Amendment in titanium(IV) chloride and chalcogenide-promoted Baylis- Hillman reaction of aldehydes with α,β-unsaturated ketones

Article abstract of DOI:10.1016/S0040-4020(00)00384-7

The Baylis-Hillman reaction can be drastically affected by the reaction temperature and Lewis base. When the reaction was carried out at < -20°C using methyl sulfide as a Lewis base in the presence of titanium(IV) chloride, the chlorinated compound 1 was

Full text of DOI:10.1016/S0040-4020(00)00384-7

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4793±4797
Amendment in Titanium(IV) Chloride and
Chalcogenide-Promoted Baylis±Hillman Reaction of Aldehydes
with a,b-Unsaturated Ketones
*
Min Shi and Jian-Kang Jiang
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, People's Republic of China
Received 14 March 2000; revised 18 April 2000; accepted 8 May 2000
AbstractÐThe Baylis±Hillman reaction can be drastically affected by the reaction temperature and Lewis base. When the reaction was
carried out at ,2208C using methyl sul®de as a Lewis base in the presence of titanium(IV) chloride, the chlorinated compound 1 was
obtained as the major product. However, if the reaction was carried out at room temperature (108C) in the presence of titanium(IV) chloride,
the elimination compound 3 was formed as a major product. q 2000 Elsevier Science Ltd. All rights reserved.
The Baylis±Hillman reaction and related processes have
become increasingly important in synthetic organic
chemistry because the resulting adducts have an array of
multifunctional groups which can be subjected to numerous
transformations.1±5 This carbon-carbon bond formation is
typically catalyzed by DABCO or tertiary phosphines.
The major drawbacks of the Baylis±Hillman reaction are
its slow reaction rate and limited scope of substrates. To
overcome these shortcomings, many efforts have been
made to use Lewis acids or various other additives to
the reaction system in order to activate carbonyl electro-
philes.6±10 Among Lewis acids, TiCl4 has been successfully
utilized to promote the Baylis±Hillman reaction in the
presence of Lewis base catalysts.11 During our investigation
on the Baylis±Hillman process, we found that the reaction
products are considerably different from those reported so
far. First of all, we carried out the reaction of p-nitrobenzal-
dehyde with methyl vinyl ketone in the presence of TiCl4 at
2788C. No reaction occurred (Condition A). After adding
20 mol% of dimethyl sul®de (Me2S) as a Lewis base, the
reaction smoothly took place to give the chlorinated product
1a as the major product, rather than product 2a which is
usually considered as the product of Baylis±Hillman
reaction (Scheme 1). For many arylaldehydes having strong
electron-withdrawing group on the phenyl ring, the
reactions proceed quickly to give 1 with high yields using
a catalytic amount of Lewis base (20 mol%) at 2788C
(Condition B). However, other arylaldehydes or aliphatic
aldehydes need stoichiometric Lewis base and higher
temperature (2208C) (Condition C) to give the correspond-
ing product 1 in moderate yields also without formation of 2
(Table 1, entry 5±8). The diphenylthiophosphoramide can
also catalyze the reaction (Table 1, entry 9), but the reaction
rate is relatively slow. We also con®rmed that the compound
1 can be easily completely transformed to compound 2 by
treating with triethylamine or 1,8-diazabicyclo[5.4.0]undec-
7-ene (DBU) (Scheme 2). The puri®cation of 1 by prepara-
tive thin layer chromatography (TLC) also caused the
Scheme 1. a: Rˆp-NO2Ph; b: Rˆm-NO2Ph; c: Rˆp-CF3Ph; d: Rˆp-EtPh; e: RˆPh; f: Rˆp-ClPh; g: RˆCH3(CH2)3.
Keywords: titanium(IV) chloride; Baylis±Hillman reaction; halogenation; Z-keto allyl chloride.
* Corresponding author. Tel.: 186-21-641-633-00; fax: 186-21-641-662-63; e-mail: mshi@pub.sioc.ac.cn
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00384-7

4794
M. Shi, J.-K. Jiang / Tetrahedron 56 (2000) 4793±4797
Table 1. Baylis±Hillman reaction of aldehydes with methyl vinyl ketone in the presence of TiCl4 and Lewis base
Entry
R
Lewis base
none
SMe2
SMe2
SMe2
SMe2
SMe2
SMe2
SMe2
Conditions
Temp. (8C)
Time (h)
Yielda (%)/1
1
2
3
4
5
6
7
8
p-NO2Ph
p-NO2Ph
m-NO2Ph
p-CF3Ph
p-EtPh
Ph
p-ClPh
CH3(CH2)3
Ab
Bc
B
278
278
278
278
220
220
220
220
12
12
12
48
72
72
72
72
±
80
80
81
51
57
52
32
B
Cd
C
C
C
9
p-NO2Ph
B
278
24
40
a Isolated yields.
b Aldehyde/TiCl4ˆ1:1.4.
c Aldehyde/TiCl4/Lewis baseˆ1:1.4:0.2.
d Aldehyde/TiCl4/Lewis baseˆ1:1.4:1.
transformation of 1 to 2. Thus, rapid ¯ash column
chromatography is necessary in order to obtain the pure
product 1.
Baylis±Hillman reaction of arylaldehydes with a,b-unsatu-
rated ketones, the Baylis±Hillman ole®n was obtained as
the only product and the formation of chlorinated products
were not mentioned at all.13 This is because they used TLC
plates to purify the reaction products. Thus our results are
very different from his ®ndings. Based on our results, in the
titanium(IV) chloride and chalcogenide-promoted Baylis±
Hillman reaction of aldehydes with a,b-unsaturated
ketones, the chlorinated product 1 is formed as the only
product, and the Baylis±Hillman ole®n 2 is derived from
the decomposition of 1.
In Scheme 3, we propose a mechanism to explain the forma-
tion of product 1. We believe that the formation of chlori-
nated compound 1 is the major reaction process in the TiCl4
promoted Baylis±Hillman reaction using Lewis base. In
fact, Kataoka also reported partial chlorination in Baylis±
Hillman reaction of arylaldehydes with a,b-unsaturated
thioesters.12 But, in his other papers dealing with the
Scheme 2.
Scheme 3.
Scheme 4. a: Rˆp-NO2Ph; b: Rˆm-NO2Ph; c: Rˆp-CF3Ph; d: Rˆp-EtPh; e: RˆPh; f: Rˆp-ClPh; g: RˆCH3(CH2)8.

M. Shi, J.-K. Jiang / Tetrahedron 56 (2000) 4793±4797
4795
Experimental
General
MPs were obtained with a Yanagimoto micro melting point
apparatus and are uncorrected. 1H NMR spectra were
recorded on a Bruker AM-300 spectrometer for solution in
CDCl3 with tetramethylsilane (TMS) as internal standard;
J values are in Hz. Mass spectra were recorded with a
HP-5989 instrument and HRMS was measured by a
Finnigan MA1 mass spectrometer. Organic solvents were
dried by standard methods when necessary. Some of the
solid compounds reported in this paper gave satisfactory
CHN microanalyses with a Carlo±Erba 1106 analyzer.
Commercially obtained reagents were used without further
puri®cation. All reactions were monitored by TLC with
Huanghai 60F254 silica gel coated plates. Flash column
chromatography was carried out using 200±300 mesh silica
gel at increased pressure.
Figure 1. The crystal structure of 3a.
Table 2. Baylis±Hillman reaction of aldehydes with methyl vinyl ketone in
the presence of TiCl4 and 20 mol% of SMe2
Entry
R
TiCl4 equiv.
Yielda (%)/3
Typical reaction procedure for the preparation of 3-
(chloromethyl)-4-hydroxy-4-(40-nitrophenyl)-2-buta-
none (1a). To a solution of dimethyl sul®de (6.20 mg,
0.1 mmol, 7.2 mL) in dichloromethane (1.3 mL) was
added titanium chloride (0.7 mL, 0.7 mmol) at 2788C.
After stirring for 5 min, a solution of p-nitrobenzaldehyde
(76 mg, 0.5 mmol) in dichloromethane (1.0 mL) and methyl
vinyl ketone (105 mg, 1.5 mmol, 123 mL) were added into
the reaction solution at 278 8C, respectively. The reaction
mixture was kept for 12 h at 278 8C. The reaction was
quenched by addition of saturated aqueous NaHCO3 solu-
tion (1.0 mL). After ®ltration, the ®ltrate was extracted with
dichloromethane (5.0 mL£2) and dried over anhydrous
MgSO4. The solvent was removed under reduced pressure
and the residue was puri®ed by a ¯ash silica gel column
chromatography to give compound 1a (103 mg, 80%) as a
colorless solid (eluent: ethyl acetate/petroleum etherˆ1/4):
mp 90±918C; IR(KBr) n 1720 cm21 (CvO); 1H NMR
(CDCl3, 300 MHz) d 2.20 (3H, s, Me), 2.93 (1H, br. s,
OH), 3.22±3.38 (1H, m), 3.67 (1H, dd, Jˆ11.3, 4.0 Hz),
3.89 (1H, dd, Jˆ11.3, 9.2 Hz), 5.11 (1H, d, Jˆ5.6 Hz),
7.56 (2H, d, Jˆ8.6 Hz, Ar), 8.25 (2H, d, Jˆ8.6 Hz, Ar);
MS (EI) m/e 258 (MH1, 0.60), 208 (M1249, 60),
71(M12186, 100); Found: C, 51.64; H, 4.94; N, 5.35%.
C11H12ClNO4 requires C, 51.27; H, 4.69; N, 5.44%.
1
2
3
4
5
6
7
p-NO2Ph
m-NO2Ph
p-CF3Ph
p-EtPh
Ph
p-ClPh
CH3(CH2)8
1.4
1.4
1.4
1.4
1.4
1.4
1.4
62
70
74
47
50
57
29
a Isolated yields.
On the other hand, if the reaction was carried out at room
temperature (108C), the major reaction product was
compound
3 (with Z-con®guration) rather than 1
(Scheme 4). The Z-con®guration was con®rmed by X-ray
analysis (Fig. 1).14 This reaction was not affected by the
Lewis base (Me2S), and in the presence or absence of
Lewis base (Me2S) the same products were obtained in
similar yields. Arylaldehydes with strong electron-
withdrawing group on the phenyl ring gave higher yields
of 3 (Table 2). Concerning the reaction mechanism, we
believe that, at room temperature, the chloride at the
titanium metal can directly attack at the vinyl carbon atom
combined with dehydration to give compound 3. Recently,
Li reported TiCl4-mediated Baylis±Hillman reaction and
aldol reaction without the direct use of a Lewis base.15
The Baylis±Hillman ole®ns were obtained when 2-cyclo-
hexene-1-one and 2-cyclopenten-1-one were employed as
the substrates at room temperature, whereas b-halogenated
aldol products were generated with an a,b-unsaturated
N-acyl benzoxalinone as the Michael-type acceptor. For
methyl vinyl ketone, it is therefore very interesting that
compound 3 was obtained as a major product.
Preparation of 3-(chloromethyl)-4-hydroxy-4-(30-nitro-
phenyl)-2-butanone (1b). This compound was prepared
in the same manner as that described above. 103 mg,
1
80%; a colorless oil; IR(KBr) n 1720 cm21 (CvO); H
NMR (CDCl3, 300 MHz) d 2.20 (3H, s, Me), 2.95 (1H,
br. s, OH), 3.20±3.35 (1H, m), 3.66 (1H, dd, Jˆ11.3,
3.9 Hz), 3.89 (1H, dd, Jˆ11.3, 9.3 Hz), 5.13 (1H, d,
Jˆ5.6 Hz), 7.54 (1H, t, Jˆ7.9 Hz, Ar), 7.69 (1H, d,
Jˆ7.6 Hz, Ar), 8.2 (1H, d, Jˆ7.6 Hz, Ar), 8.25 (1H, s,
Ar); MS (EI) m/e 257 (M1, 0.60), 208 (M1249, 60),
71(M12186, 100); [HRMS (EI) m/z 239.0353
(M12H2O). C11H10O3NCl requires M2H2O, 239.0349].
In conclusion, we found that the titanium(IV) chloride
promoted Baylis±Hillman reaction is not as simple as
previously reported. The reaction temperature and presence
of Lewis base can drastically effect the reaction product.
Efforts are underway to elucidate the mechanistic details
of this reaction and to disclose the scope and limitations
of this reaction. Moreover we are planning to synthesize
chiral sul®des and utilize them as chiral ligands to achieve
the enantioselective Baylis±Hillman reaction. Work in this
direction is currently in progress.
Preparation of 3-(chloromethyl)-4-hydroxy-4-(40-tri-
¯uoromethylphenyl)-2-butanone (1c). This compound
was prepared in the same manner as that described above.
114 mg, 81%; a colorless oil; IR(KBr) n 1720 cm21

4796
M. Shi, J.-K. Jiang / Tetrahedron 56 (2000) 4793±4797
1
(CvO); H NMR (CDCl3, 300 MHz) d 2.13 (3H, s, Me),
2.65 (1H, br. s, OH), 3.22±3.37 (1H, m), 3.70 (1H, dd,
Jˆ10.2, 3.9 Hz), 3.89 (1H, dd, Jˆ10.2, 10.2 Hz), 5.02
(1H, d, Jˆ6.1 Hz), 7.37 (2H, d, Jˆ8.0 Hz, Ar), 7.64 (2H,
d, Jˆ8.0 Hz, Ar); MS (EI) m/e 280 (M1, 0.45), 243
(M1237, 40), 43 (M12237, 100); [HRMS (EI) m/z
262.0377 (M12H2O). C12H10OClF3 requires M2H2O,
262.0372].
7.2 mL) in dichloromethane (1.3 mL) was added titanium
chloride (0.7 mL, 0.7 mmol) at room temperature. After
stirring for 5 min, a solution of p-nitrobenzaldehyde
(76 mg, 0.5 mmol) in dichloromethane (1.0 mL) and methyl
vinyl ketone (105 mg, 1.5 mmol, 123 mL) were added into
the reaction at room temperature. The reaction mixture was
kept for 48 h at room temperature. The reaction was
quenched by addition of saturated aqueous NaHCO3 solu-
tion (1.0 mL). After ®ltration, the ®ltrate was extracted with
dichloromethane (5.0 mL£2) and dried over anhydrous
MgSO4. The solvent was removed under reduced pressure
and the residue was puri®ed by ¯ash silica gel column chro-
matography to give compound 3a (74 mg, 62%) as a color-
less solid (eluent: ethyl acetate/petroleum etherˆ1/8): mp
134±1368C; IR(KBr) n 1640 cm21 (CvO); 1H NMR
(CDCl3, 300 Hz) d 2.55 (3H, s, Me), 4.38 (2H, s, CH2),
7.69 (1H, s), 7.75 (2H, d, Jˆ8.6 Hz, Ar), 8.35 (2H, d,
Jˆ8.6 Hz, Ar); MS (EI) m/e 239 (M1, 0.40), 222
(M1217, 40), 115 (M12124, 100); Found: C, 54.94; H,
3.92; N, 5.87%. C11H10ClNO3 requires C, 55.13; H, 4.21;
N, 5.84%.
Preparation of 3-(chloromethyl)-4-hydroxy-4-(40-ethyl-
phenyl)-2-butanone (1d). This compound was prepared
in the same manner as that described above. 62 mg, 51%;
a colorless solid; mp 69±718C; IR(KBr) n 1720 cm21
(CvO); 1H NMR (CDCl3, 300 MHz) d 1.21 (3H, t,
Jˆ7.7 Hz), 2.02 (3H, s, Me), 2.15 (1H, br. s, OH), 2.63
(2H, q, Jˆ7.7 Hz), 3.22±3.37 (1H, m), 3.80 (1H, dd,
Jˆ10.7, 3.8 Hz), 3.90 (1H, dd, Jˆ10.7, 10.7 Hz), 4.82
(1H, d, Jˆ7.2 Hz), 7.10±7.32 (4H, m, Ar); MS (EI) m/e
222 (M1218, 1.20), 191 (M1249, 20), 135 (M12105,
100); [HRMS (EI) m/z 240.0908 (M1). C13H17O2Cl requires
M, 240.0917].
Preparation of 3-(chloromethyl)-4-hydroxy-4-phenyl-2-
butanone (1e). This compound was prepared in the same
manner as that described above. 61 mg, 57%; a colorless oil;
IR(KBr) n 1720 cm21 (CvO); 1H NMR (CDCl3, 300 MHz)
d 2.02 (3H, s, Me), 2.45 (1H, br. s, OH), 3.22±3.37 (1H, m),
3.78 (1H, dd, Jˆ10.7, 3.8 Hz), 3.90 (1H, dd, Jˆ10.4,
10.4 Hz), 4.84 (1H, d, Jˆ6.9 Hz), 7.10±7.32 (5H, m, Ar);
MS (EI) m/e 212 (M1, 1.05), 163 (M1249, 60), 107
(M12105, 100); [HRMS (EI) m/z 212.0594 (M1).
C11H13O2Cl requires M, 212.0604].
Preparation of 3-(chloromethyl)-4-(30-nitrophenyl)-3-
buten-2-one (3b). This compound was prepared in the
same manner as that described above. 84 mg, 70%; a color-
less solid; mp 130±1328C; IR(KBr) n 1640 cm21 (CvO);
1H NMR (CDCl3, 300 MHz) d 2.55 (3H, s, Me), 4.40 (2H, s,
CH2), 7.70 (1H, s), 7.71 (1H, t, Jˆ7.7 Hz, Ar), 7.96 (1H, d,
Jˆ7.7 Hz, Ar), 8.30 (1H, dd, Jˆ8.2, 1.3 Hz, Ar), 8.44 (1H,
s, Ar); MS (EI) m/e 239 (M1, 60), 222 (M1217, 50), 115
(M12124, 50), 43 (M12196, 100); [HRMS (EI) m/z
239.0351 (M1). C11H10ClNO3 requires M, 239.0349].
Preparation of 3-(chloromethyl)-4-hydroxy-4-(40-chloro-
phenyl)-2-butanone (1f). This compound was prepared in
the same manner as that described above. 64 mg, 52%; a
colorless oil; IR(KBr) n 1720 cm21 (CvO); 1H NMR
(CDCl3, 300 MHz) d 2.0 (3H, s, Me), 2.50 (1H, br. s,
OH), 3.20±3.32 (1H, m), 3.75 (1H, dd, Jˆ10.7, 3.8 Hz),
3.87 (1H, dd, Jˆ10.7, 10.7 Hz), 4.82 (1H, d, Jˆ6.7 Hz),
7.10±7.32 (4H, m, Ar); MS (EI) m/e 246 (M1, 1.20), 121
(M12125, 20), 91 (M12155, 100); [HRMS (EI) m/z
246.0210 (M1). C11H12O2Cl2 requires M, 246.0214].
Preparation of 3-(chloromethyl)-4-(40-tri¯uoromethyl-
phenyl)-3-buten-2-one (3c). This compound was prepared
in the same manner as that described above. 97 mg, 74%; a
colorless solid; mp 43±458C; IR(KBr) n 1640 cm21
1
(CvO); H NMR (CDCl3, 300 MHz) d 2.54 (3H, s, Me),
4.39 (2H, s, CH2), 7.70 (1H, s), 7.60±7.76 (4H, m, Ar); MS
(EI) m/e 262 (M1, 100), 193 (M1269, 70), 183 (M1279,
50), 115 (M12147, 40); [HRMS (EI) m/z 262.0381 (M1).
C12H10ClF3O requires M, 262.0372].
Preparation of 3-(chloromethyl)-4-(40-ethylphenyl)-3-
buten-2-one (3d). This compound was prepared in the
same manner as that described above. 52 mg, 47%; a color-
Preparation of 3-(chloromethyl)-4-hydroxy-4-butyl-2-
butanone (1g). This compound was prepared in the same
manner as that described above. 31 mg, 32%; a colorless oil;
IR(KBr) n 1720 cm21 (CvO); 1H NMR (CDCl3, 300 MHz)
d 0.89 (3H, t, Jˆ7.1 Hz), 1.10±1.60 (6H, m), 2.08 (1H, s,
OH), 2.34 (3H, s, Me), 3.0±3.10 (1H, m), 3.60±3.85 (3H,
m); MS (EI) m/e 192 (M1, 0.80), 155 (M1237, 30), 43
(M12149, 100); [HRMS (EI) m/z 192.0908 (M1).
C9H17O2Cl requires M, 192.0917].
1
less oil; IR(KBr) n 1640 cm21 (CvO); H NMR (CDCl3,
300 MHz) d 1.28 (3H, t, Jˆ7.1 Hz), 2.51 (3H, s, Me), 2.67
(2H, q, Jˆ7.1 Hz), 4.48 (2H, s, CH2), 7.31 (2H, d,
Jˆ8.0 Hz), 7.55 (2H, d, Jˆ8.0 Hz), 7.69 (1H, s); MS (EI)
m/e 222 (M1, 30), 193 (M1229, 100), 128 (M1294, 40);
[HRMS (EI) m/z 222.0809 (M1). C13H15ClO requires M,
222.0811].
The physical data of the known product 3-[(40-nitro-
Preparation of 3-(chloromethyl)-4-phenyl-3-buten-2-one
(3e). This compound was prepared in the same manner as
that described above. 49 mg, 50%; a colorless oil; IR(KBr)
phenyl)hydroxymethyl]-3-buten-2-one (2a).9,16 Mp 66±
688C; H NMR (CDCl3, 300 MHz) d 2.36 (3H, s, Me),
1
1
3.26 (1H, br. s, OH), 5.68 (1H, s), 6.05 (1H, s), 6.28 (1H,
s), 7.56 (2H, d, Jˆ8.6 Hz, Ar), 8.19 (2H, d, Jˆ8.6 Hz, Ar).
n 1640 cm21 (CvO); H NMR (CDCl3, 300 MHz) d 2.52
(3H, s, Me), 4.46 (2H, s, CH2), 7.31±7.50 (3H, m, Ar),
7.51±7.61 (2H, m, Ar), 7.71 (1H, s); MS (EI) m/e 194
(M1, 100), 115 (M1279, 40), 43 (M12151, 40);
[HRMS (EI) m/z 194.0498 (M1). C11H11ClO requires M,
194.0492].
Typical reaction procedure for the preparation of 3-
(chloromethyl)-4-(40-nitrophenyl)-3-buten-2-one (3a).
To a solution of dimethyl sul®de (6.20 mg, 0.1 mmol,

M. Shi, J.-K. Jiang / Tetrahedron 56 (2000) 4793±4797
4797
Preparation of 3-(chloromethyl)-4-(40-chlorophenyl)-3-
References
buten-2-one (3f). This compound was prepared in the
same manner as that described above. 65 mg, 57%; a color-
less solid; mp 87±89 8C; IR(KBr) n 1640 cm21 (CvO); 1H
NMR (CDCl3, 300 MHz) d 2.51 (3H, s, Me), 4.42 (2H, s,
CH2), 7.46 (2H, d, Jˆ8.6 Hz), 7.54 (2H, d, Jˆ8.6 Hz), 7.69
(1H, s); MS (EI) m/e 228 (M1, 20), 193 (M1235, 40), 149
(M1279, 40), 115 (M12113, 40), 43 (M12185, 100);
[HRMS (EI) m/z 228.0110 (M1). C11H10Cl2O requires M,
228.0109].
1. For reviews, see: (a) Ciganek, E. Org. React. 1997, 51, 201.
(b) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron 1996, 52,
8001. (c) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44,
4653.
2. Brzezinski, L. J.; Rafel, S.; Leahy, J. M. J. Am. Chem. Soc.
1997, 119, 4317.
3. Marko, I. E.; Giles, P. G.; Hindley, N. J. Tetrahedron 1997, 53,
1015.
4. Richter, H.; Jung, G. Tetrahedron Lett. 1998, 39, 2729.
5. Barrett, A. G. M.; Cook, A. S.; Kamimura, A. Chem. Commun.
1999, 2533.
Preparation of 3-(chloromethyl)-4-nonyl-3-buten-2-one
(3g). This compound was prepared in the same manner as
that described above. 52 mg, 29%; a colorless oil; IR(KBr)
6. Kunidig, E. P.; Xu, L. H.; Romanens, P.; Bernardinelli, G.
Tetrahedron Lett. 1993, 34, 7049.
1
n 1640 cm21 (CvO); H NMR (CDCl3, 300 MHz) d 0.83
(3H, t, Jˆ7.1 Hz, Me), 1.10±1.40 (12H, m, CH2), 1.40±1.60
(2H, m, CH2), 2.36 (3H, s, Me), 2.34 (2H, td, Jˆ7.6,
7.6 Hz), 4.32 (2H, s, CH2), 6.85 (1H, t, Jˆ7.6 Hz); MS
(EI) m/e 244 (M1, 20), 209 (M1235, 40), 109 (M12135,
70), 43 (M12201, 100); [HRMS (EI) m/z 244.1596 (M1).
C14H25ClO requires M, 244.1594].
7. Aggarwal, V.; Mereu, A.; Tarver, G. J.; MaCague, R. J. Org.
Chem. 1998, 63, 7183.
8. Kawamura, M.; Kobayashi, S. Tetrahedron Lett. 1999, 40,
1539.
9. Kataoka, T.; Iwama, T.; Tsujiyama, S.-I.; Iwamura, T.;
Watanaba, S.-I. Tetrahedron 1998, 54, 11813.
10. Ono, M.; Nishimura, K.; Nagaoka, Y.; Tomioka, K.
Tetrahedron Lett. 1999, 40, 1509.
Crystallography
A suitable single crystal with 0.20£0.20£0.30 mm3 dimen-
sions obtained by recrystallization of 3a from CH2Cl2/petro-
leum ether (1/6) was mounted at the top of a glass capillary.
Crystal data have been given in the references and notes.14
Data were collected on a Rigaku AFC7R diffractometer
with graphite-monochromated Mo-Ka radiation lˆ
11. (a) Nagaoka, Y.; Yomioka, K. J. Org. Chem. 1998, 63, 6428.
(b) Harrowven, D.; Hannam, J. C. Tetrahedron 1999, 55, 9341.
12. Kataoka, T.; Iwama, T.; Kinoshita, S.; Tsujiyama, Y.;
Iwamura, T.; Watanabe, S. Synlett 1999, 197.
13. (a) Kataoka, T.; Iwama, T.; Tsujiyama, S.; Kanematsu, K.;
Iwamura, T.; Watanabe, S. Chem. Lett. 1999, 257. (b) Kataoka,
T.; Iwama, T.; Tsujiyama, S. Chem. Commun. 1998, 197.
14. The crystal data of 3a: empirical formula: C22H20N2O6Cl2;
Formula weight: 479.32; crystal color, habit: colorless, prismatic;
crystal dimensions: 0.20£0.20£0.30 mm3; Crystal system: mono-
Ê
0.71069 A using the v22u technique at 208C. A total of
2525 unique re¯ection was collected. The data were
collected for Lorentz polarization effects. The structure
was solved by direct methods and expanded using Fourier
techniques. The non-hydrogen atoms were re®ned aniso-
tropically by full-matrix least squares. All hydrogen atoms
were included in calculated position. All calculations were
performed using the texsan crystallographic software
package. Final R and Rw values were 0.066 and 0.061 for
1110 observed re¯ection. This crystal structure has been
deposited at the Cambridge Crystallographic Data Centre
and allocated the deposition number: CCDC 142973.
Ê
clinic; lattice type: primitive; lattice type: aˆ7.524(2) A,
Ê
Ê
Ê 3
bˆ17.541(3) A, cˆ17.07(1) A, bˆ98.64(4)8, Vˆ2227(1) A ;
space group: P21/n (#14);
Z
valueˆ4; Dcalcˆ1.429 g/cm3;
F000ˆ992.00; m(MoKa)ˆ3.33 cm21; Rˆ0.066, Rwˆ0.061.
15. Li, G.; Wei, H.-X.; Gao, J.; Caputo, T. D. Tetrahedron Lett.
2000, 41, 1.
16. Iwama, T.; Tsujiyama, S.-I.; Kinoshita, H.; Kanamatsu, K.;
Tsurukami, Y.; Iwamura, T.; Watanabe, S.-I.; Kataoka, T. Chem.
Pharm. Bull. 1999, 47, 956.
Acknowledgements
We thank Prof. Albert S. C. Chan and the National Natural
Sciences Foundation of China for ®nancial support.