BF3 · Et2O-induced decomposition of ethyl 2-diazo-3-hydroxy-3,3-diarylpropanoates in acetonitrile: A novel approach to 2,3-diaryl β-enamino ester derivatives

Article abstract of DOI:10.1021/jo802775q

The BF₃·Et₂O-induced decomposition of ethyl 2-diazo-3-hydroxy-3,3-diarylpropanoates, prepared by the addition of a series of benzophenones to ethyl diazo(lithio)acetate, is reported and studied. By using acetonitrile as a solvent, the corresponding N-acyl β-enamino ester derivatives are obtained in good yields and with a diverse regioselectivity as the result of 1,2-aryl migration in the vinyl cation intermediates. The factors that govern the migratory aptitude as well as the mechanistic aspects of the reaction are discussed.

Full text of DOI:10.1021/jo802775q

SCHEME 1. Synthesis of r-Diazo-ꢀ-hydroxy Esters
BF3 ·Et2O-Induced Decomposition of Ethyl
2-Diazo-3-hydroxy-3,3-diarylpropanoates in
Acetonitrile: A Novel Approach to 2,3-Diaryl
ꢀ-Enamino Ester Derivatives
Antimo Gioiello, Francesco Venturoni, Benedetto Natalini,
and Roberto Pellicciari*
SCHEME 2. BF3 ·Et2O-Induced Decomposition of Cyclic
and Acyclic r-Diazo-ꢀ-hydroxy Esters
Dipartimento di Chimica e Tecnologia del Farmaco,
UniVersita` degli Studi di Perugia, Via del Liceo 1,
06123 Perugia, Italy
rp@unipg.it
ReceiVed December 26, 2008
trifluoride etherate (BF3 ·Et2O), they are transiently transformed
by nitrogen loss into the corresponding vinyl cation intermediate
which exhibits different transformation profiles according,
mainly, to the solvent employed. Thus, exposure of 3, prepared
by reaction of cyclohexanone with ethyl diazo(lithio)acetate
(LiEDA), to BF3 ·Et2O (1.5 equiv) in pentane afforded lactone
4 in 75% yield, while ethyl 2-(acetamidomethyl)-1-cyclohex-
enecarboxylate (5) was the major product (38%), besides minor
amounts of 4 (23%) when the same reaction was carried out in
acetonitrile (Scheme 2a).1d Interestingly, the BF3 ·Et2O-catalyzed
decomposition in acetonitrile of ethyl 2-diazo-2-(1-hydroxycy-
clopentyl)acetate (6) gave a different transformation profile. In
this case, indeed, R- and ꢀ-enamino ester derivatives 7 and 8
were found to be the only reaction products, in 55% and 6%
yield, respectively (Scheme 2b).1d As a last example, when the
acyclic ꢀ-diazo ester 9 was exposed to BF3 ·Et2O in acetonitrile,
the enamine 10 was obtained as the major product (53%), while
indenes 11 and 12 were isolated in minor amounts (Scheme
2c).1d
The BF3 · Et2O-induced decomposition of ethyl 2-diazo-3-
hydroxy-3,3-diarylpropanoates, prepared by the addition of
a series of benzophenones to ethyl diazo(lithio)acetate, is
reported and studied. By using acetonitrile as a solvent, the
corresponding N-acyl ꢀ-enamino ester derivatives are ob-
tained in good yields and with a diverse regioselectivity as
the result of 1,2-aryl migration in the vinyl cation intermedi-
ates. The factors that govern the migratory aptitude as well
as the mechanistic aspects of the reaction are discussed.
R-Diazo-ꢀ-hydroxy esters of type 1a and 1b (Scheme 1)
easily prepared by aldol-type condensation of ethyl diazoacetate
(EDA, 2) with an aldehyde or a ketone,1 respectively, are
versatile compounds endowed with a wealth of potential
synthetic applications.2
It has previously been reported,1c,d,3 in particular, that when
derivatives 1b obtained from ketonic substrates, and therefore
missing of the hydrogen atom R to the diazo moiety, are
decomposed in the presence of stoichiometric amounts of boron
The “R-diazoesters/BF3 ·Et2O/acetonitrile route” to ꢀ-enamino
ester derivatives, illustrated by the previous examples, is of great
synthetic value because of the possibility to give access to
biological active compounds4 such as R-5 and ꢀ-amino acids,6
alkaloids,7 and peptides.8 Although several approaches for the
(1) (a) Schollkopf, U.; Frasnelli, H.; Hoppe, D. Angew. Chem., Int. Ed. Engl.
1970, 9, 300–301. (b) Wenkert, E.; McPherson, A. A. J. Am. Chem. Soc. 1972,
94, 8084–8190. (c) Pellicciari, R.; Natalini, B.; Cecchetti, S.; Fringuelli, R.
J. Chem. Soc., Perkin Trans. 1 1985, 3, 493–497. (d) Pellicciari, R.; Natalini,
B.; Sadeghpour, B. M.; Marinozzi, M.; Snyder, J. P.; Williamson, B. L.; Kuethe,
J. T.; Padwa, A. J. Am. Chem. Soc. 1996, 118, 1–12. (e) Moody, C. J. Synthesis
1998, 1039–1042. (f) Jiang, N.; Qu, Z.; Wang, J. Org. Lett. 2001, 3, 2989–
2992. (g) Jiang, N.; Wang, J. Tetrahedron Lett. 2002, 43, 1285–1287. (h)
Sreedhar, B.; Balasubrahmanyam, V.; Sridhar, C.; Nagendra Prasad, M. Catal.
Commun. 2005, 6, 517–519. (i) Kantam, M. L.; Chakrapani, L.; Ramani, T.
Tetrahedron Lett. 2007, 48, 6121–6123.
(2) For reviews see: (a) Zhang, Z.; Wang, J. Tetrahedron 2008, 64, 6577–
6605. (b) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds; Wiley-Interscience: New York,
1998. (c) Ye, T.; McKervey, M. A. Chem. ReV. 1994, 94, 1091–1160.
(3) Pellicciari, R.; Natalini, B.; Sadeghpour, B. M.; Rosato, G. C.; Ursini,
A. J. Chem. Soc., Chem. Commun. 1993, 1798–1800.
(4) (a) Torii, S.; Okumoto, H.; Xu, L. H. Tetrahedron Lett. 1990, 31, 7175–
7178. (b) Hong, C. Y.; Kishi, Y. J. Am. Chem. Soc. 1992, 114, 7001–7006. (c)
Baindur, N.; Rutledge, A.; Triggle, D. J. J. Med. Chem. 1993, 36, 3743–3745.
(d) Poindexter, G. S.; Licause, J. F.; Dolan, P. L.; Foey, M. A.; Combs, C. M.
J. Org. Chem. 1993, 58, 3811–3820.
(5) Felice, E.; Fioraventi, S.; Pellacani, L.; Tardella, P. A. Tetrahedron Lett.
1999, 40, 4413–4416, and the references cited herein.
(6) For recent reviews see: (a) Bruneau, C.; Renaud, J.-L.; Jerphagnon, T.
Coord. Chem. ReV. 2008, 252, 532–544. (b) Juaristi, E. EnantioselectiVe Synthesis
of ꢀ-Amino Acids; Wiley-VCH: New York, 1997. (c) Jerphagnon, T.; Renaud,
J.-L.; Bruneau, C. Tetrahedron: Asymmetry 2004, 15, 2101–2111. (d) Liu, M.;
Mukund, S. Tetrahedron 2002, 58, 7991–8035.
3520 J. Org. Chem. 2009, 74, 3520–3523
10.1021/jo802775q CCC: $40.75 2009 American Chemical Society
Published on Web 04/02/2009

TABLE 1. Synthesis of Ethyl 2-Diazo-3-hydroxy-3-aryl-3-
phenylpropanoates 14a-f
SCHEME 3. Mechanism of the Formation of 3,3-Diaryl
r-Enamino and 2,3-Diaryl ꢀ-Enamino Esters from
Benzophenones
educt
Ar
C6H5-
p-NO2C6H4-
p-OMeC6H4-
p-ClC6H4-
p-MeC6H4-
p-FC6H4-
products
isolated yielda
a
b
c
d
e
f
14a10
14b
14c
14d
14e
82%
60%
64%
98%
73%
37%
14f
a Calculated after purification by flash chromatography on silica gel.
TABLE 2. BF3 ·Et2O-Induced Decomposition of Ethyl
2-Diazo-3-hydroxy-3-aryl-3-phenylpropanoates 14a-f
products ratioa
1,2-Ph shift
1,2-Ar shift
educt
isolated yield
E-19:Z-19
E-20:Z-20
13a
13b
13c
13d
13e
13f
90%
87%
90%
92%
97%
88%
51:49
36:21
6b:18
7:35
0:43
18b:58
11:47
synthesis of these derivatives have been reported,9 most of them
suffer from limitations, and new, facile, and efficient methods
for their preparation are therefore still required.
19b:27b
19:21
19b:35b
36:24
a Calculated after purification by flash chromatography on silica gel.
With this aim in mind and as a further extension of our study
in the field, we have prepared a series of ethyl 2-diazo-3-
hydroxy-3-aryl-3-phenylpropanoates (14a10-f), starting from the
corresponding 4-substituted benzophenones (13a-f), and ex-
plored their BF3 ·Et2O-induced decomposition (Scheme 3). By
using acetonitrile as a solvent, the corresponding ꢀ-enamino
ester derivatives are the only products formed during the reaction
as the result of 1,2-aryl or 1,2-phenyl migration in the corre-
sponding vinyl cations 16a-f. The factors that affect the vinyl
rearrangement as well as the mechanistic aspects of the reaction
are herein reported and discussed.
b Obtained as an inseparable isomeric E- or Z-mixture (the relative ratios
1
were calculated by H NMR).
1
FIGURE 1. Diagnostic H NMR NOE for 19a-f and 20a-f.
Ethyl 2-diazo-3-hydroxy-3-aryl-3-phenylpropanoates 14a-f
were prepared by adding the corresponding benzophenones
13a-f to a THF solution of LiEDA salt at -78 °C (Table 1).
After the addition completion, the reaction mixture was
quenched at the same temperature with a THF solution of acetic
acid followed by workup to furnish the desired compounds
14a-e in good yields, except for the 14f obtained in 37% yield
(Table 1, educt f).
SCHEME 4. Ozonolysis of the Products Resulting from
14a-f BF3 ·Et2O-Induced Decomposition Reaction
(7) (a) Paulvannan, K.; Schwarz, J. B.; Stille, J. R. Tetrahedron Lett. 1993,
34, 215–218. (b) Paulvannan, K.; Stille, J. R. J. Org. Chem. 1994, 59, 1613–
1620. (c) Barta, N. S.; Brode, A.; Stille, J. R. J. Am. Chem. Soc. 1994, 116,
6201–6206. (d) Cook, G. R.; Beholz, L. G.; Stille, J. R. J. Org. Chem. 1994, 59,
3575–3584. (e) Blot, J.; Baidou, A.; Bellec, C.; Fargeau-Bellasoued, M.-C.;
Celerier, J.-P.; Lhommet, G.; Gardette, D.; Gramain, J.-C. Tetrahedron Lett.
1997, 38, 8511–8514. (f) David, C.; Blot, J.; Bellec, C.; Fargeau-Bellasoued,
M.-C.; Haviari, G.; Celerier, J.-P.; Lhommet, G.; Gramain, J.-C.; Gardette, D.
J. Org. Chem. 1999, 64, 3122–3131.
(8) For reviews see: (a) Wu, Y.-D.; Han, W.; Wang, D.-P.; Gao, Y.; Zhao,
Y.-L.; Beholz, L. G. Acc. Chem. Res. 2008, 41, 1418–1427. (b) Seebach, D.;
Beck, A. K.; Bierdaum, D. J. Chem. BiodiVersity 2004, 1, 1111–1239. (c)
Seebach, D.; Abele, S.; Gademann, K.; Guichard, G.; Hintermann, T.; Jaun, B.;
Matthews, J. L.; Schreiber, J. V.; Oberer, L.; Hommer, U.; Widmer, H. HelV.
Chim. Acta 1998, 81, 932–982. (d) Seebach, D.; Overhand, M.; Ku¨hnle, N. M.;
Martinoni, B. HelV. Chim. Acta 1996, 79, 913–941.
The R-diazo-ꢀ-hydroxy esters 14a-f thus obtained were
dissolved in acetonitrile, and the resulting mixture was added
dropwise at room temperature to a solution of freshly distilled
BF3 ·Et2O (1.5 equiv), affording the corresponding enamino
esters arising from 1,2-phenyl- (19a-f) and 1,2-aryl-shifts
(20a-f), respectively, in high yields (87-97%, Table 2).
The reaction products were identified by NMR and NOESY
spectroscopy analysis: diagnostic 1H NMR NOE enhancements
were observed, indeed, between (i) HA-HC and HB-HD in
Z-19a-f and Z-20a-f, (ii) HA′-HD and HA′-HC in Z-19a-f,
and (iii) HA′ -HA and HA′′ -HB in Z-20a-f (Figure 1).
To further confirm their structures, compounds 19a-f and
20a-f were submitted to ozonolysis affording the corresponding
R-ketoesters 22 and 25a-f as the sole products of reaction
(Scheme 4), thus ruling out that the decomposition of ethyl
2-diazo-3-hydroxy-3-aryl-3-phenylpropanoates 14a-f gives ex-
clusively ꢀ-enamino acid derivatives.
(9) (a) Palmieri, G.; Cimarelli, C. ARKIVOC (GainesVille, FL, U.S.) 2006,
Vi, 104–126, and the references cited herein. (b) Mangelinckx, S.; Van Vooren,
P.; De Clerck, D.; Fu¨lo¨p, F.; De Kimpe, N. ARKIVOC (GainesVille, FL, U.S.)
2006, iii, 202–209. (c) Lenin, L.; Raju, R. M. ARKIVOC (GainesVille, FL, U.S.)
2006, xiii, 204–209. (d) Ramtohul, Y. K.; Chartrand, A. Org. Lett. 2007, 9, 1029–
1032. (e) Hebbache, H.; Hank, Z.; Boutamine, S.; Meklati, M.; Bruneau, C.;
Renaud, J.-L. C. R. Chim. 2008, 11, 612–619.
(10) Nagao, K.; Chiba, M.; Kim, S. W. Synthesis 1983, 197, 199.
J. Org. Chem. Vol. 74, No. 9, 2009 3521

In conclusion, we reported the BF3 ·Et2O-induced decomposi-
tion reaction of a series of R-diazo-ꢀ-hydroxy esters prepared
from the corresponding benzophenones. The reaction proceeds
via 1,2-aryl or 1,2-phenyl migration of the R-aryl-R-phenylvinyl
cation, a process which resulted in strong dependence on the
electronic properties of the aryl substituents. We believe that
this methodology may provide facile access to a variety of aryl
substituted N-acyl ꢀ-enamino esters, useful building blocks for
the synthesis of chiral ꢀ-amino acids as well as other biologically
important compounds.
FIGURE 2. Plot of parametrized resonance effect (Reff) versus log 20/
19.
Experimental Section
General Procedure for the Synthesis of Ethyl 2-Diazo-3-
hydroxy-3-aryl-3-phenylpropanoates 14a-f. To a stirring solution
of LDA [prepared from addition of n-BuLi (1.6 mmol) to a -78
°C solution of diisopropylamine (2 mmol) in THF (2.5 mL)] was
added a cooled solution of EDA (2; 1.5 mmol) in dry THF (2.5
mL) at -78 °C in 15 min. After 10 min from the end of the addition,
a THF (5 mL) solution of benzophenone (13a-f; 1 mmol) in THF
(5 mL) was then added in 10 min at -78 °C. After 15 min a cooled
(-78 °C) solution of AcOH (0.15 mL) in THF (10 mL) was added
in 5 min. The reaction mixture was taken into H2O and extracted
with EtOAc (3 × 25 mL). The combined organic fractions were
dried over with Na2SO4 and evaporated in vacuum. The crude
residue was purified with flash chromatography eluting with a
solution of Hex/EtOAc (9:1, v:v).
SCHEME 5. Isomerization of E-20b into Z-20b
A deeper inspection of the results reported in Table 2 revealed
that 1,2-phenyl and 1,2-aryl migration, which dominated over
the solvent trapping, was influenced by the electronic effect
imposed by the ring substituents. In particular, it is interesting
to note that the presence of a p-NO2 substituent (Table 2, educt
13b) reduces the migratory aptitude of the aryl group, while a
1,2-aryl shift is favored with p-OMe, p-Cl, p-Me, and p-F
substitution (Table 2, educt 13c-f). To substantiate this
electronic effect, the relative migratory aptitude of the aryl
groups, indicated as the logarithm of the 20/19 ratio, was
analyzed with their respective parametrized resonance effects
(Reff), inductive effects (F), and Hammett σ values.11 As shown
in Figure 2, the data fit well to Reff (r2 ) 0.91), indicating that
an aryl with electron-donating group (for mesomeric effect) is
endowed with a higher tendency to migrate at the more
electrophilic carbon, in agreement with the R-vinyl cation
formation.12 On the contrary, no correlation was observed either
with the inductive effects (F) or with the Hammett σ values
(data not shown), thus ruling out that the resonance is the only
electronic parameter which influences the aryl migration process.
Ethyl 2-Diazo-3-hydroxy-3,3-diphenylpropanoate (14a)10: yel-
low solid; 82% yield. 1H NMR (200 MHz, CDCl3) δ: 1.27 (t, 3H,
J ) 7.2 Hz), 4.25 (q, 2H, J ) 7.2 Hz), 4.98 (br, 1H), 7.31-7.43
(m, 10H). 13C NMR (50 MHz, CDCl3) δ: 14.3, 61.3, 78.9, 126.8,
128.1, 143.3, 167.3.
Ethyl 2-Diazo-3-hydroxy-3-(4-chlorophenyl)-3-phenylpropanoate
1
(14d): yellow solid; 98% yield. H NMR (200 MHz, CDCl3) δ:
1.29 (t, 3H, J ) 7.2 Hz), 4.27 (q, 2H, J ) 7.2 Hz), 5.00 (br, 1H),
7.27-7.44 (m, 9H). 13C NMR (50 MHz, CDCl3) δ: 14.3, 61.4, 78.5,
126.7, 128.3, 128.4, 128.5, 134.1, 142.2, 142.8, 167.2.
General Procedure for Decomposition of Ethyl 2-Diazo-3-
hydroxy-3-aryl-3-phenylpropanoates 14a-f. To a magnetically
stirred solution of freshly distilled BF3 ·Et2O (1.66 mmol) in dry
acetonitrile (5 mL) was added a solution of R-diazo-ꢀ-hydroxy ester
14a-f (1.11 mmol) in dry acetonitrile (30 mL) with a syringe pump
(0.02 mmol/min) at room temperature. After the end of the addition,
the reaction mixture was stirred for additional 30 min at room
temperature and then poured into a saturated solution of NaHCO3
(75 mL), extracted with EtOAc (3 × 25 mL), dried over Na2SO4,
filtered, and concentrated in vacuum. The crude residue was purified
by flash chromatography eluting with a solution of petroleum ether/
EtOAc (6:4, v:v).
The decomposition of the ethyl 2-diazo-3-hydroxy-3-phenyl-
3-(4-nitro-phenyl)propanoate (14b) deserves an additional com-
1
ment. Indeed, while the TLC and the H NMR of the crude
reaction mixture showed the formation of four distinct products
(two low polar and two more polar), unexpectedly, only
derivatives Z-19b, Z-20b, and E-19b were recovered after
purification. We supposed that 3-acetylamino-2-(4′-nitro-phen-
yl)-3-phenyl-acrylic acid ethyl ester (E-20b) underwent an acidic
trans-cis isomerization, maybe induced by silica gel, as the
result of a low inversion energy barrier and a strong push-pull
system made more effective by the presence of an electron-
withdrawing group (-NO2) at the R-carbonyl position (Scheme
5).13 A further energy contribution to the trans-cis inversion
derives from the presence in the Z-form of a stabilizing
intramolecular hydrogen bond between the carbonyl and the
enamine group, absent in the corresponding E-isomers.
Ethyl (2Z)-3-(Acetylamino)-2,3-diphenylacrylate (Z-19a): yellow-
brown oil; 44% yield. UV (H2O, CH3CN): 230.38, 301.48. 1H NMR
(400 MHz, CDCl3) δ: 1.21 (t, 3H, J ) 7.1 Hz), 2.13 (s, 3H), 4.20
(q, 2H, J ) 7.1 Hz), 6.94-6.95 (m, 2H), 7.01-7.06 (m, 2H),
7.06-7.13 (m, 6H), 11.34 (s, 1H). 13C NMR (100 MHz, CDCl3)
δ: 14.1, 25.0, 60.9, 113.2, 126.3, 127.2, 127., 127.9, 128.7, 131.8,
135.2, 135.2, 151.5, 168.3, 169.3. Anal. Calcd for C19H19NO3: C,
73.77; H, 6.19; N, 4.53. Found: C, 73.64; H, 6.56; N, 4.32.
Ethyl (2E)-3-(Acetylamino)-2,3-diphenylacrylate (E-19a): white
solid (mp: 156-157 °C); 46% yield. UV (H2O, CH3CN): 225.79,
1
292.26. H NMR (400 MHz, CDCl3) δ: 0.91 (t, 3H, J ) 7.1 Hz),
1.81 (s, 3H), 3.95 (q, 2H, J ) 7.1 Hz), 6.81 (s, 1H), 7.33-7.44
(m, 10H). 13C NMR (100 MHz, CDCl3) δ: 13.6, 23.6, 61.0, 123.4,
128.1, 128.3, 128.4, 129.1, 129.1, 135.3, 136.6, 140.8, 168.7. Anal.
Calcd for C19H19NO3: C, 73.77; H, 6.19; N, 4.53. Found: C, 73.54;
H, 6.48; N, 4.51.
(11) Hansch, C.; Leo, A.; Taft, R. W. Chem. ReV. 1991, 91, 165–195.
(12) (a) Jiang, N.; Ma, Z.; Qu, Z.; Xing, X.; Xie, L.; Wang, J. J. Org. Chem.
2003, 68, 893–900. (b) van Dorp, J. W.; Lodder, G. J. Org. Chem. 2008, 73,
5416–5428.
Ethyl (2Z)-3-(Acetylamino)-3-(4-chlorophenyl)-2-phenylacrylate
(Z-19d): yellow oil; 32% yield. UV (H2O, CH3CN): 234.02, 303.65.
1H NMR (400 MHz, CDCl3) δ: 1.20 (t, 3H, J ) 7.1 Hz), 2.14 (s,
(13) Sandstrom, J. Top. Stereochem. 1983, 14, 83–181.
3522 J. Org. Chem. Vol. 74, No. 9, 2009

3H), 3.69 (s, 3H), 4.19 (q, 2H, J ) 7.1 Hz), 6.92-6.94 (m, 4H),
7.05 (psd, 2H, J ) 8.6 Hz), 7.09-7.10 (m, 3H), 11.34 (s, 1H). 13
NMR (100 MHz, CDCl3) δ: 14.1, 25.0, 61.1, 113.7, 126.6, 127.4,
127.7, 130.0, 131.7, 133.7, 133.8, 134.7, 150.3, 168.4, 169.2. Anal.
Calcd for C19H18ClNO3: C, 66.38; H, 5.28; N, 4.07. Found: C,
66.74; H, 5.58; N, 3.89.
61.0, 111.8, 127.5, 127.6, 128.1, 128.6, 132.3, 133.1, 133.7, 134.9,
152.1, 168.3, 169.0. Anal. Calcd for C19H18ClNO3: C, 66.38; H,
5.28; N, 4.07. Found: C, 66.51; H, 5.78; N, 3.83.
C
Ethyl (2E)-3-(Acetylamino)-2-(4-chlorophenyl)-3-phenylacrylate
(E-20d): white solid (mp:153-155 °C); 10% yield. UV (H2O,
1
CH3CN): 227.88, 296.56. H NMR (400 MHz, CDCl3) δ: 0.90 (t,
Ethyl (2E)-3-(Acetylamino)-3-(4-chlorophenyl)-2-phenylacrylate
3H, J ) 7.1 Hz), 1.83 (s, 3H), 3.95 (q, 2H, J ) 7.1 Hz), 6.79 (br,
1H), 7.27 (psd, 2H, J ) 8.6 Hz), 7.37-7.43 (m, 7H). 13C NMR
(100 MHz, CDCl3) δ: 13.5, 23.6, 61.1, 123.0, 128.1, 128.3, 129.3,
130.6, 134.0, 134.3, 136.5, 141.4, 168.4, 168.4. Anal. Calcd for
C19H18ClNO3: C, 66.38; H, 5.28; N, 4.07. Found: C, 66.23; H, 5.31;
N, 4.02.
(E-19d): white solid (mp: 157-158 °C); 6.5% yield. UV (H2O,
1
CH3CN): 228.26, 295.23. H NMR (400 MHz, CDCl3) δ: 0.97 (t,
3H, J ) 7.1 Hz), 1.84 (s, 3H), 3.98 (q, 2H, J ) 7.1 Hz), 6.82 (br,
1H), 7.32-7.38 (m, 6H), 7.41-7.45 (m, 2H). 13C NMR (100 MHz,
CDCl3) δ: 13.7, 23.6, 61.1, 124.1, 128.5, 128.6, 129.1, 129.2, 129.3,
130.6, 135.0, 139.9, 168.3, 168.3. Anal. Calcd for C19H18ClNO3:
C, 66.38; H, 5.28; N, 4.07. Found: C, 66.49; H, 5.18; N, 3.95.
Ethyl (2Z)-3-(Acetylamino)-2-(4-chlorophenyl)-3-phenylacrylate
(Z-20d): yellow oil; 43% yield. UV (H2O, CH3CN): 233.43, 303.62.
1H NMR (400 MHz, CDCl3) δ: 1.20 (t, 3H, J ) 7.1 Hz), 2.12 (s,
3H), 4.19 (q, 2H, J ) 7.1 Hz), 6.87 (psd, 2H, J ) 8.6 Hz),
6.98-7.00 (m, 2H), 7.04 (psd, 2H, J ) 8.6 Hz), 7.10-7.14 (m,
3H), 11.36 (br, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.1, 25.0,
Supporting Information Available: Detailed description of
experimental procedures, a listing of all spectroscopic data,
elemental analysis, as well as copies of NMR spectra (1H and
13C NMR). This material is available free of charge via the
Internet at http://pubs.acs.org.
JO802775Q
J. Org. Chem. Vol. 74, No. 9, 2009 3523