Ryoda et al.
4.30. [R]24D: -98.1 (c ) 0.51, MeOH). (-)-(S,S)-Diamine (-)-
7. The similar desalting of the above salt afforded (-)-7, [R]26
[R]24D: +106.2 (c ) 1.01, CHCl3). PF6 Salt. NH4PF6 (20 mg, 0.12
mmol) was added to a solution of 5 (50 mg, 0.12 mmol) in acetone
(0.45 mL) at 0 °C, and the whole was stirred at 0 °C for 1 min.
The solvent was evaporated in vacuo, and the residue was triturated
with H2O (0.4 mL). After removal of the supernatant, the residue
was dried under vacuum at 100 °C for 24 h and then recrystallized
from hexane-CH2Cl2 to give the PF6 salt (51 mg, 76%) as a
colorless powder. Mp: 174-175 °C. IR νmax cm-1: 1622 (CdN).
1H NMR (500 MHz): δ (ppm) 1.66 (s, 6H), 2.83 (s, 6H), 2.86 (m,
1H), 3.09 (dd, J ) 14.6, 2.4 Hz, 1H), 3.48 (br, 1H), 4.02 (d, J )
6.1 Hz, 2H), 4.32-4.35 (m, 1H), 4.48 (s, 2H), 5.90 (d, J ) 10.7
Hz, 1H), 6.99 (d, J ) 6.1 Hz, 2H), 7.04 (d, J ) 7.3 Hz, 2H), 7.20-
7.28 (m, 4H), 7.39 (dif. d, J ) 6.1 Hz, 3H), 7.46 (dif t, J ) 7.3 Hz,
2H). 13C NMR (125 MHz): δ (ppm) 18.5, 34.0, 38.5, 59.9, 64.2,
70.2, 126.4, 127.2, 127.5, 129.0, 129.1, 129.5, 131.0, 133.2, 136.4,
137.5, 160.2. LRFABMS m/z: 429 [(M - PF6)+]. [R]23D: +61.8
(c ) 0.1, CHCl3). Anal. Calcd for C28H34N3O‚PF6: C, 58.64; H,
5.98; N, 7.33. Found: C, 58.32; H, 5.94; N, 7.14.
:
D
-20.3 (c ) 0.1, CHCl3) (the ee was estimated to be 96% by HPLC).
(4S,5S)-Bis(2-methylphenyl)imidazolin-2-one (12). A solution
of the (-)-(S,S)-diamine 7 (191 mg, 0.80 mmol) and N,N′-
carbonyldiimidazole (170 mg, 1.05 mmol) in 1,2-dimethoxyethane
(8 mL) was refluxed for 2.5 h. After evaporation of the solvent,
the residue was purified by column chromatography (CHCl3) to
afford 12 (210 mg, 99%) as colorless prisms, mp 220-223 °C,
which were recrystallized from hexane-ethyl acetate. IR νmax cm-1
:
3215 (NH), 1707 (CdO). 1H NMR (400 MHz): δ (ppm) 1.77 (s,
6H), 4.84 (br, 2H), 4.95 (s, 2H), 7.05 (d, J ) 7.5 Hz, 2H), 7.20
(ddd, J ) 7.4, 7.4, 1.4 Hz, 2H), 7.30 (ddd, J ) 7.5, 7.5, 0.9 Hz,
2H), 7.70 (dd, J ) 7.9, 1.3 Hz, 2H). 13C NMR (100 MHz): δ (ppm)
18.7, 62.1, 126.4, 126.8, 128.1, 130.6, 135.7, 137.9, 162.8. HREIMS
m/z: 266.1426 (calcd for C17H18N2O 266.1419). Anal. Calcd for
C17H18N2O: C, 76.66; H, 6.81; N, 10.52. Found: C, 76.69; H, 6.71;
N, 10.56. [R]21D: +18.1 (c ) 1.0, CHCl3).
(4R,5R)-2-[(S)-1-Benzyl-2-hydroxyethyl]imino-1,3-dimethyl-
4,5-bis(2-methylphenyl)imidazolidine (ent-5). Similar treatment
using a solution of ent-14, derived from ent-7 (189 mg, 0.65 mmol),
in dry CH2Cl2 (3.0 mL) and a solution of (S)-phenylalaninol (98
mg, 0.65 mmol) and triethylamine (0.2 mL, 1.38 mmol) in dry CH2-
Cl2 (0.2 mL) gave ent-5 (238 mg, 86% from ent-14) as colorless
needles, mp 141-144 °C, which were recrystallized from hexane-
benzene. Anal. Calcd for C28H33N3O: C, 78.65; H, 7.78; N, 9.83.
Found: C, 78.43; H, 7.74; N, 9.75. [R]25D: -105.0 (c ) 1.01,
CHCl3).
(4S,5S)-1,3-Dibenzyl-4,5-diphenylimidazolidin-2-one (16). A
mixture of the urea 15 (3.54 g, 14.9 mmol), tetra-n-butylammonium
iodide (1.65 g, 4.47 mmol), benzyl bromide (5.60 g, 32.8 mmol),
and sodium hydride (55% in oil, 1.43 g, 32.8 mmol) in DMF (44.4
mL) was stirred at rt for 2 days, quenched with methanol (0.24
mL, 5.93 mmol) followed by 1.5 N HCl (70 mL), and extracted
with ethyl acetate (80 mL and 35 mL). The combined organic
solutions were washed with 20% Na2S2O3 aq (50 mL), water (59
mL), and brine (59 mL), dried (MgSO4), and evaporated. Purifica-
tion of the residue by column chromatography (toluene to ethyl
acetate/toluene ) 3:97) gave 16 (6.0 g, 97%) as colorless solids.
Mp: 145.5-147.5 °C (lit.29 mp 147 °C). 1H NMR (300 MHz): δ
(ppm) 3.61 and 5.08 (d, J ) 14.9 Hz, each 2H), 4.04 (s, 2H), 6.95-
6.97 (m, 4H), 7.13-7.15 (m, 4H), 7.24-7.30 (m, 12H).
(4S,5S)-1,3-Dibenzyl-4,5-diphenylimidazolidin-2-thione (17).
A mixture of the benzylurea 16 (2.0 g, 4.78 mmol) and Lawesson’s
reagent (3.87 g, 9.56 mmol) in o-xylene (20 mL) was heated at
145 °C for 24 h and quenched with methanol (30 mL) and 5%
HCl aq (8 mL). The resulting biphasic solution was stirred at rt
overnight. The organic layer was separated, and the aqueous phase
was extracted with toluene (20 mL). The combined organic solutions
were washed with water (30 mL × 9) and brine (30 mL), dried
(MgSO4), and evaporated. Purification of the residue by column
chromatography (ethyl acetate/hexane ) 2:98) gave 17 (1.88 g,
91%) as colorless prisms, mp 177-179 °C, which were recrystal-
lized from ether-hexane. IR: no characteristic absorption. 1H NMR
(300 MHz): δ (ppm) 3.77 and 5.88 (d, J ) 14.9 Hz, each 2H),
4.31 (s, 2H), 6.95-6.99 (m, 4H), 7.22-7.30 (m, 16H). 13C NMR
(75 MHz): δ (ppm) 48.9, 69.1, 127.0, 127.6, 128.4, 128.5, 128.6,
129.0, 135.9, 138.2, 182.4. HREIMS m/z: 434.1824 (calcd for
C29H26N2S 434.1817). [R]22D: -183 (c ) 1.02, CHCl3).
(4S,5S)-1,3-Dimethyl-4,5-bis(2-methylphenyl)imidazolidin-2-
one (13). To a mixture of sodium hydride (60% in oil, 78 mg,
1.96 mmol), which was washed with dry hexane under argon, in
DMF (0.2 mL) was added a solution of the urea 12 (201 mg, 0.76
mmol) in DMF (2.1 mL) followed by methyl iodide (0.15 mL, 2.42
mmol), and the whole was stirred at rt for 22 h. After acidification
with 5% HCl aq, the mixture was extracted with ethyl acetate (10
mL × 3). The combined organic solutions were washed with water
(30 mL × 5) and brine (100 mL), dried (MgSO4), and evaporated.
Purification of the residue by column chromatography (hexane/
ethyl acetate ) 1:1) gave 13 (217 mg, 98%) as colorless prisms,
mp 133-134.5 °C, which were recrystallized from hexane-ethyl
acetate. 1H NMR (400 MHz): δ (ppm) 1.69 (s, 6H), 2.67 (s, 6H),
4.43 (s, 2H), 7.05 (d, J ) 7.5 Hz, 2H), 7.20 (dd, J ) 7.4, 1.2 Hz,
2H), 7.24 (br, 2H), 7.47 (br, 2H). 13C NMR (100 MHz): δ (ppm)
18.6, 29.8, 65.8, 126.3, 126.8, 127.4, 127.8, 127.9, 136.6, 162.2.
[R]25 +128.1 (c ) 1.0, CHCl3). HREIMS m/z: 294.1732 (calcd
D
for C19H22N2O 294.1732).
(4S,5S)-2-Chloro-1,3-dimethyl-4,5-bis(2-methylphenyl)imida-
zolium Chloride (14). A mixture of the urea 13 (740 mg, 2.51
mmol) and oxalyl chloride (1.1 mL, 12.7 mmol) in benzene (17
mL) was refluxed for 24 h, and the excess of oxalyl chloride and
benzene were evaporated. The residual brownish solids obtained
were used for next step without further purification. 1H NMR (400
MHz): δ (ppm) 1.78 (s, 6H), 3.21 (s, 6H), 5.69 (s, 2H), 7.09-
7.44 (m, 6H), 8.13 (br, 2H).
(4S,5S)-2-[(R)-1-Benzyl-2-hydroxyethyl]imino-1,3-dimethyl-
4,5-bis(2-methylphenyl)imidazolidine (5). To an ice-cooled solu-
tion of (R)-phenylalaninol (309 mg, 2.04 mmol) and triethylamine
(0.7 mL, 4.08 mmol) in dry CH2Cl2 (0.2 mL) was added a solution
of the (S,S)-chloroamidine 14 (714 mg, 2.04 mmol) in dry CH2Cl2
(10 mL), and the whole was stirred under ice cooling for 1.5 h.
The mixture was diluted with CH2Cl2 (48 mL) and washed with
10% citric acid aq (48 mL). The aqueous solution was extracted
with CH2Cl2 (50 mL × 3). The combined organic solutions were
evaporated, and the residue was partitioned with water (80 mL)
and toluene (80 mL). The aqueous solution was basified with a
small amount of 30% NaOH aq and extracted with CH2Cl2 (20
mL × 4). The combined organic solutions were washed with brine,
dried (K2CO3), and evaporated to give 5 (605 mg, 56% from 13)
as colorless needles, mp 142-144 °C, which were recrystallized
from hexane-benzene. IR νmax cm-1: 1630 (CdN). 1H NMR (400
MHz): δ (ppm) 1.55 (dif s, 6H), 2.58 and 2.72 (dif s, each 3H),
2.83 (dif dq, J ) 6.8, 6.8 Hz, 2H), 3.56 and 3.58 (dd, J ) 10.0, 5.9
Hz, each 1H), 3.99 and 4.00 (dif s, each 1H), 4.23-4.29 (m, 1H),
6.97 (br d, J ) 7.6 Hz, 2H),7.15 (dd, J ) 7.3, 7.3 Hz, 2H), 7.21
(m, 4H), 7.26-7.35 (m, 5H), 7.56 (br s, 1H). 13C NMR (125
MHz): δ (ppm) 18.5, 33.2, 36.9, 40.3, 59.0, 66.1, 67.8, 70.6, 125.8,
126.6, 126.9, 127.6, 128.1, 129.7, 130.3, 136.4, 136.8, 140.1, 158.0.
LRFABMS m/z: 429 [(M + 2H)+]. Anal. Calcd for C28H33N3O:
C, 78.65; H, 7.78; N 9.83. Found: C, 78.19; H, 7.74; N, 9.73.
(4S,5S)-1,3-Dibenzyl-2-chloro-4,5-diphenylimidazolium Chlo-
ride (18). To a suspension of the thiourea 17 (1.88 g, 4.33 mmol)
in dry toluene (24 mL) was added oxalyl chloride (3.4 mL, 39.0
mmol). The resulting solution was heated at 80 °C for 30 h under
nitrogen. The separated colorless precipitates were collected by
filtration in a stream of nitrogen to afford 18 (1.77 g, 84%) as
hygroscopic colorless solids with 97% purity, which were used for
1
next step without further purification. H NMR (300 MHz): δ
(29) Ishii, K. Ph.D. Thesis, University of Tokyo, 1997.
140 J. Org. Chem., Vol. 73, No. 1, 2008