Dynamic Kinetic Transformation of Sulfinyl Chlorides
J . Org. Chem., Vol. 67, No. 2, 2002 355
2
H, J ) 3.6 Hz), 4.84 (d, 2H, J ) 2.9 Hz), 5.82 (d, 2H, J ) 3.6
2.66-2.79 (m, 2H), 3.47-3.55 (m, 2H), 3.67(s, 6H), 6.75(d, 2H,
J ) 8.2 Hz), 7.07(t, 2H, J ) 7.5 Hz), 7.36(ddd, 2H, J ) 1.7,
1
3
Hz). C NMR (C
6
D
6
, 125 MHz) δ: 23.8, 24.1, 24.2, 24.4, 25.1,
2
1
8
5.5, 35.1, 36.1, 36.8, 37.0, 47.8, 67.2, 72.4, 79.5, 81.1, 83.6,
7.5, 8.2 Hz), 7.58 (dd, 2H, J ) 1.7, 7.5 Hz). 13C NMR (CDCl
3
,
+
05.2, 110.3, 113.1. HRMS: calcd for C38
25.3165, found 825.3164 (0.2 ppm).
H
58
O
14NaS
2
(M + Na)
125 MHz) δ: 43.6, 55.5, 110.6, 121.3, 125.8, 129.5, 132.2, 154.8.
1 25
-
IR (cm , νSO): 1036. [R]
(c 0.5, CHCl ). Anal. Calcd for C16
Found: C, 56.75; H, 5.25.
(R,S)-Bis(o-a n isylsu lfin yl)eth a n e [14(R,S)]. Purified by
flash column chomatography (CH Cl /acetone/hexane, 3:2:6).
D
) +446 (c 0.5, ethanol). [R]
D
) +650
1
,2:5,6-Di-O-isop r op ylid en e-R-D-glu cofu r a n osyl Meth -
3
18 4 2
H O S
: C, 56.78; H, 5.36.
a n esu lfin a te (8). Diasteoreomerically pure methanesulfinate
8
1
pyridine in THF or DIPEA in toluene according to the
published method.8 Methanesulfinyl chloride 24 was obtained
using Hermann methodology, by treating dimethyl disulfide
R
S
and 8S
S
were prepared by condensation of 1 equiv of DAG
and 1.2 equiv of methanesulfinyl chloride 24 at -78 °C using
2
2
1
3
White solid. H NMR (CDCl , 500 MHz) δ: 3.03-3.07 (m, 2H),
a
3.23-3.27 (m, 2H), 3.83(s, 6H), 6.89(d, 2H, J ) 8.2 Hz), 7.14
(t, 2H, J ) 7.7 Hz), 7.44 (ddd, 2H, J ) 1.6, 7.7, 8.2 Hz), 7.67
5
7
13
with sulfuryl chloride in acetic acid.
(dd, 2H, J ) 1.6, 7.7 Hz). C NMR (CDCl , 125 MHz) δ: 43.1,
3
Gen er a l P r oced u r e for P r ep a r a tion of Ch ir a l Bis-
su lfoxid es by Nu cleop h ilic Su bstitu tion on Ch ir a l Bisu l-
fin a tes. Bis-sulfoxides 10-17 were obtained by addition of 2
equiv of RM (R ) alkyl or aryl, M ) MgBr or Li) to a solution
of 1,2-bis-sulfinate esters 6 or 7 in toluene, at 0 °C. The
mixture was stirred for 1 h, quenched with saturated aqueous
55.8, 110.9, 121.4, 125.8, 129.3, 132.4, 155.1.
(S,S)-Bis(p -t olylsu lfin yl)et h a n e [15(S,S)]. 1H NMR
(CDCl
3.34 (m, 2H), 7.37 and 7.26 (AA’BB’ system, 8H). C NMR
(CDCl , 125 MHz) δ: 21.3, 47.7, 123.8, 130.0, 139.0, 141.7.
[R]25
) -272 (c 0.5, methanol). HRMS: calcd for C16
306.0748, found 306.0754 (2.2 ppm).
3
, 500 MHz) δ: 2.38 (s, 6H), 2.68-2.75 (m, 2H), 3.27-
13
3
D
18 2 2
H O S
NH
4 2 2
Cl solution, extracted with ethyl acetate and Cl CH , and
purified by flash chromatography.
(R,S)-Bis(p-tolylsu lfin yl)eth a n e [15(R,S)]. The spectro-
scopical data of the meso-11(R,S) are taken from a mixture of
In the case of 1,2-bis-(alkylsulfinyl)ethanes 10-12, the
workup was different: After the reaction mixture was stirred
for 1 h, 1 equiv of TFA was added and the solvent removed
under vacuo. The residue was extracted with ether in order
to remove the DAGOH, and after treatment with Mixed bed
resin (Sigma TMD-8; 1:1 mixture of strong cation and anion-
exchange resin) to remove the remaining salts, it was purified
by column chromatography on silica gel. The starting bis-
sulfinate ester, yields, specific rotations, and absolute configu-
rations are collected in Table 2.
1
bis-sulfoxides 11, enriched in the (R,S) diastereoisomer. H
NMR (CDCl
.40 (AA′BB′ system, 8H).
S,S)-Bis(2-p yr id ylm eth a n esu lfin yl)eth a n e [16(S,S)].
Purified by column chromatography (ethyl acetate/methanol
3
, 500 MHz) δ: 2.39 (s, 6H), 2.98 (s, 4H), 7.30 and
7
(
1
1
(
)
0:1). H NMR (CDCl
AB system, 4H, J ) 12.9 Hz, ∆υ ) 31.4 Hz), 7.18 (ddd, 2H, J
1.1, 4.9, 7.7 Hz), 7.30 (dt, 2H, J ) 1.1, 7.7 Hz), 7.66 (td, 2H,
3
, 500 MHz) δ: 3.00-3.29 (m, 4H), 4.18-
1
3
J ) 1.8, 7.7 Hz), 8.55 (ddd, 2H, J ) 1.1, 1.8, 74.9 Hz). C NMR
(
[R]
(
CDCl
3
, 125 MHz) δ: 42.8, 59.2, 123.0, 125.1, 136.7, 149.8.
) +105 (c 1.0, CHCl ). HRMS: calcd for C14
(
S,S)-Bis(m eth ylsu lfin yl)eth a n e [10(S,S)]. White solid.
2
5
1
D
3
17 2 2 2
H N O S
Crystallized from ethanol-ethyl acetate. Mp: 130-132 °C. H
NMR (CDCl , 500 MHz) δ: 2.66 (s, 6H), 2.97-3.06 (m, 2H),
.21-3.29 (m, 2H). C NMR (CDCl
M + 1)+ 309.0731, found 309.0726 (1.8 ppm).
(R,R)-Bis(2-p yr id ylm eth a n esu lfin yl)eth a n e [16(R,R)].
Purified by column chomatography (ethyl acetate/methanol,
3
1
3
3
3
, 125 MHz) δ: 38.8, 46.2.
) +281 (c 0.5, ethanol). Anal. Calcd
: C, 31.15; H, 6.53. Found: C, 31.49; H, 6.50.
R,R)-Bis(m eth ylsu lfin yl)eth a n e [10(R,R)]. This com-
pound shows the same spectroscopic data as the 10(S,S)
-1
25
IR (cm , νSO) 1026. [R]
for C
D
2
5
1
)
0:1). Spectroscopical data identical to those of 12(S,S). [R]
-110 (c 0.8, CHCl ).
S ,S )-Bis(t er t -b u t oxyca r b on ylm e t h a n e su lfin yl)e t h -
D
4
10 2 2
H O S
3
(
(
2
5
a n e [17(S,S)]. Purified by crystallization from ethanol/hexane
enantiomer. [R]
(M + 1) 155.0200, found 155.0199 (1.1 ppm).
R,S)-Bis(m eth ylsu lfin yl)eth a n e [10(R,S)]. The spectro-
D
) -153 (c 0.5, CHCl
3
). HRMS: calcd for
1
+
and ethyl acetate/hexane. White solid. Mp: 110-111 °C. H
4 11 2 2
C H O S
NMR (CDCl , 500 MHz) δ: 1.49 (s, 9H), 3.22-3.29 (m, 2H),
3
(
3
.37-3.44 (m, 2H), 3.70 (s, 4H). 13C NMR (CDCl
3
, 125 MHz)
) +137 (c 1.05, CHCl ).
26 6 2
H O S : C, 47.44; H, 7.39. Found: C, 47.35;
scopic data of meso-10 are taken from a mixture of bis-
sulfoxides 10, enriched in the (R,S) diastereoisomer. H NMR
2
5
1
δ: 27.9, 44.2, 57.0, 84.0, 163.6. [R]
Anal. Calcd for C14
H, 7.21.
D
3
(
3
CDCl
.24 (m, 2H). C NMR (CDCl
R,R)-Bis(eth ylsu lfin yl)eth a n e [11(R,R)]. White solid.
3
500 MHz) δ: 2.65 (s, 6H), 2.99-3.03 (m, 2H), 3.20-
13
3
, 125 MHz) δ: 39.2, 46.5.
(
R,S)-Bis(ter t-b u t oxyca r b on ylm e t h a n e su lfin yl)e t h -
(
1
a n e [17(R,S)]. The spectroscopical data of the meso-17(R,S)
Crystallized from ethanol-ethyl acetate. Mp: 98-100 °C. H
NMR (CDCl
2
3
are taken from a mixture of bis-sulfoxides 17, enriched in the
3
, 500 MHz) δ: 1.33 (t, 6H, J ) 7.5 Hz), 2.72-
system, 4H), 2.94-3.01 (m, 2H),
) δ: 6.9, 43.6, 46.2. IR
) -142 (c 0.9, EtOH). HRMS: calcd
1
(
R,S) diastereoisomer. H NMR (CDCl
3
, 500 MHz) δ: 1.47 (s,
.82 (AB fragment of an ABX
3
.13-3.20 (m, 2H).
1
3
18H), 3.20-3.24 (m, 2H), 3.68 (AB system, 4H, J ) 14 Hz, ∆υ
) 16.3 Hz). C NMR (CDCl , 125 MHz) δ: 29.9, 44.3, 55.3,
C NMR (CDCl
3
13
-
1
25
3
(
cm , νSO): 1015. [R]
D
+
84.0, 163.6.
for C
6
H
15
O
2
S
2
(M + 1) 183.0513, found 183.0516 (-1.3 ppm).
(
R,R)-Bis(ter t-b u t oxyca r b on ylm et h a n esu lfin yl)et h -
(
S,S)-Bis(isopr opylsu lfin yl)eth an e [12(S,S)]. White solid.
a n e [17(R,R)]. Purified by crystallization from ethanol/hexane
1
Crystallized from ethanol-ethyl acetate. Mp: 65-70 °C.
NMR (CDCl ) δ: 1.25 (d, 6H, J ) 6.9 Hz), 1.32 (d, 6H, J ) 6.9
Hz), 2.85 (hept, 2H, J ) 6.9 Hz), 2.90-2.99 (m, 2H), 3.06-
H
and ethyl acetate/hexane. Specrospcopical data are identical
3
2
5
to those of the 17(S,S) enantiomer. [R]
D
) -138 (c 1.0,
CHCl ).
3
1
3
3
.15 (m, 2H). C NMR (CDCl
3
) δ: 15.1, 15.8, 41.3, 51.2. IR
P r ep a r a tion of En a n tiop u r e Ar yl (or Alk yl) Meth yl
Su lfoxid es. Gen er a l P r oced u r e. Methyl sulfoxides 25-28
were obtained in high yields by the addition of 1.2 equiv of
ArMgX (or RMgX) to a solution of diaceton-D-glucose (S)-
-
1
25
(
cm , νSO): 1030. [R]
D
) -149 (c 0.8, EtOH). HRMS: calcd
+
for C
8
H
19
O
2
S
2
(M + 1) 211.0826, found 211.0828 (-0.9 ppm).
(
R,R)-Bis(ter t-bu tylsu lfin yl)eth an e [13(R,R)]. White solid.
1
Crystallized from ethyl acetate-hexane. Mp: 154-156 °C. H
NMR (CDCl , 500 MHz) δ: 1.23 (s, 18H), 2.84-3.00 (m, 4H).
methanesulfinate 8S
stirred for 1h, quenched with saturated aqueous NH
solution, extracted with CH Cl , and purified by flash chro-
S
in toluene at 0 °C. The mixture was then
3
4
Cl
1
3
-1
C NMR (CDCl
3
, 125 MHz) δ: 22.8, 39.3, 53.8. IR (cm , νSO):
) +245 (c 0.5, ethanol). HRMS: calcd for C10
M + 1) 239.1139, found 239.1137 (0.8 ppm).
R,S)-Bis(ter t-bu tylsu lfin yl)eth a n e [13(R,S)]. H NMR
CDCl , 500 MHz) δ: 1.27 (s, 18H), 2.75-2.79 (m, 2H), 2.95-
.99 (m, 2H). C NMR (CDCl
R,R)-Bis(o-a n isylsu lfin yl)eth a n e [14(R,R)]. Purified by
flash column chomatography (CH Cl /acetone/hexane, 3:2:6).
White solid. Mp: 148-150 °C. H NMR (CDCl , 500 MHz) δ:
2
5
2
2
1
(
033. [R]
D
23 2 2
H O S
matography. Yields, specific rotations, and absolute configura-
+
tions are collected in Table 2.
1
(
1
(
S)-ter t-Bu tyl Meth yl Su lfoxid e (25). H NMR (CDCl
3
,
(
2
3
13
5
00 MHz) δ: 1.25 (s, 9H), 2.35 (s, 3H). C NMR (CDCl
3
, 125
). HRMS:
1
3
3
, 125 MHz) δ: 22.8, 40.4, 54.1.
25
MHz) δ: 22.5, 31.5, 52.6. [R]
calcd for C
ppm).
D
) +7.8 (c. 7, CHCl
3
(
+
5
H
12OS (M + 1) 120.0608, found 120.0609 (-0.5
2
2
1
3
1
(
S)-o-Tolyl Meth yl Su lfoxid e (26). H NMR (CDCl
3
, 500
MHz) δ: 2.33 (s, 3H), 2.64 (s, 3H), 7.13-7.18 (m, 1H), 7.34-
(57) Youn, J . H.; Hermann, R. Tetrahedron Lett. 1986, 27, 1493.
7.41 (m, 2H), 7.88-7.93 (s, 1H). 13C NMR (CDCl
3
, 125 MHz)