Heck reactions of 2-substituted enol ethers with aryl bromides catalysed by a tetraphosphine/palladium complex

Article abstract of DOI:10.1016/j.tetlet.2005.11.071

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/ [PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of β-substituted enol ethers with aryl bromides. Employing β-methoxystyrene, 3-ethoxyacrylonitrile or methyl 3-methoxyacrylate, the regioselective α-arylation of these enol ethers was observed in all cases, and mixtures of Z and E isomers were generally obtained, which in many cases yielded a single ketone product after acid treatment. The stereoselectivity of this reaction depends on steric and electronic factors, and better stereoselectivities in favour of Z isomers were observed with electron-rich or sterically congested aryl bromides. Better yields were obtained for this reaction with electron-rich or sterically congested aryl bromides than with electron-poor aryl bromides. This observation suggests that with these β-substituted enol ethers the rate-limiting step of the catalytic cycle is not the oxidative addition of the aryl bromide to the palladium complex.

Full text of DOI:10.1016/j.tetlet.2005.11.071

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 459–462
Heck reactions of 2-substituted enol ethers with aryl bromides
catalysed by a tetraphosphine/palladium complex
Ahmed Battace,a Touriya Zair,b Henri Douceta,* and Maurice Santellia,*
a
`
´
Laboratoire de Synthese Organique, UMR 6180 CNRS, Universite d’Aix-Marseille III: Chirotechnologies: catalyse et biocatalyse,
ˆ
Faculte´ des Sciences de Saint Je´rome, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
bLaboratoire de Chimie Organique Applique´e, Faculte´ des Sciences, Universite´ Moulay Ismail, BP 4010,
Beni M’mhammed, 50000 Meknes, Morocco
Received 3 October 2005; revised 10 November 2005; accepted 15 November 2005
Available online 1 December 2005
Abstract—cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C3H5)]2 efficiently catalyses the Heck reaction
of b-substituted enol ethers with aryl bromides. Employing b-methoxystyrene, 3-ethoxyacrylonitrile or methyl 3-methoxyacrylate,
the regioselective a-arylation of these enol ethers was observed in all cases, and mixtures of Z and E isomers were generally obtained,
which in many cases yielded a single ketone product after acid treatment. The stereoselectivity of this reaction depends on steric and
electronic factors, and better stereoselectivities in favour of Z isomers were observed with electron-rich or sterically congested aryl
bromides. Better yields were obtained for this reaction with electron-rich or sterically congested aryl bromides than with electron-
poor aryl bromides. This observation suggests that with these b-substituted enol ethers the rate-limiting step of the catalytic cycle is
not the oxidative addition of the aryl bromide to the palladium complex.
Ó 2005 Elsevier Ltd. All rights reserved.
The palladium-catalysed Heck vinylation reaction is one
of the most powerful methods for the formation of C–C
bonds.1 The efficiency of several catalysts for the reac-
tion of aryl halides with acrylates or styrene derivatives
has been studied in detail. On the other hand, the reac-
tion involving 1,2-disubstituted alkenes has attracted
less attention. These alkenes are less reactive than termi-
nal alkenes. Most of the results described with 1,2-disub-
stituted alkenes were obtained with cinnamates,
crotonates or benzalacetone.2,3 A few results have been
described with 2-substituted enol ethers.4–6 For example,
the reaction of ethyl (E)-3-ethoxy acrylate and iodoben-
zene, 4-iodoanisole or 3-iodopyridine can be performed
with Pd–C (5%) as catalyst.4 The reaction involving
3,3,3-trifluoro-1-methoxypropene and iodobenzene,
4-iodonitrobenzene, 3-iodopyridine or iodo-4-bromo-
benzene with Pd(OAc)2 (3%)/PPh3 (6%) as catalyst and
Ag2CO3 as base (1 equiv) also proceeds.5 1-Butoxy-
prop-1-ene reacts with iodobenzene or 4-bromonitro-
benzene employing Pd(PPh3)4 (1%), but mixtures of
isomers and low yields were obtained.6 To our knowl-
edge, the Heck reaction involving b-methoxystyrene7
or 3-ethoxyacrylonitrile has not been described. More-
over, there still remains a need for a general protocol
for Heck reactions in the presence of 2-substituted enol
ethers especially with aryl bromides.
In order to obtain stable and efficient palladium catal-
ysts, we have prepared the new tetraphosphine ligand,
cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)-
cyclopentane or Tedicyp8 (Fig. 1). We have already
reported the results obtained in allylic substitution,8
for Suzuki cross-coupling9 and for Sonogashira alkynyl-
ation10 using Tedicyp as the ligand. We have also
reported several results for Heck vinylation.11–13 We
had observed that with our catalyst, good results could
be obtained for the reaction of n-butylvinyl ether or
ethyleneglycol vinyl ether with aryl bromides.12 Satisfac-
tory results in terms of substrate/catalyst ratio were also
been obtained for the reaction with disubstituted alkenes
Ph2P
PPh2
Ph2P
PPh2
*
Corresponding authors. Tel.: +33 4 91 28 84 16; fax: +33 4 91 98 38
65 (H.D.); tel.: +33 4 91 28 88 25 (M.S.); e-mail addresses:
henri.doucet@univ.u-3mrs.fr; m.santelli@univ.u-3mrs.fr
Tedicyp
Figure 1.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.071

460
A. Battace et al. / Tetrahedron Letters 47 (2006) 459–462
such as methyl crotonate, ethyl cinnamate or benz-
alacetone.13 In order to further establish the require-
ments for a successful Heck reaction with our catalytic
system, we herein report on the reaction of a variety
of aryl bromides with the 2-substituted enol ethers:
b-methoxystyrene, 3-ethoxyacrylonitrile or methyl
3-methoxyacrylate.
butylbromobenzene, 4-bromotoluene or 4-bromoanisole
(Table 1, entries 1–7). This observation indicates that
the rate-limiting step of the reaction with this enol ether
is not the oxidative addition of the aryl bromide to the
palladium complex, but probably the insertion of the
enol ether in the Ar–Pd bond. We also studied the influ-
ence of ortho-substituents on the aryl bromide for this
reaction and we observed that 1-bromonaphthalene,
2-methylbromobenzene or 2,4,6-trimethylbromobenz-
ene gave similar yields than 4-methylbromobenzene
(Table 1, entries 11–13). However, for steric reasons,
with 2,4,6-trimethylbromobenzene the Z isomer was
selectively obtained. The heteroaromatic substrates
3-bromoquinoline and b-methoxystyrene also led to
the expected adduct in good yield (Table 1, entry 14).
The mixtures of stereoisomers obtained with b-methoxy-
styrene were hydrolysed into the corresponding ketones
using a mixture of THF/H2O/HCl (or H2SO4). The
stereoselectivity of this reaction is irrelevant as the out-
come of these reaction is the ketone product.
The regioselectivity of the insertion of Heck reaction is
controlled both by the electronic properties of the alk-
enes and by steric factors. Electron-poor alk-1-enes such
as acrylates, acrylonitrile or styrene generally lead very
selectively to the b-arylated alkenes. On the other hand,
electron-rich alk-1-enes such as n-butylvinyl ether often
gave mixtures of a- and b-arylated alkenes.1 Electronic
effects do indeed play a major role in arylations of enol
ethers. With our Tedicyp/palladium catalyst, we had
observed with n-butylvinyl ether that, in all cases, mixtures
of linear and branched products were obtained.12a For
these reasons, the regioselectivity of reaction with the
unsymmetrical disubstituted alkenes: b-methoxystyrene,
3-ethoxyacrylonitrile or methyl 3-methoxyacrylate can
be predicted and should lead to regioselective insertions
to give the isomers a and b of Scheme 1.
Next, we studied the reactivity of 3-ethoxyacrylonitrile
(Table 1, entries 15–26). With this enol ether, very low
conversions were obtained with 4-bromoacetophenone
or 4-trifluoromethylbromobenzene. On the other
hand, with 4-fluorobromobenzene, 4-bromotoluene, 4-
t-butylbromobenzene or 6-methoxy-2-bromonaphthal-
ene complete conversions and good yields of arylated
ethoxyacrylonitrile were obtained (Table 1, entries
15–18). These para-substituted aryl bromides gave regio-
selectively 3-aryl-3-ethoxyacrylonitrile derivatives but
mixtures of Z (12–35%) and E (88–65%) isomers were
obtained.
For this study, based on previous results,12,13 DMF was
chosen as the solvent. The reactions were performed
under argon employing a 1:2 ratio of [Pd(C3H5)Cl]2/
Tedicyp as catalyst. We first studied the reactivity of
b-methoxystyrene with 4-t-butylbromobenzene using
a few bases at 100–150 °C. Low conversions were
observed in the presence of 1 mol % catalyst with K2CO3,
Na2CO3 or NaOAc as bases or at 100–130 °C. The best
yield was obtained with NaHCO3 at 150 °C. Next, we
examined the reaction of b-methoxystyrene with several
aryl bromides employing 1% catalyst (Scheme 1, Table
1, entries 1–14). As expected, with this alkene, we
observed a regioselective addition of the aryl bromides
to give the corresponding b-aryl-b-methoxystyrene
derivatives. The Tedicyp–Pd catalyst system is tolerant
of a variety of aryl bromides for the reaction with
b-methoxystyrene. Electron-poor aryl bromides such
as 4-bromoacetophenone or 4-bromobenzaldehyde led
to the coupling adducts in lower conversions and yields
than the reactions performed with electron-rich 4-t-
Employing the sterically congested aryl bromides:
2-bromotoluene, 1-bromonaphthalene, 2,4,6-trimethyl-
bromobenzene
or
2,4,6-triisopropylbromobenzene
larger amounts of Z isomers were formed (66–93%)
(Table 1, entries 21–24). On the other hand, with the
p-electron deficient heteroaromatic substrates, 3-bromo-
pyridine or 3-bromoquinoline, the E isomers were
obtained in 91% and 90% selectivities, respectively
(Table 1, entries 25 and 26). The separation of Z and
E 3-aryl-3-ethoxyacrylonitrile isomers was possible by
chromatography on silica gel.
R3
R2O
R2O
R2O
[Pd(C3H5)Cl]2 / 0.5 Tedicyp,
DMF, NaHCO3, 150 oC
R3
R1
R1
+
Br
R1
R3
R1 = H, Me, iPr, tBu,OMe, F, CF3, MeCO, CHO
R2 = Me and R3 = CO2Me
Z : 1a-27a
E : 1b-27b
R
2 = Et and R3 = CN
R2 = Me and R3 = Ph
HCl or H2SO4,
THF, H2O, 25 oC
R3
O
R1
1c-13c and 25c-27c
Scheme 1.

A. Battace et al. / Tetrahedron Letters 47 (2006) 459–462
461
Table 1. Heck reactions with 2-substituted enol ethers catalysed by the Tedicyp–palladium complex (Scheme 1)14,15
Entry
Aryl halide
Alkene
Ratio Z (a)/E(b)
Isolated product
Yieldc (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
4-Bromoacetophenone
4-Bromobenzaldehyde
4-Trifluoromethylbromobenzene
4-Fluorobromobenzene
4-Bromotoluene
4-t-Butylbromobenzene
4-Bromoanisole
6-Methoxy-2-bromonaphthalene
Iodobenzene
b-Methoxystyrenea
65/35
69/31
72/28
67/33
62/38
63/37
54/46
51/49
33/67
66/34
57/43
62/32
100/0
71/29
12/88
35/65
30/70
27/73
40/60
23/77
75/25
77/23
66/34
93/7
1c
2c
58
60
62
78
80
79
77d
82
79
74
84
79
74d
73
79
76
82
84
80
88
81
77
73d
76
78
80
62
60d
56
b-Methoxystyrenea
b-Methoxystyrenea
3c
4c
b-Methoxystyrenea
b-Methoxystyrenea
5c
6c
b-Methoxystyrenea
b-Methoxystyrenea
7c
8c
b-Methoxystyrenea
b-Methoxystyrenea
9c
9c
Bromobenzene
b-Methoxystyrenea
1-Bromonaphthalene
2-Methylbromobenzene
2,4,6-Trimethylbromobenzene
3-Bromoquinoline
4-Fluorobromobenzene
4-Bromotoluene
4-t-Butylbromobenzene
6-Methoxy-2-bromonaphthalene
Iodobenzene
Bromobenzene
1-Bromonaphthalene
2-Bromotoluene
2,4,6-Trimethylbromobenzene
2,4,6-Triisopropylbromobenzene
3-Bromopyridine
b-Methoxystyrenea
10c
11c
b-Methoxystyrenea
b-Methoxystyrenea
12c
13c
b-Methoxystyrenea
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
3-Ethoxyacrylonitrileb
Methyl (E)-3-methoxyacrylate
Methyl (E)-3-methoxyacrylate
Methyl (E)-3-methoxyacrylate
14a,b
15a,b
16a,b
17a,b
18a,b
18a,b
19a,b
20a,b
21a,b
22a,b
23a,b
24a,b
25c
9/91
3-Bromoquinoline
4-t-Butylbromobenzene
4-Bromoanisole
10/90
49/51e
NDe,f
NDe,f
26c
27c
2-Bromotoluene
Conditions: catalyst [Pd(C3H5)Cl]2/Tedicyp 1:2, see Ref. 7 (0.01 equiv), ArX (1 equiv), enol ether (2 equiv), NaHCO3 (2 equiv), DMF, 20 h, 150 °C,
under argon, isolated yields, ratio Z/E calculated with 1H NMR of the crude mixtures.
a Ratio Z/E: 2/98.
b Ratio Z/E: 35/65.
c Isolated yields of the mixture of Z (a)+E (b) isomers (entries 15–26) or hydrolysed products c (entries 1–14 and 27–29).
d The reaction performed under similar conditions with [Pd(C3H5)Cl]2/PPh3 1:4 as catalyst gave 7c, 12c or 26c in 16–25% yields and 21a,b in 38%
yield.
e Partial deprotection into the corresponding ketones c was observed before treatment with HCl or H2SO4.
f Not determined.
Finally, we performed a few reactions with methyl (E)-3-
methoxyacrylate (Table 1, entries 27–29). The formation
of mixtures of Z and E 3-aryl-3-methoxyacrylates was
observed, and, with this alkene a partial hydrolysis of
the arylated enol ethers occurs during the Pd-catalysed
reactions to give directly the 3-aryl-3-oxopropionic acid
methyl esters. The formation of side-products was also
observed with this alkene. Hydrolysis of these mixtures
gave the 3-aryl-3-oxopropionic acid methyl esters in
moderate yields.
have been observed. The stereoselectivity of the reactions
strongly depends on the electron properties and the steric
hindrance of the aryl bromides. As expected, larger
amounts of Z isomers were obtained with sterically
congested aryl bromides. Higher reactions rates were
observed with the electron-rich than with electron-
deficient aryl bromides. This observation indicates that
the rate-limiting step of this reaction is not the oxidative
addition of the aryl bromide to the palladium complex,
but more likely the insertion of the enol ether in the Ar–
Pd bond of the intermediate: Ar(X)Pd(RCH@CHOR0)
to give Ar(R)CH–CH(PdX)(OR0). Steric factors may
also be important for the reductive elimination step with
our bulky tetraphosphine ligand. Steric strain is a driving
force in many Pd catalysed reactions. With our systems a
catalytic intermediate might be a P2PdArX(alkene) pen-
ta-coordinate complex type with two arms of the ligand
detached. Apart from achieving excellent regiocontrol,
another advantage is that b-methoxystyrene, 3-eth-
oxyacrylonitrile and methyl (E)-3-methoxyacrylate are
commercially available. The hydrolysis of these arylated
enolesters gives a very simple access to a wide variety of
acetophenone derivatives.
A few reactions were also performed with these 2-substi-
tuted enol ethers using PPh3 as ligand, but low yields of
adducts were obtained and side products were formed
with this catalytic system.
In summary, with the Tedicyp/palladium complex, the
Heck vinylation of several aryl bromides with 2-substi-
tuted enol ethers can be performed in high regioselectivi-
ties and good yields. The reactivity of three 2-substituted
enol ethers has been studied: b-methoxystyrene, 3-eth-
oxyacrylonitrile and methyl (E)-3-methoxyacrylate. In
all cases, regioselective a-arylations of these enol ether

462
A. Battace et al. / Tetrahedron Letters 47 (2006) 459–462
Synlett 2003, 841; (f) Lemhadri, M.; Doucet, H.; Santelli,
Acknowledgements
M. Tetrahedron 2004, 60, 11533; (g) Berthiol, F.; Doucet,
H.; Santelli, M. Tetrahedron Lett. 2004, 45, 5633; (h)
Berthiol, F.; Doucet, H.; Santelli, M. Eur. J. Org. Chem.
2005, 1367; (i) Battace, A.; Zair, T.; Doucet, H.; Santelli,
M. J. Organomet. Chem. 2005, 690, 3790.
´ ´
We thank the CNRS and the ÔConseil General des Bou-
ches-du-Rhoˆne, FrÕ, for providing financial support.
12. (a) Feuerstein, M.; Doucet, H.; Santelli, M. Tetrahedron
Lett. 2002, 43, 2191; (b) Kondolff, I.; Doucet, H.; Santelli,
M. Synlett 2004, 1561.
References and notes
13. Kondolff, I.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2003, 44, 8487.
1. For reviews on the palladium-catalysed Heck reaction see:
(a) Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2; (b)
Beletskaya, I.; Cheprakov, A. Chem. Rev. 2000, 100, 3009;
(c) Withcombe, N.; Hii (Mimi), K. K.; Gibson, S.
Tetrahedron 2001, 57, 7449; (d) Littke, A.; Fu, G. Angew.
Chem., Int. Ed. 2002, 41, 4176; (e) Farina, V. Adv. Synth.
Catal. 2004, 346, 1553; (f) Bedford, R. B.; Cazin, C. S. J.;
Holder, D. Coord. Chem. Rev. 2004, 248, 2283; (g)
Dupont, J.; Consorti, C. S.; Spencer, J. Chem. Rev.
2005, 105, 2527.
14. As a typical experiment for reactions with b-methoxysty-
rene or methyl (E)-3-methoxyacrylate: (Table 1, entry 4)
The reaction of 4-fluorobromobenzene (0.175 g, 1 mmol),
b-methoxystyrene (0.268 g, 2 mmol) and NaHCO3
(0.168 g, 2 mmol) at 150 °C over 20 h in dry DMF
(5 mL) with cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphino-
methyl)cyclopentane/[PdCl(C3H5)]2 complex (0.01 mmol)
under argon affords the corresponding products (Z)-1-
methoxy-2-phenyl-1-(4-fluorophenyl)ethene (4a) and (E)-
2. For selected examples of Heck reactions with cinnamates
or crotonates: (a) Melpolder, J.; Heck, R. J. Org. Chem.
1976, 41, 265; (b) Cortese, N.; Ziegler, C.; Hrnjez, B.;
Heck, R. J. Org. Chem. 1978, 43, 2952; (c) Moreno-
1-methoxy-2-phenyl-1-(4-fluorophenyl)ethene (4b) as
a
mixture of isomers. Ratio 4a (Z)/4b (E) determined by
1H NMR on the crude mixture: 67/33. Characteristic band
1
´
of the mixture of isomers: H NMR (300 MHz, CDCl3):
Manas, M.; Perez, M.; Roser, P. Tetrahedron Lett. 1996,
˜
d = 6.04 (s, 1H, CH@C (Z)), 5.82 (s, 1H, CH@C (E)). This
unseparable mixture of isomers was hydrolysed into the
corresponding ketone using a mixture THF/H2O/HCl to
give 1-(4-fluorophenyl)-2-phenylethanone 4c in 78%
(0.167 g) isolated yield. 1H NMR (300 MHz, CDCl3):
d = 8.02 (dd, J = 7.4 and 5.5 Hz, 2H), 7.35–7.20 (m, 5H),
7.11 (t, J = 7.4 Hz, 2H), 4.25 (s, 2H).
37, 7449; (d) Gurtler, C.; Buchwald, S. Chem. Eur. J. 1999,
¨
5, 3107; (e) Littke, A.; Fu, G. J. Am. Chem. Soc. 2001, 123,
6989; (f) Calo, V.; Nacci, A.; Monopoli, A.; Lopez, L.; di
Cosmo, A. Tetrahedron 2001, 57, 6071.
3. For examples of Heck reactions with (E)-benzalacetone or
(E)-benzalacetophenone: (a) Cacchi, S.; Arcadi, A. J. Org.
Chem. 1983, 48, 4236; (b) Amorese, A.; Arcadi, A.;
Bernocchi, E.; Cacchi, S.; Cerrini, S.; Fereli, W.; Ortar, G.
Tetrahedron 1989, 45, 813.
4. For examples of Heck reactions with ethyl (E)-3-ethoxy
acrylate: Sakamoto, T.; Kondo, Y.; Kashiwagi, Y.;
Yamanaka, H. Heterocycles 1988, 27, 257.
5. For examples of Heck reactions with 3,3,3-trifluoro-1-
methoxypropene: Shi, G.-Q.; Huang, X.-H.; Hong, F. J.
Chem. Soc., Perkin Trans. 1 1996, 763.
6. For examples of Heck reactions with 1-butoxyprop-1-ene:
Andersson, C. M.; Hallberg, A.; Daves, G. D., Jr. J. Org.
Chem. 1987, 52, 3529.
15. As a typical experiment for reactions with 3-ethoxyacrylo-
nitrile: (Table 1, entry 21) The reaction of 1-bromo-
naphthalene (0.207 g, 1 mmol), 3-ethoxyacrylonitrile
(0.194 g, 2 mmol) and NaHCO3 (0.168 g, 2 mmol) at
150 °C over 20 h in dry DMF (5 mL) with cis,cis,cis-
1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/
[PdCl(C3H5)]2 complex (0.01 mmol) under argon affords
the corresponding products (Z)-3-ethoxy-3-naphthalen-1-
ylacrylonitrile (19a) and (E)-3-ethoxy-3-naphthalen-1-
ylacrylonitrile (19b) after evaporation and filtration on
silica gel as a mixture of isomers in 81% (0.181 g) isolated
1
7. For reactions with related substrates, see: (a) Nilsson, P.;
Larhed, M.; Hallberg, A. J. Am. Chem. Soc. 2001, 123,
8217; (b) Nilsson, P.; Larhed, M.; Hallberg, A. J. Am.
Chem. Soc. 2003, 125, 3430.
yield. Ratio 19a (Z)/19b (E) determined by H NMR on
the crude mixture: 75/25. These isomers were separated by
chromatography on silica gel. Isomer Z 19a: 1H NMR
(300 MHz, CDCl3): d 7.92 (d, 1H, J = 8.3 Hz), 7.85 (m,
2H), 7.64 (d, 1H, J = 7.0 Hz), 7.60–7.47 (m, 3H), 4.90 (s,
`
8. Laurenti, D.; Feuerstein, M.; Pepe, G.; Doucet, H.;
1H), 4.07 (q, 2H, J = 7.0 Hz), 1.43 (t, 3H, J = 7.0 Hz). 13
C
Santelli, M. J. Org. Chem. 2001, 66, 1633.
9. Feuerstein, M.; Laurenti, D.; Bougeant, C.; Doucet, H.;
Santelli, M. Chem. Commun. 2001, 325.
10. Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli, M. Org.
Biomol. Chem. 2003, 2235.
11. (a) Feuerstein, M.; Doucet, H.; Santelli, M. J. Org. Chem.
2001, 66, 5923; (b) Feuerstein, M.; Doucet, H.; Santelli,
M. Synlett 2001, 1980; (c) Berthiol, F.; Feuerstein, M.;
Doucet, H.; Santelli, M. Tetrahedron Lett. 2002, 43, 5625;
(d) Berthiol, F.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2003, 44, 1221; (e) Berthiol, F.; Doucet, H.; Santelli, M.
NMR (75 MHz, CDCl3): d 174.0, 133.6, 130.9, 130.4,
128.5, 127.7, 126.9, 126.3, 124.9, 124.6, 117.8, 74.2, 65.8,
14.1. Anal. Calcd for C15H13NO: C, 80.69; H, 5.87.
Found: C, 80.48; H, 5.97. Isomer E 19b: 1H NMR
(300 MHz, CDCl3): d 8.00–7.85 (m, 3H), 7.62–7.45 (m,
4H), 4.71 (s, 1H), 3.93 (q, 2H, J = 7.0 Hz), 1.25 (t, 3H,
J = 7.0 Hz). 13C NMR (75 MHz, CDCl3): d 172.7, 133.2,
131.0, 130.8, 130.4, 128.5, 127.6, 127.5, 126.7, 125.0, 124.6,
116.6, 77.7, 66.9, 15.2. Anal. Calcd for C15H13NO: C,
80.69; H, 5.87. Found: C, 80.80; H, 5.78.