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J. Varga et al. / Tetrahedron: Asymmetry 12 (2001) 745–753
ified with 1 M H2SO4 (pH 2). The precipitate was
filtered off, washed with water, dried and crystallised
from EtOH–DMF to yield sulfoxide (−)-4 (13.2 g);
[h]25546=−541 (c=0.5, DMF); e.e. >97%.
3.4.3. Methyl (S)-(+)-2-[8-(N-methylcarbamoyl)-1-naph-
thylsulfinyl]benzoate. Mp 262–273°C; [h]25456=+437 (c=
0.1, DMF); e.e. >86%; IR wmax (KBr)/cm−1 3300m
(NH), 1715vs, 1633vs, (CꢁO), 1033vs (SꢁO).
3.5. (S)-(+)-Spiro[3H-2,1-benzoxathiol-3%-one-1,1%-3H-
2,1-benzazathiol]-2-methyl-3-one (S)-(+)-2
3.3. (R)-(−)- and (S)-(+)-2-[8-(N-Methylcarbamoyl)-1-
naphthylsulfinyl]benzoic acid 7
To a stirred solution of sulfoxide (R)-(+)-1 (1.82 g, 6
mmol, [h]25456=+42.1 (c=0.5, DMF)) in dichloro-
methane (60 mL) was added sulfopropionic acid9
(1.39 g, 10.2 mmol) at −78°C. Stirring was continued
for 1 h at −78°C, then for 12 h at room temperature.
Dichloromethane was removed then cold water (5 mL)
was added to the residue. The crystals separated were
collected by filtration, washed with EtOH and
diethylether, dried and crystallised from pyridine–ether
to give (S)-(+)-2 (0.95 g, 55%); [h]25456=+181 (c=0.5,
DMF); e.e. >99%, mp 299–301°C; IR wmax (KBr)/cm−1
To a hot solution of racemic sulfoxide 78 (60.1 g, 0.17
mol) and Na2CO3 (9.0 g, 0.085 mol) in water (510 mL)
was added (−)-strychnine nitrate (33.8 g, 0.085 mol) in
hot water (340 mL). After standing for 4 days at room
temperature crystals which precipitated were collected
by filtration and dried, then recrystallised from water to
give the strychnine salt of (−)-7 (33.6 g); [h]25456=−255
(c=0.5, DMF); mp 207–221°C.
A solution of the strychnine salt of (−)-7 (33.0 g) in
water (170 mL) with 1 M NaOH (53 mL) and
dichloromethane (200 mL) was stirred for 1 h at room
temperature. The aqueous phase was separated, washed
with dichloromethane (50 mL) and acidified with 1 M
H2SO4 (pH 2). The precipitated (−)-enantiomer of 7
was collected by filtration, washed with water and dried
(16.1 g); [h]25456=−501 (c=0.5, DMF); e.e. >89%; mp
224–227°C; IR wmax (KBr)/cm−1 3160–2200br (OH),
3285m (NH), 1705vs (CꢁO carboxyl), 1600vs, 1545vs
1
1700vs, 1650vs (CꢁO); H NMR (80 MHz, DMSO-d6)
l 3.30 (s, 3H), 7.37–8.42 (m, ArH).
3.6. (R)-(+)-Spiro[3H-2,1-benzazathiol-2%-methyl-3%-one-
1,1%-naphtho-[1,8-d,e]-3H-2,1-oxathiin-3-one] (R)-(+)-5
To a solution of sulfoxide (R)-(−)-4 (4.72 g, 14.1 mmol,
[h]25546=−541 (c=0.5, DMF)) in dichloromethane (150
mL) was added DCC (6.8 g, 32.4 mmol) and the
mixture stirred for 72 h at room temperature. DCU was
filtered off and the filtrate was evaporated to 20 mL,
then mixed with pentane (150 mL). After standing
overnight the crystals separated were collected by filtra-
tion, dried and crystallised from acetone to give (R)-
(+)-5 (1.0 g, 21%); mp 198–199°C, [h]25456=+623 (c=0.5,
DMF); e.e. >97%; IR wmax (KBr)/cm−1 1700vs, 1630vs
1
(amide), 1025vs (SꢁO); H NMR (80 MHz, DMSO-d6)
l 2.62 (d, 3H, J=4.2 Hz), 7.0–8.3 (m, ArH).
To prepare the (+)-enantiomer of 7, the mother liquor
obtained from the crude strychnine salt of (−)-7 was
evaporated to 500 mL then acidified with 1 M H2SO4
(pH 2). The precipitate was filtered off, washed with
water and dried. To the hot solution of the above crude
7 (29.5 g) in water (250 mL) was added (−)-strychnine
nitrate (16.6 g, 0.042 mol) in hot water (170 mL). After
standing overnight at 20°C, the aqueous phase was
separated from the precipitate and the residue was
crystallised from EtOH to afford the strychnine salt of
(+)-7 (9.8 g). Sulfoxide (+)-7 was liberated by stirring
the above salt (9.8 g) with aq. NaOH (1.12 g in 100 mL
of water) for 5 h. Strychnine was filtered off and the
filtrate was acidified with 1 M H2SO4 (pH 2). The
crystals were filtered off, washed with water and dried
to give (S)-(+)-7 (4.8 g). E.e.=86%, [h]25456=+485 (c=
0.5, DMF).
1
(CꢁO); H NMR (80 MHz, DMSO-d6) l 2.78 (s, 3H),
7.40–8.80 (m, ArH).
3.7. (S)-(+)-Spiro[3H-2,1-benzoxathiol-3%-one-1,1%-naph-
tho-[1,8-d,e]-3H-1,2-thiazine-2-methyl-3-one] (S)-(+)-8
To a solution of sulfoxide (S)-(+)-7 (4.53 g, 12.8 mmol,
[h]25546=+485 (c=0.5, DMF)) in dichloromethane (100
mL) DCC was added (2.25 g, 25.4 mmol) and the
mixture was stirred for 2 days. Additional DCC (2.25 g,
25.4 mmol) was added and the stirring was continued
for 2 days. DCU precipitated was filtered off, the
filtrate was evaporated to 5 mL and pentane (150 mL)
was poured into the residue. The precipitate was filtered
off, dried and crystallised from acetone to afford (S)-
25
546
3.4. Selected data for methyl esters of (+)-1, (−)-4 and
(+)-7
(+)-8 (2.0 g, 47%); mp 258–262°C, [h] =161 (c=0.5,
DMF); e.e. >97%; IR wmax (KBr)/cm−1 1645vs, 1640vs
1
(CꢁO); H NMR (80 MHz, DMSO-d6) l 3.54 (s, 3H),
7.42–8.05 (m, ArH).
3.4.1. Methyl (R)-(+)-2-[2-(N-methylcarbamoyl)phenyl-
sulfinyl]benzoate. Mp 124–133°C; [h]25456=+81 (c=0.5,
DMF); e.e. >99%; IR wmax (KBr)/cm−1 3260m (NH),
1727vs, 1712vs, 1670vs, 1642vs (CꢁO), 1600vs, 1010vs
(SꢁO).
3.8. General procedure for the preparation of sulfonium
tetrafluoroborates (R)-(+)-3, (S)-(+)-6 and (R)-(+)-9
To a stirred solution of spiro-l4-sulfanes (S)-(+)-2,
(R)-(+)-5 and (S)-(+)-8 (3 mmol) in dichloromethane
(30 mL) was added trimethyloxonium tetrafluoroborate
(0.46 g, 3.03 mmol). After stirring for 4 h at 20°C ether
was poured into the mixture. The crystals formed were
collected by filtration, washed with ether and dried.
3.4.2. Methyl (R)-(−)-8-[2-(N-methylcarbamoyl)phenyl-
sulfinyl)-1-naphthoate. Mp 182–197°C; [h]25456=−469 (c=
0.5, DMF); e.e. >97%; IR wmax (KBr)/cm−1 3275m
(NH), 1640vs, 1720vs, (CꢁO), 1010vs (SꢁO).