Z-selective synthesis of α,β-unsaturated amides with triphenylsilylacetamides

Article abstract of DOI:10.1021/jo0161936

With the purpose of developing a method of preparing Z-α,β-unsaturated amides, the Peterson reaction of the (triphenylsilyl)acetamide Ph₃SiCH₂COX (1, X = NBn₂; 3, X = NMe₂) with various aldehydes was examined. The reaction of aromatic aldehydes gave selectivities up to >97:3. It was found that the selectivity was a function of the electronic nature of the aromatic ring and higher Z selectivity was attained with electron-rich aldehydes. With aliphatic aldehydes selectivities up to 92:8 were achieved, and unlike with analogous phosphorus reagents, less sterically hindered aldehydes gave higher Z selectivity. Also, 3, which has a smaller amide group than 1, tended to give rise to higher selectivity. A comparison with the reaction of trimethylsilyl analogues revealed the significance of the phenyl substituents on the silyl group.

Full text of DOI:10.1021/jo0161936

J . Org. Chem. 2002, 67, 4093-4099
4093
Z-Selective Syn th esis of r,â-Un sa tu r a ted Am id es w ith
Tr ip h en ylsilyla ceta m id es†
Satoshi Kojima,* Hiroki Inai, Tsugihiko Hidaka, Tomohide Fukuzaki, and Katsuo Ohkata
Department of Chemistry, Graduate School of Science, Hiroshima University, Kagamiyama,
Higashi-Hiroshima, 739-8526 J apan
skojima@sci.hiroshima-u.ac.jp
Received October 11, 2001
With the purpose of developing a method of preparing Z-R,â-unsaturated amides, the Peterson
reaction of the (triphenylsilyl)acetamide Ph3SiCH2COX (1, X ) NBn2; 3, X ) NMe2) with various
aldehydes was examined. The reaction of aromatic aldehydes gave selectivities up to >97:3. It was
found that the selectivity was a function of the electronic nature of the aromatic ring and higher
Z selectivity was attained with electron-rich aldehydes. With aliphatic aldehydes selectivities up
to 92:8 were achieved, and unlike with analogous phosphorus reagents, less sterically hindered
aldehydes gave higher Z selectivity. Also, 3, which has a smaller amide group than 1, tended to
give rise to higher selectivity. A comparison with the reaction of trimethylsilyl analogues revealed
the significance of the phenyl substituents on the silyl group.
In tr od u ction
olefination, reagents bearing a trimethylsilyl (TMS)
group have been widely utilized to complement reagents
of the Wittig type.2 However, for reactions involving
disubstituted olefin products with electron-withdrawing
groups, geometric mixtures with low selectivity are
usually obtained. Silicon differs greatly from its phos-
phorus counterpart, where high selectivity for both (E)-
and (Z)-olefins has been established for certain electron-
withdrawing groups. Previous amide formation with
Peterson reagents bearing the TMS group is no excep-
tion.14 To get around this problem, we decided to consider
a more bulky and more electronegative silyl group, the
triphenylsilyl group. This silyl group has proven to be
relevant in combination with the cyano group for the
preparation of Z-â-substituted acrylonitriles in earlier
examinations by others.8 In accordance with expectations,
we have realized the first highly Z-selective preparation
of R,â-unsaturated amides. We have also found that
higher selectivity could be achieved with smaller sub-
stituents upon the nitrogen atom. Herein we describe our
results.15
The versatility of geometry-defined olefins makes them
good building blocks in organic synthesis. Of particular
potential are olefins bearing carbon-based electron-
withdrawing groups, such as the ester group, since not
only are these groups viable of further functionalization
but they also activate the double-bond moiety for reac-
tions such as Michael addition and pericyclic reactions.
In many such reactions, the stereochemistry of the
product is dependent upon the geometry of the olefin.
Among the methods of choice for obtaining such units
with concomitant formation of a carbon-carbon bond are
the Wittig reaction and the Horner-Wadsworth-Em-
mons (HWE) reaction, which utilize phosphorus,1 and the
Peterson reaction, which utilizes silicon.2 Since disubsti-
tuted olefins bearing an electron-withdrawing group of
E geometry are thermodynamically more stable than
their Z counterparts, they are rather easy to come by,
while methods available for moderate to highly selective
preparation for the latter are rather limited. Although
it is desirable to have a direct Z-selective method for the
preparation of disubstituted R,â-unsaturated amides
from aldehydes, no such method could be found among
them, and we thus decided to seek for an efficient
method. When the project was begun, the only methods
available were preparative ones for olefins bearing the
ester,3-7 the cyano,8-12 and methyl ketone group as the
electron-withdrawing moiety.13 To accomplish our objec-
tive, we decided to look into the Si platform. In Peterson
(5) (a) Ando, K. Tetrahedron Lett. 1995, 36, 4105-4108. (b) Ando,
K. J . Org. Chem. 1997, 62, 1934-1939. (c) Ando, K. J . Org. Chem.
1998, 63, 8411-8416. (d) Ando, K. J . Org. Chem. 1999, 64, 8406-
8408. (e) Ando, K. J . Synth. Org. Chem. J pn. 2000, 58, 869-876.
(6) Kojima, S.; Takagi, R.; Akiba, K. J . Am. Chem. Soc. 1997, 119,
5970-5971.
(7) Kokin, K.; Motoyoshiya, J .; Hayashi, S.; Aoyama, H. Synth.
Commun. 1997, 27, 2387-2392.
(8) (a) Yamakado, Y.; Ishiguro, M.; Ikeda, N.; Yamamoto, H. J . Am.
Chem. Soc. 1981, 103, 5568-5570. (b) Haruta, R.; Ishiguro, M.; Furuta,
K.; Mori, A.; Ikeda, N.; Yamamoto, H. Chem. Lett. 1982, 1093-1096.
(c) Furuta, K.; Ishiguro, M.; Haruta, R.; Mori, A.; Ikeda, N.; Yamamoto,
H. Bull. Chem. Soc. J pn. 1984, 57, 2768-2776.
† Dedicated to Prof. B. M. Trost.
(1) (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863-
927. (b) Kelly, S. E. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: Oxford, U.K., 1991; Vol. 1, pp
730-817. (c) J ohnson, A. W. Ylides and Imines of Phosphorus; Wiley-
Interscience: New York, 1993. (d) Kolodiazhnyi, O. I. Phosphorus
Ylides, Wiley-VCH: Weinheim, Germany, 1999. (e) Ando, K. J . Synth.
Org. Chem. J pn. 2000, 58, 869-876.
(9) Sato, Y.; Niinomi, Y. J . Chem. Soc., Chem. Commun. 1982, 56-
57.
(10) Matsuda, I.; Okada, H.; Izumi, Y. Bull. Chem. Soc. J pn. 1983,
56, 528-532.
(11) Palomo, C.; Aizpurua, J . M.; Aurrekoetxea, N. Tetrahedron Lett.
1990, 31, 2210-2212.
(2) (a) Ager, D. J . Synthesis 1984, 384-398. (b) Ager, D. J . Org.
React. 1990, 42, 1-223.
(12) Zhang, T. Y.; O’Toole, J . C.; Dunigan, J . M. Tetrahedron Lett.
1998, 39, 1461-1464.
(3) Larcheveque, M.; Debal, A. J . Chem. Soc., Chem. Commun. 1981,
877-878.
(13) Yu, W.; Su, M.; J in, Z. Tetrahedron Lett. 1998, 40, 6725-6728.
(14) For the use of Me3SiCH2CONMe2 with LDA, see: Woodbury,
R. P.; Rathke, M. W. J . Org. Chem. 1978, 43, 1947-1949.
(4) Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405-4408.
10.1021/jo0161936 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/10/2002

4094 J . Org. Chem., Vol. 67, No. 12, 2002
Kojima et al.
Ta ble 2. Solven t Effect u p on th e Rea ction of
Sch em e 1
P h (CH2)2CHOa
entry
solvent
temp (°C)
Z:Eb
yield (%)c
1
2
3
4
5
THF
-78
-78
-78
-78
-95
91:9
91:9
74:26
71:29
94:6
77
53
15
64
58
THFd
ether
THF/HMPA
THF
Sch em e 2
a
The reactions were carried out with KHMDS as base unless
noted otherwise. b Determined by 500 MHz 1H NMR measurement
of the crude mixture. c Combined isolated yield of (E)- and (Z)-
d
olefins. The reaction was carried out with NaHMDS as base.
Ta ble 3. Rea ction s of 1 a n d 7 w ith KHMDS a s Ba sea
entry
R
product
Z:Eb
yield (%)c
Ta ble 1. Cou n ter ca tion Effect u p on th e Rea ction
of P h CHOa
1
2
3
4
5
6
7
8
Ph (7a )
8a
8b
8c
8d
8e
8f
8g
8h
8i
>97:3
>97:3
81:19
88:12
91:9
59:41
81:19
91:9
88
87
72
91
92
47
99
77
82
0
entry
base
temp (°C)
Z:Eb
yield (%)c
p-MeOC6H4 (7b)
o-MeOC6H4 (7c)
p-ClC6H4 (7d )
2-furyl (7e)
1
2
3
n-BuLi
NaHMDS
KHMDS
-78 to 0
-78
-78
54:46
80:20
>97:3
85
93
97
2-pyridyl (7f)
(E)-PhCHdCH (7g)
PhCH2CH2 (7h )
cyclohexyl (7i)
Ph(CH3)CH (7j)
t-Bu (7k )
a
b
All reactions were carried out at -78 °C. Determined by 500
MHz 1H NMR measurement of the crude mixture. c Combined
isolated yield of (E)- and (Z)-olefins.
9
10
11
83:17
8j
8k
0
Resu lts a n d Discu ssion
a
All reactions were carried out in THF at -78 °C with KHMDS
as base. Determined by 500 MHz 1H NMR measurement of the
b
The Peterson reagents 1-4 (Scheme 1) examined for
the reactions were prepared by treating the lithium
enolate of N,N-dibenzylacetamide, N-benzylacetamide,
N,N-dimethylacetamide, and N,N-diisopropylacetamide
with triphenylsilyl chloride. The trimethylsilyl derivative
5 was prepared similarly with trimethylsilyl chloride. In
all the cases, the yields were moderate to high (69-89%),
indicating that regioselectively favored C-silylation over
O-silylation.16
crude mixture. c Combined isolated yield of (E)- and (Z)-olefins.
turned out to be lower. The use of NaHMDS in place of
KHMDS led surprisingly to identical selectivity (entry
2), in contrast to examinations with benzaldehyde.
The scope of the reaction using 1 was examined under
the standard conditions of using THF and KHMDS,
which proved to be commonly effective for both benzal-
dehyde and 3-phenylpropionaldehyde, at a temperature
of -78 °C (Table 3). For 4-substituted benzaldehyde
derivatives, complete Z selectivity was achieved (entry
2), with p-anisaldehyde (7b) bearing the electron-donat-
ing MeO group, whereas a dropoff in selectivity was
observed with the electronegative Cl substituent of 7d
(entry 4). Although, generally in HWE reactions, steri-
cally hindered 2-substituted aromatic aldehydes are more
Z selective than their 4-substituted counterparts, the
Peterson reaction here gave lower selectivity with the
2-MeO substrate 7c than for the 4-MeO substrate 7b
(entry 3). With heterocyclic aldehydes, the highly elec-
tronegative 2-pyridylaldehyde (7f) showed low selectivity
(entry 6), whereas the reaction of furfural (7e) was highly
Z selective (entry 5). The conjugated (E)-cinnamaldehyde
(7g) also furnished the Z product as the predominant
isomer (entry 7).
The reaction of reagent 1, bearing potentially remov-
able benzyl substituents, was first examined (Scheme 2).
The geometry of the products was determined by the
characteristic coupling constants between the two olefinic
protons. For representative products, the NOE was
measured between these protons to confirm our assign-
ments. Since a countercation effect is usually observed
for the analogous HWE reaction, the reaction with
several metal-containing bases was carried out with
benzaldehyde (7a ) as substrate (Table 1). Whereas the
reaction with n-BuLi was essentially unselective (entry
1), NaHMDS furnished the product with a fair 4:1 ratio
(entry 2), and KHMDS gave the (Z)-amide 8a -Z as the
exclusive product (entry 3, >97:3), thus revealing that
the effect of the countercation is quite significant. More
common bases such as NaH and t-BuOK did not work.
The reaction of 1a with 3-phenylpropionaldehyde (7h ),
an aliphatic aldehyde, was examined at -78 °C with
KHMDS as the optimum base. This aldehyde was also
found to be highly Z selective (91:9), although not
exclusive. To improve the selectivity, an examination of
solvents was carried out (Table 2). However, attempts
to decrease (entry 3, ether) or increase (entry 4, THF-
HMPA mixture) the solvent polarity did not prove
rewarding. Lowering the reaction temperature did lead
to a slight increase in selectivity (entry 5), but the yield
As for aliphatic aldehydes, cyclohexanecarboxaldehyde
(7i), an R-branched olefin, reacted to give the (Z)-olefin
as the major product (entry 9). Here again as in the case
of o- and p-anisaldehyde, sterics seemed to have caused
lower selectivity. In contrast to cyclohexanecarboxalde-
hyde (7i), 2-phenylpropionaldehyde (7j) did not give any
desired product. This indicates that with readily enoliz-
able aldehydes, enolization is favored over the olefination
reaction. Apparently due to steric factors, pivalaldehyde
(7k ) was unreactive, as were other carbonyl compounds
such as ketones and cyclic acid anhydrides.
(15) For preliminary results see: Kojima. S.; Inai, H.; Hidaka, T.;
Ohkata, K. Chem. Commun. 2000, 1795-1796.
(16) For the regioselectivity of silylation see: (a) Rathke, M. W.;
Sullivan, D. F. Synth. Commun. 1973, 3, 67-72. (b) Hudrlik, P. F.;
Peterson, D.; Chou, D. Synth. Commun. 1975, 5, 359-365. (c) Larson,
G. L.; Fuentes, L. M. J . Am. Chem. Soc. 1981, 103, 2418-2419.
The electronic effect observed in aromatic aldehydes
with KHMDS as base was more obvious upon using
n-BuLi as the base (Table 4), with the Z selectivity

Z-Selective Synthesis of R,â-Unsaturated Amides
Ta ble 4. Rea ction s of 1 a n d 7 w ith n -Bu Li a s Ba sea
J . Org. Chem., Vol. 67, No. 12, 2002 4095
Ta ble 7. Differ en tly Su bstitu ted Rea gen ts 1, 5, a n d 6a
yield
entry
R
product
Z:Eb
yield (%)c
entry
reagent
R
product Z:Eb (%)c
1
2
3
p-MeOC6H4 (7b)
Ph (7a )
p-ClC6H4 (7d )
8b
8a
8d
69:31
54:46
43:57
94
85
95
1
2
3
4
5
6
7
8
Ph3SiCH2CONBn2 (1) Ph (7a )
Me3SiCH2CONBn2 (5) Ph (7a )
8a
8a
10a
10a
>97:3 88
27:73 63
71:29 82
58:42 80
Ph3SiCH2CO2Et (6)
Ph (7a )
Ph (7a )
a
All reactions were carried out in THF at -78 °C for 1 h and
Ph3SiCH2CO2Et (6)d
b
Ph3SiCH2CONBn2 (1) PhCH2CH2 (7h ) 8h
Me3SiCH2CONBn2 (5) PhCH2CH2 (7h ) 8h
91:9
77
0
then the temperature was raised slowly to 0 °C. Determined by
500 MHz 1H NMR measurement of the crude mixture. c Combined
Ph3SiCH2CO2Et (6)
PhCH2CH2 (7h ) 10h
PhCH2CH2 (7h ) 10h
77:23 78
62:38 68
isolated yield of (E)- and (Z)-olefins.
Ph3SiCH2CO2Et (6)d
Ta ble 5. Rea ction s of 3 a n d 7 w ith KHMDS a s Ba sea
a
All reactions were carried out in THF at -78 °C with KHMDS
as base unless noted otherwise. Determined by 500 MHz 1H
b
entry
R
product
Z:Eb
yield (%)c
NMR measurement of the crude mixture. c Combined isolated yield
1
2
3
4
5
6
7
Ph (7a )
9a
9b
9c
9d
9h
9i
>97:3
>97:3
78:22
97:3
92:8
88:12
78
99
53
66
72
44
0
d
of (E)- and (Z)-olefins. t-BuOK was used as base.
p-MeOC6H4 (7b)
o-MeOC6H4 (7c)
p-ClC6H4 (7d )
PhCH2CH2 (7h )
cyclohexyl (7i)
Ph(CH3)CH (7j)
Ta ble 8. Com p etition Rea ction sa
yield
entry
1
reagent
R
Z:Eb (%)c
9j
Ph3SiCH2CONMe2 (3)
PhCH2CH2 (7h ) 91:9
Ph (7a ) >97:3 56
(PhO)2P(O)CH2CO2Et (11) PhCH2CH2 (7h ) 85:15
Ph (7a ) 88:12
33
a
All reactions were carried out in THF at -78 °C with KHMDS
2
3
4
67
32
60
0
59
40
as base. Determined by 500 MHz 1H NMR measurement of the
b
crude mixture. c Combined isolated yield of (E)- and (Z)-olefins.
Ta ble 6. Rea ction s of 3 a n d 7 w ith n -Bu Li a s Ba sea
Ph3SiCH2CONMe2 (3)
PhCH2CH2 (7h ) 91:9
Ph(CH3)CH (7j)
(PhO)2P(O)CH2CO2Et (11) PhCH2CH2 (7h ) 82:18
Ph(CH3)CH (7j) 87:13
entry
R
product
Z:Eb
yield (%)c
a
1
2
3
p-MeOC6H4 (7b)
Ph (7a )
p-ClC6H4 (7d )
9b
9a
9d
>97:3
90:10
90:10
95
87
54
All reactions were carried out in THF at -78 °C with KHMDS
as base. The ratio was reagent:base:aldehyde 7h :aldehyde 7a (or
b
7j) ) 1:1:1:1. Determined by 500 MHz 1H NMR measurement
of the crude mixture. c Combined isolated yield of (E)- and (Z)-
olefins.
a
All reactions were carried out in THF at -78 °C for 1 h and
b
then the temperature was raised slowly to 0 °C. Determined by
500 MHz 1H NMR measurement of crude mixture. c Combined
ylsilyl reagent 5 using KHMDS as base, as shown in
Table 7.10 The reaction of 5 with benzaldehyde (7a )
resulted in a complete turnaround in selectivity, favoring
(E)-olefin formation (entry 2), while that with 3-phenyl-
propionaldehyde (7h ) gave no olefin product (entry 6).
The effect of having an amide in the place of an ester
group was next checked out with the ester analogue 6,
which bears the same triphenylsilyl group. The reaction
of 6 with benzaldehyde (7a ) (entry 3) and 3-phenylpro-
pionaldehyde (7h ) (entry 7) with KHMDS as base gave
the corresponding electron-deficient olefins as Z:E ) 71:
29 and 77:23 mixtures, respectively. These ratios are
clearly inferior compared with those of the corresponding
amide (entries 1 and 5). These results imply that the
electronic nature of the amide group has a bearing on
the selectivity. In contrast to the amide reagents, t-BuOK
could be used as base with the ester reagent 6, albeit
leading to somewhat lower selectivity (entries 4 and 8).
Another point to note is that the Si-based reagent 1 gave
higher Z selectivity than the corresponding HWE reagent
(an analogue of the Ando ester reagent) carrying the
same dibenzylamide group (i.e., 94:6 for benzaldehyde).
Especially significant was the reaction of aliphatic alde-
hydes, where selectivity was low or in some cases even
E selective for the HWE reagent (i.e. the highest selectiv-
ity was only 67:33 for 3-phenylpropionaldehyde).17,18
Since several aspects indicated that our Peterson
reagent differed from the Z-selective Ando reagent (9)
based on esters, we examined the chemoselectivity by
carrying out competitive reactions (Table 8). Thus, the
reaction with a reagent:aliphatic aldehyde 7h :aromatic
isolated yield of (E)- and (Z)-olefins.
decreasing from 69:31 (p-MeOC6H4CHO) down to 43:57
(p-ClC6H4CHO) with increasing electronegativity of the
aryl group.
Products with a secondary amide substituent were
envisioned to expand the utility of this system, and thus,
attempts with 2, which bears only one benzyl substituent,
were also carried out. However, under no conditions could
olefin formation be observed. The major reaction path in
this case was decomposition of the Peterson reagent,
evident from the nearly quantitative recovery of desilyl-
ated acetamide from the reaction mixture.
We next turned our attention toward the size of the
alkyl substituents upon the nitrogen atom. To assess our
amide reagents, the reaction of 3 was examined under
standard conditions (Table 5). A large increase in Z
selectivity was observed for p-ClC6H4CHO (7d ) (entry 4),
thus indicating that the less sterically hindered amide
is favorable for higher selectivity. As for aliphatic alde-
hydes, a slight increase was seen for the hindered
cyclohexylcarboxaldehyde 7i (entry 6).
The steric effect of the nitrogen substituents was more
obvious with the use of n-BuLi as base (Table 6). For the
three aromatic aldehydes (7a ,b,d ) examined, all gave
much higher Z selectivity than 1, while the same sub-
stituent effect order was retained as for 1. Especially with
p-anisaldehyde (7b), complete selectivity was attained.
This represents a rare case of high Z selectivity using a
lithium reagent in double-bond-forming chemistry.
Reactions for extremely sterically hindered 4 with
isopropyl groups were sluggish, and decomposition of
reagent was found to be the predominantly followed
route.
(17) Kojima, S.; Hidaka, T.; Ohba, Y.; Ohkata, K. Phosphorus,
Sulfur, Silicon 2002, 177, 729-732.
(18) Prof. Ando of the University of the Ryukyus has recently
reported on similar amide reagents (no examples on N,N-dibenzyl
amide) based on the Wadsworth-Emmons reaction: Ando, K. Synlett
2000, 1272-1274.
The efficacy of the triphenylsilyl group was demon-
strated by a comparison with the reactions of trimeth-

4096 J . Org. Chem., Vol. 67, No. 12, 2002
Kojima et al.
Sch em e 3
aldehyde 7a reactant ratio of 1:1:1 for 11 slightly favored
the product from the aliphatic aldehyde (entry 2). This
is in line with expectations from a electronic standpoint.
However, 3 turned out to slightly favor the aromatic
aldehyde (entry 1). A comparison between an unbranched
aldehyde and an R-branched aldehyde for 11 revealed
that the aldehydes are hardly differentiated (entry 4).
With 3, as expected from the above independent reac-
tions, only the unbranched aldehyde gave rise to product.
A decrease in yield compared with the result when the
aldehyde was used alone implies that when an enolizable
compound is present, enolization could compete to some
extent with olefination.
On the basis of empirical results, the general mecha-
nism for the Peterson reaction can be depicted as in
Scheme 3.2,20 The kinetic aldol products of the initial
addition of enolates to aldehydes in the Peterson reaction
with reagents bearing electron-withdrawing groups have
been determined to be erythro intermediates (corre-
sponding to in t-2-Z) upon examinations of aldol adducts
in the reaction of Me3SiCH2CO2R.3 The same has been
assumed in HWE reactions.19 In contrast to HWE reac-
tions, however, the retro-aldol reaction leading back to
enolate in t-1 and aldehyde in the Peterson reaction has
generally been considered to be of less significance.2,3
Intramolecular ring closure of the oxide in t-2-Z gives the
pentacoordinated intermediate in t-3-Z. In HWE reac-
tions, it is commonly accepted that olefin is formed
directly from the pentacoordinated oxidophosphorane
intermediate (corresponding to intermediates in t-3 in
Scheme 2) in a concerted manner. However, to account
for the generally low selectivity, it has been suggested
in the Peterson reaction that olefin formation is stepwise
from the pentacoordinated silicate such as in t-3. That
is, the cleavage of the Si-C bond in in t-3 gives an enolate
such as in t-4 as a short-lived intermediate and elimina-
tion of the silyloxide group follows to give the product.2,19
The presence of an intermediate such as in t-4 allows
C-C single-bond rotation to compete with the ensuing
elimination step, thus opening the opportunity for inter-
mediates such as in t-4-Z to change conformation to the
thermodynamically favored in t-4-E, the precursor to the
(E)-olefin.
the substitution of Me groups with Ph on Si does not
facilitate the retro-aldol reaction from in t-2-Z, then the
unexpectedly high Z selectivity (for a Peterson type
reaction) disclosed here can be rationalized by consider-
ation of in t-4-Z. The Ph groups raise the nucleofugacity
of the silyloxy group, and this in turn raises the rate of
olefin formation relative to single-bond rotation, thus
leading to higher Z content in the olefinic product. This
also accounts for the fact that (Z)-olefins are favored even
with ester reagents, as compared with corresponding
trimethylsilyl reagents.2 The presence of the amide group
works in an additive manner. Since the electron-donating
ability of nitrogen compared with that of oxygen leads
to destabilization of the enolate anion in t-4-Z, compared
with the ester group, the extrusion of silyl oxide becomes
more facile, whereas the rate of single-bond rotation
should remain essentially the same, whether the electron-
withdrawing group be an amide or an ester. Electron-
donating aryl groups (MeO compared with Cl) and
localized charge in the enolate due to the difference in
countercations (K+ compared with Li+) should further
assist in destabilizing in t-4-Z, resulting in facilitated
olefin formation and thus Z selectivity. With Li+, the
retro processes could also be more important, thus
explaining the lower selectivity in general.
Con clu sion
In summary, we have developed a highly geometry
selective method of preparing Z-unsaturated amides
based upon the Peterson reaction using the triphenylsilyl
group. Through the examination of substituent effects
upon the nitrogen atom of the amide moiety, it was
revealed that the selectivity and reactivity were sensitive
to the size of the substituents, with higher selectivity for
the smaller groups. It was also found that the use of
phenyl groups in the place of methyl groups upon silicon
was essential.
Exp er im en ta l Section
Gen er a l Con sid er a tion s. Melting points were measured
on a Yanaco micro melting point apparatus and are uncor-
rected. 1H and 13C NMR spectra were measured on a J EOL
J NM-LA500 spectrometer with CDCl3 as solvent. 1H NMR
chemical shifts are given in relative ppm from either internal
TMS (δ 0.0) or residual CHCl3 (δ 7.26). 13C NMR chemical
shifts are given in relative ppm from internal CDCl3 (δ 77.0).
High-resolution mass spectra were measured on a J EOL J MS-
SX102A spectrometer under electron ionization conditions (70
eV). Elemental analyses (CHN) were carried out on a Perkin-
Elmer 2400CHN elemental analyzer.
The results we have obtained here can be nicely
rationalized with this mechanism. If we can assume that
(19) Ando, K. J . Org. Chem. 1999, 64, 6815-6821 and references
therein.
(20) Yamamoto, K.; Tomo, Y.; Suzuki, S. Tetrahedron Lett. 1980,
21, 2861-2864.

Z-Selective Synthesis of R,â-Unsaturated Amides
J . Org. Chem., Vol. 67, No. 12, 2002 4097
All reactions were carried under N2. THF and ether were
freshly distilled from Na-benzophenone prior to use. Liquid
aldehydes were distilled before use. Silica gel column chro-
matography was carried out using Merck 7734 (63-200 mesh)
or 9385 (230-400 mesh). Preparative thin-layer chromatog-
raphy was carried out with plates prepared with Merck 7730.
N,N-Diben zyl(tr ip h en ylsilyl)a ceta m id e (1). To diben-
zylamine (4.04 mL, 21.0 mmol) and triethylamine (3.22 mL,
23.1 mmol) in THF (50 mL) was added acetyl chloride (1.49
mL, 21.0 mmol) at 0 °C. After it was stirred for 3 h at room
temperature, the solution was quenched with aqueous NaH-
CO3. After the usual workup, crude N,N-dibenzylacetamide
was obtained as a liquid. Without further purification, this
was dissolved in THF (10 mL) and added at -78 °C to LDA
prepared from n-butyllithium (1.50 M in hexane, 28.8 mL, 43.2
mmol) and diisopropylamine (6.0 mL, 42.8 mmol). After it was
warmed to 0 °C, the resulting solution was recooled to -78
°C, and triphenylsilyl chloride (6.10 g, 20.7 mmol) in THF (10
mL) was added at this temperature. The solution was quenched
with saturated NH4Cl after stirring for 2 h at room temper-
ature. After the usual workup, the product was subjected to
column chromatography (silica gel, 10/1 v/v hexane/ethyl
acetate) and then recrystallized (hexane/CH2Cl2) to give N,N-
dibenzyl(triphenylsilyl)acetamide (1) in 76% yield (7.9 g) as
colorless crystals. Mp: 111-114 °C. 1H NMR (CDCl3, 500
MHz): δ 7.59-6.90 (m, 25H), 4.49 (s, 2H), 4.10 (s, 2H), 2.88
(s, 2H). 13C NMR (CDCl3, 125 MHz): δ 171.9, 137.2, 136.6,
135.0, 133.7, 129.8, 128.8, 128.5, 128.3, 127.9, 127.4, 127.1,
126.4, 50.7, 48.2, 22.6. HRMS: calcd for C34H31NOSi 497.2175,
found 497.2177. Anal. Calcd for C34H31NOSi: C, 82.05; H, 6.28;
N, 2.81. Found: C, 82.11; H, 6.36; N, 2.79.
N-Ben zyl(tr iph en ylsilyl)acetam ide (2). A procedure simi-
lar to that for 1 was applied. Benzylamine (1.5 mL, 14 mmol),
triethylamine (2.2 mL, 15 mmol), and acetyl chloride (1.0 mL,
14 mmol) gave N-benzylacetamide as a crude product, which
was treated with LDA from n-butyllithium (1.53 M in hexane,
20.1 mL, 31 mmol) and diisopropylamine (4.1 mL, 31 mmol),
followed by triphenylsilyl chloride (4.13 g, 14 mmol), to give
N-benzyl(triphenylsilyl)acetamide (2) in 79% yield (4.5 g) as
colorless crystals. Mp: 155-157 °C. 1H NMR (CDCl3, 500
MHz): δ 7.57-7.33 (m, 15H), 7.20-7.17 (m, 3H), 6.92-6.89
(m, 2H), 5.23 (bs, 1H), 4.19 (s, 1H), 4.18 (s, 1H), 2.64 (s, 2H).
13C NMR (CDCl3, 125 MHz): δ 170.4, 138.0, 135.7, 133.3,
130.0, 128.5, 128.1, 127.7, 127.2, 43.8, 26.3. HRMS: calcd for
2.35 mL, 3.6 mmol), diisopropylamine (0.51 mL, 3.9 mmol),
and trimethylsilyl chloride (0.38 mL, 3.0 mmol) was obtained
N,N-dibenzyl(trimethylsilyl)acetamide 5 in 89% yield (0.79 g)
as a colorless oil. 1H NMR (CDCl3, 500 MHz): δ 7.39-7.16
(m, 10H), 4.59 (s, 2H), 4.39 (s, 2H), 2.11 (s, 2H), 0.14 (s, 9H).
13C NMR (CDCl3, 125 MHz): δ 172.9, 137.8, 136.6, 128.8,
128.4, 128.3, 127.5, 127.2, 126.4, 50.6, 47.6, 25.5, -0.9. Anal.
Calcd for C19H25NOSi: C, 73.26; H, 8.09; N,4.50. Found: C,
73.34; H, 8.08; N, 4.56.
Gen er a l P r oced u r es for th e P eter son Rea ction , Given
a s Exa m p les of th e Rea ction of Ben za ld eh yd e. With
KHMDS a s Ba se (Meth od A). To a solution of N,N-dibenzyl-
(triphenylsilyl)acetamide (1; 206 mg, 0.415 mmol) in THF (4
mL) cooled to -78 °C was added KHMDS (0.5 M in toluene,
0.98 mL, 0.49 mmol). After it was stirred for 30 min at 0 °C,
the solution was recooled to -78 °C. To this solution was added
benzaldehyde (7a ; 39.0 mg, 0.368 mmol) in THF (2.5 mL), and
stirring was continued for 3 h. Water was then added to
quench the solution, and extraction was carried out with ether.
After the usual workup and chromatographic purification by
preparative TLC (SiO2, 5/1 hexane/ethyl acetate), (Z)-N,N-
dibenzylcinnamamide (8a ) was obtained in 88% yield (106 mg,
Z:E = >97:3).
With n -Bu Li a s Ba se (Meth od B). To a solution of N,N-
dibenzyl(triphenylsilyl)acetamid (1; 206 mg, 0.415 mmol) in
THF (5 mL) cooled to -78 °C was added n-BuLi (1.53 M in
hexane, 0.27 mL, 0.42 mmol). After it was stirred for 30 min
at 0 °C, the solution was recooled to -78 °C. To this solution
was added benzaldehyde (7a ; 38.8 mg, 0.366 mmol) in THF
(2 mL), and stirring was continued for 1 h, after which the
solution was slowly warmed to 0 °C. Water was then added to
quench the reaction, and extraction was carried out with ether.
After the usual workup and chromatographic purification by
preparative TLC (SiO2, 5/1 hexane/ethyl acetate), a mixture
of (Z)- and (E)-N,N-dibenzylcinnamamide (8a ) was obtained
in 85% yield (102 mg, Z:E ) 54:46). The isomers were
separated by TLC (SiO2, 5/1 hexane/ethyl acetate).
(Z)-N,N-Diben zyl-3-p h en ylp r op -2-en a m id e (8a -Z). Pale
yellow oil. 1H NMR (CDCl3, 500 MHz): δ 7.39-7.20 (m, 13H),
7.06 (d, J ) 6.7 Hz, 2H), 6.66 (d, J ) 12.8 Hz, 1H), 6.18 (d, J
) 12.8 Hz, 1H), 4.59 (s, 2H), 4.38 (s, 2H). NOE: 9.9%. 13C NMR
(CDCl3, 125 MHz): δ 169.3, 136.6, 136.3, 135.4, 134.0, 129.1,
128.9, 128.6, 128.6, 128.6, 127.7, 127.6, 127.2, 127.2, 123.2,
50.6, 46.8. HRMS: calcd for
327.1633.
C23H21NO 327.1623, found
C
27H25NOSi 407.1705, found 407.1716. Anal. Calcd for C27H25-
NOSi: C, 79.57; H, 6.18; N, 3.44. Found: C, 79.50; H, 6.06;
N, 3.42.
(E)-N,N-Diben zyl-3-p h en ylp r op -2-en a m id e (8a -E). Col-
orless solid. Mp: 128-131 °C. H NMR (CDCl3, 500 MHz): δ
1
N,N-Dim eth yl(tr ip h en ylsilyl)a ceta m id e (3). A proce-
dure similar to that for 1 was applied. From N,N-dimethylac-
etamide (0.56 mL, 6.0 mmol), LDA from n-butyllithium (1.53
M in hexane, 4.7 mL, 7.2 mmol), diisopropylamine (1.0 mL,
7.8 mmol), and triphenylsilyl chloride (1.70 g, 6.0 mmol) was
obtained N,N-dimethyl(triphenylsilyl)acetamide (3) in 69%
7.86 (d, J ) 15.5 Hz, 1H), 7.47-7.21 (m, 15H), 6.90 (d, J )
15.5 Hz, 1H), 4.72 (s, 2H), 4.61 (s, 2H). 13C NMR (CDCl3, 125
MHz): δ 167.4, 144.0, 137.5, 136.8, 135.3, 129.8, 129.1, 128.9,
128.8, 128.5, 128.0, 127.9, 127.6, 126.7, 117.4, 50.2, 49.0.
HRMS: calcd for C23H21NO 327.1623, found 327.1626.
(Z)-N,N-Dib en zyl-3-(4-m et h oxyp h en yl)p r op -2-en a m -
id e (8b-Z). Following method A, 1 (176 mg, 0.353 mmol),
KHMDS (0.5 M in toluene, 0.88 mL, 0.44 mmol), and p-
methoxybenzaldehyde (7b; 38.1 mg, 0.280 mmol) gave (Z)-N,N-
dibenzyl-3-(4-methoxyphenyl)prop-2-enamide in 87% yield
(86.6 mg, Z:E = >97:3) as an oil.
1
yield (1.43 g) as colorless crystals. Mp: 116-118 °C. H NMR
(CDCl3, 500 MHz): δ 7.61-7.59 (m, 6H), 7.42-7.35 (m, 9H),
2.80 (s, 2H), 2.73 (s, 3H), 2.54 (s, 3H). 13C NMR (CDCl3, 125
MHz): δ 171.1, 135.7, 133.6, 129.7, 127.8, 38.1, 35.1, 22.5.
HRMS: calcd for C22H23NOSi 345.1549, found 345.1582. Anal.
Calcd for C22H23NOSi: C, 76.48; H, 6.71; N, 4.05. Found: C,
76.56; H, 6.82; N, 4.11.
Following method B, 1 (176 mg, 0.353 mmol), n-BuLi (1.53
M in hexane, 0.23 mL, 0.35 mmol), and p-methoxybenzalde-
hyde (7b; 39.3 mg, 0.289 mmol) gave N,N-dibenzyl-3-(4-
methoxyphenyl)prop-2-enamide (8b) in 94% yield (97 mg, Z:E
) 69:31) as an oil. The E and Z isomers could not be separated.
N,N-Bis(m eth yleth yl)(tr ip h en ylsilyl)a ceta m id e (4). A
procedure similar to that for 1 was applied. From N,N-
diisopropylacetamide (1.00 g, 7.00 mmol), LDA from n-butyl-
lithium (1.6 M in hexane, 8.80 mL, 14.0 mmol), diisopropyl-
amine (2.00 mL, 14.2 mmol), and triphenylsilyl chloride (2.47
g, 8.39 mmol) was obtained N,N-dimethyl(triphenylsilyl)-
acetamide 4 in 45% yield (1.27 g) as a colorless solid. This
compound gradually decomposed upon standing. Mp: 139-
141 °C. 1H NMR (CDCl3, 500 MHz): δ 7.67-7.58 (m, 6H),
7.46-7.33 (m, 9H), 3.71 (sept, J ) 6.7 Hz, 1H), 3.33 (bs, 1H),
2.77 (s, 2H), 1.22 (d, J ) 6.7 Hz, 6H), 0.83 (d, J ) 6.7 Hz, 6H).
HRMS: calcd for C26H31NOSi 401.2175, found 401.2178.
N,N-Diben zyl(tr im eth ylsilyl)a ceta m id e (5). A procedure
similar to that of 1 was applied. From N,N-dibenzylacetamide
(0.72 g, 3.0 mmol), LDA from n-butyllithium (1.53 M in hexane,
1
8b-Z: H NMR (CDCl3, 500 MHz) δ 7.36-7.27 (m, 10H), 7.09
(d, J ) 8.5 Hz, 2H), 6.73 (d, J ) 8.5 Hz, 2H), 6.59 (d, J ) 12.6
Hz, 1H), 6.05 (d, J ) 12.6 Hz, 1H), 4.59 (s, 2H), 4.39 (s, 2H),
3.80 (s, 3H); 13C NMR (CDCl3, 125 MHz) d 169.3, 159.7, 136.5,
136.3, 133.6, 130.0, 129.0, 128.7, 128.5, 127.9, 127.5, 127.4,
127.1, 120.7, 113.7, 55.1, 50.4, 46.6; HRMS calcd for C24H23
NO2 357.1729, found 357.1716.
-
(E)-N,N-Dib en zyl-3-(4-m et h oxyp h en yl)p r op -2-en a m -
id e (8b-E). 1H NMR (CDCl3, 500 MHz): δ 7.82 (d, J ) 15.5
Hz, 1H), 7.41 (d, J ) 8.8 Hz, 2H), 7.39-7.22 (m, 10H), 6.86 (d,
J ) 8.8 Hz, 2H), 6.77 (d, J ) 15.5 Hz, 1H), 4.71 (s, 2H), 4.60
(s, 2H), 3.81 (s, 3H).

4098 J . Org. Chem., Vol. 67, No. 12, 2002
Kojima et al.
(Z)-N,N-Dib en zyl-3-(2-m et h oxyp h en yl)p r op -2-en a m -
id e (8c-Z). Following method A, 1 (176 mg, 0.353 mmol),
KHMDS (0.5 M in toluene, 0.88 mL, 0.44 mmol), and o-
methoxybenzaldehyde (7c; 38.6 mg, 0.284 mmol) gave N,N-
dibenzyl-3-(2-methoxyphenyl)prop-2-enamide (8c) in 72% yield
(72.6 mg, Z:E ) 81:19) as an oil. The E and Z isomers could
not be separated. 8c-Z: 1H NMR (CDCl3, 500 MHz) δ 7.45 (dd,
J ) 7.6, 1.5 Hz, 1H), 7.31-7.23 (m, 9H), 7.19-7.15 (m, 1H),
7.07-7.03 (m, 1H), 6.97 (d, J ) 12.5 Hz, 1H), 6.83 (d, J ) 8.2
Hz, 1H), 6.79 (t, J ) 7.6 Hz, 1H), 6.18 (d, J ) 12.5 Hz, 1H),
4.54 (s, 2H), 4.35 (s, 2H), 3.76 (s, 3H); 13C NMR (CDCl3, 125
MHz) δ 169.5, 156.8, 136.5, 136.3, 129.8, 129.7, 129.4, 128.8,
128.7, 128.4, 127.5, 127.3, 127.1, 124.5, 122.7, 120.4, 110.4,
55.3, 50.3, 46.5; HRMS calcd for C24H23NO2 357.1729, found
357.1723.
(E)-N,N-Dib en zyl-3-(2-m et h oxyp h en yl)p r op -2-en a m -
id e (8c-E). 1H NMR (CDCl3, 500 MHz): δ 8.08 (d, J ) 15.5
Hz, 1H), 7.40-7.22 (m, 10H), 7.19-7.15 (m, 2H), 7.05 (d, J )
15.5 Hz, 1H), 7.07-7.03 (m, 1H), 6.92-6.87 (m, 1H), 4.72 (s,
2H), 4.60 (s, 2H), 3.80 (s, 3H).
(Z)-N,N-Dib en zyl-3-(4-ch lor op h en yl)p r op -2-en a m id e
(8d -Z). Following method A, 1 (206 mg, 0.413 mmol), KHMDS
(0.5 M in toluene, 0.85 mL, 0.425 mmol), and p-chlorobenzal-
dehyde (7d , 38.9 mg, 0.276 mmol) gave N,N-dibenzyl-3-(4-
chlorophenyl)prop-2-enamide (8d ) in 91% yield (91.2 mg, Z:E
) 88:12). The isomers were separated by TLC (SiO2, 5/1
hexane/ethyl acetate).
were separated by TLC (SiO2, 5/1 hexane/ethyl acetate). 8f-Z:
off-white solid; mp 71-72 °C; 1H NMR (CDCl3, 500 MHz) δ
8.45 (d, J ) 5.1 Hz, 1H), 7.57 (td, J ) 7.3, 1.8 Hz, 1H), 7.45 (d,
J ) 7.3 Hz, 2H), 7.39-7.28 (m, 7H), 7.15-7.13 (m, 3H), 6.67
(d, J ) 12.5 Hz, 1H), 6.32 (d, J ) 12.5 Hz, 1H), 4.64 (s, 2H),
4.43 (s, 2H); 13C NMR (CDCl3, 125 MHz) δ 169.6, 153.6, 149.3,
136.8, 136.6, 136.5, 132.0, 129.1, 128.8, 128.4, 127.5, 127.3,
127.1, 126.7, 123.7, 122.8, 50.5, 46.6; HRMS calcd for C22H20N2O
328.1576, found 328.1583.
(E)-N,N-Diben zyl-3-(2-p yr id yl)p r op -2-en a m id e (8f-E).
Viscous off-white oil. 1H NMR (CDCl3, 500 MHz): δ 8.57 (d, J
) 4.3 Hz, 1H), 7.82 (d, J ) 15.0 Hz, 1H), 7.68 (td, J ) 7.6, 1.5
Hz, 1H), 7.59 (d, J ) 15.0 Hz, 1H), 7.46-7.03 (m, 12H), 4.69
(s, 2H), 4.65 (s, 2H). 13C NMR (CDCl3, 125 MHz): δ 166.9,
153.3, 149.8, 142.1, 137.1, 136.9, 136.5, 128.9, 128.6, 128.3,
127.7, 127.4, 126.9, 124.9, 123.9, 121.5, 50.0, 48.3. HRMS:
calcd for C22H20N2O 328.1576, found 328.1584.
(Z,E)-N,N-Diben zyl-5-p h en ylp en ta -2,4-d ien a m id e (8g-
Z). Following method A, 1 (181 mg, 0.363 mmol), KHMDS (0.5
M in toluene, 0.72 mL, 0.36 mmol), and trans-cinnamaldehyde
(7g; 38.5 mg, 0.291 mmol) gave N,N-dibenzyl-5-phenylpenta-
2,4-dienamide in 99% yield (103 mg, E,Z:E,E ) 81:19). The
isomers were separated by TLC (SiO2, 5/1 hexane/ethyl
acetate). 8g-Z: colorless solid; mp 89-90 °C; 1H NMR (CDCl3,
500 MHz) δ 7.88 (ddd, J ) 15.8, 11.3, 1.2 Hz, 1H), 7.50-7.19
(m, 15H), 6.76 (d, J ) 15.8 Hz, 1H), 6.62 (ddd, J ) 11.3, 11.3,
1.2 Hz, 1H), 6.11 (d, J ) 11.3 Hz, 1H), 4.68 (s, 2H), 4.53 (s,
2H); 13C NMR (CDCl3, 125 MHz) δ 168.0, 140.6, 139.2, 137.5,
136.7, 136.7, 129.1, 128.8, 128.8, 128.7, 128.5, 127.8, 127.6,
Following method B, 1 (365 mg, 0.733 mmol), n-BuLi (1.53
M in hexane, 0.50 mL, 0.765 mmol), and p-chlorobenzaldehyde
(7d ; 51.5 mg, 0.366 mmol) gave N,N-dibenzyl-3-(4-chlorophen-
yl)prop-2-enamide (8d ) in 95% yield (126 mg, Z:E ) 43:57) as
an oil. The isomers were separated by TLC (SiO2, 5/1 hexane/
ethyl acetate). 8d -Z: colorless solid; mp 68-70 °C; 1H NMR
(CDCl3, 500 MHz) δ 7.36-7.25 (m, 10 H), 7.18 (d, J ) 8.5 Hz,
2H), 7.07 (m, 2H), 6.60 (d, J ) 12.5 Hz, 1H), 6.20 (d, J ) 12.5
Hz, 1H), 4.57 (s, 2H), 4.38 (s, 2H); 13C NMR (CDCl3, 125 MHz)
δ 168.7, 136.3, 136.0, 134.3, 133.7, 132.8, 129.8, 128.9, 128.8,
128.6, 128.5, 127.7, 127.6, 127.0, 123.7, 50.4, 46.7; HRMS calcd
for C23H2037ClNO 363.1204, found 363.1207; HRMS calcd for
127.4, 126.8, 125.4, 119.4, 50.6, 47.9; HRMS calcd for C25H23
NO 353.1780, found 353.1783.
-
(E,E)-N,N-Diben zyl-5-p h en ylp en ta -2,4-d ien a m id e (8g-
E). Colorless solid. Mp: 104-106 °C. 1H NMR (CDCl3, 500
MHz): δ 7.62 (ddd, J ) 14.6, 9.4, 0.9 Hz, 1H), 7.50-7.15 (m,
15H), 6.88 (t, J ) 14.6 Hz, 1H), 6.87 (d, J ) 9.4 Hz, 1H), 6.47
(d, J ) 14.6 Hz, 1H), 4.69 (s, 2H), 4.56 (s, 2H). 13C NMR
(CDCl3, 125 MHz): δ 167.3, 143.9, 139.5, 136.3, 135.0, 130.1,
129.0, 128.7, 128.6, 128.4, 127.9, 127.7, 127.4, 127.1, 126.9,
126.5, 120.4, 50.0, 48.8. HRMS: calcd for C25H23NO 353.1780,
found 353.1771.
C
23H2035ClNO 361.1233, found 361.1225.
(E)-N,N-Diben zyl-3-(4-ch lor op h en yl)p r op -2-en a m id e
(Z)-N,N-Diben zyl-5-p h en ylp en t-2-en a m id e (8h -Z). Fol-
lowing method A, 1 (178 mg, 0.358 mmol), KHMDS (0.5 M in
toluene, 0.72 mL, 0.36 mmol), and 3-phenylpropionaldehyde
(7h ; 41.3 mg, 0.308 mmol) gave N,N-dibenzyl-5-phenylpent-
2-enamide (8h ) in 77% yield (84.1 mg, Z:E ) 91:9) as an oil.
The E and Z isomers could not be separated. The replacement
of KHMDS with NaHMDS resulted in 54% yield and an
identical selectivity of Z:E ) 91:9. 8h -Z: 1H NMR (CDCl3, 500
MHz) δ 7.36-7.09 (m, 15H), 6.08 (dt, J ) 11.6, 1.5 Hz, 1H),
5.96 (dt, J ) 11.6, 7.0 Hz, 1H), 4.57 (s, 2H), 4.25 (s, 2H), 2.80-
2.77 (m, 4H); NOE 6.2%; 13C NMR (CDCl3, 125 MHz) δ 168.0,
141.4, 141.1, 137.0, 136.2, 128.7, 128.4, 128.3, 128.2, 128.1,
127.4, 127.2, 126.4, 125.7, 122.3, 49.9, 47.0, 35.0, 30.9; HRMS
calcd for C25H25NO 355.1909, found 355.1922.
(8d -E). Mp: 131-134 °C. Colorless solid. 1H NMR (CDCl3, 500
MHz): δ 7.80 (d, J ) 15.5 Hz, 1H), 7.39-7.26 (m, 12H), 7.21
(d, J ) 7.6 Hz, 2H), 6.86 (d, J ) 15.5 Hz, 1H), 4.71 (s, 2H),
4.60 (s, 2H). 13C NMR (CDCl3, 125 MHz): δ 166.9, 142.4, 137.2,
136.6, 135.5, 133.6, 129.0, 129.0, 128.9, 128.6, 128.3, 127.7,
127.5, 126.5, 117.8, 50.0, 48.9. HRMS: calcd for C23H2037ClNO
363.1204, found 363.1217. HRMS: calcd for C23H2035ClNO
361.1233, found 361.1232.
(Z)-N,N-Diben zyl-3-(2-fu r yl)p r op -2-en a m id e (8e-Z). Fol-
lowing method A, 1 (164 mg, 0.330 mmol), KHMDS (0.5 M in
toluene, 0.67 mL, 0.335 mmol), and furfural (7e; 20.8 mg, 0.217
mmol) gave N,N-dibenzyl-3-(2-furyl)prop-2-enamide (8e) in
92% yield (63.4 mg, Z:E ) 91:9). The isomers were separated
by TLC (SiO2, 5/1 hexane/ethyl acetate). 8e-Z: off-white solid;
mp 59-61 °C; 1H NMR (CDCl3, 500 MHz) δ 7.40-7.24 (m, 9H),
7.14 (d, J ) 7.0 Hz, 2H), 6.64 (d, J ) 3.4 Hz, 1H), 6.48 (d, J )
12.8 Hz, 1H), 6.37 (dd, J ) 3.4, 1.8 Hz, 1H), 6.03 (d, J ) 12.8
Hz, 1H), 4.63 (s, 2H), 4.45 (s, 2H); 13C NMR (CDCl3, 125 MHz)
δ 168.7, 150.8, 143.3, 136.9, 136.4, 129.0, 128.8, 128.4, 127.6,
127.4, 127.0, 122.1, 119.0, 112,7, 111.7, 50.5, 46.7; HRMS calcd
for C21H19NO2 317.1416, found 317.1421.
(E)-N,N-Dib en zyl-5-p h en ylp en t -2-en a m id e (8h -E). 1H
NMR (CDCl3, 500 MHz): δ 7.67 (dt, J ) 16.7, 1.5 Hz, 1H),
7.42-7.08 (m, 15H), 6.24 (dt, J ) 14.9, 1.5 Hz, 1H), 4.62 (s,
2H), 4.42 (s, 2H), 2.75 (t, J ) 7.3 Hz, 2H), 2.51 (td, J ) 7.3,
1.5 Hz, 2H).
(Z)-N,N-Diben zyl-3-cycloh exylp r op -2-en a m id e (8i-Z).
Following method A, 1 (120 mg, 0.242 mmol), KHMDS (0.5 M
in toluene, 0.48 mL, 0.24 mmol), and cyclohexanecarboxalde-
hyde (7i; 22.8 mg, 0.203 mmol) gave N,N-dibenzyl-3-cyclo-
hexylprop-2-enamide (8i) in 83% yield (56.0 mg, Z:E ) 83:17).
The isomers were separated by TLC (SiO2, 10/1 hexane/ethyl
(E)-N,N-Diben zyl-3-(4-fu r yl)p r op -2-en a m id e (8e-E). Off-
1
white oil. H NMR (CDCl3, 500 MHz): δ 7.62 (d, J ) 14.9 Hz,
1H), 7.41-7.19 (m, 11H), 6.84 (d, J ) 14.9 Hz, 1H), 6.56 (d, J
) 3.4 Hz, 1H), 6.43 (dd, J ) 3.4, 1.8 Hz, 1H), 4.69 (s, 2H), 4.59
(s, 2H). 13C NMR (CDCl3, 125 MHz): δ 167.30, 151.77, 144.19,
135.14, 130.76, 130.24, 129.09, 128.77, 128.48, 128.07, 127.57,
126.89, 114.81, 114.31, 112.32, 50.15, 48.80. HRMS: calcd for
1
acetate). 8i-Z: pale yellow oil; H NMR (CDCl3, 500 MHz) δ
7.37-7.21 (m, 8H), 7.15 (d, J ) 7.3 Hz, 2H), 5.99 (d, J ) 11.5
Hz, 1H), 5.75 (dd, J ) 11.5, 9.7 Hz, 1H), 4.60 (s, 2H), 4.46 (s,
2H), 2.88-2.79 (m, 1H), 1.79-1.67 (m, 5H), 1.39-1.28 (m, 2H),
1.21-1.14 (m, 1H), 1.14-1.04 (m, 2H); 13C NMR (CDCl3, 125
MHz) δ 168.7, 147.8, 135.1, 129.0, 128.7, 128.5, 128.0, 127.7,
127.5, 126.9, 120.0, 50.6, 47.2, 38.3, 32.7, 26.1, 25.7; HRMS
calcd for C23H27NO 333.2093, found 333.2082.
C
21H19NO2 317.1416, found 317.1411.
(Z)-N,N-Diben zyl-3-(2-p yr id yl)p r op -2-en a m id e (8f-Z).
Following method A, 1 (205 mg, 0.412 mmol), KHMDS (0.5 M
in toluene, 0.84 mL, 0.42 mmol), and 2-pyridylaldehyde (7f;
39.1 mg, 0.365 mmol) gave N,N-dibenzyl-3-(2-pyridyl)prop-2-
enamide (8f) in 47% yield (56.1 mg, Z:E ) 59:41). The isomers
(E)-N,N-Diben zyl-3-cycloh exylp r op -2-en a m id e (8i-E).
1
Pale yellow oil. H NMR (CDCl3, 500 MHz): δ 7.39-7.21 (m,

Z-Selective Synthesis of R,â-Unsaturated Amides
J . Org. Chem., Vol. 67, No. 12, 2002 4099
8H), 7.17 (d, J ) 7.3 Hz, 2H), 7.02 (dd, J ) 15.2, 7.3 Hz, 1H),
6.23 (dd, J ) 15.2, 1.2 Hz, 1H), 4.64 (s, 2H), 4.50 (s, 2H), 2.15-
2.07 (m, 1H), 1.76-1.68 (m, 4H), 1.67-1.60 (m, 1H), 1.31-
1.07 (m, 5H). 13C NMR (CDCl3, 125 MHz): δ 167.7, 153.1,
137.6, 136.9, 129.0, 128.6, 128.5, 127.7, 127.4, 126.7, 117.7,
50.0, 48.6, 40.9, 32.1, 26.0, 25.8. HRMS: calcd for C23H27NO
333.2093, found 333.2083.
(Z)-N,N-Dim eth yl-3-p h en ylp r op -2-en a m id e (9a -Z). Fol-
lowing method A, 3 (143 mg, 0.415 mmol), KHMDS (0.5 M in
toluene, 0.98 mL, 0.49 mmol), and benzaldehyde (7a ; 40.2 mg,
0.379 mmol) gave N,N-dimethyl-3-phenylprop-2-enamide (9a )
in 78% yield (51.5 mg, Z:E ) >97:3) as an oil.
158.1, 137.7, 130.5, 128.9, 124.3, 120.5, 118.4, 111.1, 55.4, 37.3,
35.8.
(Z)-N,N-Dim et h yl-3-(4-ch lor op h en yl)p r op -2-en a m id e
(9d -Z). Following method A, 3 (152 mg, 0.440 mmol), KHMDS
(0.5 M in toluene, 0.90 mL, 0.45 mmol), and p-chlorobenzal-
dehyde (7d ; 43.3 mg, 0.308 mmol) gave N,N-dimethyl-3-(4-
chlorophenyl)prop-2-enamide (9d ) in 66% yield (42.3 mg, Z:E
) 97:3) as an oil. Following method B, 3 (138 mg, 0.399 mmol),
n-butyllithium (1.54 M in hexane, 0.26 mL, 0.400 mmol), and
p-chlorobenzaldehyde (7d , 28.4 mg, 0.202 mmol) gave N,N-
dimethyl-3-(4-chlorophenyl)prop-2-enamide (9d ) in 54% yield
(22.8 mg, Z:E ) 90:10) as an oil. The E and Z isomers could
not be separated. 9d -Z: 1H NMR (CDCl3, 500 MHz) δ 7.31 (d,
J ) 8.8 Hz, 2H), 7.28 (d, J ) 8.8 Hz, 2H), 6.59 (d, J ) 12.5 Hz,
1H), 6.07 (d, J ) 12.5 Hz, 1H), 2.98 (s, 3H), 2.86 (s, 3H); 13C
NMR (CDCl3, 125 MHz) δ 168.4, 134.1, 134.0, 132.0, 129.4,
128.6, 123.9, 37.4, 34.3; HRMS calcd for C11H1237ClNO 211.0578,
found 211.0572; HRMS calcd for C11H1235ClNO 209.0607, found
209.0606.
Following method B, 3 (156 mg, 0.452 mmol), n-butyllithium
(1.53 M in hexane, 0.30 mL, 0.452 mmol), and benzaldehyde
(7a ; 38.5 mg, 0.363 mmol) gave N,N-dimethyl-3-phenylprop-
2-enamide (9a ) in 87% yield (55.3 mg, Z:E ) 90:10) as an oil.
1
The E and Z isomers could not be separated. 9a -Z: H NMR
(CDCl3, 500 MHz) δ 7.36-7.26 (m, 5H), 6.65 (d, J ) 12.5 Hz,
1H), 6.05 (d, J ) 12.5 Hz, 1H), 2.98 (s, 3H), 2.83 (s, 3H). NOE
5.7%. 13C NMR (CDCl3, 125 MHz) δ 168.8, 135.5, 133.1, 128.4,
128.3, 128.0, 123.3, 37.3, 34.2; HRMS calcd for C11H13NO
175.0997, found 175.1013.
(E)-N,N-Dim et h yl-3-(4-ch lor op h en yl)p r op -2-en a m id e
1
(9d -E). H NMR (CDCl3, 500 MHz): δ 7.61 (d, J ) 15.5 Hz,
1H), 7.45 (d, J ) 8.5 Hz, 2H), 7.34 (d, J ) 8.5 Hz, 2H), 6.86 (d,
J ) 15.5 Hz, 1H), 3.17 (s, 3H), 3.07 (s, 3H).
1
(E)-N,N-Dim eth yl-3-p h en ylp r op -2-en a m id e (9a -E). H
NMR (CDCl3, 500 MHz): δ 7.67 (d, J ) 15.5 Hz, 1H), 7.54-
7.52 (m, 2H), 7.38-7.30 (m, 3H), 6.89 (d, J ) 15.5 Hz, 1H),
3.16 (br s, 3H), 3.09 (br s, 3H).
(Z)-N,N-Dim et h yl-3-(4-m et h oxyp h en yl)p r op -2-en a m -
id e (9b-Z). Following method A, 3 (122 mg, 0.353 mmol),
KHMDS (0.5 M in toluene, 0.88 mL, 0.44 mmol), and p-
methoxybenzaldehyde (7b; 40.2 mg, 0.295 mmol) gave N,N-
dimethyl-3-(4-methoxyphenyl)prop-2-enamide (9b) in 99% yield
(60.1 mg, Z:E ) >97:3) as an oil.
(Z)-N,N-Dim eth yl-5-p h en ylp en t-2-en a m id e (9h -Z). Fol-
lowing method A, 3 (113 mg, 0.328 mmol), KHMDS (0.5 M in
toluene, 0.78 mL, 0.39 mmol), and 3-phenylpropionaldehyde
(7h ; 40.3 mg, 0.300 mmol) gave N,N-dimethyl-5-phenylpent-
2-enamide (9h ) in 72% yield (44 mg, Z:E ) 92:8) as an oil.
1
The E and Z isomers could not be separated. 9h -Z: H NMR
(CDCl3, 500 MHz) δ 7.28-7.25 (m, 2H), 7.21-7.16 (m, 3H),
5.99 (dt, J ) 11.6, 1.5 Hz, 1H), 5.91 (dt, J ) 11.6, 7.0 Hz, 1H),
2.91 (s, 6H), 2.77-2.67 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ
167.7, 141.3, 139.9, 128.4, 128.2, 125.8, 122.6, 37.4, 35.1, 34.5,
30.6; HRMS calcd for C13H17NO 203.1310, found 203.1343.
(E)-N,N-Dim eth yl-5-p h en ylp en t-2-en a m id e (9h -E). 1H
NMR (CDCl3, 500 MHz): δ 7.30-7.27 (m, 2H), 7.20-7.17 (m,
3H), 6.89 (dt, J ) 15.2, 7.0 Hz, 1H), 6.22 (dt, J ) 15.2, 1.2 Hz,
1H), 2.99 (s, 6H), 2.78 (t, J ) 7.3 Hz, 2H), 2.53 (tdd, J ) 7.3,
7.0, 1.2 Hz, 2H).
Following method B, 3 (122 mg, 0.353 mmol), n-butyllithium
(1.53 M in hexane, 0.23 mL, 0.353 mmol), and p-methoxyben-
zaldehyde (7b; 39.2 mg, 0.288 mmol) gave N,N-dimethyl-3-(4-
methoxyphenyl)prop-2-enamide (9b) in 95% yield (56.0 mg, Z:E
) >97:3) as an oil. The E and Z isomers could not be separated.
1
9b-Z: H NMR (CDCl3, 500 MHz) δ 7.31 (d, J ) 8.5 Hz, 2H),
6.84 (d, J ) 8.5 Hz, 2H), 6.58 (d, J ) 12.5 Hz, 1H), 5.93 (d, J
) 12.5 Hz, 1H), 3.81 (s, 3H), 2.99 (s, 3H), 2.87 (s, 3H); NOE
5.7%; 13C NMR (CDCl3, 125 MHz) δ 169.1, 159.5, 132.8, 129.6,
(Z)-N,N-Dim eth yl-3-cycloh exylp r op -2-en a m id e (9i-Z).
Following method A, 3 (153 mg, 0.443 mmol), KHMDS (0.5 M
in toluene, 0.90 mL, 0.45 mmol), and cyclohexanecarboxalde-
hyde (7i; 34.2 mg, 0.305 mmol) gave N,N-dimethyl-3-cyclo-
hexylprop-2-enamide (9i) in 44% yield (24.4 mg, Z:E ) 88:12).
The isomers were separated by TLC (SiO2, 4/1 hexane/ethyl
128.2, 121.1, 113.8, 55.1, 37.4, 34.2; HRMS calcd for C12H15
NO2 205.1103, found 205.1105.
-
(Z)-N,N-Dim et h yl-3-(2-m et h oxyp h en yl)p r op -2-en a m -
id e (9c-Z). Following method A, 3 (134 mg, 0.390 mmol),
KHMDS (0.5 M in toluene, 0.78 mL, 0.390 mmol), and
2-methoxybenzaldehyde (7c; 40.5 mg, 0.297 mmol) gave N,N-
dimethyl-3-(2-methoxyphenyl)prop-2-enamide (9c) in 53% yield
(32.2 mg, Z:E ) 78:22) as a pale yellow oil. The E and Z
isomers could not be separated. 9c-Z: 1H NMR (CDCl3, 500
MHz) δ 7.35-7.22 (m, 2H), 6.96-6.83 (m, 2H), 6.93 (d, J )
12.5 Hz, 1H), 6.02 (d, J ) 12.5 Hz, 1H), 3.82 (s, 3H), 2.91 (s,
3H), 2.76 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 169.2, 156.8,
129.7, 129.0, 128.7, 124.8, 122.9, 120.5, 110.5, 55.4, 37.4, 34.3;
HRMS (FAB) calcd for C12H16NO2 206.1181, found 206.1187.
(E)-N,N-Dim et h yl-3-(2-m et h oxyp h en yl)p r op -2-en a m -
id e (9c-E). 1H NMR (CDCl3, 500 MHz): δ 7.91 (d, J ) 15.5
Hz, 1H), 7.49 (dd, J ) 7.62, 1.22 Hz, 1H), 7.35-7.22 (m, 1H),
7.00 (d, J ) 15.5 Hz, 1H), 6.96-6.83 (m, 2H), 3.86 (s, 3H),
3.14 (s, 3H), 3.05 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 167.3,
1
acetate). 9i-Z: pale yellow oil; H NMR (CDCl3, 500 MHz) δ
5.87 (d, J ) 11.6 Hz, 1H), 5.70 (dd, J ) 11.6, 9.8 Hz, 1H), 3.02
(s, 3H), 2.98 (s, 3H), 2.77-2.65 (m, 1H), 1.76-1.60 (m, 5H),
1.38-1.24 (m, 2H), 1.22-1.01 (m, 3H); 13C NMR (CDCl3, 125
MHz) δ 168.1, 146.7, 119.9, 38.0, 37.9, 34.7, 32.6, 26.0, 25.5;
HRMS calcd for C11H19NO 181.1467, found 181.1476.
(E)-N,N-Dim eth yl-3-cycloh exylp r op -2-en a m id e (9i-E).
1
Pale yellow oil. H NMR (CDCl3, 500 MHz): δ 6.83 (dd, J )
15.2, 7.0 Hz, 1H), 6.18 (dd, J ) 15.2, 1.5 Hz, 1H), 3.07 (s, 3H),
3.00 (s, 3H), 2.18-2.08 (m, 1H), 1.81-1.72 (m, 4H), 1.71-1.63
(m, 1H), 1.35-1.24 (m, 2H), 1.24-1.11 (m, 3H). 13C NMR
(CDCl3, 125 MHz): δ 167.4, 151.5, 117.8, 40.9, 37.5, 35.9, 32.2,
26.2, 26.0.
J O0161936