4
730
T. Kataoka et al. / Tetrahedron 56 (2000) 4725±4731
(b) Compound 8a (128 mg, 0.5 mmol) isolated by recycling
preparative HPLC eluting with CHCl was submitted to
Treatment of 7 with TiCl4
3
preparative TLC on silica gel eluting with ethyl acetate±
hexane (1:1, v/v) to give 7 (109 mg, 99%).
(a) Hydrogen chloride was bubbled into a solution of 7
(110 mg, 0.5 mmol) and TiCl (55 ml, 0.5 mmol) in dry
4
CH Cl (1.5 ml) at room temperature. The mixture was stir-
2
2
red at the same temperature for 1 h and worked up as
mentioned above. The products and their ratio were listed
in Entry 2 in Table 1.
Reaction of benzaldehyde with 5
To a stirred solution of benzaldehyde (53 mg, 0.5 mmol), 5
(
70 mg, 1 mmol), and 6 (16 mg, 0.05 mmol) in dry CH Cl2
2
(b) A solution of 7 (110 mg, 0.5 mmol) and TiCl (55 ml,
4
(
1.5 ml) was added dropwise TiCl (55 ml, 0.5 mmol) at
4
0.5 mmol) in dry CH Cl (1.5 ml) was stirred at 08C for
2
2
0
1
8C. The mixture was stirred at the same temperature for
h, and the reaction was quenched by the addition of satu-
10 min. The mixture was worked up as mentioned above.
The products and their ratio were listed in Entry 3 in Table 1.
rated aqueous NaHCO (2 ml). The inorganic precipitate
3
TM
was removed by ®ltration through Celite , and the ®ltrate
was dried (MgSO ) and evaporated under reduced pressure.
(c) A solution of 7 (110 mg, 0.5 mmol) and TiCl (55 ml,
4
0.5 mmol) in dry CH Cl (1.5 ml) was stirred at 08 C for
2
4
2
The residue was puri®ed by column chromatography on
silica gel eluting with ethyl acetate±hexane (1:10, v/v) to
give 3-chloromethyl-4-hydroxy-4-phenylbutan-2-one (9)
30 min. The mixture was worked up as mentioned above.
The products and their ratio were listed in Entry 4 in Table 1.
(
83 mg, 78%) as a mixture of diastereoisomers, with a
(d) NaH (20 mg, 0.5 mmol) was added in small portions to a
solution of 7 (110 mg, 0.5 mmol) in dry CH Cl (1.5 ml) at
08C. TiCl (55 ml, 0.5 mmol) was added dropwise to the
4
mixture, and the whole was stirred at the same temperature
for 1 h. The mixture was worked up as mentioned above. A
complex mixture was obtained, and the products could not
be separated.
ratio of 9a:9b3:1. The obtained diastereoisomers were
2
2
separated by recycling preparative HPLC eluting with
CHCl . syn-Isomer 9a. Pale orange oil; H NMR (CDCl )
1
3
3
d: 2.01 (3H, s, CH ), 2.53 (1H, br, s, OH), 3.32 (1H, ddd,
3
J4, 7, and 10.5 Hz, 3-H), 3.78 (1H, dd, J4 and 11 Hz,
CH Cl), 3.87 (1H, dd, J10.5 and 11 Hz, CH Cl), 4.85 (1H,
2
2
1
3
d, J7 Hz, benzylic H), 7.29±7.39 (5H, m, ArH); C NMR
(
CDCl ) d: 32.4 (q), 41.8 (t), 61.4 (d), 73.5 (d), 126.1 (d),
3
Addition of hydrogen chloride to 7
2
28.4 (d), 128.8 (d), 140.8 (s), 209.3 (s); IR (KBr, cm ):
1
1
3
441 (OH), 1713 (CvO), 701 (C±Cl); MS (EI) m/z (rel. int.
Hydrogen chloride was bubbled into a solution of 7 in
CDCl in an NMR tube. The mixture was allowed to
1
): 212 (8%, M ), 77 (100%). Anal. Calcd for C H ClO :
%
C, 60.97; H, 6.16. Found: C, 61.11; H, 6.03. anti-Isomer 9b.
1
1
13
2
3
1
stand for 5 h at room temperature and submitted to H
1
Brown oil; H NMR (CDCl ) d: 2.23 (3H, s, CH ), 3.27 (1H,
1
NMR spectroscopy. The H NMR spectrum showed peaks
of 8a, 8b, 10, and 7, with a ratio of 1:2.7:0.6:1.8.
3
3
ddd, J4.4, 7.8, and 8.3 Hz, 3-H), 3.43 (1H, dd, J4.4 and
1
3
1.2 Hz, CH Cl), 3.58 (1H, dd, J8.3 and 11.2 Hz, CH Cl),
2
2
.64 (1H, dd, J5 and 11 Hz, CH Cl), 4.92 (1H, d,
Product analysis of the reactions of acrylonitrile (22) and
cyclopentenone (25) with p-nitrobenzaldehyde (4)
2
1
3
J7.8 Hz, benzylic H), 7.32±7.40 (5H, m, ArH); C
NMR (CDCl ) d: 32.5 (q), 42.3 (t), 60.4 (d), 73.9 (d),
3
1
26.1 (d), 128.5 (d), 128.8 (d), 140.9 (s), 210.1 (s); IR
The chalcogeno-Baylis±Hillman reactions of acrylonitrile
(22) and cyclopentenone (25) with p-nitrobenzaldehyde
(4) were conducted under the same conditions in the litera-
2
KBr, cm ): 3458 (OH), 1715 (CvO), 1516 and 1347
1
(
(
1
NO ); MS (EI) m/z (rel. int. %): 212 (8%, M ), 107
2
3
(
100%). HRMS Calcd for C H ClNO 212.0604, found
1
ture. The crude products were analyzed by NMR spectro-
1
12
4
2
12.0593.
scopy before puri®cation by chromatography. The product
ratio of syn-2-chloromethyl-3-hydroxy-3-(p-nitrophenyl)-
propiononitrile (23a), the anti-isomer 23b and 2-[1-hy-
droxy-1-(p-nitrophenyl)methyl]acrylonitrile (24) 23a:23b:
Stability of 8a in CDCl3
2
45.6:1.1:1 was obtained from the intensities of the
A solution of a mixture of 8a in CDCl was allowed to stand
3
peaks of benzylic protons at d 5.29 for 23a, d 5.20 for
23b and d 5.46 for 24. The peaks of 3-chloro-2-[1-hydroxy-
1-( p-nitrophenyl)methyl]cyclopentanone were not observed
in the H NMR spectrum of the crude product obtained
from the reaction of 25 with 4 but those of cyclopentenone
26 were observed.
1
for 2 days at room temperature and was then submitted to H
1
NMR spectroscopy. The H NMR spectrum showed peaks
1
of a-methylene aldol 7, 3-chloromethyl-4-(p-nitrophenyl)-
but-4-en-2-one (10), 8a, and 8b, with a ratio of 5:6:10:10.
6
1
0: mp 127±128.58 C; light-yellow prisms (EtOAc/hexane);
1
H NMR (CDCl ) d: 2.55 (3H, s, 1-H), 4.38 (2H, s, CH ),
3
2
7
.71 (1H, s, 4-H), 7.75 and 8.33 (each 2H, d, J8.8 Hz,
X-Ray study of syn-3-chloromethyl-4-hydroxy-4-(p-
nitrophenyl)butane-2-one (8a)
1
ArH); C NMR (CDCl ) d: 26.0 (q), 36.8 (t), 124.0 (d),
3
3
130.2 (d), 139.6 (s), 140.1 (d), 140.4 (s), 148.0 (s), 196.6 (s);
IR (KBr, cm ): 1665 (CvO), 1500 and 1335 (NO ); MS
2
1
2
A colorless prismatic crystal of C H ClNO having
11 12
4
1
EI) m/z (rel. int. %): 239 (13%, M ), 222 (100%). Anal.
(
Calcd for C H ClNO : C, 55.13; H, 4.21; N, 5.84. Found:
approximate dimensions of 0.20£0.20£0.30 mm was
mounted on a glass ®ber. All measurements were made on
a Rigaku AFC5R diffractometer with graphic mono-
chromated Mo-Ka radiation and a 12 kW rotating anode
generator.
1
1
10
3
C, 55.04; H, 4.19; N, 5.72. The (Z)-con®guration of 10 was
determined from the NOE enhancement between 4-H and
CH by 7%.
3