G. Zhao et al. / Tetrahedron: Asymmetry 13 (2002) 2095–2098
2097
In all cases, the reductions afforded the corresponding
b-hydroxy sulfones in excellent chemical yields. It is
noteworthy that aromatic b-keto sulfones were reduced
with excellent enantioselectivities (94–97% e.e.). To gain
insight on the effect of the electron density of the
aromatic ring, a series of b-keto sulfones bearing a
different substituent at the para position on the phenyl
group was studied. The results show that the electron
density of the aromatic ring has little effect on the
enantioselectivity. Notably, higher enantioselectivity
could be obtained when the reduction occurred at the
more hindered carbonyl group.
cally active b-hydroxyl sulfones. Due to the efficiency,
low-cost and high enantioselectivity observed, the
method represents a very useful alternative to previ-
ously reported procedures.
4. Experimental
4.1. General
All reactions were carried out under a dry Ar atmo-
sphere. THF was freshly distilled over sodium/benzo-
phenone ketyl before use. b-Keto sulfones were pre-
pared according to the reported procedure and further
purified by crystallization.
Under the above optimal reaction conditions, homoge-
neous sulfonamide 2 promoted the reduction of 2-
(phenylsulfonyl)actophenoneacetophenone
to
give
86.9% e.e.—less than the polymer-supported sulfon-
amide 1 (Scheme 2).
4.2. Typical procedure for the asymmetric reduction of
b-keto sulfones
Me3SiCl (0.132 mg, 1.2 mmol) was added to a suspen-
sion of NaBH4 (45 mg, 1.2 mmol) in THF (10 mL). The
suspension was heated under reflux and stirred for 1 h.
The polymeric catalyst 1 (98 mg, 0.25 mmol) was added
and the reaction mixture was heated under reflux for a
further 0.5 h. Then a THF (10 mL) solution of 2-
(phenylsulfonyl)acetophenone (260 mg, 1 mmol) was
added at a rate of 3 mL/h by syringe pump. After the
addition was complete, the mixture was treated with
water and filtered. The polymeric catalyst was washed
several times with EtOAc and water. The resulting
aqueous solution was extracted with EtOAc (3×10 mL)
and dried with MgSO4. The solution was evaporated
and purified by Silica gel chromatography to give a
Scheme 2.
Significantly, after the reduction was complete the poly-
mer-supported sulfonamide 1 could be recovered by
simple filtration followed by washing with water, and
methanol. Recycling of the chiral polymer catalyst was
tested by the reduction of 2-(phenylsulfonyl)aceto-
phenone (Table 2). The results showed that the chiral
polymeric catalyst could be reused at least five times
with little or no loss of performance.
1
white solid (258 mg, 98% yield); mp 93–94°C; H NMR
(300 MHz, CDCl3): l 3.25 (1H, dd, J=14.3 and 2.0
Hz), 3.40 (1H, dd, J=14.3 and 10.0 Hz), 3.69 (1H, s,
CHOH), 5.19 (1H, dd, J=10.0 and 2.0 Hz), 7.29–7.73
(10H, m, 2Ph); IR: 3343 (OH), 1286–1135 (SO2) cm−1;
[h]2D0=+31.8 (c 2.15, CHCl3) {lit.6b [h]2D7=+29.0 (c 1.0,
CHCl3)}. The optical yield was determined to be 94%
by chiralcel AD column chromatography (eluent:
VHexane:Vi-PrOH=4:1).
Table 2. The recycling of polymer-supported sufonylamide 1
Acknowledgements
We are grateful to the Ministry of Sciences and Tech-
nology, the State Key Project of Basic Research (Pro-
ject 973, No. G 2000048007) and the National Natural
Science Foundation of China for financial support.
Run (No.)
Yield (%)a
E.e. (%)b
1
2
3
4
5
98
97
99
98
98
94
95
96
94
97
References
a Isolated yield after column purification or distillation.
b Determined by chiral HPLC.
1. Phansavath, P. B.; Ratovelomanana-Vidal, V.; Genet, J.
P.; Touati, A. R.; Hornri, T.; Hassine, B. B. Tetrahedron:
Asymmetry 1999, 10, 1369.
3. Conclusion
2. Sato, T.; Okumura, Y.; Itai, J.; Fujisawa, T. Chem. Lett.
1988, 1537.
The results reported here offer a simple and highly
enantioselective methodology for the synthesis of opti-
3. Tanikaga, R.; Hosoya, K.; Kaji, A. J. Chem. Soc., Perkin
Trans. 1 1987, 1799.
Zhao, Gang
