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two clear phases over the course of the extraction. One
equivalent was extracted into the dichloromethane phase to
form the complexes [CoIII(3)(N-Bn-AA)], while the second
equivalent was dissolved in the aqueous phase where the
ee values were found to be 90.1 and 99.0% in favor of (S)-N-
benzylvaline and (S)-N-benzylleucine, respectively (Table 2,
entries 2, 3). The extraction of N-benzylphenylalanine under
the same conditions also proceeded in high yield with one
equivalent of substrate extracted into the organic phase
through formation of [CoIII(3)(N-Bn-Phe)] (Table 2, entry 4).
The unbound substrate, (S)-N-benzylphenylalanine remained
as a suspension and could be isolated by filtration or dissolved
into the aqueous phase by treatment with NaOH. Again, a
high ee value was observed (93.3% ee). Treatment of the
complexes [CoIII(3)(N-Bn-AA)] with aqueous sodium
dithionite released the opposite enantiomer in quantitative
yield and with consistent ee values (see the Supporting
Information).
Resolution of racemic N-benzyl amino acids using only
dichloromethane and no water was also attempted (Table 2,
entries 5–8, method C). In all cases, one equivalent of the
substrate was complexed by [CoIII(3)(OAc)] and dissolved
into the dichloromethane phase, while the uncomplexed solid
material could be isolated simply by filtration. Enantioselec-
tivities of 94.2 and 92.7% ee were observed for the recovered
N-benzylvaline and N-benzylphenylalanine, respectively
(Table 2, entries 5, 6). Thus, method C represents a more
practical procedure for less hydrophilic amino acids with no
loss of enantioselectivity. Conversely, and surprisingly, N-
benzylalanine showed only poor enantioselectivity by this
method (Table 2, entry 7), which could be somewhat
improved by lowering the temperature, with 65.8% ee
obtained at ꢀ108C (Table 2, entry 8).
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94% (S) and 93% (R) for the complexed ([CoIII(ent-1)(N-Bn-
Ala)]) and the uncomplexed amino acid, respectively (see
Ref. [8]).
In conclusion, we have developed a novel approach to the
resolution of racemic N-benzyl a-amino acids in excellent
yields and enantiomeric excesses by using the lipophilic chiral
salen–cobalt(iii) complex [CoIII(3)(OAc)]. The complexed
amino acid can then be released by a reductive (CoIII!CoII)
counterextraction with aqueous sodium dithionite. The orig-
inal chiral cobalt(iii) complex can be regenerated and reused
with essentially no loss of reactivity and selectivity. We are
actively investigating the scope of this methodology using
different substrates as well as its large-scale application in an
industrial environment.
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Received: November 18, 2005
Published online: March 10, 2006
Keywords: amino acids · chiral resolution · cobalt ·
.
molecular recognition · N,O ligands
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substantially from the conditions used by Fujii et al. (a homoge-
neous MeOH/H2O solution (5:1), see Refs. [8,9]). The results
obtained by Fujii et al. could be nicely reproduced by perform-
ing this separation under the original conditions.
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