Pd-catalyzed cross-coupling reactions of hydrazones: Regioselective synthesis of highly branched dienes

Article abstract of DOI:10.1021/jo402153t

The regioselective formation of highly branched dienes is a challenging task. Design and exploration of alternative working models to achieve such a regioselectivity to accomplish highly branched dienes is considered to be a historical advancement of Heck reaction to construct branched dienes. On the basis of the utility of carbene transfer reactions, in the reaction of hydrazones with Pd(II) under oxidative conditions, we envisioned obtaining a Pd-bis-carbene complex with α-hydrogens, which can lead to branched dienes. Herein, we report a novel Pd-catalyzed selective coupling reaction of hydrazones in the presence of t-BuOLi and benzoquinone to form the corresponding branched dienes. The utility of the Pd catalyst for the cross-coupling reactions for synthesizing branched conjugated dienes is rare. The reaction is very versatile and compatible with a variety of functional groups and is useful in synthesizing heterocyclic molecules. We anticipate that this Pd-catalyzed cross-coupling reaction will open new avenues for synthesizing useful compounds.

Full text of DOI:10.1021/jo402153t

Article
pubs.acs.org/joc
Pd-Catalyzed Cross-Coupling Reactions of Hydrazones:
Regioselective Synthesis of Highly Branched Dienes
Devi Prasan Ojha and Kandikere Ramaiah Prabhu*
Department of Organic Chemistry, Indian Institute of Science, Bangalore, Karnataka 560 012, India
S
* Supporting Information
ABSTRACT: The regioselective formation of highly branched dienes is a
challenging task. Design and exploration of alternative working models to
achieve such a regioselectivity to accomplish highly branched dienes is
considered to be a historical advancement of Heck reaction to construct
branched dienes. On the basis of the utility of carbene transfer reactions,
in the reaction of hydrazones with Pd(II) under oxidative conditions, we
envisioned obtaining a Pd-bis-carbene complex with α-hydrogens, which
can lead to branched dienes. Herein, we report a novel Pd-catalyzed
selective coupling reaction of hydrazones in the presence of t-BuOLi and
benzoquinone to form the corresponding branched dienes. The utility of the Pd catalyst for the cross-coupling reactions for
synthesizing branched conjugated dienes is rare. The reaction is very versatile and compatible with a variety of functional groups
and is useful in synthesizing heterocyclic molecules. We anticipate that this Pd-catalyzed cross-coupling reaction will open new
avenues for synthesizing useful compounds.
INTRODUCTION
■
Transition-metal-mediated cross-coupling reactions have been
revolutionary for carbon−carbon-bond-forming reactions,
particularly for the synthesis of conjugated dienes and
polyenes.1 Conjugated dienes and polyenes have been
accomplished by employing organometallic nucleophiles such
as boronic acids and its ester derivatives and organic halides,
such as vinyl halides, vinyl sulfonates, and vinyl phosphates.2
Among the transition-metal-catalyzed reactions for C−C-bond-
forming reactions, Pd-catalyzed reactions are the most
prominent. Coupling reactions such as Stille, Heck, Suzuki−
Miyaura, Sonagashira, Negishi, and Kumada are a few
prominent coupling reactions that have found very frequent
citations and applications because of their extensive utility in
organic synthesis. Ru-catalyzed en-yne metathesis has a
remarkable output considering the ease of stereo- and
regioselectivity in the construction of 1,3-dienes.3 However,
the challenges faced by chemists in synthesizing complex
natural products has prompted the discovery of a large number
of coupling reactions that are more efficient and atom
economical and that lead to the synthesis of molecular scaffolds
that are not easily accessible. Alkenes and 1,3-butadiene
derivatives are an important class of organic compounds that
can be accessed by Pd-catalyzed cross-coupling reactions.
Conjugated dienes are important synthons in organic synthesis
and are often synthesized by coupling reactions of alkenes with
vinyl halides.4 Generally, linear dienes such as A (Figure 1) can
be easily synthesized, whereas the synthesis of branched dienes
such as B (Figure 1) is cumbersome.5 The regioselective
formation of a branched diene (B) is a highly challenging task,
which has been rarely achieved by coupling vinyl halides with
organometallic reagents. Therefore, the design and exploration
Figure 1. Linear and branched dienes (R2 ≠ H; R3 ≠ H).
of alternative working models to achieve such a regioselectivity
would be considered a historical advancement of the Heck
reaction to construct branched dienes of type B. A Mizaroki−
Heck reaction between an electronically biased olefin and vinyl
halide in the presence of Pd can form a conjugated linear diene
of type A.6 Similarly, a reaction of olefin with vinyl boronic acid
can lead to conjugated branched diene such as B.5 Similarly,
branched dienes can be accessed by employing Ru hydride-
catalyzed dienyl isomerization reactions.7 However, using a
stoichiometric amount of SmI2−Ac2O results in the formation
of branched dienes along with rearranged products.8 Branched
dienes can also be accessed using a transmetalation strategy by
an organolithium-induced Shapiro reaction.9 A large amount of
precedence in the literature is available to show that there have
been devoted efforts for Pd-catalyzed cross-coupling reactions
for synthesizing linear conjugated dienes,10 whereas their utility
in synthesizing branched conjugated dienes has not been
explored except for a recent report.8b
In this context and in light of our earlier study on Pd-
catalyzed cross-coupling reactions,11 we present our recent
discovery, a novel Pd-catalyzed selective coupling reaction of
hydrazones in the presence of base and oxidant to form the
Received: September 27, 2013
Published: November 18, 2013
© 2013 American Chemical Society
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a
Table 1. Optimization Studies for the Formation of 1,3-Branched Dienes
b
entry
[Pd]
base
oxidizing agent
ligand
yield (%)
1
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(OAc)2
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
Cs2CO3
Ag2CO3
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
t-BuOLi
none
none
none
0
2
benzoxazole
trace
70
3
p-BQ
benzoxazole (20 mol %)
none
4
p-BQ
0
5
p-BQ
N-phenylurea (20 mol %)
diazabutadiene (20 mol %)
xphos (20 mol %)
trace
60
6
p-BQ
7
p-BQ
65
8
p-BQ
PPh3(20 mol %)
25
9
(NH4)2S2O8 (2.5 equiv)
xphos (20 mol %)
trace
trace
nd
nd
0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
(NH4)2S2O8 (2.5 equiv)
xphos (20 mol %)
PIDA (1.5 equiv)
xphos (20 mol %)
Cu(OAc)2 (1.3 equiv)
xphos (20 mol %)
CuI (1.2 equiv)
CuI (20 mol %)
p-BQ
xphos (20 mol %)
xphos (20 mol %)
0
IPr·HCl (20 mol %)
P(Cy)3 (20 mol %)
bibenzoxazole (20 mol %)
P(O-Tol)3 (20 mol %)
bibenzoxazole (20 mol %)
bibenzoxazole (20 mol %)
bibenzoxazole (20 mol %)
bibenzoxazole (20 mol %)
bibenzoxazole (40 mol %)
bibenzoxazole (40 mol %)
bibenzoxazole (40 mol %)
nd
40
p-BQ
p-BQ
80
p-BQ
42
p-BQ
<10
nd
nd
trace
84
Pd2(dba)3
p-BQ
Pd(PPh3)4
p-BQ
PdCl2
p-BQ
Pd(PPh3)2Cl2
Pd(PPh3)4
p-BQ
none
nd
nd
none
p-BQ
a
b
Reaction conditions: 1a (0.47 mmol), [Pd] (5 mol %), ligand (40 mol %), oxidant (1 mmol), base (1.5 mmol), dioxane (3 mL). Isolated yields.
nd, not detected.
corresponding branched dienes. A Pd-catalyzed coupling
reaction of tosylhydrazones with a variety of nucleophiles to
obtain corresponding dienes has been explored in greater detail
by Barluenga and Wang.12 In developing coupling reactions, Pd
chemistry has witnessed exceptional efforts and growth in terms
of quantity and quality. Hence, it provides an excellent avenue
to accomplish the anticipated conjugated olefins by employing
suitable cross-coupling reactions. In this direction, the utility of
a carbene complex as the carbon source has been exemplified
using carbene chromium(0) complexes in the presence of Pd
catalyst or bis-hydrazones in the presence of Rh(II)
complexes.13 Interestingly, these two efforts have led to the
formation of corresponding olefins. However, the latter case,
which uses a Rh(II) complex, was extensively used to
synthesize polycyclic aromatic compounds. Interestingly, none
of these methods were adopted to synthesize branched
conjugated olefins. Nevertheless, a recent report by Wang
and co-workers illustrated the synthesis of branched dienes
using a Pd-catalyzed three-component reaction of allenes, aryl
halides, and diazo compounds.14 On the basis of the utility of
carbene-transfer reactions,13a we postulated that in the reaction
of hydrazones with Pd(II) under oxidative conditions it might
be possible to obtain a Pd-bis-carbene complex with α-
hydrogens, which can lead to branched dienes by facile β-
hydride eliminations.
RESULTS AND DISCUSSION
■
Formation of 1,3-Branched Dienes. To evaluate this
hypothesis, we began our studies by employing 4-methox-
yacetophenone N-tosylhydarazone (1a) as a model substrate
with a variety of bases, oxidants, and ligands in the presence of a
few Pd(II) catalysts (Table 1). An extensive screening study
indicated that bistriphenylphosphine palladium dichloride
(Pd(PPh3)2Cl2) is the most suitable catalyst for this trans-
formation. Initially, the reactions of N-tosylhydarazone 1a using
tert-BuOLi as base in dioxane at 100 °C, either in the absence
or in the presence of ligands, did not furnish expected diene 2a
(entries 1 and 2, Table 1). Because benzoquinone is known to
promote reductive elimination in Pd-catalyzed coupling
reactions15 and also can function as a terminal oxidant, we
envisioned that benzoquinone may be a suitable oxidant for the
present coupling reaction. Hence, performing the same reaction
in the presence of benzoquinone resulted in the formation of
branched diene 2a in 70% yield (entry 3). To the best of our
knowledge, the formation of a branched diene with Pd(II)
catalyst using hydrazone is difficult. Encouraged by this result,
we continued our studies (i) using a variety of bases such as
tert-BuOLi, Cs2CO3, and Ag2CO3; (ii) a variety of oxidants
such as (NH4)2S2O8, PIDA, Cu(OAc)2, and CuI; (iii) ligands
such as benzoxazole, bibenzoxazole, N-phenylurea, diazabuta-
diene, XPHOS, tert-butyl-XPHOS, PPh3, P(o-Tol)3, diethyl-
phosphite, and NHC-precursor (IPr·HCl). After undertaking a
thorough screening study, it was found that Pd(PPh3)2Cl2 is the
most suitable catalyst with benzoquinone as oxidant (2 equiv),
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bibenzoxazole as ligand (40 mol %), and tert-BuOLi (3 equiv)
as base at 100 °C for the homocoupling of 1a to the product 2a
in good yield (84%, entry 23, Table 1). Furthermore, it was
found that the reaction does not proceed with Pd(PPh3)4 in the
absence of oxidant or in the absence of Pd catalyst (entries 24
and 25, Table 1). These observations clearly indicates that
Pd(II) is essential for the coupling reaction.
Table 2. Substrate Scope for the Formation of 1,3-Branched
Dienes
a
As can be seen in Table 2, a variety of hydrazones were
reacted with Pd(II) catalyst under optimal reaction conditions
(entry 23, Table 1). The reaction proceeded well with
substituted acetophenone derivatives such as 1b−g. It is
noteworthy that acetophenones that were substituted with
electron-donating groups (entries 1 and 2, 1a and 1b, Table 2)
as well as electron-withdrawing groups underwent a smooth
reaction under the optimal conditions (entries 4−7, 1d−g,
Table 2). Interestingly, a remarkable chemoselectivity was
observed in the reaction of halo-substituted hydrazone
derivatives. Under the reaction conditions, no cross-condensa-
tion product was observed between the hydrazone and
haloarenes in the reaction of bromo-substituted hydrazone
derivatives of acetophenone (entry 4. Table 2).11 To the best of
our knowledge, the selectivity observed in these examples is
rare.8b Furthermore, it was noticed that the reaction is versatile
because dibenzyloxy-substituted hydrazone derivatives of
acetophenone (1h) underwent a smooth reaction to furnish
the corresponding branched dienes 2h in excellent yield (92%,
entry 8, Table 2). The scope of the method was extended to
study the reaction of hydrazones of naphthyl ethanones. Hence,
the reaction of hydrazones of 1-naphthylethanone (1i) and 2-
naphthylethanone (1j) under the optimized conditions yielded
the corresponding branched dienes 2i and 2j in good yields
(entries 9 and 10, Table 2). Additionally, the hydrazone of 1-
(thiophen-2-yl)ethanone 1k furnished the corresponding
branched diene 2k in 92% yield (entry 11, Table 2), indicating
that the strategy can be extended to synthesize branched dienes
containing heterocyclic compounds. The broad scope of the
transformation was further extended by subjecting an
unactivated substrate such as hydrazone of 4-phenylbutan-2-
one (1l) to the optimal reaction conditions to find
corresponding branched diene 2l and 3l in good yield (71%,
6:4 2l/3l) (entry 12, Table 2).
Synthesis of Highly Substituted Branched Dienes. Our
attempts to employ identical reaction conditions to obtain
highly substituted branched dienes were not fruitful. Therefore,
in search of suitable reaction conditions, we undertook a
screening study by employing the hydrazone of 1,2-
diphenylethanone 4a as a model precursor (Table 3). Earlier
conditions using Pd(PPh3)2Cl2, benzoquinone as an oxidant,
and bibenzoxazole as a ligand (20 mol %) at 100 °C yielded
expected product branched diene 5a as a minor product along
with stilbene (6a) as a major product (entry 1, Table 3).
Therefore, to develop a protocol to obtain the branched dienes,
the hydrazone of 4a was subjected to a variety of reaction
conditions (Table 3). As can be seen, increasing the amount of
ligand (bibenzaoxazole) to 40 mol % resulted in the formation
of 5a in 56% yield (entry 2, Table 4). Changing the ligand to
XPHOS (20 mol %) resulted in the formation of 5a in 66%
yield (entries 3, Table 3). It was found that PdCl2 or Pd(OAc)2
were not useful catalysts, as these reactions did not afford the
expected product but resulted in the formation of stilbene 6a in
almost quantitative yields (entries 4 and 5, Table 3). Further
enhancement in the formation of branched diene to 80% yield
was realized by increasing the amount of XPHOS to 40 mol %
a
Reaction conditions: 1 (0.4 mmol), Pd(PPh3)2Cl2 (5 mol %),
bibenzoxazole (40 mol %), p-BQ (1 mmol), t-BuOLi (1.5 mmol),
dioxane (3 mL). Isolated yields.
b
and performing the reaction in DMF (entry 6). Because ligands
are known to have a role in promoting coupling reactions,16
a
more nucleophilic phosphine ligand such as P(Cy)3 was
employed for the coupling reaction. However, this reaction
resulted in the formation of branched diene 5a in lower yield
(60%), and the formation of stilbene was observed (entry 7,
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Table 3. Optimization Studies for the Formation of 1,3-
Branched Dienes
Table 4. Substrate Scope for the Formation of 1,3-Branched
Dienes
a
a
b
yield (%)
entry
1
[Pd]
ligand
solvent
dioxane
5a
30
6
Pd(PPh3)2Cl2 bibenzoxazole
(20 mol %)
60
2
Pd(PPh3)2Cl2 bibenzoxazole
(40 mol %)
dioxane
56
40
3
4
5
6
7
8
Pd(PPh3)2Cl2 xphos (20 mol %)
dioxane
dioxane
dioxane
DMF
66
33
99
99
nd
nd
nd
PdCl2
xphos (20 mol %)
xphos (20 mol %)
trace
trace
80
Pd(OAc)2
Pd(PPh3)2Cl2 xphos (20 mol %)
Pd(PPh3)2Cl2 P(Cy)3 (20 mol %) dioxane
60
Pd(PPh3)2Cl2 diethylphosphite
(20 mol %)
DMF
90
c
9
Pd(PPh3)2Cl2 diethylphosphite
(20 mol %)
DMF
(MS 4 Å)
93
nd
a
Reaction conditions: 4a (0.47 mmol), [Pd] (5 mol %), ligand (40
mol %), p-BQ (1 mmol), t-BuOLi (1.5 mmol), solvent (3 mL).
Isolated yields. Molecular sieves (4 Å, 200 mg). nd, not detected.
b
c
Table 3). Recently, it was reported that phosphites can strongly
bind to Pd(II) complexes.17 Therefore, we thought that using
tri-coordinate phosphite as a ligand could be effective to
promote reductive elimination to furnish highly branched
dienes and to avoid the formation of undesired olefin. As
predicted, using diethylphosphite as a ligand brought a
spectacular difference in the formation of product 5a (90%,
entry 8), which was further improved to 93% using molecular
sieves (4 Å) in the reaction (93%, entry 9).
With a validated optimal condition in hand, the substrate
scope was extended, and the results are tabulated in Table 4. α-
Substituted hydrazone derivatives of acetophenone such as 4a
and 4b under the optimal reaction conditions formed
corresponding branched diene 5a (93%, E/E ratio 100)18 and
5b (77%, E/E ratio 71), respectively (entries 1 and 2, Table 4).
Similarly, the substrates carrying halogen substitution such as
4c and 4d formed the corresponding branched dienes 5c and
5d in good yields with expected selectivity (entries 3 and 4,
Table 4). Further, tetrasubstituted hydrazone (4e) and
hydrazone of tetralone (4f) furnished corresponding con-
jugated dienes 5e and 5f in 68% and 81%, respectively (entries
5 and 6, Table 4).
a
Reaction conditions: 4 (0.4 mmol), Pd(PPh3)2Cl2 (5 mol %),
diethylphosphite (40 mol %), p-BQ (1 mmol), t-BuOLi (1.5 mmol),
DMF (3 mL), molecular sieves (4 Å, 200 mg). Isolated yields. E/E
to Z/Z isomer ratio. E/Z.
b
c
d
precursor, which was prepared using 1-(2-aminophenyl)-
ethanone (7) and corresponding phenacyl bromide (8)
(Scheme 1). The bis-hydrazone of 2-((2-acetylphenyl)-
amino)-1-(4-chlorophenyl)ethanone (10a) was subjected to
the present reaction conditions, resulting in the formation of
corresponding quinoline derivative 3-(4-chlorophenyl)-4-meth-
ylquinoline 11a in 63% yield (Scheme 1, also see Supporting
a
Scheme 1. Synthesis of Quinolines
Novel Approach for the Synthesis of Quinolines and
Other Applications. The opportunity to form a C−C bond
using the present method led us to devise a new strategy for
constructing cyclic compounds. Particularly, the syntheses of
nitrogen-containing heterocyclic compounds were addressed
because they are biologically and pharmaceutically active
molecules and widely occur in nature.19 Among them, the
synthesis of quinoline derivatives is attractive owing to their
utility in medicinal applications as well as their utility as dyes
and antioxidants.20 In addition, most of the synthetic methods
that are available for the synthesis of quinoline adopted the
condensation of amines and carbonyl compounds.21 To test the
efficacy of the method, we used diketone derivative 2-((2-
acetylphenyl)amino)-1-(4-chlorophenyl)ethanone (9a) as the
a
Reaction conditions: (a) 7 (20 mmol), 8 (10 mmol) in MeCN (20
mL), rt, 24 h. (b) TsNHNH2, 1 h, diaoxane. (c) 10 (0.4 mmol),
Pd(PPh3)2Cl2 (5 mol %), Ligand (40 mol %), p-BQ (1 mmol), t-
BuOLi (1.5 mmol), DMF (3 mL), molecular sieves (4 Å, 200 mg). (d)
Isolated yields.
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Information Table S1 for screening studies). Similarly, the bis-
hydrazone of 2-((2-acetylphenyl)amino)-1-(4-methoxyphenyl)-
ethanone (10b) underwent a facile reaction to furnish
quinoline derivative 3-(4-chlorophenyl)-4-methylquinoline
(11b) in moderate yield (Scheme 1).
The application of this method is further emphasized by
synthesizing dienestrol derivatives, which are estrogen
receptors22 (Scheme 2). As seen in Scheme 1, hydrazone 12
catalyst under the optimal conditions. As expected, correspond-
ing branched diene 2g was isolated in 68% yield (Scheme 3).
This in situ reaction was further extended to 5-acetyl-1,3-
phenylene dibenzoate (14b) and 1-(3-fluorophenyl)propan-1-
one (14c), resulting in the formation of corresponding dienes
2h and 5d in good yields (Scheme 3).
To expand the utilily of this coupling reaction, a scaling-up
study was undertaken (Scheme 4). As can be seen, tosyl
hydrazone 4a (2 g, 5.5 mmol) under the optimized condition
furnished prodcut 5a in 62% isolated yield.
a
Scheme 2. Synthesis of Dienestrol Derivatives
a
Scheme 4. Scaling-up Experiment
a
Reaction conditions: 4a (2 g, 5.5 mmol), Pd(PPh3)2Cl2 (5 mol %, 75
mg), diethyl phosphite (300 mg, 40 mol %), p-BQ (1.2 g, 11 mmol, 2
equiv), t-BuOLi (1.3 g, 16 mmol, 3 equiv), DMF (12 mL), molecular
b
sieves (4 Å, 1 g). Isolated yield.
Mechanistic Studies. A tentative mechanism is proposed
in Scheme 5. Bis-hydrazone 10b in the presence of base forms
a
Reaction conditions: 12 (0.4 mmol), Pd(PPh3)2Cl2 (5 mol %), ligand
Scheme 5. Tentative Mechanism
(40 mol %), p-BQ (1 mmol), t-BuOLi (1.5 mmol), DMF (3 mL),
molecular sieves (4 Å, 200 mg).
under the optimal conditions furnished corresponding diene
13, which is a PTB (p-tolylbenzyl)-protected dienestrol that
can be further manipulated to dienestrol,23 diethylstilbestrol,24
and indenestrol25 using known methods.
One-Pot Reaction Using Ketone as Precursor. The
utility of hydrazones as the precursor for Pd-catalyzed cross-
coupling reactions led to the idea to employ ketones as
precursors to access the corresponding branched dienes in a
one-pot reaction. As can be seen in Scheme 3, an in situ one-
pot method to synthesize branched dienes using ketones as the
precursor is illustrated. 1-(2-Fluorophenyl)ethanone (14a) is
reacted with tosyl hydrazine followed by the addition of Pd
a
Scheme 3. One-Pot Reaction
the corresponding diazo compound (I). Furthermore, it was
found that the diazo derivative of p-methoxy acetophenone
(15) under the optimal reaction conditions underwent a
smooth transformation to corresponding diene 2a in 67% yield
(see Supporting Information, Scheme S1). This experimet
indicates that the reaction is probably going through the
corresponding diazo intermediate I. In addition, Pd(PPh3)2Cl2
reacts with ligand to form complex II (corresponding signal was
observed in ESI-MS, see the Supporting Information).
Complex II inserts into diazocompound I to furnish key
intermediate III via seven-membered palladacycle. Pd-inserted
a
Reaction conditions: (1) TsNHNH2, 1,4-diaoxane. (2) Pd(PPh3)2Cl2
(5 mol %), ligand (40 mol %), p-BQ (1 mmol), t-BuOLi (1.5 mmol),
DMF (3 mL), molecular sieves (4 Å, 200 mg).
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complex III is a highly reactive species, which cannot be
isolated. However, the corresponding molecular ion peak was
observed in the ESI-MS spectral analysis of the reaction mixture
(see Supporting Information). Furthermore, complex III loses
HCl to generate complex IV, which forms diene V and
generates Pd(II). Diene V aromatizes to 11b.
EtOAc (100 mL) and extracted sequentially with H2O (50
mL), 5% citric acid (50 mL), and brine (25 mL). The organic
layer was dried (Na2SO4), filtered through a pad of silica gel,
and in some cases further purified by a silica gel column to yield
the product.
Preparation of 2-((2-Acetylphenyl)amino)-1-(4-chlorophenyl)-
ethanone (9a). Yield = 93% (2.66 g), yellow solid, mp 140−143
1
°C. Rf = 0.4 (EtOAc/hexane 1:5). H NMR (400 MHz, CDCl3): δ
CONCLUSIONS
■
2.59 (s, 3H), 4.64 (s, 2H), 6.60−6.67 (m, 2H), 7.35 (t, J = 8 Hz, 1H),
7.45 (d, J = 8 Hz, 2H), 7.77 (d, J = 8 Hz, 1H), 7.94 (d, J = 8 Hz, 2H).
13C NMR (100 MHz, CDCl3): δ 200.7, 192.7, 149.4, 140.0, 134.9,
133.1, 132.7, 129.2, 129.1, 118.4, 114.9, 11.8, 49.5, 27.8. IR (neat,
cm−1): 3325, 2934, 1725, 1780, 1598, 1493, 1443, 1022, 900, 775, 700.
HRMS (ESI): calcd for C16H14ClNO2 (M + Na), 310.0611; found,
310.0613.
We have discovered a novel Pd-catalyzed selective coupling
reaction of hydrazones in the presence of t-BuOLi and
benzoquinone to form the corresponding branched olefin.
The utility of Pd catalyst for the cross-coupling reactions for
synthesizing branched conjugated dienes is rare. The reaction is
very versatile and compatible with a variety of functional
groups. The reaction was well-exploited to show the
applicability of the methodology for accessing heterocyclic
molecules, which may have good synthetic implications.
Additionally, an in situ reaction was conceived using ketones
as starting matetials in a one-pot reaction. Considerable
progress was made to understand the reaction mechanism,
and further work in our laboratory is underway to explore the
applications of this reaction.
Preparation of bis-N-Tosylhydrazones. General Procedure for
Converting Dicarbonyl Compounds to Bis-N-tosylhydrazones. A
solution of pure dicarbonyl compound (2.0 mmol) in methanol/
toluene (3:1 mL) was stirred and heated at 60 °C until the dicarbonyl
compound was dissolved. Then, TsNHNH2 (0.763 g, 4.1 mmol, 2.05
equiv) was added to the mixture. After approximately 2 h, the crude
products could be obtained as solid precipitates. The precipitates were
washed by petroleum ether and kept in a desiccator under vacuum to
afford the pure products. If the crude products could not be obtained
as solid precipitates after the reaction was completed (TLC), then the
solvent was removed by vacuum and the solid was used without
further purification. The yields of corresponding N-tosylhydrazone
derivatives were about ∼80%, and the reaction took 2 h in general
(usually 2 mol % TsOH was added to promote the reaction).
Characterization Data. 4,4′-(Buta-1,3-diene-2,3-diyl)bis-
(methoxybenzene) (2a). Yield = 84% (52 mg), colorless solid, mp
107−109 °C. Rf = 0.4 (hexane). 1H NMR (400 MHz, CDCl3): δ 3.76
(s, 6H), 5.23 (d, J = 1.4 Hz, 2H), 5.46 (d, J = 1.4 Hz, 2H), 6.78 (d, J =
8.7 Hz, 4H), 7.3 (d, J = 8.8 Hz, 4H). 13C NMR (100 MHz, CDCl3): δ
159.0, 149.3, 132.6, 128.4, 114.3, 113.5, 55.2. IR (neat, cm−1): 3422,
2969, 1597, 1474, 1454, 1168, 1065, 1038. HRMS (ESI): calcd for
C18H18O2 (M + H), 267.1385; found, 267.1387. The physical data
were identical to those previously reported.25
EXPERIMENTAL SECTION
■
General Procedure for the Homocoupling Reactions of
Tosylhydrazones. A well-stirred mixture of N-tosylhydrazone (0.4
mmol), p-BQ (1 mmol, 2 equiv), bibenzoxazole or diethylphosphite
(40 mol %), and Pd(PPh3)2Cl2 (0.0067 mmol, 5 mol %) in dioxane (3
mL) under nitrogen was heated at 100 °C. To this hot clear solution
was added t-BuOLi (1.5 mmol) at 100 °C until the completion of the
reaction (monitored by TLC). Then, the reaction mixture was cooled
to room temperature, diluted with EtOAc, and passed through a short
Celite pad. The solvent was evaporated under reduced pressure and
purified on a silica gel column.
General Procedure for the Intramolecular Coupling Reac-
tion of Tosylhydrazones. A well-stirred mixture of bis-N-
tosylhydrazone (0.4 mmol), p-BQ (1 mmol, 2 equiv), diethylphosphite
(40 mol %), Pd(PPh3)2Cl2 (0.0067 mmol, 5 mol %), and molecular
sieves in DMF (3 mL) under nitrogen was heated at 100 °C. To this
hot clear solution was added t-BuOLi (1.5 mmol) at 100 °C until the
completion of the reaction (monitored by TLC). Then, the reaction
mixture was cooled to room temperature, diluted with EtOAc, and
passed through a short Celite pad. The solvent was evaporated under
reduced pressure and purified on a silica gel column.
4,4′-(Buta-1,3-diene-2,3-diyl)bis(methylbenzene) (2b). Yield =
1
91% (53 mg), colorless solid, mp 57−59 °C. Rf = 0.55 (hexane). H
NMR (400 MHz, CDCl3): δ 2.29 (s, 6H), 5.25 (d, J = 1.5 Hz, 2H), 5.5
(d, J = 1.5 Hz, 2H), 7.27 (d, J = 7.8 Hz, 4H), 7.59 (d, J = 7.8 Hz, 4H).
13C NMR (100 MHz, CDCl3): δ 149.7, 137.3, 137.1, 128.8, 127.2,
115.3, 21.1. IR (neat, cm−1): 3086, 3923, 1904, 1797, 1605, 1503,
1436, 1183. HRMS (ESI): calcd forC18H18 (M + H), 235.1487; found,
235.1483. The physical data were identical to those previously
reported.25
General Procedure for the Homocoupling Reaction of in
Situ Generated Tosylhydrazones. A mixture of ketone (0.4 mmol,
1 equiv) and tosylhydrazide (0.42 mmol, 1.05 equiv) was stirred at 100
°C for 1 h in DMF (1 mL) as solvent. To this were added p-
benzoquinone (1 mmol, 2 equiv), ligand (40 mol %), and
Pd(PPh3)2Cl2 (0.0067 mmol) in 1,4-dioxane (3 mL) under nitrogen
followed by the addition of t-BuOLi (1.5 mmol) at 100 °C until the
completion of the reaction (monitored by TLC). Then, the reaction
mixture was cooled to room temperature, diluted with EtOAc, and
passed through a short Celite pad. The solvent was evaporated under
reduced pressure and purified on a silica gel column.
Buta-1,3-diene-2,3-diyldibenzene (2c). Yield = 93% (49 mg),
colorless solid, mp 44−45 °C. Rf = 0.5(hexane). 1H NMR (400 MHz,
CDCl3): δ 5.31 (s, 2H), 5.53 (s, 2H), 7.22−7.28 (m, 6H), 7.38−7.4
(m, 4H). 13C NMR (100 MHz, CDCl3): δ 149.8, 140.2, 128.2, 127.6,
127.5, 116.3. IR (neat, cm−1): 2924, 1598, 1493, 1443, 1022, 900, 775,
700. MS-DI (m/ z): 206 (M+), 191 (M-CH2), 178 (M-2CH2). The
physical data were identical to those previously reported.25
4,4′-(Buta-1,3-diene-2,3-diyl)bis(bromobenzene) (2d). Yield =
1
87% (87 mg), colorless solid, mp 78−80 °C. Rf = 0.65 (hexane). H
NMR (400 MHz, CDCl3): δ 5.3 (d, J = 1.3 Hz, 2H), 5.5 (d, J = 1.3 Hz,
2H), 7.21 (d, J = 8.5 Hz, 4H), 7.38 (d, J = 8.5 Hz, 4H). 13C NMR (100
MHz, CDCl3): δ 148.4, 138.7, 131.4, 129.1, 121.7, 117.0. IR (neat,
cm−1): inactive. MS-DI (m/z): 284 (M-HBr), 204 (M-2HBr). The
physical data were identical to those previously reported.26
General Procedure for the Preparation of Dicarbonyl
Compounds.
4,4′-(Buta-1,3-diene-2,3-diyl)bis(fluorobenzene) (2e). Yield = 76%
(45 mg), colorless solid, mp 48−51. Rf = 0.7 (hexane). 1H NMR (400
MHz, CDCl3): δ 5.29 (d, J = 1.4 Hz, 2H), 5.48 (d, J = 1.4 Hz, 2H),
6.92−6.97 (m, 4H), 7.3−7.34 (m, 4H). 13C NMR (100 MHz, CDCl3):
δ 162.4 (d, J = 250 Hz), 148.7, 136.0, 129.1 (d, J = 7.8 Hz), 116.3,
115.1 (d, J = 21 Hz). IR (neat, cm−1): 3432, 1647, 1033, 1016. MS-DI
(m/z): 242 (M+), 227 (M-CH2). The physical data were identical to
those previously reported.27
Aniline (20 mmol) and bromoacetophenone (10 mmol) were
combined in MeCN (20 mL) and allowed to stand at rt for 24
h. Solid aniline-HBr was filtered off, and the filtrate was
concentrated under vacuum. The residue was dissolved in
12141
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The Journal of Organic Chemistry
Article
3,3′-(Buta-1,3-diene-2,3-diyl)bis(nitrobenzene) (2f). Yield = 83%
(55 mg), colorless solid, mp 90−92 °C. Rf = 0.5 (EtOAc/hexane
Hz, 2H), 7.27−7.33 (m, 6H), 7.43−7.5 (m, 7H), 7.54−7.66 (m, 9H).
13C NMR (100 MHz, CDCl3): δ 141.0, 139.2, 139.0, 130.39, 130.28,
128.75, 128.71, 128.67, 127.14, 127.0, 126.9, 126.8, 126.7, 126.6,
126.3. IR (neat, cm−1): 2925, 2853, 1598, 1485, 1333, 1114, 1074,
1020, 907, 849, 765, 737, 691. HRMS (ESI): calcd for C30H26 (M +
Na), 409.1932; found, 409.1932.
1
1:10). H NMR (400 MHz, CDCl3): δ 5.5 (s, 2H), 5.7 (s, 2H), 7.47
(t, J = 8 Hz, 2H), 7.68 (d, J = 7 Hz, 2H), 8.12 (d, J = 8 Hz, 2H), 8.23
(s, 2H). 13C NMR (100 MHz, CDCl3): δ 148.4, 146.9, 141.1, 133.4,
129.5, 122.8, 122.3, 119.6. IR (neat, cm−1): 3431, 2919, 1559, 1526,
1348, 1099, 912, 808, 743. HRMS (ESI): calcd for C16H12N2O4 (M +
Na), 319.0695; found, 319.0695.
4,4′-(Hexa-2,4-diene-3,4-diyl)bis(chlorobenzene) (5c). Yield =
1
82% (55 mg), colorless solid, mp 62−65 °C. Rf = 0.55 (hexane). H
2,2′-(Buta-1,3-diene-2,3-diyl)bis(fluorobenzene) (2g). Yield = 79%
NMR (400 MHz, CDCl3): δ 1.44 (d, J = 6.4 Hz, 6H), 5.25 (q, J = 7
Hz, 2H), 7.08−7.2 (m, 5H), 7.34−7.36 (m, 4H), 7.5 (d, J = 6 Hz, 4H).
13C NMR (100 MHz, CDCl3): δ 143.7, 138.0, 131.2, 130.3, 130.0,
129.6, 128.3, 128.1, 127.99, 126.0, 15.2, 12.5. IR (neat, cm−1): 2924,
2853, 1593, 1489, 1263, 1089, 1015, 814, 668. MS-DI (m/z): 304 (M
+ 1), 287 (M-CH3), 275 (M-CH3CH), 232 (M-2HCl).
1
(46 mg), colorless solid, mp 54−56 °C. Rf = 0.6 (hexane). H NMR
(400 MHz, CDCl3): δ 5.22 (s, 2H), 5.31 (2H), 7.03−7.13 (m, 4H),
7.24−7.34 (m, 4H). 13C NMR (100 MHz, CDCl3): δ 159.9 (d, J =
246.2 Hz), 143.8, 131.4, 129.2 (d, J = 8.6 Hz), 128.4 (d, J = 14.3 Hz),
123.8, 119.3, 115.55 (d, J = 22.7 Hz). IR (neat, cm−1): 3433, 2924,
2853, 1844, 1616, 1580, 1234, 1200, 918, 758. MS-DI (m/z): 242
(M+), 227 (M-CH2).
3,3′-(Hexa-2,4-diene-3,4-diyl)bis(fluorobenzene) (5d). Yield =
75% (75 mg), colorless liquid. Rf = 0.5 (hexane). 1H NMR (400
MHz, CDCl3): δ 1.45 (d, J = 7 Hz, 6H), 5.26 (q, J = 7 Hz, 2H), 6.89
(d, J = 10 Hz, 2H), 6.93−6.98 (m, 4H), 7.31−7.36 (m, 2H). 13C NMR
(100 MHz, CDCl3): δ 162.7 (d, J = 244 Hz), 141.9 (d, J = 7.5 Hz),
129.5 (d, J = 8 Hz), 125.99, 125.6 (d, J = 2.5 Hz), 116.78 (d, J = 20.5
Hz), 113.5 (d, J = 21.6 Hz), 15.1. IR (neat, cm−1): 3398, 2927, 2854,
1610, 1582, 1435, 1265, 1069, 785. MS-DI (m/z): 270 (M+), 255 (M-
CH3), 241 (M-CH3CH).
(((Buta-1,3-diene-2,3-diylbis(benzene-5,3,1-triyl)tetrakis(oxy))-
tetrakis(methylene))tetrabenzene (2h). Yield = 92% (73 mg),
1
colorless solid, mp 140−142 °C. Rf = 0.4 (EtOAc/hexane 1:20). H
NMR (400 MHz, CDCl3): δ 4.98 (s, 8H), 5.27 (s, 2H), 5.5 (s, 2H),
6.5 (s, 2H), 6.65 (s, 4H), 7.28−7.4 (m, 20H). 13C NMR (100 MHz,
CDCl3): δ 159.7, 149.3, 142.2, 136.8, 128.5, 127.9, 127.6, 116.6, 106.9,
101.3, 70.0. IR (neat, cm−1): 3422, 2869, 1587, 1454, 1434, 1158,
1055, 1028, 834. HRMS (ESI): calcd for C44H38O4 (M + H),
631.2848; found, 631.2848.
Hexa-2,4-diene-2,3,4,5-tetrayltetrabenzene (5e). Yield = 68% (68
mg), colorless liquid. R = 0.5 (hexane). 1H NMR (400 MHz,
f
1,1′-(Buta-1,3-diene-2,3-diyl)dinaphthalene (2i). Yield = 68% (46
CDCl3): δ 7.52 (d, J = 8 Hz, 1 H), 7.38−7.34 (m, 5H), 7.29−7.17 (m,
7H), 7.1−7.04 (m, 3H), 6.94−6.92 (d, J = 7.8 Hz, 2H), 6.83 (s, 1H),
6.46 (s, 1H). 13C NMR (100 MHz, CDCl3): δ 143.9, 142.1, 138.7,
138.3, 137.4, 129.1, 128.9, 128.4, 128.3, 128.1, 127.8, 127.6, 127.1,
126.8, 126.5, 126.4, 126.0, 125.98, 21.1, 17.45. IR (neat, cm−1): 3070,
3026, 3012, 2934, 2862, 1965, 1586, 1480, 1462, 1360, 1037, 866. MS-
DI (m/z) (relative intensity): 386 (100), 356 (13), 281 (73), 265
(16), 219 (40).
3,3′,4,4′-Tetrahydro-1,1′-binaphthalene (5f). Yield = 81% (50
mg), colorless liquid. Rf = 0.5 (hexane). 1H NMR (400 MHz, CDCl3):
δ 2.36−2,41 (m, 4H), 2.88 (t, J = 7 Hz, 4H), 6.07 (t, J = 4.5 Hz, 2H),
6.90 (d, J = 7.7 Hz, 2H), 6.99 (t, J = 7.4 Hz, 2H), 7.07 (t, J = 7.4 Hz,
2H), 7.14 (d, J = 7.7 Hz, 2H). 13C NMR (100 MHz, CDCl3): δ
138.35, 135.8, 134.7, 127.99, 127.35, 126.7, 126.3, 125.1, 28.2, 23.3. IR
(neat, cm−1): 3057, 3017, 2932, 2881, 2829, 2598, 1484, 1450, 1265,
1157, 1039, 939. MS-DI (m/z): 258 (M+), 129 (vinyl radical). The
physical data were identical to those previously reported.29
1
mg), colorless solid, mp 175−177 °C. Rf = 0.35 (hexane). H NMR
(400 MHz, CDCl3): δ 5.08 (s, 2H), 5.24 (d, J = 1, 2H), 7.49−7.55 (m,
8H), 7.85−7.9 (m, 4H), 8.16 (dd, J = 8.5 Hz, J = 1.4 Hz, 2H). 13C
NMR (100 MHz, CDCl3): δ 148.4, 139.1, 133.6, 132.3, 128.2, 127.6,
126.8, 126.1, 125.9, 125.7, 125.3, 120.8. IR (neat, cm−1): 2922, 2851,
1817, 1593, 1575, 1506, 915, 800, 777. Anal. Calcd for C24H18: C,
94.08; H, 5.92. Found: C, 93.97; H, 6.06.
2,2′-(Buta-1,3-diene-2,3-diyl)dinaphthalene (2j). Yield = 91% (61
1
mg), colorless solid, mp 142−145 °C. Rf = 0.35 (hexane). H NMR
(400 MHz, CDCl3): δ 5.46 (d, J = 1.4 Hz, 2H), 5.74 (d, J = 1.6 Hz,
2H), 7.38−7.4 (m, 4H), 7.6−7.62 (m, 2H), 7.72−7.76 (m, 6H), 7.85
(s, 2H). 13C NMR (100 MHz, CDCl3): δ 149.7, 137.5, 133.2, 132.8,
128.3, 127.7, 126.6, 125.9, 125.8, 125.5, 116.99. IR (neat, cm−1): 3423,
3055, 1580, 1266, 747. Anal. Calcd for C24H18: C, 94.08; H, 5.92.
Found: C, 93.97; H, 6.06. The physical data were identical to those
previously reported.26
2,2′-(Buta-1,3-diene-2,3-diyl)dithiophene (2k). Yield = 92% (51
4,4′-(Hexa-2,4-diene-3,4-diyl)bis(((4-methylbenzyl)oxy)benzene)
1
1
mg), brown liquid. Rf = 0.8 (hexane), unstable at rt. H NMR (400
(13). Yield = 42% (35 mg), colorless liquid. Rf = 0.4 (hexane). H
MHz, CDCl3): δ 5.25 (s, 2H), 5.6 (s, 2H), 6.88−6.91 (m, 2H), 6.94−
6.95 (m, 2H), 7.15−7.17 (m, 2H). 13C NMR (100 MHz, CDCl3): δ
143.5, 142.5, 127.4, 126.0, 124.8, 114.2. IR (neat, cm−1): 3443, 2921,
1662, 1518, 1415, 1236. MS-DI (m/z): 218 (M+), 203 (M-CH2). The
physical data were identical to those previously reported.26
(3,4-Dimethylenehexane-1,6-diyl)dibenzene (2l and 3l). Yield =
71% (62 mg), colorless liquid. Rf = 0.4 (hexane). 1H NMR (400 MHz,
CDCl3): δ 2.55−2.61 (m, 4H), 2.73−2.8 (m, 4H), 4.99 (s, 2H), 5.17
(s, 2H), 7.17−7.2 (m, 10H), 7.25−7.31 (m, 8H). 13C NMR (100
MHz, CDCl3): δ 146.7, 142.2, 138.5, 128.55, 128.53, 128.4, 128.37,
128.3, 126.1, 125.8, 112.2, 36.1, 35.1, 20.47, 14.5. IR (neat, cm−1):
3025, 2922, 2854, 1605, 1454, 1178. MS-DI (m/ z): 262 (M+), 171
(M-CH2Ph). The physical data were identical to those previously
reported.28
NMR (400 MHz, CDCl3): δ 2.05 (d, J = 6.8 Hz, 6H), 2.23 (s, 6H),
6.38 (q, J = 6.8 Hz, 2H), 6.83 (d, J = 8.8 Hz, 4H), 6.95 (d, J = 8 Hz,
4H), 7.4 (d, J = 8 Hz, 4H), 7.28−7.39 (m, 6H), 7.47 (d, J = 8.8 Hz,
4H). 13C NMR (100 MHz, CDCl3): δ 158.1, 136.9, 135.0, 133.9,
132.4, 129.45, 128.5, 125.48, 128.1, 127.46, 114.3, 69.9, 20.8, 16.8. IR
(neat, cm−1): 2994, 2843, 1583, 1489, 1243, 1099, 1035. HRMS
(ESI): calcd for C34H34O2 (M+), 474.2559; found, 474.2556.
Characterization Data for Quinolone Derivatives. 3-(4-
Chlorophenyl)-4-methylquinoline (11a). Yield = 63% (19 mg),
1
colorless liquid. R = 0.4 (EtOAc/hexane 1:5). H NMR (400 MHz,
f
CDCl3): δ 2.6 (s, 3H), 7.34 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz,
2H), 7.74 (t, J = 7.2 Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 8
Hz, 1H), 8.76 (s, 1H). 13C NMR (100 MHz, CDCl3): δ 151.1, 147.1,
140.7, 137.1, 133.8, 133.3, 131.2, 130.0, 129.1, 128.7, 127.9, 126.9,
124.2, 22.68. IR (neat, cm−1): 2920, 2850, 1651, 1457, 1261, 1017,
913, 744. HRMS (ESI): calcd for C16H12ClN (M + H), 254.0737;
found, 254.0738.
(1E,3E)-Buta-1,3-diene-1,2,3,4-tetrayltetrabenzene (5a). Yield =
1
93% (68 mg), colorless solid, mp 170−172 °C. Rf = 0.5 (hexane). H
NMR (400 MHz, CDCl3): δ 6.3 (s, 2H), 6.73−6.75 (m, 4H), 7.0−
7.02 (m, 6H), 7.24−7.32 (m, 4H), 7.37−7.42 (m, 6H). 13C NMR
(100 MHz, CDCl3): δ 145.5, 139.7, 137.2, 131.6, 130.3, 129.4, 128.7,
127.7, 127.3, 126.5. IR (neat, cm−1): 3077, 3056, 3022, 2924, 2852,
1955, 1596, 1490, 1442, 1350, 1027, 866, 761, 753, 692. Anal. Calcd
for C28H22: C, 93.81; H, 6.19. Found: C, 93.76; H, 6.26. The physical
data were identical to those previously reported.25
3-(4-Methoxyphenyl)-4-methylquinoline (11b). Yield = 56% (16
1
mg), yellow liquid. Rf = 0.35 (EtOAc/hexane 1:5). H NMR (400
MHz, CDCl3): δ 2.61 (s, 3H), 3.89 (s, 3H), 7.04 (d, J = 8 Hz, 2H),
7.32 (d, J = 8 Hz, 2H), 7.34 (t, J = 7.8 Hz, 1H), 7.72 (t, J = 7.8 Hz,
1H), 8.09 (d, J = 8.4, 1H), 8.13 (d, J = 8.4 Hz, 1H), 8.8 (s, 1H). 13C
NMR (100 MHz, CDCl3): δ 159.2, 151.7, 134.1, 131.5, 131.1, 129.9,
128.7, 128.0, 127.8, 126.7, 126.4, 124.2, 113.9, 55.3, 15.6. IR (neat,
cm−1): 2930, 2860, 1641, 1467, 1271, 1027, 903. HRMS (ESI): calcd
for C17H15NO (M + H), 250.1232; found, 250.1234.
4,4″-(Hexa-2,4-diene-3,4-diyl)di-1,1′-biphenyl (5b). Yield = 77%
1
(59 mg), colorless solid, mp 231−233 °C. Rf = 0.35 (hexane). H
NMR (400 MHz, CDCl3): δ 1.52 (d, J = 6.6 Hz, 6H), 5.36 (q, J = 7
12142
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Article
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ASSOCIATED CONTENT
■
S
* Supporting Information
Ligands employed for screening and control studies, Ortep
diagram of 5a, plausible mechanism for stereoselectivity for the
formation of highly substituted branched dienes, screening
studies for optimization for intramolecular reaction, 1H and 13
C
spectra and spectral data for all compounds, and reaction of
diazo compound 15 with Pd(PPh3)2Cl2. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: prabhu@orgchem.iisc.ernet.in; Tel.: +91-80-
22932887; Fax: +91-80-23600529.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge support from IISc, RL Fine Chem, and CSIR
(no. 01/2415/10-EMR-II). We thank Dr A. R. Ramesha for
useful discussions. D.P.O. thanks UGC for a senior research
fellowship.
(25) Eom, D.; Park, S.; Park, Y.; Ryu, T.; Lee, P. H. Org. Lett. 2012,
14, 5392−5395.
(26) Nakayama, J.; Machida, H.; Saito, R.; Akimoto, K.; Hoshino, M.
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