ate enantioselectivity (up to 76% ee).7 The catalytic enan-
tioselective version of this reaction with bisoxazoline-copper
complexes was also investigated by Jørgensen and co-
workers,19 although, in the case of reaction of 2-methylfuran
(silvan) and ethyl glyoxylate, the enantioselectivity was low
(45% ee),20 in contrast to high ee values in the case of
anilines (usually >80% ee). However, in the case of the F-C
reactions of furans, other electrophiles, e.g., imines3a,21 and
R,ꢀ-unsaturated carbonyl compounds,22 gave better results.
It was of interest for us to find an efficient and readily
accessible catalytic system for the reaction of furans with
glyoxylates. Jørgensen’s19 and our7 studies in this field
showed that bisoxazoline and salen metal complexes were
not efficient enough in this case. We focused our attention
on chiral BINOL-type ligands23 and found that their com-
plexes with Ti(IV), generated from BINOL and Ti(OPri)4,
were efficient catalysts for this reaction. The BINOL/Ti(IV)
complexes were successfully introduced to asymmetric
synthesis by Mikami24 and Keck,25 e.g., to ene, hetero-
Diels-Alder, allylation,26 and Mukaiyama aldol reactions.
Mikami27 also reported the first enantioselective F-C
reactions of protected phenols with trifluoroacetaldehyde,
catalyzed by the BINOL/Ti(IV) complexes. These complexes
were also successfully applied in the reaction of glyoxylates
with anilines by Ding et al.28 and recently with indoles,29
whereas the BINOL/Zr(IV) complexes were used in the
reactions of R,ꢀ-unsaturated carbonyl compounds with
indoles.30
Scheme 1
.
Application of Furanyl R-Hydroxyacetates in the
Synthesis
synthesis of multifunctional chain compounds,9 higher-
carbon sugars,10 aza sugars,11 and, e.g., in the synthesis of
papulacandin D.12
The literature reports a few methods for the synthesis of
optically pure 2-furanyl-hydroxyacetates or their derivatives
by applying enzymatic resolution of racemic mixtures using
lipases,13 kinetic resolution using the Sharpless reagent,14
reduction of furanyl-substituted 1,2-dicarbonyl compounds,15
or addition of cyanides to furfurals.16 The appropriate 1,2-
diols of type II can be obtained via Sharpless asymmetric
dihydroxylation of 5-substituted vinylfurans12 or reduction
of corresponding furanyl hydroxymethyl ketones,17 and the
simplest one (R ) H) from the sugar derivatives (e.g.,
d-glucal).18
Compared to the above-mentioned methods, the synthesis
of optically pure furanyl derivatives of type I or II via the
F-C reaction directly from easily accessible furans and
glyoxylates seems to be a very attractive and competitive
approach. Until now, there is no effective, catalytic enanti-
oselective method for the synthesis of 2-furanyl-hydroxy-
acetates directly from furans. Recently, we published a highly
diastereoselective reaction of furans with chiral (1R,2S,5R)-
8-phenylmenthyl glyoxylate promoted by magnesium
bromide.6b Our previous attempts with chiral catalysts, e.g.,
salen-cobalt complexes, led to the F-C products of moder-
Now we describe the first highly enantioselective Friedel-
Crafts reaction of variously substituted furans 1a-m with
n-butyl glyoxylate (2). At the beginning, the reaction of 2
with 2-methylfuran (1a) was investigated (Scheme 2).
Catalysts were generated in situ from either (R)-BINOL (L1)
or (R)-6,6′-dibromo-BINOL (L2) and Ti(OPri)4 in toluene
at ambient temperature. In our study, the titanium complex
of 6,6′-dibromo-BINOL (2 mol %) gave higher enantiose-
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observed for pyruvates instead of ethyl glyoxylate.
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