836
J. Liu et al. / Tetrahedron: Asymmetry 19 (2008) 832–837
white solid in quantitative yield, 4.5 g, 99% yield. 1H NMR
(CDCl3) d: 7.49 (d, J = 9, 2H), 7.42–7.37 (m, 5H), 6.92 (d,
J = 9, 2H), 5.09 (s, 2H) ppm; ESI-MS [M+H]+ 282.3.
0.1 mmol) in 20 ml of methanol was stirred at room tem-
perature for 24 h under an atmosphere of H2. Then the
reaction mixture was filtered and washed with 5 ml of
methanol. The combined organic solution was evaporated
in vacuum. The residue was purified by chromatography
(5% methanol in chloroform as eluents) to yield a colorless
powder (465 mg, 99% yield). 1H NMR ((CD3)2SO) d: 10.07
(s, 1H), 7.95 (d, J = 8.7 Hz, 2H), 7.25 (s, 1H), 7.02–7.24 (m,
10H), 6.50 (d, J = 8.7 Hz, 2H), 4.79 (m, 1H, CH), 4.60 (m,
1H), 1.25 (s, 9 H) ppm. APCI-MS [M+H]+ 469.2.
4.1.3. Polyethylene glycol monomethyl ether tosylate. To
polyethylene glycol monomethyl ether (MW750) (7.5 g,
10 mmol) and p-toluenesulfonyl chloride (7.5 g, 40 mmol)
in methylene chloride (50 ml) was added 2 ml (20 mmol)
of pyridine under a nitrogen atmosphere. The reaction mix-
ture was stirred at room temperature for 5 h. The resulting
solution was poured into 100 ml of 10% HCl and extracted
twice with methylene chloride (50 ml). The combined or-
ganic layers were dried over anhydrous magnesium sulfate
and filtered. The solvent was removed under reduced pres-
sure to give a yellow oil. The crude product could be fur-
ther purified by column chromatography (ethyl acetate/
methanol = 4:1 as eluents) to yield a colorless liquid,
4.1.7. Boc-PEG-BsDPEN ligand. A solution of tert-butyl-
(1S,2S)-2-(4-hydroxyphenylsulfonamido)-1,2-diphenyleth-
ylcarbamate (469 mg, 1 mmol), poly(ethylene glycol)
monomethyl ether tosylate (905 mg, 1 mmol), and Cs2CO3
(652 mg, 2 mmol) in 10 ml of acetone was heated at reflux
for 24 h. The residue was triturated with CH2Cl2. The ex-
tract was filtered and dried over Na2SO4. Evaporation of
the solvent in vacuum gave the crude product, which was
further purified by chromatography (5% methanol in chlo-
roform as eluents) to yield a yellow oil, 850 mg, 65% yield.
1H NMR (CDCl3) d: 8.28 (s, 1H), 7.95 (d, J = 8.7 Hz, 2H),
7.25 (s, 1H), 7.02–7.24 (m, 10H), 6.50 (d, J = 8.7 Hz, 2H),
4.79 (m, 1H, CH), 4.60 (m, 1H), 1.25 (s, 9H) ppm.
1
6.8 g, 75% yield. H NMR (CDCl3) d: 7.79 (d, J = 8.4,
2H), 7.34 (d, J = 8.4, 2H), 4.16 (t, J = 4.5, 2H), 4.15 (t,
J = 4.8, 2H), 3.68 (t, J = 4.8, 2H), 3.63 (m, 56H), 3.57 (s,
3H), 3.37 (s, 3H) ppm.
4.1.4. N-((1S,2S)-2-Amino-1,2-diphenylethyl)-4-(benzyloxy)-
benzenesulfonamide. To a solution of (1S,2S)-1,2-diphen-
ylethane-1,2-diamine (836 mg, 2 mmol) and triethylamine
(0.28 ml, 2 mmol) in anhydrous dichloromethane (10 ml)
was added dropwise a solution of 4-(benzyloxy)benzene-
1-sulfonyl chloride (565 mg, 2 mmol) in dichloromethane
(5 ml) at 0 °C. The mixture was stirred at 0 °C for 2 h
and allowed to warm to room temperature. Water (5 ml)
was added and the two layers were separated. The aqueous
layer was extracted twice with 5 ml of dichloromethane and
the combined organic layers were washed with brine and
water and subsequently dried over sodium sulfate. The
solvent was removed under reduced pressure. The crude
N-((1S,2S)-2-amino-1,2-diphenylethyl)-4-(benzyloxy)benz-
enesulfonamide was purified by column chromatography
(5% methanol in ethyl acetate as eluents) to give a white
4.1.8. PEG-BsDPEN ligand. Boc-PEG-BsDPEN ligand
(850 mg, 0.7 mmol) was added to a mixture of trifluoroace-
tic acid (10 ml) and methylene chloride (10 ml). The mix-
ture was stirred at room temperature for 4 h and then
poured into water (10 ml). Aqueous sodium hydroxide
was added to adjust the pH value up to 10. The organic
layer was separated and the aqueous layer was extracted
twice with methylene chloride (5 ml). The combined organ-
ic layers were dried over anhydrous sodium sulfate. The
solvent was removed under reduced pressure to give a yel-
1
low oil, 730 mg, 95% yield. H NMR (CDCl3) d: 10.07 (s,
1H), 7.95 (d, J = 8.7 Hz, 2H), 7.25 (s, 1H), 7.02–7.24 (m,
10H), 6.50 (d, J = 8.7 Hz, 2H), 4.79 (m, 1H, CH), 4.60
(m, 1H), 1.25 (s, 9H) ppm. APCI-MS is shown in Figure 1.
1
solid, 780 mg, 85% yield. H NMR (CDCl3) d: 7.41–7.39
(m, 4H), 7.33 (d, J = 9, 2H), 7.14–7.10 (m, 10H), 6.71 (d,
J = 9, 2H), 5.04 (s, 2H) 4.35 (d, J = 5, 1H), 4.11 (d,
J = 5, 1H), 1.53 (br, 2H) ppm; APCI-MS [M+H]+ 459.2.
4.2. General procedure for asymmetric transfer
hydrogenation
4.1.5. tert-Butyl-(1S,2S)-2-(4-(benzyloxy)phenylsulfonami-
do)-1,2-diphenylethylcarbamate.
A suspension of [RuCl2(p-cymene)]2 (3 mg, 0.005 mmol)
and PEG-BsDPEN [(S,S), 16 mg, 0.012 mmol] in H2O
(2 ml) was purged with argon and stirred at 40 °C for
1 h. Then, HCOONa (340 mg, 5.0 mmol) and a ketone
(1.0 mmol) were introduced to the catalyst solution. The
mixture was purged with argon and stirred at room temper-
ature. After a certain period of time, the organic com-
pounds were extracted with hexane (6 ml). The
conversion was determined by GC with an HP-5 capillary
column, and the enantioselectivity was determined by chi-
ral HPLC analysis.
A
solution
of
N-
((1S,2S)-2-amino-1,2-diphenylethyl)-4-(benzyloxy)benzene-
sulfonamide (458 mg, 1.0 mmol), DIBOC (262 mg,
1.2 mmol), and Et3N (202 mg, 2 mmol) in 20 ml of CH2Cl2
was stirred at room temperature for 4 h. The solution was
washed with 5% aq HCl. The organic phase was separated
and dried over Na2SO4. The crude product was purified by
chromatography (chloroform as eluents) to yield a white
1
powder, 544 mg, 98% yield. H NMR (CDCl3) d: 7.45 (d,
J = 8.8 Hz, 2H), 7.38–7.40 (m, 5H), 7.34 (s, 1H), 6.78–
7.16 (m, 10H), 6.76 (d, J = 8.8 Hz, 2H), 5.20 (s, 2H), 4.78
(m, 1H), 4.55 (m, 1H), 1.47 (s, 9H) ppm. APCI-MS
[M+H]+ 559.2.
4.3. General procedure of catalyst recycling in asymmetric
transfer hydrogenation of acetophenone in water
4.1.6. tert-Butyl-(1S,2S)-2-(4-hydroxyphenylsulfonamido)-
1,2-diphenylethylcarbamate.
(1S,2S)-2-(4-(benzyloxy)phenylsulfonamido)-1,2-diphenyl-
A suspension of [RuCl2(p-cymene)]2 (3 mg, 0.005 mmol)
and PEG-BsDPEN [(S,S), 16 mg, 0.012 mmol] in H2O
(2 ml) was purged with argon and stirred at 40 °C for
1 h. Then, HCOONa (340 mg, 5.0 mmol) and acetophe-
A solution of tert-butyl-
ethylcarbamate (559 mg, 1 mmol) and 10% Pd/C (11 mg,