Selenoxides Stabilized by Intramolecular Coordination
J . Org. Chem., Vol. 64, No. 22, 1999 8247
m/z 321 (M+, 80Se), 230, 214, 135, 91, 78; HRMS calcd for
C
2-((Dim eth yla m in o)m eth yl)d ip h en yl Selen id e (6). To
[R]435 -757.4 (c 0.50, CHCl3); CD (cyclohexane) λ 211 ([θ] -3.0
× 104), 225 (8.8 × 103), 279 (-3.7 × 104) nm; CD (MeOH) λ
205 ([θ] -1.1 × 104), 219 (2.4 × 104), 261 (-3.6 × 104) nm;
NMR, 13C NMR, 77Se NMR, IR, UV, and MS spectra were
almost the same as those of the racemic one.
16H19NO80Se 321.0632, found 321.0590.
1
HRMS calcd for C16H19NO80Se 321.0632, found 321.0598. H
a THF solution (30 mL) of 2-((dimethylamino)methyl)bromo-
benzene (1.84 g, 8.60 mmol) was added dropwise n-butyl-
lithium solution (1.6 N hexane solution, 10.8 mL, 17.2 mmol)
at -20 °C. After the solution was stirred for 2 h at -20 °C, a
THF solution (10 mL) of diphenyl diselenide (2.68 g, 8.60
mmol) was added dropwise to the solution at -20 °C. The
solution was stirred for an additional 21 h at room tempera-
ture. The solution was poured into water, and the product was
extracted with ether. The ether solution was washed with
brine and dried over magnesium sulfate. After removal of the
solvent in vacuo, purification by silica gel column chromatog-
raphy (chloroform) gave selenide 6 in 49% yield (1.22 g): 1H
NMR (500 MHz, CDCl3) δ 2.23 (s, 6H), 3.51 (s, 2H), 7.02-
7.55 (m, 9H); 13C NMR (125 MHz, CDCl3) δ 44.7, 64.4, 126.0,
127.5, 127.8, 129.2, 129.6, 131.6, 131.9, 134.0, 135.1, 139.5;
MS (EI) m/z 291 (M+, 80Se), 276, 245, 214, 183, 141, 78, 58.
r a c-2-((Dim et h yla m in o)m et h yl)d ip h en yl Selen oxid e
(r a c-3). To a methanol solution (180 mL) of selenide 6 (2.79
g, 9.60 mmol) was added dropwise tert-butyl hypochlorite (1.10
mL, 9.60 mmol) at -30 °C. After additional stirring for 6 h at
room temperature, the solution was poured into water, and
20 mL of 2 N NaOH solution was added. The solvent was
removed in vacuo, and water was added to the residue. The
product was extracted with benzene, washed with brine, and
dried over magnesium sulfate. After removal of the solvent in
vacuo, purification by silica gel column chromatography
(dichloromethane/methanol ) 10/1) followed by recrystalliza-
tion from dichloromethane/hexane gave the corresponding
selenoxide rac-3 in 79% yield (2.33 g): mp 132.0-134.0 °C;
1H NMR (500 MHz, CDCl3) δ 2.02 (s, 6H), 3.18 (d, 1H, J )
13.9 Hz), 3.58 (d, 1H, J ) 13.9 Hz), 7.18-8.46 (m, 9H); 13C
NMR (125 MHz, CDCl3) δ 44.1, 62.8, 127.2, 127.5, 128.3, 128.8,
129.2, 130.5, 130.7, 138.6, 141.5, 144.6; 77Se NMR (95 MHz,
CDCl3) δ 879; IR (KBr) νmax 2830, 1610, 1430, 1020, 965, 845,
795, 745, 690 cm-1; UV (cyclohexane) λmax 222 (ꢀ 1.4 × 104),
261 (3.2 × 103) nm; UV (MeOH) λmax 218 (ꢀ 1.6 × 104), 258
(sh, 4.2 × 103) nm; MS (EI) m/z 307 (M+, 80Se), 292, 276, 263,
(R)-(+)-Ben zyl 2-((Dim eth yla m in o)m eth yl)p h en yl Se-
len oxid e {(R)-(+)-2}: 100% ee; [R]D 299.2 (c 0.50, CHCl3);
[R]435 791.6 (c 0.50, CHCl3); CD (cyclohexane) λ 211 ([θ] 3.2 ×
104), 224 (-1.4 × 104), 279 (4.3 × 104) nm; CD (MeOH) λ 206
([θ] 1.9 × 104), 220 (-3.1 × 104), 265 (4.6 × 104) nm; HRMS
calcd for C16H19NO80Se 321.0632, found 321.0598. 1H NMR,
13C NMR, 77Se NMR, IR, UV, and MS spectra were almost the
same as those of the racemic one.
(S)-(-)-2-((Dim eth yla m in o)m eth yl)d ip h en yl Selen ox-
id e {(S)-(-)-3}: mp 68.0-69.0 °C; 100% ee; [R]D -48.1 (c 0.26,
CHCl3); [R]435 -117.8 (c 0.26, CHCl3); CD (cyclohexane) λ 208
([θ] 5.6 × 104), 228 (-6.3 × 104), 275 (-7.8 × 103) nm; CD
(MeOH) λ 208 ([θ] -1.4 × 104), 226 (-6.2 × 104), 247 (2.7 ×
103), 277 (-4.6 × 103) nm; HRMS calcd for C15H17NO80Se
1
307.0475, found 307.0520. H NMR, 13C NMR, 77Se NMR, IR,
UV, and MS spectra were almost the same as those of the
racemic one.
(R)-(+)-2-((Dim eth yla m in o)m eth yl)d ip h en yl Selen ox-
id e {(R)-(+)-3}: mp 63.0-64.0 °C; 90% ee; [R]D 37.2 (c 0.17,
CHCl3); [R]435 86.0 (c 0.17, CHCl3); CD (cyclohexane) λ 205 ([θ]
-5.8 × 104), 227 (4.9 × 104), 276 (5.4 × 103) nm; CD (MeOH)
λ 208 ([θ] 1.2 × 104), 226 (4.1 × 104), 247 (-2.0 × 103), 278
(3.1 × 103) nm; HRMS calcd for C15H17NO80Se 307.0475, found
307.0500. 1H NMR, 13C NMR, 77Se NMR, IR, UV, and MS
spectra were almost the same as those of the racemic one.
Syn t h esis of (S)-(-)-2-((Dim et h yla m in o)m et h yl)-4′-
m eth yld ip h en yl Su lfoxid e {(S)-(-)-9}. To an ether solution
(125 mL) of (S)s-(-)-menthyl-(-)-p-toluenesulfinate (100% ee;
1.47 g, 5.00 mmol)11,12 was added 2-((dimethylamino)methyl)-
phenylmagnesium bromide, prepared from 2-((dimethylami-
no)methyl)bromobenzene (2.25 g, 10.5 mmol) and magnesium
(3.77 g), dropwise at 0 °C.12,13 After additional stirring for 1 h
at room temperature, the mixture was poured into brine. The
product was extracted with ether and dried over magnesium
sulfate. After removal of the solvent in vacuo, purification by
gel permeation chromatography gave (S)-(-)-sulfoxide {(S)-
(-)-9} in 90% yield (1.23 g): 91% ee; [R]D -81.6 (c 1.26, CHCl3);
[R]D -105.9 (c 1.39, acetone); [R]435 -192.9 (c 1.26, CHCl3);
[R]435 -245.3 (c 1.39, acetone); CD (cyclohexane) λ 226 ([θ] -4.2
× 104), 252 (1.0 × 104), 284 (-2.2 × 103) nm; CD (MeCN) λ
226 ([θ] -7.0 × 104), 251 (1.1 × 104), 274 (-2.7 × 103) nm; CD
247, 214, 185, 169, 157, 91, 78, 58. Anal. Calcd for C15H17
-
NOSe: C, 58.83; H, 4.57; N, 5.59. Found: C, 58.88; H, 4.51;
N, 5.66.
Op tica l Resolu tion of Ra cem ic Selen oxid es by Mea n s
of High -P er for m a n ce Liqu id Ch r om a togr a p h y Usin g a n
Op tica lly Active Colu m n . Optical resolutions of racemic
selenoxides rac-1, -2, and -3 were performed by HPLC using
optically active columns packed with amylosecarbamate de-
rivative/silica gel (Daicel Chiralpak AS, 4.6 × 250 mm for an
analytical scale and 10 × 250 mm for a preparative scale)
eluted by hexane/ethanol (75/25). On a preparative scale,
typically, 150 mg of racemic selenoxide was charged to the
column. A 50 mg sample of the first-eluted selenoxide and a
50 mg sample of the second-eluted selenoxide were collected,
and each of the collected components was charged again to
the column, separately. Finally, ca. 10-20 mg of optically pure
selenoxides was obtained except for the case of (+)-3.
(S)-(-)-2-((Dim eth yla m in o)m eth yl)p h en yl Meth yl Se-
len oxid e {(S)-(-)-1}: 100% ee; [R]D -120.8 (c 0.32, CHCl3);
[R]435 -313.2 (c 0.32, CHCl3); CD (cyclohexane) λ 207 (sh, [θ]
1.1 × 104), 221 (-6.3 × 103), 231 (1.8 × 103), 270 (-2.4 × 104)
nm; CD (MeOH) λ 216 ([θ] 2.6 × 103), 234 (-7.3 × 103), 247
(-7.0 × 103) nm; HRMS calcd for C10H15NO80Se 245.0319,
1
(MeOH) λ 219 ([θ] 1.9 × 104), 232 (-4.9 × 104) nm; H NMR
(500 MHz, CDCl3) δ 2.08 (s, 6H), 2.35 (s, 3H), 3.19 (d, 1H, J )
13.3 Hz), 3.70 (d, 1H, J ) 13.3 Hz), 7.21 (d, 2H, J ) 8.0 Hz),
7.28 (d, 1H, J ) 7.6 Hz), 7.38 (dd, 1H, J ) 7.6, 7.6 Hz), 7.47
(dd, 1H, J ) 7.6, 7.6 Hz), 7.53 (d, 2H, J ) 8.0 Hz), 8.06 (d, 1H,
J ) 7.6 Hz); 13C NMR (125 MHz, CDCl3) δ 21.3, 44.3, 61.1,
125.6, 125.9, 128.5, 129.3, 129.6, 130.4, 137.7, 140.7, 142.9,
144.9; IR (neat) νmax 2930, 1460, 1180, 1040, 820 cm-1; UV
(MeCN) λmax 202 (ꢀ 4.0 × 104), 238 (1.8 × 104) nm; UV (MeOH)
λmax 206 (ꢀ 3.3 × 104), 238 (1.9 × 104) nm; MS (EI) m/z 274
(M+ + 1), 213, 134, 91. Anal. Calcd for C16H19NOS: C, 70.29;
H, 7.00; N, 5.12. Found: C, 70.04; H, 7.05; N, 5.03.
Kin etic Stu d ies for th e Ra cem iza tion of Op tica lly
Active Selen oxid es. The kinetic studies for racemization of
optically active selenoxides 1-3 were carried out in 7 mM
solution at 27 °C, and the rates of racemization were calculated
on the basis of their specific rotations.
1
found 245.0315. H NMR, 13C NMR, 77Se NMR, IR, UV, and
MS spectra were almost the same as those of the racemic one.
(R)-(+)-2-((Dim eth yla m in o)m eth yl)p h en yl Meth yl Se-
len oxid e {(R)-(+)-1}: 100% ee; [R]D 119.8 (c 0.23, CHCl3);
[R]435 296.6 (c 0.23, CHCl3); CD (cyclohexane) λ 206 (sh, [θ]
-9.0 × 103), 220 (4.7 × 103), 229 (-1.5 × 103), 270 (2.1 × 104)
nm; CD (MeOH) λ 214 ([θ] -4.2 × 103), 234 (8.8 × 103), 247
(8.5 × 103) nm; HRMS calcd for C10H15NO80Se 245.0319, found
245.0292. 1H NMR, 13C NMR, 77Se NMR, IR, UV, and MS
spectra were almost the same as those of the racemic one.
(S)-(-)-Ben zyl 2-((Dim eth yla m in o)m eth yl)p h en yl Se-
len oxid e {(S)-(-)-2}: 100% ee; [R]D -300.4 (c 0.50, CHCl3);
Ack n ow led gm en t. This work was financially sup-
ported in part by a Grant-in-Aid for Scientific Research
on Priority Area and General Scientific Research from
the Ministry of Education, Science, Sports, and Culture,
J apan.
J O990993N