Substituted functional olefins through lateral sequential lithiation/silylation/condensation of tertiary aromatic amides: A ligand for phosphane-free palladium-catalyzed Suzuki coupling reactions

Article abstract of DOI:10.1002/ejoc.201101284

An unprecedented lateral sequential lithiation/silylation/condensation of tertiary aromatic amides has been developed that provides an efficient method to build up functional olefins in good yields. In addition, we have established an efficient and simple method that involves UV/Vis, fluorescence, and NMR analyses, to detect the interaction between transition-metal salts and functional olefins containing tertiary amides. This has enabled a highly efficient palladium-catalyzed Suzuki coupling reaction in the presence of tertiary aromatic amide-derived olefin ligands to be developed. The best results were obtained by employing 2 mol-% Pd(OAc)₂, 2 equiv. Cs ₂CO₃, a reaction temperature of 80 °C, dioxane as the solvent, and phosphane-free olefin 2d as ligand. Copyright

Full text of DOI:10.1002/ejoc.201101284

FULL PAPER
DOI: 10.1002/ejoc.201101284
Substituted Functional Olefins Through Lateral Sequential Lithiation/
Silylation/Condensation of Tertiary Aromatic Amides: A Ligand for
Phosphane-Free Palladium-Catalyzed Suzuki Coupling Reactions
Li-Wen Xu,*[a,b] Xi-Huai Chen,[a] Hao Shen,[a] Yuan Deng,[a] Jian-Xiong Jiang,[a]
Kezhi Jiang,[a] Guo-Qiao Lai,[a] and Chun-Qi Sheng[a]
Keywords: Lithiation / Silylation / Olefination / Palladium / Cross-coupling
An unprecedented lateral sequential lithiation/silylation/
condensation of tertiary aromatic amides has been developed
that provides an efficient method to build up functional ole-
tiary amides. This has enabled a highly efficient palladium-
catalyzed Suzuki coupling reaction in the presence of tertiary
aromatic amide-derived olefin ligands to be developed. The
fins in good yields. In addition, we have established an ef- best results were obtained by employing 2 mol-% Pd(OAc)2,
ficient and simple method that involves UV/Vis, fluores-
cence, and NMR analyses, to detect the interaction between
transition-metal salts and functional olefins containing ter-
2 equiv. Cs2CO3, a reaction temperature of 80 °C, dioxane as
the solvent, and phosphane-free olefin 2d as ligand.
construction of tertiary aromatic amide-derived olefins
through one-pot lateral sequential lithiation/silylation/con-
densation (Scheme 1). Inspired by the lithiation method re-
ported by Clayden et al.,[4] we investigated the one-pot se-
quential reactions of amide 1 with a range of carbonyl com-
pounds. Herein, we describe the successful development of
lateral sequential lithiation/silylation/condensation of terti-
ary aromatic amides through key and directed lithiation to
generate functional olefins. Furthermore, it was found that
functional olefins with tertiary aromatic amides could be
used as sensitive fluorescent probes to detect interactions
between transition metals and the olefin, which led us to
the develop an effective and unreactive olefin ligand for use
in palladium-catalyzed Suzuki coupling reactions.
Introduction
Olefins are arguably the most important and basic build-
ing blocks in organic synthesis. In the realm of olefin chem-
istry, the significance of substituted olefins is reflected in
the important and potential applications of olefin-contain-
ing compounds in organic synthesis, optical materials, me-
dicinal chemistry, polymeric materials, molecular devices,
and organic conductors.[1] Therefore, for large-scale appli-
cations, it is beneficial to develop more convenient synthetic
routes to structurally divergent olefins. During the past cen-
tury, significant achievements have been made in the syn-
thesis of substituted olefins, nevertheless, highly efficient re-
gio- and chemoselective methods to generate substituted
olefins bearing different carbon-linked functional groups
still presents a particular challenge in organic synthesis.[2]
In the last few decades, directed remote lithiation of terti-
ary aromatic amides have received considerable attention
because of their use in the regioselective synthesis of nonbi-
aryl atropisomers and chiral aromatic amide derivatives.[3]
Although several electrophiles, such as aldehydes and si-
lanes, have been introduced to the tertiary aromatic amides,
to the best of our knowledge, there are no reports on the
Scheme 1. The construction of olefins directed by lithiation.
Results and Discussion
[a] Key Laboratory of Organosilicon Chemistry and Material
Technology of Ministry of Education,
Hangzhou Norma University,
The Synthesis of Aromatic Amide-Derived Olefins (2)
through One-Pot Lateral Sequential Lithiation/Silylation/
Condensation
Hangzhou 310012, P. R. of China
Fax: +86-571-28865135
E-mail: liwenxu@hznu.edu.cn
licpxulw@yahoo.com
Initially, we focused on using N,N-diisopropyl-2-methyl-
benzamide (1) as a scaffold for the direct lithiation and sub-
sequent transformation. We were particularly interested in
the tertiary amide moiety of compound 1 because it is able
[b] College of Chemistry & Chemical Engineering,
Yangzhou University,
Yangzhou 225002, P. R. of China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101284.
290
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Phosphane-Free Palladium-Catalyzed Suzuki Coupling
to direct a lithium to the CH3 center of 1, which would be
beneficial to the lateral lithiation and subsequent silylation
and condensation. In this procedure, treatment of 1 in tetra-
hydrofuran (THF) at –78 °C with three equivalents of
sBuLi in the presence of N,N,NЈ,NЈ-tetramethylethylenedi-
amine (TMEDA) for one hour, was followed by the sequen-
tial addition of trimethylsilyl chloride (TMSCl) and benzal-
dehyde. Initial experimental results demonstrated that, in
the clean reaction of 1 with sBuLi in THF, as expected,
the aromatic amide was double laterally lithiated and then
sequentially silylated or alkylated, leading to the formation
of functionalized olefin 2a in good yield (90%; Scheme 2).
The appending olefin was obtained as a mixture of Z/E
isomers (70:30); the olefin geometry was determined by the
1H NMR chemical shift and coupling constant as well as
by infrared spectroscopic analysis.[5]
Scheme 2. Lateral sequential lithiation/silylation/condensation of
amide 1a.
It seems likely that this sequential lithiation/silylation/
condensation actually occurs in five steps (Scheme 3). First,
the lithiation was promoted by s-butyl lithium by deproton-
ation at low temperature to give i-2, which leads to the aro-
matic tertiary amide-derived silane through silylation, from
which product 3 was successfully obtained. Lithiation of 3
resulted in a second deprotonation and then to nucleophilic
addition to the aldehyde to generate intermediate i-3. In the
last step of desilylation and hydroxy group formation, sim-
ilar to Peterson olefination,[6] the olefin 2a was formed in a
(Z)-selective manner (Z/E = 65:35).
Scheme 4. Lateral sequential lithiation/silylation/condensation of
amides 1.
lithiation/silylation/condensation proceeded smoothly un-
der the optimized conditions, and the conjugated olefins 2
from tertiary aromatic amides were obtained in moderate
to good isolated yields. Aliphatic aldehydes and ketones
also gave the corresponding olefins in moderate yields and
regioselectivities. Interestingly, the use of chalcone and α,β-
unsaturated aldehyde as the electrophiles also furnished the
corresponding conjugated dienes 2c and 2k in good yields.
Therefore, this procedure should be useful for the construc-
tion of carbon–carbon double bonds, which is particularly
Scheme 3. A mechanistic pathway to olefins.
As shown in Scheme 4, various carbonyl compounds important for the development of optical organic molecules
were used as electrophiles, including aldehydes and ketones, because π-conjugated molecules have emerged as promising
in this sequential reaction. As hoped, the lateral sequential materials for the application in flexible, low-cost, and light-
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L.-W. Xu et al.
FULL PAPER
weight electronic devices.[7] Figure 1 shows the X-ray crystal of intermolecular interaction, especially for assessing the in-
structure of 2d, which demonstrated the (Z)-isomer of al- teraction of metals with receptors.[9] As shown in Figure 2,
kene formed.
the fluorescence properties of olefin 2a and mixtures of 2a
with transition-metal salts in dichloromethane were
studied. Interestingly, the observed effects of transition-
metal salts on the positions of the fluorescence bands are
clear, and there was an apparent increase of fluorescence
intensity in the order: Pd(OAc)2 Ͼ Rh(OAc)2 Ͼ IrCl4Na Ͼ
RhCl3 Ͼ AuCl3 Ͼ IrCl4 Ͼ IrCl3. These data suggest that
the coordination of these metal ions to olefin 2a takes place
in varying degrees. In addition, there is no evidence in fluo-
rescence spectroscopy for the interaction between RuCl3
and 2a, in which the fluorescence intensity is observed in
almost complete agreement with that of 2a in the absence
of any transition metal salt. Among the metal salts screened
in this study, Pd(OAc)2 was found to be the best choice,
with promising interactions in the metal–olefin complex
(line f in Figure 2). This behavior is probably the result of
the strong coordination or interaction between palladium
and olefin 2a, which hinders the vibration and rotation of
the bonds in the olefin and phenyl units. Thus, we have
established a simple yet highly selective method to deter-
mine which metals interact with bifunctional aromatic
amide-derived olefin 2a; this should enable olefin 2a and
others to work as new and effective ligands in palladium
catalysis.
Figure 1. X-ray crystal structure of 2d (CCDC-837440).
Despite the fact that the E/Z selectivity was generally
low to moderate, this new simplified version of the one-
pot Peterson olefination could successfully be applied to the
synthesis of aromatic olefins with ortho-functional groups.
Of particular potential are olefins of type 2, bearing tertiary
aromatic amides, in which two types of functional groups,
olefin and amide, are viable for further functionalization
and application. Therefore, except that the successful strat-
egy in the preparation of functional olefins through amide-
directed lateral lithiation/olefination has been developed,
the exploring of the potential application of compound 2
in organic transformation is highly desired.
Investigation of the Interaction between Olefin 2 and
Transition Metals by UV/Vis and Fluorescence
Spectroscopy
It is well-known that olefins have well-defined donor
(filled π) orbitals, thus, a characteristic of olefins is the abil-
ity to coordinate to transition metals to form organometal-
lic complexes. This is of great importance in the field of
transition-metal catalysis because the transition-metal–ole-
fin complex could be employed as a catalyst precursor to
activate substrates on the basis of ligand-exchange reac-
tions.[8] Because olefins of type 2 are multifunctional, they
are considered to be interesting and effective ligands that
are capable of simultaneously being involved in two binding
interactions in homogeneous transition-metal catalysis. In
an attempt to establish a strong interaction between transi-
tion-metal salts and olefins 2, we chose to investigate the
interaction between olefin 2a and several typical transi-
tional-metal salts by UV/Vis and fluorescence spectroscopy.
Figure 2. Changes in the fluorescence spectra upon excitation of 2a
and mixtures of 2a with an equimolar amount of transition metals
at 289 nm: (a) 2a alone; (b) AuCl3; (c) IrCl3; (d) IrCl4; (e) IrCl6Na;
(f) Pd(OAc)2; (g) Rh(OAc)2; (h) RhCl3; (i) RuCl3.
The Application of Olefin 2 as Ligand in the Palladium-
Catalyzed Suzuki Coupling Reaction
We then studied the application of functionalized olefins
The interaction between olefin 2a and transition-metal 2 in organic synthesis. In fact, much attention has focused
salts in dichloromethame was first examined by using UV/ upon the use of palladium–olefin complexes in organic syn-
Vis spectroscopy (Figure S2; see the Supporting Infor- thesis.[10,11] However, to the best of our knowledge, except
mation). Comparison of the absorption spectra of 2a with for [Pd2(dba)3], there are few reports on the development
a mixture of 2a and a range of transition metals revealed of olefin–ligand systems in palladium-catalyzed organic
only small differences in the two strong absorption bands transformations.[11] In this context, on the basis of above
at 230 and 285–293 nm. Therefore, it was difficult to con- hypothesis and findings, we found that olefin 2a and related
firm the coordination of the metal with olefin 2a.
compounds could work as unusual ligands in the palla-
Fluorescence spectroscopy has been shown to be a dium-catalyzed Suzuki coupling reaction. The Suzuki cross-
powerful and highly sensitive analytical tool for the study coupling reaction is one of the most important methods for
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Phosphane-Free Palladium-Catalyzed Suzuki Coupling
the construction of new carbon–carbon bonds and for the saturated aldehydes or enones, such as 2c and 2k, were
formation of symmetric and nonsymmetric biaryls that are found to be effective in promoting the Suzuki coupling re-
found in a myriad of application as privileged molecules or action, giving the coupling product in moderate yields (57–
macromolecules, such as polymers, biologically active com- 69% yield; Table 1, entries 3 and 10). However, the olefins
pounds, ligands, and many useful materials.[12] However, al- derived from aromatic ketones (2f, 2g, 2h, 2n, and 2o)
though recent developments have led to an expansion of showed low to moderate activity (15–57% yield; Table 1,
the coupling reaction, and many efficient palladium catalyst entries 6, 7, 8, 12, and 13), for example, only 15% yield was
systems have been developed over the last few decades, the obtained in the presence of olefin 2n (Table 1, entry 11).
principal drawbacks are often the time required, difficulties These results suggested that olefin 2a or 2d acted as the
in operation, and the availability, stability in air, and cost best ligand in this cross-coupling reaction, and these results
of the palladium complexes and phopshine ligands. are consistent with the fluorescence analysis. Although the
Furthermore, many palladium complexes suffer from low Z- or E-olefin have not so far been isolated, it should be
functional group tolerance, and/or air- or moisture-sensitiv- noted that the catalytic activity of the Z- and E-olefins are
ity. Herein, we report the olefin 2 promoted phosphane-free different, according to our preliminary results. For example,
palladium-catalyzed Suzuki cross-coupling reaction that when the ratio of Z/E is 30:70, the yield of palladium-cata-
takes place with outstanding functional group tolerance un- lyzed Suzuki reaction is low (19% yield; Table 1, entry 18).
der mild conditions without special inert atmosphere tech-
niques.
In the next evaluation, the activities of ligands 2a and 2d
were determined in the Suzuki coupling reaction of various
Inspired by the procedure reported by Tao and Boy- aromatic bromides. As depicted in Scheme 5, the palla-
kin,[13] the evaluation of olefins 2 as ligands was carried dium-catalyzed Suzuki coupling reaction promoted by ole-
out under the reported conditions in which a mixture of 4- fin 2d can be employed with both electron-deficient and
bromoanisole and phenylboronic acid was treated with electron-rich bromides. In most cases, the biphenyl products
2 mol-% Pd(OAc)2 and 2 equiv. Cs2CO3 in dioxane at 80 °C of the coupling reaction were obtained in excellent yields
for 3 h (Table 1). Among the olefins investigated, mono- (up to 99%). For example, when electronically activated,
substituted olefins with terminal alkene moieties, such as 2a nonactivated, or deactivated aromatic bromide substrates
and 2d, showed promising activity, giving the corresponding such as 4-bromobenzaldehyde, 1-bromo-4-fluorobenzene,
biaryl product in good yields (Table 1; 75–77% yield). and 1-bromo-2-methylbenzene, were coupled with phen-
Alkyl-substituted 2i displayed clear positive activity (54% ylboroic acid, good to excellent yields were achieved in the
yield; Table 1, entry 9), and conjugate dienes from α,β-un- presence of the olefin ligand 2d. Impressively, whereas only
moderate conversion rate and product yield was observed
with 2-bromopyridine, excellent yields were found for aryl
bromides containing a carbonyl group, such as 2-bromo-4-
methoxybenzaldehyde, 2-bromobenzaldehyde, 2-bromo-4-
Table 1. Screening of olefin ligands 2 in the palladium-catalyzed
Suzuki coupling reaction.[a]
Entry
Ligand
Yield [%][b]
[c]
1
2
3
4
5
6
7
8
–
15
75
57
77
48
36
57
40
54
69
74
15
25
48
61
26
70
19
2a
2c
2d
2e
2f
2g
2h
2i
2k
2l
2n
2o
2p
2q
1a
2a[d]
2a[e]
9
10
11
12
13
14
15
16
17
18
[a] Reaction conditions: 4-bromoanisole (1.0 mmol), phenylboronic
acid (1.2 mmol), Cs2CO3 (2.0 mmol), dioxane (3.0 mL), 80 °C, 3 h.
[b] Isoalted yield. [c] No ligand used. [d] Z/E ratio 50:50. [e] Z/E
ratio 30:70.
Scheme 5. Reactivities of electron-deficient and electron-rich brom-
ides catalyzed by palladium/olefin 2d catalyst system in dioxane.
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General Procedure for the Preparation of 4 by Lithiation/Silylation/
Peterson Condensation: sec-Butyllithium (2.4 equiv.) was added to
a solution of N,N-diisopropyl-2-methylbenzamide (1) and TMEDA
(2.4 equiv.) in THF at –78 °C under argon. The resulting orange
solution was stirred at this temperature for 1 h, followed by ad-
dition of chlorotrimethylsilane (2.0 equiv.). The reaction was stirred
for a further 2 h, then the carbonyl compound (1.5 equiv.; aldehyde
or ketone), was added at –78 °C. The reaction mixture was warmed
to room temperature and stirred for 18 h, then poured into water,
and extracted into EtOAc. The combined extracts were dried with
(trifluoromethyl)benzaldehyde, and 1-(4-bromophenyl)etha-
none, as well as 4-bromobenzenamine; all these functional
groups (CHO, amino, and ketone) were tolerated. Thus, the
olefin-promoted palladium-catalyzed Suzuki coupling reac-
tion presented herein is simple, highly convenient, and uni-
versally applicable. Although these studies did not provide
the exact structure of the palladium–olefin complex di-
rectly, these results confirm that the olefin moiety is very
important to the palladium-catalyzed Suzuki coupling reac-
tion and could explain why mono-substituted olefin 2a or magnesium sulfate, and concentrated under reduced pressure to
give the crude product. The product was purified by column
chromatography (silica gel, petroleum/ethyl acetate).
2d exhibits better activity in the Suzuki coupling reaction.
N,N-Diisopropyl-2-styrylbenzamide (2a): White solid; yield 90%
(mixture of isomers); E:Z = 70:30; Rf = 0.4 (ethyl acetate/hexane,
Conclusions
1
1:5). FTIR (NaCl, neat): ν = 1623 [CON(C H ) ] cm–1. H NMR
˜
3
7 2
(400 MHz, CDCl3): δ = 7.70 (d, J = 8.0 Hz, 0.3 H), 7.48 (d, J =
8.0 Hz, 0.7 H), 7.38–7.25 (m, 8 H), 7.13–7.09 (m, 1 H), 6.65 (d, J
= 4 Hz, 1 H), 3.88–3.62 (m, 1 H), 3.57–3.49 (m, 1 H), 1.68–1.58
(m, 6 H), 1.15–1.04 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 170.2, 138.6, 138.4, 131.4, 130.6, 129.6, 128.9, 128.8, 128.4,
128.3, 127.7, 127.5, 127.3, 127.3, 126.5, 125.4, 125.4, 125.3, 125.1,
51.1, 45.9, 20.8, 20.5 ppm. GC–MS: m/z (%) = 307.16 (28), 292.08
(2), 264.07 (6), 207.01 (100), 178.01 (55), 152.00 (8), 77.00 (2).
HRMS (ESI): Calcd. for [C21H25NO+Na]+ 330.1834; found
330.1848.
We have developed an unprecedented lateral sequential
lithiation/silylation/Peterson condensation of tertiary aro-
matic amides, providing an efficient method to build up
functional olefins in good yields. As a result of ortho-met-
alation, a clear effect of the tertiary aromatic amide was to
direct the double lithiation successfully even in the presence
of a bulky silicon-based group. In addition, we have estab-
lished an efficient and simple method to detect the coordi-
nation or interaction between transition-metal salts and
functional olefin-containing tertiary amides by fluorescence
spectroscopy. This has led to the development of a highly
efficient palladium catalyst for phosphane-free Suzuki cou-
pling reactions in the presence of the tertiary aromatic
amide-derived olefins. The cross-coupling reaction can be
performed under mild conditions and provides a simple
protocol for the preparation of biaryls. This development is
also expected to offer a new olefin ligand for palladium
catalysis and provides an alternative strategy for cross-cou-
pling reactions in general. Further applications of this type
of olefin ligand to transition-metal catalysis are being devel-
oped in our group.
2-(2,2-Diphenylvinyl)-N,N-diisopropylbenzamide (2b): Light-yellow
solid; Yield: 89%; Rf = 0.4 (ethyl acetate/hexane, 1:5). FTIR (NaCl,
neat): ν = 1621 [CON(C H ) ] cm–1. 1H NMR (400 MHz, CDCl ):
˜
3
7 2
3
δ = 7.23–7.19 (m, 8 H), 7.11–7.08 (m, 2 H), 7.06–7.02 (m, 2 H),
6.94 (s, 1 H), 6.87–6.83 (m, 1 H), 6.69 (d, J = 8 Hz, 1 H), 3.80–
3.73 (m, 1 H), 3.42–3.36 (m, 1 H), 1.51 (d, J = 8 Hz, 3 H), 1.37
(d, J = 8 Hz, 3 H), 1.06 (dd, J = 16, 8 Hz, 6 H) ppm. 13C NMR
(100 MHz,CDCl3): δ = 170.5, 143.6, 143.0, 140.1, 139.6, 133.2,
130.3, 129.3, 128.6, 128.2, 127.6, 127.3, 127.1, 124.9, 124.6, 51.1,
45.9, 20.9, 20.8, 20.4 ppm. GC–MS: m/z (%) = 383.15 (57), 283.05
(100), 265.04 (51), 253.07 (30), 239.02 (19), 206.95 (19), 178.04 (18),
105.02 (17), 76.95 (15). HRMS (ESI): Calcd. for [C27H29NO+H]+
384.2327; found 384.2303.
2-(2,4-Diphenylbuta-1,3-dienyl)-N,N-diisopropylbenzamide
(2c):
Light-yellow solid; yield 60% (mixture of isomers); Z/E = 59:41;
Experimental Section
R = 0.4 (ethyl acetate/hexane, 1:5). FTIR (NaCl, neat): ν = 1630
˜
f
[CON(C3H7)2] cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.55–7.23
(m, 12 H), 7.15–7.11 (m, 2 H), 6.93–6.84 (1 H), 6.71–6.22 (m, 2 H),
3.80–3.67 (m, 1 H),3.62–3.41 (m, 1 H), 1.73–1.37 (m, 6 H), 1.24–
1.05 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.5, 142.7,
142.3, 141.6, 139.3, 139.2, 138.1, 137.4, 137.3, 134.5, 133.8, 133.4,
132.7, 131.9, 130.4, 129.6, 129.1, 128.9, 128.7, 128.6, 128.3, 128.2,
127.8, 127.6, 127.3, 127.0, 126.7, 126.6, 126.5, 125.1, 124.8, 51.1,
51.0, 46.0, 45.8, 21.0, 20.9, 20.8, 20.6, 20.4, 20.2 ppm. GC–MS: m/z
(%) = 409.27 (100), 324.15 (29), 309.11 (35), 291.06 (25), 281.11
(35), 231.06 (59), 202.03 (79), 191.07 (35), 90.97 (60), 76.89 (21).
HRMS (ESI): Calcd. for [C29H31NO+H]+ 410.2484; found
410.2481.
Flash column chromatography was performed over silica (200–
300 mesh). 1H and 13C NMR spectra were recorded at 400 and
100 MHz, respectively, with an Advance (Bruker) 400 MHz spec-
trometer, and were referenced to the internal solvent signals. Thin
layer chromatography was performed using silica gel F254 TLC
plates and visualized with ultraviolet light. EI and CI mass spectra
were performed with a Trace DSQ GC/MS spectrometer. Data are
reported in the form of (m/z). The substrates, including s-butyllith-
ium, were commercially available and used directly. ESI-MS analy-
ses of the samples were obtained with an LCQ advantage mass
spectrometer (ThermoFisher Company, USA), equipped with an
ESI ion source operated in the positive ionization mode, with data
acquisition using the Xcalibur software (Version 1.4). UV/Vis ab-
sorption and circular dichroism spectra were recorded with MOS-
450/AF-CD and Evolution-300 instruments, respectively. X-ray dif-
fraction data sets were collected with Bruker APEX DUO and
Bruker APEX-II CCD diffractometers. Programs used: data collec-
tion Bruker APEX2,[14a] data reduction Bruker SAINT, absorption
correction for multi-scan, structure solution SHELX-97,[14b] struc-
ture refinement SHELXL-97,[14b] graphics Bruker SHELXTL.[14b]
N,N-Diisopropyl-2-(4-methylstyryl)-benzamide (2d): White solid;
yield 55% (mixture of isomers); Z/E = 80:20; Rf = 0.4 (ethyl acet-
ate/hexane, 1:5). FTIR (NaCl, neat): ν = 1624 [CON(C H ) ] cm–1.
˜
3
7 2
1H NMR (400 MHz, CDCl3): δ = 7.70–35 (m, 1 H), 7.33–7.27 (m,
1 H), 7.25–7.18 (m, 2 H), 7.16–7.09 (m, 3 H), 7.06–6.60 (m, 3 H),
3.90–3.62 (m, 1 H), 3.57–3.46 (m, 1 H), 2.37–2.32 (m, 3 H), 1.68–
1.58 (m, 6 H), 1.14–1.03 (m, 6 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.2, 138.6, 137.1, 133.9, 133.7, 131.3, 130.5, 129.6,
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Phosphane-Free Palladium-Catalyzed Suzuki Coupling
129.5, 128.9, 128.8, 128.3, 127.6, 127.5, 127.3, 126.6, 126.5, 125.4,
125.3, 125.1, 124.4, 51.1, 51.0, 45.9, 21.3, 20.8, 20.7, 20.6,
FTIR (NaCl, neat): ν = 1634 [CON(C H ) ] cm–1
(400 MHz, CDCl3): δ = 7.51–7.09 (m, 4 H), 7.04–6.41 (m, 1 H),
.
1H NMR
˜
3
7 2
20.5 ppm. GC–MS: m/z (%) = 321.20 (28), 278.11 (6), 221.05 (100), 6.27–5.68 (m, 1 H), 3.64–3.55 (m, 1 H), 3.53–3.50 (m, 1 H), 2.38–
178.02 (50), 114.97 (9), 83.95 (20). HRMS (ESI): Calcd. for
2.15 (m, 2 H), 1.60–1.55 (m, 6 H), 1.26 (s, 14 H), 1.13–1.03 (m, 6
H), 0.88 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.5,
137.1, 134.5, 134.0, 133.3, 129.2, 128.1, 127.6, 126.8, 126.6, 125.9,
125.2, 125.2, 125.0, 50.9, 50.8, 45.8, 33.3, 31.9, 30.0, 29.6, 29.3,
29.1, 28.8, 22.7, 20.8, 20.7, 20.6, 20.4, 14.1 ppm. GC–MS: m/z (%)
= 357.38 (100), 314.45 (51), 272.14 (56), 244.23 (50), 230.14 (72),
188.08 (38), 144.99 (79), 131.04 (74), 115.02 (49), 69.06 (57).
HRMS (ESI): Calcd. for [C24H39NO+H]+ 358.3110; found
358.3107.
[C22H27NO+H]+ 322.2171; found 322.2174.
N,N-Diisopropyl-2-(–2-methyl-4-phenylbuta-1,3-dienyl)benzamide
(2e): White solid; yield 70% (mixture of isomers); Rf = 0.4 (ethyl
acetate/hexane, 1:5). FTIR (NaCl, neat): ν = 1626 [CON-
˜
1
(C3H7)2] cm–1. H NMR (400 MHz, CDCl3): δ = 7.45–7.18 (m, 10
H), 6.95–6.59 (m, 2 H), 3.62–3.53 (m, 1 H), 3.49–3.42 (m, 1 H),
2.11–2.07 (m, 3 H), 1.63–1.48 (m, 6 H), 1.03–0.95 (m, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.3, 170.3, 138.9, 138.7, 137.6,
137.5, 137.0, 135.7, 133.7, 133.5, 130.7, 129.7, 129.5, 128.7, 128.6,
127.9, 127.7, 127.7, 127.6, 127.5, 127.1, 126.8, 126.7, 126.5, 125.0,
50.9, 50.8, 45.8, 20.9, 20.8, 20.4, 20.3, 20.2, 14.0 ppm. GC–MS: m/z
(%) = 347.26 (100), 304.15 (16), 262.15 (42), 247.10 (71), 229.10
(49), 204.05 (52), 146.01 (76), 91.05 (60). HRMS (ESI): Calcd. for
[C24H29NO+H]+ 348.2327; found 348.2321.
N,N-Diisopropyl-2-(–3-methyl-4-phenylbuta-1,3-dienyl)benzamide
(2k): White solid; yield 65% (mixture of isomers); Rf = 0.4 (ethyl
acetate/hexane, 1:5). FTIR (NaCl, neat): ν = 1628 [CON-
˜
(C3H7)2] cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.80–7.30 (m, 4
H), 7.27–7.18 (m, 4 H), 7.15–7.13 (m, 1 H), 7.00–6.35 (m, 3 H),
3.77–3.60 (m, 1 H), 3.54–3.45 (m, 1 H), 2.22–2.08 (m, 1 H), 1.86
(s, 2 H), 1.64–1.56 (m, 6 H), 1.12–1.04 (m, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.2, 138.3, 137.7, 136.5, 135.2, 134.2,
132.4, 130.2, 129.3, 129.1, 128.2, 127.5, 127.2, 126.7, 126.1, 124.7,
51.0, 45.8, 21.0, 20.8, 20.7, 20.5, 20.4, 18.4 ppm. GC–MS: m/z (%)
= 347.26 (70), 332.11 (33), 304.17 (33), 247.07 (100), 203.06 (44),
128.05 (25), 76.99 (6). HRMS (ESI): Calcd. for [C24H29NO+H]+
348.2327; found 348.2325.
N,N-Diisopropyl-2-(2-p-tolylprop-1-enyl)benzamide (2f): Light-yel-
low solid; yield 70% (mixture of isomers); Rf = 0.4 (ethyl acetate/
hexane, 1:5). FTIR (NaCl, neat): ν = 1624 [CON(C H ) ] cm–1. 1H
˜
3
7 2
NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 8 Hz, 1 H), 7.37–7.32
(m, 1 H), 7.28–7.24 (m, 1 H), 7.20–7.14 (m, 1 H), 7.10–7.06 (m, 3
H), 6.94–6.89 (m, 1 H), 6.79–6.48 (m, 1 H), 3.74–3.58 (m, 1 H),
3.75–3.40 (m, 1 H), 2.34 (d, J = 12 Hz, 3 H), 2.18 (dd, J = 8.8 Hz,
3 H), 1.63–1.49 (m, 6 H), 1.20–0.97 (m, 6 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.7, 170.4, 140.0, 139.6, 138.5, 138.0,
137.1, 136.8, 133.7, 129.8, 129.6, 129.1, 129.0, 128.0, 127.7, 127.2,
126.8, 126.3, 125.6, 124.9, 124.7, 124.0, 123.2, 51.0, 50.8, 45.9, 45.7,
26.9, 21.2, 21.1, 20.9, 20.8, 20.5, 20.3, 17.1 ppm. GC–MS: m/z (%)
= 335.27 (23), 292.12 (3), 235.08 (100), 221.04 (32), 191.04 (22),
114.97 (28), 76.95 (3). HRMS (ESI): Calcd. for [C23H29NO+H]+
336.2327; found 336.2305.
N,N-Diisopropyl-2-[(2-methylcyclohexylidene)methyl]benzamide
(2l): White solid; yield 60% (mixture of isomers); Rf = 0.4 (ethyl
acetate/hexane, 1:5). FTIR (NaCl, neat): ν = 1628 [CON-
˜
(C3H7)2] cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.26–7.14 (m, 4
H), 6.27–6.13 (m, 1 H), 3.65–3.53 (m, 1 H), 3.50–3.44 (m, 1 H),
3.09–2.69 (m, 1 H), 2.42–1.98 (m, 2 H), 1.81–1.66 (m, 3 H), 1.57–
1.49 (m, 8 H), 1.34–1.22 (m, 4 H), 1.12–1.02 (m, 9 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 170.5, 148.3, 148.2, 148.0, 138.7,
129.9, 129.7, 128.9, 127.5, 127.4, 126.3, 126.2, 126.1, 124.3, 119.2,
117.1, 50.8, 50.7, 45.8, 45.6, 39.2, 38.9, 37.0, 36.7, 33.2, 31.0, 29.7,
29.3, 28.6, 28.4, 28.0, 25.8, 25.5, 21.2, 21.1, 20.8, 20.5, 20.4, 18.8,
18.7 ppm. GC–MS: m/z (%) = 313.20 (49), 270.14 (15), 212.07
(100), 197.03 (44), 156.99 (48), 145.00 (34), 128.00 (30), 114.97 (29),
85.98 (74). HRMS (ESI): Calcd. for [C21H31NO+H]+ 314.2484;
found 314.2468.
2-[(2,3-Dihydroinden-1-ylidene)methyl]-N,N-diisopropylbenzamide
(2g): White solid; yield 56% (mixture of isomers); Rf = 0.4 (ethyl
acetate/hexane, 1:5). FTIR (NaCl, neat): ν = 1626 [CON-
˜
(C3H7)2] cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.61–7.08 (m, 8
H), 6.99–6.13 (m, 1 H), 3.76–3.61 (m, 1 H), 3.51–3.33 (m, 1 H),
3.94–2.13 (m, 4 H), 1.62–1.47 (m, 6 H), 1.13–0.86 (m, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.6, 170.5, 145.9, 145.5, 145.0,
144.4, 142.8, 142.4, 138.9, 138.5, 135.4, 134.0, 130.5, 130.1, 128.4,
128.2, 127.9, 127.6, 126.8, 126.5, 126.2, 126.2, 125.3, 125.1, 125.0,
124.7, 123.7, 120.3, 119.6, 115.7, 51.0, 50.9, 45.9, 45.8, 37.8, 31.0,
30.8, 30.6, 20.8, 20.7, 20.6, 20.5, 20.4 ppm. GC–MS: m/z (%) =
333.24 (49), 232.08 (100), 215.06 (89), 178.03 (7), 76.92 (4). HRMS
(ESI): Calcd. for [C23H27NO+H]+ 334.2171; found 334.2169.
2-(But-1-enyl)-N,N-diisopropylbenzamide (2m): White solid; yield
70 % (mixture of isomers); Rf = 0.4 (ethyl acetate/hexane, 1:5).
FTIR (NaCl, neat): ν = 1628 [CON(C H ) ] cm–1 1H NMR
.
˜
3
7 2
(400 MHz, CDCl3): δ = 7.50–7.10 (m, 4 H), 6.45–6.42 (d, J =
12 Hz, 1 H), 6.31–5.69 (m, 1 H), 3.59 (s, 1 H), 3.48 (s, 1 H), 2.29–
2.21 (m, 2 H), 1.58–1.40 (m, 6 H), 1.07–1.04 (m, 9 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 170.5, 170.3, 138.4, 137.1, 135.8,
134.6, 133.9, 133.6, 129.3, 128.1, 127.6, 126.8, 125.6, 125.6, 125.2,
125.1, 124.9, 50.9, 45.8, 45.7, 29.7, 26.1, 22.0, 20.8, 20.7, 20.6, 20.4,
14.3, 13.2 ppm. GC–MS: m/z (%) = 259.16 (36), 216.08 (41), 188.03
(11), 159.02 (35), 131.00 (100), 114.97 (18), 90.96 (24), 76.94 (5).
HRMS (ESI): Calcd. for [C21H31NO+H]+ 260.2014; found
260.2020.
N,N-Diisopropyl-2-(2-phenylprop-1-enyl)benzamide (2h): Yellow oil;
yield 69% (mixture of isomers); Z/E = 60:40; Rf = 0.4 (ethyl ace-
tate/hexane, 1:5). FTIR (NaCl, neat): ν = 1632 [CON(C H ) ] cm–1.
˜
3
7 2
1H NMR (400 MHz, CDCl3): δ = 8.20–7.59 (m, 1 H), 7.53–7.46
(m, 1 H), 7.44–7.37 (m, 1 H), 7.35–7.27 (m, 2 H), 7.20–7.03 (m, 3
H), 6.95–6.87 (m, 1 H), 6.73–6.51 (m, 1 H), 3.85–3.60 (m, 1 H),
3.58–3.41 (m, 1 H), 2.31–2.06 (m, 3 H), 1.65–1.50 (m, 6 H), 1.22–
0.98 (m, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.8, 141.6,
139.9, 138.4, 134.3, 133.5, 129.7, 129.6, 128.6, 128.4, 128.1, 127.8,
127.7, 127.4, 127.3, 127.1, 127.0, 126.5, 125.8, 124.9, 124.8, 124.7,
123.4, 51.1, 50.9, 46.0, 45.9, 26.9, 20.8, 20.5, 20.4, 20.3 ppm. GC–
MS: m/z (%) = 321.20 (23), 278.16 (3), 221.05 (100), 203.02 (15),
178.02 (23), 114.96 (28), 76.87 (4). HRMS (ESI): Calcd. for
[C22H27NO+H]+ 322.2171; found 322.2176.
2-(2,2-Di-p-tolylvinyl)-N,N-diisopropyl-4,5-dimethylbenzamide (2n):
White solid; yield 75%; Rf = 0.4 (ethyl acetate/hexane, 1:5). FTIR
1
(NaCl, neat): ν = 1619 [CON(C H ) ] cm–1. H NMR (400 MHz,
˜
3
7 2
CDCl3): δ = 7.25–7.23 (m, 2 H), 7.18 (d, J = 8 Hz, 2 H), 7.07–7.04
(m, 4 H), 6.89 (d, J = Hz, 2 H 8 H), 6.50 (s, 1 H), 3.89–3.82 (m, 1
H), 3.47–3.40 (m, 1 H), 2.32 (s, 6 H), 2.16 (s, 3 H), 1.88 (s, 3 H),
1.57 (d, J = 8 Hz, 3 H), 1.46 (d, J = 8 Hz, 3 H), 1.10 (dd, J = 8,
16 Hz, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.9, 142.3,
140.5, 137.6, 137.4, 137.1, 136.9, 135.4, 135.4, 130.8, 130.2, 130.1,
N,N-Diisopropyl-2-(undec-1-enyl)benzamide (2i): Yellow solid; yield
70 % (mixture of isomers); Rf = 0.4 (ethyl acetate/hexane, 1:5).
Eur. J. Org. Chem. 2012, 290–297
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
295

L.-W. Xu et al.
FULL PAPER
129.2, 129.2, 128.8, 127.4, 126.5, 126.0, 123.6, 51.0, 45.8, 21.3, 21.2,
2 mol-%), olefin 4a or 4d (4 mol-%), and dioxane (3 mL) was
21.0, 20.8, 20.8, 20.5, 19.5, 19.5 ppm. GC–MS: m/z (%) = 439.47
heated to 80 °C with stirring. Aryl halide (1 mmol) and arylboronic
(52), 340.18 (100), 324.19 (10), 309.28 (10), 281.14 (16), 248.07 (20), acid (1.2 mmol) were added to the solution, and the reaction was
206.87 (34), 161.45 (17), 133.05 (18). HRMS (ESI): Calcd. for
carried out at 80 °C for 3–4 h. After the solution was cooled to
room temperature, the resulting suspension was extracted four
times with diethyl ether (4–15 mL). The combined ether phase was
analyzed by GC/MS and then concentrated. Further purification
of the product was achieved by flash chromatography on a silica
gel column. All of the products prepared are known[15] and were
[C31H37NO+H]+ 440.2953; found 440.2945.
2-[2,2-Bis(4-fluorophenyl)vinyl]-N,N-diisopropyl-4,5-dimethylbenz-
amide (2o): Light-yellow solid; yield 73%; Rf = 0.4 (ethyl acetate/
hexane, 1:5). FTIR (NaCl, neat): ν = 1620 [CON(C H ) ] cm–1. 1H
˜
3
7 2
NMR (400 MHz, CDCl3): δ = 7.32–7.29 (m,1 H), 7.24–7.20 (m, 2
H), 7.15–7.12 (m, 2 H), 7.04–6.98 (m, 3 H), 6.88 (d, J = 12 Hz, 2
H), 6.48 (s, 1 H), 3.88–3.81 (m, 1 H), 3.48–3.42 (m, 1 H), 2.17 (s,
3 H), 1.92 (s, 3 H), 1.56 (d, J = 4 Hz, 3 H), 1.42 (d, J = 4 Hz, 3
H), 1.12 (t, J = 4 Hz, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 170.7, 140.4, 139.2, 137.4, 135.9, 132.0 (JC,F = 7.8 Hz), 130.2,
129.1 (JC,F = 7.9 Hz), 128.2, 126.1, 125.1, 115.5, 115.2, 51.0, 45.8,
20.9, 20.4, 19.5 ppm. GC–MS: m/z (%) = 447.28 (47), 347.15 (100),
331.12 (4), 304.12 (8), 288.05 (11), 207.03 (6), 174.00 (4), 83.99
(15). HRMS (ESI): Calcd. for [C29H31F2NO+H]+ 448.2452; found
448.2466.
1
characterized by H NMR and GC–MS analyses.
Supporting Information (see footnote on the first page of this arti-
cle): General remarks, NMR and IR spectroscopic data for the
products.
Acknowledgments
Financial support by the National Natural Science Foundation of
China (NSFC) (grant numbers 20973051 and 21173064), Zhejiang
Provincial Natural Science Foundation of China (ZPNSFC) (grant
number Y4090139), and Program for Excellent Young Teachers in
Hangzhou Normal University (HNUEYT) (grant number JTAS
2011-01-014) is appreciated.
2-(Cyclopentylidenemethyl)-N,N-diisopropylbenzamide (2p): Light-
yellow liquid; yield 55%; Rf = 0.4 (ethyl acetate/hexane, 1:5). FTIR
1
(NaCl, neat): ν = 1633 [CON(C H ) ] cm–1. H NMR (400 MHz,
˜
3
7 2
CDCl3): δ = 7.40 (d, J = 8 Hz, 1 H), 7.29–7.25 (m, 1 H), 7.18–7.11
(m, 2 H), 6.39 (t, J = 4 Hz, 1 H), 3.61–3.54 (m, 1 H), 3.51–3.44
(m, 1 H), 2.60–2.31 (m, 4 H), 1.82–1.76 (m, 1 H), 1.69–1.65 (m, 3
H), 1.57 (dd, J = 4.8 Hz, 6 H), 1.03 (dd, J = 8, 12 Hz, 6 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.7, 148.4, 138.1, 134.7, 127.8,
127.7, 126.0, 124.3, 117.8, 50.8, 45.7, 35.5, 27.0, 25.5, 20.8, 20.7,
20.4, 20.3 ppm. GC–MS: m/z (%) = 285.21 (45), 242.14 (18), 184.05
(100), 167.03 (82), 129.01 (29), 114.99 (23), 86.01 (39). HRMS
(ESI): Calcd. for [C19H27NO+H]+ 286.2171; found 286.2184.
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2-(Cycloheptylidenemethyl)-N,N-diisopropylbenzamide (2q):
1
Colourless oil; yield 62%; Rf = 0.4 (ethyl acetate/hexane, 1:5). H
NMR (400 MHz, CDCl3): δ = 7.28–7.26 (m, 2 H), 7.21–7.19 (m, 1
H), 7.13–7.12 (m, 1 H), 6.33 (s, 1 H), 3.61–3.55 (m, 1 H), 3.50–3.43
(m, 1 H), 2.57–2.49 (m, 1 H), 2.44–2.28 (m, 3 H), 1.66–1.53 (m, 14
H), 1.04 (dd, J = 8, 12 Hz, 6 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.5, 146.1, 138.1, 134.5, 129.3, 127.5, 126.2, 124.7,
122.6, 50.7, 45.7, 38.5, 31.4, 29.7, 29.4, 28.8, 27.4, 20.8, 20.8, 20.5,
20.4 ppm. GC–MS: m/z (%) = 313.27 (34), 270.18 (17), 212.11 (51),
157.03 (43), 128.03 (36), 86.02 (100). HRMS (ESI): Calcd. for
[C21H31NO+H]+ 314.2484; found 314.2484.
General Procedure for the Preparation of 3 through Lateral Lithi-
ation and Silylation: sec-Butyllithium (1.2 equiv.) was added to a
solution of N,N-diisopropyl-2-methylbenzamide (1) and TMEDA
(1.2 equiv.) in THF at –78 °C. The resulting orange solution was
then stirred at this temperature for 1 h, followed by addition of
chlorotrimethylsilane (1.5 equiv.). The reaction was warmed to
room temperature and stirred for 12 h, then poured into water and
extracted into EtOAc. The combined extracts were dried with mag-
nesium sulfate and concentrated under reduced pressure to give the
crude product. The product was purified by column chromatog-
raphy (silica gel; petroleum/ethyl acetate).
N,N-Diisopropyl-2-[(trimethylsilyl)methyl]benzamide (3): Colourless
oil; yield 90 %; Rf = 0.4 (ethyl acetate/hexane, 1:5). 1H NMR
(400 MHz, CDCl3): δ = 7.17–7.13 (m,1 H), 7.05–7.00 (m,3 H),
3.64–3.57 (m, 1 H), 3.48–3.41 (m, 1 H), 2.02 (s, 2 H), 1.54 (d, J =
4 Hz, 6 H), 1.09 (d, J = 8 Hz, 3 H), 1.01 (d, J = 8 Hz, 3 H), 0 (s,
9 H) ppm. GC–MS: m/z (%) = 290.31 (3), 276.12 (61), 248.05 (57),
234.11 (25), 206.93 (37), 191.92 (16), 118.97 (100), 89.94 (14).
General Procedure for Suzuki Reaction under Mild Aerobic Condi-
tions: A mixture of Cs2CO3 (0.212 g, 2 mmol), Pd(OAc)2 (4 mg,
296
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Eur. J. Org. Chem. 2012, 290–297

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Published Online: November 9, 2011
Eur. J. Org. Chem. 2012, 290–297
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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