S. Robin, G. Rousseau
27.2, 127.5, 128.2, 129.3, 132.1, 136.3, 138.0, 143.0. Ϫ MS (EI); 5-Bromo-5,6-dihydro-2-methoxy-6-phenyl-4H-1,3-oxazine (2c):
FULL PAPER
1
(
1
m/z,%): 65 (14), 91 (81), 115 (24), 130 (40), 155 (36), 286 (100),
White solid. Ϫ H NMR (250 MHz, CDCl
3
): δ ϭ 3.65Ϫ3.90 (m, 2
3
4
29 (0.78). Ϫ C19
.25; found C 69.18, H 7.13, N 4.24.
23 2
H O NS (329.4554): calcd. C 69.27, H 7.04, N
H), 3.75 (s, 3 H), 4.20 (dq, J ϭ 8.1, and 4.6 Hz, 1 H), 5.25 (d, J ϭ
1
3
8.1 Hz, 1 H), 7.25Ϫ7.45 (m, 5 H). C NMR (CDCl
3
): δ ϭ 44.8,
4
9.4, 54.9, 82.3, 126.7, 128.6, 128.7, 129.1, 136.6, 152.9.
Preparation of (؎)-4-Methyl-N-[(E)-1-methyl-3-phenylallyl]-4-ben-
zenesulfonamide (3d): Tosylamide 3d was obtained using the
(
(
(
2R*,3S*)-3-Bromo-1-(4-methylphenylsulfonyl)-2-phenylazetidine
[8]
method described by Bosnich from trans 4-phenyl-but-3-en-2-one
2 g, 13.7 mmol). The oxime was reduced, without purification,
with zinc/AcOH to give (E)-1-methyl-3-phenylallylamine (8)
678.4 mg, 4.6 mmol) which was purified by distillation under re-
1
11a or 2d): White solid. Ϫ H NMR (250 MHz, CDCl
s, 3 H), 3.96 (dd, J ϭ 7.0 and 7.5 Hz, 1 H), 4.17 (ddd, J ϭ 7.0,
.0, and 6.5 Hz, 1 H), 4.31 (dd, J ϭ 7.0 and 7.5 Hz, 1 H), 4.99 (d,
3
): δ ϭ 2.48
(
7
(
J ϭ 6.5 Hz, 1 H), 7.3Ϫ7.5 (m, 7 H), 7.69 (d, J ϭ 8.3 Hz, 2 H). Ϫ
13
duced pressure (120Ϫ180 °C at 15 Torr). Yield: 34% from the start-
ing ketone. Tosylation using the method described above for the
preparation of 3b led to the tosylamide 3d (60% yield). White solid,
m.p. 81.5 °C. Spectral data were in agreement with those already
described.[
C NMR: δ ϭ 21.6, 38.9, 57.1, 75.9, 126.1, 127.8, 128.4, 128.7,
1
(
(
28.9, 131.4, 137.2, 144.6. Ϫ MS (EI); m/z (%): 51 (26), 65 (31), 77
33), 91 (82), 103 (33), 118 (34), 130 (35), 155 (100), 184 (18), 222
47), 286 (14). Ϫ C16 16BrNO S: calcd. C 52.47, H 4.40, N 3.82;
H
2
20]
found C 52.75, H 4.44, N 3.91.
Preparation of 4-Methyl-N-[(1S)-(E)-1-methyl-3-phenylallyl]-4-ben-
zenesulfonamide (3d): This amine was prepared by the reaction of
(
(
2R*,3R*)-3-Bromo-1-(4-methylphenylsulfonyl)-2-phenylazetidine
11aЈ): White solid. Ϫ H NMR (250 MHz, CDCl ): δ ϭ 2.45 (s, 3
3
1
[9]
4-methyl-N-[(1S)-1-methyl-2-oxoethyl]benzenesulfonamide (9)
H), 3.94 (m, 1 H), 4.44 (dd, J ϭ 9.7 and 7.3 Hz, 1 H), 4.57 (ddd,
J ϭ 7.3, 7.3 and 2.9 Hz, 1 H), 5.23 (d, J ϭ 7.3 Hz, 1 H), 7.15Ϫ7.5
(
with benzylidenetriphenylphosphorane. A solution of phenylli-
thium in hexane (2 , 2.5 mL, 5 mmol) was added at Ϫ40 °C under
argon to a suspension of benzyltriphenylphosphonium chloride
1
3
m, 7 H), 7.69 (d, J ϭ 8.3 Hz, 2 H). Ϫ C NMR δ 21.6, 38.9, 57.3,
6
8.8, 127.5, 127.9, 128.3, 128.5, 129.8, 131.9, 136.0, 144.5.
(1.6 g, 4 mmol) in THF. The mixture was stirred for 30 min at Ϫ40
°
C and the aldehyde 9 (0.466 g, 2 mmol) in THF solution was ad-
(
2R*,3S*,4S*)-3-Bromo-1-(4-methylphenylsulfonyl)-2,4-diphenyl-
ded. After one night at room temp., water was added. The aqueous
layer was extracted with dichloromethane (3ϫ20 mL) and the or-
ganic phase was dried (Na
1
azetidine (11b): White solid, m.p. 86.4 °C. Ϫ H NMR (250 MHz,
CDCl ): δ ϭ 2.48 (s, 3 H), 3.96 (dd, J ϭ 6.8 Hz, 1 H), 5.0 (d, J ϭ
.8 Hz, 2 H), 7.25Ϫ7.57 (m, 7 H), 7.62 (d, J ϭ 8.3 Hz, 2 H). Ϫ
3
2
SO
4
). The solvent was evaporated under
6
13
C
reduced pressure. The residue was purified by flash liquid chroma-
tography over silica gel (ether/pentane, 25:75 to 50:50) to give tosyl-
amide 3d (0.268 g, 0.89 mmol, 22% yield). The enantiomeric excess
measured by HPLC (chiracel OD-H column) was found to be 80%.
NMR (CDCl
3
): δ ϭ 21.5, 47.6, 72.0, 126.4, 128.2, 128.7, 128.8,
1
29.6, 132.5, 137.3, 144.5. Ϫ MS (EI); m/z (%): 51 (12), 65 (13), 77
17), 91 (31), 103 (26), 155 (10), 184 (100), 184 (98), 206 (22), 362
22). Ϫ C22 20BrNO S: calcd. C 59.86, H 4.57, N 3.18; found C
9.61, H 4.51, N 2.94.
(
(
H
2
D 3
Ϫ α ϭ Ϫ103 (c ϭ 1.25, CDCl ).
5
Preparation of N-[(E)-1,1-Dimethyl-3-phenylallyl]-4-methylben-
zenesulfonamide (3e): This amine was obtained by tosylation of (E)-
(
2R*,3S*,4S*)-3-Bromo-2-isopropyl-1-(4methylphenylsulfonyl)-4-
1
phenylazetidine (11c): White solid, m.p. 96 °C. Ϫ H NMR
250 MHz, CDCl ): δ ϭ 1.03 (d, J ϭ 6.8 Hz, 3 H), 1.07 (d, J ϭ
.8 Hz, 3 H), 2.20 (m, 1 H), 2.46 (s, 3 H), 3.87 (dd, J ϭ 6.4 and
.4 Hz, 1 H), 4.04 (dd, J ϭ 6.4 and 5.6 Hz, 1 H), 4.85 (d, J ϭ
[10]
1
,1-dimethyl-3-phenylallylamine
ously reported (74% yield). White solid, m.p. 75 °C. Ϫ H NMR
250 MHz, CDCl ): δ ϭ 1.47 (s, 6 H), 2.35 (s, 3 H), 4.93 (bs, 1 H),
.95 (d, J ϭ 18 Hz, 1 H), 6.37 (d, J ϭ 18 Hz, 1 H), 7.10Ϫ7.35 (m,
following the conditions previ-
(
3
1
6
6
6
(
3
5
7
2
1
6
1
3
.4 Hz, 1 H), 7.25Ϫ7.5 (m, 7 H), 7.65 (d, J ϭ 8.3 Hz, 2 H). Ϫ
): δ ϭ 16.5, 17.7, 21.5, 31.1, 40.8, 72.1, 75.1, 126.0,
28.2, 128.5, 128.6, 129.6, 132.2, 137.6, 144.3. Ϫ MS (EI); m/z (%):
1 (49), 57 (21), 65 (31), 77 (22), 91 (85), 103 (20), 130 (28), 155
C
13
H), 7.75 (d, J ϭ 6.0 Hz, 2 H). Ϫ C NMR (CDCl
3
): δ ϭ 21.3,
NMR (CDCl
1
4
3
8.2 (2C), 56.7, 126.3 (2C), 127.0 (2C), 127.2, 127.4, 128.2 (2C),
2
29.3 (2C), 136.3, 139.7, 142.7, 142.8. Ϫ C18H21NO S: calcd. C
8.54, H 6.71, found C 68.65, H 6.88.
(100), 182 (16), 260 (76), 284 (54), 328 (44), 409 (0.51).
Preparation of 4-Methyl-N-(3-methylbut-2-enyl)benzenesulfonamide
[21]
(2R*,3S*,4R*)-3-Bromo-2-isopropyl-1-(4-methylphenylsulfonyl)-4-
(
3f): A mixture of 1-bromo-3-methylbut-2-ene (2.7 g, 18 mmol),
p-tolylsulfonamide (4.6 g, 27.1 mmol), potassium carbonate
3.75 g, 27.1 mmol) and acetone (100 mL) was heated overnight at
1
phenylazetidine (11cЈ): White solid. Ϫ
CDCl ): δ ϭ 1.20 (d, J ϭ 6.8 Hz, 3 H), 1.25 (d, J ϭ 6.8 Hz, 3 H),
.37 (s, 3 H), 2.41 (m, 1 H), 4.47 (m, 1 H), 4.72 (dd, J ϭ 7.8 Hz,
J ϭ 6 Hz, 1 H), 5.38 (d, J ϭ 6 Hz, 1 H), 7.02Ϫ7.45 (m, 7 H), 7.67
H NMR (250 MHz,
(
3
2
reflux. The acetone was removed under reduced pressure and the
residue was dissolved in an ether/water mixture. The aqueous layer
was extracted with ether and the organic layers dried (Na SO ).
2 4
1
3
(
d, J ϭ 8.3 Hz, 2 H). Ϫ C NMR (CDCl
3
): δ ϭ 18.3, 19.1, 21.4,
1.1, 45.5, 72.0, 76.0, 127.0, 128.3, 128.3, 128.9, 129.1, 134.2, 137.5,
42.8. Ϫ C19 22BrNO S (11cϪ11cЈ): calcd. C 55.89, H 5.43, N
.43; found C 55.28, H 5.47, N 3.22.
3
1
3
The solvent was evaporated under reduced pressure and the residue
was purified by flash liquid chromatography over silica gel (ether/
pentane, 25:75) to afford tosylamide 3f (3.1 g, 12.9 mmol, 72%
yield). Spectral data were in agreement with those already de-
scribed.[
H
2
(
2R*,3S*,4S*)-3-Bromo-2-methyl-1-(4-methylphenylsulfonyl)-4-
22]
1
phenylazetidine (11d): White solid, m.p. 143.8 °C. Ϫ H NMR
(250 MHz, CDCl ): δ ϭ 1.52 (d, J ϭ 6.2 Hz, 3 H), 2.46 (s, 3 H),
General Procedure for the Cyclization of Compounds 1a؊1d, 3a؊3f:
3
A
solution of BBH (0.374 g, 0.8 mmol) in dichloromethane 3.69 (dd, J ϭ 6.7 and 6.7 Hz, 1 H), 4.11 (m, 1 H), 4.77 (d, J ϭ
1
3
(20 mL) was added at room temp. over 6 h to a solution of sub-
6.7 Hz, 1 H), 7.07Ϫ7.5 (m, 7 H), 7.67 (d, J ϭ 8.3 Hz, 2 H). Ϫ
C
3
strate 1 or 3 (0.6 mmol) in dichloromethane (20 mL). After com- NMR (CDCl ): δ ϭ 19.9, 21.5, 46.4, 66.6, 72.9, 126.3, 128.4, 128.7,
plete addition, the mixture was stirred for 12 h. Silica gel (1 g) was
added and the solvent removed under reduced pressure. The isol-
128.8, 129.8, 137.4, 144.6. Ϫ MS (EI); m/z (%): 41 (27), 57 (17), 83
(12), 91 (40), 103 (18), 132 (16), 145 (10), 155 (75), 182 (22), 195
ated powder was deposited on the top of a silica gel column. The (17), 224 (11), 259 (33), 260 (68), 299 (27), 300 (100), 301 (23), 379
product was then purified by elution with a ether/pentane mixture. (6), 381 (6).
3010
Eur. J. Org. Chem. 2000, 3007Ϫ3011