D.-Z. Xu et al. / Tetrahedron 66 (2010) 8899e8903
8903
d
(ppm) 1.24e1.31 (m, 1H), 1.49e1.73 (m, 3H), 2.87 (t, 2H,
J¼7.2 Hz), 3.15e3.31 (m, 2H), 3.40 (dd, 1H, J1¼3.2 Hz, J2¼12.0 Hz);
13C NMR (100 MHz, D2O):
(ppm) 22.97, 25.39, 45.21, 59.88,
1.0 mL/min, 254 nm, syn: t1¼23.8, t2¼27.4, 54% ee; anti: t1¼30.8,
t2¼41.77), 38% ee.
d
60.91; 31P NMR (162 MHz, D2O)
d 4.29; HRMS calcd for
Acknowledgements
20
C5H13NO3Pþ Mþ 166.0628, found 166.0628; [
CH3OH).
a
]
þ34.4ꢀ (c 0.5,
D
This work was financially supported by the National Natural
Science Foundation of China (grant no. 20672061, China) and Na-
tional Basic Research Program of China (973 Program) (no.
2010CB833301). We also thank the Nankai University State Key
Laboratory of Elemento-Organic Chemistry for support.
4.2.4. Hydrochloric acid salts of ((S)-pyrrolidin-2-yl)methyl dihy-
drogen phosphate 5. To a dry round-bottom flask with magnetic
stir bar were added 180 mL dry CH2Cl2 and POCl3 (12.1 g,
80 mmol) at 0 ꢀC via an ice bath. To this solution was added
a solution of N-Boc-L-prolinol (1.6 g, 8.0 mmol) in 20 mL CH2Cl2 via
Supplementary data
cannula, dropwise, under argon at 0 ꢀC. The reaction was allowed
to stir at the same temperature for 2 h. Then the reaction mixture
was warmed to room temperature and stirred overnight. The or-
ganic solvents and POCl3 was evaporated to give a colorless oil,
which was used without further purification. To a solution of the
oil in CH2Cl2 (20 mL) was added dropwise 8 mL HCl at 0 ꢀC, and
stirring was continued at room temperature overnight. The sol-
vent was removed, and the residue was purified by chromatog-
raphy (ethyl acetate/MeOH 6:1 then 2:1) to give 1.26 g (73% yield)
Supplementary data associated with this article can be found in
References and notes
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of 5 as a wax; 1H NMR (400 MHz, D2O):
1.94e2.20 (m, 3H), 3.30 (t, 2H, J¼7.6 Hz), 3.73e3.90 (m, 2H),
d (ppm) 1.73e1.90 (m, 1H),
4.01e4.13 (m, 1H); 13C NMR (100 MHz, D2O):
d (ppm) 24.07, 25.91,
45.56, 60.39, 62.73; 31P NMR (162 MHz, D2O)
for C5H13NO4Pþ Mþ 182.0577, found 182.0578; [
CH3OH).
d 4.32; HRMS calcd
20
a
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D
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To a mixture of catalyst 3 (6.4 mg, 0.02 mmol) in [Bmin][BF4]
(0.5 mL) NaHCO3 (1.0 mg, 0.01 mmol) was added at room tem-
perature under air. The reaction mixture was stirred for 10 min,
then cyclohexanone (208 mL, 2.0 mmol) and trans-b-nitrostyrene
(30 mg, 0.2 mmol) were added. The homogeneous reaction mixture
was stirred at room temperature for 45 h. 5 mL H2O was added, the
mixture was extracted with ethyl acetate three times (5 mLꢂ3) and
the combined extracts were washed with brine, then dried over
anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The residue was purified by flash silica gel chromatog-
raphy (ethyl acetate/hexane 1:6) to afford the Michael adduct 8a
(49 mg, 99% yield) as white solid. syn/anti¼99/1 (by 1H NMR), The
ee was determined by HPLC analysis (Chiralpak AD-H, i-PrOH/
hexane¼10/90, 0.5 mL/min, 254 nm, tr (minor)¼24.0 min, tr
(major)¼31.5 min), 84% ee.
4.4. Representative procedure for the Aldol reaction
To a mixture of catalyst 3 (6.4 mg, 0.02 mmol) in DMSO (0.5 mL)
NaHCO3 (1.0 mg, 0.01 mmol) was added at room temperature under
air. The reaction mixture was stirred for 10 min, then cyclohexa-
none (208
mL, 2.0 mmol) and 4-nitrobenzaldehyde (30 mg,
0.2 mmol) were added. The homogeneous reaction mixture was
stirred at room temperature for 24 h. H2O (5 mL) was added, the
mixture was extracted with ethyl acetate three times (5 mLꢂ3) and
the combined extracts were washed with brine, then dried over
anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. The residue was purified by flash silica gel chromatog-
raphy (ethyl acetate/hexane 1:6) to afford the pure Aldol product 10
(48 mg, 95% yield). syn/anti¼37/63 (by 1H NMR), The ee was de-
termined by HPLC analysis (Chiralpak AD-H, i-PrOH/hexane¼8/92,
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