Stereoselective chlorination of new type baylis-hillman adducts by bis(Trichloromethyl)carbonate with the aid of catalytic amount of triphenylphosphine oxide

Article abstract of DOI:10.2174/157017810791112469

The chlorination of the new type Baylis-Hillman adducts by bis(trichloromethyl)carbonate (BTC) with the aid of catalytic amount of triphenylphosphine oxide (Ph₃PO) was achieved with high yields and high stereoselectivities. A plausible mechanis

Full text of DOI:10.2174/157017810791112469

Letters in Organic Chemistry, 2010, 7, 229-234
229
Stereoselective Chlorination of New Type Baylis-Hillman Adducts by
bis(Trichloromethyl)carbonate with the Aid of Catalytic Amount of
Triphenylphosphine Oxide
Weihui Zhong*, Lingjuan Hong and Yemin Zheng
Key Laboratory of Pharmaceutical Engineering (Ministry of Education), College of Pharmaceutical Sciences, Zhejiang
University of Technology, Hangzhou 310014, P.R. China
Received November 19, 2009: Revised January 16, 2010: Accepted January 22, 2010
Abstract: The chlorination of the new type Baylis-Hillman adducts by bis(trichloromethyl)carbonate (BTC) with the aid
of catalytic amount of triphenylphosphine oxide (Ph3PO) was achieved with high yields and high stereoselectivities. A
plausible mechanism is presented.
Keywords: New type Baylis-Hillman adducts, chlorination, triphenylphosphine oxide, bis(trichloromethyl)carbonate,
stereoselectivity.
INTRODUCTION
RESULT AND DISCUSSION
Baylis-Hillman adducts have been successfully utilized
as valuable intermediates for stereoselective synthesis of
different multifunctional molecules [1,2]. In particular, the
halogenation of Baylis-Hillman adducts has attracted much
attention in recent years [3,4], since they can be employed
for the synthesis of various natural bioactive products and
their analogues, such as micanecic acid, kizanolide, rennin
inhibitor A-72517, ꢀ-lactams, ꢁ-methylene-ꢂ-butyrolactones
and flavonoids [5]. To date, various reagents have been used
to promote the conversion to corresponding chlorides, such
as strong acids (HCl/H2SO4) [6], organic acid halides (MsCl,
oxalyl chloride [7]), complex systems (Cl3CCONH2-Ph3P,
HCA-PPh3 complex, NCS/Me2S, POCl3/DMF, PPh3/CCl4,
TCT/DMF) [8], Lewis acid (iron(III) or indium(III) chloride,
AlCl3, TiCl4) [9], [bmim][HSO4] [10] and Silica chloride
[11]. However, most of reported methods suffered from
certain limitations, including the use of concentrated acids
[6], the need to use O-acetyl derivatives of Baylis-Hillman
adducts [12] as well as requirement for complex
experimental procedures.
Initially, the Baylis-Hillman adduct [3] (Z)-methyl-
5-chloro-5-(4-fluorophenyl)-3-hydroxy-2-methylenepent-4-
enoate 1a was subjected to chlorination with theꢀVilsmeier
reagent derived from BTC/DMF system instead of
traditional POCl3/DMF system (Scheme 1). Unfortunately,
almost no stereoselectivity was observed. The products
(2Z,4Z)-methyl-5-chloro-2-(chloromethyl)-5-(4-fluorophenyl)
penta-2,4-dienoate 2a and its isomer (2E,4Z)-3a were
isolated with 46% and 44%, respectively.
Stimulated
by
our
previous
finding
that
dichlorotriphenylphosphine (PPh3Cl2) can be formed from
Ph3PO and BTC [14], we examined the activity of PPh3Cl2
as chlorination reagent for the conversion of 1a into the
corresponding allyl chlorides [15] (Scheme 2). Surprisingly,
treatment of the new type Baylis-Hillman adduct 1a with
PPh3Cl2 generated in situ could afford 2a in higher yield and
stereoselectivity.
One drawback of this reaction was related to the fact that
Ph3PCl2 is quite sensitive to water and difficult to detect.
Considering that BTC is an efficient chlorination reagent in
organic synthesis [16], we reasoned that a reaction cycle
could be established between Ph3PO and PPh3Cl2 in the
above reaction. To our delight, when the protocol was
applied, 2 were successfully obtained (Fig. 1), indicating that
the reaction cycle could proceed smoothly.
Recently we successfully prepared a new type Baylis-
Hillman adducts via Vilsmeier reaction of ketones with
bis(trichloromethyl)carbonate (BTC)/DMF system to
construct chlorovinyl aldehydes, followed by sonochemical
Baylis-Hillman reaction under solvent-free condition [3]. In
continuation of our research on the application of Baylis-
Hillman adducts for construction of heterocylces [13], we
herein described a high stereroselective chlorization of the
new type Baylis-Hillman adducts to the corresponding allyl
chlorides by using BTC with the aid of catalytic amount of
triphenylphosphine oxide (Ph3PO).
Subsequently, we found that an experiment carried out
with a catalytic amount (10%) of Ph3PO did not affect the
yield (Table 1, entry 6). However, the reaction did not take
place with 5 mmol% of Ph3PO (Table 1, entry 7).
A plausible reaction mechanism [2,14] is shown in
Scheme 3. Firstly, the reaction of BTC with PPh3O catalyzed
by Et3N gives intermediate A, which then reacts with the
Baylis-Hillman adduct to give the alkoxyphosphonium salt
B. Chloride nucleophilic attack leads to the trisubstituted
allyl chloride with regeneration of Ph3PO.
*Address correspondence to this author at the Key Laboratory of
Pharmaceutical Engineering (Ministry of Education), College of
Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou
310014, P.R. China; Fax: (0086)57188320752;
E-mail: pharmlab@zjut.edu.cn
1570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

230 Letters in Organic Chemistry, 2010, Vol. 7, No. 3
Zhong et al.
Cl
OH
Cl
DABCO
COOMe
COOMe
CHO
+
50 oC
F
solvent-free
F
1a
H
Cl
Cl
OH
CO2Me
CO2Me
BTC/DMF
CH2Cl2
r.t., 1h
H
Cl
F
F
1a
2a (Z, Z)-isomer, 46%
3a (E, Z)-isomer, 44%
Scheme 1.
ꢀ
O
Et3N
O
PPh3
+
Ph3PCl2
Cl
CO2
+
Cl3CO
Cl
OCCl3
CH2Cl2
H
OH
CO2Me
CO2Me
PPh3Cl2
CH2Cl2
r.t., 40min
H
Cl
F
F
1a
2a (Z, Z)-isomer, 89%
3a (E, Z)-isomer, <5%
Scheme 2.
Cl
EWG
R1
Ph3PO
BTC
CO2
R2
Cl
2
Cl
OH
EWG
Ph3PCl2
R1
R2
1
R1 = aryl, alkyl, R2 = H, CH3 or (CH2)2
EWG = CO2Me, CO2Et, CN et al
Fig. (1).
Table 1. Chlorination of Compound 1a Under Various Conditionsa
Entry
Ph3PO (mmol%)
Temp. (oC)
Time
Yield of 2a (%)b
1
2
3
4
5
6
7
100
50
50
30
20
10
5
0
40 min
2 h
89
54c
89
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
5 h
8 h
88
10 h
10 h
2 days
88
89
Tracec
aReaction conditions: 1a (1 mmol), Et3N (3 drops), BTC (0.67 mmol), solvents (3 mL) were used. bIsolated yields based on 1a. c1a was recovered.

Stereoselective Chlorination of New Type Baylis-Hillman Adducts
Letters in Organic Chemistry, 2010, Vol. 7, No. 3
231
O
Cl3CO
OCCl3
CO2
OH
[Ph3PCl] Cl
+
O
PPh3
Et3N
A
Cl
Cl
EWG
R1
Cl
H
EWG
Cl
R1
R2
PPh3
R2
1
Cl
O
2
EWG
Cl
R1 = aryl, alkyl
R2 = H, CH3 or (CH2)2
EWG = CO2Me, CO2Et, CN et al
R1
R2
B
Scheme 3.
With the optimized conditions in hand, we then expanded
the scope of the reaction and verified the compatibility with
functional groups and structural features. According to Table
2, the substrates with ester moiety could provide the desired
(Z,Z)-isomers with high stereoselectivities in good yields. In
the case of nitrile moiety, (E,Z)-isomer 3n was isolated
(Table 2, entry 14). Among substrates bearing aryl groups,
the yields of those containing electron-donating (Table 2,
entry 10) were slightly higher than electron-withdrawing
groups (Table 2, entry 3), but there was not much difference
respecting reaction time and stereoselectivities.
Further, we investigated the chlorination of methyl 2-((2-
chloro-6-methylquinolin-3-yl)(hydroxy)methyl)acrylate 1o
by BTC with the aid of 10 mmol% Ph3PO (Scheme 4).
Gratifyingly, the desired product (Z)-2o was successfully
isolated in good yield (87%) with high stereoselectivity.
The stereochemistry of the conversion has been
1
confirmed by H NMR, and NOE effect. 1H NMR spectra of
2a showed typical chemical shifts of Ha (7.90 ppm) and Hb
(7.04 ppm), while 7.49 ppm of Ha and 7.99 ppm of Hb were
revealed in compound 3a. It was found that large NOE
existed between Hb and Hc of 2a, while in the case of 3a,
Table 2. The Chlorination of New Type Baylis-Hillman Adductsa
Entry
R1
R2
EWG
Time (h)
Product
Yield (%)b
1
2
1a: p-FC6H4
1b: p-ClC6H4
1c: m-ClC6H4
1d: m-ClC6H4
1e: p-NO2C6H4
1f: C6H5
H
H
H
H
H
H
H
H
H
H
CO2Me
CO2Me
CO2Me
CO2Et
10
10
10
10
11
10
10
9
2a
2b
2c
2d
2e
2f
89
89
90
88
86
90
89
91
90
93
3
4
5
CO2Me
CO2Me
CO2Et
6
7
1g: C6H5
2g
2h
2i
8
1h: p-MeC6H4
1i: p-MeC6H4
1j: p-MeOC6H4
CO2Me
CO2Et
9
9
10
CO2Me
8
2j
11
12
CO2Me
CO2Me
10
15
2k
2l
89
80
1k:
H
1l:
13
14
1m: C6H5
1n: C6H5
CH3
H
CO2Me
CN
10
10
2m
3nc
85
88
aReaction conditions: 1 (1 mmol), Et3N (3 drops), BTC (0.67 mmol), CH2Cl2 (3 mL) were used. bIsolated yields based on 1. cThe conformation of 3n is (E,Z)-style.

232 Letters in Organic Chemistry, 2010, Vol. 7, No. 3
Zhong et al.
CHO
Cl
DABCO
CO2Me
BTC/DMF
CH2Cl2
N
H
O
N
OH
Cl
CO2Me
Cl
CO2Me
BTC/PPh3O
CH2Cl2
r.t., 9h
N
Cl
N
1o
2o ( 87%)
Scheme 4.
7.49 ppm
Cl
7.90 ppm
Ha
large NOE
Cl
CO2Me
Hc
Ha
Hb
Hc
Cl
F
Cl
Hb
CO2Me
F
7.04 ppm
large NOE
7.99 ppm
3a
2a
Fig. (2).
evident NOE was observed between Ha and Hc (Fig. 2).
Integrated with the hydrogen NOE effect in benzene ring, it
could be readily identified that compound 2a should be
(Z,Z)-isomer while compound 3a should be (E,Z)-isomer as
the major configuration in this case.
(2Z,4Z)-Methyl-5-chloro-2-(chloromethyl)-5-(4-fluoro-
phenyl)penta-2,4-dienoate (2a); typical procedure
To a mixture of (Z)-methyl 5-chloro-5-(4-fluorophenyl)-
3-hydroxy-2-methylenepent- 4-enoate 1a (270.7 mg, 1
mmol), Ph3PO (27.8 mg, 0.1 mmol) and Et3N (10.1 mg, 0.1
mmol) in CH2Cl2 (3 mL), was added dropwise a solution of
BTC (199.0 mg, 0.67 mmol) in CH2Cl2 (2 mL) at 0 °C. The
mixture was stirred at room temperature for 10 h. Then
reaction was quenched with water (5 mL) and extracted with
CH2Cl2 (3 ꢁ20 mL). The combined organic layer was
successively washed with brine, dried over anhydrous
Na2SO4 and concentrated in vacuum to obtain a crude
product, which was purified by flash column
chromatography on silica gel (petroleum ether : ethyl acetate
= 20:1 as eluent) to give the desired product 2a (257.2 mg,
yield: 89%). Light yellow solid, mp: 87.0-88.5 oC. IR (KBr)
CONCLUSION
In summary, we have successfully developed a new
method for the synthesis of allyl chlorides by using
Ph3PO/BTC system. The mild cycle reaction condition,
convenient operational procedure, high stereoselectivity and
good yield were the notable advantages. The application of
the new type Baylis-Hillman adducts and chlorides have
been developing in our lab.
ꢀ
max: 3132, 1670, 1507, 1152, 833 cm-1. 1H NMR (400 MHz,
EXPERIMENTAL
General
CDCl3) ꢁ: 3.87 (s, 3 H), 4.51 (s, 2 H), 7.04 (d, J = 11.2 Hz,1
H), 7.12 (t, J = 8.8 Hz, 2 H), 7.71-7.74 (m, 2 H), 7.90 (d, J =
11.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3) ꢁ: 37.1, 52.1,
115.5(2C), 119.1, 128.8(2C), 129.1, 132.9, 137.3, 141.7,
163.6 (d, JCF = 250.6 Hz), 165.9. MS (EI) m/z 290 (M+2, 2),
288 (M+, 7), 255 (30), 253 (M-Cl, 100). HRMS (EI) m/z
calcd for C13H11Cl2FO2: 288.0120; found: 288.0131.
Melting points were determined with a Büchi B-540
capillary melting point apparatus and are uncorrected.
Infrared spectra were recorded on a Thermo Nicolet Avatar-
1
370 instrument, using samples as KBr plates. H NMR and
13C NMR spectra were measured in CDCl3 with
tetramethylsilane (TMS, ꢀ = 0) as an internal standard on a
Varian-400 MHz spectrometer at 400 and 100 MHz or
Bruker Avance DRX 500 spectrometer at 500 and 125 MHz.
Chemical shifts (ꢀ) were expressed in ppm and coupling
constants J given in Hz. Mass spectra were obtained with a
Trace DSQ mass spectrometer. High resolution mass spectra
were recorded using an Agilent 6210 TOF mass
spectrometer.
(2Z,4Z)-Methyl-5-chloro-2-(chloromethyl)-5-(4-chloro-
phenyl)penta-2,4-dienoate (2b)
o
Light yellow solid, mp: 108.3-109.9 C. IR (KBr) ꢀmax
:
1
3132, 1712, 1435, 1180, 833 cm-1. H NMR (400 MHz,
CDCl3) ꢁ: 3.87 (s, 3 H), 4.51 (s, 2 H), 7.08 (d, J = 11.6Hz, 1
H), 7.40 (d, J = 8.8Hz, 2 H), 7.67 (d, J = 8.8Hz, 2 H), 7.89
(d, J = 11.6Hz, 1 H). 13C NMR (100 MHz, CDCl3) ꢁ: 37.7,

Stereoselective Chlorination of New Type Baylis-Hillman Adducts
Letters in Organic Chemistry, 2010, Vol. 7, No. 3
233
52.8, 120.1, 128.6(2C), 129.2(2C), 130.1, 135.7, 136.8,
137.7, 142.2, 166.5. MS (EI) m/z 304 (M+, 2), 271 (66), 269
(M-Cl, 100), 209 (28). HRMS (EI) m/z calcd for
C13H11Cl3O2: 303.9825; found: 303.9808.
128.6(2C), 129.6(2C), 130.3, 136.9, 137.4, 143.1, 165.7. MS
(EI) m/z 286 (M+2, 5), 284 (M+, 9), 251 (M-Cl, 40), 249 (75),
185 (100). HRMS (EI) m/z calcd for C14H14Cl2O2: 284.0371;
found: 284.0360.
(2Z,4Z)-Methyl-5-chloro-2-(chloromethyl)-5-(3-chloro-
phenyl)penta-2,4-dienoate (2c)
(2Z,4Z)-Methyl-5-chloro-2-(chloromethyl)-5-p-tolylpenta-
2,4-dienoate (2h)
o
o
Light yellow solid, mp: 99.2-100.9 C. IR (KBr) ꢀmax
:
Yellow solid, mp: 72.4-74.2 C. IR (KBr) ꢀmax: 3129,
3132, 1693, 1435, 1176, 784 cm-1. H NMR (400 MHz,
CDCl3) ꢁ: 3.88 (s, 3 H), 4.51 (s, 2 H), 7.10 (d, J = 11.2 Hz, 1
H), 7.35-7.42 (m, 2 H), 7.61 (d, J = 7.6 Hz, 1 H), 7.71 (s, 1
H), 7.89 (d, J = 11.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3)
ꢁ: 37.6, 52.8, 120.8, 125.5, 127.5, 130.2, 130.6(2C), 135.2,
137.5, 139.1, 141.8, 166.5. MS (EI) m/z 304 (M+, 2), 271
(66), 269 (M-Cl, 100), 209 (24). HRMS (EI) m/z calcd for
C13H11Cl3O2: 303.9825; found: 303.9840.
1720, 1603, 1430, 1169, 819 cm-1. H NMR (400 MHz,
1
1
CDCl3) ꢁ: 2.40 (s, 3 H), 3.86 (s, 3 H), 4.51 (s, 2 H), 7.08 (d,
J =11.6 Hz, 1 H), 7.24 (t, J = 8.4 Hz, 2 H), 7.63 (d, J = 8.4
Hz, 2 H), 7.93 (d, J = 11.6 Hz, 1 H). 13C NMR (100 MHz,
CDCl3) ꢁ: 21.3, 37.5, 52.4, 118.6, 128.8 (2C), 129.2,
129.4(2C), 134.2, 138.0, 140.9, 143.6, 166.3. MS (EI) m/z
284 (M+, 2), 251 (30), 249 (M-Cl, 100), 189 (57). HRMS
(EI) m/z calcd for C14H14Cl2O2: 284.0393; found: 284.0381.
(2Z,4Z)-Ethyl-5-chloro-2-(chloromethyl)-5-(3-chloro-
phenyl)penta-2,4-dienoate (2d)
(2Z,4Z)-Ethyl-5-chloro-2-(chloromethyl)-5-p-tolylpenta-
2,4-dienoate (2i)
o
o
Yellow solid, mp: 75.5-77.4 C. IR (KBr) ꢀmax: 3132,
Yellow solid, mp: 79.0-81.0 C. IR (KBr) ꢀmax: 3134,
1699, 1626, 1400, 1185, 788 cm-1. H NMR (400 MHz,
1699, 1599, 1182, 814 cm-1. 1H NMR (400 MHz, CDCl3) ꢁ:
1.37 (t, J = 6.8 Hz, 3 H), 2.40 (s, 3 H), 4.32 (dd, J = 14.4 Hz,
2 H), 4.51 (s, 2 H), 7.08 (d, J = 11.2 Hz, 1 H), 7.24 (t, J =
8.4 Hz, 2 H), 7.63 (d, J = 8.0 Hz, 2 H), 7.92 (d, J = 11.2 Hz,
1 H). 13C NMR (100 MHz, CDCl3) ꢁ: 14.2, 21.3, 37.6, 61.3,
118.6, 127.0(2C), 129.0, 129.3(2C), 134.1, 137.7, 140.9,
143.3, 165.8. MS (EI) m/z 298 (M+, 4), 265 (32), 263 (M-Cl,
100), 199 (91), 189 (31). HRMS (EI) m/z calcd for
C15H16Cl2O2: 298.0527; found: 298.0512.
1
CDCl3) ꢁ: 1.37 (t, J = 7.2 Hz, 3 H), 4.33 (dd, J = 14.4 Hz, 2
H), 4.51 (s, 2 H), 7.10 (d, J = 11.2 Hz, 1 H), 7.34-7.41 (m, 2
H), 7.60 (d, J = 7.6 Hz, 1 H), 7.70 (s, 1 H), 7.88 (d, J = 11.2
Hz, 1 H). 13C NMR (100 MHz, CDCl3) ꢁ: 14.2, 37.3, 61.5,
120.5, 125.1, 127.1, 129.8, 130.2, 130.6, 134.8, 136.8, 138.7,
141.1, 165.6. MS (EI) m/z 320 (M+, 5), 285 (M-Cl, 60), 283
(94), 221 (33), 219 (100). HRMS (EI) m/z calcd for
C14H13Cl3O2: 317.9981; found: 318.0002.
(2Z,4Z)-Methyl-5-chloro-2-(chloromethyl)-5-(4-nitro-
phenyl)penta-2,4-dienoate (2e)
(2Z,4Z)-Methyl-5-chloro-2-(chloromethyl)-5-(4-methoxy-
phenyl)penta-2,4-dienoate (2j)
o
o
Yellow solid, mp: 116.7-119.0 C. IR (KBr) ꢀmax: 3133,
Yellow solid, mp: 97.5-99.3 C. IR (KBr) ꢀmax: 3132,
1713, 1401, 1349, 1268, 845 cm-1. H NMR (400 MHz,
1700, 1594, 1178, 1084, 828 cm-1. H NMR (400 MHz,
1
1
CDCl3) ꢁ: 3.89 (s, 3 H), 4.53 (s, 2 H), 7.24 (d, J = 11.2 Hz, 1
H), 7.90 (q, J = 5.6 Hz, 3 H), 8.29 (d, J = 8.8Hz, 2 H). 13C
NMR (100 MHz, CDCl3) ꢁ: 37.1, 52.7, 122.6, 123.9(2C),
127.9(2C), 131.6, 136.6, 140.1, 142.6, 148.4, 165.9. MS (CI)
m/z 316 (M+1, 5), 282 (25), 280 (M-Cl, 75), 250 (34), 248
(100). HRMS (CI) m/z calcd for C13H11Cl2NO4: 315.0065;
found: 315.0043.
CDCl3) ꢁ: 3.86 (s, 6 H), 4.51 (s, 2 H), 6.94 (d, J = 8.8 Hz, 2
H), 7.02 (d, J = 11.2 Hz, 1 H), 7.69 (d, J = 8.8 Hz, 2 H),
7.92 (d, J = 11.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3) ꢁ:
38.0, 52.7, 55.8, 114.3(2C), 117.9, 128.5, 129.0(2C), 129.7,
138.5, 143.6, 161.8, 166.7. MS (EI) m/z 300 (M+, 8), 267
(38), 265 (M-Cl, 100), 233 (24), 231 (90). HRMS (EI) m/z
calcd for C14H14Cl2O3: 300.0320; found: 300.0339.
(2Z,4Z)-Methyl-2-(chloromethyl)-5-chloro-5-phenylpenta-
2,4-dienoate (2f)
(Z)-Methyl-3-(1-chloro-3,4-dihydronaphthalen-2-yl)-2-
(chloromethyl)acrylate (2k)
o
o
Light yellow solid, mp: 58.7-60.2 C. IR (KBr) ꢀmax
:
Yellow solid, mp: 70.3-71.8 C. IR (KBr) ꢀmax: 3132,
3133, 1712, 1612, 1176, 762 cm-1. H NMR (500 MHz,
CDCl3) ꢁ: 3.87 (s, 3 H), 4.51 (s, 2 H), 7.11 (d, J = 11.0 Hz, 1
H), 7.43-7.45 (m, 3 H), 7.73-7.74 (m, 2 H), 7.93 (d, J = 11.0
Hz, 1 H). 13C NMR (125 MHz, CDCl3) ꢁ: 37.5, 52.5, 119.5,
127.1(2C), 128.7(2C), 129.3, 130.5, 137.0, 137.8, 143.4,
166.3. MS (EI) m/z 270 (M+, 4), 237 (33), 235 (M-Cl, 100),
203 (23), 175 (64). HRMS (EI) m/z calcd for C13H12Cl2O2:
270.0214; found: 270.0205.
1713, 1432, 1287, 1153 cm-1. 1H NMR (400 MHz, CDCl3) ꢁ:
2.83-2.92 (m, 4 H), 3.87 (s, 3 H), 4.40 (s, 2 H), 7.17-7.19 (m,
1 H), 7.26-7.70 (m, 2 H), 7.68-7.70 (m, 1 H), 7.90 (s, 1 H).
13C NMR (100 MHz, CDCl3) ꢁ: 27.8, 28.4, 38.8, 52.5, 125.7,
127.0, 128.6, 129.5, 130.2, 132.3, 134.8, 136.7, 141.3, 166.6.
MS (CI) m/z 297 (M+1, 6), 263 (31), 261 (M-Cl, 100).
HRMS (CI) m/z calcd for C15H14Cl2O2:296.0371; found:
296.0388.
1
(2Z,4Z)-Ethyl-5-chloro-2-(chloromethyl)-5-phenylpenta-
2,4-dienoate (2g)
(2Z,4Z,6E)-Methyl-5-chloro-2-(chloromethyl)-7-phenyl-
hepta-2,4,6-trienoate (2l)
o
o
Light yellow solid, mp: 57.7-59.2 C. IR (KBr) ꢀmax
:
Light yellow solid, mp: 50.1-51.7 C. IR (KBr) ꢀmax
:
3132, 1700, 1605, 1400, 1264 cm-1. H NMR (400 MHz,
CDCl3) ꢁ: 1.36 (t, J = 7.2 Hz, 3 H), 4.31 (dd, J = 14.8 Hz, 2
H), 4.51 (s, 2 H), 7.11 (d, J = 11.6 Hz, 1 H), 7.41-7.43 (m, 3
H), 7.71-7.73 (m, 2 H), 7.92 (d, J = 11.6 Hz, 1 H). 13C NMR
(100 MHz, CDCl3) ꢁ: 14.2, 37.4, 61.4, 119.5, 128.4,
3383, 1711, 1636, 1405, 686 cm-1. H NMR (400 MHz,
CDCl3) ꢁ: 3.85 (s, 3 H), 4.49 (s, 2 H), 6.76 (d, J = 12.0 Hz, 1
H), 6.99 (d, J = 14.8 Hz, 1 H), 7.23-7.27 (m, 1 H), 7.31-7.40
(m, 3 H), 7.49-7.50 (m, 2 H), 7.91 (d, J = 12.0 Hz, 1 H). 13C
NMR (100 MHz, CDCl3) ꢁ: 37.1, 52.1, 123.0, 125.3,
1
1

234 Letters in Organic Chemistry, 2010, Vol. 7, No. 3
Zhong et al.
Damodar, K.; Ravikanth, B. A mild and efficient method for
chlorination of Baylis-Hillman adducts using PPh3/Cl3CCONH2).
Helv. Chim. Acta, 2007, 90, 2037; (d) Das, B.; Majhi, A.; Banerjee,
127.2(2C), 128.3, 128.6(2C), 129.0, 135.2, 136.4, 137.0,
141.6, 165.9. MS (EI) m/z 296 (M+, 2), 263 (21), 261 (M-Cl,
51), 247 (24), 201 (76) , 165 (100). HRMS (EI) m/z calcd for
C15H14Cl2O2: 296.0371; found: 296.0385.
J.; Chowdhury, N.; Venkateswarlu, K.
A highly efficient
stereoselective synthesis of (Z)-and (E)-allyl iodides from Baylis-
Hillman adducts. Tetrahedron Lett., 2005, 46, 7913.
Yuasa, Y.; Yuasa, Y.; Tsuruta, H. The synthesis of (S)-3-
acetylthio-2-benzylpropionic acid from (Z)-2-chloromethyl-3-
phenylprop-2-enoic acid by asymmetric hydrogenation: a chiral
building block of an enkephalinase Inhibitor. Aust. J. Chem., 1998,
51, 511.
Lawrence, N.J.; Crump, J.P.; McGown, A.T.; Hadfield, J.A.
Reaction of Baylis-Hillman products with Swern and Dess-Martin
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(2Z,4Z)-Methyl-5-chloro-2-(chloromethyl)-4-methyl-5-phe-
nylpenta-2,4-dienoate (2m)
[6]
o
Light yellow solid, mp: 65.1-67.0 C. IR (KBr) ꢀmax
:
3129, 1700, 1634, 1500, 1185 cm-1. H NMR (400 MHz,
CDCl3) ꢀ: 2.32 (s, 3 H), 3.72 (s, 3 H), 4.32 (s, 2 H), 7.32-
7.33 (m, 6 H). 13C NMR (100 MHz, CDCl3) ꢀ: 20.0, 38.4,
52.2, 127.9, 128.1(2C), 128.3, 128.8, 129.2(2C), 137.6,
137.7, 142.9, 166.3. MS (EI) m/z 285 (M+, 6), 251 (34), 249
(M-Cl, 100), 234 (21), 199 (47). HRMS (EI) m/z calcd for
C14H14Cl2O2: 284.0371; found: 284.0349.
1
[7]
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(a) Ameer, F.; Drewes, S.E.; Houston-McMillan, M.S.; Kaye, P.T.
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(a) Basavaiah, D.; Pandiaraju, S.; Padmaja, K. The Friedel-Crafts
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(2E,4Z)-5-Chloro-2-(chloromethyl)-5-phenylpenta-2,4-die-
nenitrile (3n)
o
Yellow solid, mp: 73.1-74.9 C. IR (KBr) ꢀmax: 3143,
2213, 1605, 1400, 1212 cm-1. 1H NMR (400 MHz, CDCl3) ꢀ:
4.28 (s, 2 H), 7.17 (d, J =11.2 Hz, 1 H), 7.42-7.50 (m, 4 H),
7.72-7.74 (m, 2 H). 13C NMR (100 MHz, CDCl3) ꢀ: 44.1,
112.0, 116.0, 120.4, 127.1(2C), 128.8(2C), 130.8, 136.1,
142.1, 143.5. MS (EI) m/z 239 (M+2, 28), 237 (M+, 43), 204
(31), 202 (M-Cl, 100), 166 (94). HRMS (EI) m/z calcd for
C12H9Cl2N: 237.0112; found: 237.0137.
[9]
(Z)-Methyl-2-(chloromethyl)-3-(6-methylquinolin-3-yl)
acrylate (2o)
o
Yellow solid, mp: 102.9-104.7 C. IR (KBr) ꢀmax: 3131,
1719, 1435, 1285, 1054 cm-1. 1H NMR (400 MHz, CDCl3) ꢀ:
2.57 (s, 3 H), 3.94 (s, 3 H), 4.40 (s, 2 H), 7.62-7.68 (m, 2
H),7.95 (d, J =8.8 Hz, 1 H), 8.04 (s, 1 H), 8.43 (s, 1 H). 13C
NMR (100 MHz, CDCl3) ꢀ: 21.6, 38.7, 52.7, 126.7, 127.2,
128.1, 131.3, 134.0, 138.0, 138.2, 138.9, 146.2, 148.7, 165.8.
MS (EI) m/z 309 (M+, 4), 276 (35), 274 (M-Cl, 100). HRMS
(EI) m/z calcd for C15H14ClNO2: 275.0713; found: 275.0732.
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