Lipase-catalyzed stereoselective resolution and desymmetrization of binaphthols

Article abstract of DOI:10.1016/S0957-4166(02)00792-9

We have investigated the use of lipoprotein lipase enzymes from Pseudomonas sp. and Pseudomonas fluorescens for the enantioselective resolution and desymmetrization of racemic binaphthols. The reactions were carried out using a non-aqueous environment (iPr₂O/acetone/vinyl acetate), and yielded mono-acetate ester products of the parent unsubstituted substrate, the 6,6′-dibromo-substrate, and the 6,6′-dimethoxy-substrate with high enantiomeric selectivity.

Full text of DOI:10.1016/S0957-4166(02)00792-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 289–291
Lipase-catalyzed stereoselective resolution and desymmetrization
of binaphthols
Marcela Ju a´ rez-Hernandez, Dean V. Johnson, Herbert L. Holland,* James McNulty and
Alfredo Capretta
Department of Chemistry, Brock University, St Catharines, Ontario L2S 3A1, Canada
Received 18 September 2002; accepted 11 November 2002
Abstract—We have investigated the use of lipoprotein lipase enzymes from Pseudomonas sp. and Pseudomonas fluorescens for the
enantioselective resolution and desymmetrization of racemic binaphthols. The reactions were carried out using a non-aqueous
environment (iPr O/acetone/vinyl acetate), and yielded mono-acetate ester products of the parent unsubstituted substrate, the
2
6,6%-dibromo-substrate, and the 6,6%-dimethoxy-substrate with high enantiomeric selectivity. © 2003 Elsevier Science Ltd. All
rights reserved.
Optically active 1,1%-binaphthyl-2,2%-diol (BINOL) has
provided a versatile template for a plethora of chiral
catalysts and auxiliaries which have been employed
stituted BINOL (X=H), but also for its 6,6%-disubsti-
tuted derivatives (X=Br, OMe): the chiral bromine
moiety can be a key to further functionalization using
the Suzuki reaction with boronic acids under the influ-
ence of a palladium catalyst, and the chiral methoxy
products may provide other such reaction opportuni-
ties. We have been able for the first time to elaborate
on the lipoprotein enzymes that allow the enantioselec-
tive preparation of BINOLs (e.g. S-1–3) and of their
corresponding desymmetrized monoester (e.g. (R)-4–6),
Scheme 1.
1
with great success in asymmetric synthesis. Illustrative
of this are reports of the use of BINOL in asymmetric
2
3
Michael additions, epoxidations, aldol condensa-
4
5
6
7
8a
tions, oxidations, reductions, alkylations, Diels–
8
Alder reactions and addition reactions involving
trimethylsilylcyanide (TMSCN). Additionally, BINOL
9
has proven useful when applied into the synthesis of
1
0
11
HIV-protease inhibitors, chiral stationary phases,
1
2
polymeric chiral ligands and has also been used as a
13
chiral resolving agent.
When vinyl acetate was employed as the acyl donor in
acetylation, a preliminary examination of ten Celite-
Direct asymmetric approaches to enantiomerically
enriched binaphthols (and analogs) include oxidative
18c
19
immobilized Iipases or lipoprotein lipases revealed
that only the lipoprotein lipase from Pseudomonas sp.
efficiently catalyzed the conversion of 1,1%-binaphthyl-
2,2%-diol (±)-1 to its corresponding monoacetate (R)-4
14
couplings, which employ chiral amines, oxovanadium
1
5
16
complexes or bile acid, or the resolution of racemic
1
7
mixtures. Though enzymatic approaches to chiral
binaphthols (through oxidation and resolution) have
(
Table 1, entry a), yielding unreacted (S)-1. In compari-
18
son to chiral compound 1, chiral 6,6%-dibromo-1,1%-
binaphthyl-2,2%-diol 2 (98% ee) has been reported to be
been reported, they are more limited. Only a single
report of a biocatalyst for the formation of one such
compound ((S)-1) has been previously reported, but
the description of the type of enzyme was incomplete.
Indeed, in a more recent report on such a biocatalytic
reaction, the authors reported that ‘all attempts
20
18c
a superior chiral catalyst for synthesis. In our hands,
±)-2 proved to be a suitable substrate for the lipo-
(
protein lipases from both Pseudomonas sp. and Pseu-
domonas fluorescens. In both cases the monoacylation
and desymmetrization proceeded with excellent selectiv-
ity (to yield (R)-5, 94 and 93% ee, respectively, Table 1
entries b and c) and (S)-6,6%-dibromo-1,1%-binaphthyl-
2,2%-diol (S)-2 (80 and 69% ee, respectively). In contrast
to (±)-2, 6,6%-dimethoxy-1,1%-binaphthyl-2,2%diol ((±)-3)
proved to be a substrate for only the lipoprotein lipase
from P. fluorescens, and acylation (to yield (R)-6)
1
8g
failed’.
We have now investigated the use of a series of
1
9
enzymes not only for selective esterification of unsub-
*
Corresponding author. Tel.: +1-905-688-5550, ext. 3403; fax: +1-
05-682-9020; e-mail: holland@chemiris.labs.brocku.ca
9
0
957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00792-9

2
90
M. Ju a´ rez-Hernandez et al. / Tetrahedron: Asymmetry 14 (2003) 289–291
Scheme 1.
Table 1.
Entry Substrate Lipoprotein
lipase
Reaction
time (h)
Binol21
Mono-acetate21
Product Yield (%)a [h] THF ee (%)b Product Yield (%)a [h] THF ee (%)c
25
D
25
D
a
b
c
(9)-1
(9)-2
(9)-2
(9)-3
Pseudomonas sp. 120
Pseudomonas sp. 126
(S)-1
(S)-2
(S)-2
(S)-3
30
46
56
52
−15.3d
55
80
69
58
(R)-4
(R)-5
(R)-5
(R)-6
32
44
30
31
+28.0e
96
94
93
78
f
g
+33.1
+29.5
−35.7
h
j
P. fluorescens
P. fluorescens
126
120
−38.8
2
2
+29.8k
l
d
−23.8
Biotransformations were typically carried out as follows: a mixture of binaphthol 1 (100 mg), vinyl acetate (600 mg), di-iso-butyl ether (4.6 mL),
acetone (dry, 0.5 mL), and a suspension of lipase (400 mg) was stirred at 240 rpm, 40°C, for 120–126 h. The final mixture was analyzed by silica
gel (8:2 toluene/ethyl acetate) and purified by evaporation followed by chromatography using fractional solvent changes of toluene/hexane (90:10)
to toluene (100) to toluene/ethyl acetate (80:20) in 2% graded solvent changes.
a
Isolated yields based on either (±)-1, 2 or 3.
Determined by HPLC analysis (Astec Chirobiotic V chiral column with 6 cm phenomex C-18 guard column, hexane:ethanol (95:5) for (S)-1 and
b
2
3
(S)-2 or 93:7 for (S)-3, 1 mL/min, 254 nm).
c
Determined by HPLC analysis (conditions, see note b) of (R)-1, (R)-2 or (R)-3 derived from (R)-4, (R)-5 and (R)-6, respectively (using
24
K CO /methanol).
2
3
d
e
f
c 1.47.
c 0.95.
c 1.36.
c 1.14.
c 1.72.
c 1.55.
c 1.26.
c 1.84.
g
h
j
k
l
occurred with only moderate selectivity (78% ee, Table
, entry d). In all cases of substrates 1–3 no diacetate
As both biocatalysts are immobilized they can be easily
recovered by filtration, which facilitates their re-use, as
enzyme deactivation is marginal. We have therefore
developed two new biocatalytic reactions for the enan-
tioselective resolution and desymmetrization of racemic
binaphthols, namely the used of lipoprotein lipases
from Pseudomonas sp. and P. fluorescens, and applied
these reactions to generate two new chiral binaphthol
products in this way, the enzymes for which are of
known commercial availability, and which are recover-
able under the reaction conditions described in Table 1.
1
was observed in the biocatalytic reaction. For the
binaphthol products (e.g. (S)-1–3) the enantiomeric
excesses (ee’s) were determined by chiral HPLC analy-
sis. To determine the enantiomeric purities of the prod-
ucts (R-4–6) (the enantiomers of which were not easily
separated by chiral HPLC), the monoesters were
hydrolyzed to their corresponding binaphthols with
K CO /methanol prior to chiroptical analysis of the
2
3
latter chiral products.

M. Ju a´ rez-Hernandez et al. / Tetrahedron: Asymmetry 14 (2003) 289–291
291
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