To 3a (312 mg, 1.0 mmol) in CH
2
Cl (5mL) at Ð40 °C under Ar was sequentially added
2
pyridine (0.25 mL, 3.0 mmol) and triflic anhydride (0.22 mL, 1.3 mmol) dropwise.
The resulting solution was allowed to warm to 0 °C (2 h) and kept at this temperature
for 5 h. Ethanol was added (2 mL, >30mmol) and the mixture was stirred at rt for 18 h.
To the resulting pale yellow solution was added 1N HCl and the product was extracted
with ether. The combined organic extract was washed once with 1N KHCO
MgSO ) and concentrated in vacuo. Flash chromatography (hexane/EtOAc 19:1) gave
b as a volatile colorless oil (89 mg, 51%).
3
, dried
(
4
4
-
1 1
IR vmax (NaCl, neat) 2222 cm ; H NMR (200 MHz, CDCl
3
) d 7.70-7.44 (m, 4H), 0.45
1
3
(
s ,
9 H ) ;
C
N M R
( 5 0
M H z , C D C l
3
)
d 144.7, 134.4, 133.3, 131.5, 129.0, 119.8, 117.2, -1.5.
3
-Thiomethylphthalimide (7b).
To a solution of N-cumylphthalimidine (5) (1.60 g, 6.0 mmol) and TMEDA (1.99 mL,
3.3 mmol, 2.2 equiv) in THF (60 mL) at Ð78 °C under Ar was slowly added s-BuLi
13.3 mmol, 2.2 equiv) via syringe. The resulting dark green, almost black solution was
stirred for 2 h before methyl disulfide (0.65 mL, 7.2 mmol, 1.2 equiv) was added. The
reaction mixture was allowed to warm slowly to rt and satd NH Cl was added. The
product was extracted with EtOAc, and the combined organic extract dried (MgSO
1
(
4
4
)
and concentrated in vacuo with a bleach trap to give the crude product. Flash
chromatography (hexane/EtOAc 3:2) gave N-cumyl-6-(thiomethyl)phthalimidine a pale
yellow solid (1.68 g, 89%), mp 167-170 °C.
-
1 1
IR vmax (KBr) 3413, 1671 cm ; H NMR (200 MHz, CDCl
d, 1H, J=9.7 Hz), 3.35 (d, 1H, J=9.7 Hz), 2.35, (s, 3H), 1.89 (s, 3H), 1.87 (s, 3H); C
N M R ( 5 0 M H z , C D C l
d 167.4, 146.9, 144.6, 138.4, 132.1, 128.1, 127.1, 126.3, 125.1, 123.8, 118.1, 81.6, 58.9,
8.9, 27.9, 13.6; HRMS calcd for C18 S: 313.1136; found 313.1149.
3
) d 7.42-7.06 (m, 8H), 5.98
1
3
(
3
)
2
H19NO
2
To a solution of N-cumyl-6-(thiomethyl)phthalimidine (940 mg, 3.0 mmol) in DMF (12
mL) under Ar at rt was added pyridinium dichromate (2.26 g, 6.0 mmol, 2.0 equiv) all
at once and the dark mixture was stirred for 2 h. Water was added and the product was
extracted with EtOAc. The combined organic extract was washed with water (3 times),
brine, and dried (MgSO
4
). Evaporation of solvent and flash chromatography
(
hexane/EtOAc 4:1) gave 6b (840 mg, 89%) as a pale yellow solid, mp 168-169 °C.
-
1 1
IR vmax (KBr) 1761, 1699 cm ; H NMR (300 MHz, CDCl
3
) d 7.61-7.20 (m, 8H), 2.53
(75 MHz, CDCl
d 169.1, 169.0, 147.1, 139.9, 134.3, 133.4, 128.8, 127.1, 126.7, 124.9, 121.1, 118.6, 62.
, 29.5, 14.4; HRMS calcd for C18 S: 311.0981; found 311.0988.
1
3
(
s, 3H), 2.04, (s, 6H);
C
NMR
3
)
1
H17NO
2
To 6b (312 mg, 1.0 mmol) was added TFA (4 mL) and the resulting solution was
stirred for 16 h at 50 °C. The solvent was removed on a rotary evaporator to give the
crude product. Gradient flash chromatography (hexane/EtOAc 19:1, then EtOAc)
afforded 7b as a bright yellow solid (168 mg, 87%), subl 195 °C.
-
1 1
IR vmax (KBr) 3188, 1771, 1717 cm ; H NMR (200 MHz, DMSO-d
6
) d 11.27 (brs,
1
3
H), 7.73 (t, 1H, J=8.1 Hz), 7.60 (d, 1H, J=8.0 Hz), 7.51 (d, 1H, J=7.0 Hz), 2.53 (s,
1
3
H ) ;
C
N M R
( 5 0
M H z ,
D M S O - d
6
)
d 168.9, 168.7, 139.0, 134.5, 133.6, 129.0, ; 1 H2 6R . 5M , S 11c8a. l1c ,d 1 f3 o. 1r
C
9
H
7
NO S: 193.0198; found 193.0207.
2