An efficient iodine-catalyzed benzylation reaction of 1,3-dicarbonyl compounds

Article abstract of DOI:10.1055/s-2008-1078216

Under mild conditions, iodine promotes the direct alkylation of 1,3-dicarbonyl compounds with benzylic alcohols or benzylic acetates. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1078216

LETTER
2535
An Efficient Iodine-Catalyzed Benzylation Reaction of 1,3-Dicarbonyl
Compounds
I
odine-Catalyze
h
d
Benzylatio
o
n
Reaction
o
n
f
1, 3-Dicarb
g
xnds ian Li, Zheng Duan,* Huaiqiu Wang, Rongqiang Tian, Qianrui Zhu, Yangjie Wu*
Chemistry Department, The Key Lab of Chemical Biology and Organic Chemistry of Henan Province, The Key and Open Lab of Applied
Chemistry of Henan Universities, Zhengzhou University, Zhengzhou 450052, P. R. of China
Fax +86(371)67979408; E-mail: duanzheng@zzu.edu.cn; E-mail: wyj@zzu.edu.cn
Received 13 May 2008
Table 1 Reaction of 1-Phenylethanol with Acetylacetonea
Abstract: Under mild conditions, iodine promotes the direct al-
kylation of 1,3-dicarbonyl compounds with benzylic alcohols or
benzylic acetates.
O
O
O
O
OH
I2 (10 mol%)
80 °C
+
Key words: iodine, catalysis, benzylation, Friedel–Crafts, C–H ac-
tivation
1a
2a
3a
Entry
1
Solvent
–
1a/2a
1:4
1:4
1:4
1:4
1:4
1:2
1:1
1:4
1:4
1:4
1:4
1:4
1:4
1:4
Time (h) Yield (%)b
2
97
99
41
0
Over the last few decades the quest for more economical
ways to the C–C bond formation has become a matter of
increasing importance among both industrial and academ-
ic research.1 The alkylation of 1,3-dicarbonyl compounds
plays an important role in modern organic synthesis.2
However, the standard protocol usually requires stoichio-
metric amount of base, and a large amount of side prod-
ucts are generated.3 Several atom-economical approaches
via acid-catalyzed addition of 1,3-dicarbonyl derivatives
to alkenes or alcohols were reported.4 The direct reaction
between 1,3-dicarbonyl derivatives and alcohols are note-
worthy, since no organic halides are generated and water
is the sole byproduct. Recently, several efficient methods
of intermolecular benzylation and alkylation of active
methylene compounds using alcohols as electrophiles
have been reported. In these processes, transition metals,
such as ruthenium,5 palladium,6 indium,7 bismuth,8 iron,2
rare-earth metal,9 and Brønsted acid,10 were used as cata-
lysts. However, the disposal of these metal salts or corro-
sive acids is troublesome and prevents their large-scale
applications.
2
MeNO2
MeCN
H2O
8
3
8
4
8
5
DCE
8
51
92
87
99
99
92
50c
85d
97e
6
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
8
7
8
8
2
9
1
10
11
12
13
14
0.5
2
2
2
f
4
–
In recent years, molecular iodine as a simple, less expen-
sive, less toxic reagent has attracted more attention in or-
ganic synthesis.11 Herein, we wish to describe the first
benzylation of activated methylene compounds catalyzed
by I2. Initially, we explored the iodine-catalyzed reaction
of phenylethyl alcohol (1a) with active methylene 2a un-
der different reaction conditions (Table 1), such as cata-
lyst loading, temperature, reaction time, substrate ratio,
and solvent. The effect of solvents on this reaction was re-
markable. Compared with the reactions using other sol-
vents (DCE, MeCN, and H2O) or in the absence of
solvents, nitromethane could improve this I2-catalyzed
benzylation reaction efficiently (Table 1, entries 1–5).
When the reaction was carried out at a lower temperature,
a All reactions were carried out with 1-phenylethanol (0.5 mmol), I2
(0.05 mmol), solvent (2 mL) at 80 °C.
b Isolated yield.
c Reaction at r.t.
d Reaction at 50 °C.
e I2 (0.025 mmol) was used.
f Without catalyst.
the target compound 3a12,13 was obtained in a low yield
(Table 1, entries 11 and 12). With 5 mol% of iodine cata-
lyst, the product could be obtained in 97% yield (Table 1,
entry 13), and no product could be isolated without the
catalyst (Table 1, entry 14). On the other hand, both the
reaction time and substrate ratio had a minor impact on
this reaction (Table 1, entries 2, 6–10). Based on these re-
sults, the best conditions with respect to product yield
were secured (5–10 mol% of iodine in MeNO2 at 80 °C)
(Table 1, entries 8 and 9). The reaction could proceed
smoothly without exclusion of moisture and air from the
reaction mixture.
SYNLETT 2008, No. 16, pp 2535–2539
x
x
.x
x
.2
0
0
8
Advanced online publication: 22.08.2008
DOI: 10.1055/s-2008-1078216; Art ID: W07808ST
© Georg Thieme Verlag Stuttgart · New York

2536
Z. Li et al.
LETTER
Under the optimized conditions, we investigated the I2- pounds. In this context, mesitylene was chosen as the nu-
catalyzed reactions of various benzylic alcohols and ben- cleophile to react with 1-phenylethanol in the presence of
zylic acetates with acetylacetone. Both electron-rich and I2. Gratifyingly, the desired alkylation product 5a could be
moderately electron-poor aromatic substrates reacted obtained in 52% yield (Scheme 1). The corresponding
smoothly with acetylacetone and the corresponding ben- alkylation products 5b and 5c could also obtained from
zylation products were isolated in excellent yields 2,5-dimethylfuran and 2,5-dimethyl-thiophene, respec-
(Table 2, entries 1–7). But when the reaction was carried tively, in good yields.14
out with the highly electron-deficient benzylic alcohol 1j,
only trace amount of the desired product was obtained
(Table 2, entry 10). When 1,1¢-diacetoxytoluene was
used, a Knoevenagel condensation product was obtained
in excellent yield (Table 2, entry 9).
OH
Ar
I2 (10 mol%)
ArH
+
MeNO2, 80 °C
4
1a
5
Further investigations were concentrated on the scope and
limitations of this reaction. Other 1,3-dicarbonyl com-
pounds were reacted with 1-phenylethanol. Benzoylace-
tone and dibenzoylmethane were almost quantitatively
converted into corresponding products under optimized
Ar =
O
S
5a (52%)
5b (78%)
5c (95%)
conditions within one hour (Table 2, entries 11 and 12). Scheme 1 Iodine-Catalyzed benzylation of arenes and heteroarenes
When 2-acetylcyclohexanone and ethyl acetoactate were
used (Table 2, entries 13 and 14), products 3m and 3n
In summary, we have developed a general and efficient I2-
were obtained in 89% and 92% yields, respectively. 1,3-
catalyzed substitution reaction of benzylic alcohols or
Cyclohexanedione provided the isomerized product 3o in
benzylic acetates with 1,3-dicarbonyl compounds, elec-
56% yield (Table 2, entry 15). The reason for this moder-
tron-rich arenes, and heterocyclic compounds. The mild
ate yield of 3o might be the lower solubility of 2f in ni-
and metal-free conditions made this method noteworthy.
The scope, mechanism, and synthetic applications of this
tromethane.
reaction are under further investigation in our group.
In order to expand the reaction scope of this I2-catalyzed
benzylation reaction, further research was carried out with
other nucleophiles instead of activated methylene com-
Table 2 Reaction of Various Benzylic Alcohols or Esters with Pentanedionesa
Entry
1
2
Time (h) Product
Yield (%)b
99c (98)d
O
OH
O
O
1
1
3a
3b
3c
O
O
2a
2a
1a
OH
2
3
Cl
2
97c
99c
Cl
O
1b
O
OH
MeO
2a
2a
1
MeO
O
1c
O
O
O
OAc
4
5
1
3d
3e
99c
1d
O
OAc
2a
1
95c
1e
Synlett 2008, No. 16, 2535–2539 © Thieme Stuttgart · New York

LETTER
Iodine-Catalyzed Benzylation Reaction of 1,3-Dicarbonyl Compounds
2537
Table 2 Reaction of Various Benzylic Alcohols or Esters with Pentanedionesa (continued)
Entry
6
1
2
Time (h) Product
Yield (%)b
O
O
OAc
2a
1
3f
99c
Br
1f
Br
O
O
OAc
7
8
2a
2a
1
3g
3h
95c
1g
OH
2
O
85c
91c
Fe
Fe
O
1h
1i
O
OAc
OAc
9
2a
2a
4
3i
3j
O
OH
c
O2N
10
20
1
–
–
1j
O
O
O
O
O
11
12
1a
3k
3l
98 (5:4)e
Ph
Ph
2b
O
O
Ph
O
1a
1
4
99
Ph
Ph
Ph
2c
O
O
O
13
1a
3m
89 (3:2)f
O
2d
O
O
O
O
O
14
15
1a
1a
2
4
3n
3o
92 (1:1)e,g
O
2e
OH
O
O
56
2f
O
a All reactions were carried out with 1 (0.5 mmol), 1,3-dicarbonyl compounds 2 (1 mmol), and I2 (0.05 mmol) at 80 °C in MeNO2 (2 mL).
b Isolated yield.
c The amount of 2 mmol of 2a was used.
d The amount of 5 mmol of 1a was used.
e The ratio of two diastereomers was determined by 1H NMR spectroscopy.
f Two diastereomers were isolated, respectively, from the mixture by preparative TLC.
g The amount of 2 mmol of 2e was used.
Synlett 2008, No. 16, 2535–2539 © Thieme Stuttgart · New York

2538
Z. Li et al.
LETTER
20.7. ESI-MS: m/z = 261.1 [M + Na+].
Supporting Information for this article is available online at
Compound 3c: 1H NMR (400 MHz, CDCl3): d = 7.12–7.08
(m, 2 H), 6.84–6.82 (m, 2 H), 3.98 (d, J = 11.3 Hz, 1 H), 3.78
(s, 3 H), 3.57–3.53 (m, 1 H), 2.26 (s, 3 H), 1.84 (s, 3 H), 1.18
(d, J = 6.9 Hz, 3 H). 13C NMR (100 MHz, CDCl3):
d = 203.6, 203.5, 158.4, 134.9, 128.2, 114.1, 76.9, 55.1,
39.7, 29.8, 29.6, 20.9. ESI-MS: m/z = 257.0 [M + Na+].
Compound 3d: 1H NMR (400 MHz, CDCl3): d = 7.22–7.18
(m, 2 H), 7.14–7.12 (m, 1 H), 6.97 (d, J = 7.8 Hz, 2 H), 6.88
(s, 1 H), 6.69 (s, 1 H), 5.48 (d, J = 11.7 Hz, 1 H), 4.94 (d,
J = 11.7 Hz, 1 H), 2.55 (s, 3 H), 2.29 (s, 3 H), 2.20 (s, 3 H),
1.99 (s, 3 H), 1.83 (s, 3 H). 13C NMR (100 MHz, CDCl3):
d = 203.7, 203.0, 141.1, 137.3, 136.7, 136.7, 134.9, 131.3,
129.6, 128.4, 126.9, 126.1, 70.5, 43.0, 30.3, 28.9, 21.7, 20.9,
20.7. Anal. Calcd for: C, 81.78; H, 7.84. Found: C, 81.74; H,
7.93.
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
The authors thank the National Natural Science Foundation of Chi-
na (No. 20772114 and 20702050), the Innovation Fund for Outstan-
ding Scholar of Henan Province (No. 0621001100), and Zhengzhou
University for financial support.
References and Notes
(1) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102,
1731.
(2) Kischel, J.; Mertins, K.; Michalik, D.; Zapf, A.; Beller, M.
Adv. Synth. Catal. 2007, 349, 865; and references cited
therein.
(3) Comprehensive Organic Synthesis, Vol. 3; Trost, B. M.;
Fleming, I., Eds.; Pergamon Press: Oxford, 1991.
(4) (a) Trost, B. M. Acc. Chem. Res. 2002, 35, 695. (b) Yao,
X.; Li, C.-J. J. Am. Chem. Soc. 2004, 126, 6884.
(5) (a) Nishibayashi, Y.; Wakiji, I.; Ishii, Y.; Uemura, S.; Hidai,
M. J. Am. Chem. Soc. 2001, 123, 3393. (b) Nishibayashi,
Y.; Yoshikawa, M.; Inada, Y.; Hidai, M.; Uemura, S. J. Org.
Chem. 2004, 69, 3408.
(6) Manabe, K.; Kobayashi, S. Org. Lett. 2003, 5, 3241.
(7) Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem. Int. Ed.
2006, 45, 793.
(8) For Bi-catalyzed, see: (a) Rueping, M.; Nachtsheim, B. J.;
Ieawsuwan, W. Adv. Synth. Catal. 2006, 348, 1033.
(b) Rueping, M.; Nachtsheim, B. J.; Kuenkel, A. Org. Lett.
2007, 9, 825.
(9) Noji, M.; Konno, Y.; Ishii, K. J. Org. Chem. 2007, 72, 5161.
(10) (a) Sanz, R.; Miguel, D.; Martinez, A.; Alvarez-Gutierrez,
J. M.; Rodriguez, F. Org. Lett. 2007, 9, 2027. (b) Sanz, R.;
Miguel, D.; Martinez, A.; Alvarez-Gutierrez, J. M.;
Rodriguez, F. Org. Lett. 2007, 9, 727.
(11) (a) Deka, N.; Kalita, D. J.; Borah, R.; Sarma, J. C. J. Org.
Chem. 1997, 62, 1563. (b) Firouzabadi, H.; Iranpoor, N.;
Hazarkhani, H. J. Org. Chem. 2001, 66, 7527. (c) Chu,
C.-M.; Huang, W.-J.; Liu, J.-T.; Yao, C.-F. Tetrahedron
Lett. 2007, 48, 6881; and references cited therein.
(12) General Procedure
Compound 3e: 1H NMR (400 MHz, CDCl3): d = 7.22–7.18
(m, 2 H), 7.14–7.11 (m, 1 H), 6.94 (d, J = 7.9 Hz, 2 H), 6.88
(s, 1 H), 5.67 (d, J = 11.3 Hz, 1 H), 4.94 (d, J = 11.3 Hz, 1
H), 2.46 (s, 3 H), 2.34 (s, 3 H), 2.28 (s, 3 H), 2.08 (s, 3 H),
1.88 (s, 3 H), 1.72 (s, 3 H). 13C NMR (100 MHz, CDCl3):
d = 203.8, 202.8, 142.0, 137.9, 135.3, 134.1, 133.8, 133.1,
131.3, 128.5, 126.8, 126.0, 71.9, 43.3, 29.8, 29.2, 21.5, 20.4,
17.1, 16.8. Anal. Calcd for: C, 81.95; H, 8.13. Found: C,
81.64; H, 8.37.
Compound 3f: 1H NMR (400 MHz, CDCl3): d = 7.32 (d,
J = 8.4 Hz, 2 H), 6.88 (s, 1 H), 6.84 (d, J = 8.3 Hz, 2 H), 6.71
(s, 1 H), 5.40 (d, J = 11.6 Hz, 1 H), 4.89 (d, J = 11.6 Hz, 1
H), 2.53 (s, 3 H), 2.29 (s, 3 H), 2.21 (s, 3 H), 1.98 (s, 3 H),
1.83 (s, 3 H). 13C NMR (100 MHz, CDCl3): d = 203.3, 202.6,
140.4, 137.3, 137.0, 136.6, 134.4, 131.5 (2C), 129.8, 128.8,
120.0, 70.4, 42.5, 30.3, 29.0, 21.7, 21.0, 20.7. Anal. Calcd
for: C, 65.12; H, 5.99. Found: C, 65.03; H, 6.04.
Compound 3g: 1H NMR (400 MHz, CDCl3): d = 7.01 (d,
J = 8.0 Hz, 2 H), 6.87–6.85 (m, 3 H), 6.69 (s, 1 H), 5.42 (d,
J = 11.7 Hz, 1 H), 4.92 (d, J = 11.7 Hz, 1 H), 2.55 (s, 3 H),
2.29 (s, 3 H), 2.26 (s, 3 H), 2.21 (s, 3 H), 2.01 (s, 3 H), 1.82
(s, 3 H). 13C NMR (100 MHz, CDCl3): d = 204.0, 203.2,
138.1, 137.3, 136.8, 136.7, 135.7, 135.1, 131.4, 129.7,
129.1, 126.9, 70.8, 42.9, 30.2, 28.9, 21.8, 21.0, 20.9, 20.8.
ESI-MS: m/z = 345.2 [M + Na+].
Compound 3h: 1H NMR (400 MHz, CDCl3): d = 4.19 (s, 5
H), 4.16–4.05 (m, 4 H), 3.59 (d, J = 9.7 Hz, 1 H), 3.29–3.25
(m, 1 H), 2.15 (s, 3 H), 1.87 (s, 3 H), 1.26 (d, J = 6.5 Hz, 3
H). 13C NMR (100 MHz, CDCl3): d = 204.5, 203.4, 91.7,
77.3, 68.8, 68.7, 67.8, 67.6, 65.4, 34.6, 32.0, 29.4, 18.3.
Anal. Calcd for: C, 65.40; H, 6.46. Found: C, 65.40; H, 6.54.
Compound 3i: 1H NMR (400 MHz, CDCl3): d = 7.50 (s, 1
H), 7.40 (s, 5 H), 2.43 (s, 3 H), 2.29 (s, 3 H). 13C NMR (100
MHz, CDCl3): d = 205.7, 196.6, 142.7, 139.9, 132.8, 130.7,
129.7, 129.0, 31.7, 26.5. ESI-MS: m/z = 211.0 [M + Na+].
Compound 3k: 1H NMR (400 MHz, CDCl3): d = 8.10–8.08
(m, 1 H), 7.49–7.04 (m, 9 H), 4.94 (d, J = 10.9 Hz, 1 H),
3.90–3.86 (m, 1 H), 1.90 (s, 3 H), 1.21 (d, J = 6.8 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 203.1, 195.2, 143.2,
137.2, 133.9, 128.9, 128.8, 128.5, 127.5, 127.0, 70.8, 41.0,
28.0, 21.6.
All procedures were carried out under air. To a 10 mL flask,
benzylic alcohols or benzylic acetates (0.5 mmol), 1,3-
dicarbonyl compounds, MeNO2 (2 mL), and molecular
iodine (13 mg, 0.05 mmol) were added successively. The
mixture was magnetically stirred at 80 °C. After completion
of the reaction (by GC), the solvent was concentrated under
reduced pressure by an aspirator, and the residue was
purified by preparative TLC using PE–EtOAc (10:1) as an
eluent to afford products.
(13) Selected Spectroscopic Data
All prepared compounds were known and identified by 1H
NMR, 13C NMR, and MS.
Compound 3a: 1H NMR (400 MHz, CDCl3): d = 7.31–7.27
(m, 2 H), 7.22–7.18 (m, 3 H), 4.04 (d, J = 11.3 Hz, 1 H),
3.63–3.55 (m, 1 H), 2.56 (s, 3 H), 1.83 (s, 3 H), 1.21 (d,
J = 6.9 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 203.5,
203.4, 143.0, 128.8, 127.3, 127.0, 76.7, 40.4, 29.8, 29.7,
20.8. ESI-MS: m/z = 227.0 [M + Na+].
Another diastereomer: 1H NMR (400 MHz, CDCl3):
d = 7.80–7.78 (m, 1 H), 7.49–7.04 (m, 9 H), 4.50 (d, J = 11.0
Hz, 1 H), 3.90–3.86 (m, 1 H), 2.23 (s, 3 H), 1.30 (d, J = 7.0
Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 203.6, 195.2,
143.5, 137.0, 133.4, 128.9, 128.6, 128.5, 127.4, 126.6, 71.4,
40.4, 27.6, 20.3.
Compound 3b: 1H NMR (400 MHz, CDCl3): d = 7.28–7.25
(m, 2 H), 7.15–7.12 (m, 2 H), 4.00 (d, J = 11.3 Hz, 1 H),
3.61–3.57 (m, 1 H), 2.26 (s, 3 H), 1.87 (s, 3 H), 1.19 (d,
J = 6.9 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 203.0,
202.9, 141.5, 132.6, 128.9, 128.6, 76.5, 39.6, 29.8, 29.6,
Compound 3l: 1H NMR (400 MHz, CDCl3): d = 8.05–8.02
(m, 2 H), 7.74 (d, J = 7.4 Hz, 2 H), 7.57–7.53 (m, 1 H), 7.46–
7.39 (m, 3 H), 7.29–7.25 (m, 4 H), 7.19–7.15 (m, 2 H), 7.09–
7.05 (m, 1 H), 5.61 (d, J = 10.1 Hz, 1 H), 4.10–4.06 (m, 1 H),
Synlett 2008, No. 16, 2535–2539 © Thieme Stuttgart · New York

LETTER
Iodine-Catalyzed Benzylation Reaction of 1,3-Dicarbonyl Compounds
2539
1.34 (d, J = 7.0 Hz, 3 H). 13C NMR (100 MHz, CDCl3):
d = 195.0, 194.6, 143.8, 137.2, 136.9, 133.6, 133.0, 128.9,
128.8, 128.5, 128.5, 128.4, 127.7, 126.6, 64.9, 41.2, 20.2.
ESI-MS: m/z = 351.3 [M + Na+].
2.30 (s, 3 H), 1.30 (d, J = 6.9 Hz, 3 H), 1.29 (t, J = 7.2 Hz, 3
H). 13C NMR (100 MHz, CDCl3): d = 202.4, 168.2, 143.3,
128.4, 127.5, 126.8, 67.6, 61.1, 39.8, 29.5, 20.4, 13.7. ESI-
MS: m/z = 257.1 [M + Na+].
Compound 3m: 1H NMR (400 MHz, CDCl3): d = 7.27–7.20
(m, 3 H), 7.14–7.12 (m, 2 H), 3.79 (q, J = 7.0 Hz, 1 H), 2.53–
2.46 (m, 2 H), 2.19–2.10 (m, 1 H), 1.97–1.92 (m, 1 H), 1.86
(s, 3 H), 1.84–1.79 (m, 2 H), 1.67–1.55 (m, 2 H), 1.30 (d,
J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d = 208.6,
205.9, 141.4, 128.7, 128.3, 127.0, 72.1, 42.7, 42.4, 28.2,
26.7, 25.9, 22.2, 17.4. ESI-MS: m/z = 267.1 [M + Na+].
Another diastereomer: 1H NMR (400 MHz, CDCl3):
d = 7.28–7.24 (m, 4 H), 7.21–7.19 (m, 1 H), 3.89 (q, J = 7.4
Hz, 1 H), 2.38–2.34 (m, 2 H), 2.16–2.07 (m, 1 H), 2.12 (s, 3
H), 1.67–1.65 (m, 1 H), 1.63–1.60 (m, 1 H), 1.47–1.43 (m, 1
H), 1.42–1.40 (m, 2 H), 1.16 (d, J = 7.4 Hz, 3 H). 13C NMR
(100 MHz, CDCl3): d = 209.2, 205.4, 141.9, 129.9, 127.8,
126.7, 72.1, 42.3, 41.5, 29.4, 27.1, 25.5, 21.9, 16.2. ESI-MS:
m/z = 267.1 [M + Na+].
Compound 3o: 1H NMR (400 MHz, CDCl3): d = 7.35–7.32
(m, 2 H), 7.28–7.25 (m, 3 H), 5.27 (s, 1 H), 5.22–5.18 (q,
J = 6.4 Hz, 1 H), 2.47–2.43 (m, 2 H), 2.30–2.26 (m, 2 H),
1.98–1.90 (m, 2 H), 1.57 (d, J = 6.4 Hz, 3 H). 13C NMR (100
MHz, CDCl3): d = 199.7, 176.5, 141.3, 128.8, 128.0, 125.3,
104.6, 76.6, 36.6, 29.3, 23.6, 21.1.
Compound 5a: 1H NMR (400 MHz, CDCl3): d = 7.26–7.21
(m, 2 H), 7.17–7.12 (m, 3 H), 6.81 (s, 2 H), 4.63 (q, J = 7.3
Hz, 1 H), 2.25 (s, 3 H), 2.10 (s, 6 H), 1.64 (d, J = 7.3 Hz, 3
H). 13C NMR (100 MHz, CDCl3): d = 145.5, 140.1, 136.6,
135.4, 130.0, 128.2, 126.9, 125.3, 37.9, 21.1, 20.8, 16.9.
Compound 5b: 1H NMR (400 MHz, CDCl3): d = 7.28–7.21
(m, 4 H), 7.17–7.14 (m, 1 H), 5.83 (s, 1 H), 3.89 (q, J = 7.2
Hz, 1 H), 2.20 (s, 3 H), 2.14 (s, 3 H), 1.50 (d, J = 7.3 Hz, 3
H). 13C NMR (100 MHz, CDCl3): d = 149.2, 146.6, 144.7,
128.4, 127.1, 125.9, 124.1, 106.0, 35.6, 22.1, 13.6, 11.7.
Compound 5c: 1H NMR (400 MHz, CDCl3): d = 7.27–7.23
(m, 2 H), 7.19–7.12 (m, 3 H), 6.50 (s, 1 H), 4.08 (q, J = 7.2
Hz, 1 H), 2.35 (s, 3 H), 2.25 (s, 3 H), 1.54 (d, J = 7.2 Hz, 3
H). 13C NMR (100 MHz, CDCl3): d = 146.3, 141.5, 135.1,
130.2, 128.4, 127.3, 125.9, 125.3, 38.3, 22.1, 15.4, 13.0.
ESI-MS: m/z = 239.4 [M + Na+].
Compound 3n: 1H NMR (400 MHz, CDCl3): d = 7.30–7.26
(m, 2 H), 7.23–7.7.19 (m, 3 H), 3.87 (q, J = 7.1 Hz, 2 H),
3.81–3.73 (m, 1 H), 3.57–3.52 (m, 1 H), 1.93 (s, 3 H), 1.23
(d, J = 6.9 Hz, 3 H), 0.94 (t, J = 7.2 Hz, 3 H). 13C NMR (100
MHz, CDCl3): d = 202.4, 168.6, 143.1, 128.7, 127.4, 126.9,
67.0, 61.5, 40.1, 29.9, 20.6, 14.1. ESI-MS: m/z = 257.1 [M +
Na+].
Another diastereomer: 1H NMR (400 MHz, CDCl3):
d = 7.30–7.26 (m, 2 H), 7.23–7.7.19 (m, 3 H), 4.23 (q,
J = 7.1 Hz, 2 H), 3.81–3.73 (m, 1 H), 3.57–3.52 (m, 1 H),
(14) During the preparation of this manuscript, a similar result
was reported, see: Srihari, P.; Bhunia, D. C.; Sreedhar, P.;
Yadav, J. S. Synlett 2008, 1045.
Synlett 2008, No. 16, 2535–2539 © Thieme Stuttgart · New York