The effective use of substituted benzoic anhydrides for the synthesis of carboxamides

Article abstract of DOI:10.1016/j.tet.2004.03.066

Various carboxamides are synthesized from the corresponding carboxylic acids and amines with high product-selectivities using 2-methyl-6-nitrobenzoic or 2,4,6-trichlorobenzoic anhydride in the presence of 4-(dimethylamino) pyridine.

Full text of DOI:10.1016/j.tet.2004.03.066

Tetrahedron 60 (2004) 4729–4733
The effective use of substituted benzoic anhydrides for the
synthesis of carboxamides
*
Isamu Shiina and Yo-ichi Kawakita
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Received 13 February 2004; accepted 17 March 2004
Abstract—Various carboxamides are synthesized from the corresponding carboxylic acids and amines with high product-selectivities using
2-methyl-6-nitrobenzoic or 2,4,6-trichlorobenzoic anhydride in the presence of 4-(dimethylamino)pyridine.
q 2004 Elsevier Ltd. All rights reserved.
1
. Introduction
(entry 1). When 4-methoxybenzoic anhydride was
employed for the model case, the amount of undesirable
benzamide increased to 34% (entry 2). The addition of
electron withdrawing substituents, such as the trifluoro-
methyl or cyano group, on the 4-position of the aromatic
moiety increased the reactivity of the anhydride but the
selectivity was not satisfactory (entries 3 and 4). Although
the reaction using 2,6-dichlorobenzoic anhydride afforded 3
in medium yield as listed in entry 5, an excellent chemical
yield of 3 and relatively good product-selectivity were
obtained when using 2,4,6-trichlorobenzoic anhydride
(TCBA, entry 6). As shown in entry 7, MNBA also
Recently, we reported several useful methods for the
synthesis of carboxylic acid derivatives using substituted
1,2
benzoic anhydrides under acidic or basic conditions. For
example, nearly equimolar amounts of carboxylic acids and
alcohols or v-hydroxycarboxylic acids react in the presence
of 2-methyl-6-nitrobenzoic anhydride (MNBA) with basic
catalysts such as 4-(dimethylamino)pyridine (DMAP) to
produce the corresponding carboxylic esters or lactones in
2
high yields. During the reaction process using MNBA, the
intermediary mixed anhydride was initially formed and it
functions as a reactive acylating reagent of alcohols to give
the desired carboxylic esters in high yields with high
product-selectivities. In this report, we would describe an
effective method for the accelerated synthesis of
Table 1. Isolated yields of carboxamide 3 and ratios of 3 to by-products
3
,4
carboxamides including sterically-hindered compounds
using substituted benzoic anhydrides by basic promoters.
2
. Results and discussion
2.1. Amidation reaction via mixed-anhydrides using
benzoic anhydrides
a
Entry
X
n
Yield of 3 (%)
Yield of BP (%)
3/BP
b
First, benzoic or several substituted benzoic anhydrides
were screened for the reaction of 3-phenylpropanoic acid (1)
with 3-phenylpropylamine (2) as shown in Table 1. The
desired carboxamide, 3-phenyl-N-(3-phenylpropyl)pro-
panamide (3), was obtained in 55% yield along with the
1
H
55
48
52
77
64
97
83
63
84
10
34
12
5
8
3
1
25
14
5.5/1
1.4/1
4.3/1
15/1
8.0/1
32/1
83/1
2.5/1
6.0/1
b
2
4-MeO
4-CF
4-CN
b
3
3
b
4
b
5
2,6-Cl
2
b
6
2,4,6-Cl
2-Me-6-NO
2,4,6-Cl
3
b
10% formation of the undesired benzamide by the addition
of 2 to the reaction mixture of 1 and benzoic anhydride
7
2
c
8
3
c
9
2-Me-6NO
2
a
1
Determined by H NMR using a crude mixture.
2 (1.0 equiv.) was added to the mixture of 1 (1.0 equiv.) and benzoic
anhydride or substituted ones (1.2 equiv.).
TCBA or NMBA (1.2 equiv.) was added to the mixture of 1 (1.0 equiv.)
and 2 (1.0 equiv.).
Keywords: Carboxamides; 2-Methyl-6-nitrobenzoic anhydride; 2,4,6-
Trichlorobenzoic anhydride; Mixed-anhydrides; 4-(Dimethyl-
amino)pyridine.
b
c
*
Corresponding author. Tel.: þ81-3-3260-4271; fax: þ81-3-3260-5609;
e-mail address: shiina@ch.kagu.sut.ac.jp
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.03.066

4
730
I. Shiina, Y. Kawakita / Tetrahedron 60 (2004) 4729–4733
Table 3. Isolated yields of various carboxamides
functions as a suitable benzoic anhydride to produce the
desired carboxamide although the yield was somewhat
lower than that of entry 6. Furthermore, TCBA or MNBA
was added to the reaction mixture of 1 and 2 in order to
determine the best structure of the benzoic part of the
anhydride for maintaining high product-selectivity. Accord-
ing to this procedure, it was revealed that the reaction using
MNBA gave preferable product-selectivity compared to that
obtained by the reaction using TCBA (entries 8 and 9).
Entry
Carboxylic acid
Amine
Product Yield
(%)
Next, some bases were screened for the reaction of 1 with 2
by the promotion of MNBA as shown in Table 2. When the
reaction was carried out using a 2.2 molar amount of
triethylamine in the absence of DMAP, the product
selectivity significantly decreased as compared to that of
the DMAP catalyzed reaction (entries 1 and 2). Further-
more, by employing other typical bases, such as N,N,N ,N -
tetramethylethylenediamine (TMEDA) and 1,8-diaza-
bicyclo[5.4.0]undec-7-ene (DBU), poor product-
selectivities and low yields of the desired amide 3 were
obtained (entries 3 and 4). On the other hand, the yield of 3
increased to 92% without any loss of the high product-
selectivity when the present reaction was performed in the
presence of a 2.2 molar amount of DMAP as a stoichio-
metric base (entry 5). It was found that the use of a
stoichiometric amount of 4-pyrrolidinopyridine (PPY) was
also effective for this reaction and the desired amide 3 was
obtained in excellent yield with high chemoselectivity
a
b
1
1
1
1
1
1
1
1
1
1
2
2
3
92
84
87
91
82
96
96
81
78
94
90
90
88
92
93
82
85
a,c
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
d
2
3
5
7
a,c
3
PhCH NH (4)
2
2
a
4
Ph
2
CHNH
2
(6)
PhCHMeNH (8)
e
0
0
5
9
(10) 11
NHMe (12) 13
2
f
6
1-Adamantyl-NH
2
e
7
PhCH
Piperidine (14)
2
e
8
15
17
19
20
21
22
23
24
e
9
PhNH
2
4
6
8
10
12
14
16
2
(16)
e
1
1
1
1
14
15
0
1
2
3
PhCHMeCOOH (18)
e
a
e
f
18
18
18
18
18
18
18
e
e
e
1
1
6
7
25
26
a
Amines (1.0 equiv.) were added to the mixture of carboxylic acids
1.2 equiv.) and MNBA (1.2 equiv.).
(
(
entry 6).
b
c
d
e
3
/BP¼141/1.
The reaction was carried out at 278 8C.
Carboxamide/benzamide¼.200/1.
Table 2. Isolated yields of carboxamide 3 and ratios of 3 to by-products
Amines (1.0 equiv.) were added to the mixture of carboxylic acids
(
1.1 equiv.) and MNBA (1.1 equiv.).
Amines (1.0 equiv.) were added to the mixture of carboxylic acids
1.3 equiv.) and MNBA (1.3 equiv.).
f
(
yields (entries 3–9). It is noteworthy that the undesired
benzamide was not produced at all except for entry 1.
2-Phenylpropanoic acid (18), a 2-branched carboxylic acid,
a
Entry
Base
Yield of 3 (%)
Yield of BP (%)
3/BP
also reacted with 2 to form the desired 2-phenyl-N-(3-
phenylpropyl)propanamide (19) in high yield (entry 10).
The amidation of 18 with other typical amines including
bulky ones gave the corresponding carboxamides in good to
excellent yields with perfect product-selectivities (entries
11–17).
b
1
Et
Et
3
N
N
20
84
47
16
92
93
68
14
47
64
trace
1.0
0.29/1
6.0/1
1/1
0.25/1
141/1
93/1
2
3
4
5
6
3
TMEDA
DBU
DMAP
PPY
c
d
a
1
Determined by H NMR using a crude mixture.
The reaction was carried out in the absence of DMAP.
The reaction was carried out in the presence of DMAP (2.2 equiv.)
without any tertiary amine.
The reaction was carried out in the presence of PPY (2.2 equiv.) without
any tertiary amine.
b
c
3. Conclusion
It is noted that the present reaction provides a convenient
and high-yielding method for the preparation of carbox-
amides from nearly equimolar amounts of free carboxylic
acids and amines which involve bulky alkyl groups. The
experimental procedure is quite simple and almost pure
carboxamides are obtained just by mixing the substrates at
room temperature.
d
The amidation proceeded at room temperature in several
other polar solvents, such as DMI (95%, 3/BP¼32/1), DMF
(
92%, 50/1), MeCN (91%, 85/1), THF (83%, 7.7/1) and
MeNO (49%, 64/1) under the same reaction conditions as
2
entry 5 in the Table 2.
Table 3 shows the yields for a variety of carboxamides
including ones derived from bulky substrates. The reactions
of 1 with benzylamine (4), diphenylmethylamine (6),
4. Experimental
4.1. General methods
1-phenylethylamine (8), 1-adamantanamine (10), benzyl-
methylamine (12), piperidine (14) and aniline (16) pro-
All reactions were carried out under argon atmosphere
in dried glassware. Dichloromethane was distilled from
ceeded to form the corresponding coupling products in high

I. Shiina, Y. Kawakita / Tetrahedron 60 (2004) 4729–4733
4731
diphosphorus pentoxide, then calcium hydride, and dried
˚
over MS 4 A. Thin layer chromatography was performed on
7.00 (m, 10H), 5.90 (br s, 1H), 4.97 (quin, J¼7.6 Hz, 1H),
13
2.83 (t, J¼7.3 Hz, 2H), 2.35 (t, J¼7.3 Hz, 2H), 1.28 (d,
1
Wakogel B5F. All melting points are uncorrected. H and
3
J¼7.6 Hz, 3H). C NMR (CDCl ) d¼171.1, 143.1, 140.7,
3
1
C NMR spectra were recorded with tetramethylsilane
TMS) or chloroform (in chloroform-d) as internal standard.
128.4, 128.4, 128.3, 127.1, 126.1, 126.0, 48.4, 38.4, 31.7,
21.5. HR MS: Calcd for C H NO (MþH ) 254.1545,
þ
(
1
7 20
found 254.1542.
4
.2. Starting materials
4.3.5. N-1-Adamantyl-3-phenylpropanamide (11). Mp
125 8C. IR (KBr) 3250, 1640, 1540 cm
2
1
1
All reagents were purchased from Tokyo Kasei Kogyo Co.,
Ltd, Kanto Chemical Co., Inc. or Aldrich Chemical Co.,
Inc., and used without further purification unless otherwise
noted. 2-Methyl-6-nitrobenzoic anhydride (MNBA) was
purchased from Tokyo Kasei Kogyo Co., Ltd (TCI, M1439)
.
H NMR
(CDCl ) d¼7.31–7.19 (m, 5H), 5.00 (br s, 1H), 2.92 (t,
3
J¼7.6 Hz, 2H), 2.37 (t, J¼7.6 Hz, 2H), 2.04 (br s, 3H), 1.92
1
3
(br d, 6H), 1.65 (br s, 6H). C NMR (CDCl ) d¼171.1,
3
141.1, 128.4, 127.1, 126.1, 51.8, 41.5, 39.5, 36.3, 31.8, 29.4.
HR MS: Calcd for C H NO (MþH ) 284.2014, found
2
d
þ
or synthesized from 2-methyl-6-nitrobenzoic acid.
1
9 26
284.2015.
4.3. Typical experimental procedure for the amidation
reaction
4.3.6. N-Benzyl-N-methyl-3-phenylpropanamide (13). A
1
2
mixture of two stereoisomers A and B. IR (neat) 1640 cm
1
.
A typical experimental procedure is described for the
reaction of 3-phenylpropanoic acid (1) with 3-phenyl-
propylamine (2); to a solution of DMAP (59.6 mg,
H NMR (CDCl ) d¼7.33–7.06 (m, 10H, AþB), 4.59 (s,
3
2aH, A), 4.45 (s, 2bH, B), 3.05–2.96 (m, 2H, AþB), 2.70–
1
3
2.64 (m, 2H, AþB), 2.94 (s, 3bH, B), 2.84 (s, 3aH, A).
C
0
.488 mmol) in dichloromethane (2.0 mL) were added
MNBA (91.6 mg, 0.266 mmol) and (40.0 mg,
.266 mmol). After having been stirred for 5 min, a solution
NMR (CDCl ) d¼172.5 (B), 172.2 (A), 141.3, 141.2, 137.3,
3
1
136.4, 128.8, 128.8, 128.5, 128.4, 127.9, 127.9, 127.5,
127.5, 127.2, 127.2, 126.1, 126.0, 53.1 (B), 50.8 (A), 35.3
(A), 34.9 (B), 34.7 (A), 33.9 (B), 31.5 (B), 31.3 (A). HR MS:
0
of 2 (30.0 mg, 0.222 mmol) in dichloromethane (1.0 mL)
was added. The reaction mixture was stirred for 14 h at
room temperature and then saturated aqueous sodium
hydrogencarbonate was added. The mixture was extracted
with dichloromethane, and the organic layer was washed
with water and brine, dried over sodium sulfate. After
filtration of the mixture and evaporation of the solvent, the
crude product was purified by thin layer chromatography to
afford 54.6 mg (92%) of 3-phenyl-N-(3-phenylpropyl)-
propanamide (3).
þ
Calcd for C H NO (MþH ) 254.1545, found 254.1541.
1
7 20
6
4.3.7. 3-Phenylpropanoylpiperidine (15). IR (neat)
1
1640 cm2
.
1
H NMR (CDCl ) d¼7.24–7.11 (m, 5H),
3
3.55 (br t, J¼5.3 Hz, 2H), 3.32 (br t, J¼5.3 Hz, 2H), 2.96
(t, J¼8.0 Hz, 2H), 2.61 (t, J¼8.0 Hz, 2H), 1.65–1.45 (br m,
1
3
6H). C NMR (CDCl ) d¼170.2, 141.4, 128.3, 128.3,
3
125.9, 46.5, 42.6, 35.0, 31.5, 26.3, 25.4, 24.4.
7
4
.3.8. N-Phenyl-3-phenylpropanamide (17). Mp 98 8C.
2
1 1
4
5
.3.1. 3-Phenyl-N-(3-phenylpropyl)propanamide (3). Mp
2
IR (neat) 3320, 1660, 1530 cm . H NMR (CDCl ) d¼7.73
3
1 1
7 8C. IR (KBr) 3260, 1640, 1540 cm . H NMR (CDCl3)
(br s, 1H), 7.42 (d, J¼7.8 Hz, 2H), 7.27–7.14 (m, 7H), 7.05
(t, J¼7.4 Hz, 1H), 2.98 (t, J¼7.8 Hz, 2H), 2.60 (t, J¼7.8 Hz,
d¼7.35–7.10 (m, 10H), 5.46 (br s, 1H), 3.15 (dt, J¼6.2,
1
3
7
2
.0 Hz, 2H), 2.85 (t, J¼7.7 Hz, 2H), 2.48 (t, J¼7.7 Hz, 2H),
2H). C NMR (CDCl ) d¼170.8, 140.5, 137.8, 128.8,
3
1
3
.34 (t, J¼7.7 Hz, 2H), 1.67 (tt, J¼7.0, 7.7 Hz, 2H).
C
128.5, 128.2, 126.2, 124.2, 120.1, 39.1, 31.5.
NMR (CDCl ) d¼172.0, 141.3, 140.7, 128.4, 128.3, 128.2,
3
4
a
1
28.2, 126.1, 125.8, 39.0, 38.3, 33.1, 31.6, 30.9. HR MS:
4.3.9. 2-Phenyl-N-(3-phenylpropyl)propanamide (19).
21 1
þ
Calcd for C H NO (MþH ) 268.1701, found 268.1700.
Mp 93 8C. IR (KBr): 3250, 1640, 1560 cm . H NMR
1
8 22
(
CDCl ) d¼7.34–7.05 (m, 10H), 5.44 (br s, 1H), 3.50 (q,
3
5
4
(
7
(
(
.3.2. N-Benzyl-3-phenylpropanamide (5). Mp 80 8C. IR
1 1
J¼7.3 Hz, 1H), 3.24–3.15 (m, 2H), 2.51 (br t, 2H), 1.76–
2
13
KBr) 3290, 1650, 1540 cm . H NMR (CDCl ) d¼7.30–
1.69 (m, 2H), 1.50 (d, J¼7.3 Hz, 3H). C NMR (CDCl )
3
3
.09 (m, 10H), 5.68 (br s, 1H), 4.36 (d, J¼5.6 Hz, 2H), 2.96
d¼174.1, 141.4, 141.3, 128.8, 128.3, 128.2, 127.5, 127.2,
1
3
t, J¼7.6 Hz, 2H), 2.48 (t, J¼7.6 Hz, 2H). C NMR
125.9, 47.0, 39.1, 33.0, 31.0, 18.4. HR MS: Calcd for
C H NONa (MþNa ) 290.1521, found 290.1495.
þ
CDCl ) d¼171.8, 140.7, 138.1, 128.6, 128.5, 128.4, 127.7,
3
18 21
1
27.4, 126.2, 43.5, 38.4, 31.7.
4
a
4.3.10. N-Benzyl-2-phenylpropanamide (20). Mp 78 8C.
IR (KBr): 3280, 1640, 1550 cm
2
1
1
4
Mp 149 8C. IR (KBr) 3340, 1640, 1540 cm . H NMR
.3.3. N-(Diphenylmethyl)-3-phenylpropanamide (7).
2
. H NMR (CDCl3)
1 1
d¼7.32–7.09 (m, 10H), 6.02 (br s, 1H), 4.34 (dd, J¼14.9,
(
(
CDCl ) d¼7.33–7.06 (m, 15H), 6.28–6.18 (m, 1H), 6.01
5.9 Hz, 1H), 4.30 (dd, J¼14.9, 5.9 Hz, 1H), 3.57 (q,
3
1
3
br s, 1H), 3.02 (t, J¼7.5 Hz, 2H), 2.58 (t, J¼7.5 Hz, 2H).
J¼7.1 Hz, 1H), 1.51 (d, J¼7.1 Hz, 3H).
C NMR
(CDCl ) d¼174.1, 141.3, 138.4, 128.8, 128.5, 127.6,
1
3
C NMR (CDCl ) d¼171.0, 141.3, 140.6, 140.6, 128.6,
3
3
1
3
3
28.6, 128.5, 128.4, 128.4, 128.3, 127.4, 127.4, 126.3, 56.8,
8.4, 31.6. HR MS: Calcd for C H NO (MþH )
127.4, 127.2, 127.2, 47.0, 43.4, 18.5. HR MS: Calcd for
þ
þ
C H NONa (MþNa ) 262.1208, found 262.1210.
16 17
2
2
22
16.1701, found 316.1699.
4
a
4
(21). Mp 134 8C. IR (KBr): 3280, 1640, 1540 cm . H
.3.11. N-(Diphenylmethyl)-2-phenylpropanamide
21 1
.3.4. 3-Phenyl-N-[(1S)-1-phenylethyl]propanamide4
a
4
21
(
9). 98% ee. Mp 92 8C. IR (KBr): 3280, 1640, 1560 cm
1
.
NMR (CDCl ) d¼7.37–6.95 (m, 15H), 6.19–6.00 (m, 1H),
3
2
1
13
[
a] ¼263.68 (c 1.03, EtOH). H NMR (CDCl ) d¼7.21–
3.59 (q, J¼7.1 Hz, 1H), 1.48 (d, J¼7.1 Hz, 3H). C NMR
D
3

4732
I. Shiina, Y. Kawakita / Tetrahedron 60 (2004) 4729–4733
(
1
CDCl ) d¼173.1, 141.5, 141.3, 141.2, 128.8, 128.5, 128.3,
Acknowledgements
3
27.5, 127.4, 127.3, 127.2, 127.1, 127.0, 56.7, 46.8, 18.3.
þ
HR MS: Calcd for C H NONa (MþNa ) 338.1521, found
The authors are grateful to Misses Hiromi Oshiumi, Minako
Hashizume, and Mr. Yu-suke Yamai for their experimental
cooperation. This work was partially supported by a Grant-
in-Aid for Scientific Research from the Ministry of
Education, Science, Sports and Culture, Japan.
2
2 21
3
38.1528.
4
panamide (22a). Mp 127 8C. IR (KBr): 3350, 1640,
1
(
1
.3.12. (2RS)-2-Phenyl-N-[(1SR)-1-phenylethyl]pro-
4
a
540 cm2 . H NMR (CDCl ) d¼7.37–7.19 (m, 10H), 5.56
1 1
3
br d, 1H), 5.09 (quin, J¼6.9 Hz, 1H), 3.53 (q, J¼7.1 Hz,
1
3
H), 1.51 (d, J¼7.1 Hz, 3H), 1.34 (d, J¼6.9 Hz, 3H).
C
NMR (CDCl ) d¼173.2, 143.2, 141.4, 128.9, 128.6,
3
References and notes
1
27.6, 127.2, 127.2, 126.0, 48.7, 47.1, 21.5, 18.6. HR MS:
þ
Calcd for C H NONa (MþNa ) 276.1365, found
1
7
19
1. (a) Shiina, I.; Miyoshi, S.; Miyashita, M.; Mukaiyama, T.
Chem. Lett. 1994, 515–518. (b) Shiina, I.; Mukaiyama, T.
Chem. Lett. 1994, 677–680. (c) Miyashita, M.; Shiina, I.;
Mukaiyama, T. Bull. Chem. Soc. Jpn 1994, 67, 210–215.
2
76.1374.
4
panamide (22b). Mp 127 8C. IR (KBr): 3240, 1640,
1
.3.13. (2RS)-2-Phenyl-N-[(1RS)-1-phenylethyl]pro-
a
4
(
d) Shiina, I.; Miyashita, M.; Nagai, M.; Mukaiyama, T.
1 1
540 cm2 . H NMR (CDCl ) d¼7.34–7.17 (m, 8H), 7.08
3
Heterocycles 1995, 40, 141–148. (e) Shiina, I.; Fukuda, Y.;
Ishii, T.; Fujisawa, H.; Mukaiyama, T. Chem. Lett. 1998,
(
dd, J¼7.7, 1.2 Hz, 2H), 5.59 (d, J¼7.1 Hz, 1H), 5.08 (quin,
J¼7.1 Hz, 1H), 3.57 (q, J¼7.3 Hz, 1H), 1.51 (d, J¼7.3 Hz,
8
31–832. (f) Shiina, I.; Fujisawa, H.; Ishii, T.; Fukuda, Y.
Heterocycles 2000, 52, 1105–1123. (g) Shiina, I. Tetrahedron
004, 60, 1587–1599.
. (a) Shiina, I.; Ibuka, R.; Kubota, M. Chem. Lett. 2002,
86–287. (b) Shiina, I.; Kubota, M.; Ibuka, R. Tetrahedron
1
3
3
1
4
2
H), 1.39 (d, J¼7.1 Hz, 3H). C NMR (CDCl ) d¼173.1,
3
43.2, 141.3, 128.8, 128.5, 127.6, 127.2, 127.1, 125.7, 48.6,
7.1, 21.9, 18.4. HR MS: Calcd for C H NONa (MþNa )
2
þ
1
7 19
2
76.1365, found 276.1320.
2
Lett. 2002, 43, 7535–7539. (c) Shiina, I.; Oshiumi, H.;
Hashizume, M.; Yamai, Y.; Ibuka, R. Tetrahedron Lett. 2004,
4
a
4
1
(
.3.14. N-1-Adamantyl-2-phenylpropanamide (23). Mp
1
2
1
36 8C. IR (KBr): 3300, 1640, 1550 cm
.
H NMR
4
5, 543–547. (d) Shiina, I.; Kubota, M.; Oshiumi, H.;
CDCl ) d¼7.34–7.22 (m, 5H), 5.11 (br s, 1H), 3.45 (q,
3
Hashizume, M. J. Org. Chem. 2004, 69, 1822–1830. (e) Tian,
J.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. Org. Lett.
J¼7.1 Hz, 1H), 2.02 (br s, 3H), 1.90 (br d, 6H), 1.63 (br t,
1
3
6
1
H), 1.46 (d, J¼7.1 Hz, 3H). C NMR (CDCl ) d¼173.2,
3
2003, 5, 3021–3024.
. (a) Benz, G. Comprehensive organic synthesis; Trost, B. M.,
42.1, 128.7, 127.5, 127.0, 51.7, 47.8, 41.4, 36.3, 29.4, 18.7.
3
þ
HR MS: Calcd for C H NONa (MþNa ) 306.1834, found
1
9 25
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 6, pp
3
06.1841.
3
81–417. (b) (CDI) Staab, H. A.; L u¨ king, M.; D u¨ rr, F. H.
.3.15. N-Benzyl-N-methyl-2-phenylpropanamide4a (24).
A mixture of two stereoisomers A and B. IR (neat):
Chem. Ber. 1962, 95, 1275–1283. (c) (DPPA) Shioiri, T.;
Ninomiya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94,
6203–6205. (d) (DEPC) Yamada, S.; Kasai, Y.; Shioiri, T.
Tetrahedron Lett. 1973, 1595–1598. (e) (BOP) Castro, B.;
Dormoy, J. R.; Evin, G.; Selve, C. Tetrahedron Lett. 1975,
4
640 cm2 . H NMR (CDCl ) d¼7.31–7.15 (m, 8H, AþB),
1 1
1
7
4
4
3
3
.01 (d, J¼7.3 Hz, 2H, AþB), 4.66 (d, J¼14.6 Hz, 1aH, A),
.65 (d, J¼16.7 Hz, 1bH, B), 4.54 (d, J¼14.6 Hz, 1aH, A),
.24 (d, J¼16.7 Hz, 1bH, B), 3.92 (q, J¼6.8 Hz, 1aH, A),
.87 (q, J¼6.8 Hz, 1bH, B), 2.93 (s, 3bH, B), 2.79 (s, 3aH,
1
219–1222. (f) (HBTU, TBTU) Knorr, R.; Trzeciak, A.;
Bannwarth, W.; Gillessen, D. Tetrahedron Lett. 1989, 30,
927–1930. (g) (HATU) Carpino, L. A. J. Am. Chem. Soc.
1
A), 1.49 (d, J¼6.8 Hz, 3aH, A), 1.46 (d, J¼6.8 Hz, 3bH, B).
1
3
1993, 115, 4397–4398. (h) (o-Hydroxybenzenesulfonyl
chloride) Cabaret, D.; Wakselman, M. Tetrahedron Lett.
C NMR (CDCl ) d¼174.1 (B), 173.7 (A), 141.9, 141.7,
3
1
1
4
37.4, 136.6, 128.8, 128.8, 128.8, 128.4, 127.8, 127.4,
27.3, 127.2, 127.1, 126.8, 126.7, 126.2, 52.9 (B), 51.1 (A),
3.4 (A), 43.1 (B), 34.7 (A), 34.2 (B), 20.9 (B), 20.8 (A). HR
1
994, 35, 9561–9564. (i) (BOMI, BDMP, BPMP, DOMP,
SOMP, FOMP, AOMP) Li, P.; Xu, J.-C. Tetrahedron 2000, 56,
4437–4445. (j) (BEP, FEP, BEPH, FEPH) Li, P.; Xu, J.-C.
Tetrahedron 2000, 56, 8119–9131. (k) (CMBI) Li, P.; Xu, J.-C.
Tetrahedron 2000, 56, 9949–9955. (l) (HOTT, TOTT, HODT,
þ
MS: Calcd for C H NONa (MþNa ) 276.1365, found
1
7 19
2
76.1349.
4
a
TODT) Albericio, F.; Baile
´
n, M. A.; Chincjilla, R.; Dodsworth,
4
1
(
6
.3.16. 2-Phenylpropanoylpiperidine (25). IR (neat):
640 cm2 . H NMR (CDCl ) d¼7.33–7.19 (m, 5H), 3.88
1 1
D. J.; Najera, C. Tetrahedron 2001, 57, 9607–9613.
(m) (Me NSO Cl) Wakasugi, K.; Nakamura, A.; Iida, A.;
2
´
3
q, J¼6.8 Hz, 1H), 3.70–3.35 (br m, 4H), 1.52–1.37 (m,
2
1
3
H), 1.44 (d, J¼6.8 Hz, 3H). C NMR (CDCl ) d¼171.7,
Nishii, Y.; Nakatani, N.; Fukushima, S.; Tanabe, Y.
Tetrahedron 2003, 59, 5337–5345. (n) (TsCl) Wakasugi, K.;
Iida, A.; Misaki, T.; Nishii, Y.; Tanabe, Y. Adv. Synth. Catal.
2003, 345, 1209–1214.
3
1
42.4, 128.8, 127.2, 126.6, 43.2, 43.2, 25.7, 24.5, 20.8. HR
þ
MS: Calcd for C H NONa (MþNa ) 240.1365, found
1
4 19
2
40.1377.
4
. (a) (DPTC) Shiina, I.; Saitoh, K.; Nakano, M.; Suenaga, Y.;
Mukaiyama, T. Collect. Czech. Chem. Commun. 2000, 65,
621–630. (b) (DPC) Shiina, I.; Suenaga, Y.; Nakano, M.;
Mukaiyama, T. Bull. Chem. Soc. Jpn 2000, 73, 2811–2818.
(c) (CDOP) Shiina, I.; Yo-ichi, K. Tetrahedron Lett. 2003,
1951–1955.
8
4
.3.17. N-Phenyl-2-phenylpropanamide (26). Mp 136 8C.
21 1
IR (neat): 3360, 1660, 1540 cm . H NMR (CDCl ) d¼7.47
3
(
br s, 1H), 7.42 (d, J¼7.8 Hz, 2H), 7.34–7.20 (m, 7H), 7.04 (t,
J¼7.3 Hz, 1H), 3.70 (q, J¼7.0 Hz, 1H), 1.56 (d, J¼7.3 Hz,
1
3
3
1
H). C NMR (CDCl ) d¼172.5, 140.9, 137.9, 129.0, 128.8,
3
27.6, 127.4, 124.2, 119.8, 47.9, 18.5.
5. (a) Matsuda, F.; Itoh, S.; Hattori, N.; Yanagiya, M.; Matsumoto,

I. Shiina, Y. Kawakita / Tetrahedron 60 (2004) 4729–4733
4733
T. Tetrahedron 1985, 41, 3625–3631. (b) Perreux, L.; Loupy,
A.; Volatron, F. Tetrahedron 2002, 58, 2155–2162.
. Avijit, B.; Sukla, J.; Kumar, R. S. J. Indian Chem. Soc. 1989,
1967, 89, 1647–1651. (c) Badr, M. Z. A.; Aly, M. M.; Abdel-
Latif, F. F. J. Org. Chem. 1979, 44, 3244–3247. (d) Cooke,
M. P., Jr.; Pollock, C. M. J. Org. Chem. 1993, 58, 7474–7481.
8. (a) Staudinger, H.; Ruzicka, L. Justus Liebigs Ann. Chem. 1911,
380, 278–303. (b) Arthur, P., Jr.; England, D. C.; Pratt, B. C.;
Whitman, G. M. J. Am. Chem. Soc. 1954, 76, 5364–5367.
6
7
6
6, 664–672.
. (a) Natta, G.; Pino, P.; Ercoli, R. J. Am. Chem. Soc. 1952, 74,
496–4498. (b) Gay, R. L.; Hauser, C. R. J. Am. Chem. Soc.
4