Catalytic C-H bond arylation of aryl imines and oxazolines in water with ruthenium(II)-acetate catalyst

Article abstract of DOI:10.1016/j.tet.2012.03.117

Ruthenium(II)-acetate catalyzed C-H bond activation/diarylations of aryl-aldimines, aryl-ketimines and phenyl-oxazolines with aryl bromides in water are reported. Water strongly favours the catalytic diarylation of aryl-ketimines and phenyl-oxazolines wit

Full text of DOI:10.1016/j.tet.2012.03.117

Tetrahedron 68 (2012) 5179e5184
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Catalytic CeH bond arylation of aryl imines and oxazolines in water with
ruthenium(II)-acetate catalyst
*
*
Bin Li, Karthik Devaraj, Christophe Darcel , Pierre H. Dixneuf
ꢀ
UMR 6226 CNRS e Universite de Rennes 1, Institut Sciences Chimiques de Rennes, laboratory “Organometallics, Materials and Catalysis”, Building 10C, campus de Beaulieu,
ꢀ ꢀ
Ave General Leclerc, 35042 Rennes Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Ruthenium(II)-acetate catalyzed CeH bond activation/diarylations of aryl-aldimines, aryl-ketimines and
phenyl-oxazolines with aryl bromides in water are reported. Water strongly favours the catalytic dia-
rylation of aryl-ketimines and phenyl-oxazolines with respect to organic solvent.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 31 January 2012
Received in revised form 21 March 2012
Accepted 30 March 2012
Available online 6 April 2012
Dedicated to Professor Zhang-Jie Shi, on the
occasion of his Tetrahedron Price and for his
contribution to catalytic CeH
functionalization
Keywords:
Ruthenium-acetate catalyst
CeH activation functionalisation
Imine arylation
Oxazolines
Catalysis in water
1. Introduction
leading to chiral heterocycles by enantioselective catalytic [3þ2]
cycloaddition.13 Several catalytic transformations of imines by CeH
Metal-catalyzed CeH bond functionalization is now offering
green and fast synthetic methods as alternatives to classical cata-
lytic cross-coupling reactions, as it avoids the previous preparation
of one or several organometallic precursors.1 The regioselective
CeH bond functionalization of arenes and heteroarenes is usually
reached by taking profit of a tolerated functional group that directs
the successive CeH bond activation and functionalization at the
neighbouring positions.2,3 Among the functional directing groups,
the imine functionality offers high potential as it is readily gener-
ated from aldehydes and ketones and it offers the key to a variety of
useful derivatives such as amines by catalytic hydrogenation,4
hydrosilylation5,6 or hydroboration,7 reactive propargylic amines
by catalytic addition of terminal alkynes,8,9 or fluorenones,10
phenanthrenes11 and phenanthridines12 via ortho CeH bond acti-
vation. Imines are able to generate azomethine intermediates
bond activation have already been reported initially with palla-
dium,14 rhodium,15 for various functionalizations16 including ary-
lation or alkenylation,14e16 and even alkylation.17
The use of cheaper ruthenium(0) has led to CeH bond func-
tionalizations of imines as first shown by Murai18 and then by
Genet and Darses19 for insertion of alkenes with ruthenium(0)
catalysts. With stable ruthenium(II) catalysts, Oi and Inoue showed
the first example of arylation20 of imines and Ackermann per-
formed arylation21 and especially monoalkylation17,22 of imines.
The sequential ruthenium(II) CeH bond arylation and hydro-
silylation of imines has just been reported in NMP for the pro-
duction of bulky amines.6
Although most of these CeH bond functionalizations were
performed in an organic solvent, the recent success obtained for the
arylation of aryl-heterocycles with carboxylato-ruthenium(II) cat-
alysts in water23 was attractive to attempt the activation/func-
tionalization of CeH bond of imines. Although imines are relatively
easily hydrolyzed in water, water is a green and safe solvent24 and
has already shown in some rare examples to increase the ruth-
enium(II) catalytic activity.23e27
* Corresponding authors. Tel.: þ33 2 23 23 62 71; fax: þ33 2 23 23 39 69
(C.D.); tel.: þ33 2 23 23 62 80; fax: þ33 2 23 23 39 69 (P.H.D.); e-mail addresses:
christophe.darcel@univ-rennes1.fr (C. Darcel), pierre.dixneuf@univ-rennes1.fr
(P.H. Dixneuf).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.117

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B. Li et al. / Tetrahedron 68 (2012) 5179e5184
We now report that the [RuCl2(p-cymene)]2/KOAc catalytic
To explore the scope of the diarylation of imines, the previous
entry 6 conditions were used at 110 ꢀC but for 36 h in order to reach
complete transformation of aldimines 1ae1e (Scheme 2, Table 2).
system in the presence of PPh3 ligand can perform the diarylation
of aryl-aldimines, ketimines and oxazolines in water containing
a base (K2CO3), and that water does increase the ruthenium(II)
catalyst activity for the diarylation of ketimines and oxazolines.
2. Results and discussion
Ruthenium(II) catalysts have been shown to be stable and able
to perform a variety of other catalytic transformations in or on
water.28,29 Recently, the sequential ruthenium(II)-catalyzed CeH
bond activation/diarylation and hydrosilylation of imines were
reported in NMP as an efficient route to bulky amines.6 However, as
NMP is not a green solvent, and as diarylation of phenyl pyridine
was recently performed in water,23 we have investigated the direct
CeH bond mono or diarylation of arylimines in water using ruth-
enium(II)/KOAc catalytic system (Scheme 1).
Scheme 2.
Table 2
Catalytic diarylation of aldimines in water with [RuCl2(p-cymene)]2/4KOAc/2PPh3
catalytic systema
Entry
1
Substrate
Product
Yieldb (%)
79
R1¼H, 3a
2
3
R1¼Me, 3b
R1¼F, 3c
76
76
Scheme 1.
4
4
70
Efforts were made to reach diarylation of aldimines (Table 1).
Conditions were first evaluated on arylation of aldimine 1a with
3 equiv of PhBr in the presence of 2.5 or 5 mol % of [RuCl2(p-cym-
ene)]2 catalyst with 1 or 2 equiv of KOAc per ruthenium atom and
4 equiv of K2CO3 as the base at 110 ꢀC for 20 h. With 2.5 mol % of
[RuCl2(p-cymene)]2, it was shown that the addition of 2 equiv of
KOAc, and 1 equiv of PPh3 per ruthenium atom could lead to high
conversion with a good ratio of diarylation (entries 2 vs 1, 3e5). The
use of only PPh3 or only KOAc additive disfavoured both conversion
and diarylation (entries 4 and 5). The best conversion and diary-
lation were reached using 5 mol % of [RuCl2(p-cymene)]2 with
1 equiv of PPh3 and 2 or 3 equiv of KOAc per ruthenium atom
(entries 6 and 7). The influence of the phosphorus ligand instead of
PPh3 was evaluated, such as P(2-furyl)3, P(tolyl)3, Ph3PO, P(OEt)3,
but did not allow to reach better conversion than with PPh3 (entries
8e11 vs 6 and 7). It is noteworthy that the presence of K2CO3 as the
base is required for the reaction (entry 12).
5
R2¼Cl, 5a
68
6
7
R2¼OMe, 5b
R2¼COMe, 5c
71
53
a
Aldimine (0.5 mmol), ArBr (1.5 mmol), K2CO3 (4 equiv), KOAc (20 mol %), PPh3
(10 mol %), [RuCl2(p-cymene)]2 (5 mol %), H2O (2 mL), at 110 ꢀC, 36 h.
b
Isolated yield.
The aldimine 1a on reaction with substituted arylbromides led
to diarylated imines 3ae3c in good isolated yields (76e79%) (en-
tries 1e3). Analogously the methoxy substituted imine 1b on re-
action with phenyl bromide was almost completely diarylated and
imine 4 was isolated in 70% yield (entry 4). Then the diarylation of
imines 1ce1e bearing a para-substituent (Cl, OMe or COMe) on the
benzene ring was then investigated. Good conversions of diarylated
products were obtained and the imines 5ae5c were isolated in 68,
71 and 53% yields, respectively (entries 5e7).
This shows that an electron withdrawing acyl group at the meta
position of the CeH bond (1e) disfavours this catalytic arylation.
Interestingly, this reaction is regioselective as only the imine, not
the acyl, is the directing group (entry 7).
The above results show that activation/arylation of aryl CeH
bonds of imines can be performed in water containing potassium
carbonate to reach very decent yields in bulky imines, without
significant hydrolysis into aldehydes. However in comparison with
the previously reported complete diarylation of various aldimines
performed in NMP at 100 ꢀC for 20 h,6 these results show that only
for aldimines water does not really favours the catalytic diarylation
using [RuCl2(p-cymene)]2 catalyst.
Table 1
Optimization for CeH bond arylation of the aldimine 1a in water with [RuCl2(p-
cymene)]2 catalysta
Entry Catalyst Additives
(mol %)
Conv.b GC-
(%)
Ratiob
yieldb (2a:3a)
(%)
1
2
3
4
5
6
7
8
2.5
2.5
2.5
2.5
5
5
5
5
5
PPh3 (5 mol %), KOAc (5 mol %)
PPh3 (5 mol %), KOAc (10 mol %)
PPh3 (10 mol %), KOAc (5 mol %)
PPh3 (10 mol %)
KOAc (20 mol %)
PPh3 (10 mol %), KOAc (20 mol %)
PPh3 (10 mol %), KOAc (30 mol %)
84
82
53
42
70
92
98
58
71
2
10:90
17:83
100:0
100:0
5:95
4:96
5:95
8:92
5:95
2
37
79
85
28
64
51
35
2
P(2-furyl)3 (10 mol %), KOAc (20 mol %) 98
9
P(tolyl)3 (10 mol %), KOAc (20 mol %)
Ph3PO (10 mol %), KOAc (20 mol %)
P(OEt)3 (10 mol %), KOAc (20 mol %)
PPh3 (10 mol %), KOAc (20 mol %)
83
83
87
14
10
11
12c
5
5
5
5:95
10:90
100:0
The diarylation of ketimines was then attempted under closely
related conditions. Thesuccessful diarylation tookplace at 120 ꢀC for
36 h in the presence of 5 mol % of [RuCl2(p-cymene)]2 with 20 mol %
of KOAc and 10 mol % of PPh3. The diarylated imines 7ae7c were
isolated in 88, 82 and 79% yields, respectively (Scheme 3, Table 3).
a
Aldimine 1a (0.25 mmol), PhBr (0.75 mmol), K2CO3 (4 equiv), [RuCl2(p-cym-
ene)]2 (2.5e5 mol %), additives, H2O (2 mL), tetradecane (10 mL) as the internal
standard.
b
Determined by GC.
Without K2CO3.
c

B. Li et al. / Tetrahedron 68 (2012) 5179e5184
5181
A very positive influence of electron withdrawing substituent
(F, CF3) was observed (entries 3 and 6) by comparison to the
electron-donating methoxy group (entry 5). These results show the
first example of ortho CeH bond Ru(II)-catalyzed functionalisation
of oxazoline in water, and that the oxazoline is easier to diarylate
than analogous aldimines or ketimines. In addition the diarylation
of phenyloxazoline is easier in water than in NMP. When the re-
action with phenyl bromide was performed in water under entry 1
conditions but at 110 ꢀC for 16 h complete diarylation was obtained
versus 120 ꢀC for 20 h in NMP.20b
The sequential catalytic diarylation of imine 1a followed by
imine hydrolysis was attempted. Using the optimized conditions
(Table 2, entry 1), the aldimine 1a was first diarylated, and HCl
solution (1 M) was then added and the reaction mixture was stirred
at rt for 4 h. The aldehyde 10 was then isolated in 86% (Scheme 5).
This result illustrates that imines are stable during catalytic CeH
bond functionalization in water as long as it is in basic media
(K2CO3). Whereas the direct arylation or diarylation of aromatic
aldehydes with ruthenium(II) catalysts cannot be achieved, this
result shows that the reversible transformation of aryl aldehydes
into imines, that behave as CeH bond activation directing groups, is
the key to perform ortho CeH bond of aldehyde and ketone via
temporary formed imines before their regeneration (Scheme 5).
Scheme 3.
Table 3
Catalytic diarylation of ketimines in water with [RuCl2(p-cymene)]2/4 KOAc/2PPh3
catalytic systema
Entry
1
Product
Yieldb (%)
88
E:Zc
R¼CF3, 7a
10:1
2
3
R¼F, 7b
82
79
10:1
10:1
R¼OMe, 7c
a
Ketimine (0.5 mmol), PhBr (1.5 mmol), K2CO3 (4 equiv), KOAc (20 mol %), PPh3
(10 mol %), [RuCl2(p-cymene)]2 (5 mol %), H2O (2 mL), at 120 ꢀC, 36 h.
b
isolated yield.
E/Z ratio of the C]N bond determined by 1H NMR.
c
These results gave evidence for two important observations: (i)
the presence of 1 equiv PPh3 per ruthenium atom favours the dia-
rylation in water whereas PPh3 had to be eliminated for the dia-
rylation of ketimine in NMP,6 (ii) the overall activation/
functionalization is considerably favoured without addition of
surfactants, in basic aqueous solution, with respect to NMP for
which more drastic conditions (160 ꢀC for 48 h) were necessary.6
Previously, it was not possible to arylate the phenyloxazoline 8 in
water with the catalytic system ruthenium(II)/KOPiv23 as the de-
rivative 8 was decomposed under the reaction conditions (100 ꢀC,
16 h). Thus we explore the diarylation of 8 in water with a variety of
para-substituted aryl bromides using similar conditions as in Table
2 for diarylation of aldimines, with KOAc and PPh3 as additives
(Scheme 4). Complete diarylation was observed when performing
the reaction at 110 ꢀC for 20 h. The diarylated oxazolines 9aee were
isolated in moderate to good yields (41e87%) (Table 4, entries 1e5).
In contrast, when the reaction was performed with 4-chlorophenyl
bromide, a low conversion was observed and the corresponding
imine 9f was isolated in only 12% yield (entry 6).
Scheme 5.
3. Conclusion
Ruthenium(II)-acetate catalyzed arylation at ortho positions of
aryl imines is shown to be possible in water. Whereas water does
not favour arylation by ruthenium(II) catalyst of aryl-aldimines, it
strongly favours the diarylation of ketimines with respect to or-
ganic solvent (NMP). The diarylation of phenyloxazoline in water
with KOAc and PPh3 as additives to ruthenium(II) catalyst can be
performed more easily than that of ketimines. Considering the easy
formation of aldimines and ketimines from aryl aldehydes and
ketones and the easy acid hydrolysis of the imines into aldehydes
and ketones, this selective diarylation of aldimines and ketimines
in basic aqueous solution with acetate-ruthenium(II) catalytic
system has potential to formally diarylate (hetero)aromatic rings
attached to aldehyde or ketone functionality, via temporary for-
mation of related directing imines.
4. Experimental section
4.1. General remarks
Scheme 4.
All reagents were obtained from commercial sources and used
as received. H2O was distilled and stored under an argon atmo-
sphere. Technical grade petroleum ether (40e60 ꢀC bp) and ethyl
acetate were used for chromatography column. 1H NMR spectra
were recorded in CDCl3 at ambient temperature on Bruker DPX-
200, AVANCE I 300, AVANCE III 400 spectrometers at 200.1, 300.1,
and 400.1 MHz, respectively, using the solvent as internal standard
(7.26 ppm). 13C NMR spectra were obtained at 50 or 100 MHz and
referenced to the internal solvent signals (central peak at
Table 4
Catalytic diarylation of 2-phenyl-oxazolines in water with [RuCl2(p-cymene)]2/4
KOAc/2PPh3 catalytic systema
Entry
1
Product
Yieldb (%)
75
R¼H, 9a
2
3
4
5
6
R¼Me, 9b
R¼F, 9c
72
84
87
41
12
R¼CF3, 9d
R¼OMe, 9e
R¼Cl, 9f
77.2 ppm). Chemical shift (d) and coupling constants (J) are given in
parts per million and in hertz, respectively. The peak patterns are
indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet, and br for broad. Infrared spectra were recorded on
a Bruker IFS28 spectrometer using KBr pellets. GC analyses were
a
2-Phenyloxazoline (0.5 mmol), ArBr (1.5 mmol), K2CO3 (4 equiv), KOAc (20 mol
%), PPh3 (10 mol %), [RuCl2(p-cymene)]2 (5 mol %), H2O (2 mL), at 110 ꢀC, 20 h.
b
Isolated yield.

5182
B. Li et al. / Tetrahedron 68 (2012) 5179e5184
performed with GC-2014 (Shimadzu) 2010 equipped with a 30-m
capillary column (Supelco, SPBTM-20, fused silica capillary col-
umn, 30 Mꢁ0.25 mmꢁ0.25 mm film thickness), was used with N2/
air as vector gas. GCeMS was measured by GCeMS-QP2010S
4.4.1. N-[(o,o0-Diphenyl)benzylidene]-p-toluidine (3a). Green solid,
yield¼79%, 136 mg, IR (KBr) 3053, 3022, 2914, 1629, 1601, 1499,
1441, 1359, 1190, 1072, 803, 758, 699 cmꢂ1 1H NMR (200 MHz,
n
;
CDCl3):
d
¼8.36 (s, 1H), 7.61e7.40 (m, 13H), 7.10 (d, 2H, J¼8.2 Hz),
(Shimadzu) with GC-2010 equipped with
a
30-m capillary
6.62 (d, 2H, J¼8.1 Hz), 2.33 (s, 3H). 13C NMR (50 MHz, CDCl3):
column (Supelco, SLBTM-5 ms, fused silica capillary column,
30 Mꢁ0.25 mmꢁ0.25 mm film thickness), was used with helium as
vector gas. HRMS was measured on Waters Q-TOF 2. The following
GC conditions were used: initial temperature 100 ꢀC, for 2 min,
then rate 10 ꢀC/min until 250 ꢀC and 250 ꢀC for 25 min.
d¼161.0, 150.0, 143.0, 141.5, 135.7, 134.3, 130.5, 130.2, 129.9, 129.5,
128.5, 127.5, 120.6, 21.4. GC: tR¼30.5 min. MS (EI): m/z: 346 (100,
[MꢂH]þ), 254 (16), 241 (15), 91 (10), 65 (11); HRMS (ESI): m/z calcd
for C26H21N [MþH]þ 348.1746, found 348.1742.
4.4.2. N-[o,o0-Di-(4-tolyl)benzylidene]-p-toluidine (3b). Yellow oil,
4.2. Typical general procedure for [RuCl2(p-cymene)]2
catalyzed arylation of aldimines and ketimines in water
(110 ꢀC for aldimines and 120 ꢀC for ketimines)
yield¼76%, 142 mg, IR (KBr)
n
3051, 3021, 2914, 2857, 1631, 1507,
1452, 1353, 1189, 1107, 818, 790, 742 cmꢂ1
;
1H NMR (200 MHz,
CDCl3):
d
¼8.33 (s, 1H), 7.60e7.20 (m, 11H), 7.07 (d, 2H, J¼8.1 Hz),
6.63 (d, 2H, J¼8.1 Hz), 2.42 (s, 6H), 2.31 (s, 3H). 13C NMR (75 MHz,
[RuCl2(p-cymene)]2 (0.025 mmol, 15.3 mg), KOAc (0.1 mmol,
10 mg), PPh3 (0.05 mmol, 13.2 mg) and K2CO3 (2 mmol, 276 mg)
were introduced in dried Schlenck tube under argon, equipped with
magnetic stirring bar. Aldimine (0.5 mmol), bromo-arene
(0.75 mmol), degassed H2O (2 mL) were added in the Schlenck
tube, which was then placed in the oil bath at required temperature
(110e120 ꢀC). The resulting mixture was allowed to stir for 36 h. The
conversion of the reaction was then analyzed by gas chromatogra-
phy. The reaction mixture was extracted with EtOAc (20 mLꢁ3), and
dried over MgSO4. The solvent was then evaporated under vacuum
and the desired product was purified by chromatography using
a silica gel column (0.5 mol % Et3N) and a mixture of petrol ether/
ethyl acetate as the eluent. The product was obtained and the mono
and diarylated products ratio was determined by 1H NMR.
CDCl3):
d
¼160.9, 149.9, 142.4, 138.1, 136.6, 135.0, 133.8, 129.9, 129.5,
129.4, 128.9, 128.7, 120.1, 21.2, 20.9. GC: tR¼35.5 min. MS (EI): m/z
(relative intensity) 375 (30, Mþ), 374 (100), 358 (5), 282 (5), 269
(10), 91(5), 51 (5). HRMS (ESI): m/z calcd for C28H25N [MþH]þ
376.2065, found 376.2067.
4.4.3. N-[o,o0-Di(4-fluorophenyl)benzylidene]-p-toluidine
(3c). Orange solid, yield¼76%, 145 mg, IR (KBr)
1629, 1602, 1507, 1453, 1359, 1224, 1190, 1157, 1095, 1014, 837,
799, 764, 739, 706 cmꢂ1 1H NMR (200 MHz, CDCl3):
¼8.28 (s,
1H), 7.58e7.30 (m, 7H), 7.18e7.00 (m, 6H), 6.60 (d, 2H, J¼8.0 Hz),
2.31 (s, 3H). 13C NMR (75 MHz, CDCl3):
¼162.2 (d, JCF¼245 Hz),
n 3022, 2920,
;
d
d
159.9, 149.3, 141.6, 136.9 (d, JCF¼3.3 Hz), 135.7, 133.9, 131.5 (d,
JCF¼8 Hz), 129.9, 129.6, 129.1, 120.1, 115.0 (d, JCF¼21 Hz), 20.9. 19
F
NMR (188 MHz, CDCl3):
d
¼ꢂ116. GC: tR¼20.5 min. MS (EI): m/z:
4.3. General procedure for [RuCl2(p-cymene)]2 catalyzed
arylation of 2-phenyl-2-oxazoline in water
382 (100, [MꢂH]þ), 290 (10), 277 (15), 91 (10), 65 (15). HRMS
(ESI): m/z calcd for C26H20NF2 [MþH]þ 384.1564, found
384.1563.
[RuCl2(p-cymene)]2 (0.025 mmol, 15.3 mg), KOAc (0.1 mmol,
10 mg), PPh3 (0.05 mmol, 13.2 mg) and K2CO3 (2 mmol, 276 mg)
were introduced in dried Schlenck tube under argon, equipped
with magnetic stirring bar. 2-Phenyl-2-oxazoline (0.5 mmol),
bromo-arene (0.75 mmol), degassed H2O (2 mL) were added in the
Schlenck tube, which was then placed in the oil bath at 110 ꢀC. The
resulting mixture was allowed to stir for 20 h. The conversion of the
reaction was then analyzed by gas chromatography. The reaction
mixture was extracted with EtOAc (20 mLꢁ3), and dried over
MgSO4. The solvent was then evaporated under vacuum and the
desired product was purified by chromatography using a silica gel
column and a mixture of petrol ether/ethyl acetate as the eluent.
The product was obtained and the mono and diarylated products
ratio was determined by 1H NMR.
4.4.4. N-[(o,o0-Diphenyl)benzylidene]-p-methoxyaniline (4). White
solid, yield¼70%, 128 mg, IR (KBr)
n
3051, 3024, 1625, 1599, 1575,
1502, 1441, 1292, 1247, 1180, 1029, 831, 803, 760, 701 cmꢂ1
;
1H
NMR (200 MHz, CDCl3):
d
¼8.34 (s, 1H), 7.56e7.38 (m, 13H), 6.80
(d, 2H, J¼8.8 Hz), 6.64 (d, 2H, J¼8.8 Hz), 3.78 (s, 3H). 13C NMR
(50 MHz, CDCl3):
d¼159.8, 158.3, 145.6, 143.0, 141.6, 134.3, 130.4,
130.1, 129.4, 128.4, 127.4, 122.0, 114.5, 55.8. GC: tR¼31.0 min. MS
(EI): m/z (relative intensity) 362 (100, [MꢂH]þ), 318 (12), 241 (20).
HRMS (ESI): m/z calcd for C26H22NO [MþH]þ 364.1696, found
364.1694.
4.4.5. N-[(o,o0-Diphenyl)-p-chlorobenzylidene]-p-toluidine
(5a). Light yellow solid, yield¼71%, 130 mg, IR (KBr)
n 3052, 3024,
2916, 1632, 1575, 1500, 1443, 1421, 1401, 1307, 1189, 1105, 1075,
4.4. Procedure for producing 2,6-diphenylbenzaldehyde by
[RuCl2(p-cymene)]2 catalyzed arylation of N-benzylidene-p-
toluidine in water
1045, 1022, 893, 873, 819, 764, 739, 700 cmꢂ1; 1H NMR (200 MHz,
CDCl3):
d
¼8.27 (s, 1H), 7.49e7.43 (m, 12H), 7.06 (d, 2H, J¼8.0 Hz),
6.58 (d, 2H, J¼8.0 Hz), 2.32 (s, 3H). 13C NMR (50 MHz, CDCl3):
d¼159.2, 149.3, 144.2, 139.8, 135.5, 134.6, 132.3, 129.6, 129.5, 128.2,
[RuCl2(p-cymene)]2 (0.025 mmol, 15.3 mg), KOAc (0.1 mmol,
10 mg), PPh3 (0.05 mmol, 13.2 mg) and K2CO3 (2 mmol, 276 mg)
were introduced in dried Schlenck tube under argon, equipped
with magnetic stirring bar. N-Benzylidene-p-toluidine (0.5 mmol),
bromobenzene (0.75 mmol), degassed H2O (2 mL) were added in
the Schlenck tube, which was then placed in the oil bath at 110 ꢀC.
The resulting mixture was allowed to stir for 36 h and then
quenched by the addition of 1 N HCl (10 mL). The resulting mixture
was stirred for 4 h at room temperature. The conversion of the
reaction was analyzed by gas chromatography. The reaction mix-
ture was extracted with EtOAc (20 mLꢁ3), and dried over MgSO4.
The solvent was then evaporated under vacuum and the desired
product was purified by chromatography using a silica gel column
and a mixture of petrol ether/ethyl acetate as the eluent.
127.5, 120.1, 110.1, 20.9. GC: tR¼32.0 min. MS (EI): m/z (relative in-
tensity) 383 (10, Mþ), 382 (33), 381 (30, Mþ), 380 (100), 275 (10),
253 (10), 239 (15), 91(15), 65 (20). HRMS (ESI): m/z calcd for
C26H20N35Cl [MþH]þ 382.1363, found 382.1368.
4.4.6. N-[(o,o0-Diphenyl)-p-methoxylbenzylidene]-p-toluidine
(5b). Orange solid, yield¼68%, 135 mg, IR (KBr)
1689, 1627, 1592, 1569, 1497, 1463, 1445, 1427, 1350, 1206, 1169,
1105, 1034, 1014, 882, 851, 823, 802, 770, 746, 700 cmꢂ1 1H NMR
(200 MHz, CDCl3):
¼8.23 (s, 1H), 7.45e7.30 (m, 10H), 7.01 (d, 2H,
J¼8.0 Hz), 6.97 (s, 2H), 6.54 (d, 2H, J¼8.0 Hz), 3.92 (s, 3H), 2.28 (s,
3H). 13C NMR (50 MHz, CDCl3):
n 3031, 2915, 2842,
;
d
d
¼159.7, 159.5, 149.8, 144.5, 141.1,
134.9, 129.8, 129.3, 127.9, 127.1, 126.6, 120.1, 115.2, 55.5, 20.9. GC:
tR¼29.4 min. MS (EI): m/z: 377 (32, Mþ), 376 (100), 333 (18), 271

B. Li et al. / Tetrahedron 68 (2012) 5179e5184
5183
(10), 91 (10), 65 (10). HRMS (ESI): m/z calcd for C27H24NO ([MþH]þ)
1513, 1452, 1243, 1099, 1038, 933, 819, 796, 760 cmꢂ1
;
1H NMR
378.1852, found 378.1851.
(300 MHz, CDCl3):
d
¼7.56e7.50 (m, 1H), 7.38 (m, 6H), 7.22 (m, 4H),
3.96 (t, 2H, J¼9.3 Hz), 3.66 (t, 2H, J¼9.3 Hz), 2.43 (s, 6H). 13C NMR
4.4.7. N-[(o,o0-Diphenyl)-p-acetylbenzylidene]-p-toluidine
(75 MHz, CDCl3):
d
¼164.3, 142.4, 138.2, 137.0, 129.7, 128.9, 128.8,
(5c). Orange solid, yield¼53%, 103 mg, IR (KBr)
1637,1500,1409, 1356,1329, 1227, 893, 821, 769, 705 cmꢂ1; 1H NMR
(300 MHz, CDCl3):
¼8.33 (s, 1H), 8.05 (s, 2H), 7.48e7.41 (m, 10H),
7.05 (d, 2H, J¼8.1 Hz), 6.57 (d, 2H, J¼8.4 Hz), 2.71 (s, 3H), 2.31 (s,
3H). 13C NMR (75 MHz, CDCl3):
n
2919, 2869, 1685,
128.5, 127.5, 67.4, 55.2, 21.3. GC: tR¼13.3 min. MS (EI): m/z: 326
(100, [MꢂH]þ), 282 (12), 163 (10), 134 (10), 120 (10). HRMS (ESI):
m/z calcd for C23H22NO [MþH]þ 328.1701, found 328.1703.
d
d¼197.7, 159.5, 149.3, 143.2, 140.3,
4.4.13. 2-[2,6-Di(4-fluorophenyl)phenyl]-oxazoline (9c). Light green
138.1, 137.1, 135.9, 130.0, 129.7, 129.5, 128.3, 127.6, 120.3, 27.0, 21.1.
GC: tR¼40.4 min. MS (EI): m/z: 389 (35, Mþ), 388 (100), 344 (10),
283 (10), 91 (10), 65 (10). HRMS (ESI): m/z calcd for C28H23NONa
[MþNa]þ 412.1677, found 412.1676.
solid, yield¼84%, 140 mg, IR (KBr)
n 3063, 2973, 2910, 1664, 1602,
1515, 1457, 1348, 1255, 1225, 1161, 1101, 1044, 938, 846, 802, 763,
701 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d¼7.56e7.37 (m, 7H),
7.13e7.07 (m, 4H), 3.94 (t, 2H, J¼9.3 Hz), 3.64 (t, 2H, J¼9.3 Hz). 13C
NMR (75 MHz, CDCl3):
d¼162.4 (d, JCF¼245 Hz), 163.8, 141.5, 136.8
4.4.8. N-{1-[o,o0-(Diphenyl)-p-trifluoromethylphenyl]ethylidene}-p-
(d, JCF¼3.4 Hz), 130.4 (d, JCF¼8.0 Hz), 129.8, 129.0, 127.8, 115.2 (d,
toluidine (7a). White solid, yield¼88%, 189 mg, E/Z¼10:1, IR (KBr)
n
JCF¼21.3 Hz), 67.4, 55.1. 19F NMR (376 MHz, CDCl3):
¼ꢂ115.3. GC:
d
3023, 2920, 1655, 1610, 1503, 1462, 1445, 1416, 1361, 1264, 1210,
tR¼18.2 min. MS (EI): m/z: 334 (100, [MꢂH]þ), 290 (25), 167 (10),
138 (5), 122 (5). HRMS (ESI): m/z calcd for C21H16NOF2 [MþH]þ
336.1200, found 336.1198.
1177, 1125, 1043, 1022, 899, 838, 824, 787, 765, 704 cmꢂ1; 1H NMR
(300 MHz, CDCl3):
d
¼7.75 (s, 2H), 7.58e7.39 (m, 10.9H), 7.24e7.22
(m, 0.3H), 7.05 (d, 2H, J¼8.4 Hz), 6.86 (d, 0.2H, J¼7.5 Hz), 6.29 (d,
0.2H, J¼7.8 Hz), 6.20 (d, 2H, J¼8.1 Hz), 2.31 (s, 3.3H), 2.17 (s, 0.3H),
4.4.14. 2-[2,6-Di(4-trifluoromethylphenyl)phenyl]-oxazoline
1.59 (s, 3H). 13C NMR (75 MHz, CDCl3):
d
¼169.1, 147.9, 143.9, 141.1,
(9d). White solid, yield¼87%, 189 mg, IR (KBr)
2926, 2907, 1668, 1618, 1328, 1246, 1162, 1115, 1068, 1038, 1017, 932,
846, 807 cmꢂ1; 1H NMR (300 MHz, CDCl3):
¼7.69 (d, 4H, J¼8.1 Hz),
n 3050, 3030, 2955,
140.1, 133.0, 130.2 (d, JCF¼32 Hz), 129.5, 128.6, 128.4, 128.0, 126.1 (d,
JCF¼3.6 Hz), 124.1 (d, JCF¼273 Hz), 118.6, 22.7, 20.9. 19F NMR
d
(376 MHz, CDCl3):
d¼ꢂ62.4 (s, 1F), ꢂ62.5 (s, 0.1F). GC: tR¼11.2 min.
7.64e7.57 (m, 5H), 7.45 (d, 2H, J¼7.5 Hz), 3.93 (t, 2H, J¼9.3 Hz), 3.63
MS (EI): m/z: 429 (60, Mþ), 428 (100), 414 (60), 323 (15), 132 (25),
(t, 2H, J¼9.3 Hz). 13C NMR (75 MHz, CDCl3):
¼163.5, 144.4, 141.3,
d
107 (20), 91 (45), 65 (40).
130.2, 130.0 (q, JCF¼32.0 Hz), 129.6, 129.1, 127.7, 125.2 (q,
JCF¼3.8 Hz), 122.6 (q, JCF¼270 Hz), 67.7, 55.3. 19F NMR (376 MHz,
4.4.9. N-{1-[o,o0-(Diphenyl)-p-fluorophenyl]ethylidene}-p-toluidine
CDCl3):
d
¼ꢂ62.5. GC: tR¼8.6 min. MS (EI): m/z: 434 (100, MþꢂH),
(7b). Red oil, yield¼82%, 155 mg, E/Z¼10:1, IR (KBr)
n
3055, 2925,
390 (15), 370 (10), 217 (5), 69 (5). HRMS (ESI): m/z calcd for
C23H15NOF6Na [MþNa]þ 458.0956, found 458.0957.
1655, 1589, 1500, 1447, 1361, 1338, 1267, 1215, 1160, 1075, 1030, 913,
868, 842, 825, 785, 765, 735, 703 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
¼7.56e7.35 (m, 10.8H), 7.21e7.16 (m, 2.4H), 7.04 (d, 2H, J¼8.1 Hz),
4.4.15. 2-[2,6-Di(4-methoxyphenyl)phenyl]-oxazoline (9e). White
6.84 (d, 0.2H, J¼7.8 Hz), 6.28 (d, 0.2H, J¼8.4 Hz), 6.19 (d, 2H,
solid, yield¼41%, 74 mg, IR (KBr)
2832, 1667, 1606, 1514, 1456, 1346, 1293, 1251, 1182, 1117, 1097, 1037,
936, 841, 802, 758 cmꢂ1 1H NMR (300 MHz, CDCl3):
n 3055, 3030, 2955, 2926, 2896,
J¼8.4 Hz), 2.30 (s, 3.3H), 2.14 (s, 0.3H), 1.55 (s, 3H). 13C NMR
(75 MHz, CDCl3): (major isomer)
d
¼169.5, 161.6 (d, JCF¼248 Hz),
;
d
¼7.52e7.47
148.2, 142.5 (d, JCF¼8 Hz), 140.5, 136.9 (d, JCF¼3 Hz), 132.7, 129.45,
(m,1H), 7.43e7,35 (m, 6H), 6.97e6.92 (m, 4H), 3.97 (t, 2H, J¼9.3 Hz),
129.39, 128.3, 127.7, 118.6, 115.9 (d, JCF¼21 Hz), 23.0, 20.9. 19F NMR
3.86 (s, 6H), 3.65 (t, 2H, J¼9.3 Hz). 13C NMR (75 MHz, CDCl3):
(376 MHz, CDCl3):
d¼ꢂ113.5 (t, 0.1F, J¼9.0 Hz), ꢂ114.1 (t, 1F,
d
¼164.4, 159.0, 142.1, 133.6, 129.8, 129.7, 128.7, 127.6, 113.6, 67.4,
J¼9.0 Hz). GC: tR¼14.2 min. MS (EI): m/z: 379 (50, Mþ), 378 (100),
55.4, 55.2. GC: tR¼18.0 min. MS (EI): m/z: 359 (30, Mþ), 358 (100),
364 (55), 273 (15), 132 (25), 91 (30), 65 (30).
343 (10), 315 (10), 179 (10).
4.4.10. N-{1-[o,o0-(Diphenyl)-p-methoxyphenyl]ethylidene}-p-tolui-
4.4.16. 2-[2,6-Di(4-chlorophenyl)]phenyl]-oxazoline
solid, yield¼12%, 23 mg, IR (KBr) 3057, 2962, 2921, 1657, 1491,
1452, 1261, 1091, 1041, 1014, 800, 759, 700 cmꢂ1 1H NMR
(9f). White
dine (7c). White solid, yield¼79%, 154 mg, E/Z¼10:1, IR (KBr)
n
n
3041, 2965, 2915, 2839, 1646, 1596, 1575, 1498, 1463, 1425, 1342,
1269, 1236, 1207, 1176, 1152, 1106, 1038, 878, 826, 765, 734,
;
(300 MHz, CDCl3):
d
¼7.57e7.52 (m, 1H), 7.42e7,32 (m, 10H), 3.95 (t,
700 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
¼7.58e7.40 (m, 10H),
2H, J¼9.3 Hz), 3.65 (t, 2H, J¼9.3 Hz). 13C NMR (100 MHz, CDCl3):
7.37e7.34 (m, 0.7H), 7.23e7.20 (m, 5H), 7.05e7.01 (m, 3.9H),
6.87e6.82 (m, 0.5H), 6.30 (d, 0.2H, J¼8.1 Hz), 6.19 (d, 2H, J¼8.1 Hz),
3.93 (s, 3H), 3.89 (s, 0.3H), 2.30 (s, 3.3H), 2.13 (s, 0.3H), 1.55 (s, 3H).
d
¼163.8, 141.4, 139.3, 133.7, 130.1, 130.0, 129.2, 128.4, 127.6, 67.6,
55.2. GC: tR¼18.0 min. MS (EI): m/z: 368 (70, [MꢂH]þ), 366 (100),
322 (10), 287 (12), 239 (10), 166 (10), 113 (12), 106 (10).
13C NMR (75 MHz, CDCl3):
d¼169.9, 158.5, 148.4, 141.6, 141.5, 132.3,
129.3, 129.2, 128.3, 128.0, 127.2, 118.5, 114.8, 55.5, 23.1, 20.8. GC:
tR¼33.6 min. MS (EI): m/z: 390 (100, [MꢂH]þ), 376 (38), 333 (12),
285 (10), 91 (21), 65 (17). HRMS (ESI): m/z calcd for C28H26NO
[MþH]þ 392.2009, found 392.2011.
4.4.17. 2,6-Diphenylbenzaldehyde (10). Yellow solid, yield¼86%,
111 mg, IR (KBr)
n 3050, 3027, 2841, 2744, 1697, 1569, 1493, 1452,
1389, 1192, 1076, 1025, 853, 810, 767, 703 cmꢂ1; 1H NMR (300 MHz,
CDCl3):
NMR (75 MHz, CDCl3):
d
¼10.00 (s, 1H), 7.66e7.61 (m, 1H), 7.51e7.38 (m, 12H). 13
C
d
¼193.7, 144.4, 139.8, 133.3, 131.7, 130.5,
4.4.11. 2-(2,6-Diphenyl)-phenyloxazoline
yield¼75%, 113 mg, IR (KBr) 3052, 2960, 2912, 2887, 2855, 1649,
1454,1359,1318,1253,1221,1102,1044, 937, 763, 701 cmꢂ1; 1H NMR
(9a). Green
solid,
129.7, 128.3, 127.8. GC: tR¼17.8 min. MS (EI): m/z (relative intensity)
n
258 (100, Mþ), 228 (30), 181 (25), 152 (25), 113 (20), 101 (22), 77 (8).
(300 MHz, CDCl3):
d
¼7.58e7.34 (m,13H), 3.92 (t, 2H, J¼9.3 Hz), 3.62
(t, 2H, J¼9.3 Hz). 13C NMR (75 MHz, CDCl3):
d
¼164.1, 142.5, 141.1,
Acknowledgements
129.7,129.0,128.7,128.1,127.6,127.4, 67.4, 55.2. GC: tR¼10.3 min. MS
(EI): m/z: 298 (100, [MꢂH]þ), 254 (25), 149 (10), 127 (10).
The authors are grateful to CNRS, the French Ministry for Re-
search, the Institut Universitaire de France (P.H.D.), the ANR pro-
gram 09-Blanc-0101-01, and the Chinese Scholarship Council for
a Ph.D. grant to B.L.
4.4.12. 2-[2,6-Di(4-tolyl)phenyl]-oxazoline
(9b). White
solid,
yield¼72%, 118 mg, IR (KBr) 3050, 3025, 2962, 2919, 2871, 1667,
n

5184
B. Li et al. / Tetrahedron 68 (2012) 5179e5184
124, 5638; (d) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2003, 125, 9584; (e) Wei, C.; Li,
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16. Cheap metal catalysts were also used for CeH activation of imines: Iron: (a)
Yoshikai, N.; Matsumoto, A.; Norinder, J.; Nakamura, E. Angew. Chem., Int. Ed.
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ꢀ
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