.9, 126.2, 126.1, 126.0, 125.5,
122.4, 116.5, 104.8, 55.4, 38.8; IR (film) 2962, 2926, 1726, 1618, 1470,
1230, 1030, 803, 734, 700, 662 cm−1; HRMS (EI) calcd for
C22H17Cl2O [(M + H)+] 367.0651, found 367.0650.
(10-Benzylphenanthren-3-yl)(methyl)sulfane (9g). White solid
(50 mg, 80%); mp 80−81 °C; Rf = 0.38 (petroleum ether/EtOAc =
1
60:1); H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 8.0 Hz, 1H), 8.53
(d, J = 1.7 Hz, 1H), 7.91 (d, J = 8.7 Hz, 1H), 7.79 (d, J = 7.4 Hz, 1H),
7.62−7.54 (m, 2H), 7.49 (s, 1H), 7.42 (dd, J = 1.9, 8.7 Hz, 1H), 7.28−
7.19 (m, 5H), 4.43 (s, 2H), 2.61 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 140.2, 136.5, 134.5, 132.2, 131.3, 129.1, 129.0, 128.7, 128.5,
128.3, 127.3, 126.9, 126.2, 126.1, 125.6, 125.5, 122.4, 120.3, 39.5, 16.1;
IR (film) 2961, 2923, 1725, 1599, 1494, 1260, 1018, 800, 699 cm−1;
HRMS (EI) calcd for C22H19S [(M + H)+] 315.1202, found 315.1209.
(10-(3-Bromobenzyl)phenanthren-3-yl)(methyl)sulfane (9h).
Pale-white solid (48 mg, 61%); mp 105−106 °C; Rf = 0.38 (petroleum
ether/EtOAc = 60:1); 1H NMR (400 MHz, CDCl3) δ 8.61 (d, J = 8.0
Hz, 1H), 8.54 (d, J = 1.7 Hz, 1H), 7.82 (dd, J = 5.1, 12.9 Hz, 2H),
7.64−7.56 (m, 2H), 7.49 (s, 1H), 7.44 (dd, J = 1.9, 8.6 Hz, 1H), 7.38
(s, 1H), 7.34−7.31 (m, 1H), 7.12 (d, J = 5.7 Hz, 2H), 4.40 (s, 2H),
2.63 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 142.6, 136.8, 133.6,
132.1, 131.6, 131.4, 130.0, 129.4, 129.2, 128.7, 128.3, 127.6, 127.3,
127.0, 126.4, 125.7, 125.3, 122.7, 122.4, 120.3, 39.2, 16.1; IR (film)
2960, 2924, 2851, 2350, 2226, 1732, 1598, 1260, 1017, 823 cm−1;
HRMS (EI) calcd for C22H18BrS [(M + H)+] 393.0307, found
393.0308.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H and 13C spectra for all products and the X-ray
structure and crystallographic data (CIF) for 9g. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: wangjb@pku.edu.cn.
Author Contributions
§M.L.H. and F.Y. contributed equally to this work.
Notes
The authors declare no competing financial interest.
J
dx.doi.org/10.1021/jo501489c | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(k) Yao, T.; Campo, M. A.; Larock, R. C. J. Org. Chem. 2005, 70,
ACKNOWLEDGMENTS
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3511−3517. (l) Mamane, V.; Hannen, P.; Furstner, A. Chem.Eur. J.
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The project was supported by National Basic Research Program
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Natural Science Foundation of China (Grants 21332002 and
21272010).
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