Iminium Salt Systems for Catalytic Asymmetric Epoxidation
J . Org. Chem., Vol. 66, No. 21, 2001 6927
oxiranes are among the best asymmetric epoxidizing
agents. In the presence of alkaline Oxone (Caroate),
Yang’s C2-symmetric ketone,16 Armstrong’s chiral R-flu-
oro ketone,17 and particularly Shi’s fructose-derived chiral
ketone catalyze the asymmetric epoxidation of a wide
variety of alkenes, including allylic and homoallylic
alcohols and ethers, with good to excellent enantioselec-
tivities.18
Oxaziridines such as those of Davis,19 and related
systems,20 are excellent reagents for the asymmetric
oxidation of sulfides to sulfoxides but are much less
successful with less potent nucleophilic substrates such
as alkenes. Oxaziridinium salts, first reported in 1976
by Lusinchi,21 are, however, extremely reactive for oxygen
transfer to nucleophilic substrates, including sulfides and
alkenes.22,23 They have been prepared both by quater-
nization of the corresponding oxaziridines and by peracid
oxidation of iminium salts. Dihydroisoquinolinium salts
1 (R ) R′ ) H) catalyze the epoxidation of simple olefins
in the presence of Oxone as the stoicheiometric oxidant,
the corresponding racemic oxaziridinium salts 2 (R ) R′
) H) being presumed to be the active oxidants.24 The first
enantiomerically pure oxaziridinium salt 2 (R ) Ph, R′
) Me; X ) BF4-) was prepared by quaternization of an
oxaziridine derived from a chiral imine, prepared in turn
in four steps from norephedrine,25 and was shown to
induce asymmetric epoxidation of alkenes. Furthermore,
the corresponding iminium salt 1 (R ) Ph, R′ ) Me; X )
BF4-) was shown to catalyze epoxidation using Oxone;
ee’s of up to ca. 40% have been obtained. Complete
retention of stereochemistry is observed, suggesting a
single-step oxygen-transfer process. A binaphthalene-
derived iminium salt has been reported to catalyze
asymmetric epoxidation of simple alkenes under similar
conditions,26 providing, for example, 1-phenylcyclohexene
oxide with 71% ee and trans-stilbene oxide with 31% ee.
Armstrong and others have shown that even acyclic
iminium salts can mediate epoxidation by Oxone.27
We have previously described our approach to a new
type of cyclic chiral iminium salt containing the asym-
metric centers in an exocyclic substituent at nitrogen, and
these iminium salts have been successfully employed in
the catalytic asymmetric epoxidation of simple alkenes,
giving ee’s of up to ca. 40% (obtained using the iso-
pinocampheyl-derived catalyst 3 as its tetraphenylborate
salt).28 A complicating feature of these processes is that
two diastereoisomeric oxaziridinium salts may be formed
by attack of oxidant at the Si or Re face of the iminium
species (illustrated below in Scheme 2). Each might
deliver the oxygen atom to either of the prochiral faces
of the alkene substrate with a different degree of enan-
tiocontrol, and they may be in competition for the alkene
substrate. On the basis that the presence of polar units
within the chiral exocyclic substituent might help to
control the diastereofacial selectivity of attack of the
iminium unit by persulfate and/or the diastereofacial
selectivity of approach of the alkene substrate to the
reactive oxidizing intermediate, we have prepared and
tested a number of catalysts from chiral amino alcohol,
amino diol, amino ether, and amino acetal precursors.
Herein, we describe the preparation and use as catalysts
of a range of iminium salts functionalized at the nitrogen
atom and prepared from amino alcohols, aminoethers,
and aminoacetals, to investigate if the additional func-
tionality could be used to control the stereochemistry of
formation of the active oxygen transfer intermediate and
hence improve epoxide ee’s.
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Resu lts a n d Discu ssion
Ca ta lyst P r ep a r a tion . We reasoned that attachment
of the controlling asymmetric centers to the iminium
nitrogen atom (e.g., on exocyclic carbon atoms) would
bring those centers nearer to the site of the reaction and
might therefore be expected to lead to higher ee’s.
We prepare our catalysts through condensation of
enantiomerically pure chiral primary amines with 2-(2-
bromoethyl)benzaldehyde 429 as shown in Scheme 1. This
approach has the great advantage that asymmetric
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