Carbon-carbon bond formations at the benzylic positions of N-benzylxanthone imines and N-benzyldi-1-naphthyl ketone imine

Article abstract of DOI:10.1016/j.tet.2009.02.034

Two N-benzyl imines are designed to allow for carbon-carbon bond formations at the aminated benzylic positions. Direct benzylic arylation reactions of N-benzylxanthone imine with aryl chlorides proceed under palladium catalysis in the presence of cesium hydroxide, yielding the corresponding benzhydrylamine derivatives. Alkylation reactions of N-benzyldi-1-naphthyl ketone imine with alkyl halides in the presence of potassium tert-butoxide afford the corresponding 1-phenylalkylamines in high yields. Conjugate addition of N-benzyldi-1-naphthyl ketone imine is also described.

Full text of DOI:10.1016/j.tet.2009.02.034

Tetrahedron 65 (2009) 5125–5131
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Carbon–carbon bond formations at the benzylic positions of N-benzylxanthone
imines and N-benzyldi-1-naphthyl ketone imine
*
*
Takashi Niwa, Takafumi Suehiro, Hideki Yorimitsu , Koichiro Oshima
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Two N-benzyl imines are designed to allow for carbon–carbon bond formations at the aminated benzylic
positions. Direct benzylic arylation reactions of N-benzylxanthone imine with aryl chlorides proceed
under palladium catalysis in the presence of cesium hydroxide, yielding the corresponding benzhy-
drylamine derivatives. Alkylation reactions of N-benzyldi-1-naphthyl ketone imine with alkyl halides in
the presence of potassium tert-butoxide afford the corresponding 1-phenylalkylamines in high yields.
Conjugate addition of N-benzyldi-1-naphthyl ketone imine is also described.
Received 20 December 2008
Received in revised form 14 February 2009
Accepted 16 February 2009
Available online 24 February 2009
Keywords:
Benzylic arylation
Palladium
Ó 2009 Elsevier Ltd. All rights reserved.
Deprotonation
Benzylic alkylation
N-Benzyl imines
1. Introduction
benzylic alkylation and conjugate addition by means of potassium
tert-butoxide.
Functionalizations of amines are important in organic synthesis.
Among possible transformations, generation of carbanions adja-
cent to nitrogen is interesting and represents umpolung of the
customary reactivity of amines. A nitrogen atom bearing an elec-
tron-withdrawing group enables the adjacent C–H bond to be
readily metalated.1 As a method for the activation, formation of
imine with aromatic ketone is promising (Scheme 1). Deprotona-
tion becomes facile due to the formation of highly delocalized
azaallyl anion.
2. Result and discussion
2.1. Palladium-catalyzed benzylic arylation of N-
benzylxanthone imine with aryl chloride
Transition-metal-catalyzed arylation of a C(sp3)–H bond with
aryl halide via deprotonation of the acidic hydrogen is a recently
developed powerful carbon–carbon bond forming strategy.3–7 We
envisioned that the strategy would be applicable to direct arylation
of N-benzyl ketimine at the benzylic position (Scheme 2). Imine 1,
readily prepared from benzylamine and aromatic ketone, has acidic
benzylic hydrogens.8 Palladium-catalyzed arylation of 1 with aryl
halide would afford 2, which is then subjected to hydrolysis to yield
3. The overall transformation represents a formal cross-coupling
R
R
R
Ar2C=O
Base
N
N
H2N
Ar
Ar
Ar
Ar
Scheme 1. Preparation of imine for base-mediated activation of C–H bond adjacent to
nitrogen.
reaction of aryl halide with an a-aminobenzyl metal.
Here we report carbon–carbon bond formations by using two N-
benzyl imines. N-Benzylxanthone imine proved to react with aryl
chloride in the presence of cesium hydroxide and a palladium
catalyst to lead to benzylic arylation of the imine.2 The other imine,
N-benzyldi-1-naphthyl ketone imine, is found to be suitable for
Ar1
Ar1
Pd cat., base
Ar2
Ar2
+
X
N
H
N
Ar
Ar
Ar
Ar
1
2
Ar1
Ar1
Ar2
Scheme 2. Concept of formal benzylic arylation of benzylamine.
* Corresponding authors. Tel.: þ81 75 383 2441; fax: þ81 75 383 2438.
E-mail addresses: yori@orgrxn.mbox.media.kyoto-u.ac.jp (H. Yorimitsu),
oshima@orgrxn.mbox.media.kyoto-u.ac.jp (K. Oshima).
3
H2N
H2N
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.02.034

5126
T. Niwa et al. / Tetrahedron 65 (2009) 5125–5131
Our initial attempt employed N-benzylbenzophenone imine
(1a) as a substrate (Scheme 3). Treatment of 1a with 4-chloro-
anisole in the presence of cesium hydroxide and catalytic amounts
of PdCl2(MeCN)2 and P(c-C6H11)3 in refluxing xylene provided the
Ph
Ph
1.2 equiv PhCl
2.5 mol % [PdCl( -C3H5)]2
N
Ph
N
O
20 mol % P(c-C6H11 3
)
1.05 equiv CsOH•H2O
corresponding arylated product 2a. However, unexpected isomer
2a0 was obtained as a byproduct. Cesium-hydroxide-mediated
benzylic deprotonation of initially formed 2a readily took place in
situ to form the corresponding azaallylic anion. The azaallylic anion
was protonated in situ to form 2a or 2a0. Iterations of the depro-
tonation/protonation sequence would afford the 3:1 mixture.
Apparently, hydrolysis of the mixture would yield a mixture of
benzhydrylamines 3a and 3b. To achieve the formal benzylic ary-
lation of benzylamine as outlined in Scheme 2, the isomerization
had to be precluded. After many attempts, we concluded that the
isomerization was inevitable.
xylene, reflux, 24 h
O
+
2a''/2a''' = 7:3
1b
2a''
Ph
Ph
N
O
Ph
cat. HCl
3 equiv NaBH3CN
EtOH, 25 °C, 2 h
HN
O
Ph
2a'''
4
then HCl aq.
C, 2 h
25 °
The inevitable isomerization eventually led us to design N-
benzylxanthone imine (1b). Treatment of 1b with chlorobenzene in
the presence of cesium hydroxide under palladium catalysis affor-
ded the corresponding coupling product 2a00 and its isomer 2a% in
a ratio of 7:3 (Scheme 4). The mixture of 2a00 and 2a% was then
reduced by means of sodium cyanoborohydride and a catalytic
amount of hydrochloric acid in ethanol to afford secondary amine 4
in the reaction flask. Further addition of an excess of hydrochloric
acid resulted in the formation of benzhydrylamine (3a) and xan-
thene (5). The oxygen-bridged xanthene moiety is the suitable
scaffold of N-benzyl imine because of the exclusive formations of 3a
and highly delocalized and thus stable 9-xanthenyl cation.
Reduction of the xanthenyl cation took place with the remaining
sodium cyanoborohydride in the same pot to form xanthene (5).
After simple acid/base extraction in a separatory funnel, the
product 3a was isolated as its hydrochloride salt 3a$HCl in 83%
overall yield. It is worth noting that each step was high yielding and
that no chromatographic purification was required during the
overall process.
Although the reaction of 1b with iodobenzene afforded a com-
plex mixture, that with bromobenzene yielded 3a$HCl in 80% yield
under otherwise the same reaction conditions. Other trialkyl-
phosphines, such as PMe3, P(c-C5H9)3, P(n-Bu)3, and P(t-Bu)3, were
inferior to P(c-C6H11)3, and 30–50% combined yields of 2a00 and 2a%
were obtained along with mixtures of unidentified byproducts. Use
of triarylphosphines including PPh3 and P(o-Tol)3 resulted in low
combined yields of 2a00 and 2a% (30–50%), which were accompa-
nied by byproducts and recovered 1a (10–30%). The 1:4 molar ratio
of Pd/P(c-C6H11)3 is important. The combined yield of 2a00 and 2a%
Ph
Ph
HCl
H2N
Ph
H3N+ Ph
Cl–
ether
3a
3a•HCl
+
83% yield from 1b
O
5
Scheme 4. Palladium-catalyzed benzylic arylation of N-benzylxanthone imine (1b).
precursor of the catalyst, other palladium complexes, including
Pd(acac)2, PdCl2(PhCN)2, and Pd(OAc)2, showed comparable yet
slightly lower catalytic activity. A temperature as high as 140 ꢀC was
essential. A similar reaction in refluxing toluene led to very low
conversion. Cesium hydroxide is the only effective base among the
bases tested. The use of KOH, t-BuOK, and Cs2CO3 gave only traces
of 2a00 and 2a%.
Table 1 shows the scope of aryl chlorides. The electronic prop-
erties of aryl chlorides have little influence on the efficiency of the
reaction. Electron-rich aryl chlorides (entries 2–4) as well as an
electron-deficient one (entry 7) reacted smoothly. However, nei-
ther acetyl nor alkoxycarbonyl moieties survived under the basic
conditions. 2-Chlorotoluene underwent the reaction similarly,
irrespective of the steric hindrance of the 2-methyl group (entry 5).
Table 1
Arylation of 1b with ArCl and isolation of benzhydrylamine derivativesa,b
Cl–
Ph
was less than 20% when a Pd/P(c-C6H11 3
)
ratio was 1:3. As the
HCl
+
1) arylation
2) reduction
3) hydrolysis
H3N
Ar
ether
Ph
3a•HCl, 3c•HCl,
3e•HCl
Ph
1b
H2N
Ar
3d•2HCl, 3h•2HCl
1.2 equiv 4-MeOC6H4Cl
5 mol% PdCl2(MeCN)2
N
N
C6H4-4-OMe
PhCOCl
Et3N
3a–h
O
Ph
Ph
Ph
2a
20 mol% P(c-C6H11 3
)
Ph
Ph
Ph
1.2 equiv CsOH•H2O
Ph
N
H
Ar
+
N
xylene (1.0 mL), reflux, 6 h
Ph
3b•Bz, 3f•Bz, 3g•Bz
60%, 2a/2a' = 3:1
Ph
C6H4-4-OMe
1a (0.50 mmol)
Entry
ArCl
Product
Yield/%
2a'
Ph
1
2
3
4
5
6
7
8
C6H5Cl
3a$HCl
3b$Bz
3c$HCl
3d$2HCl
3e$HCl
3f$Bz
83
75
73
82
73
47c
71
80
4-MeOC6H4Cl
4-MeC6H4Cl
4-Me2NC6H4Cl
Ph
O
H2N
Ph
C6H4-4-OMe
Ph
Ph
2-MeC6H4Cl
3b
hydrolysis
4-CH2]CHC6H4Cl
4-Me2NC(]O)C6H4Cl
2-Chloropyridine
+
3g$Bz
3h$2HCl
Ph
NH2
a
The reaction conditions are the same as shown in Scheme 4.
Instead of treatment with HCl, benzoylation of 3b, 3f, and 3g was performed for
O
C6H4-4-OMe
Ph
b
3a
purification (entries 2, 6, and 7).
c
Formic acid was used instead of hydrochloric acid to remove the xanthenyl
Scheme 3. Palladium-catalyzed benzylic arylation of N-benzylbenzophenone imine
(1a).
group.

T. Niwa et al. / Tetrahedron 65 (2009) 5125–5131
5127
The reaction of 4-chlorostyrene provided the desired product 3f$Bz
in moderate yield (entry 6), although the aryl chloride can alter-
natively undergo polymerization via intermolecular Mizoroki–
Heck reaction,9 forming oligo(4-phenylenevinylene). Installation of
a 2-pyridyl ring at the benzylic position was facile (entry 8).
The scope of the aryl group of N-(arylmethyl)xanthone imines
was not satisfactorily wide (Scheme 5). For instance, 1f having an
electron-donating methoxy group suffered from very low conver-
sion, probably due to the slower deprotonation.
8b was contaminated with its isomer 8b0, starting material 1b, and
1b0 that is the regioisomer of 1b.
There is a report of the efficient reaction of N-benzylbenzo-
phenone imine (1a) with allyl bromide under similar reaction
conditions to yield allylated product 8a in high yield selectively.10
However, we could not reproduce the result, and the reaction
resulted in formation of a mixture of 8a and diallylated 9a as well as
moderate conversion (Scheme 8).
Ph
Ph
Cl–
Ar
N
N
Ar
1) phenylation
with PhCl
+
Ph
Ph
H3N
3c•HCl (Ar = 4-MeC6H4), 60%
Ar
Ph
t
1) BuOK
Ph
Ph
Ph
Ph
N
O
2) reduction
3) hydrolysis
8a 49%
1a 3%
9a 9%
2) allyl bromide
N
Ph
THF, 25 °C, 1.5 h
4) neutralization
or benzoylation
O
Ph
N
1a
Ph
N
H
Ph
1c (Ar = 4-MeC6H4)
1d (Ar = 1-naphthyl)
1e (Ar = 3-CF3C6H4)
Ph
1a' 36%
Ph
3i•Bz (Ar = 1-naphthyl), 48%
3j•Bz (Ar = 3-CF3C6H4), 58%
3b•Bz (Ar = 4-MeOC6H4), 2%
1f (Ar = 4-MeOC6H4)
Scheme 8. Allylation of 1a.
Scheme 5. Scope of N-(arylmethyl)xanthone imines.
We thought that increasing the steric hindrance at the ketimine
scaffold led to cleaner allylation, avoiding the second allylation.
Finally, di-1-naphthyl ketone imine 1h proved to be converted to
monoallylated product 10a exclusively (Table 2, entry 1). Removal
The benzylic arylation offers a new route to 9-fluorenylamine
derivatives (Scheme 6). The palladium-catalyzed cross-coupling
reaction of 1g with o-chlorophenylboronic acid yielded biaryl 6.
The intramolecular benzylic arylation of 6 constructed fluorenyl-
amine skeleton, eventually affording 7.
Table 2
Alkylation of 1h and isolation of 1-phenylalkylamine derivatives
Ph
Ph
t
Br
1) 1.2 equiv BuOK
N
N
R
4 mol % Pd(PPh3)4
2) 1.2 equiv R–X
N
O
(HO)2B
Cl
1.5 equiv NaOH
+
THF, 25 °C, time
DME/H2O, reflux, 24 h
1h
10
1g
1) cat. [PdCl( -C3H5)]2
cat. P(c-C6H11 3
1.0 equiv PhCOCl
2.0 equiv Et3N
CH2Cl2, 25 °C, 2 h
10 equiv NH2OH•HCl
2.0 equiv pyridine
)
Ph
O
Ph
CsOH•H2O
xylene, reflux, 24 h
EtOH/H2O
N
O
Cl
H2N
R
Ph
N
R
MW, 150 °C, 30 min
H
2) reduction
3) hydrolysis
4) acetylation
11
AcHN
11•Bz
7 70%
Entry
R–X
Br
Time/h
10, yield%a
11$Bz, yield%b
6 60%
Scheme 6. Synthesis of fluorenylamine.
1
2.5
5.0
2.5
10a, 100
10b, 89d
10c, 90d,g
11a$Bz, 90
11b$Bz, 71e,f
11c$Bz, 61f
2c
3
Cl
Br
Br
Ph
2.2. Benzylic alkylation of N-benzyldi-1-naphthyl ketone
imine with alkyl halides or acrylamides
4
5
2.0
1.5
10d, 100d
10e, 89
11d$Bz, 62f
11e$Bz, 78
We next examined allylation of 1b with allyl bromide in the
presence of a base. Treatment of 1b with potassium tert-butoxide in
THF at 25 ꢀC followed by addition of allyl bromide afforded the
desired allylated product 8b in only 35% yield (Scheme 7). Product
Cl
Cl
6
1.0
10b, 73d
11b$Bz, 77f,h
7
8
9
Br
Ph
1.0
4.5
6.0
10f, 89d
10g, 91
10h, 82
11f$Bz, 78
11g$Bz, 87
11h$Bz, 71
Br
Br
Br
Ph
Ph
N
N
10
24
10i, NDd,i
11i$Bz, 50
t
O
O
1) BuOK
a
NMR yield.
8b 35%
8b' 30%
2) allyl bromide
b
c
d
e
f
Isolated yield based on 1h.
E/Z¼83:17.
1b
THF, 25 °C, 1.5 h
Ph
Microwave irradiation was performed for 1.0 h to complete the liberation of 11.
E/Z¼85:15.
N
1b 9%
Linear product, PhCONHCH(Ph)CH2CH]CR1R2, was exclusively obtained with-
out contamination by the corresponding branched isomer, PhCONHCH(Ph)
CR1R2CH]CH2.
O
g
h
i
t
A larger amount of BuOK (2.0 equiv) was used.
1b' 21%
E/Z¼90:10.
Scheme 7. Allylation of 1b.
Not determined.

5128
T. Niwa et al. / Tetrahedron 65 (2009) 5125–5131
of the di-1-naphthylmethylene moiety was successful upon treat-
ment of 10a with hydroxylamine in aqueous ethanol at 150 ꢀC
under microwave irradiation. It is worth noting that heating 10a
conventionally for 24 h at reflux afforded a complex mixture con-
taining none of 11a. The amine 11a was isolated as its benzamide
derivative 11a$Bz.
The reaction of 1h with crotyl chloride occurred at the chlori-
nated carbon of crotyl chloride in an SN2 manner (entry 2). Cin-
namyl bromide and prenyl bromide also underwent SN2 reaction
similarly (entries 3 and 4). On the other hand, the reaction with 3-
chloro-1-butene took place in an SN20 mode to yield 11b$Bz ex-
clusively (entry 6). The potassium salt of 1h is bulky enough to react
with allylic electrophiles selectively at the less hindered position.
The regioselectivity of the reaction complements that of the re-
action of benzaldehyde imine with allylic nucleophiles (Scheme 9).
Not only allylic electrophiles but also alkyl halides underwent
nucleophilic substitution (entries 7–10). Primary alkyl bromides
reacted smoothly, although 2-bromobutane was less reactive to
afford the corresponding amide 11i$Bz in 50% yield.
3. Conclusion
Two N-benzyl imines are designed to allow for carbon–carbon
bond formations at the aminated benzylic positions, which repre-
sent umpolung of the customary reactivity of amines. Direct ben-
zylic arylation reactions of N-benzylxanthone imine with aryl
chlorides proceed under palladium catalysis in the presence of
cesium hydroxide, yielding the corresponding benzhydrylamine
derivatives. As for nucleophilic alkylation and conjugate addition,
N-benzyldi-1-naphthyl ketone imine is the suitable imine to react
with alkyl halides and acrylamides in the presence of potassium
tert-butoxide.
4. Experimental
4.1. General
4.1.1. Instrumentation
1H NMR (500 MHz) and 13C NMR (126 MHz) spectra were taken
on a Varian Unity INOVA 500 spectrometer and were recorded in
Acrylamides are good Michael acceptors that underwent con-
jugate addition of 1h with the aid of potassium tert-butoxide
(Scheme 10). The resulting 1,4-adducts 12a and 12b were then
treated with hydroxylamine to release the corresponding amines.
Imine 12a was converted to the anticipated amine 13 in excellent
CDCl3 [using tetramethylsilane (for 1H,
d
¼0.00 ppm) and CDCl3 (for
13C,
(for 1H,
d
¼77.2 ppm) as an internal standard] or DMSO-d6 [using DMSO
d
¼2.50 ppm) and DMSO-d6 (for 13C,
¼39.7 ppm) as an
d
internal standard]. IR spectra were determined on a SHIMADZU
FTIR-8200PC spectrometer. Mass spectra were determined on
a JEOL Mstation 700 spectrometer. Melting points were determined
on Yanaco micro melting point apparatus. TLC analyses were per-
formed on commercial glass plates bearing a 0.25-mm layer of
Merck Silica gel 60F254. Silica gel (Wakogel 200 mesh) was used for
column chromatography. Elemental analyses were carried out at
the Elemental Analysis Center of Kyoto University.
yield. In contrast,
g-phenyl-g-butyrolactam (14) was exclusively
obtained from 12b under the same reaction conditions. The differ-
ence would be due to the ability of the NR2 group as a leaving group.
Regioselectivity by the present approach
Ph
Ph
t
X
BuOK,
N
N
The reactions under microwave conditions were carried out
using a focused microwave unit (Biotage InitiatorÔ). The maximum
irradiation power is 400 W. Each reaction was run in a 5-mL glass
pressure vial, which is a commercially available vial special for the
Biotage InitiatorÔ. It took 4 min to reach 150 ꢀC. After reaching the
indicated temperatures, controlled microwave irradiation started
and continued for 30 (or 60) min, keeping the reaction temperature
constant.
(1-Np = 1-naphthyl)
1-Np
1-Np
1-Np
1-Np
10b
1h
Regioselectivity by the customary approach
Ph
Ph
Metal
HN
R
N
R
Scheme 9. Regioselectivity in synthesizing homoallylamines.
4.1.2. Materials
Unless otherwise noted, materials obtained from commercial
suppliers were used without further purification. Toluene and xy-
lene were purchased from Wako Pure Chemical Co. and stored over
slices of sodium. Cesium hydroxide monohydrate was purchased
from Nacalai Tesque. Tricyclohexylphosphine was purchased from
Strem. Allylpalladium(II) chloride dimer was obtained from Aldrich
Chemicals. Preparations of imines are shown below. Acrylamides
were prepared by reactions of acryloyl chloride with secondary
amine.
Ph
t
0.2 equiv BuOK
NR2
NR2
1.2 equiv
N
O
O
1h
THF, 25 °C, 2 h
12a (NR2 = NEt2) 88% NMR yield
12b (NR2 = NMePh) 100% NMR yield
Ph
10 equiv NH2OH•HCl
2.0 equiv pyridine
4.2. Experimental procedures
Ph
NEt2
or
HN
O
H2N
EtOH/H2O
4.2.1. Synthesis of N-benzyl imines
MW, 150 °C, 1 h
O
13
The synthesis of 1b is representative. A solution of titanium(IV)
chloride (4.1 mL, 37.5 mmol) in toluene (50 mL) was slowlyadded to
a solution of xanthone (9.8 g, 50 mmol) and benzylamine (24.6 mL,
225 mmol) in toluene (150 mL) at 0 ꢀC. The resulting mixture was
stirred for 30 min at ambient temperature, and then for 6 h at reflux.
Diethyl ether (200 mL) was added, and the reaction mixture was
passed through a pad of Celite and the precipitate was washed with
diethyl ether (40 mLꢁ3). The solvent was removed under reduced
pressure. N-Benzylxanthone imine (1b) was recrystallized from
hexane/toluene as a white solid (13.1 g, 46 mmol) in 92% yield.
Other imines were prepared in a similar fashion.
(via 12a)
14
52% overall yield
1.0 equiv PhCOCl
2.0 equiv Et3N
CH2Cl2, 25 °C, 2 h
(via 12b)
O
Ph
NEt2
Ph
N
H
13•Bz
O
84% overall yield
(via 12a and 13)
Scheme 10. Conjugate addition of 1h to acrylamides.

T. Niwa et al. / Tetrahedron 65 (2009) 5125–5131
5129
4.2.2. Typical procedure for synthesis of benzhydrylamine
hydrochlorides (Table 1)
dichloromethane (5 mL). After the mixture was stirred for 2 h at
room temperature, the reaction was quenched with water (10 mL).
The product was extracted with chloroform (5 mLꢁ3). The com-
bined organic layer was dried over sodium sulfate and concentrated
in vacuo. Silica gel column purification (hexane/ethyl acetate¼5:1)
provided N-benzhydrylbenzamide 3f$Bz (146 mg, 0.47 mmol) in
47% overall yield.
Synthesis of benzhydrylamine hydrochloride (3a$HCl) is repre-
sentative. Cesium hydroxide monohydrate (0.18 g, 1.05 mmol) and
allylpalladium chloride dimer (9.1 mg, 0.025 mmol) were placed in
a 20-mL two-necked reaction flask equipped with a Dimroth con-
denser under argon atmosphere. Tricyclohexylphosphine (0.5 M in
toluene, 0.40 mL, 0.20 mmol), xylene (2.0 mL), N-benzylxanthone
imine (1b) (285 mg, 1.0 mmol), and chlorobenzene (0.12 mL,
1.2 mmol) were sequentially added at ambient temperature. The
resulting mixture was heated at reflux for 24 h. After the mixture
was cooled to room temperature, a saturated aqueous ammonium
chloride solution (5 mL) was added. The product was extracted
with chloroform (10 mLꢁ3). The combined organic layer was dried
over sodium sulfate and concentrated in vacuo. The residue in-
cluded a mixture of imines 2a00 and 2a% (7:3), which was used for
the next step without further purification.
A drop of hydrochloric acid (12 M) was added to a solution of the
crude mixture of 2a00 and 2a% and sodium cyanoborohydride
(189 mg, 3.0 mmol) in ethanol (5 mL). The resulting mixture was
stirred at 25 ꢀC for 2 h. Hydrochloric acid (12 M, 5 mL) and water
(1 mL) were then added, and the resulting mixture was stirred at
25 ꢀC for 2 h. The reaction was quenched with water (10 mL), and
diethyl ether (10 mL) was then added. The product was extracted
with hydrochloric acid (1 M, 5 mLꢁ3). The combined aqueous layer
was neutralized with sodium hydroxide and extracted with
chloroform (5 mLꢁ3). The combined organic layer was dried over
sodium sulfate and concentrated in vacuo. The residue containing
amine 3a was used for the next step without further purification.
Hydrochloride in ether (1.0 M, 2.0 mL, 2.0 mmol) was added to
a solution of the crude amine 3a in methanol (5 mL). After the
mixture was stirred for 2 h at room temperature, the solvent was
removed in vacuo. Anhydrous ether (20 mL) was added to the
resulting mixture. Insoluble materials were collected by filtration
to yield benzhydrylamine hydrochloride (3a$HCl) (183 mg,
0.83 mmol, 83% overall yield).
4.2.4. Procedure for Suzuki–Miyaura cross-coupling reaction
of imine 1g with o-chlorophenylboronic acid
Sodium hydroxide (30 mg, 0.75 mmol), tetrakis(triphenyl-
phosphine)palladium (11.6 mg, 0.01 mmol), o-chlorophenylboronic
acid (152 mg, 1.0 mmol), and imine 1g (182 mg, 0.50 mmol) were
placed in a 20-mL two-necked reaction flask equipped with
a Dimroth condenser under argon atmosphere. Dimethoxyethane
(3.0 mL) and water (0.5 mL) were sequentially added at ambient
temperature. The resulting mixture was heated at 100 ꢀC for 24 h.
After the mixture was cooled to room temperature, a saturated
aqueous ammonium chloride solution (5 mL) was added. The
product was extracted with ethyl acetate (10 mLꢁ3). The combined
organic layer was dried over sodium sulfate and concentrated in
vacuo. Chromatographic purification through a short silica gel
column (hexane/ethyl acetate¼1:1) provided crude product. The
yield of the product 6 (60%) was determined by 1H NMR mea-
surement with 1,1,2,2-tetrachloroethane as an internal standard.
The residue was used to synthesize 7 without further purification.
4.2.5. Synthesis of N-(9-fluorenyl)acetamide (7)
Cesium hydroxide monohydrate (0.88 g, 0.53 mmol) and allyl-
palladium chloride dimer (4.6 mg, 0.013 mmol) were placed in
a 20-mL two-necked reaction flask equipped with a Dimroth con-
denser under argon atmosphere. Tricyclohexylphosphine (0.5 M in
toluene, 0.2 ml, 0.10 mmol), xylene (2.5 mL), and crude imine 6
described above were sequentially added at ambient temperature.
The resulting mixture was heated at reflux for 24 h. After the
mixture was cooled to room temperature, a saturated aqueous
ammonium chloride solution (5 mL) was added. The product was
extracted with chloroform (10 mLꢁ3). The combined organic layer
was dried over sodium sulfate and concentrated in vacuo. The
residue was used for the next step without further purification.
A drop of hydrochloric acid (12 M) was added to a solution of the
crude imine described above and sodium cyanoborohydride (90 mg,
1.5 mmol) in ethanol (2.5 mL). The resulting mixture was stirred at
25 ꢀC for 2 h. Hydrochloric acid (12 M, 2.5 mL) and water (0.5 mL)
were then added, and the resulting mixture was stirred at 25 ꢀC for
2 h. The reaction was quenched with water (5 mL), and diethyl ether
(5 mL) was then added. The product was extracted with hydro-
chloric acid (1 M, 3 mLꢁ3). The combined aqueous layer was neu-
tralized with sodium hydroxide and extracted with chloroform
(5 mLꢁ3). The combined organic layer was dried over sodium sul-
fate and concentrated in vacuo. The residue containing 9-fluo-
renylamine was used for the next step without further purification.
Acetyl chloride (0.11 mL, 1.5 mmol) was added to a solution of
the crude amine and triethylamine (0.21 mL, 1.5 mmol) in
dichloromethane (5 mL). After the mixture was stirred for 2 h at
room temperature, the reaction was quenched with water (10 mL).
The product was extracted with chloroform (5 mLꢁ3). The com-
bined organic layer was dried over sodium sulfate and concentrated
in vacuo. Silica gel column purification (hexane/ethyl acetate¼5:1)
provided N-(9-fluorenyl)acetamide (7, 47 mg, 0.21 mmol) in 70%
isolated yield starting from 6.
4.2.3. Procedure for synthesis of N-benzhydrylbenzamides (Table 1)
The synthesis of 3f is representative. Cesium hydroxide mono-
hydrate (0.18 g, 1.05 mmol) and allylpalladium chloride dimer
(9.1 mg, 0.025 mmol) were placed in a 20-mL two-necked reaction
flask equipped with a Dimroth condenser under argon atmosphere.
Tricyclohexylphosphine (0.5 M in toluene, 0.40 mL, 0.20 mmol), xy-
lene (2.0 mL), N-benzylxanthone imine (1b) (285 mg, 1.0 mmol), and
p-chlorostyrene (0.14 mL, 1.2 mmol) were sequentially added at
ambient temperature. The resulting mixture was heated at reflux for
24 h. After the mixture was cooled to room temperature, a saturated
aqueous ammonium chloride solution (5 mL) was added. The prod-
uct was extracted with chloroform (10 mLꢁ3). The combined organic
layer was dried over sodium sulfate and concentrated in vacuo. The
residue included a mixture of the corresponding imines 2f00 and 2f%,
which was used for the next step without further purification.
A drop of formic acid was added to a solution of the crude
mixture of 2f00 and 2f% and sodium cyanoborohydride (189 mg,
3.0 mmol) in ethanol (5 mL). The resulting mixture was stirred at
80 ꢀC for 2 h. Formic acid (5 mL) and water (1 mL) were then added,
and the resulting mixture was stirred at 80 ꢀC for 2 h. The reaction
was quenched with water (10 mL), and diethyl ether (10 mL) was
then added. The product was extracted with hydrochloric acid (1 M,
5 mLꢁ3). The combined aqueous layer was neutralized with so-
dium hydroxide and extracted with chloroform (5 mLꢁ3). The
combined organic layer was dried over sodium sulfate and con-
centrated in vacuo. The residue containing amine 3f was used for
the next step without further purification.
4.2.6. Typical procedure for alkylation with allyl/alkyl
halides (Table 2)
Benzoyl chloride (0.12 mL, 1.0 mmol) was added to a solution of
the crude amine 3f and triethylamine (0.28 mL, 2.0 mmol) in
Synthesis of N-(3-methyl-1-phenyl-3-butenyl)benzamide (11e$Bz)
is representative. Potassium tert-butoxide (1.0 M in tetrahydrofuran,

5130
T. Niwa et al. / Tetrahedron 65 (2009) 5125–5131
1.2 mL, 1.2 mmol) was added to a solution of N-benzyldi-(1-naphthyl)
ketone imine 1h (372 mg, 1.0 mmol) in tetrahydrofuran (5.0 mL) at
25 ꢀC and the reaction mixture was stirred for 10 min. Methallyl
chloride (0.12 mL,1.2 mmol) was then added, and the reaction mixture
was stirred for 1.5 h at ambient temperature. A saturated aqueous
ammonium chloride solution (5 mL) was added, and the product was
extracted with ethyl acetate (5 mLꢁ3). The combined organic layer
was dried over sodium sulfate and concentrated in vacuo. The residue
included imine 10e, which was used for the next step without further
purification.
combined organic layer was dried over sodium sulfate and con-
centrated in vacuo. Silica gel column purification (hexane/ethyl
acetate¼5:1) provided N-(3-methyl-1-phenyl-3-butenyl)benza-
mide (13$Bz, 142 mg, 0.42 mmol) in 84% overall yield.
4.3. Characterization data
Compounds 1a–1g,2 the hydrochloride salt or benzoylated 3a–
3j,2 7,2 11a$Bz,11 and 1412 showed the identical spectra according to
the literature.
The crude imine and hydroxylamine hydrochloride (700 mg,
10 mmol) were placed in a 5-mL glass pressure vial. The vial was
flushed with argon and sealed with a PTFE-silicone septum. Pyri-
dine (0.16 mL, 2.0 mmol), ethanol (2.5 mL), and water (1.0 mL) were
added, and the suspension was heated at 150 ꢀC with stirring for
30 min in the microwave reactor. The mixture was then cooled to
room temperature. Water was added, and the product was
extracted with hydrochloric acid (1 M, 5 mLꢁ3). The combined
aqueous layer was neutralized with sodium hydroxide and
extracted with chloroform (5 mLꢁ3). The combined organic layer
was dried over sodium sulfate and concentrated in vacuo. The
residue contained the corresponding amine, which was used for
the next step without further purification.
Benzoyl chloride (0.12 mL, 1.0 mmol) was added to a solution of
the crude amine and triethylamine (0.28 mL, 2.0 mmol) in
dichloromethane (5 mL). After the mixture was stirred for 2 h at
room temperature, the reaction was quenched with water (10 mL).
The product was extracted with chloroform (5 mLꢁ3). The com-
bined organic layer was dried over sodium sulfate and concentrated
in vacuo. Silica gel column purification (hexane/ethyl acetate¼5:1)
provided N-(3-methyl-1-phenyl-3-butenyl)benzamide (11e$Bz,
206 mg, 0.78 mmol) in 78% overall yield.
4.3.1. N-(Di-1-naphthylmethylidene)benzylamine (1h)
IR (Nujol) 2954, 1686, 1559, 1507, 784, 776 cmꢂ1 1H NMR
;
(CDCl3)
d
4.56 (d, J¼15.0 Hz, 1H), 4.66 (d, J¼15.0 Hz, 1H), 7.22–7.26
(m, 2H), 7.30–7.38 (m, 6H), 7.43–7.46 (m, 1H), 7.49–7.55 (m, 4H),
7.79–7.87 (m, 3H), 7.92–7.95 (m, 2H), 9.14 (d, J¼8.0 Hz, 1H); 13C
NMR (CDCl3)
d 59.0, 124.7, 125.5, 125.60, 125.64, 126.1, 126.58,
126.64, 126.8, 127.29, 127.34, 128.2, 128.56, 128.60, 128.8, 129.0,
129.2, 130.3, 130.7, 131.3, 133.7, 134.6, 136.7, 137.5, 140.5, 169.2. Anal.
Calcd for C28H21N: C, 90.53; H, 5.70%. Found: C, 90.64; H, 5.66%.
Mp 108–110 ꢀC.
4.3.2. N-[(E)-1-Phenyl-3-pentenyl]benzamide (11b$Bz)
IR (Nujol) 3324, 1632, 1528, 1340, 965, 721 cmꢂ1 1H NMR
;
(CDCl3)
d
1.6 (ddt, J¼6.5, 1.0, 1.0 Hz, 3H), 2.61 (dd, J¼6.5, 6.5 Hz, 2H),
5.22 (dt, J¼6.5, 6.5 Hz, 1H), 5.35–5.41 (m, 1H), 5.57–5.64 (m, 1H),
6.39 (br d, J¼6.5 Hz, 1H), 7.24–7.29 (m, 2H), 7.33–7.36 (m, 3H), 7.42–
7.44 (m, 2H), 7.49–7.52 (m, 1H), 7.74–7.77 (m, 2H); 13C NMR (CDCl3)
d
18.2, 39.7, 53.3, 126.5, 126.6, 126.7, 127.1, 127.5, 128.8, 129.4,
131.7, 134.9, 142.1, 166.8. HRMS (DI-FABþ) (m/z) observed:
265.1463 (
107–109 ꢀC.
D
¼1.4 ppm). Calcd for C18H19NO [Mþ]: 265.1467. Mp
4.2.7. Typical procedure for alkylation with acrylamides
(Scheme 10)
4.3.3. N-[(E)-1,4-Diphenyl-3-butenyl]benzamide (11c$Bz)
IR (Nujol) 3362, 2953, 2362, 1636, 1522, 1465, 961 cmꢂ1 1H
;
Synthesis of 4-benzoylamino-N,N-diethyl-4-phenylbutanamide
(13$Bz) is representative. Potassium tert-butoxide (1.0 M in tet-
rahydrofuran, 0.1 mL, 0.1 mmol) was added to a solution of 1h
(186 mg, 0.50 mmol) in tetrahydrofuran (2.5 mL) at 25 ꢀC and the
reaction mixture was stirred for 10 min. A solution of N,N-
diethylacrylamide (76 mg, 0.60 mmol) in tetrahydrofuran (1.0 mL)
was then added, the reaction mixture was stirred for 2 h at am-
bient temperature. A saturated aqueous ammonium chloride so-
lution (5 mL) was added, and the product was extracted with
ethyl acetate (5 mLꢁ3). The combined organic layer was dried
over sodium sulfate and concentrated in vacuo. The residue
containing imine 12a was used for the next step without further
purification.
The crude imine and hydroxylamine hydrochloride (350 mg,
5.0 mmol) were placed in a 5-mL glass pressure vial. The vial was
flushed with argon and sealed with a PTFE-silicone septum. Pyri-
dine (0.080 mL, 1.0 mmol), ethanol (2.5 mL), and water (1.0 mL)
were added, and the suspension was heated at 150 ꢀC with stirring
for 60 min in the microwave reactor. The mixture was then cooled
to room temperature. Water was added, and the product was
extracted with hydrochloric acid (1 M, 5 mLꢁ3). The combined
aqueous layer was neutralized with sodium hydrocarbonate and
extracted with chloroform (5 mLꢁ3). The combined organic layer
was dried over sodium sulfate and concentrated in vacuo. The
resulting mixture was used for the next step without further
purification.
NMR (CDCl3)
d
2.81–2.91 (m, 2H), 5.37 (dt, J¼6.5, 6.5 Hz, 1H), 6.13
(dt, J¼15.5, 6.5 Hz, 1H), 6.46 (br d, J¼8.0 Hz, 1H), 6.52 (d, J¼15.5 Hz,
1H), 7.20–7.23 (m, 1H), 7.26–7.31 (m, 5H), 7.35–7.42 (m, 6H), 7.47–
7.50 (m, 1H), 7.75–7.76 (m, 2H); 13C NMR (CDCl3)
d 39.9, 53.4, 125.6,
126.4, 126.7, 127.1, 127.6, 127.7, 128.7, 128.8, 129.0, 131.7, 133.7, 134.7,
137.2, 141.7, 166.9. HRMS (DI-FABþþ) (m/z) observed: 327.1617
(D
¼1.9 ppm). Calcd for C23H21NO [M ]: 327.1623. Mp 168–170 ꢀC.
4.3.4. N-(4-Methyl-1-phenyl-3-pentenyl)benzamide (11d$Bz)
IR (Nujol) 3370,1637,1525,1465, 707 cmꢂ1; 1H NMR (CDCl3)
d 1.63
(s, 3H),1.69 (s, 3H), 2.63 (dd, J¼7.0, 7.0 Hz, 2H), 5.09–5.12 (m,1H), 5.21
(dt, J¼7.0, 7.0 Hz, 1H), 6.42 (d, J¼7.0 Hz, 1H), 7.24–7.28 (m, 1H), 7.32–
7.37 (m, 4H), 7.41–7.44 (m, 2H), 7.48–7.51 (m, 1H), 7.75–7.77 (m, 2H);
13C NMR (CDCl3)
d 18.2, 26.0, 34.9, 53.8,119.5,126.7,127.1,127.4,128.8
(ꢁ2), 131.6, 134.9, 135.5, 142.2, 166.9. Anal. Calcd for C19H21NO: C,
81.68; H, 7.58%. Found: C, 81.81; H, 7.68%. Mp 103–105 ꢀC.
4.3.5. N-(3-Methyl-1-phenyl-3-butenyl)benzamide (11e$Bz)
IR (Nujol) 3360, 1635, 1529, 1490, 1364, 901, 757 cmꢂ1; 1H NMR
(CDCl3)
d 1.76 (s, 3H), 2.56–2.65 (m, 2H), 4.82 (s, 1H), 4.86 (s, 1H),
5.30–5.34 (m, 1H), 6.45 (br s, 1H), 7.23–7.27 (m, 1H), 7.31–7.37 (m,
4H), 7.41 (dd, J¼7.5, 7.5 Hz, 2H), 7.46–7.50 (m,1H), 7.75–7.77 (m, 2H);
13C NMR (CDCl3)
d 22.1, 45.4, 51.7, 114.1, 126.5, 127.1, 127.5, 128.7,
128.8, 131.6, 134.7, 142.4, 142.5, 166.9. Anal. Calcd for C18H19NO: C,
81.47; H, 7.22%. Found: C, 81.48; H, 7.27%. Mp 119–121 ꢀC.
Benzoyl chloride (0.070 mL, 0.5 mmol) was added to a solution
of the crude amine and triethylamine (0.14 mL, 1.0 mmol) in
dichloromethane (2.5 mL). After the mixture was stirred for 2 h at
room temperature, the reaction was quenched with water (5 mL).
The product was extracted with chloroform (5 mLꢁ3). The
4.3.6. N-(1,2-Diphenylethyl)benzamide (11f$Bz)
IR (Nujol) 3348, 1635, 1521, 1465, 1082, 700 cmꢂ1 1H NMR
;
(CDCl3)
d
3.23 (d, J¼7.0 Hz, 2H), 5.47 (dt, J¼7.0, 7.0 Hz, 1H), 6.48 (br
s, 1H), 7.10 (d, J¼7.0 Hz, 2H), 7.18–7.33 (m, 8H), 7.38 (dd, J¼7.0,
7.0 Hz, 2H), 7.47 (dd, J¼7.0, 7.0 Hz, 1H), 7.67 (d, J¼7.0 Hz, 2H); 13C

T. Niwa et al. / Tetrahedron 65 (2009) 5125–5131
5131
NMR (CDCl3)
d
42.8, 55.0, 126.8, 126.9, 127.0, 127.6, 128.6, 128.7,
Acknowledgements
128.8, 129.5, 131.6, 134.7, 137.4, 141.7, 166.9. HRMS (DI-EIþ) (m/z)
observed: 301.1462
301.1467. Mp 173–175 ꢀC.
(D
¼1.6 ppm). Calcd for C21H19NO [Mþ]:
This work is supported by Grants-in-Aid for Scientific Research
and GCOE Research from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan. T.N. acknowledges JSPS for financial
support.
4.3.7. N-(2-Cyclopropyl-1-phenylethyl)benzamide (11g$Bz)
IR (Nujol) 3360, 2360, 1631, 1521, 802, 702 cmꢂ1
(CDCl3) 0.07–0.19 (m, 2H), 0.42–0.50 (m, 2H), 0.62–0.70 (m, 1H),
;
1H NMR
d
1.78–1.87 (m, 2H), 5.28 (dt, J¼7.0, 7.0 Hz, 1H), 6.58 (br s, 1H), 7.24–
References and notes
7.28 (m, 1H), 7.32–7.38 (m, 4H), 7.40–7.43 (m, 2H), 7.47–7.50 (m,
1H), 7.77–7.79 (m, 2H); 13C NMR (CDCl3)
d 4.6, 4.7, 8.0, 41.4, 54.6,
1. Reviews: (a) Beak, P.; Zajdel, W. J.; Reitz, D. B. Chem. Rev. 1984, 84, 471–523; (b)
Gawley, R. E. Curr. Org. Chem. 1997, 1, 71–94; (c) O’Donnell, M. J. Acc. Chem. Res.
2004, 37, 506–517.
2. A part of this work was communicated: Niwa, T.; Yorimitsu, H.; Oshima, K. Org.
Lett. 2008, 10, 4689–4691.
126.7, 127.1, 127.5, 128.5, 128.8, 131.6, 134.9, 142.5, 166.8. Anal. Calcd
for C18H19NO: C, 81.47; H, 7.22%. Found: C, 81.34; H, 7.26%. Mp 127–
130 ꢀC.
3.
a-Arylation of carbonyls: (a) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36,
234–245; (b) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 12382–
12383; (c) Palucki, M.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 11108–11109;
(d) Satoh, T.; Inoh, J.; Kawamura, Y.; Kawamura, Y.; Miura, M.; Nomura, M. Bull.
Chem. Soc. Jpn. 1998, 71, 2239–2246; (e) Muratake, H.; Natsume, M. Tetrahedron
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4. Intermolecular arylation at the activated benzylic or allylic positions: (a) Inoh,
J.; Satoh, T.; Pivsa-Art, S.; Miura, M.; Nomura, M. Tetrahedron Lett. 1998, 39,
4673–4676; (b) Dyker, G.; Heiermann, J.; Miura, M.; Inoh, J.; Pivsa-Art, S.; Satoh,
T.; Nomura, M. Chem.dEur. J. 2000, 6, 3426–3433; (c) Dyker, G.; Heiermann, J.;
Miura, M. Adv. Synth. Catal. 2003, 345, 1127–1132; (d) Niwa, T.; Yorimitsu, H.;
4.3.8. N-(1-Phenylpentyl)benzamide (11h$Bz)
IR (Nujol) 3286, 2955, 2374, 1631, 1558, 1325, 701 cmꢂ1; 1H NMR
(CDCl3)
d
0.89 (t, J¼7.0 Hz, 3H), 1.26–1.41 (m, 4H), 1.85–1.97 (m, 2H),
5.17 (dt, J¼7.0, 7.0 Hz, 1H), 6.31 (br d, J¼7.0 Hz, 1H), 7.25–7.28 (m,
1H), 7.33–7.50 (m, 7H), 7.76 (d, J¼7.0 Hz, 2H); 13C NMR (CDCl3)
d
14.1, 22.7, 28.6, 36.2, 54.1, 126.8, 127.1, 127.6, 128.7, 128.9,
131.6, 134.9, 142.6, 166.8. HRMS (DI-EIþ) (m/z) observed:
267.1627 (
D
¼1.4 ppm). Calcd for C18H21NO [Mþ]: 267.1623. Mp
Oshima, K. Org. Lett. 2007, 9, 2373–2375; (e) Mousseau, J. J.; Larivee, A.; Char-
ette, A. B. Org. Lett. 2008, 10, 1641–1643; (f) Campeau, L.-C.; Schipper, D. J.;
Fagnou, K. J. Am. Chem. Soc. 2008, 130, 3266–3267.
´
130–132 ꢀC.
5. Intramolecular arylative cyclization at the benzylic positions: (a) Ren, H.;
Knochel, P. Angew. Chem., Int. Ed. 2006, 45, 3462–3465; (b) Ren, H.; Li, Z.;
Knochel, P. Chem. Asian J. 2007, 2, 416–433; (c) Dong, C.-G.; Hu, Q.-S. Angew.
Chem., Int. Ed. 2006, 45, 2289–2292; (d) Hu, Q.-S. Synlett 2007, 1331–1345; (e)
Catellani, M.; Motti, E.; Ghelli, S. Chem. Commun. 2000, 2003–2004; (f) Salcedo,
A.; Neuville, L.; Zhu, J. J. Org. Chem. 2008, 73, 3600–3603.
4.3.9. N-(2-Methyl-1-phenylbutyl)benzamide (11i$Bz)
IR (Nujol) 3281, 2954, 1631, 1558, 1465, 701 cmꢂ1 1H NMR
;
(CDCl3)
d
0.86 (d, J¼7.0 Hz, 3H), 0.95 (t, J¼7.5 Hz, 3H), 1.17–1.27 (m,
1H), 1.61–1.69 (m, 1H), 1.90–1.98 (m, 1H), 5.04 (dd, J¼8.0, 8.0 Hz,
1H), 6.42 (br s, 1H), 7.23–7.30 (m, 1H), 7.29–7.35 (m, 4H), 7.41–7.45
(m, 2H), 7.47–7.50 (m, 1H), 7.76–7.79 (m, 2H); 13C NMR (CDCl3)
6. Arylation of N-tert-butylhydrazones as an acyl anion equivalent: Takemiya, A.;
Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 14800–14801.
7. Other C(sp3)–H arylation involving cleavage of less acidic hydrogens: (a) Zait-
sev, V. G.; Shabashov, D.; Daugulis, O. J. Am. Chem. Soc. 2005, 127, 13154–13155;
(b) Shabashov, D.; Daugulis, O. Org. Lett. 2005, 7, 3657–3659; (c) Reddy, B. V. S.;
Reddy, L. R.; Corey, E. J. Org. Lett. 2006, 8, 3391–3394; (d) Kalyani, D.; Deprez, N.
R.; Desai, L. V.; Sanford, M. S. J. Am. Chem. Soc. 2005, 127, 7330–7331; (e) Giri, R.;
Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.; Saunders, L. B.; Yu, J.-Q. J. Am.
Chem. Soc. 2007, 129, 3510–3511; (f) Barder, T. E.; Walker, S. D.; Martinelli, J. R.;
Buchwald, S. L. J. Am. Chem. Soc. 2005, 127, 4685–4696; (g) Pastine, S. J.; Gribkov,
D. V.; Sames, D. J. Am. Chem. Soc. 2006, 128, 14220–14221; (h) Lafrance, M.;
Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2007, 129, 14570–14571; (i) Wata-
nabe, T.; Oishi, S.; Fujii, N.; Ohno, H. Org. Lett. 2008, 10, 1759–1762.
8. The pKa value of the benzylic protons of Ph2C]NCH2Ph was reported to be 24.3
in dimethyl sulfoxide at 25 ꢀC. See: Bordwell, F. G. Acc. Chem. Res. 1988, 21,
456–463.
d
11.6, 16.3, 25.6, 40.1, 58.6, 127.1, 127.2, 127.4, 128.7, 128.8,
131.6, 135.0, 141.6, 166.9. HRMS (DI-EIþ) (m/z) observed:
267.1626 (
161–162 ꢀC.
D
¼1.2 ppm). Calcd for C18H21NO [Mþ]: 267.1623. Mp
4.3.10. 4-Benzoylamino-N,N-diethyl-4-phenylbutanamide (13$Bz)
IR (Nujol) 3325, 1731, 1615, 1528, 1488, 1075, 700 cmꢂ1; 1H NMR
(CDCl3)
d
1.05 (t, J¼7.0 Hz, 3H), 1.08 (t, J¼7.0 Hz, 3H), 2.13–2.19 (m,
1H), 2.35–2.50 (m, 3H), 3.16–3.42 (m, 4H), 5.09–5.13 (m, 1H), 7.22
(dddd, J¼7.5, 7.5, 1.0, 1.0 Hz, 1H), 7.30–7.33 (m, 2H), 7.35–7.37 (m,
2H), 7.40–7.43 (m, 2H), 7.45–7.48 (m,1H), 7.89–7.92 (m, 2H), 8.35 (d,
9. Heitz, W.; Brugging, W.; Freund, L.; Gailberger, M.; Greiner, A.; Jung, H.;
Kampschulte, U.; Niessner, N.; Osan, F.; Schmidt, H. W.; Wicker, M. Makromol.
Chem. 1988, 189, 119–127.
10. Gainelli, G.; Giacomini, D.; Trere´, A.; Boyl, P. P. J. Org. Chem. 1996, 61, 5134–5139.
11. Roy, U. K.; Roy, S. Tetrahedron Lett. 2007, 48, 7177–7180.
J¼6.5 Hz, 1H); 13C NMR (CDCl3)
d 13.2, 14.1, 30.2, 30.4, 40.7, 42.2,
55.0, 126.4, 127.2, 127.3, 128.5, 128.7, 131.4, 134.3, 143.0, 166.6, 172.7.
HRMS (DI-EIþ) (m/z) observed: 338.1991 (
D¼0.9 ppm). Calcd for
C21H26N2O2 [Mþ]: 338.1994.
12. Miller, R. D.; Goelitz, P. J. Org. Chem. 1981, 46, 1616–1618.