Asymmetric borane reduction of prochiral ketones by polymer-supported chiral sulfonamides

Full text of DOI:10.1021/jo000779v

J . Org. Chem. 2001, 66, 303-304
303
Sch em e 1. Asym m etr ic Red u ction of Keton es by
Asym m etr ic Bor a n e Red u ction of P r och ir a l
Keton es by P olym er -Su p p or ted Ch ir a l
Su lfon a m id es
Hom ogen ou s Ch ir a l Su lfon a m id e 2.
J ian-bing Hu, Gang Zhao,* Gao-sheng Yang, and
Zuo-ding Ding
Shanghai Institute of Organic Chemistry, Chinese Academy
of Science, 354 Fenglin Lu, Shanghai 200032, China
zhaog@pub.sioc.ac.cn
Received May 22, 2000
Polymer-supported (PS) sulfonamides have been pre-
pared by treating polymeric sulfonyl chlorides with (S)-
diphenylprolinol. The PS sulfonamides were investigated
as catalysts for the reduction of ketones by borane-
dimethyl sulfide complex. When the reductions were
conducted in refluxing THF with 15mol % 1f as catalyst,
excellent chemical yields and enantiomeric excess were
obtained. In addition to being recyclable, the catalyst
provided greater enantioselectivity than the homoge-
neous catalyst 2.
Sch em e 2 . P r ep a r a tion of P olym er -Su p p or ted
Ch ir a l Su lfon a m id es
The enantioselective reduction of prochiral ketones by
chiral catalysts and reagents has received intensive
interests in the past 20 years.1 A variety of homogeneous
chiral catalysts and reagents have been developed for the
reduction.2 However, the recovery and purification of
these catalysts and reagents are problematic. Immobili-
zation of chiral catalysts or reagents offers a solution to
the problem. The intrinsic advantages of polymer-sup-
ported catalysts are that they can be used in excess and
recovered by filtration at the end of reaction without loss
of activity.3 Several polymer-supported catalysts derived
from chiral amino alcohol have been developed for
reductions, but only few of them have displayed a high
enantioselectivity due to the polymer matrix restricting
the mobility of the catalytic site.4
Recently, we reported that the reduction of aromatic
ketones using a catalytic amount (10 mol %) of homoge-
neous chiral sulfonamides provided secondary alcohols
with 55-91% ee5 (Scheme 1). We demonstrated that
stereoselectivity is temperature dependent, with higher
reaction temperatures preferable (refluxing toluene).
Under the optimal reaction conditions, homogeneous
sulfonamide 2 was applied to the reductions of acetophe-
none and R-bromoacetophenone to give 55% ee and 85%
ee, respectively.
Resu lts a n d Discu ssion
Syn th esis of Ca ta lysts. The preparation of 1 is a two-
step sequence starting from styrene-divinylbenzene
cross-linked polymers (1% or 2% divinylbenzene) (Scheme
2). Initially, chlorosulfonylation of the polymer beads was
performed as described in the literature.6 We made an
effort to maximize the amount of loading sites in the
beads in order to increased the density of reactive sites,
but full chlorosulfonylation of 3 was not achieved. Ir-
respective of the cross-linking in the original resin (1 or
2%), the post-sulfonylated resin has 4.1-4.7 mmol/g of
available sulfonyl chloride. The second step, the synthesis
of the polymer-supported chiral sulfonamides was ac-
complished by treating 4 with an excess of (s)-diphenyl-
prolinol in the presence of Et3N in CH2Cl2.
In this paper, we report asymmetric reduction of
prochiral ketones in the presence of polymer-supported
chiral sulfonamides 1 as catalysts.
Exa m in a tion of Rea ction Con d ition s. It is well-
known that the stereoselectivity of reduction is effected
profoundly by solvent, temperature and the amount of
catalyst. To examine these effects, the reduction of
acetophenone was investigated at various reaction condi-
tions. Two solvents (THF and toluene) and a wide range
of 1% and 2% cross-linked polystyrene resins with
different degrees of functionalization were investigated.
Typical procedure for the reduction: BH3‚SMe2 (0.11
mmol) was added to a suspension of the catalyst in THF
(5 mL). The suspension was stirred and refluxed for 1h.
Then a THF (5 mL) solution of acetophenone (0.121 g,
0.1 mmol) was added slowly in 30 min. After the reaction
(1) Reviews: (a) Singh, V. K. Synthesis 1992, 605. (b) Corey, E. J .;
Helal, C. J . Angew. Chem., Int. Ed. Eng. 1998, 37, 1986.
(2) (a) Wilhelm, T.; Thomas, M.; J urgen, M. Tetrahedron: Asymmetry
1997, 8, 2033. (b) Mukund, P. S.; Gregory, R. C.; Pingrong, L.
Tetrahedron Lett. 1999, 40, 2477.
(3) Shuttleworth, S. J .; Allin, S. M.; Sharma, P. K. Synthesis 1997,
1217.
(4) (a) Itsuno, S.; Ito, K.; Hirao, A.; Nakahama, S. J . Chem. Soc.,
Perkin Trans. 1 1984, 2887. (b) Itsuno, S.; Nakano, M.; Ito, K.; Hirao,
A.; Owa, M.; Kanda, N.; Nakahama, S. Ibid 1985, 2615. (c) Itsuno, S.;
Sakuri, Y.; Shimizu, K.; Ito, K. Ibid 1990, 1859. (d) Caze, C.; EI Moualij,
N.; Hodge, P.; Lock, C. J .; Ma, J . Ibid 1995, 2755. (e) Caze, C.; EI
Moualij, N.; Hodge, P.; Lock, C. J . Polymer 1995, 621. (f) Felder, M.;
Giffels, G.; Wandrey, C. Tetrahedron: Asymmetry 1997, 8, 1975.
(5) Yang G. S.; Hu J . B.; Zhao G.; Ding Y.; Tang M. H. Tetrahedron:
Asymmetry 1999, 10, 4307.
(6) Emerson, D. W.; Emerson, R. R.; J oshi, S. C.; Sorensen, E. M.;
Turek, J . E. J . Org. Chem. 1979, 44, 4634.
10.1021/jo000779v CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/01/2000

304 J . Org. Chem., Vol. 66, No. 1, 2001
Notes
Ta ble 1. Effect of Tem p er a tu r e, Solven t, a n d Ca ta lysta ,b
Ta ble 2. Asym m etr ic Red u ction of P r och ir a l Keton es
Usin g P olym er -Su p p or ted Ch ir a l Su lfon a m id e 1fa
polymer
amount of
yieldc
(%)
eed
entry catalyst catalyst (%) solvent T (°C)
(%)
entry
ketone
yield (%) ee (%) configng
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a
1b
1c
1d
1e
1f
1f
1f
1f
1f
1f
1f
1f
1f
15
15
15
10
10
5
10
15
20
15
10
15
20
15
THF
THF
THF
THF
THF
toluene reflux
toluene reflux
toluene reflux
toluene reflux
toluene rt
reflux
reflux
reflux
reflux
reflux
87
89
93
92
90
92
91
91
89
86
91
95
89
86
63.5
75.0
84.5
65.6
68.2.
50.5
63.3
89.1
84.8
0
1
2
3
4
5
6
7
8
p-bromoacetophenone
R-chloroacetophenone
p-methoxyacetophenone
â-acetonaphthone
p-nitroacetophenone
R-bromoacetophenone
benzylacetone
98
98
96
98
99
99
99
86
94.2b
91.2b
84.0c
89.7b
95.9d
93.8b
52.9e
82.7f
R
S
R
R
R
S
R
R
1,1,1-triphenylacetone
a
Molar ratio: ketone/BH3‚SMe2 ) 1.0:1.1; isolated yields after
b
column purification. Determined by HPLC analysis using Daicel
THF
THF
THF
THF
reflux
reflux
reflux
rt
71.8
92.5
75.0
24.2
chiralcel OJ column (eluent: hexane/2-propanol ) 9:1). c Deter-
mined by chiralcel AS column (eluent: hexane/2-propanol ) 8:2).
d
Determined by chiralcel OJ column (eluent: hexane/2-propanol
) 85:15). e Determined by chiralcel OD column (eluent: hexane/
a
2-propanol ) 9:1). f Determined by chiralcel AD column (eluent:
Molar ratio, PhCOCH3/BH3‚SMe2 ) 1.0:1.1 and the absolute
b
g
configuration was R. Cross-linking in the original resin for 1a -c
hexane/2-propanol ) 9:1). The absolute configuration were de-
and 1d -f are 1% and 2%, respectively. Sulfonamide content in
resin 1a (2.23 mmol/g), 1b (2.26 mmol/g), 1c (2.29 mmol/g), 1d
(2.12 mmol/g), 1e (2.28 mmol/g), and 1f (2.29 mmol/g). c Isolated
yield after column purification. Determined by HPLC analysis
using Diacel chiralcel OJ column (eluent: hexane/2-propanol )
9:1).
termined by optical rotation.
Con clu sion
d
In summary, we have developed a new heterogeneous
catalyst of polymer-supported sulfonamides for the enan-
tioselective borane reduction of prochiral ketones. The
enantiomeric excess with polymer catalyst 1f were better
than those obtained with homogeneous catalyst 2. The
catalyst can be recycled at least five times with minimal
loss of catalytic performance.
was completed, the mixture was treated with water and
filtered, washing several times with EtOAc and water.
The results are showed in Table 1.
Exp er im en ta l Section
All reactions were carried out under nitrogen. THF was dried
over sodium and freshly distilled before use. Toluene was
distilled over calcium hydride. Acetophenone and benzylacetone
were dried and distilled over calcium hydride. Other ketones
were further purified by recrystallization before use. (S)-Diphen-
ylprolinol was prepared according to the literature procedures.7
Borane-dimethyl sulfide was obtained from Aldrich Chemical
Co. 1 and 2% cross-linked polystyrene resins (200-400 mesh)
were obtained from Merck Company. The purity of all reagents
were checked by NMR spectroscopy.
Gen er a l P r oced u r e for P r ep a r a tion of P olym er ic Ca ta -
lyst 1. To (S)-diphenyprolinol (1.0 g, 4 mmol) in CH2Cl2 (30 mL)
and Et3N (0.14 mL, 1 mmol) was added polymeric sulfonyl
chloride 4f (2% divinylbenzene; Cl ) 4.73 mmols/g; 0.214 g; 1
mmol of Cl) at room temperature. The mixture was stirred for
Several conclusions can be drawn: (1) Higher reaction
temperatures afforded higher enantiomeric excess (entry
9 vs 11, 13 vs 14). (2) In both solvent systems, the ee
increased as the molar percentage of catalyst increased,
but only up to 15 mol %. (3) THF is a more effective
solvent for the reduction. The best ee was obtained when
the reaction was carried out in refluxing THF with 15mol
% catalyst 1f. Accordingly, all subsequent reductions
were performed under this condition. (4) Under similar
reaction conditions, the polymeric catalyst 1f was better
than the homogeneous catalyst 2 (see entry 7 and Scheme
1). (5) Comparison of entries 1, 2 vs 3 and 4, 5 vs 11
indicated that enantioselectivity was influenced by the
degree of functionalization. Better enantiomeric excess
can be obtained with higher degree of functionalization.
(6) Entries 3 and 12 suggested that the polymer catalyst
from 2% DVB was better than that from 1% DVB.
Having established the best reaction conditions, the
application of 1f to the reduction of other prochiral
ketones was investigated using a catalytic amount 15mol
% 1f in refluxing THF. Table 2 summarized these results.
All reductions gave excellent yields and good enantio-
meric excess. The results demonstrated that electron
density of the aromatic ring had a significant impact on
the enantioselectivity. Comparison of the results obtained
with acetophenone, p-methoxyacetophenone and p-ni-
troacetophenone indicated that an electron-withdrawing
group was helpful for high enantioselectivity.
3
days. The polymer was then filtered and washed with
methanol, water, methanol-water (V/V ) 1:1), and methanol,
respectively. After drying in vacuo at 50 °C for 5 h, 0.451 g
polymer was obtained. The chemical composition is summarized
in Table 1.
Gen er a l P r oced u r e for Asym m etr ic Red u ction of P r o-
ch ir a l Keton es Usin g P olym er -Su p p or ted Ca ta lyst 1 a n d
Bor a n e. BH3‚SMe2 (1.1 mmol) was added to a suspension of
polymeric catalyst 1f (2.29 mmol/g; 200-400 mesh; 0.061 g; 0.15
mmol of N) in THF (5 mL). The suspension was stirred and
refluxed for 1 h. Then a THF (5 mL) solution of acetophenone
(0.121 g, 1 mmol) was added within 30 min. After the addition
was completed, the mixture was treated with water and filtered
and washed several times with EtOAc and water. The filtrate
and washings were combined, extracted with EtOAc (3 × 10 mL),
and dried with MgSO4. The solution was evaporated and purified
by silica gel chromatography to give pure product in 95% yield:
20
[R]D 48.6 (c 1.24, CHCl3). The ee was determined to be 92.5%
by chiralcel OJ column.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures, chiral HPLC, and 1H NMR data for the reduction of
ketones. The material is available free of charge via the
Internet at http://pubs.acs.org.
Recyclin g of Ca ta lyst 1f. As we described above, one
of the advantages of polymer-supported catalyst is its
easy recovery by filtration. The recycling of 1f was
investigated by the reduction of p-nitroacetophenone. The
catalyst was recovered and reused five times with no loss
of catalytic efficiency (95.8-96.5% ee).
J O000779V
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W.; Grabowski, E. J . J . Org. Chem. 1991, 56, 751.