Bromophilic substitution/carbophilic substitution cascade reactions of α,α-dibromo-2-methoxyacetophenone with C-, N- and O-nucleophiles

Article abstract of DOI:10.1016/j.tetlet.2010.07.057

α,α-Dibromo-2-methoxyacetophenone reacts, under mild reaction conditions, with C-, N- and O-nucleophiles via a bromophilic substitution/protonation/carbophilic substitution cascade process to afford α-monosubstituted-2-methoxyacetophenones in moderate to good yield. The only exception from this reaction pathway is the reaction with the anion derived from malononitrile in which 2-aroyl-1,1,3,3-tetracyanopropene is obtained.

Full text of DOI:10.1016/j.tetlet.2010.07.057

Tetrahedron Letters 51 (2010) 4851–4855
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Tetrahedron Letters
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Bromophilic substitution/carbophilic substitution cascade reactions of
a,a-dibromo-2-methoxyacetophenone with C-, N- and O-nucleophiles
a
a,b
a
a,b,
*
´
´
´
Jovana Tatar , Rade Markovic , Milovan Stojanovic , Marija Baranac-Stojanovic
a Center for Chemistry ICTM, PO Box 473, 11000 Belgrade, Serbia
b Faculty of Chemistry, University of Belgrade, Studentski trg 16, PO Box 158, 11000 Belgrade, Serbia
a r t i c l e i n f o
a b s t r a c t
Article history:
a
,
a
-Dibromo-2-methoxyacetophenone reacts, under mild reaction conditions, with C-, N- and O-nucleo-
Received 20 May 2010
Revised 22 June 2010
Accepted 9 July 2010
Available online 14 July 2010
philes via a bromophilic substitution/protonation/carbophilic substitution cascade process to afford
a
-
monosubstituted-2-methoxyacetophenones in moderate to good yield. The only exception from this
reaction pathway is the reaction with the anion derived from malononitrile in which 2-aroyl-1,1,3,3-tet-
racyanopropene is obtained.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
a,a-Dibromomethylketone
Bromophilic reaction
Nucleophilic substitution
Cascade reactions
Nucleophilic substitution reactions, occurring by the attack of a
nucleophile on a carbon atom, are the widely studied reactions in
organic chemistry. Less familiar are nucleophilic substitutions at
halogens, known as halophilic reactions1 (SNX, Scheme 1).
could be extended to other nucleophiles, such that dibromides
could be used as synthetic equivalents of monobromo derivatives,
thereby circumventing the additional debromination step. For this
purpose, a,a-dibromo-2-methoxyacetophenone (3) was chosen as
These reactions usually take place if the normal (SNC) substitu-
tion reaction is made difficult, and/or if the resulting carbanion is
stabilized by electron-withdrawing substituents. For example, per-
haloalkanes are rather inert towards nucleophilic displacement
reactions, but they can undergo halophilic attack by a range of
nucleophiles.2 Halophilic reactions have also been observed for
a substrate, since it can easily be obtained by bromination of
2-methoxyacetophenone with bromine in CHCl3; the correspond-
ing monobromo derivative is not as easy to prepare.13a Herein, we
report the first combined bromophilic substitution/carbophilic sub-
stitution reactions directed towards the preparation of syntheti-
cally valuable 1,4-dicarbonyl compounds,14
-hydroxy ketones.16
The 1,4-dicarbonyl compounds 7a–d were obtained, under mild
reaction conditions, by the reaction of -dibromo-2-methoxyace-
a
-phthalimido15 and
a
-halo sulfones,3
a
-halo ketones,4
a
-halo nitriles,5 halogenated
a
nitroalkanes,6 diethyl bromo-7 and diethyl dibromomalonate,8
3-methyl-5-trichloromethyl-1,2,4-oxadiazole,9 2-halomethyl-
5-nitrofurans10 and geminal5 and vicinal dihalides.5,11 In many
cases halophilic attack results in protonation of the carbanion 2,
that is, reductive dehalogenation.3,4,9,10
a,a
tophenone (3) with 3–4 mol equiv of carbanions derived from ac-
tive methylene compounds 4a–d (Scheme 2, Table 1).17 The
formation of the products 7a–d occurs via a stepwise process begin-
ning with a relatively rare bromophilic attack of the C-nucleophile
on dibromide 3 yielding, after protonation of the initially formed
carbanion, monobromide 6 and monobrominated active methylene
compounds 5a–d. The existence of monobromide 6 as an interme-
diate was confirmed by TLC18 (eluent:toluene; Rf = 0.4), carried out
Selective
a-monobromination of methyl ketones can be difficult
a,a-Dibromo derivatives can be formed as the side
to achieve.12
products, or even as the major products.13 In such cases, an addi-
tional step, involving selective debromination, is needed to afford
bromomethylketones,13b which are important synthetic intermedi-
ates. In our previous communication,13a we reported that ortho-
substituted
a,a-dibromoacetophenones undergo nucleophile-in-
duced cascade reactions giving rise to
a-monosubstituted aceto-
Y1
C
Y2
Y1
C−
Y2
2
phenone derivatives in good to high yields (Nu = CNÀ, SCNÀ, AcSÀ,
−
IÀ, N3 and AcOÀ). It was envisaged that this mode of reactivity
À
+
+
Nu
Nu
R
X
R
X
1
* Corresponding author. Tel.: +381 11 3336740; fax: +381 11 2636061.
E-mail address: mbaranac@chem.bg.ac.rs (M. Baranac-Stojanovic´).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.057

4852
J. Tatar et al. / Tetrahedron Letters 51 (2010) 4851–4855
O
OMe
O
CN
O
OMe
R
R1
R1
O
OEt
R
8
O
10a-c
6
,
K2CO3
(R = CN;
R1 = OEt)
31%
16-30% 4a-c, K2CO3
OMe
O
OMe
O
R
OMe
O
O
R1
O
Br
K2CO3, MeCN
(or DMF), r.t.
Br
R
4a-d,
R1
K2CO3
R
+
R1
+
O
Br
59-77%
Br
5a-d
4a-d
3
6
7a-d
K2CO3
a: R = COMe; R1 = Me
11%
5c
(R = CO2Et; R1 = OEt)
,
K2CO3
(R = CO2Et;
: R = COPh; R1 = OEt
b
6%
c: R = CO2Et; R1 = OEt
R
1 = OEt)
CO2Et
: R = CN; R1 = OEt
O
O
d
OMe
O
EtO
EtO
OEt
OEt
CO2Et
CO2Et
EtO2C
O
O
11
9
Scheme 2.
30 min after the reaction had started, and by isolation of 6 after
work-up of the reaction. The next step involved nucleophilic
substitution of the bromine in 6 by a second mol equiv of the
C-nucleophile 4a–d which resulted in the formation of products
7a–d in moderate to good yields (59–77%). In the case of 7d
(R = CN; R1 = OEt) a further reaction with the monobromide 6 oc-
169.0(DMSO-d6)/170.2(acetone-d6) and 49.1(DMSO-d6)/50.1(ace-
tone-d6) ppm, both due to non-protonated C-atoms, as determined
by
a
DEPT experiment. Quantitative 13C NMR measurement
showed that each of the signals at 115.4/116.4 ppm, 117.6/
118.5 ppm and 49.1/50.1 ppm was due to two C-atoms, whereas
the signal at 169.0/170.2 ppm was due to one C-atom. The latter
signal was attributed to the double bonded carbon next to the car-
bonyl group. These data indicate the equivalence of the C(1) and
C(3) atoms of the tetracyanopropene moiety, which can be ex-
plained by the existence of rapid prototropic tautomerism as
shown in Figure 1. The value of 49.1/50.1 ppm corresponds to
the mean value of the calculated shifts21 for the C(1) (ꢀ87 ppm)
and C(3) (ꢀ14 ppm) atoms. The non-existence of the CH signal in
the 1H NMR spectrum and inability to obtain any C–H correlation
by 2D NMR techniques can be ascribed to a broadening of the CH
signal to such an extent that it merged with the base line. Another
possible explanation is that the recorded spectra are for the carb-
anion formed by the ionization of the highly acidic C-hydrogen
in tetracyanopropenes.22
curred yielding 1,5-diketone
8 in 31% yield, whereas 7c
(R = CO2Et; R1 = OEt) was alkylated with diethyl bromomalonate
(5c) to give the tetraester 9 in low yield (6%). On the other hand,
the
a-bromo compounds 5a–c reacted with excess of C-nucleo-
philes to give dimers 10a–c (16–30%). In the case of diethyl
bromomalonate (5c), the base-assisted coupling followed by
HBr elimination yielded the tetrasubstituted alkene 1119 (11%),
isolated as a mixture with 10c. A small amount of epoxide 1220
(8%, Table 1, entry 3) was also formed in the reaction of dibro-
mide 3 with diethyl malonate. It accompanied the isolated main
product 7c (10% by weight) and could not be separated from it
using standard techniques.
Similarly, the reactions of 2-methoxy-a,a-dibromoacetophe-
none (3) with potassium phthalimide, potassium carbonate in
DMF/H2O and the previously reported13a reaction with KCN pro-
ceeded via the bromophilic substitution/protonation/carbophilic
Although the exact mechanism for the formation of compound
14 is as yet, not known, it may be consistent with a double SN2 dis-
placement reaction on 3 followed by oxidation.
substitution cascade process to give
a-phthalimido ketone 13a,
The reaction of 2-methoxy-a,a-dibromoacetophenone (3) with
a
-hydroxy ketone 13b and nitrile 13c (Scheme 3, Table 2). In the
excess pyridine in wet MeCN resulted in C–C bond cleavage and
the formation of 2-methoxybenzoic acid (16) (Scheme 5), probably
via initial formation of the pyridinium salt 15 which was then
cleaved to the acid 16.23
case of CNÀ as the nucleophile, the second step was slow enough
to allow isolation of the monobromide 6 when 1 equiv of nucleo-
phile was employed (Table 2, entry 4).
The reaction of 2-methoxy-
a
,
a
-dibromoacetophenone (3) with
In conclusion, we have shown that 2-methoxy-a,a-dibromoace-
3 equiv of the anion derived from malononitrile17 took a different
reaction path. Monobromide 6 was not detected as an intermediate
and an intense yellow-coloured product was formed, the structure
of which was assigned as 2-aroyl-1,1,3,3-tetracyanopropene 14
(Scheme 4).
tophenone reacts with 3–4 mol equiv of carbanions derived from
the active methylene compounds via a three-step cascade process
involving bromophilic substitution/protonation/carbophilic substi-
tution, to give
the main products. This reaction could be useful for the synthesis
of -monosubstituted methyl ketones when their monobromo
a-monosubstituted 2-methoxyacetophenones, as
In the 1H NMR spectrum of 14 only signals belonging to the aro-
matic portion of the molecule and OMe group could be seen, both
in DMSO-d6 and acetone-d6 solutions. The 13C NMR spectrum
showed eight signals due to the 2-methoxybenzoyl group, but only
four signals arising from the tetracyanopropene moiety, two for
the CN groups at 115.4(DMSO-d6)/116.4(acetone-d6) and
117.6(DMSO-d6)/118.5(acetone-d6) ppm, and two signals at
a
derivatives are not readily available. If 1 mol equiv of KCN was
used, only the bromophilic reaction occurred, allowing the isola-
tion of an
a-bromo-2-methoxyacetophenone. The a-brominated
active methylene compounds, formed in the first step of the cas-
cade process, react further to form dimers, or a tetrasubstituted al-
kene. The only exception from this reaction pathway was the

Table 1
The reactions of 2-methoxy-a,a-dibromoacetophenone (3) with active methylene compounds 4a–d
Entry
Nucleophile
Conditions
Products (yields)a
O
O
O
O
O
O
O
OMe
O
4a
1
4a (3 equiv), K2CO3 (3 equiv), DMF, rt, 30 min
O
7a (63%)
10a (29%)
O
O
O
OEt
O
O
O
OMe
O
Ph
OEt
Ph
EtO
EtO
Ph
Ph
4b
2
4b (3 equiv), K2CO3 (3 equiv), MeCN, rt, 24 h
O
7b
(77%)
O
10b (30%)
OMe CO2Et
O
O
O
O
O
O
O
O
OEt
O
O
O
O
O
O
O
O
O
OMe
O
EtO
EtO
OEt
OEt
EtO
NC
OEt
OEt
EtO
EtO
OEt
OEt
CO2Et
EtO
EtO
OEt
OEt
4c
3
4
4c (4 equiv), K2CO3 (4 equiv), MeCN, rt, 24 h
O
EtO2C
9 (6%)
CO2Et
b
7c
(77%)
12 (8%)b
10c (16%)c
11 (11%)c
O
OMe
O
CN
OMe
O
CN
O
OMe
OEt
OEt
4d (3 equiv), K2CO3 (3 equiv), DMF, rt, 2.5 h
4d
O
OEt
(31%)
O
(59%)
7d
8
a
b
c
Yield of isolated product.
Yield was determined from the 1H NMR spectrum of the mixture of 7c and 12.
Yield was determined from the 1H NMR spectrum of the mixture of 10c and 11.

4854
J. Tatar et al. / Tetrahedron Letters 51 (2010) 4851–4855
OMe
O
OMe
O
O
OMe
O
OMe
O
Br
Br
N
Br pyridine (20 equiv.),
wet MeCN, 60 °C, 27 h
Nu−
Br
Br
Br
3
6
15
3
35-64% Nu−
O
76%
a
: N
Nu =
OMe
O
OMe
O
Nu
b
: OH
c: CN
OH
13a-c
16
Scheme 3.
Scheme 5.
Acknowledgement
Table 2
The reactions of 2-methoxy-
a,a-dibromo-acetophenone (3) with potassium phthal-
imide, K2CO3 in DMF/H2O and KCN
This research was partially supported by the Ministry of Science
of the Republic of Serbia, Grant No. 142007 (to R.M.)
Entry Nucleophile
Conditions
Product (yield)a
O
O
References and notes
OMe
O
O
N
Me2CO/H2O, rt,
24 h
N
1. Zefirov, N. S.; Makhon’kov, D. I. Chem. Rev. 1982, 82, 615–624.
2. (a) Li, X.; Pan, H.; Jiang, X. Tetrahedron Lett. 1984, 25, 4937–4940; (b) Li, X.; Pan,
H.; Jiang, X.; Zhan, Z. Angew. Chem., Int. Ed. Engl. 1985, 24, 871–872; (c)
Wakselman, C.; Tordeux, M. J. Org. Chem. 1985, 50, 4047–4051; (d) Li, X.; Jiang,
X.; Pan, H.; Hu, J. W.; Fu Pure Appl. Chem. 1987, 59, 1015–1020; (e) Li, X.; Pan,
H.; Jiang, X. Tetrahedron Lett. 1987, 28, 3699–3702; (f) Li, X.; Hu, J. Tetrahedron
Lett. 1987, 28, 6317–6320; (g) Cox, D. G.; Burton, D. J. J. Org. Chem. 1988, 53,
366–374; (h) Li, J.; Qiao, J. X.; Smith, D.; Chen, B.-C.; Salvati, M. E.; Roberge, J. Y.;
Balasubramanian, B. N. Tetrahedron Lett. 2007, 48, 7516–7519.
3. (a) Langler, R. F.; Pincock, J. A. Can. J. Chem. 1977, 55, 2316–2322; (b) Grossert, J.
S.; Dubey, P. K.; Elwood, T. Can. J. Chem. 1985, 63, 1263–1267; (c) Galvagni, M.;
Kelleher, F.; Paradisi, C.; Scorrano, G. J. Org. Chem. 1990, 55, 4454–4456.
4. (a) Seshadri, R.; Pegg, W. J.; Israel, M. J. Org. Chem. 1981, 46, 2596–2598; (b)
Taner, D. D.; Chen, J. J. J. Org. Chem. 1992, 57, 662–666.
1
O
O
13a
(64%)
(2 equiv)
OMe
OMe
OMe
OH
K2CO3 (3 equiv),
DMF/H2O, rt, 94 h
2
3
4
H2O (or OHÀ)
CNÀ (3 equiv)
CNÀ (1 equiv)
13b
(35%)
O
CN
Me2CO/H2O, rt,
24 h
5. Dahl, O. J. Chem. Soc., Perkin Trans. 1 1978, 947–953.
6. (a) Al-Khalil, S. I.; Bowman, W. R. Tetrahedron Lett. 1984, 25, 461–464; (b)
Fishwick, B. R.; Rowles, D. K. J. Chem. Soc., Perkin Trans. 1 1986, 1171–1179.
7. Shen, Y.; Yang, B. J. Chem. Soc., Chem. Commun. 1988, 1394–1395.
8. Mebane, R. C.; Smith, K. M.; Rucker, D. R.; Foster, M. P. Tetrahedron Lett. 1999,
40, 1459–1462.
9. Gentile, A. M.; Mencarelli, P. Gazz. Chim. Ital. 1988, 118, 609–610.
10. Beadle, C. D.; Bowman, W. R.; Prousek, J. Tetrahedron Lett. 1984, 25, 4979–4982.
11. (a) Speciale, A. J.; Tung, C. C. J. Org. Chem. 1963, 28, 1353–1357; (b) Tung, C. C.;
Speciale, A. J. J. Org. Chem. 1963, 28, 1521–1523; (c) Kwok, W. K.; Miller, S. I. J.
Org. Chem. 1970, 35, 4034–4037; (d) Baciocchi, E.; Lillocci, C. J. Chem. Soc.,
Perkin Trans. 2 1973, 38–41; (e) Yasui, S.; Itoh, K.; Ohno, A. Heteroat. Chem.
2001, 12, 217–222.
13c
(64%)
Br
O
Me2CO/H2O, rt,
22 h
6 (49%)
a
Yield of isolated product.
12. Kimpe, N. D.; Verhe, R. In The Chemistry of
-Haloimines; Patai, S., Rappoport, Z., Eds.; J. Wiley & Sons: Chichester, 1998; p
1.
13. (a) Tatar, J.; Baranac-Stojanovic´, M.; Stojanovic´, M.; Markovic´, R. Tetrahedron
Lett. 2009, 50, 700–703; (b) Diwu, Z.; Beachdel, C.; Klaubert, D. H. Tetrahedron
Lett. 1998, 39, 4987–4990.
14. (a) Rao, Y. S. Chem. Rev. 1976, 76, 625–649; (b) Ohkuma, T.; Kitamura, M.;
Noyori, R. Tetrahedron Lett. 1990, 31, 5509–5512; (c) Stauffer, F.; Neier, R. Org.
Lett. 2000, 2, 3535–3537; (d) Braun, R. U.; Zeitler, K.; Müller, T. J. J. Org. Lett.
2001, 3, 3297–3300; (e) Minetto, G.; Raveglia, L. F.; Taddei, M. Org. Lett. 2004, 6,
389–392; (f) Banik, B. K.; Samajdar, S.; Banik, I. J. Org. Chem. 2004, 69, 213–216.
15. (a) Gupta, P.; Shah, B. A.; Parshad, R.; Qazi, G. N.; Taneja, S. C. Green Chem. 2007,
9, 1120–1125; (b) Aiwen, L.; Shulin, W.; Minsheng, H.; Xumu, Z. J. Am. Chem.
Soc. 2004, 126, 1626–1627; (c) Wang, Y.-Q.; Lu, S.-M.; Zhou, Y.-G. Org. Lett.
2005, 7, 3235–3238; (d) Hu, A.; Lin, W. Org. Lett. 2005, 7, 455–458.
16. (a) Arjun Reddy, M.; Bhanumathi, N.; Rama Rao, K. Tetrahedron Lett. 2002, 43,
3237–3238; (b) Zacuto, M. J.; Cai, D. Tetrahedron Lett. 2005, 46, 447–450.
17. General procedure for the synthesis of 1,4-dicarbonyl compounds 7a–d and 2-
aroyl-1,1,3,3-tetracyanopropene 14: A mixture of active methylene compound
4a–d (0.6 mmol), or malononitrile (0.6 mmol) and K2CO3 (0.6 mmol) in DMF or
a-Haloketones, a-Haloaldehydes and
a
OMe O
Br
OMe
O
CN
CN
CN
CH (CN) K CO
3,
2
2,
2
MeCN, r.t., 24 h
Br
48%
NC
3
14
Scheme 4.
OCH3
OCH3
O
O
NC
CN
NC
CN
1
3
MeCN (2.1 mL) was stirred at rt for 15 min and 2-methoxy-a,a-
CN CN
CN CN
dibromoacetophenone (3) (0.2 mmol in the case of 4a, 4b, 4d and
malononitrile; 0.15 mmol in the case of 4c) was added. The mixture was
stirred at room temperature for the time specified in Table 1, then evaporated
and the residue was partitioned between CHCl3 and H2O, or EtOAc and H2O in
the case of the reaction with malononitrile. The organic layer was dried with
anhyd Na2SO4, evaporated and chromatographed (eluent:gradient PE/EtOAc).
Figure 1.
reaction with the anion formed from malononitrile, yielding 2-ar-
oyl-1,1,3,3-tetracyanopropene, which exists in a very fast prototro-
pic equilibrium when dissolved in DMSO-d6 or acetone-d6.
Compound 7a: yield: 63%; colourless oil; IR (neat):
1242, 757 cmÀ1 1H NMR (200 MHz, CDCl3, keto/enol ratio:74:26): (keto form)
d 2.32 (s, 6H, 2 CH3), 3.61 (d, 2H, J = 6.6 Hz, CH2), 3.94 (s, 3H, CH3O), 4.34 (t, 1H,
mmax 1725, 1699, 1666, 1595,
;

J. Tatar et al. / Tetrahedron Letters 51 (2010) 4851–4855
4855
J = 6.6 Hz, CH), 6.96–7.04 (m, 2H, H3-Ph and H5-Ph), 7.45–7.54 (m, 1H, H4-Ph),
7.73–7.78 (m, 1H, H6-Ph), (enol form) d 2.05 (s, 6H, 2 CH3), 3.96 (s, 3H, CH3O),
3.97 (s, 2H, CH2), 6.96–7.07 (m, 2H, H3-Ph and H5-Ph), 7.45–7.54 (m, 1H, H4-
Ph), 7.66–7.70 (m, 1H, H6-Ph), 16.85 (s, 1H, OH); 13C NMR (50.3 MHz, CDCl3):
(keto form) d 29.81, 42.92, 55.55, 63.02, 111.63, 120.73, 126.49, 130.68, 134.35,
159.13, 198.21, 203.72, (enol form) d 23.20, 42.53, 55.55, 104.71, 111.52,
120.95, 127.96, 130.24, 133.75, 158.40, 191.76, 199.64; HRMS: calcd for
(s, 3H, CH3O), 7.12 (t, 1H, J = 7.5 Hz, H5-Ph), 7.24 (d, 1H, J = 8.5 Hz, H3-Ph),
7.68–7.72 (m, 1H, H4-Ph), 7.74–7.76 (m, 1H, H6-Ph); the CH signal was not
observed in the 1H NMR; 13C NMR (125.79 MHz, DMSO-d6): d 49.11, 56.55,
113.63, 115.36, 117.62, 121.25, 122.87, 131.69, 137.26, 160.42, 169.01, 190.41;
HRMS: calcd for C15H9N4O2 (M+H)+: 277.0720; found: 277.0723.
18. The authentic monobromide, used for comparison by TLC and NMR, was
obtained by reaction of
(Table 2).
a,a-dibromoacetophenone with 1 mol equiv of KCN
C
14H17O4 (M+H)+: 249.1121; found: 249.1117; Compound 7b:24 yield: 77%;
colourless oil; IR (neat):
1736, 1683, 1597, 1245, 759 cmÀ1 1H NMR
(200 MHz, CDCl3): 1.17 (t, 3H, J = 7.1 Hz, CH3), 3.78 (dd, 2H, J = 6.8 Hz,
m
;
19. (a) The compound 11 was characterized on the basis of 1H NMR, 13C NMR and
HPLC/HRMS. The 1H NMR and 13C NMR were also compared with the literature
data (Ref. 19b,c); 1H NMR (500.26 MHz, CDCl3): d 1.32 (t, 3H, J = 7.2 Hz, CH3),
4.32 (q, 2H, J = 7.2 Hz, CH2O); 13C NMR (125.79 MHz, CDCl3): d 13.78, 62.52,
d
J = 1.2 Hz, CH2), 3.90 (s, 3H, CH3O), 4.16 (q, 2H, J = 7.1 Hz, CH2O), 5.10 (t, 1H,
J = 6.8 Hz, CH), 6.95–7.02 (m, 2H, H3-Ph and H5-Ph), 7.43–7.64 (m, 4H, H4-Ph,
m- and p-Ph), 7.76–7.80 (m, 1H, H6-Ph), 8.06–8.10 (m, 2H, o-Ph); 13C NMR
(50.3 MHz, CDCl3): d 13.84, 43.21, 49.16, 55.44, 61.47, 111.54, 120.55, 126.54,
128.60, 128.82, 130.68, 133.39, 134.17, 136.12, 159.15, 169.62, 195.20, 198.06;
HRMS: calcd for C20H20O5Na (M+Na)+: 363.1203; found: 363.1227; Compound
135.36, 162.33; HRMS: calcd for
C
14H21O8 (M+H)+: 317.1231; found:
317.1228.; (b) Peng, R.-F.; Wang, G.-W.; Shen, Y. B.; Li, Y.-J.; Zhang, T.-H.; Liu,
Y.-C.; Murata, Y.; Komatsu, K. Synth. Commun. 2004, 34, 2117–2126; (c)
Saalfrank, R. W.; Rost, W. Angew. Chem. 1985, 97, 870–871.
7c: yield: 77%; colourless oil; IR (neat):
m
1753, 1597, 1248, 761 cmÀ1
;
1H NMR
20. Since the compound 12 accompanied the main product 7c it was characterized
on the basis of additional signals which appeared in the 1H NMR and 13C NMR
spectra of 7c and on the basis of HPLC/HRMS. 1H NMR (200 MHz, CDCl3): d 1.32
(t, 3H, J = 7.2 Hz, CH3), 4.31 (q, 2H, J = 7.2 Hz, CH2O); 13C NMR (50.3 MHz,
CDCl3): d 13.68, 63.04, 162.19; due to a low concentration of 12, the signal
belonging to quaternary C was not visible in the spectrum; HRMS: calcd for
(200 MHz, CDCl3): d 1.29 (t, 6H, J = 7.2 Hz, 2 CH3), 3.65 (d, 2H, J = 7.4 Hz, CH2),
3.93 (s, 3H, CH3O), 4.02 (t, 1H, J = 7.4 Hz, CH), 4.23 (q, 4H, J = 7.2 Hz, 2 CH2O),
6.96–7.03 (m, 2H, H3-Ph and H5-Ph), 7.44–7.53 (m, 1H, H4-Ph), 7.76–7.81 (m,
1H, H6-Ph); 13C NMR (50.3 MHz, CDCl3): 13.86, 42.84, 47.47, 55.39, 61.40,
111.48, 120.53, 126.51, 130.57, 134.12, 159.04, 169.26, 197.77; HRMS: calcd
for C16H21O6 (M+H)+: 309.1333; found: 309.1332; Compound 7d: yield: 59%;
C
14H21O9 (M+H)+: 333.1180; Found: 333.1182.
yellowish oil; IR (neat):
m
2252, 1745, 1670, 1597, 1246, 762 cmÀ1
;
1H NMR
21. Pretsch, E.; Seibl, J.; Simon, W.; Clerc, T. Tabellen zur Strukturaufklärung
Organischer Verbindungen mit Spektroskopischen Methoden; Springer Verlag:
Berlin, Heidelberg, 1981.
22. Urushibara, Y.; Takebayashi, M. Bull. Chem. Soc. Jpn. 1936, 11, 569–575.
23. (a) Brussoti, G.; Habermann, J.; Azzolina, O.; Collina, S. Lett. Org. Chem. 2006, 3,
943–947; (b) King, L. C. J. Am. Chem. Soc. 1944, 66, 894; (c) Pearson, R. G. J. Am.
Chem. Soc. 1947, 69, 3100–3103.
(200 MHz, CDCl3): d 1.34 (t, 3H, J = 7.2 Hz, CH3), 3.56–3.85 (m, 2H, CH2), 3.95 (s,
3H, CH3O), 4.11 (dd, 1H, JAX = 5.6 Hz, JBX = 6.6 Hz, CH), 4.29 (q, 2H, J = 7.2 Hz,
CH2O), 6.99–7.06 (m, 2H, H3-Ph and H5-Ph), 7.49–7.58 (m, 1H, H4-Ph), 7.84–
7.89 (m, 1H, H6-Ph); 13C NMR (50.3 MHz, CDCl3): d 13.86, 32.21, 43.17, 55.53,
62.94, 111.67, 116.73, 120.86, 125.40, 131.00, 134.99, 159.46, 165.74, 195.07;
HRMS: calcd for
Compound 14: yield: 48%; yellow solid, mp >300 °C; IR (KBr):
2194, 1669, 1486, 1226, 754 cmÀ1 1H NMR (500.26 MHz, DMSO-d6): d 3.89
C
14H15NO4Na (M+Na)+: 284.0893; found: 284.0894;
2237, 2209,
m
24. Caplin, G. A.; Ollis, W. D.; Sutherland, I. O. J. Chem. Soc. (C) 1968, 2302–2310.
;