Enantioselective olefin epoxidation using axially chiral biaryl azepinium salts as catalysts. Rapid in-situ screening and origin of the stereocontrol

Article abstract of DOI:10.1002/adsc.200800022

To unravel the origin of the stereocontrol in epoxidation reactions of unfunctionalized alkenes by diastereomeric biaryl oxaziridinium salts, two series of novel iminium cations were prepared. These moieties combine (R _a)-dimethylbiphenyl or (R

Full text of DOI:10.1002/adsc.200800022

FULL PAPERS
DOI: 10.1002/adsc.200800022
Enantioselective Olefin Epoxidation using Axially Chiral Biaryl
Azepinium Salts as Catalysts. Rapid in-situ Screening and Origin
of the Stereocontrol
Roman Novikov,a GØrald Bernardinelli,b and JØrôme Lacoura,*
a
DØpartement de Chimie Organique, University of Geneva, Quai Ernest-Ansermet 30, 1211 Geneva 4, Switzerland
Fax : (+41)-22-328-7396; e-mail: Jerome.Lacour@chiorg.unige.ch
Laboratoire de Cristallographie, University of Geneva, Quai Ernest Ansermet 24, 1211 Geneva 4, Switzerland
b
Received: January 11, 2008; Published online: April 11, 2008
Dedicated to Prof. Andreas Pfaltz on the occasion of his 60th anniversary
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: To unravel the origin of the stereocontrol derivatives have displayed similar or better asymmet-
in epoxidation reactions of unfunctionalized alkenes ric efficiency than the classical binaphthyl deriva-
by diastereomeric biaryl oxaziridinium salts, two tives. A structural analysis was performed in search
series of novel iminium cations were prepared. These of a correlation between the origin of the stereocon-
moieties combine (Ra)-dimethylbiphenyl or (Ra)- trol/level of enantioselectivity in the products, and
5,5’,6,6’,7,7’,8,8’-octahydrobinaphthyl
cores
with dihedral angles around the biaryl twist of the cata-
chiral exocyclic appendages derived from commer- lysts.
cially available (S)- or (R)-3,3-dimethylbutan-2-
amine and (S)- or (R)-1-phenylpropan-1-amine.
Under biphasic enantioselective olefin epoxidation Keywords: atropisomers; catalysis; chiral amines;
conditions, in-situ generated bromide salts of these chirality; epoxidation; in-situ formation
Introduction
Chiral non-racemic epoxides are useful precursors in
synthetic chemistry, and frequent structures in natural
products, often related to their biological activity.[1]
Quite a few efficient catalytic methods exist for their
preparation from olefins and many of them are based
on transition metals such as the Katsuki–Sharpless or have been reported,[8] many of them using biarylaze-
Katsuki–Jacobsen protocols.[2,3] In recent years, much pinium salts as catalysts. Typical structures are bi-
effort has been devoted to the development of orga- phenyl 1,[9] doubly-bridged biphenyl (DBB) 2,[10] and
nocatalyzed epoxidation conditions that afford metal- binaphthyl 3 iminium salts,[9c,e,f,11] which are detailed
free procedures; the catalysts being perhydrate, diox- in Figure 1. Further to the stereogenic biaryl element,
irane, oxaziridine, or oxoammonium moieties as well most of these chiral salts bear an exocyclic chiral ap-
as ammonium or oxaziridinium salts.[4]
pendage noted R* on the diagram.
Oxaziridinium ions are attractive alternatives to the
Interestingly, in compounds 1 and 2, the stereocon-
commonly used dioxiranes.[5] These organic salts are trol over the reaction is provided by this exocyclic
effective oxygen transfer reagents towards nucleophil- chiral appendage. It is particularly true for the deriva-
ic substrates[6] and electron-rich unfunctionalized ole- tives made from enantiopure l-acetonamine[9a,b] and
fins in particular. Moreover, the propensity of imini- 3,3-dimethylbutan-2-amine (S or R enantiomer)[9c]
um ions to react with Oxoneꢀ triple salt to generate which are the best chiral auxiliaries for this type of
the oxaziridinium species renders the development of catalytic moieties. If this is not surprising for the
catalytic processes possible [Eq. (1)].[7] Quite a few tropos derivatives of type 1,[12] it is more astonishing
successful enantioselective variants of the reaction for the atropos derivatives of type 2 that are configu-
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factor in the sense of the enantioselective induction.
However, a declaration of the presence of two extra
aromatic groups is falling short of any rational explan-
ation. For us, it was clear that other parameters could
well influence the reaction – and the dihedral angle q
around the central bond joining the aromatic rings in
particular (Figure 2). It is indeed known that such a
parameter can be crucial on the level of asymmetric
induction obtained in enantioselective catalytic reac-
tions.[15] In the present case, we wondered if a low di-
hedral angle value at the junction of the rings (q~40–
458) would entice a stronger (dominant) influence of
chiral exocyclic appendage R* whereas higher values
Figure 1. Biphenyl 1, doubly-bridged biphenyl (DBB) 2, bi-
naphthyl 3 iminium catalysts and typical chiral exocyclic ap- (q~538 and higher) would lead to the predominance
pendages R* derived from l-acetonamine or 3,3-dimethyl-
butan-2-amine.
of the biaryl element for the stereocontrol of the ep-
oxidation reaction; this predominance of the axial
over the centered chirality resulting also possibly in
higher enantiomeric excesses values for the epoxides.
To test this hypothesis, it was decided to synthesize
two configurationally stable biphenyl systems for
rationally stable at room temperature and under the
reaction conditions.[10,13]
For compounds 3, the origin of the stereocontrol el- which the q dihedral angle would be similar to that of
ement is exactly the opposite. In this case, the atropos the binaphthyl derivatives. Ideally, the two systems
binaphthyl core has a overwhelming stereochemical would have (slightly) lower and higher q values than
influence. The enantioselectivity of the epoxidation compounds of type 3, respectively. In the first in-
reaction is solely controlled by the configuration of stance, a lower level of enantioselectivity ought to be
the biaryl moiety and not by the exocyclic append- reached with a possible influence of the chiral exocy-
age.[11b–d] Essentially identical ee values are obtained clic appendage whereas, in the second case, higher
in reactions of prochiral olefins in the presence of dia- levels of stereoinduction should be observed with the
stereomeric iminium salts that differ only by the con- biaryl system acting solely for the stereocontrol. Al-
figuration of the exocyclic appendage, and this in ternatively, this analysis performed with q values
favor of epoxides of identical configurations. In most could be performed with the “external” dihedral
of these above-mentioned studies with compounds of angle F. Herein, in a search for such derivatives, we
type 1, 2 and 3, the counterion associated with the report the reactivity of 6,6’-dimethylbiphenylazepini-
iminium ions have been either tetraphenylborate or um and 5,5’,6,6’,7,7’,8,8’-octahydrobinaphthyl azepini-
TRISPHAT anions which act a priori as liphophilic um cations of type 4 and 5 (Figure 3). Structural infor-
genenions.[14]
mation on these derivatives is provided by the X-ray
For the stereocontrol of the epoxidation reaction, analysis of amines or ammonium precursors. Two
there was thus a clear dichotomy between the catalyt- series of diastereomeric derivatives were prepared
ic behavior of biphenyl compounds 1 and 2 on one from (S)- or (R)-3,3-dimethylbutan-2-amine and (S)-
side and binaphthyl derivatives 3 on the other. To the or (R)-1-phenylpropan-1-amine, and the results of the
best of our knowledge, no explanation has been so far epoxidation studies are reported in the following
given to account for this difference. Minimally, one paragraphs. In order to expedite the screening pro-
can consider that the chemical nature of the biaryls at cess, a protocol of in-situ generation of iminium bro-
play – biphenyl vs. binaphthyl – is the determining mide catalysts was used – some of the results using
Figure 2. Stereochemical influence as a function of q and F dihedral angles (measured inside and outside the N-containing
seven membered-ring respectively).
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Enantioselective Olefin Epoxidation using Axially Chiral Biaryl Azepinium Salts
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Figure 3.
this protocol being compared with that of fully isolat-
ed iminium salts of the tetraphenylborate family.
Results and Discussion
Catalyst Selection and Preparation
As just mentioned, our initial goal was to design, de-
velop and study two novel biphenyl azepinium cata-
lysts for which the q angle would be similar to that of
binaphthyl derivatives with, ideally, (slightly) lower
and higher dihedral angle values, respectively. How-
ever and unfortunately, at the start of the study, little
structural information was found in the literature on
biaryl azepines or azepinium salts to help us in the se-
lection of the catalyst skeletons. In fact, an extensive
search of the Cambridge Structural Database re-
vealed only 35 structures of seven-membered ring
biaryl azepine derivatives with very little structural
overlap between the compounds. A precise determi-
Figure 4. Biaryl azepine derivatives and dihedral angles q
(bold) and F (italic): 6 (HMBAZO), 7 (GEMQOE), 8
(GEMQUK),
9
(GAVKET),
10
(WIPJAG),
11
(NUBGOG), 12 (WIPJIO), 13 (XEBNIB), 14 (HOVGII).
nation of the nature of the q angle in this family of decided to investigate dimethylbiphenyl azepinium
compounds was therefore impossible to achieve from cations of type 4 as catalysts and verify if a reactivity
literature precedents. Nevertheless, an analysis of the difference could be found with 3 in the context of the
data revealed that some of these compounds could be epoxidation chemistry. Furthermore, taking into ac-
grouped into sub-families from which some trends count the possible importance of F, we considered
could be inferred. These moieties (6–14) are detailed that the second system of study ought to be a
in Figure 4; the CSD refcodes corresponding to the 5,5’,6,6’,7,7’,8,8’-octahydrobinaphthyl
azepinium
structures are detailed in the caption text and the di- cation of type 5 (Figure 3); strong repulsion between
hedral angle(s) q (and F) mentioned on the drawing. the hydrogenated rings leading possibly to higher F
Clearly, two groups could be discerned based on q values than systems 3 and 4 and hence a better selec-
values. On the one hand, biphenyl and doubly-bridged tivity in the epoxidation reactions.
biphenyl moieties (6 to 10) presented rather low dihe-
The synthesis of the 6,6’-dimethylbiphenylazepine
dral angle values (qꢀ45.98) whereas, on the other amines (15a to 15d), precursors to catalysts of type 4,
hand, quite higher values (q>528) were observed for was realized in three steps starting from highly enan-
dimethylbiphenyl and binaphthyl derivatives. Un- tioenriched (ꢁ)-(M)-6,6’-dimethylbiphenyl-2,2’-dicar-
fortunately, very little difference was noticed between boxylic acid (96.7% ee, Scheme 1).[16] Reduction with
the q values of latter two classes of compounds (11 to lithium aluminum hydride gave the corresponding
14). This observation was rather disappointing. How- diol (16, 82%)[17] which was oxidized to the desired di-
ever, a closer investigation of the second sub-family aldehyde (17) with excellent yield (94%) following an
revealed rather large differences between the q and F already reported protocol.[18]
dihedral angles measured inside and outside the N-
Reductive amination in the presence of enantio-
containing seven membered-ring, respectively (see pure amines a to d (Figure 5) using NaBH3CN in
Figure 4). Considering that (i) the F (rather than q) MeCN provided the desired compounds 15a to 15d in
ought to be more sensitive to the nature of the sub- decent to good yields (67–97%). Diastereomeric 15a/
stituents positioned at the 6,6’-position of the biphen- 15b and 15c/15d were obtained as single enantiomers
yl and (ii) F values mentioned on Figure 4 might not after purification; no trace of stereomeric entities
1
be representative of the derivatives under study, we being evidenced in the H NMR analysis.
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Scheme 1. Synthesis of azepines 15a to 15d.
Catalytic hydrogenation of (Ra)-BINOL (Pd/C,
EtOH) and subsequent recrystallization from n-hep-
tane provided (Ra)-2,2’-dihydroxy-5,5’,6,6’,7,7’,8,8’-oc-
tahydro-1,1’-binaphthyl in more than 99% enantio-
meric purity.[20] This compound was then treated with
triflic anhydride (CH2Cl2, pyridine, 08C) to form the
(Ra)-2,2’-ditrifluoromethanesulfonyloxy-
Figure 5. Selected amines for the formation of diastereo-
meric biphenyl and binaphthyl azepines.
5,5’,6,6’,7,7’,8,8’-
The synthesis of the binaphthyl azepines 18a and isolated yield. Palladium-mediated carbonylation of
18b was previously reported using as starting material the bistriflate [Pd(OAc)2, dppp, (i-Pr)2NEt, MeOH,
(Ra)-2,2’-bis(bromomethyl)-1,1’-binaphthyl.[9e]
Two DMSO] provided the known 2,2’-bis(carbomethoxy)-
octahydro-1,1’-binaphthyl (20) in 86%
AHCTREUNG
novel binaphthyl azepines 18c and 18d were prepared 5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphthyl
(21)
in
following a procedure similar to the one described good yield (87–90%).[21] The reduction with lithium
above and this in 76% and 72% yield, respectively aluminum hydride in diethyl ether gave the desired
[Eq. (2)].
bisdiol (22) in almost quantitative yield. The subse-
quent oxidation (PCC, CH2Cl2) proceeded smoothly
and afforded pure bisaldehyde (23) in 86–89% yield
which was the starting material for the synthesis of all
four octahydrobinaphthyl azepines 19a, 19b, 19c and
19d. The derivatives were subjected to the reductive
amination procedure used for the synthesis of aze-
pines 15a to 15d [amines a to d (2.0 equiv.), 23
(1.0 equiv.), NaBH3CN (4.0 equiv.), MeCN]. Surpris-
ingly, this protocol was not successful. After 24 h,
only a moderate conversion of starting aldehyde was
The four novel 5,5’,6,6’,7,7’,8,8’-octahydrobinaphth- observed. Nevertheless, using a slightly modified pro-
yl azepines 19a, 19b, 19c and 19d were prepared in six tocol [amines a to d (1.1 equiv.), 23 (1.0 equiv.),
steps starting from commercially available enantio- NaBH3CN (2.0 equiv.), MeOH, catalytical amount of
pure (Ra)-BINOL (Scheme 2).[19]
glacial AcOH], azepines 19a to 19d were provided in
Scheme 2. Synthesis of azepines 19a to 19d.
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moderate and decent yields (47–76%). With these eral amine functional groups, and DBB azepines in
(Ra)-H8-binaphthyl azepines in hand, catalysts [5a] particular. To overcome this problem, milder reaction
[BPh4] to [5d]
C
tailed below [Eq. (3)].
than I2/KOAc. However, the oxidation occurs quite
slowly. In our group, it was found that the process can
be greatly accelerated (20 min vs. hours) by perform-
ing the reaction without AIBN and using chloroform
or dichloromethane as solvent instead of carbon tetra-
chloride.[9e,11c] The bromide counterion of the iminium
salts was then exchanged to more lipophilic anions of
TRISPHAT type in a second series of experiments.
However, recently, we wondered about the necessi-
ty of isolating the iminium salts altogether and wheth-
er the bromide precursors generated in-situ could not
Treatment of tertiary amines 19a to 19d with NBS be used directly as catalysts. It was thus decided to
in dichloromethane provided a rapid and clean forma- test this hypothesis with all azepines 15a to 15d, 18a
tion of the desired iminium salts [5a][Br] to [5d][Br] to 18d and 19a to 19d – and then compare the reactiv-
in 5 min. Subsequent anion exchange metathesis in ity of one of the systems with that of a classical, iso-
acetonitrile with sodium tetraphenylborate and tritu- lated, tetraphenylborate salt.
ration/recrystallization in EtOH gave catalysts [5a]
[BPh4] to [5d][BPh4] in appropriate yields (48–61%) transformation, NMR tube experiments were per-
for two steps. formed in conditions similar to what would be the re-
To check the validity of the amine to iminium ion
ACHTREUNG
Finally, for four azepine derivatives (or their hydro- action conditions [NBS (1.0 equiv.), CD2Cl2, see next
1
gen chloride salts), monocrystals were obtained and section]. H NMR spectra of the crude reaction mix-
their structural X-ray analysis was performed.[22] The tures indicated the clean conversion of the azepine
ORTEP views of 15c, 18c·HCl, 19c·HCl, and 19d are moieties to the corresponding iminium bromide salts
reported in Figure 6 along with q and F values.
of the amines [Eq. (4), Table 1]. The formation of the
Interestingly, assuming little structural perturbation
from the protonation and quite opposite to the Cam-
bridge Structural Database situation, rather strong
differences were observed for q and F in the three
biaryl series. As it could be expected, the 6,6’-dime-
thylbiphenyl azepine 15c presented the lowest dihe-
dral angle values. Comparison with 18c·HCl to
19c·HCl indicated that this q angle changes only mod-
erately, whereas a strong variation of the F angle
could be noticed with values increasing from 57.58 to unsaturated species [3a][Br] to [3d][Br], [4a][Br] to
61.08 and 67.08, respectively. Diastereomeric struc- [4d][Br], [5a][Br] to [5d][Br] was particularly easily to
tures 19c·HCl and 19d are also remarkably similar. monitor in the 10 to 12 ppm region as singlet signals
With that information in hands, the catalysts behavior corresponding to the CH=N+ proton appear (e.g.,
was studied.
Figure 7). Globally, higher frequencies were observed
Table 1. In-situ formation of iminium salts.[a] Chemical shifts
of the CH=N+ proton (1H NMR).
Iminium Salt Formation
As already mentioned, the enantioselective epoxida-
tion of unfunctionalized alkenes is possible using imi-
nium species as organocatalysts – these compounds
being usually prepared prior to the epoxidation step
and, for instance, by the oxidation of tertiary amine
precursors. Oxidation of tertiary amines to iminium
salts is indeed feasible and literature precedents have
indicated that a mixture of I2 and KOAc is a useful
oxidative combination for that transformation.[9b,23]
However, this protocol leads to many by-products
and is not appropriate for compounds containing sev-
Iminium
salt
d,
Iminium
d,
ppm
Iminium
salt
d,
ppm
ppm salt
[4a][Br]
[4b][Br]
[4c][Br]
[4d][Br]
10.98 [3a][Br]
10.42 [3b][Br]
10.87 [3c][Br]
11.31 [3d][Br]
11.21 [5a][Br]
10.57 [5b][Br]
11.47 [5c][Br]
11.54 [5d][Br]
10.79
10.25
11.00
10.99
[a]
Conditions: 0.2 mmol of azepine, 0.2 mmol of NBS in
0.5 mL of CD2Cl2, 5 min, 400 MHz. Chemical shifts are
given relative to Me4Si with the solvent resonance used
as the internal standard (CD2Cl2 d=5.32 ppm).
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Figure 6. Chemical structures and ORTEP views of (a) 15c, (b) salt 18c·HCl, (c) salt 19c·HCl and (d) 19d. Ellipsoids are pre-
sented at the 50% probability level. Dihedral angles q (bold) and F (italic) are indicated with a mean value of uncertainty
of 0.58.
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Figure 7. 1H NMR spectra (CD2Cl2, 400 MHz) of (a) 19c and (b) in-situ generated [5c][Br].
for the chemical shifts of the iminium protons of the usually allows the ready isolation of the epoxides
derivatives 3 and the lowest values for the derivatives after the oxidation reaction. To perform the reaction
of 5; derivatives of amines b and d presenting the with the in-situ bromide catalysts derived from 15a to
lowest and highest frequencies in each series respec- 15d, 18a to 18d and from 19a to 19d, the only modifi-
tively (Table 1).
cation to the protocol was the separated treatment of
the azepines with NBS (CH2Cl2, 5 min) and the addi-
tion of the resulting solution to a mixture of the other
reagents. The results for the various experiments are
reported in Table 2, Table 3, Table 4 and Table 5.
Enantioselective Epoxidation Reactions
Having established the feasibility of the in-situ oxida- Only the enantiomeric excesses are reported as the
tion of the various biarylazepines to the correspond- purpose of this study was essentially the evaluation of
ing iminium salts, we decided to use these species di- the sense of induction of the enantioselective transfor-
rectly for our study on the influence the dihedral mation and the global asymmetric efficiency of the
angle of the biaryl moieties on the enantioselectivity catalysts. Information about the reactivity will be
of the epoxidation reaction.
One set of epoxidation conditions (5 mol% catalyst,
Table 2. Epoxidation of olefins S1, S2, S3 using catalysts [4a]
Oxoneꢀ/CH2Cl2/NaHCO3/18-crown-6/H2O) and three
[Br], [3a][Br], [5a][Br]. Enantiomeric excesses (%).[25]
different prochiral trisubstituted unfunctionalized al-
kenes were selected for the study (Figure 8) – these
alkenes being chosen for their proven record of per-
forming well in iminium-catalyzed epoxidation reac-
tions.[7–11] The biphasic CH2Cl2/H2O protocol, which
has been detailed previously,[9b,c] is easy to run and
Alkene
[4a][Br]
[3a][Br]
[5a][Br]
Configuration
S1
S2
S3
75
78
60
80
67
46
87
82
63
(+)-(1R,2S)
(ꢁ)-(1S,2S)
(ꢁ)-(1S,2S)
Table 3. Epoxidation of olefins S1, S2, S3 using catalysts [4b]
[Br], [3b][Br], [5b][Br]. Enantiomeric excesses (%).[25]
Alkene
[4b][Br]
[3b][Br]
[5b][Br]
Configuration
S1
S2
S3
57
67
44
85
75
54
92
83
67
(+)-(1R,2S)
(ꢁ)-(1S,2S)
(ꢁ)-(1S,2S)
Figure 8. Prochiral trisubstituted alkenes.
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Table 4. Epoxidation of olefins S1, S2, S3 using catalysts [4c]
[Br], [3c][Br], [5c][Br]. Enantiomeric excesses (%).[25]
That said, divergences in the outcome can still be
found for the diastereomeric catalysts and rather
strong differences between the ee values of reactions
performed with [4a][Br] and [4b][Br] were observed
(e.g., for alkene S3 the catalyst [4a][Br] provided ep-
oxide formation with 60% ee, then catalyst [4b][Br]
with 44% ee). This difference is attenuated in the re-
actions of catalysts [3a][Br] and [3b][Br] (for substrate
S3 the catalysts [3a][Br] and [3b][Br] gave epoxide
with 46% ee and 54% ee, respectively) and becomes
Alkene
[4c][Br]
[3c][Br]
[5c][Br]
Configuration
S1
S2
S3
68
63
58
76
59
42
82–88[a]
72
61
(+)-(1R,2S)
(ꢁ)-(1S,2S)
(ꢁ)-(1S,2S)
[a]
In the particular case of the epoxidation of 1-phenyl-3,4-
dihydronaphthalene with salt [5c][Br], and contrary to
the other reactions, a large deviation in the enantiomeric
excess values was observed while performing multiple minimal with [5a][Br] and [5b][Br] (alkene S3, 63%
runs of the reactions. Rather than indicate an average,
we have decided to put the range of the ee values ob-
served.
ee observed with catalyst [5a][Br] and 67% ee with
catalyst [5b][Br]). These results then probably indi-
cate that the H8-binaphthyl skeleton has a stronger
stereochemical influence than the binaphthyl and 6,6’-
dimethylbiphenyl structures, respectively.
Now if one compares together the selectivity of the
other diastereomeric catalysts derived from 1-phenyl-
propan-1-amine, that is [4c][Br] with [4d][Br], [3c]
[Br] with [3d][Br] and [5c][Br] with [5d][Br], the
same kind of observations can be made. Again the
levels of stereoinduction in the (Ra,S) and (Ra,R)
series can be different, but in this case the (Ra,R)-con-
figurated catalysts are most effective in terms of enan-
tioselectivity than the (Ra,S)-series. The configuration
of the epoxides is again controlled by the axial stereo-
Table 5. Epoxidation of olefins S1, S2, S3 using catalysts [4d]
[Br], [3d][Br], [5d][Br]. Enantiomeric excesses (%).[25]
Alkene
[4d][Br]
[3d][Br]
[5d][Br]
Configuration
S1
S2
S3
85
77
53
91
69
34
88
69
57
(+)-(1R,2S)
(ꢁ)-(1S,2S)
(ꢁ)-(1S,2S)
given when necessary in the course of the study. Im- genic element of the iminium salts and it does not
portantly, all iminium salts from [3a][Br] to [3d][Br], change with an inversion of the configuration of the
[4a][Br] to [4d][Br], [5a][Br] to [5d][Br] behaved as exocyclic appendage.
catalysts under this set of conditions. As catalysts of
From these studies, one can conclude that larger
type 4 have in general been less effective than that of twist angles around the biaryl axes lead indeed to the
type 3 and 5, data in the tables have indicated with predominance of the axially chiral stereogenic ele-
the catalysts positioned in the following order 4!3! ment over the exocyclic centred one; the chemistry of
5, from left to right.
iminiums 4 and 5 confirming the observations made
If one compares the selectivity of the diastereo- previously for the binaphthyl series 3. Furthermore, if
meric catalysts derived from 3,3-dimethylbutan-2- one assumes that the crystallographic trends observed
amine together – that is [4a][Br] with [4b][Br], [3a] for the amine and ammoniums species detailed above,
[Br] with [3b][Br] and [5a][Br] with [5b][Br], some hold for iminium salts as well, then one can draw a
definite trends can be observed. First, the levels of correlation between the enantioselectivity of the pro-
stereoinduction in the (Ra,S) and (Ra,R) series are dif- cess and the dihedral angle F of the biaryl systems. It
ferent. For catalysts [4a][Br] and [4b][Br] much better can be clearly seen on the results of the epoxidation
ee values were observed with (Ra,S)-configurated cat- reactions of [4b][Br], [3b][Br] and [5b][Br]. Moving
alyst [4a][Br] (Table 2, Table 3). For diastereomeric from the a priori smallest dihedral angle to the big-
series [3a][Br] and [3b][Br], [5a][Br] and [5b][Br], it gest, from [4b][Br] to [5b][Br], one can see an in-
is the opposite as better ee values were found with crease of the enantioselectivity for all substrates. For
(Ra,R)-configurated catalysts. This indicates a sensitiv- the other catalysts, this correlation can also be found
ity of the reaction to the global stereoisomeric envi- for alkene S1. For olefins S2 and S3, the situation is
ronment of the catalysts. However, importantly, an different as the two biphenyl series (4 and 5) are
identical sense of induction was obtained for the ep- more selective than the binaphthyl one – the differ-
oxides in all experiments. These results indicate that ence between the iminiums 4 and 5 remaining al-
the two new types of biphenyl frameworks are, like in though modest. Globally, the best results in terms of
the binaphthyl series, more influential as chiral auxil- enantioselectivity have been achieved with the cata-
iaries than the exocyclic appendage derived from 3,3- lysts derived from the H8-binaphthyl skeleton.
dimethylbutan-2-amine. In fact, the configuration of
However, although interesting, these results were
the epoxides remains the same while using catalysts obtained with a “new” untested protocol of epoxida-
with opposite absolute configuration at the chiral exo- tion using in-situ generated bromide iminium salts.
cyclic appendage.
Care was thus taken to compare this outcome with
1120
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Adv. Synth. Catal. 2008, 350, 1113 – 1124

Enantioselective Olefin Epoxidation using Axially Chiral Biaryl Azepinium Salts
FULL PAPERS
Table 6. Epoxidation of olefins S1, S2, S3 using catalysts [5a]
[Br], [5a][BPh4], [5b][Br], [5b][BPh4]. Enantiomeric excess-
es (%).[25]
ertheless, the global trends determined for the bro-
mide salts remained with the tetraphenylborate coun-
terion – just the selectivity can be better with the
more lipophilic counterion (with the exception of
olefin S2).
G
ACHTREUNG
Alkene [5a] [5a]
A
C
[Br]
[Br]
S1
S2
S3
87
82
63
87
80
67
92
83
67
91
81
72
(+)-(1R,2S)
(ꢁ)-(1S,2S)
(ꢁ)-(1S,2S)
Conclusions
We have described two new classes of biaryl azepini-
um salts that behave as effective catalysts for the
enantioselective epoxidation of prochiral olefins. We
have been able to show that the origin of the predom-
inance of the axially chiral stereogenic element is to
be found in the dihedral angle values for the biaryl
twist – and the external angle F in particular. The
larger the angle, the better it is for the asymmetric
transfer. We have further used an oxidation protocol
that allows a rapid assay for the enantioselective effi-
ciency by in-situ oxidation of tertiary amine precur-
sors to bromide iminium salts; the development of
this assay revealing a first counterion effect in this
iminium-catalyzed epoxidation chemistry.[26]
Table 7. Enantioselective epoxidation of olefins S1, S2, S3
using catalysts [5c][Br], [5c][BPh4], [5d][Br], [5d][BPh4]. En-
antiomeric excesses (%).[25]
A
ACHTREUNG
Alkene [5c] [5c]
A
G
[Br]
[Br]
88
S1
82–
88[a]
72
88
94
(+)-(1R,2S)
S2
S3
67
77
69
57
68
68
(ꢁ)-(1S,2S)
(ꢁ)-(1S,2S)
61
[a]
In the particular case of the epoxidation of 1-phenyl-3,4-
dihydronaphthalene with salt [5c][Br], and contrary to
the other reactions, a large deviation in the enantiomeric
excess values was observed while performing multiple
runs of the reactions. Rather than indicate an average,
we have decided to put the range of the ee values ob-
served.
Experimental Section
For analytical data of compounds 15, 18, 19, 22, 23 and salts
[5][BPh4]. ECD spectra of 15c, salt 18c·HCl, salt 19c·HCl
A
and 19d and comparison with that of the crystals used in the
X-ray structural analyses, see Supporting Information.
that of more classical isolated salts. We selected for
the comparison study commercially available tetra-
phenylborate as lipophilic counterion. The synthesis
General Procedure for the Synthesis of Azepines 15a
to 15d
of the four derived iminium salts, [5a][BPh4] to [5d]-
N
ACHTREUNG
To a solution of (Ra)-6,6’-dimethyl-1,1’-biphenyl-2,2’-dicarb-
oxaldehyde[18] (100 mg, 0.42 mmol, 1.0 equiv.) in MeCN
(5 mL) the corresponding enantiopure amine (a to d,
2.0 equiv.) was added. After 15 min of stirring NaBH3CN
(106 mg, 1.68 mmol, 4.0 equiv.) was added to the reaction
mixture and the resulting colorless solution was stirred for
23 h at room temperature. The reaction mixture was
quenched by addition of AcOH (0.24 mL, 10.0 equiv.),
stirred for 10 min, then diluted with MeOH (1 mL) and
DCM (30 mL). The resulting solution was washed with 2M
aqueous solution of NaOH (30 mL). The organic phase was
separated and the aqueous phase extracted with CH2Cl2 (2”
25 mL). Combined organic layers were washed with brine
(25 mL), dried (MgSO4), filtered, concentrated under
vacuum and purified.
tions were performed under the same reaction condi-
tions and the novel salts behaved unsurprisingly as
catalysts. The results are given in Table 6 and Table 7.
For catalysts [5a][Br] and [5a]
[5b][BPh4], little difference in the enantioselectivity
A
ACHTREUNG
of the epoxidation reaction is observed (Table 6). For
alkenes S1 and S2 the ee values are either identical or
slightly lower, while for substrate S3 the values are
always better by 4–5% with the isolated salt. If one
compares [5a]
N
N
termined for the bromides salts are perfectly applica-
ble.
Surprinsingly, for [5c][Br] and [5c]
and [5d][BPh4], the situation is different (Table 7).
A
ACHTREUNG
Substantial variations in ee values can be noticed in
all direct comparisons of the bromide and BPh4 salts.
The stronger counterion effect is observed for alkene
S3. This ionic interplay is something that was not ob-
served previously in our group or others in this field
of epoxidation chemistry. At this stage, it is too early
to speculate on this counterion effect which is ex-
General Procedure for the Synthesis of Azepines 18c
and 18d
In a 25-mL round-bottomed flask containing a solution of
enantiopure 1-phenylpropylamine (110 mg, 0.818 mmol,
1.2 equiv.) in acetonitrile (10 mL) was added (Ra)-2,2’-bis-
A
(300 mg,
0.682 mmol,
tremely sensitive to the olefin structure at play. Nev- 4.0 equiv.). The mixture was heated at reflux for ca. 5 h
Adv. Synth. Catal. 2008, 350, 1113 – 1124
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
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Roman Novikov et al.
FULL PAPERS
[monitoring by thin layer chromatography (TLC)], allowed
to cool down to room temperature and filtered though a
Celite plug washed with CH2Cl2. Evaporation of the solvent
under reduced pressure gave the crude product which was
purified by column chromatography.
General Procedure for the Synthesis of Iminium Salts
[5a]
A
G
To a solution of substrate in CH2Cl2 (5 mL for 200 mg of
starting tertiary amine) NBS (1.0 equiv.) was added in small
portions (exothermic reaction). The resulting deep yellow
solution was stirred for 5 min at ambient temperature. A so-
lution of sodium tetraphenylborate (1.0 equiv. in 2 mL of
MeCN) was added in one portion, and the resulting mixture
was stirred for 5 min. The suspension was diluted with
CH2Cl2 (15 mL), washed twice with water (2”15 mL), dried
(MgSO4), filtered and concentrated under vacuum. The
crude product was purified by trituration/recrystallization
from ethanol. The resulting salts were dried in high vacuum
at 808C.
Synthesis of (Ra)-5,5’,6,6’,7,7’,8,8’-Octahydro-1,1’-bi-
naphthyl-2,2’-dimethanol (22)
To a suspension of LiAlH4 (6.66 mmol, 0.25 g, 2.0 equiv.) in
dry diethyl ether (30 mL) (Ra)-2,2’-bis(carbomethyl)-
5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphthyl[21] was added as a
solid in small portions at 08C. After the addition, the result-
ing mixture was stirred at room temperature for 0.5 h, re-
fluxed for 0.5 h and recooled to 08C. Water (20 mL) was
added carefully via an addition funnel and concentrated
HCl was added slowly until the mixture became homogene-
ous. Diethyl ether (20 mL) was added and the resulting two-
phase mixture was separated. The aqueous layer was ex-
tracted with ether (2”20 mL). The combined organic layers
were washed with 10% aqueous solution of NaHCO3
(30 mL), brine (30 mL) and dried under MgSO4. Evapora-
tion of the solvent under reduced pressure provided pure
product as a white amorphous solid; yield: 1.06 g (99%).
Typical Biphasic Enantioselective Epoxidation
Procedure with in-situ Prepared Catalysts
In a 5-mL flask equipped with a magnetic stirring bar,
NaHCO3 (67.0 mg, 0.80 mmol, 4.0 equiv.) was added to
800 mL of water. Oxoneꢀ (132.0 mg, 0.21 mmol, 1.0 equiv.)
was then added and the solution stirred for 2 min until effer-
vescence subsided. 500 mL of a 0.4 mol/L solution of the
alkene (0.20 mmol, 1.0 equiv.) and naphthalene (0.20 mmol,
1.0 equiv., internal reference) in CH2Cl2 was added and the
resulting biphasic mixture was cooled to 08C with an ice-
bath. The catalyst was prepared by mixing the azepine pre-
cursor and NBS (10.0 mmol each, 5 mol%) in CH2Cl2
(500 mL) for five minutes. The resulting solution was added,
followed by a solution of 18-crown-6 (1.0 mg, 5.0 mmol, 2.5
mol%) in CH2Cl2 (200 mL). After 5 min at 08C without any
stirring, the reaction mixture was then vigorously stirred at
that temperature for 2 h.
Synthesis of (Ra)-5,5’,6,6’,7,7’,8,8’-Octahydro-1,1’-bi-
naphthyl-2,2’-dicarboxaldehyde (23)
A round-bottomed flask (100 mL), equipped with a magnet-
ic stirring bar, containing PCC (9.6 mmol, 2.06 g, 3.0 equiv.)
was charged with dry CH2Cl2 (15 mL). A solution of sub-
strate (3.2 mmol, 1.03 g, 1.0 equiv.) in CH2Cl2 (15 mL) was
added to the resulting suspension in one portion. The result-
ing dark mixture was vigorously stirred for 3 h at ambient
temperature, then diethyl ether (30 mL) was added. The
mixture was stirred for 10 min, filtered through silica gel
plug topped with a layer of Celite, which was then washed
with ether. The filtrate was concentrated under reduced
pressure to provide a green solid. Subsequent purification
by column chromatography on silica gel gave pure product
as a colorless solid; yield: 86–89%.
Crystal Structures Determination
Cell dimensions and intensities were measured at 200 K on
a Stoe IPDS diffractometer with graphite-monochromated
MoKa radiation (l=0.71073 Š). The structures were solved
by direct methods (SIR-97),[27] and all other calculations
were performed with the XTAL system[28] and ORTEP[29]
programs. The Flack parameter (x) was refined for the HCl
salt compounds 18c and 19c [x=0.00(8) and ꢁ0.01(7), re-
spectively] and was fixed to 0.0 for compound 15c and 19d
for which the absolute configurations were known from the
syntheses (see Supporting Information for the CD spectra of
the measured crystals).
Crystallographic data (excluding structure factors) for the
structures reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplemen-
tary publication nos. CCDC 673551, 673552, 673553, and
673554. These data can be obtained free of charge from The
General Procedure for the Synthesis of Azepines 19a
to 19d
To a suspension of aldehyde 23 (100 mg, 0.314 mmol,
1.0 equiv.) in MeOH (4 mL) the corresponding enantiopure
amine (a to d, 1.1 equiv.) was added. After few minutes of
stirring, NaBH3CN (40 mg, 0.628 mmol, 2.0 equiv.) and gla-
cial acetic acid (2 drops) were added to the reaction mixture
and the resulting colorless solution was stirred for 1 day at
ambient temperature. The reaction mixture was quenched
by addition of an aqueous solution of NaOH (1M, 25 mL).
Diethyl ether (25 mL) was added and the resulting two-
phase mixture separated. The aqueous phase was extracted
with ether (2”15 mL). The combined organic layers were
washed with brine (25 mL), dried (MgSO4), filtered, concen-
trated under vacuum and purified by preparative TLC on
silica gel plates (20”20 cm, 2 mm, EtOAc/hexane, 1:5).
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif or on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax.:
(internat.) + 44 1223/336–033; e-mail: deposit@ccdc.cam.
ac.uk].
Supporting Information
General methods and materials are given in the Supporting
Information.
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Adv. Synth. Catal. 2008, 350, 1113 – 1124

Enantioselective Olefin Epoxidation using Axially Chiral Biaryl Azepinium Salts
FULL PAPERS
2002, 43, 8257–8260; c) J. Vachon, C. PØrollier, D.
Monchaud, C. Marsol, K. Ditrich, J. Lacour, J. Org.
Chem. 2005, 70, 5903–5911; d) P. C. B. Page, B. R.
Buckley, G. A. Rassias, A. J. Blacker, Eur. J. Org.
Chem. 2006, 803–813; e) J. Vachon, C. Lauper, K. Di-
trich, J. Lacour, Tetrahedron: Asymmetry 2006, 17,
2334–2338; f) P. C. B. Page, B. R. Buckley, D. Barros,
A. J. Blacker, B. A. Marples, M. R. J. Elsegood, Tetra-
hedron 2007, 63, 5386–5393.
Acknowledgements
We thank the Swiss National Foundation, and the Federal
Office for Education and Science for the financial support
this work.
References
[10] J. Vachon, S. Rentsch, A. Martinez, C. Marsol, J.
[1] J. Marco-Contelles, M. T. Molina, S. Anjum, Chem.
Rev. 2004, 104, 2857–2900.
[2] E. N. Jacobsen, A. Pfaltz, H. Yamamoto, (Eds.), Com-
prehensive Asymmetric Catalysis, Volumes I–III,
Springer, Berlin, 1999.
[3] N. End, L. Macko, M. Zehnder, A. Pfaltz, Chem. Eur.
J. 1998, 4, 818–824; N. End, A. Pfaltz, Chem.
Commun. 1998, 589–590.
Lacour, Org. Biomol. Chem. 2007, 5, 501–506.
[11] a) V. K. Aggarwal, M. F. Wang, Chem. Commun. 1996,
191–192; b) P. C. B. Page, R. Buckley Benjamin, A. J.
Blacker, Org. Lett. 2004, 6, 1543–1546; c) M.-H. Gon-
Åalves, A. Martinez, S. Grass, P. C. B. Page, J. Lacour,
Tetrahedron Lett. 2006, 47, 5297–5301; d) P. C. B. Page,
M. M. Farah, B. R. Buckley, A. J. Blacker, J. Org.
Chem. 2007, 72, 4424–4430.
[12] K. Mikami, K. Aikawa, Y. Yusa, J. J. Jodry, M. Yama-
naka, Synlett 2002, 1561–1578; K. Mikami, M. Yama-
naka, Chem. Rev. 2003, 103, 3369–3400.
[4] W. Adam, C. R. Saha-Moller, P. A. Ganeshpure, Chem.
Rev. 2001, 101, 3499–3548.
[5] P. Barbaro, C. Bianchini, Chemtracts 2001, 14, 274–277;
W. Adam, C. R. Saha-Moeller, C.-G. Zhao, Org. React.
2002, 61, 219–516; X.-Y. Wu, X. She, Y. Shi, J. Am.
Chem. Soc. 2002, 124, 8792–8793; R. Curci, L. D’Ac-
colti, C. Fusco, Acc. Chem. Res. 2006, 39, 1–9; D.
Goeddel, L. Shu, Y. Yuan, O. A. Wong, B. Wang, Y.
Shi, J. Org. Chem. 2006, 71, 1715–1717.
[6] G. Hanquet, X. Lusinchi, Tetrahedron Lett. 1993, 34,
5299–5302; L. Bohe, M. Lusinchi, X. Lusinchi, Tetrahe-
dron 1999, 55, 155–166; A. Gluszynska, I. Mackowska,
M. D. Rozwadowska, W. Sienniak, Tetrahedron: Asym-
metry 2004, 15, 2499–2505; R. E. delRio, B. Wang, S.
Achab, L. Bohe, Org. Lett. 2007, 9, 2265–2268.
[13] M. Tichy, J. Gunterova, J. Zavada, Collect. Czech.
Chem. Commun. 1997, 62, 1080–1088; M. Tichy, M.
Budesinsky, J. Gunterova, J. Zavada, J. Podlaha, I. Cis-
arova, Tetrahedron 1999, 55, 7893–7906.
[14] TRISPHAT stands for tris(tetrachlorobenzenediolato)-
phosphate(V), see: J. Lacour, C. Ginglinger, C. Grivet,
G. Bernardinelli, Angew. Chem. 1997, 109, 660–662;
Angew. Chem. Int. Ed. Engl. 1997, 36, 608–609; F. Fa-
varger, C. Goujon-Ginglinger, D. Monchaud, J. Lacour,
J. Org. Chem. 2004, 69, 8521–8524; J. Lacour, R.
Frantz, Org. Biomol. Chem. 2005, 3, 15–19; S. Con-
stant, J. Lacour, Top. Curr. Chem. 2005, 250, 1–41; J.
Lacour, D. Linder, Chem. Rec. 2007, 7, 275–285.
[15] S. Jeulin, S. Duprat de Paule, V. Ratovelomanana-
Vidal, J.-P. Genet, N. Champion, P. Dellis, Angew.
Chem. 2004, 116, 324–329; Angew. Chem. Int. Ed.
2004, 43, 320–325; D. E. Kim, C. Choi, I. S. Kim, S.
Jeulin, V. Ratovelomanana-Vidal, J.-P. Genet, N. Jeong,
Adv. Synth. Catal. 2007, 349, 1999–2006 and references
cited therein.
[7] G. Hanquet, X. Lusinchi, P. Milliet, C. R. Acad. Sci.,
Ser. II: Mec., Phys., Chim., Sci. Terre Univers 1991,
313, 625–628; X. Lusinchi, G. Hanquet, Tetrahedron
1997, 53, 13727–13738.
[8] L. Bohe, G. Hanquet, M. Lusinchi, X. Lusinchi, Tetra-
hedron Lett. 1993, 34, 7271–7274; P. C. B. Page, G. A.
Rassias, D. Bethell, M. B. Schilling, J. Org. Chem. 1998,
63, 2774–2777; A. Armstrong, G. Ahmed, I. Garnett,
K. Goacolou, J. S. Wailes, Tetrahedron 1999, 55, 2341–
2352; P. C. B. Page, G. A. Rassias, D. Barros, D. Bethell,
M. B. Schilling, J. Chem. Soc. Perkin Trans. 1 2000,
3325–3334; S. Minakata, A. Takemiya, K. Nakamura,
I. Ryu, M. Komatsu, Synlett 2000, 1810–1812; I. Wash-
ington, K. N. Houk, J. Am. Chem. Soc. 2000, 122,
2948–2949; P. C. B. Page, G. A. Rassias, D. Barros, A.
Ardakani, B. Buckley, D. Bethell, T. A. D. Smith,
A. M. Z. Slawin, J. Org. Chem. 2001, 66, 6926–6931;
M.-K. Wong, L.-M. Ho, Y.-S. Zheng, C.-Y. Ho, D.
Yang, Org. Lett. 2001, 3, 2587–2590; P. C. B. Page, D.
Barros, B. R. Buckley, A. Ardakani, B. A. Marples, J.
Org. Chem. 2004, 69, 3595–3597; P. C. B. Page, B. R.
Buckley, H. Heaney, A. J. Blacker, Org. Lett. 2005, 7,
375–377; P. C. B. Page, D. Barros, B. R. Buckley, B. A.
Marples, Tetrahedron: Asymmetry 2005, 16, 3488–3491;
P. C. B. Page, B. R. Buckley, D. Barros, A. J. Blacker,
H. Heaney, B. A. Marples, Tetrahedron 2006, 62, 6607–
6613.
[16] S. Kanoh, H. Muramoto, N. Kobayashi, M. Motoi, H.
Suda, Bull. Chem. Soc. Jpn. 1987, 60, 3659–3662.
[17] G. Wittig, H. Zimmermann, Chem. Ber. 1953, 86, 629–
640.
[18] M. Tichy, J. Holanova, J. Zavada, Tetrahedron: Asym-
metry 1998, 9, 3497–3504.
[19] For a recent article on the preparation and the use of a
5,5’,6,6’,7,7’,8,8’-octahydrobinaphthyl azepine, see J.
Ruan, G. Lu, L. Xu, Y.-M. Li, A. S. C. Chan, Adv.
Synth. Catal. 2008, 350, 76–84.
[20] A. Korostylev, V. I. Tararov, C. Fischer, A. Monsees, A.
Borner, J. Org. Chem. 2004, 69, 3220–3221.
[21] A. K. Unni, N. Takenaka, H. Yamamoto, V. H. Rawal,
J. Am. Chem. Soc. 2005, 127, 1336–1337.
[22] All the seven-membered rings adopt a twist-boat con-
formation with a pseudo two-fold axis passing through
the N atom and show minimum DC2 values of 0.021,
0.011, 0.001 and 0.041 for compound 15c, 18c·HCl,
19c·HCl and 19d, respectively. For an article describing
DC2 values, see: M. Nardelli, Acta Crystallogr., Sect. C:
Cryst. Struct. Commun. 1983, 39, 1141–1142.
[9] a) P. C. B. Page, G. A. Rassias, D. Barros, A. Ardakani,
D. Bethell, E. Merifield, Synlett 2002, 580–582; b) J.
Lacour, D. Monchaud, C. Marsol, Tetrahedron Lett.
Adv. Synth. Catal. 2008, 350, 1113 – 1124
ꢁ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1123

Roman Novikov et al.
FULL PAPERS
[23] N. J. Leonard, G. W. Leubner, J. Am. Chem. Soc. 1949,
71, 3408–3411.
[24] A. Mary, D. Z. Renko, C. Guillou, C. Thal, Bioorg.
Med. Chem. 1998, 6, 1835–1850.
von Matt, S. J. Miller, J. A. Murry, R. D. Norcross,
E. A. Shaughnessy, K. R. Campos, J. Am. Chem. Soc.
1999, 121, 7582–7594; E. P. Kꢂndig, C. M. Saudan, G.
Bernardinelli, Angew. Chem. 1999, 111, 1297–1301;
Angew. Chem. Int. Ed. 1999, 38, 1219–1223; J. Lacour,
V. Hebbe-Viton, Chem. Soc. Rev. 2003, 32, 373–382;
A. Macchioni, Chem. Rev. 2005, 105, 2039–2074.
[27] A. Altomare, M. C. Burla, M. Camalli, G. L. Cascara-
no, C. Giacovazzo, A. Guagliardi, A. G. G. Moliterni,
G. Polidori, R. Spagna, J. Appl. Crystallogr. 1999, 32,
115–119.
[25] Conditions: 5 mol% of catalyst, 2.5 mol% 18-C-6, 1.1
equiv. Oxoneꢀ, 4.0 equiv. NaHCO3, CH2Cl2/H2O (3:2),
2 h, 08C. Average of at least two runs. The enantiomer-
ic excesses were determined by CSP-GC (S2, Chiraldex
Hydrodex b-3P) or CSP-HPLC (S1 and S3, CHIRAL-
CEL-ODH, 0.5 mLminꢁ1, hexane:i-PrOH, 95:5, l=
230 nm). The configuration indicated is that of the re-
sulting epoxide.
[26] For leading references and reviews on counterion ef-
fects in enantioselective catalysis, see: A. Lightfoot, P.
Schnider, A. Pfaltz, Angew. Chem. 1998, 110, 3047–
3050; Angew. Chem. Int. Ed. 1998, 37, 2897–2899;
D. A. Evans, D. M. Barnes, J. S. Johnson, T. Lectka, P.
[28] S. R. Hall, H. D. Flack, J. M. Stewart (Eds.), XTAL3.2
Userꢀs Manual, Universities of Western Australia and
Maryland, 1992.
[29] C. K. Johnson, ORTEP II, Report ORNL-5138, Oak
Ridge National Laboratory, Oak Ridge, TN, 1976.
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