bound to the beads, but that, as expected, the (S,S)-diol 5a bound
in higher yields. The ketalisation yield was, however, only 57%
even when equimolar amounts of (S,S)-diol 5a and ketone 1
were used (entry 1). This may be due in part to some of the
bound ketone being inaccessible due to steric crowding.13 The
diol recovered from the beads had a 42% ee of the (S,S)-diol 5a.
With an equimolar amount of racemate (i.e. 0% ee) as the
starting material (entry 2) the diol recovered from the beads had
a 39% ee of the (S,S)-diol 5a. This rose to a 47% ee when the
recovered diol was recycled (entry 3). The initial result (entry 2)
indicates that 65% of the original (S,S)-diol 5a bound to the
beads whereas 29% of the (R,R)-diol 3a bound, i.e. the yield
ratio for the enantiomers was 2.2:1.
Apart from resolving racemates, other useful applications of
the present type of system could involve raising the ee of
reaction products from asymmetric syntheses. This might be
achieved either by concentrating the major enantiomer or by
removing the minor enantiomer. Starting with a mixture of
butane-2,3-diol enantiomers having an 80% ee of the (S,S)-
isomer 5a, see entry 4, the diol recovered from the beads had a
The ketalisation yields were lower starting with racemic
mixtures of the (R,R)- and (S,S)-trans-cyclohexane-1,2-diols
and dimethyl (R,R)- and (S,S)-tartrates (entries 8–10) but the
recovered diols had higher ee, 55 and 72% respectively, than
with butan-2,3-diol. Thus, the more significant the steric
interactions the greater the discrimination between the enantio-
mers but the lower the chemical yield. It should be noted here
that with a perfect discrimination between the enantiomers and
all the ketone residues of 1 fully available, starting with
racemates the ketalisation yields would be only 50%. As
expected the enantiomers which bound in the higher yields were
the (S,S)-enantiomer 5b and (R,R)-enantiomer 5c. The results
using the racemates as starting materials indicate yield ratios of
6.9:1 with the enantiomeric diols 5b and 3b and 6.1:1 with the
enantiomeric diols 5c and 3c.
The keto steroid had no tendency to detach from the beads
under the reaction conditions used in this study. Thus, no steroid
1
was detected by H NMR spectroscopy in any of the diol
fractions. Indeed, the FT–IR spectrum of the PS ketone 1 at the
end of the experiments was indistinguisable from that when first
prepared. All the above results were obtained with one batch of
resin, thus demonstrating that the PS ketone 1 can be
recycled.
9
0% ee. Similarly a starting material with 90% ee gave a
product of 94% ee. This rose to a 97% ee when the recovered
diol was recycled (entry 6). Thus through three cycles (entries
4
–6) the ee of the (S,S)-diol 5a was raised from 80 to 97%.
This initial study shows that significant separations of
enantiomers can be achieved using the procedure outlined in
Scheme 1. The procedure could undoubtedly be automated.
Future work is being directed towards identifying chiral
molecules which are more discriminating between the enantio-
mers and which permit higher loadings to be achieved.
We thank the EPSRC for financial support.
Attempts to remove the (S,S)-enantiomer 5a from a mixture
having an 80 ee of the (R,R)-enantiomer 3a was less successful
(
entry 7). After treating a five-fold excess of the mixture with
the beads, the ee of recovered unbound diol had increased to
only 82%. Evidently the binding of the preferred (S,S)-diol 5a
was almost entirely offset by the large proportion of the (R,R)-
diol 3a present.
Footnotes
*
†
E-mail: philip.hodge@man.ac.uk
3b-Hydroxy-5a-cholestan-7-one, mp 168 °C (lit., 170.5–171.5) and
1
0
Table 1 Separation via ketal formation with PS keto steroid 1
20
11
20
[a]
D
233 (c 2 in chloroform) {lit., [a] 236 (c 1.6 in chloroform)}, was
D
12
prepared by oxidising cholesteryl acetate with chromic acid, hydro-
genating (Pd–charcoal) the product, then hydrolysing the ester group.
Starting materiala
Recovered diolb
Enantiomer Ketalisation
Enantiomer
Ee (%)c in excess
References
Entry 3,5 Ee (%) in excess
yield (%)
1
(a) Polymer-supported Reactions in Organic Synthesis, ed. P. Hodge
and D. C. Sherrington, Wiley, Chichester, 1980; (b) Syntheses and
Separations Using Functional Polymers, ed. D. C. Sherrington and P.
Hodge, Wiley, Chichester, 1988; (c) Polymeric Reagents and Catalysts,
ed. W. T. Ford, ACS Symposium Series 308, Washington D.C., 1986.
1d
2
3
4
5
a
a
a
a
a
a
a
b
b
c
0
0
—
—
57
47
37
43
49
42
42
39
47
90
94
97
82
55
92
72
S,S
S,S
S,S
S,S
S,S
S,S
R,R
S,S
S,S
R,R
e
f
39
80
90
94
80
0
S,S
S,S
S,S
S,S
R,R
—
2 R. B. Merrifield, J. Am. Chem. Soc., 1963, 85, 2149.
3 P. Hodge, Chem. Ind., 1979, 624; J. M. J. Fr e´ chet, ch. 6 in ref. 1(a).
4 G. Lowe, Chem. Soc. Rev., 1996, 25, 309.
5 N. K. Terrett, M. Gardner, D. W. Gordon, R. J. Kobylecki and J. Steele,
Tetrahedron, 1995, 51, 8135.
e
i
6
7
g
h
g
90
f
8
9
0
11
20
9
80
0
S,S
—
e
1
6 P. Hodge and J. Waterhouse, J. Chem. Soc., Perkin Trans. 1, 1983,
2
319.
a
Except where indicated otherwise, ratio of diol to ketone was 1:1. b Except
7 E. Seymour and J. M. J. Fr e´ chet, Tetrahedron Lett., 1976, 3669.
8 T. M. Fyles and C. C. Leznoff, Can. J. Chem., 1976, 54, 935.
9 M. J. Farrall and J. M. J. Fr e´ chet, J. Org. Chem., 1976, 41, 3877.
10 H. R. Nace and G. A. Crosby, J. Org. Chem., 1979, 44, 3105.
11 D. H. R. Barton and J. D. Cox, J. Chem. Soc., 1948, 783.
12 H. C. Meuley, US Pat. 2505646, (Chem. Abstr., 1950, 44, 6894).
13 P. Hodge, J. Kemp, E. Khoshdel and G. M. Perry, Reactive Polymers,
1985, 3, 299.
where indicated otherwise, the diol fraction examined was that obtained by
deketalisation. The recoveries were > 97%. c Unless indicated otherwise,
the ees were determined both by polarimetry and chiral GC. The results
were in close agreement (±1%). Polarimetry was based literature values
2
0
20
20
(
+
ref. 14): [a]
20.0 (c 20 in H
DEX CB stationary phase. Ratio of diol to ketone was 2:1. Ee determined
D
+13.0 (neat) for 5a; [a]
D 2 D
+ 36.7 (c 0.45 in H O) for 5b; [a]
2
O) for 5c. Chiral GC was carried out using a CP-Chirosil-
d
e
f
g
by polarimetry only. Ee determined by GC only. This experiment used a
five-fold excess of the diol and focused on the unbound diol. Percentage
14 Dictionary of Organic Compounds, 5th edn.,, Chapman and Hall, New
York, 1982.
h
i
of starting material not bound.
The unbound diol fraction was
examined.
Received in Cambridge, UK, 15th April 1997; 7/02567J
1396
Chem. Commun., 1997