A Practical Synthesis of α,β-Unsaturated Imides, Useful Substrates for Asymmetric Conjugate Addition Reactions

Article abstract of DOI:10.1002/1615-4169(200210)344:9<953::AID-ADSC953>3.0.CO;2-A

We report an improved synthesis of α,β-unsaturated imides, a class of compounds that has been identified as broadly useful in (salen)aluminum-catalyzed asymmetric conjugate addition reactions. An efficient, scaleable procedure for the synthesis of phospho

Full text of DOI:10.1002/1615-4169(200210)344:9<953::AID-ADSC953>3.0.CO;2-A

UPDATES
A Practical Synthesis of a,b-Unsaturated Imides, Useful
Substrates For Asymmetric Conjugate Addition Reactions
Steven N. Goodman, Eric N. Jacobsen*
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138 USA
Fax: ( ‡ 1)-617-496-1880, e-mail: jacobsen@chemistry.harvard.edu
Received: June 28, 2002; Accepted: July 19, 2002
The route that we reported previously for the synthesis
Abstract: We report an improved synthesis of a,b-
unsaturated imides, a class of compounds that has
À
À
of 1 employed a Horner Wadsworth Emmons (HWE)
reaction of phosphonate imide 4 and aldehydes
(Eq. 2).[1,3] The procedure involved generation of the
been
identified
as
broadly
useful
in
(salen)aluminum-catalyzed asymmetric conjugate
addition reactions. An efficient, scaleable procedure
for the synthesis of phosphonate imide reagent 4 is
À
dianion of 4 (2 equiv. n-BuLi, 0.2 M THF, 78 8C),
followed by addition of an excess of aldehyde (3 equiv.).
After stirring several hours at room temperature, the
product was isolated by column chromatography after
work-up. While this approach effectively generated
small quantities of substrates for screening purposes,
many of its features made it unattractive for large-scale
preparation. Problems associated with temperature
control, high dilution, and use of an excess of alkyllithi-
um base had to be resolved.
À
described, as well as a DBU-mediated Horner
Wadsworth Emmons reaction that affords the target
À
compounds in high yield and (E)-selectivity and with
good functional group tolerance.
À
Keywords: asymmetric catalysis; Horner Wads-
worth Emmons reactions; imides; synthetic meth-
ods; Wittig reactions
À
O
O
O
P
O
O
1. 2 equiv. n-BuLi
In 1999, we reported the (salen)aluminum-catalyzed
asymmetric conjugate addition of azide to a,b-unsatu-
rated imides (Eq. 1).[1] Compounds of the general
structure 1 were found to be particularly good sub-
strates for the preparation of b-amino acid precursors
(3) in highly enantioenriched form. Since this discovery,
a variety of other nucleophiles (e.g., HCN, malononi-
trile, arenethiols) have been identified in effective
asymmetric Al(salen)-catalyzed 1,4-additions to this
class of conjugate acceptors.[2] Given the growing
importance of these a,b-unsaturated imides as sub-
strates in asymmetric catalytic reactions, we have
pursued practical and general methods for their prep-
aration. We report here a significant advance in that
regard.
THF, –78 °C
EtO
EtO
N
Ph
ꢀ2†
H
N
Ph
2. RCHO
H
R
4
1
Optimization of the coupling reaction would be impos-
sible without a practical, efficient route to phosphonate
reagent 4. The published procedure, outlined in Eq. 3,
begins with diethylphosphonoacetic acid (5). Treatment
with pivaloyl chloride (PivCl) and pyridine in dichloro-
methane (0.3 M) affords the mixed anhydride which,
after removal of the pyridinium salts by filtration, is
treated with benzamide overnight in refluxing toluene
(0.2 M). Column chromatography afforded pure phos-
phonate product.[1] Although the sequence reliably
generated 4, the relatively high cost of reagents and
the use of chromatographic purification made it difficult
to execute on large scale.
O
O
O
O
catalyst 2
N
Ph
N
Ph
H
H
HN3
R
N3
R
1
3
R = Alkyl (93 - 99% ee)
R = Ph (60% ee)
ꢀ1†
N
O
N
Al
X
1. PivCl, pyridine,
O
P
O
O
O
P
O
t-Bu
O
t-Bu
CH2Cl2
EtO
EtO
EtO
EtO
ꢀ3†
t-Bu
t-Bu
N
Ph
2. benzamide,
toluene, reflux
OH
H
2
X = Me, N3, Cl, O[Al(salen)]
5
4
Adv. Synth. Catal. 2002, 344, No. 9
¹ 2002 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 1615-4150/02/34409-953 956 $ 17.50+.50/0
953

Steven N. Goodman, Eric N. Jacobsen
UPDATES
N-(chloroacetyl)benzamide 6 in 75 80% yield.[4] Heat-
ing this compound to 80 8C[5] in the presence of 2.5 equiv.
triethyl phosphite (Michaelis Arbuzov conditions )
afforded the desired phosphonate imide in 77% yield
after recrystallization. This two-step synthesis of 4 is
experimentally straightforward, requires no chroma-
tography, uses inexpensive reagents, circumvents the
use of solvent and base, and is readily scaleable.
O
O
O
O
110 °C
+
Cl
Cl
N
Ph
[6]
H2N
Ph
À
Cl
H
6
77% crystalline yield
O
P
O
O
(EtO)3P
EtO
EtO
N
Ph
80 °C
H
4
With an improved route to phosphonate 4 in hand, we
were in a position to turn our attention to the HWE
reaction. After screening a variety of bases, we were
pleased to find that 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU) promoted the coupling of 4 with aldehydes
exceptionally well, providing high yields of the desired
(E)-olefin products.[7] Surprisingly, lowering the amount
of DBUfrom two equiv. to one had no appreciable effect
on product formation in terms of rate or yield. Although
the imide N-H is the most acidic proton of the system
(pKa ~12 13, versus pKa ~19 20 for the a-phospho-
nate protons),[8] it is apparent that its deprotonation
does not lead to a productive pathway. Instead, the low
concentration of the enolate that is generated appa-
rently reacts very efficiently with the aldehyde to form
the product irreversibly.
We discovered subsequently that other acidic func-
tionalities, such as free hydroxy groups, are also
tolerated in the reaction mixture. In fact, water can be
employed as solvent without any deleterious effect on
the reaction, obviating any need to run the reaction
under inert atmosphere or dried glassware. The out-
come is not altered by changing the concentration or
order ofaddition of reagents; the base can evenbe added
last to a mixture of phosphonate and aldehyde without
aldehyde decomposition. Thus, from an experimental
standpoint, this procedure appears to be very robust.
The new HWE reaction has been performed success-
fully on a variety of aldehydes. Table 1 lists the results
obtained from a select subset of interesting examples. In
almost all instances, the products were formed in > 98:2
E:Z selectivity as determined by 1H NMR of the
unpurified reaction mixture.[9] Some salient features of
these results merit specific comment: (1) high yields of
product are obtained using equimolar amounts (or a
very slight excess) of each component in very short
reaction times; (2) the reactions are conducted entirely
at room temperature and high concentration (1.0
M THF); (3) the HWE reaction is successful on a wide
variety of aliphatic, aromatic and heteroaromatic
aldehydes; (4) both electron-rich and electron-deficient
aldehydes are suitable substrates, though the latter tend
to undergo reaction with significantly faster rates; and
(5) a variety of unprotected functional groups are
compatible with this HWE reaction, including free
hydroxy groups (entries 3 and 4), esters (entry 9), and
77% crystalline yield
Scheme 1. An improved synthesis of phosphonate 4.
Table 1. DBU-mediated HWE reaction of various aldehydes with
phosphonate imide 4.[a]
O
O
O
P
O
O
DBU
O
EtO
EtO
+
N
Ph
N
H
Ph
THF, RT
H
R
H
R
7 - 16
4
Product
Yield [%][b]
entry
1[c]
Time
4 h
R
Me
7
90
Me
2[d,e]
1.5 h
45 min
4 h
8
BnO
91
87
82
92
96
90
91
94
92
O
HO
HO
3
9
4
10
11
12
13
14
15
16
5[d]
1 h
N
6
30 min
5 min
10 min
30 min
15 min
N
O2N
O2N
7
8
9
MeO2C
Me
O
10
[a]
[b]
Unless otherwise noted, all reactions were performed using 1.0
mmol phosphonate imide 4, 1.0 mmol aldehyde, and 1.0 mmol
DBU in 1.0 mL THF at room temperature.
Isolated yield after aqueous workup and purification. Yields are of
the pure (E)-isomer.
[c]
[d]
[e]
1.1 mmol aldehyde was used.
1.05 mmol aldehyde was used.
Reaction was conducted at 0 °C.
We have achieved an improved synthesis of 4, as depict- ketones (entry 10).[10] Furthermore, most of the a,b-
ed in Scheme 1. Benzamide and chloroacetyl chloride unsaturated imide products are crystalline, allowing for
are heated to 110 8C in the absence of solvent to produce simple purification without chromatography.
954
Adv. Synth. Catal. 2002, 344, 953 956

A Practical Synthesis of a,b-Unsaturated Imides
UPDATES
THF (1.0 mL) was added, followed by DBU(0.15 mL,
1.0 mmol) and the appropriate aldehyde (1.0 1.1 mmol).
[Caution: A slight initial exotherm can be detected after
addition of aldehyde, but this can be controlled with an
external water bath.] Upon completion of the reaction (as
determined by TLC analysis), the reaction mixture was diluted
with EtOAc (10 mL) and water (5 mL). In some cases, the
product precipitated directly from the biphasic solution, and
could be isolated by filtration and washing with Et2O
(Procedure A). Alternatively, the layers were separated, and
the aqueous portion extracted with additional EtOAc (10 mL).
The combined organic extracts were washed with brine (5 mL),
dried over Na2SO4, concentrated under vacuum and the
material purified by column chromatography (Procedure B).
In summary, we have developed a practical method
for the synthesis of a,b-unsaturated imides 1, useful
substrates in a number of asymmetric catalytic con-
jugate addition reactions. A scaleable synthesis of the
phosphonate imide 4 provides this intermediate in good
yield without use of solvent or chromatography. Finally,
the critical HWE reaction is a practical, highly selective
DBU-mediated transformation that is tolerant of a wide
range of functionality.
Experimental Section
N-(5-Methylhex-2-enoyl)-benzamide (7): The product was
obtained as a white powder in 90% yield, using 1.1 mmol
aldehyde and Procedure B; mp 84.5 85.5 8C; Rf ˆ 0.33 (1:4
General Remarks
All commercial reagents were used as received. DBUwas
purchased from Aldrich; benzamide, chloroacetyl chloride and
triethyl phosphite from Alfa Aesar. Unless noted otherwise, no
special precautions against water and oxygen were taken.
EtOAc:hexanes); IR (film): n ˆ 3295, 2959, 1725, 1679, 1640,
À
1
1
1481, 1255, 1167, 706 cm ; H NMR (500 MHz, CDCl3): d ˆ
8.58 (s, 1H), 7.89 (m, 2H), 7.63 (tt, J ˆ 1.0 Hz, 7.5 Hz, 1H), 7.53
(t, J ˆ 7.5 Hz, 2H), 7.22 (m, 1H), 7.15 (d, J ˆ 15.5 Hz, 1H), 2.23
(dt, J ˆ 1.0 Hz, 7.0 Hz, 2H), 1.85 (sept, J ˆ 6.5 Hz, 1H), 0.99 (d,
J ˆ 7.0 Hz, 6H); 13C NMR (100 MHz, CDCl3): d ˆ 168.1, 166.2,
150.7, 133.0, 132.9, 128.6, 128.0, 123.8, 41.7, 27.9, 22.3; MS
(APCI): m/z ˆ 232 ([M ‡ H], 100%).
Synthesis of Phosphonate Imide 4
Benzamide (12.1 g, 0.100 mol) and chloroacetyl chloride
(8.20 mL, 0.103 mol) were added to a 100-mL flask equipped
with a magnetic stirbar and condenser, and the mixture was
heated to 110 8C under a balloon of nitrogen. Within 5 min, the
mixture became homogeneous, then gradually became orange
and solidified. After 30 min, the mixture was cooled and
volatile by-products removed under vacuum. The solid residue
was triturated with Et2O (30 mL), and the product was
collected by filtration to yield N-(chloroacetyl)benzamide
(6); yield: 15.2 g (77%), which was employed in the next step
without further purification.[4,5]
N-(4-Benzyloxybut-2-enoyl)-benzamide (8): The product
was obtained as a white solid in 91% yield, using 1.05 mmol
aldehyde and Procedure B; mp 93 94 8C; Rf ˆ 0.37 (3:7
EtOAc:hexanes); IR (film): n ˆ 3276, 3066, 2855, 1724, 1679,
À
1
1
1495, 1250, 1156, 704 cm ; H NMR (500 MHz, CDCl3): d ˆ
8.44 (s, 1H), 7.88 (d, J ˆ 8.0 Hz, 2H), 7.64 (dt, J ˆ 1.0 Hz, 7.0 Hz,
1H), 7.54 (t, J ˆ 7.5 Hz, 2H), 7.41 (m, 5H), 7.34 (m, 1H), 7.24
(dt, J ˆ 4.5 Hz, 15.5 Hz, 1H), 4.64 (s, 2H), 4.30 (m, 2H);
13C NMR (100 MHz, CDCl3): d ˆ 166.9, 165.7, 146.5, 137.7,
133.3, 132.9, 129.0, 128.5, 127.9, 127.8, 127.8, 122.7, 72.9, 69.0;
MS (APCI): m/z ˆ 296 ([M ‡ H], 100%).
Crude N-(chloroacetyl)benzamide (15.2 g, 0.077 mol) was
placed in a 100-mL flask equipped with a stirbar and an air-
cooled condenser. P(OEt)3 (32.9 mL, 0.196 mol) was added,
and the mixture was heated to 80 8C under nitrogen until the
starting material was fully consumed (24 30 h, as determined
by TLC analysis). After the solution was allowed to cool to
room temperature, hexanes (30 mL) were added to the stirred
mixture, and the clear top layer was then decanted. This
process was repeated (3 Â 15 mL hexanes) to remove the
excess P(OEt)3. The remaining residue was then recrystallized
from ca. 3:1 toluene:hexanes (100 110 mL) to afford the
desired phosphonate imide (4) as a slightly off-white solid;
yield: 17.7 g (77%); mp 61 63 8C; Rf ˆ 0.21 (EtOAc); IR
N-[3-(5-Hydroxymethylfuran-2-yl)-acryloyl]-benzamide
(9): The product was obtained as a white solid in 87% yield,
according to Procedure B: mp 158 159 8C; Rf ˆ 0.14 (1:1
EtOAc:hexanes); IR (film): n ˆ 3278, 1719, 1621, 1486, 1253,
À
1
1
1148, 698 cm ; H NMR (600 MHz, acetone-d6): d ˆ 9.98 (s,
1H), 8.03 (d, J ˆ 7.8 Hz, 2H), 7.63 (dt, J ˆ 1.2 Hz, 7.2 Hz, 1H),
7.54 (m, 3H), 7.39 (d, J ˆ 15.0 Hz, 1H), 6.81 (d, J ˆ 3.6 Hz, 1H),
6.44 (d, J ˆ 3.6 Hz, 1H), 4.59 (d, J ˆ 6.0 Hz, 2H), 4.48 (t, J ˆ
6.0 Hz, 1H); 13C NMR (100 MHz, acetone-d6): d ˆ 166.9, 166.8,
159.5, 151.5, 134.4, 133.4, 131.5, 129.2, 128.9, 117.8, 117.7, 110.3,
57.2; MS (APCI): m/z ˆ 272 ([M ‡ H], 100%).
N-[3-(3-Hydroxyphenyl)-acryloyl]-benzamide (10): The
product was obtained as a white solid in 82% yield, using
(film): n ˆ 3248, 3156, 2986, 2939, 1747, 1687, 1513, 1247, 1028,
À
709 cm ; 1H NMR (600 MHz, CDCl3): d ˆ 9.69 (s, 1H), 7.91 (d,
1
Procedure A;
mp
186 187.5 8C;
Rf ˆ 0.33
(1:1
EtOAc:hexanes); IR (film): n ˆ 3264, 1725, 1625, 1480, 1256,
J ˆ 7.8 Hz, 2H), 7.58 (d, J ˆ 7.8 Hz, 1H), 7.48 (m, 2H), 4.18 (m,
4H), 3.42 (d, J ˆ 21.0 Hz, 2H), 1.32 (dt, J ˆ 1.8 Hz, 7.2 Hz, 6H);
13C NMR (100 MHz, CDCl3): d ˆ 165.2, 165.1, 133.3, 132.5,
129.0, 127.9, 63.0 (d, J ˆ 6.8 Hz), 36.5 (d, J ˆ 129.7 Hz), 16.3 (d,
J ˆ 6.1 Hz); MS (APCI): m/z ˆ 300 ([M ‡ H], 100%).
À
1
1153, 704 cm ; 1H NMR (500 MHz, acetone-d6): d ˆ 10.02 (s,
1H), 8.60 (s, 1H), 8.05 (d, J ˆ 7.5 Hz, 2H), 7.73 (d, J ˆ 15.5 Hz,
1H), 7.67 (m, 2H), 7.57 (m, 2H), 7.30 (t, J ˆ 8.0 Hz, 1H), 7.18
(dd, J ˆ 2.5 Hz, 4.0 Hz, 2H), 6.94 (dd, J ˆ 2.5 Hz, 7.5 Hz, 1H);
13C NMR (100 MHz, acetone-d6): d 167.1, 166.9, 158.6, 144.9,
137.0, 134.4, 133.4, 130.7, 129.3, 128.9, 121.4, 120.6, 118.3, 115.0;
MS (APCI): m/z ˆ 268 ([M ‡ H], 100%).
General Procedure for the Synthesis of a,b-
Unsaturated Imide Substrates
N-(3-Pyridin-2-ylacryloyl)-benzamide (11): The product
was obtained as a white solid in 92% yield, using 1.05 mmol
aldehyde and Procedure B: mp 169.5 170 8C; Rf ˆ 0.61
(EtOAc); IR (film): n ˆ 3280, 1725, 1674, 1632, 1479, 1152,
A 10-mL round-bottom flask equipped with a magnetic stirbar
was charged with phosphonate imide 4 (299 mg, 1.00 mmol).
Adv. Synth. Catal. 2002, 344, 953 956
955

Steven N. Goodman, Eric N. Jacobsen
UPDATES
À
1
1
707 cm ; H NMR (400 MHz, acetone-d6): d ˆ 10.17 (s, 1H),
8.66 (d, J ˆ 4.0 Hz, 1H), 8.06 (d, J ˆ 7.2 Hz, 2H), 8.01 (d, J ˆ
15.2 Hz, 1H), 7.87 (dt, J ˆ 1.6 Hz, 7.6 Hz, 1H), 7.82 (d, J ˆ
15.2 Hz, 1H), 7.66 (m, 2H), 7.53 (m, 2H), 7.39 (dd, J ˆ 5.2 Hz,
7.6 Hz, 1H); 13C NMR (100 MHz, acetone-d6): d ˆ 166.5, 166.3,
153.4, 150.4, 143.2, 137.2, 133.9, 133.0, 128.8, 128.5, 124.9, 124.8,
124.7; MS (APCI): m/z ˆ 253 ([M ‡ H], 100%).
Procedure A:
mp
182.5 183.5 8C;
Rf ˆ 0.38
(1:1
EtOAc:hexanes); IR (KBr): n ˆ 3281, 1671, 1612, 1357, 1245,
À
696 cm ; 1H NMR (500 MHz, CDCl3): d ˆ 8.60 (s, 1H), 8.02 (d,
1
J ˆ 8.0 Hz, 2H), 7.92 (s, 2H), 7.92 (d, J ˆ 8.0 Hz, 2H), 7.76 (d,
J ˆ 8.0 Hz, 2H), 7.67 (dt, J ˆ 1.5 Hz, 7.8 Hz, 1H), 7.57 (t, J ˆ
7.5 Hz, 2H), 2.66 (s, 3H); 13C NMR (100 MHz, CDCl3): d ˆ
197.4, 167.2, 165.9, 144.9, 138.9, 138.3, 133.5, 132.8, 129.2, 128.9,
128.7, 127.7, 121.8, 26.8; MS (APCI): m/z ˆ 294 ([M ‡ H],
80%).
N-(3-Pyridin-3-ylacryloyl)-benzamide (12): The product
was obtained as a white solid in 96% yield, using Proce-
dure B: mp 151.5 152.5 8C; Rf ˆ 0.40 (EtOAc); IR (film): n ˆ
À
1
3232, 3090, 2919, 1704, 1675, 1625, 1328, 1252, 706 cm ;
1H NMR (500 MHz, CDCl3): d ˆ 8.82 (d, J ˆ 2.0 Hz, 1H), 8.63
(dd, J ˆ 1.0 Hz, 4.5 Hz, 1H), 8.55 (s, 1H), 8.00 (dt, J ˆ 1.5 Hz,
7.5 Hz, 1H), 7.92 (t, J ˆ 2.5 Hz, 2H), 7.89 (dd, J ˆ 1.5 Hz,
7.5 Hz, 2H), 7.65 (t, J ˆ 7.0 Hz, 1H), 7.54 (t, J ˆ 8.0 Hz, 2H),
7.37 (dd, J ˆ 4.5 Hz, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d ˆ 151.4, 150.5, 142.8, 142.6, 134.6, 133.5, 132.8, 130.4, 129.2,
Acknowledgements
This work was supported by the NIH under GM-59316.
References and Notes
À
127.9, 127.7, 123.8, 121.5; MS (APCI): m/z ˆ 251 ([M H],
100%).
[1] J. K. Myers, E. N. Jacobsen, J. Am. Chem. Soc. 1999, 121,
8959.
[2] Q. Chen, G. M. Sammis, M. S. Taylor, E. N. Jacobsen,
manuscripts in preparation.
[3] An alternative synthesis of b-aryl-a,b-unsaturated imides
has been reported, involving reaction of a,b-unsaturated
acid chlorides and the sodium salt of benzamide. This
procedure is convenient for readily available acid
chlorides, see: Y. S. Laxmi, D. S. Iyengar, J. Chem. Soc.
Perkin Trans. 1 1995, 3043.
[4] J. B. Polya, T. M. Spotsword, Recl. Trav. Chim. Pays-Bas
1947, 67, 927.
[5] Heating to higher temperatures leads to unwanted
oxazoline formation, see: R. M. Rodehorst, T. H. Koch,
J. Am. Chem. Soc. 1975, 97, 7298.
[6] a) A. K. Bhattacharya, G. Thyagarajan, Chem. Rev. 1981,
81, 415; b) B. A. Arbuzov, Pure App. Chem. 1964, 9, 307.
[7] Na2CO3, K2CO3, Et3N, and DABCO were not as
effective as DBU. Ba(OH)2 afforded high reactivity,
but the E/Z selectivity was much lower than that
obtained with DBU. For an early example of the use of
DBUin highly E-selective HWE reactions, see: U.
Schmidt, H. Griesser, V. Leitenberger, A. Lieberknecht,
R. Mangold, R. Meyer, B. Riedl, Synthesis 1992, 487.
[8] F. G. Bordwell, Acc. Chem. Res. 1988, 21, 456.
[9] Benzyloxyacetaldehyde (entry 2) showed a 95:5 E:Z
selectivity.
[10] Thus far, the only substrates we have identified to be
incompatible with this protocol are tautomerizable
electron-rich aromatic aldehydes (e.g., 4-hydroxybenzal-
dehyde or pyrrole-2-carboxaldehyde) or aliphatic alde-
hydes susceptible to b-elimination under basic conditions
(e.g., 3-silyloxypropionaldehyde).
N-[3-(3-Nitrophenyl)-acryloyl]-benzamide (13): The prod-
uct was obtained as white needles in 90% yield, using
Procedure A:
mp
228.5 229 8C;
Rf ˆ 0.45
(1:1
EtOAc:hexanes); IR (KBr): n ˆ 3238, 3094, 1677, 1616, 1529,
À
1
1357, 1251, 697 cm ; 1H NMR (600 MHz, DMSO-d6): d ˆ
11.19 (s, 1H), 8.50 (s, 1H), 8.26 (d, J ˆ 9.6 Hz, 1H), 8.11 (d,
J ˆ 9.6 Hz, 1H), 7.95 (d, J ˆ 9.6 Hz, 2H), 7.81 (d, J ˆ 19.2 Hz,
1H), 7.75 (t, J ˆ 10.2 Hz, 1H), 7.65 (t, J ˆ 9.0 Hz, 1H), 7.54 (t,
J ˆ 9.0 Hz, 2H), 7.46 (d, J ˆ 19.8 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6): d ˆ 166.6, 165.4, 148.3, 140.5, 136.3, 134.4, 133.2,
132.9, 130.6, 128.5, 128.4, 124.5, 124.3, 122.1; MS (APCI):
m/z ˆ 297 ([M ‡ H], 100%).
N-[3-(4-Nitrophenyl)-acryloyl]-benzamide (14): The prod-
uct was obtained as a pale yellow solid in 91% yield, according
to
Procedure A:
mp
220 221 8C;
Rf ˆ 0.46
(1:1
EtOAc:hexanes); IR (KBr): n ˆ 3241, 3109, 1715, 1677, 1621,
À
1
1
1518, 1342, 1246, 697 cm ; H NMR (500 MHz, DMSO-d6):
d ˆ 11.26 (s, 1H), 8.29 (d, J ˆ 8.5 Hz, 2H), 7.94 (t, J ˆ 8.0 Hz,
4H), 7.78 (d, J ˆ 16.0 Hz, 1H), 7.65 (t, J ˆ 7.5 Hz, 1H), 7.54 (t,
J ˆ 7.5 Hz, 2H), 7.47 (d, J ˆ 15.5 Hz, 1H); 13C NMR (100 MHz,
DMSO-d6): d ˆ 166.7, 165.6, 148.0, 141.0, 140.4, 133.2, 132.9,
129.2, 128.6, 128.5, 125.6, 124.2; MS (APCI): m/z ˆ 295
À
([M H], 100%).
4-(3-Benzoylamino-3-oxopropenyl)-benzoic acid methyl
ester (15): The product was obtained as a white solid in 94%
yield, using Procedure A: mp 201 201.5 8C; Rf ˆ 0.42 (1:1
EtOAc:hexanes); IR (KBr): n ˆ 3277, 1711, 1670, 1611, 1344,
À
1
1
1283, 701 cm ; H NMR (400 MHz, DMSO-d6): d ˆ 11.22 (s,
1H), 8.01 (d, J ˆ 8.4 Hz, 2H), 7.93 (dd, J ˆ 1.2 Hz, 8.0 Hz, 2H),
7.79 (d, J ˆ 8.4 Hz, 2H), 7.73 (d, J ˆ 15.6 Hz, 1H), 7.64 (dt, J ˆ
1.2 Hz, 7.2 Hz, 1H), 7.53 (t, J ˆ 8.0 Hz, 2H), 7.42 (d, J ˆ
15.6 Hz, 1H), 3.85 (s, 3H); 13C NMR (100 MHz, DMSO-d6):
d ˆ 166.7, 165.7, 165.6, 141.6, 139.0, 133.3, 132.9, 130.7, 129.8,
‡
128.5, 128.4, 128.3, 124.0, 52.3; MS (EI): m/z ˆ 309 ([M] ,
100%).
N-[3-(4-Acetylphenyl)-acryloyl]-benzamide (16): The
product was obtained as a white solid in 92% yield, using
956
Adv. Synth. Catal. 2002, 344, 953 956