Heteroatom as a promotor: Synthesis of polyfunctionalized benzenes and naphthalenes

Article abstract of DOI:10.1021/jo2004555

Construction of a new benzene via the electrocyclization of diene-allene is an efficient protocol to access polysubstituted benzenes from simple, readily available starting materials. In this paper, we present a comprehensive study of a heteroatom-promote

Full text of DOI:10.1021/jo2004555

ARTICLE
pubs.acs.org/joc
Heteroatom as a Promotor: Synthesis of Polyfunctionalized
Benzenes and Naphthalenes
Hongwei Zhou,* Yanpeng Xing, Jinzhong Yao, and Yun Lu
Department of Chemistry, Zhejiang University (Campus Xixi), Hangzhou 310007, PR China
S Supporting Information
b
ABSTRACT: Construction of a new benzene via the electro-
cyclization of dieneÀallene is an efficient protocol to access
polysubstituted benzenes from simple, readily available starting
materials. In this paper, we present a comprehensive study of a
heteroatom-promoted propargylÀallenyl isomerization and
electrocyclization for the facile and efficient synthesis of poly-
functionalized benzenes and naphthalenes. As a result of the
readily accessible starting materials, simple operation, and mild conditions, this reaction should be an appealing strategy in organic
synthesis.
Scheme 1. Synthesis of the Substrates
’ INTRODUCTION
The benzenoid aromatic compounds are arguably the most
ubiquitous class in nature and the laboratory. Generally, there
are only two ways to prepare them: direct functionalization to
benzene or construction of a new benzene. Direct functionali-
zation to benzene, because of the effect of the substituent(s),
might encounter difficulty in some cases. Thus, construction
of a new benzene remains an efficient protocol to access
polysubstituted benzenes from simple, readily available starting
materials.
The 6π-electrocyclization could offer the skeleton of a ben-
zene ring, and the electrocyclization of dieneÀallenes could
construct a benzene ring due to the unstable properties of the
cyclization product isotoluene.1À3 However, building suitable
dieneÀallenes may become the main challenge for developing
facile and efficient synthetic methods. A good solution is
propargylÀallenyl isomerization, which means only readily avail-
able propargyl dienes are used as the substrates (Scheme 1).
In a preliminary communication, we reported sulfur-assisted
propargylÀallenyl isomerizations and electrocyclizations for the
synthesis of polyfunctionalized benzenes and naphthalenes.4 On
the basis of our previous understanding of the propargylÀallenyl
isomerization5À12 and the enediyneÀalleneyne isomerization,13À17
we wish to report the full details of heteroatom (O, N, and S)-
promoted propargylÀallenyl isomerization and electrocycliza-
tion, which may offer convenient protocols to various polysub-
stituted benzenes.
Luckily, upon treatment of (2E,4Z)-ethyl 5-phenyl-8-(p-tolyloxy)
octa-2,4-dien-6-ynoate (1a) with 1.2 equiv of DBU in acetonitrile
at 50 °C for 6 h, the expected product, ethyl 3-(p-tolyloxy-
methyl)biphenyl-4-carboxylate (2a), was obtained in 91% yield
(Table 1, entry 1). The amide analogue of 1a, (2E,4Z)-N-methyl-
N,5-diphenyl-8-(p-tolyloxy)octa-2,4-dien-6-ynamide (1b), could
proceed with similar isomerization and electrocyclization to give
N-methyl-N-phenyl-3-(p-tolyloxymethyl)biphenyl-4-carboxamide
(2b) in 77% yield (entry 2). Notably, the electron-withdrawing
groups (ester, acyl, or amide group) of 1, which could increase
the acidity of the methylene group adjacent to the oxygen atom
and shorten the reaction time, can be replaced by a phenyl group,
although the result is rather sluggish (entry 6).
The result from the entry 6 of Table 1 showed that the
electron-withdrawing groups in substrates are as essential as we
thought in the preliminary communication.4 Without the elec-
tron-withdrawing group, the propargylÀallenyl isomerization
and electrocyclization might still be possible in the presence of
DBU with the assistance of heating. Treatment of (Z)-phenyl
(4-phenylhepta-4,6-dien-2-ynyl)sulfane (3a) in acetonitrile at
65 °C for 6 h gave (biphenyl-3-ylmethyl)(phenyl)sulfane (4a)
in 82% yield (Table 2, entry 1), and a series of thioprop-1-ynyl
dienes offered satisfactory results (Table 2).
’ RESULTS AND DISCUSSION
Reasonably, the oxygen-promoted propargylÀallenyl isomer-
izations and electrocyclizations were first investigated. The
difference between sulfur and oxygen is that the latter could
increase the acidity of the adjacent methylene group less than the
former. Thus, we chose DBU as the base instead of triethylamine.
Received: March 5, 2011
Published: May 11, 2011
r
2011 American Chemical Society
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Table 1. Oxygen-Promoted Propargyl-Allenyl Isomerization and Electrocyclization a
a Substrate 1a (0.5 mmol) and base (1.0 mmol) in acetonitrile (3 mL) under a N2 atmosphere.
Scheme 2. Oxidation and Pyrolytic Elimination of 4m
6-dien-2-ynyl)-N-p-tolylacetamide (5b) as the substrate. Fortunately,
we obtained N-(biphenyl-3-ylmethyl)-N-p-tolylacetamide (6b) in
good yield (entry 2). It is noteworthy that the introduction of the
electron-withdrawinggroup onthe nitrogen not only improves the
reaction itself but also affords a useful way to get functionalized
amine derivatives (Table 3).
As mentioned, the heteroatoms, which triggered the propargylÀ
allenyl isomerization in the substrates, are also a very useful part
of the products prepared by the above protocols and could be
used as a convenient chemical handle for preparing other
compounds. We treated 4m with NaIO4 in aqueous methanol
then heated it in toluene at 110 °C for an oxidation/pyrolytic
elimination, and 4-phenyl-2-vinylbiphenyl (7) was isolated in
62% yield (Scheme 2).
We treated 6j in HCl/MeOH at 110 °C and obtained
2-(4-chlorophenyl)-5-phenylisoindolin-1-one (8) in almost
quantitative yield (Scheme 3). Isoindolin-1-one derivatives,
which exhibit a variety of biological activities, are known as an
important class applied widely in pharmaceutical fields.18À20
Then our attention was diverted to nitrogen. Amines might
provide more choices for the functionalization of the products
than ethers or sulfanes. We chose (2E,4Z)-ethyl 8-(methyl-
(phenyl)amino)-5-phenylocta-2,4-dien-6-ynoate (5a) as the start-
ing material and obtained ethyl 3-((methyl(phenyl)amino)-
methyl)biphenyl-4-carboxylate (6a) in 78% yield after heating for
6 h (Table 3, entry 1). However, we recovered just the starting
material if the ester group was replaced by hydrogen or a phenyl
group. For increasing the acidity of the methylene group adjacent
to the nitrogen atom, we introduced an electron-withdrawing
group on the nitrogen and chose (Z)-N-(4-phenylhepta-4,
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Table 2. Sulfur-Promoted PropargylÀAllenyl Isomerization and Electrocyclizationa
a Substrate 3a (0.5 mmol) and base (1.0 mmol) in acetonitrile (3 mL) under a N2 atmosphere.
Scheme 3. Acidolysis and Cyclization of 6j
Scheme 4. Plausible Mechanism
There are two plausible pathways for this reaction: electrocycliza-
tion of dieneÀallenes or electrocyclization of dieneÀalkyne
(Bergman and MyersÀSaito-type cyclization). Thus, we prepared
(2Z,4E)-ethyl 5-phenyltrideca-2,4-dien-6-ynoate (9), which could
be thought of as a C-analogue of 1e for replacing the heteroatom by
carbon, and conducted the reaction under the same conditions.
Only the starting materials were recovered, illustrating that the
heteroatom might play a role in promoting the reaction (Scheme 4).
We then synthesized 3m deuterated on the methenyl group
adjacent to the sulfur atom and conducted the reaction under the
same conditions. The methenyl group of 4m was protonated, and
the deuterium moved to the new benzene ring, demonstrating
that a propargylÀallene isomerization and aromatization of the
intermediate isotoluene occurred (Scheme 5).
’ CONCLUSION
In summary, we have presented here a comprehensive study of
the heteroatom-promoted propargylÀallenyl isomerizations and
electrocyclizations for the facile and efficient synthesis of poly-
functionalized benzenes and naphthalenes. As a result of the
readily accessible starting materials, simple operation, and mild
conditions, this reaction should be an appealing strategy in
organic synthesis. Further studies on the synthetic application
are currently ongoing.
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Table 3. Nitrogen-Promoted PropargylÀAllenyl Isomerization and Electrocyclizationa
a Substrate 5a (0.5 mmol) and base (1.0 mmol) in acetonitrile (3 mL) under a N2 atmosphere.
monitored by TLC until completion (6 h). After evaporation, chroma-
tography on silica gel (hexane/ethyl acetate 40/1) of the reaction
mixture afforded 158 mg of 2a: yield 91%; 1H NMR (400 MHz, CDCl3)
δ 8.14À8.12 (d, J = 8.0 Hz, 1H), 8.04À8.03 (m, 1H), 7.65À7.63 (m,
2H), 7.61À7.59 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 7.49À7.45 (m, 2H),
7.42À7.38 (m, 1H), 7.12À7.10 (d, J = 8.0 Hz, 2H), 6.98À6.95 (m, 2H),
5.55 (s, 2H), 4.43À4.37 (q, J = 7.2 Hz, 2H), 2.31 (s, 3H), 1.43À1.39 (t, J =
7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 167.1, 157.0, 145.4, 140.6,
140.3, 131.6, 130.4, 130.2, 129.1, 128.4, 127.6, 127.0, 126.4, 126.0, 115.1,
68.7, 61.3, 20.8, 14.6; IR (neat, cmÀ1) 2984, 1712, 1509, 1245, 755; HRMS
calcd for C23H22O3 346.1569, found 346.1560.
Scheme 5. Control Experiment
N-Methyl-N-phenyl-3-(p-tolyloxymethyl)biphenyl-4-
carboxamide (2b). To a solution of 0.5 mmol of 1b in 3 mL of
acetonitrile was charged 1 mmol of DBU under a N2 atmosphere at 60 °C.
The reaction was monitored by TLC until completion (12 h). After
evaporation, chromatography on silica gel (hexane/ethyl acetate 7/1) of
1
the reaction mixture afforded 157 mg of 2b: yield 77%; H NMR (500
MHz, DMSO-d6, 80 °C) δ 7.73 (s, 1H), 7.60À7.59 (d, J = 7.5 Hz, 2H),
7.44À7.41(m, 3H), 7.36À7.33(t, J = 7.5 Hz, 1H), 7.30À7.21(m, 5H),
7.16À7.11(m, 3H), 6.95À6.94 (d, J = 9.0 Hz, 2H), 5.21 (s, 2H), 3.36 (s,
3H), 2.25 (s, 3H); 13C NMR (DMSO-d6, 125 MHz, 80 °C) δ 168.5, 156.1,
143.4, 140.0, 138.7, 134.9, 134.7, 129.4, 128.8, 128.5, 128.4, 127.9, 127.3,
’ EXPERIMENTAL SECTION
Ethyl 3-(p-Tolyloxymethyl)biphenyl-4-carboxylate (2a).
To a solution of 0.5 mmol of 1a in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 50 °C. The reaction was
126.3, 126.2, 126.1, 126.0, 124.9, 114.5, 67.5, 37.1, 19.6; IR (neat, cmÀ1
)
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2921, 1638, 1373, 1233, 695; HRMS calcd for C28H 25NO2 407.1885,
found 407.1893.
(t, J = 7.6 Hz, 2H), 7.43À7.40 (m, 1H), 7.13À7.11 (d, J = 8.4 Hz, 2H),
6.97À6.95 (d, J = 8.4 Hz, 2H), 5.49 (s, 2H), 2.68 (s, 3H), 2.32 (s, 3H);
13C NMR (CDCl3, 100 MHz) δ 200.4, 156.6, 145.0, 139.9, 139.8, 133.9,
130.7, 130.2, 129.9, 128.9, 128.2, 127.3, 126.2, 125.5, 114.8, 68.6, 28.8,
20.5; IR (neat, cmÀ1) 2923, 1665, 1508, 1245, 768; HRMS calcd for
C22H20O2 316.1463, found 316.1466.
Ethyl 3-(p-Tolyloxymethyl)-2-naphthoate (2c). To a solu-
tion of 0.5 mmol of 1c in 3 mL of acetonitrile was charged 1 mmol of
DBU under a N2 atmosphere at reflux. The reaction was monitored by
TLC until completion (24 h). After evaporation, chromatography on
silica gel (hexane/ethyl acetate 30/1) of the reaction mixture afforded
93 mg of 2c: yield 58%; 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H),
8.17 (s, 1H), 7.96À7.94 (d, J = 8.0 Hz, 1H), 7.90À7.88 (d, J = 8.0 Hz,
1H), 7.62À7.53 (m, 2H), 7.15À7.13 (d, J = 8.0 Hz, 2H), 7.01À6.99
(d, J = 8.4 Hz, 2H), 5.61 (s, 2H), 4.47À4.42 (q, J = 7.2 Hz, 2H), 2.33
(s, 3H), 1.47À1.43 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
δ 167.4, 157.0, 135.2, 135.1, 132.6, 131.9, 130.4, 130.2, 129.0, 128.6,
Phenyl(3-(p-tolyloxymethyl)biphenyl-4-yl)methanone (2h).
To a solution of 0.5 mmol of 1h in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 50 °C. The reaction was
monitored by TLC until completion (6 h). After evaporation, chroma-
tography on silica gel (hexane/ethyl acetate 20/1) of the reaction
mixture afforded 129 mg of 2h: yield 68%; 1H NMR(400 MHz, CDCl3)
δ 7.98 (s, 1H), 7.87À7.86 (d, J = 7.2 Hz, 2H), 7.68À7.66 (d, J = 7.2 Hz,
2H), 7.62À7.59 (m, 2H), 7.53À7.46 (m, 5H), 7.43À7.39 (m, 1H),
7.04À7.01 (d, J = 8.4 Hz, 2H), 6.77À6.75 (d, J = 8.4 Hz, 2H), 5.28
(s, 2H), 2.26 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 197.5, 156.4,
143.7, 140.1, 138.2, 137.8, 135.9, 133.1, 130.2, 130.2, 129.8, 128.9, 128.4,
128.0, 127.3, 127.1, 125.6, 114.7, 67.8, 20.5; IR (neat, cmÀ1) 2924, 1647,
1510, 1239, 698; HRMS calcd for C27H22O2 378.1620, found 378.1629.
1-(3-(p-Tolyloxymethyl)naphthalen-2-yl)ethanone (2i).
To a solution of 0.5 mmol of 1i in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at reflux. The reaction was
monitored by TLC until completion (24 h). After evaporation, chro-
matography on silica gel (hexane/ethyl acetate 15/1) of the reaction
mixture afforded 80 mg of 2i: yield 55%; 1H NMR (400 MHz, CDCl3)
δ 8.37 (s, 1H), 8.18 (s, 1H), 7.94À7.92 (d, J = 7.6 Hz, 1H), 7.88À7.86
(d, J = 8.0 Hz, 1H), 7.62À7.53 (m, 2H), 7.11À7.09 (d, J = 8.4 Hz, 2H),
6.96À6.94 (d, J = 8.4 Hz, 2H), 5.53 (s, 2H), 2.76 (s, 3H), 2.30 (s, 3H);
13C NMR (CDCl3, 125 MHz) δ 200.8, 156.7, 134.8, 134.6, 134.0, 131.6,
131.5, 130.2, 130.0, 128.7, 128.6, 127.9, 126.9, 126.8, 114.9, 68.8, 28.8,
20.5; IR (neat, cmÀ1) 2923, 1666, 1509, 1267, 748; HRMS calcd for
C20H18O2 290.1307, found 290.1308.
128.1, 127.0, 126.9, 126.6, 115.1, 69.0, 61.4, 20.8, 14.6; IR (neat, cmÀ1
)
2978, 1704, 1512, 1240, 805; HRMS calcd for C21H20O3 320.1412,
found 320.1411.
N-Methyl-N-phenyl-3-(p-tolyloxymethyl)-2-naphthamide
(2d). To a solution of 0.5 mmol of 1d in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at reflux. The reaction was
monitored by TLC until completion (24 h). After evaporation, chro-
matography on silica gel (hexane/ethyl acetate 7/1) of the reaction
mixture afforded 118 mg of 2d: yield 62%; 1H NMR (500 MHz, DMSO-
d6, 80 °C) δ 7.96 (s, 1H), 7.85À7.84 (d, J = 8.5 Hz, 1H), 7.74À7.72
(d, J = 7.5 Hz, 1H), 7.67 (s, 1H), 7.51À7.45 (m, 2H), 7.34À7.32 (d, J =
7.5, 2H), 7.23À7.20 (t, J = 7.8 Hz, 2H), 7.13À7.11 (d, J = 8.0 Hz, 2H),
7.09À7.06 (t, J = 7.5 Hz, 1H), 6.98À6.95 (m, 2H), 5.30 (s, 2H), 3.38 (s,
3H), 2.26 (s, 3H); 13C NMR (DMSO-d6, 125 MHz, 80 °C) δ 168.6,
156.2, 143.7, 133.3, 131.9, 131.8, 131.1, 129.4, 128.8, 128.4, 127.2, 127.2,
127.1, 126.9, 126.6, 126.2, 126.2, 125.9, 114.5, 78.7, 67.8, 19.6; IR
(neat, cmÀ1) 2920, 1665, 1506, 1251, 691; HRMS calcd for C26H 23NO2
381.1729, found 381.1731.
Ethyl 3-(Butoxymethyl)biphenyl-4-carboxylate (2e). To a
solution of 0.5 mmol of 1e in 3 mL of acetonitrile was charged 1 mmol of
DBU under a N2 atmosphere at 60 °C. The reaction was monitored by
TLC until completion (12 h). After evaporation, chromatography on
silica gel (hexane/ethyl acetate 30/1) of the reaction mixture afforded
(3-(Butoxymethyl)biphenyl-4-yl)(phenyl)methanone (2j).
To a solution of 0.5 mmol of 1j in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 60 °C. The reaction was
monitored by TLC until completion (12 h). After evaporation, chro-
matography on silica gel (hexane/ethyl acetate 30/1) of the reaction
mixture afforded 103 mg of 2j: yield 60%; 1H NMR (400 MHz, CDCl3)
δ 7.88À7.85 (m, 2H), 7.82 (b, 1H), 7.68À7.66 (m, 2H), 7.63À7.56 (m,
2H), 7.51À7.45 (m, 5H), 7.43À7.39 (m, 1H), 4.68 (s, 2H), 3.41À3.38
(t, J = 6.6 Hz, 2H), 1.48À1.41 (m, 2H), 1.29À1.22 (m, 2H), 0.84À0.80
(t, J = 7.6 Hz, 3H); 13C NMR (CDCl3, 125 MHz) δ 197.7, 143.3, 140.3,
139.3, 137.8, 136.4, 133.0, 130.1, 129.6, 128.9, 128.3, 127.9, 127.3, 127.1,
125.4, 70.8, 70.5, 31.6, 19.2, 13.9; IR (neat, cmÀ1) 3029, 2927, 1662,
1313, 698; HRMS calcd for C24H24O2 344.1776, found 344.1782.
1-(3-(Butoxymethyl)biphenyl-4-yl)ethanone (2k). To a so-
lution of 0.5 mmol of 1k in 3 mL of acetonitrile was charged 1 mmol of
DBU under a N2 atmosphere at 60 °C. The reaction was monitored by
TLC until completion (12 h). After evaporation, chromatography on
silica gel (hexane/ethyl acetate 20/1) of the reaction mixture afforded 86
1
130 mg of 2e: yield 83%; H NMR (400 MHz, CDCl3) δ 8.06À8.04
(d, J = 8.0 Hz, 1H), 7.97À7.96 (m, 1H), 7.69À7.66 (m, 2H), 7.58À7.56
(dd, J1 = 8.0 Hz, J2 = 2.0 Hz, 1H), 7.51À7.47 (m, 2H), 7.43À7.39
(m, 1H), 4.99 (s, 2H), 4.43À4.38 (q, J = 7.2 Hz, 2H), 3.64À3.61 (t, J =
6.6 Hz, 2H), 1.73À1.66 (m, 2H), 1.50À1.42 (m, 5H), 0.99À0.96 (t, J =
7.4 Hz, 3H); 13C NMR(CDCl3, 100 MHz) δ 166.9, 144.7, 141.8, 140.2,
131.0, 128.8, 127.9, 127.2, 126.9, 126.0, 125.2, 70.8, 70.6, 60.7, 31.8, 19.4,
14.2, 13.9; IR (neat, cmÀ1) 2958, 1711, 1254, 1079, 755; HRMS calcd
for C20H24O3 312.1725, found 312.1717.
4-Phenyl-2-(p-tolyloxymethyl)biphenyl (2f). To a solution of
0.5 mmol of 1f in 3 mL of acetonitrile was charged 1 mmol of DBU under
a N2 atmosphere at reflux. The reaction was monitored by TLC until
completion (24 h). After evaporation, chromatography on silica gel
(hexane/ethyl acetate 60/1) of the reaction mixture afforded 97 mg of
2f: yield 55%; 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.65À7.61
(m, 3H), 7.46À7.38 (m, 7H), 7.36À7.33 (m, 2H), 7.05À7.03 (d, J = 8.0
Hz, 2H), 6.80À6.78 (d, J = 8.4 Hz, 2H), 4.96 (s, 2H), 2.26(s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 156.5, 140.8, 140.6, 140.5, 140.2, 134.7,
130.6, 130.1, 129.8, 129.2, 128.8, 128.3, 128.2, 127.4, 127.3, 127.2, 126.7,
114.8, 68.3, 20.4; IR (neat, cmÀ1) 3029, 2923, 1509, 1233, 697; HRMS
calcd for C26H22O 350.1671, found 350.1676.
1-(3-(p-Tolyloxymethyl)biphenyl-4-yl)ethanone (2g). To a
solution of 0.5 mmol of 1g in 3 mL of acetonitrile was charged 1 mmol of
DBU under a N2 atmosphere at 50 °C. The reaction was monitored by
TLC until completion (6 h). After evaporation, chromatography on
silica gel (hexane/ethyl acetate 15/1) of the reaction mixture afforded
111 mg of 2g: yield 70%; 1H NMR (400 MHz, CDCl3) δ 8.11 (s, 1H),
7.95À7.93 (d, J = 8.0 Hz, 1H), 7.66À7.62 (t, J = 8.4 Hz, 3H), 7.50À7.47
1
mg of 2k: yield 61%; H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H),
7.85À7.83 (d, J = 8.0 Hz, 1H), 7.67À7.65 (d, J = 7.6 Hz, 2H), 7.59À7.57
(dd, J1 = 8.0 Hz, J2 = 2.0 Hz, 1H), 7.50À7.47 (t, J = 7.4 Hz, 2H),
7.43À7.39 (t, J = 7.4 Hz, 1H), 4.89 (s, 2H), 3.61À3.58 (t, J = 6.6 Hz,
2H), 2.64 (s, 3H), 1.71À1.64 (m, 2H), 1.48À1.42 (m, 2H), 0.98À0.94
(t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 125 MHz) δ 200.9, 144.6, 141.0,
140.1, 134.7, 130.2, 128.9, 128.1, 127.3, 126.4, 125.3, 71.0, 31.9, 29.1,
19.5, 14.0; IR (neat, cmÀ1) 2957, 1675, 1253, 1098, 764; HRMS calcd
for C19H22O2 282.1620, found 282.1625.
1-(4-Isopentyl-2-(p-tolyloxymethyl)phenyl)ethanone (2l).
To a solution of 0.5 mmol of 1l in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 60 °C. The reaction was
monitored by TLC until completion (6 h). After evaporation, chroma-
tography on silica gel (hexane/ethyl acetate 25/1) of the reaction
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mixture afforded 120 mg of 2l: yield 77%; 1H NMR (400 MHz, CDCl3)
δ 7.81À7.79 (d, J = 7.6 Hz, 1H), 7.67 (s, 1H), 7.23À7.21 (d, J = 8.0, 1H),
7.12À7.10 (d, J = 8.4 Hz, 2H), 6.95À6.93 (d, J = 8.4 Hz, 2H), 5.43
(s, 2H), 2.72À2.68 (t, J = 7.6 Hz, 2H), 2.63 (s, 3H), 2.32 (s, 3H),
1.61À1.51 (m, 3H), 0.96À0.95 (d, J = 6.4 Hz, 6H); 13C NMR (CDCl3,
125 MHz) δ 200.5, 156.7, 148.3, 139.3, 132.8, 130.5, 130.1, 129.9, 127.6,
chromatography on silica gel (hexane) of the reaction mixture afforded
88 mg of 4d: yield 63%; 1H NMR (400 MHz, CDCl3) δ 8.03À8.01 (d,
J = 8.0 Hz, 1H), 7.70À7.68 (d, J = 8.0 Hz, 1H), 7.51À7.46 (m, 2H),
7.42À7.36 (m, 3H), 7.30À7.25 (m, 2H), 7.23À7.19 (m, 1H), 4.30
(s, 2H), 2.65 (s, 3H), 2.55 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
137.0, 133.7, 132.7, 132.6, 132.5, 132.0, 130.5, 129.1, 128.4, 127.3, 126.7,
126.0, 125.1, 124.1, 39.4, 16.3, 15.3; MS (m/z) 278 (M, 25), 169 (M À
109, 100); IR (neat, cmÀ1) 3050, 2921, 1580, 1477, 735; HRMS calcd
for C19H18S 278.1129, found 278.1126.
126.9, 114.9, 68.7, 40.3, 34.0, 28.8, 27.7, 22.5, 20.5; IR (neat, cmÀ1
)
2955, 1675, 1510, 1240, 813; HRMS calcd for C21H26O2 310.1933,
found 310.1926.
(4-Isopentyl-2-(p-tolyloxymethyl)phenyl)(phenyl)metha-
none (2m). To a solution of 0.5 mmol of 1m in 3 mL of acetonitrile was
charged 1 mmol of DBU under a N2 atmosphere at 40 °C. The reaction
was monitored by TLC until completion (6 h). After evaporation,
chromatography on silica gel (hexane/ethyl acetate 40/1) of the
(Biphenyl-3-ylmethyl)(butyl)sulfane (4e). To a solution of
0.5 mmol of 3e in 3 mL of acetonitrile was charged 1 mmol of DBU
under a N2 atmosphere at 50 °C. The reaction was monitored by TLC
until completion (6 h). After evaporation, chromatography on silica gel
(hexane) of the reaction mixture afforded 106 mg of 4e: yield 83%; 1H
NMR (400 MHz, CDCl3) δ 7.62À7.60 (m, 2H), 7.56 (s, 1H),
7.49À7.43 (m, 3H), 7.41À7.34 (m, 2H), 7.32À7.30 (m, 1H), 3.78
(s, 2H), 2.49À2.45 (t, J = 7.6 Hz, 2H), 1.60À1.54 (m, 2H), 1.42À1.37
(m, 2H), 0.92À0.88 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ
141.7, 141.3, 139.5, 129.1, 129.0, 128.0, 127.9, 127.6, 127.4, 126.0, 36.7,
31.6, 31.5, 22.2, 13.9; MS (m/z) 256 (M, 80), 167 (M À 89, 100); IR
(neat, cmÀ1) 3031, 2924, 1699, 1456, 755, 698; HRMS calcd for
C17H20S 256.1286, found 256.1280.
(1-(4-Methylnaphthalen-2-yl)ethyl)(phenyl)sulfane (4f).
To a solution of 0.5 mmol of 3f in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 50 °C. The reaction was
monitored by TLC until completion (12 h). After evaporation, chro-
matography on silica gel (hexane) of the reaction mixture afforded 104
mg of 4f: yield 75%; 1H NMR (400 MHz, CDCl3) δ 8.01À7.99 (m, 1H),
7.81À7.79 (m, 1H), 7.56À7.55 (m, 1H), 7.54À7.48 (m, 2H), 7.44
(s, 1H), 7.39À7.36 (m, 2H), 7.27À7.22 (m, 3H), 4.55À4.49 (q, J = 7.1
Hz, 1H), 2.73 (s, 3H), 1.77À1.76 (d, J = 7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) δ 140.4, 135.5, 135.0, 133.7, 132.7, 132.3, 129.0,
128.7, 127.4, 126.6, 126.1, 125.9, 124.5, 124.2, 48.5, 22.6, 19.7; MS
(m/z) 278 (M, 20), 169 (M À 109, 100); IR (neat, cmÀ1) 3056, 2968,
1601, 1441, 744; HRMS calcd for C19H18S 278.1129, found 278.1128.
Phenyl((3-phenylnaphthalen-2-yl)methyl)sulfane (4g). To
a solution of 0.5 mmol of 3g in 3 mL of acetonitrile was charged 1 mmol
of DBU under a N2 atmosphere at 50 °C. The reaction was monitored by
TLC until completion (6 h). After evaporation, chromatography on
silica gel (hexane) of the reaction mixture afforded 114 mg of 4g: yield
70%; 1H NMR (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.85À7.83 (m, 1H),
7.82À7.79 (m, 1H), 7.76 (s, 1H), 7.53À7.43 (m, 7H), 7.24À7.23
(m, 4H), 7.22À7.19 (m, 1H), 4.24 (s, 2H); 13C NMR (CDCl3, 100 MHz)
δ 141.1, 140.7, 136.8, 133.2, 132.9, 132.8, 130.5, 129.8, 129.4, 129.2, 129.0,
128.5, 127.9, 127.7, 127.5, 126.7, 126.5, 126.4, 37.8; MS (m/z) 326 (M,
15), 217 (M À 109, 66); IR (neat, cmÀ1) 3054, 2923, 1699, 1480, 1439,
739, 696; HRMS calcd for C23H18S 326.1129, found 326.1131.
1
reaction mixture afforded 103 mg of 2m: yield 55%; H NMR (400
MHz, CDCl3) δ 7.83À7.81 (d, J = 7.6 Hz, 2H), 7.61À7.56 (m, 2H),
7.48À7.44 (t, J = 7.4 Hz, 2H), 7.38À7.36 (d, J = 8.0 Hz, 1H), 7.21À7.19
(d, J = 7.6 Hz, 1H), 7.04À7.02 (d, J = 8.4 Hz, 2H), 6.76À6.74 (d, J = 8.8
Hz, 2H), 5.22 (s, 2H), 2.74À7.70 (t, J = 7.8 Hz, 2H), 2.27 (s, 3H),
1.65À1.54 (m, 3H), 0.98À0.97 (d, J = 6.0 Hz, 6H); 13C NMR (CDCl3,
125 MHz) δ 197.8, 156.4, 146.6, 138.0, 137.7, 134.5, 132.9, 130.1, 129.9,
129.8, 128.4, 128.3, 126.8, 114.7, 67.9, 40.5, 33.9, 27.7, 22.5, 20.5; IR
(neat, cmÀ1) 2955, 1659, 1510, 1237, 702; HRMS calcd for C26H28O2
372.2089, found 372.2092.
(Biphenyl-3-ylmethyl)(phenyl)sulfane (4a). To a solution of
0.5 mmol of 3a in 3 mL of acetonitrile was charged 1 mmol of DBU
under a N2 atmosphere at 50 °C. The reaction was monitored by TLC
until completion (6 h). After evaporation, chromatography on silica gel
(hexane) of the reaction mixture afforded 113 mg of 4a: yield 82%; 1H
NMR (400 MHz, CDCl3) δ 7.57À7.55 (d, J = 8.0 Hz, 2H), 7.51À7.48
(m, 2H), 7.46À7.43 (t, J = 7.4 Hz, 2H), 7.40À7.34 (m, 4H), 7.31À7.27
(m, 3H), 7.24À7.20 (m, 1H), 4.19 (s, 2H); 13C NMR (CDCl3, 100
MHz) δ 141.7, 141.2, 138.3, 136.6, 130.4, 129.2, 129.2, 129.0, 128.0,
127.6, 127.4, 126.8, 126.3, 39.5; MS (m/z) 276 (M, 38), 167 (M À 109,
100); IR (neat, cmÀ1) 3057, 2922, 1579, 1477, 692; HRMS calcd for
C19H16S 276.0973, found 276.0965.
((4-Methylnaphthalen-2-yl)methyl)(phenyl)sulfane (4b).
To a solution of 0.5 mmol of 3b in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 50 °C. The reaction was
monitored by TLC until completion (6 h). After evaporation, chroma-
tography on silica gel (hexane) of the reaction mixture afforded 106 mg
of 4b: yield 80%; 1H NMR (400 MHz, CDCl3) δ 8.03À8.01 (m, 1H),
7.83À7.81 (m, 1H), 7.62 (s, 1H), 7.57À7.51 (m, 2H), 7.43À7.39
(m, 3H), 7.33À7.29 (m, 2H), 7.26À7.22 (m, 1H), 4.30 (s, 2H), 2.73
(s, 3H); 13C NMR (CDCl3, 100 MHz) δ136.6, 134.8, 134.4, 133.5, 131.9,
129.8, 128.9, 128.4, 127.7, 126.4, 126.3, 125.9, 125.7, 124.0, 39.4, 19.3; MS
(m/z) 264 (M, 82), 155 (M À 109, 100); IR (neat, cmÀ1) 3056, 2920,
1691, 1477, 738; HRMS calcd for C18H16S 264.0973, found 264.0964.
(Naphthalen-2-ylmethyl)(phenyl)sulfane (4c). To a solution
of 0.5 mmol of 3c in 3 mL of acetonitrile was charged 1 mmol of DBU
under a N2 atmosphere at 50 °C. The reaction was monitored by TLC
until completion (6 h). After evaporation, chromatography on silica gel
(hexane) of the reaction mixture afforded 100 mg of 4c: yield 80%; 1H
NMR (400 MHz, CDCl3) δ 7.85À7.81 (m, 2H), 7.79À7.77 (m, 1H),
7.71 (s, 1H), 7.51À7.47 (m, 3H), 7.37À7.36 (m, 2H), 7.29À7.25
(m, 2H), 7.22À7.19 (m, 1H), 4.30 (s, 2H); 13C NMR (CDCl3, 100
MHz) δ 136.3, 134.9, 133.3, 132.6, 130.0, 128.8, 128.3, 127.7, 127.6,
127.4, 127.0, 126.4, 126.1, 125.8, 39.4; MS (m/z) 250 (M, 35), 141
(M À 109, 100); IR (neat, cmÀ1) 3054, 2921, 1579, 1477, 754; HRMS
calcd for C17H14S 250.0816, found 250.0818.
Butyl((4-phenyllbiphenyl-2-yl)methyl)sulfane (4h). To a
solution of 0.5 mmol of 3h in 3 mL of acetonitrile was charged 1 mmol
of DBU under a N2 atmosphere at 50 °C. The reaction was monitored by
TLC until completion (6 h). After evaporation, chromatography on
silica gel (hexane) of the reaction mixture afforded 120 mg of 4h: yield
72%; 1H NMR (400 MHz, CDCl3) δ 7.77 (s, 1H), 7.70À7.69 (m, 2H),
7.58À7.55 (m, 1H), 7.52À7.46 (m, 6H), 7.44À7.36 (m, 3H), 3.79
(s, 2H), 2.48À2.44 (t, J = 7.2 Hz, 2H), 1.49À1.46 (m, 2H), 1.39À1.34
(m, 2H), 0.91À0.87 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
δ 141.3, 141.1, 140.9, 140.6, 136.6, 130.9, 129.7, 129.1, 129.0, 128.4,
127.6, 127.4, 127.4, 125.8, 34.3, 32.3, 31.7, 22.2, 13.9; MS (m/z) 332 (M,
10), 243 (M À 89, 40); IR (neat, cmÀ1) 3026, 2924, 1601, 1476, 697;
HRMS calcd for C23H24S 332.1599, found 332.1602.
((3,4-Dimethylnaphthalen-2-yl)methyl)(phenyl)sulfane (4d).
To a solution of 0.5 mmol of 3d in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 50 °C. The reaction was
monitored by TLC until completion (12 h). After evaporation,
Butyl(naphthalen-2-ylmethyl)sulfane (4i). To a solution of
0.5 mmol of 3i in 3 mL of acetonitrile was charged 1 mmol of DBU under
a N2 atmosphere at 60 °C. The reaction was monitored by TLC until
completion (12 h). After evaporation, chromatography on silica gel
4587
dx.doi.org/10.1021/jo2004555 |J. Org. Chem. 2011, 76, 4582–4590

The Journal of Organic Chemistry
ARTICLE
(hexane) of the reaction mixture afforded 100 mg of 4i: yield 87%;
1H NMR (400 MHz, CDCl3) δ 7.86À7.82 (m, 2H), 7.74 (s, 1H),
7.55À7.47 (m, 3H), 3.90 (s, 2H), 2.49À2.45 (t, J = 7.6 Hz, 2H),
1.64À1.57 (m, 2H), 1.46À1.39 (m, 2H), 0.94À0.90 (t, J = 7.4 Hz, 3H);
13C NMR (CDCl3, 100 MHz) δ 136.3, 133.6, 132.8, 128.6, 127.9, 127.9,
127.4, 126.4, 126.0, 36.8, 31.6, 31.3, 22.3, 13.9; MS (m/z) 230 (M, 95),
141 (M À 89, 100); IR (neat, cmÀ1) 3053, 2925, 1632, 1459, 748;
HRMS calcd for C15H18S 230.1129, found 230.1133.
reaction mixture afforded 135 mg of 6a: yield 78%; 1H NMR (400 MHz,
CDCl3) δ 8.16À8.14 (d, J = 8.0 Hz, 1H), 7.59À7.56 (m, 2H),
7.53À7.51 (m, 2H), 7.44À7.40 (m, 2H), 7.38À7.34 (m, 1H),
7.27À7.23 (t, J = 7.8, 2H), 6.77À6.73 (m, 3H), 5.02 (s, 2H),
4.45À4.40 (q, J = 7.1 Hz, 2H), 3.12 (s, 3H), 1.47À1.44 (t, J = 7.0
Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 167.5, 150.0, 145.4, 142.2,
140.4, 132.1, 129.4, 129.1, 128.3, 127.8, 127.5, 126.0, 125.5, 116.8, 112.4,
61.2, 56.6, 39.0, 14.7; IR (neat, cmÀ1) 2896, 1713, 1506, 1253, 745;
HRMS calcd for C23H23NO2 345.1729, found 345.1735.
((3-Methylnaphthalen-2-yl)methyl)(phenyl)sulfane (4j).
To a solution of 0.5 mmol of 3j in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 50 °C. The reaction was
monitored by TLC until completion (6 h). After evaporation, chroma-
tography on silica gel (hexane) of the reaction mixture afforded 106 mg
of 4j: yield 80%; 1H NMR (400 MHz, CDCl3) δ 7.78À7.77 (d, J = 7.2
Hz, 1H), 7.73À7.71 (d, J = 7.2 Hz, 1H), 7.68 (s, 1H), 7.61 (s, 1H),
7.47À7.37 (m, 4H), 7.32À7.24 (m, 3H), 4.29 (s, 2H), 2.62 (s, 3H); 13C
NMR (CDCl3, 100 MHz) δ 136.7, 135.0, 134.1, 133.3, 132.3, 130.8,
129.1, 128.8, 128.7, 127.6, 127.1, 126.9, 126.1, 125.5, 38.2, 19.9; MS
(m/z) 264 (M, 35), 155 (M À 109, 100); IR (neat, cmÀ1) 3026, 2922,
1698, 1480, 737; HRMS calcd for C18H16S 264.0973, found 264.0979.
Butyl((4-methylnaphthalen-2-yl)methyl)sulfane (4k). To a
solution of 0.5 mmol of 3k in 3 mL of acetonitrile was charged 1 mmol of
DBU under a N2 atmosphere at 60 °C. The reaction was monitored by
TLC until completion (12 h). After evaporation, chromatography on
silica gel (hexane) of the reaction mixture afforded 104 mg of 4k: yield
85%; 1H NMR (400 MHz, CDCl3) δ 7.98À7.95 (m, 1H), 7.81À7.79
(m, 1H), 7.55 (s, 1H), 7.50À7.47 (m, 2H), 7.34 (s, 1H), 3.83 (s, 2H),
2.69 (s, 3H), 2.45À2.41 (t, J = 7.4 Hz, 2H), 1.59À1.53 (m, 2H),
1.41À1.35 (m, 2H), 0.90À0.87 (t, J = 7.2 Hz, 3H); 13C NMR
(CDCl3, 100 MHz) δ 135.8, 135.1, 133.7, 132.0, 128.5, 128.0, 126.1,
125.9, 125.8, 124.2, 36.8, 31.6, 31.2, 22.3, 19.6, 13.9; MS (m/z) 244 (M,
95), 155 (M À 89, 100); IR (neat, cmÀ1) 3030, 2926, 1602, 1464, 747;
HRMS calcd for C16H20S 244.1286, found 244.1288.
((4-Phenylbiphenyl-2-yl)methyl)(phenyl)sulfane (4l). To a
solution of 0.5 mmol of 3l in 3 mL of acetonitrile was charged 1 mmol of
DBU under a N2 atmosphere at 30 °C. The reaction was monitored by
TLC until completion (3 h). After evaporation, chromatography on
silica gel (hexane) of the reaction mixture afforded 155 mg of 4l: yield
88%; 1H NMR (400 MHz, CDCl3) δ 7.70À7.69 (m, 1H), 7.63À7.61 (d,
J = 7.6 Hz, 2H), 7.60À7.57 (dd, J = 8 Hz, 1H), 7.51À7.47 (m, 6H),
7.44À7.37 (m, 3H), 7.32À7.23 (m, 5H), 4.19 (s, 2H); 13C NMR
(CDCl3, 100 MHz) δ 141.4, 140.8, 140.8, 140.6, 136.7, 135.3, 131.0,
130.6, 129.6, 129.3, 129.2, 129.1, 128.6, 127.7, 127.6, 127.4, 126.8, 126.2,
37.5; MS (m/z) 352 (M, 15), 243 (M À 109, 62); IR (neat, cmÀ1) 3056,
2924, 1579, 1476, 694; HRMS calcd for C25H20S 352.1286, found
352.1291.
N-(Biphenyl-3-ylmethyl)-N-p-tolylacetamide (6b). To a so-
lution of 0.5 mmol of 5b in 3 mL of acetonitrile was charged 1 mmol of
DBU under a N2 atmosphere at reflux. The reaction was monitored by
TLC until completion (12 h). After evaporation, chromatography on
silica gel (hexane/ethyl acetate 5/1) of the reaction mixture afforded 144
mg of 6b: yield 91%; 1H NMR (400 MHz, CDCl3) δ 7.53À7.51
(m, 2H), 7.47À7.45 (d, J = 7.6 Hz, 1H), 7.42À7.38 (m, 3H), 7.35À7.30
(m, 2H), 7.20À7.17 (d, J = 7.6 Hz, 1H), 7.12À7.10 (d, J = 8.0 Hz, 2H),
6.90À6.87 (d, J = 8.4 Hz, 2H), 4.93 (s, 2H), 2.33 (s, 3H), 1.89 (s, 3H);
13C NMR (CDCl3, 125 MHz) δ 170.6, 141.2, 141.0, 140.3, 138.2, 137.8,
130.2, 128.8, 128.7, 128.0, 127.8, 127.6, 127.3, 127.2, 126.1, 52.9, 22.7,
21.1; IR (neat, cmÀ1) 3030, 2925, 1653, 1389, 908, 728; HRMS calcd for
C22H21NO 315.1623, found 315.1631.
Ethyl 3-((N-p-Tolylacetamido)methyl)biphenyl-4-carbox-
ylate (6c). To a solution of 0.5 mmol of 5c in 3 mL of acetonitrile
was charged 1 mmol of DBU under a N2 atmosphere at 50 °C. The
reaction was monitored by TLC until completion (6 h). After evapora-
tion, chromatography on silica gel (hexane/ethyl acetate 5/1) of the
reaction mixture afforded 176 mg of 6c: yield 91%; 1H NMR (400 MHz,
CDCl3) δ 7.91À7.89 (d, J = 8.0 Hz, 1H), 7.73 (s, 1H), 7.60À7.58 (d, J =
8.0 Hz, 2H), 7.50À7.43 (m, 3H), 7.39À7.36 (m, 1H), 7.11À7.09 (d, J =
8.0 Hz, 2H), 6.96À6.94 (d, J = 8.0 Hz, 2H), 5.42 (s, 2H), 4.21À4.15
(q, J = 7.1 Hz, 2H), 2.30 (s, 3H), 1.92 (s, 3H), 1.31À1.28 (t, J = 7.2 Hz,
3H); 13C NMR (CDCl3, 125 MHz) δ 170.9, 167.1, 144.7, 140.6, 140.0,
139.3, 137.7, 131.1, 130.1, 128.9, 128.6, 128.1, 128.1, 127.7, 127.3, 125.5,
60.9, 50.6, 22.7, 21.0, 14.2; IR (neat, cmÀ1) 2981, 1710, 1655, 1254, 730;
HRMS calcd for C25H25NO3: 387.1834, found 387.1839.
N-((4-Acetylbiphenyl-3-yl)methyl)-N-p-tolylacetamide (6d).
To a solution of 0.5 mmol of 5d in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 40 °C. The reaction was
monitored by TLC until completion (6 h). After evaporation, chroma-
tography on silica gel (hexane/ethyl acetate 3/1) of the reaction mixture
1
afforded 170 mg of 6d: yield 95%; H NMR (400 MHz, CDCl3) δ
7.80À7.79 (m, 1H), 7.73À7.71 (d, J = 8.0 Hz, 1H), 7.64À7.62 (m, 2H),
7.55À7.53 (dd, J = 8.0 Hz, 1H), 7.51À7.47 (m, 2H), 7.43À7.40 (m,
1H), 7.15À7.13 (d, J = 8.0 Hz, 2H), 7.00À6.98 (d, J = 8.0 Hz, 2H), 5.34
(s, 2H), 2.42 (s, 3H), 2.34 (s, 3H), 1.95 (s, 3H); 13C NMR (CDCl3, 125
MHz) δ 201.1, 170.8, 144.4, 140.7, 139.9, 138.4, 137.7, 136.3, 130.2,
129.9, 129.0, 128.2, 128.0, 127.7, 127.3, 125.4, 50.6, 29.2, 22.7, 21.0; IR
(neat, cmÀ1) 3032, 1654, 1512, 1251, 727; HRMS calcd for C24H23NO2
357.1729, found 357.1724.
N-((4-Benzoylbiphenyl-3-yl)methyl)-N-p-tolylacetamide
(6e). To a solution of 0.5 mmol of 5e in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 40 °C. The reaction was
monitored by TLC until completion (6 h). After evaporation, chroma-
tography on silica gel (hexane/ethyl acetate 3/1) of the reaction mixture
afforded 189 mg of 6e: yield 90%; 1H NMR (400 MHz, CDCl3) δ 7.86
(s, 1H), 7.64À7.62 (d, J = 7.2 Hz, 2H), 7.54À7.45 (m, 6H), 7.41À7.39
(d, J = 7.2 Hz, 1H), 7.36À7.32 (t, J = 7.8 Hz, 2H), 7.30À7.28 (d, J = 8.4
Hz, 1H), 6.95À6.93 (d, J = 8.4, Hz, 2H), 6.81À6.79 (d, J = 8.4 Hz, 2H),
5.18 (s, 2H), 2.20 (s, 3H), 1.86 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
197.3, 170.7, 143.5, 140.0, 139.8, 138.0, 137.6, 137.5, 137.2, 132.9, 130.2,
130.1, 129.6, 129.0, 128.8, 128.1, 128.0, 127.7, 127.3, 125.0, 48.9, 22.6,
21.0; IR (neat, cmÀ1) 3032, 1654, 1282, 909, 728; HRMS calcd for
C29H25NO2 419.1885, found 419.1882.
(1-(4-Phenylbiphenyl-2-yl)ethyl)(phenyl)sulfane (4m). To
a solution of 0.5 mmol of 3m in 3 mL of acetonitrile was charged 1 mmol
of DBU under a N2 atmosphere at 30 °C. The reaction was monitored by
TLC until completion (3 h). After evaporation, chromatography on
silica gel (hexane) of the reaction mixture afforded 154 mg of 4m: yield
84%; 1H NMR (400 MHz, CDCl3) δ 7.92À7.91 (m, 1H), 7.70À7.68
(m, 2H), 7.54À7.49 (m, 3H), 7.45À7.41 (m, 4H), 7.33À7.31 (m, 2H),
7.27À7.26 (m, 1H), 7.21 (s, 5H), 4.61À4.55 (q, J = 7.1 Hz, 1H),
1.65À1.63 (d, J = 6.4 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ
141.3, 141.1, 141.0, 140.5, 135.4, 133.0, 130.6, 129.6, 129.1, 129.0, 128.8,
128.4, 127.7, 127.5, 127.4, 126.4, 125.8, 44.3, 23.3; MS (m/z) 366 (M,
10), 257 (M À 109, 100); IR (neat, cmÀ1) 3056, 2922, 1579, 1475, 694;
HRMS calcd for C26H22S 366.1442, found 366.1449.
Ethyl 3-((Methyl(phenyl)amino)methyl)biphenyl-4-carbox-
ylate (6a). To a solution of 0.5 mmol of 5a in 3 mL of acetonitrile
was charged 1 mmol of DBU under a N2 atmosphere at 60 °C. The
reaction was monitored by TLC until completion (6 h). After evapora-
tion, chromatography on silica gel (hexane/ethyl acetate 20/1) of the
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ARTICLE
N-((4-Methylbiphenyl-2-yl)methyl)-N-p-tolylacetamide (6f).
To a solution of 0.5 mmol of 5f in 3 mL of acetonitrile was charged 1 mmol
of DBU under a N2 atmosphere at 60 °C. The reaction was monitored by
TLC until completion (6 h). After evaporation, chromatography on silica
gel (hexane/ethyl acetate 5/1) of the reaction mixture afforded 180 mg of
7.47À7.44 (t, J = 7.2 Hz, 2H), 7.41À7.37 (t, J = 7.4 Hz, 1H), 7.25À7.19 (m,
4H), 5.34 (s, 2H), 4.36À4.31 (q, J = 7.2 Hz, 2H), 1.41À1.37 (m, 12H); 13
C
NMR (CDCl3, 125 MHz) δ 166.9, 154.5, 145.0, 141.6, 139.9, 131.6, 130.9,
129.0, 128.7, 128.2, 128.2, 127.3, 127.2, 126.8, 125.7, 125.3, 81.1, 61.0, 52.6,
28.2, 14.3; IR (neat, cmÀ1) 2977, 1701, 1606, 1251, 756; HRMS calcd for
C27H28ClNO4 465.1707, found 465.1713.
1
6f: yield 92%; H NMR (400 MHz, CDCl3) δ 7.81À7.80 (m, 1H),
7.68À7.66 (d, J = 7.6 Hz, 2H), 7.53À7.46 (m, 3H), 7.40À7.36 (t, J = 7.4
Hz, 1H), 7.29À7.27 (m, 3H), 7.21À7.19 (d, J = 8.0 Hz, 1H), 7.05À7.03
(d, J = 8.0 Hz, 2H), 6.94À6.91 (m, 2H), 6.76À6.74 (d, J = 8.4 Hz, 2H),
4.99 (s, 2H), 2.33 (s, 3H), 1.88 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ
170.7, 141.1, 140.7, 140.4, 140.3, 140.0, 137.6, 135.5, 130.3, 130.0, 129.2,
128.9, 127.9, 127.8, 127.6, 127.4, 127.2, 126.9, 125.7, 49.3, 22.6, 21.1; IR
(neat, cmÀ1) 3029, 1652, 1477, 1388, 729; HRMS calcd for C28H25NO
391.1936, found 391.1947.
4-Methyl-2-vinylbiphenyl (7). To a solution of NaIO4 (1.1
mmol) in water (6 mL) was added 4m (1.0 mmol) in 12 mL of MeOH,
followed by a heating at 40 °C for 18 h. After evaporation to remove
MeOH, the reaction rescue (product, NaIO3, and water) was diluted
with 30 mL of water and extracted with EtOAc. The extracts were
washed with water and dried over anhydrous Na2SO4. Evaporation of
the EtOAc afforded directly the crude product for the next step. The
solution of the crude product in 5 mL of toluene was heated at 110 °C for
3 h. Evaporation of toluene and chromatography on silica gel (eluent:
petroleum ether) of the reaction mixture afforded the desired product 7
(159 mg, 62%): 1H NMR (400 MHz, CDCl3) δ 7.91À7.90 (m, 1H),
7.72À7.70 (d, J = 7.6 Hz, 2H), 7.62À7.59 (dd, J = 7.6 Hz, 1H),
7.53À7.48 (m, 3H), 7.46À7.39 (m, 6H), 6.86À6.79 (m, 1H),
5.85À5.80 (m, 1H), 5.30À5.27 (m, 1H); 13C NMR (CDCl3, 100 MHz)
δ 140.9, 140.5, 140.4, 139.8, 136.1, 136.0, 130.6, 129.8, 128.8, 128.1,
127.4, 127.2, 127.1, 126.5, 124.6, 115.0; IR (neat, cmÀ1) 3056, 1576,
1473, 911, 696; HRMS calcd for C20H16 256.1252, found 256.1255.
2-(4-Chlorophenyl)-5-phenylisoindolin-1-one (8). A 20-mL
tube was charged 6j (0.5 mmol) and a saturated HCl/MeOH solution
(5 mL). The tube was sealed and placed in an oil bath (110 °C) for 30 h
at which time it was opened. After evaporation, the reaction mixture was
washed with water (2 Â 10 mL) to afford 8 (153 mg, 96%): mp
216À218 °C; 1H NMR (400 MHz, CDCl3) δ 7.98À7.96 (d, J = 7.2 Hz,
1H), 7.87À7.85 (d, J = 8.8 Hz, 2H), 7.74À7.71 (m, 2H), 7.65À7.63
(d, J = 7.6 Hz, 2H), 7.52À7.48 (t, J = 7.4 Hz, 2H), 7.44À7.38 (m, 3H),
4.92 (s, 2H); 13C NMR (CDCl3, 125 MHz) δ 163.8, 145.7, 140.6, 140.2,
138.1, 132.1, 129.6, 129.2, 129.0, 128.3, 127.9, 127.5, 124.5, 121.3, 120.5,
50.668; IR (neat, cmÀ1) 2922, 1679, 1489, 1376, 692; HRMS calcd for
C20H14ClNO 319.0764, found 319.0766.
1-(3-((Methyl(phenyl)amino)methyl)biphenyl-4-yl)-
ethanone (6g). To a solution of 0.5 mmol of 5g in 3 mL of acetonitrile
was charged 1 mmol of DBU under a N2 atmosphere at 50 °C. The
reaction was monitored by TLC until completion (6 h). After evapora-
tion, chromatography on silica gel (hexane/ethyl acetate 10/1) of the
reaction mixture afforded 92 mg of 6g: yield 58%; 1H NMR (400 MHz,
CDCl3) δ 7.96À7.94 (d, J = 8.0 Hz, 1H), 7.63À7.59 (m, 2H),
7.53À7.52 (d, J = 6.8 Hz, 2H), 7.45À7.41 (t, J = 7.4 Hz, 2H),
7.39À7.36 (m, 1H), 7.26À7.22 (m, 2H), 6.76À6.72 (m, 3H), 4.94
(s, 2H), 3.09 (s, 3H), 2.68 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ
200.9, 149.7, 144.9, 141.4, 139.9, 134.9, 131.1, 129.1, 128.9, 128.1, 127.2,
126.1, 125.1, 116.6, 112.2, 56.6, 38.8, 29.2; IR (neat, cmÀ1) 2921, 1665,
1506, 1251, 689; HRMS calcd for C22H21NO 315.1623, found
315.1624.
N-(2-Acetyl-5-isopentylbenzyl)-N-p-tolylacetamide (6h).
To a solution of 0.5 mmol of 5h in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 50 °C. The reaction was
monitored by TLC until completion (3 h). After evaporation, chroma-
tography on silica gel (hexane/ethyl acetate 3/1) of the reaction mixture
1
afforded 169 mg of 6h: yield 96%; H NMR (400 MHz, CDCl3) δ
7.55À7.53 (d, J = 7.2 Hz, 1H), 7.34 (s, 1H), 7.11À7.09 (d, J = 8.0 Hz,
3H), 6.93À6.91 (d, J = 8.4 Hz, 2H), 5.25 (s, 2H), 2.67À2.63 (t, J = 8.0
Hz, 2H), 2.34 (s, 3H), 2.31 (s, 3H), 1.93 (s, 3H), 1.59À1.47 (m, 3H),
0.95À0.93 (d, J = 6.0 Hz, 6H); 13C NMR (CDCl3, 125 MHz) δ 201.1,
170.7, 147.4, 140.6, 137.8, 137.6, 135.1, 130.1, 129.6, 129.4, 127.7, 126.7,
50.4, 40.3, 33.8, 29.0, 27.6, 22.7, 22.5, 21.0; IR (neat, cmÀ1) 2971, 1673,
1648, 1384, 1052; HRMS calcd for C23H29NO2 351.2198, found
351.2191.
’ ASSOCIATED CONTENT
S
Supporting Information. Proton and carbon NMR spec-
b
tra of products and experimental procedures for the synthesis of
the substrates. This material is available free of charge via the
Internet at http://pubs.acs.org.
N-(2-Benzoyl-5-isopentylbenzyl)-N-p-tolylacetamide (6i).
To a solution of 0.5 mmol of 5i in 3 mL of acetonitrile was charged
1 mmol of DBU under a N2 atmosphere at 50 °C. The reaction was
monitored by TLC until completion (3 h). After evaporation, chroma-
tography on silica gel (hexane/ethyl acetate 4/1) of the reaction mixture
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: zhouhw@zju.edu.cn.
1
afforded 151 mg of 6i. yield 73%; H NMR (400 MHz, CDCl3) δ
7.53À7.47 (m, 3H), 7.43 (s, 1H), 7.34À7.31 (t, J = 7.6 Hz, 2H),
7.14À7.12 (d, J = 8.0 Hz, 1H), 7.08À7.06 (d, J = 7.6 Hz, 1H), 6.94À6.92
(d, J = 8.0 Hz, 2H), 6.78À6.76 (d, J = 8.0 Hz, 2H), 5.12 (s, 2H),
2.69À2.65 (t, J = 7.8 Hz, 2H), 2.20 (s, 3H), 1.87 (s, 3H), 1.62À1.50 (m,
3H), 0.97À0.96 (d, J = 6.8 Hz, 6H); 13C NMR (CDCl3, 125 MHz) δ
197.5, 170.6, 146.3, 139.7, 137.7, 137.5, 135.9, 132.6, 130.2, 130.2, 130.0,
129.3, 128.0, 127.7, 126.3, 48.6, 40.5, 33.8, 27.7, 22.6, 22.6, 21.0; IR
(neat, cmÀ1) 2955, 1657, 1604, 1270, 705; HRMS calcd for C28H31NO2
413.2355, found 413.2343.
Ethyl 3-((tert-Butoxycarbonyl(4-chlorophenyl)amino)meth-
yl)biphenyl-4-carboxylate (6j). To a solution of 0.5 mmol of 5j in
3 mL of acetonitrile was charged 1 mmol of DBU under a N2 atmosphere at
40 °C. The reaction was monitored by TLC until completion (3 h). After
evaporation, chromatography on silica gel (hexane/ethyl acetate 15/1) of
the reaction mixture afforded 205 mg of 6j: yield 88%; 1H NMR (400 MHz,
CDCl3) δ 8.06À8.04 (d, J = 8.4 Hz, 1H), 7.70 (s, 1H), 7.60À7.54 (m, 3H),
’ ACKNOWLEDGMENT
Dedicated to the memory of Prof. Xian Huang. Financial
support was received from the Natural Science Foundation of
China (Nos. 20702046 and 20972134).
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