Synthesis and Application of Chiral Phospholane Ligands
COMMUNICATIONS
hydrochloric acid (200 mL Â 2), water (100 mL), and brine
(100 mL). The solvent was removed under reduced pressure,
and the residue was recrystallized from toluene À methanol to
give 7 as a white solid; yield: 24.30 g (87%); mp 142 143 8C;
1H NMR (CDCl3): d 1.31 (36H, s), 3.68 (6H, s), 6.71 6.74
(1H, m), 7.07 (4H, d, J 7.6 Hz), 7.15 7.23 (2H, m), 7.57 7.60
(1H, m); 31P NMR (CDCl3): d À 3.1 (s); EI-MS: m/z 626
Under a nitrogen atmosphere, a 1.6 M solution of n-
butyllithium in hexane (5.67 mL, 9.1 mmol) was added drop-
wise to a solution of the crude 9 (5.00 g) in THF (100 mL) at
0 8C. The solution was stirred at 0 8C for 1 h and then a solution
of (2R,5R)-2,5-hexanediolcyclicsulfate(1.64 g, 9.1 mmol)[5c] in
THF (30 mL) was added dropwise at 0 8C. The reaction
mixture was allowed to warm to room temperature and then
stirred for 1 h. A 1.6 M solution of n-butyllithium in hexane
(5.67 mL, 9.1 mmol) was again added dropwise to the reaction
mixture at 0 8C. The reaction mixture was stirred at room
temperature for 15 h. Methanol (1 mL) was added to quench
any excess n-butyllithium remaining and the solvents were
evaporated under reduced pressure. The residue was dissolved
in diethyl ether (60 mL) and the insoluble material was filtered
off. The filtrate was evaporated and the residue was purified
by flash chromatography on silica gel (hexane/
dichloromethane 3/1 to 1/1) to give 5d as a white solid; yield:
2.41 g (36% from 7); mp 65 66 8C; [a]D29: 118.8 (c 1.00,
CH2Cl2); 1H NMR (CD2Cl2): d 0.73 (3H, dd, J 7.2, 9.3 Hz),
1.05 (3H, J 7.1, 13.7 Hz), 1.29 (18H, s), 1.30 (18H, s), 1.49
1.61 (2H, m), 2.00 2.06 (1H, m), 2.15 2.35 (2H, m), 2.48 2.58
(1H, m), 3.65 (3H, s), 3.65 (3H, s), 6.92 6.95 (1H, m), 7.05 (2H,
d, J 7.1 Hz), 7.09 (2H, d, J 7.1 Hz), 7.21 7.24 (1H, m),
7.28 7.31 (1H, m), 7.50 7.52 (1H, m); 31P NMR (CD2Cl2): d
À 1.80 (d, J 160 Hz), À 13.0 (d, J 160 Hz); EI-MS: m/z
(M ).
1-Bis(3,5-di-tert-butyl-4-methoxyphenyl)phosphino-2-
[(2S,5S)-2,5-dimethylphospholano]benzene (5d)
Under a nitrogen atmosphere, a 1.6 M solution of n-butyllithi-
um in hexane (16.2 mL, 25.2 mmol) was added dropwise to a
solution of 7 (15.00 g, 24.0 mmol) in THF (150 mL) at À 78 8C
for 30 min. The solution was stirred at À 78 8C for 1 h and then
diethyl chlorophosphonite (4.15 g, 25.2 mmol) was added
dropwise. The reaction mixture was allowed to warm to room
temperature and then stirred for 15 h. After evaporation of the
solvent, the residue was dissolved in diethyl ether (50 mL) and
the insoluble material was filtered off. The filtrate was
evaporated and the residue was purified by chromatography
through a short alumina column (hexane/ethyl acetate 4/1)
to give a 77:23 mixture of 8 and bis(3,5-di-tert-butyl-4-
methoxyphenyl)phenylphosphine as a pale yellow, waxy solid.
The ratio of a mixture was determined by 1H NMR. The crude
product 8 was used for the next reaction without further
purification; yield: 14.03 g.
660 (M ).
8: 1H NMR (CD2Cl2): d 1.00 (6H, t, J 7.0 Hz), 1.29 (36H,
s), 3.51 3.57 (2H, m), 3.65 (6H, s), 3.78 3.82 (2H, m), 7.03
(4H, d, J 7.7 Hz), 7.30 7.34 (2H, m), 7.39 7.40 (1H, m),
7.86 7.89 (1H, m); 31P NMR (CD2Cl2): d À 17.5 (d, J
149 Hz), 150.1 (d, J 149 Hz).
[Rh(cod)(5d)]OTf
Under a nitrogen atmosphere, a solution of 5d (100.0 mg,
0.151 mmol) in dichloromethane (3 mL) was added dropwise
to a stirred solution of [Rh(cod)2]OTf (67.5 mg, 0.144 mmol) in
dichloromethane (2 mL) at room temperature. The mixture
was stirred for 30 min, and the solvent was removed under
reduced pressure. The residue was recrystallized from di-
chloromethane-diethyl ether to give the title complex as a
orange-yellow solid; yield: 140.0 mg (95%); 1H NMR (CD2Cl2):
d 1.12 (3H, dd, J 7.1, 15.3 Hz), 1.29 1.35 (3H, m), 1.33
(18H, s), 1.35 (18H, s), 1.52 1.64 (1H, m), 1.90 2.02 (1H, m),
2.08 2.18 (1H, m), 2.23 2.76 (11H, s), 3.71 (3H, s), 3.73 (3H,
s), 4.68 4.75 (1H, m), 5.04 5.11 (1H, m), 5.42 5.54 (2H, m),
7.30 (2H, d, J 12.1 Hz), 7.37 (2H, d, J 12.1 Hz), 7.50 7.54
(1H, m), 7.56 7.61 (1H, m), 7.65 7.71 (1H, m), 7.73 7.77
(1H, m); 31P NMR (CD2Cl2): d 61.4 (dd, J 27, 148 Hz), 74.8
(dd, J 27, 148 Hz).
Bis(3,5-di-tert-butyl-4-methoxyphenyl)phenylphosphine):
1H NMR (CD2Cl2): d 1.32 (36H, s), 3.67 (6H, s), 7.13 (4H, d,
J 8.2 Hz), 7.24 7.29 (2H, m), 7.30 7.35 (3H, m); 31P N MR
(CD2Cl2): d À 4.3 (s).
Under a nitrogen atmosphere, trimethylsilyl chloride
(4.89 g, 45.0 mmol) was added to a suspension of lithium
aluminum hydride (1.71 g, 45.0 mmol) in THF (75 mL) at À
30 8C. The resulting mixture was allowed to warm to room
temperature and then stirred for 1.5 h. A solution of the crude 8
(10.00 g) in THF (50 mL) was then added dropwise to the
reducing mixture at À 30 8C over 30 min. The resulting
mixture was allowed to warm to room temperature and then
stirred for 16 h. A solution of water (20 mL) in THF (20 mL)
followed by 1 Naqueous sodium hydroxide (30 mL) was added
slowly dropwise, and the two layers were separated. After the
organic layer was concentrated, diethyl ether (50 mL) and
water (20 mL) were added to the residue and then the two
layers were separated. The organic layer was washed with
water (20 mL Â 2) and dried over sodium sulfate. The solvent
was removed under reduced pressure to give a 70:30 mixture of
9 and bis(3,5-di-tert-butyl-4-methoxyphenyl)phenylphosphine
as a white, waxy solid. The ratio of the mixture was determined
by 1H NMR. The crude product 9 was used for the next reaction
without further purification; yield: 8.20 g.
Asymmetric Hydrogenation of (Z)-N-Benzoyl-1-
phenylpropenamine (3)
[Rh(cod)(5d)]OTf (1.8 mg, 0.0018 mmol), (Z)-N-benzoyl-1-
phenylpropenamine 3 (214 mg, 0.90 mmol) and methanol
(3 mL) were charged to a 100 mL stainless steel autoclave
under a nitrogen stream. Hydrogen (0.4 MPa) was introduced
and the mixture was stirred for 15 h at 30 8C. The conversion
and ee of (S)-N-benzoyl-1-phenylpropylamine 4 were deter-
mined by capillary GLC analysis using an SPB-1 column and by
1
9: H NMR (CD2Cl2): d 1.31 (36H, s), 3.67 (6H, s), 3.95
(2H, dd, J 12.3, 205.3 Hz), 6.86 6.89 (1H, m), 7.07 (4H, d,
J 8.2 Hz), 7.21 7.22 (2H, m), 7.53 7.57 (1H, m); 31P N MR HPLC analysis using a CHIRALCEL OD-H column ( > 99%
(CD2Cl2): d À 124.3 (d, J 92 Hz), À 9.6 (d, J 92 Hz).
conversion, 99% ee).
Adv. Synth. Catal. 2003, 345, 180 184
183