Notes
J . Org. Chem., Vol. 64, No. 16, 1999 6113
Ta ble 1. Liter a tu r e Cor r ela tion betw een Op tica l
Rota tion a n d Absolu te Con figu r a tion of 1
these derivatives, measured in acetone on one side and
in chloroform on the other, are summarized in Table 2.
Interestingly, it appears that three out of seven of these
compounds indeed exhibited a switch of their optical
rotation sign from one solvent to the other. Apparently,
para-substituted derivatives do not lead to such an
inversion, whereas the others do. This may be a conse-
quence of the different intrinsic electronic distribution
implied in each of these molecules, thus favoring or
disfavoring intermolecular interactions (i.e., formation of
clusters for instance) due to hydrogen bonds occurrence.
From the various above-described results the following
conclusions can be drawn: (a) the optical rotation mea-
sured for the (R)-1 enantiomer is negative in either
chloroform or ethanol solution; (b) this sign is inverted
to positive if the measurement is performed in acetone.
It can therefore be deduced (a) that the sign of the optical
rotation observed for (R)-1 by Fujisawa6 should be
positive (instead of negative as described) and (b) that
two other previously proposed absolute configurations of
1 must be corrected. These are the above cited attribu-
tions by (a) Hassine et al.12 and (b) J anssen and col-
leagues.15 Indeed, in this last case, an (S)-1 absolute
configuration was deduced from a negative optical rota-
tion in chloroform solution, as compared with a positive
value measured in acetone by J ohnson and colleagues4
for the (R)-1 enantiomer. Therefore, it appears that,
owing to the above-described solvent-dependent optical
rotation sign inversion we have observed, this correlation
must be inverted to (R).
Interestingly enough, this enantiomer was obtained via
enantioselective biocatalyzed hydrolysis of R-methylsty-
rene oxide 1, using a recombinant epoxide hydrolase from
Agrobacterium radiobacter. If our assumption was cor-
rect, the enantioselectivity of this enzyme should there-
fore be opposite to the one we have ourselves observed
on the same substrate using the Aspergillus niger
enzyme.1b To confirm this point, and therefore to ascer-
tain our stereochemical analysis, biohydrolysis of racemic
1 using a sample of the A. radiobacter enzyme was
checked. Our results indicate that this was the case
indeed, the A. niger epoxide hydrolase hydrolyzing pref-
erentially the (R)-1 enantiomer (thus leaving the (S)
enantiomer unreacted), whereas the A. radiobacter showed
a high preference for hydrolyzing the (S)-1 antipode,
leading to the recovery of the (R)-1 enantiomer. Interest-
ingly enough, it therefore appears that, at least for this
particular substrate, these two biocatalysts are nicely
enantiocomplementary, i.e., allowing preparation, at will,
of either enantiomer of 1 in enantiopure form.
entry absol config sign solvent
[R]D
20
2.9
1.90
6.9
2.86
2.7
?
c
T, °C ref
1
2
3
4
5
6
7
8
9
S
S
-
+
+
-
+
-
+
+
+
-
neat
neat
8.3
?
0.36
5
11
11
?
25
20
23
?
20
25
25
3
EtOH
acetone
acetone
EtOH
acetone
?
R
S
4
11
12
5
13
1b
14
15
R
R
R
S
R
S
0.7
?
EtOH
acetone
CHCl3
1.25 2.09
1.2
7.8
1.28
3.84
10
ADmix-â Sharpless catalyst, as described recently.7 The
(R) absolute configuration of this diol was ascertained
independently via chemical correlation with atrolactic
acid of established absolute configuration.8 Cyclization
of 3, via a stereochemically unambiguous chemical route
(described in Scheme 1) was then performed, thus leading
to (R)-1.
As a second approach, this (R)-1 epoxide was further
transformed into (-)-(S)-2-phenyl-2-butanol 4 following
the way previously described by Fujisawa et al.6 Due to
the reaction mechanism involved, and considering the
structure of the obtained product, its absolute configu-
ration can be deduced unambiguously as being (S)-4. This
is also consistent with the previous attribution achieved
independently by Cram and colleagues.9
To check the coherence of the absolute configuration
determinations described in the literature for compounds
1, 3 and 4, we then measured the optical rotation for each
of these products using at least three different solvents,
i.e., ethanol, chloroform, and acetone. The obtained
values are indicated in Scheme 1. Interestingly it appears
(a) that, for diol 3 as well as for alcohol 4, no inversion of
the optical rotation sign was observed, whatever the
solvent used. Therefore, it can be deduced that the
absolute configuration claimed for both these products
in the literature are correct even if they were deduced
from measurements achieved using different solvents.
However, this is not the case for epoxide 1. Indeed, the
sign of its optical rotation switched from positive to
negative depending on the solvent used. Therefore, the
absolute configuration claimed for this product in the
recent literature might be incorrect, depending on the
optical rotation sign used as a reference by the authors.
Having these results in hands, we considered it was
of importance to similarly check the behavior of various
other aromatic epoxides derivatives we have recently
prepared in the context of our work devoted to the
synthesis of enantiopure epoxides using biocatalysis.10
Comparison of the optical rotation sign for several of
Con clu sion
In the course of this work, we have unambiguously
established the optical rotation/absolute configuration
(3) Mitsui, S.; Imaizumi, S. Nippon Kagaku Zasshi 1965, 86, 219.
(4) J ohnson, C. R.; Schroeck, C. W. J . Am. Chem. Soc. 1968, 90,
6852.
(5) Fujisawa, T.; Takemura, I.; Ukaji, Y. Tetrahedron Lett. 1990,
31, 5479.
(6) Fujisawa, T.; Funabora, M.; Ukaji, Y.; Sato, T. Chem. Lett. 1988,
59.
(11) J ohnson, C. R.; Kirchhoff, R. A.; Reischer, R. J .; Katekar, G. F.
J . Am. Chem. Soc. 1973, 95, 4287.
(12) Hassine, B.; Gorsane, M.; Geerts-Evrard, F.; Pecher, J .; Martin,
R. H.; Castelet, D. Bull. Soc. Belg. 1986, 95, 547.
(7) Becker, H.; King, S. B.; Taniguchi, M.; Vanhessche, K. P. M.;
Sharpless, K. B. J . Org. Chem. 1995, 60, 3941.
(8) (a) Eliel, E. L.; Freeman, J . P. J . Am. Chem. Soc. 1952, 74, 923.
(b) Brewster, J . H. J . Am. Chem. Soc. 1956, 78, 4061. (c) Inch, T. D.;
Ley, R. V.; Rich, P. J . Chem. Soc. (C) 1968, 1693.
(9) Cram, D. J .; Allinger, J . J . Am. Chem. Soc. 1954, 76, 4516.
(10) (a) Archelas, A.; Furstoss, R. TIBTECH 1998, 16, 108. (b)
Archelas, A.; Furstoss, R. Biocatalysis. From discovery to application.
In Topics in Current Chemistry; Fessner, W.-D., Ed.; Springer: Berlin,
1998; Vol. 200, pp 159-191.
(13) Zhang, W.; Loebach, J . L.; Wilson, S. R.; J acobsen, E. N. J . Am.
Chem. Soc. 1990, 112, 2801.
(14) Wang, Z.-X.; Shi, Y. J . Org. Chem. 1997, 62, 8622.
(15) Spelberg, J . H. L.; Rink, R.; Kellogg, R. M.; J anssen, D. B.
Tetrahedron: Asymmetry 1998, 9, 459.
(16) Mentioned in the Fluka Company catalog.
(17) Unpublished result. This epoxide was obtained as residual
compound using whole cells of A. niger as biocatalyst.
(18) J ohnson, C. R.; Stark, C. J ., J r. J . Org. Chem. 1996, 47, 1193.
(19) Ramon, D. J .; Yus, M. Tetrahedron Lett. 1998, 39, 1239.