Asymmetric epoxidation of alkenes in fluorinated media, catalyzed by second-generation fluorous chiral (salen)manganese complexes

Article abstract of DOI:10.1002/1099-0690(200112)2001:24<4639::AID-EJOC4639>3.0.CO;2-W

The synthesis of sterically hindered chiral (salen)manganese complexes bearing perfluoroalkyl ponytails and their use in asymmetric epoxidation reactions are described. For better understanding of the relative influences of steric and electronic effects o

Full text of DOI:10.1002/1099-0690(200112)2001:24<4639::AID-EJOC4639>3.0.CO;2-W

FULL PAPER
Asymmetric Epoxidation of Alkenes in Fluorinated Media, Catalyzed by
Second-Generation Fluorous Chiral (Salen)manganese Complexes
[
a]
[b]
[b]
[a]
Marco Cavazzini, Amedea Manfredi, Fernando Montanari, Silvio Quici, and
Gianluca Pozzi*[
a]
Dedicated to Professor Guy Ourisson on the occasion of his 75th birthday
Keywords: Biaryls / Biphasic catalysis / Epoxidations / Fluorinated ligands / Manganese
The synthesis of sterically hindered chiral (salen)manganese
complexes bearing perfluoroalkyl ponytails and their use in
and 5,5Ј) in the ligand. Second generation catalysts (Mn-
6)C 15COO and (Mn-7)C 15COO were successfully em-
7
F
7
F
asymmetric epoxidation reactions are described. For better ployed in the fluorous biphase epoxidation of alkenes with
understanding of the relative influences of steric and elec- PhIO as the oxidant and pyridine N-oxide as an additive. Ep-
tronic effects on the enantioselectivity of the fluorous cata- oxide yields (68−98%) and ees (50−92%) were similar to
lysts, the epoxidation of 1,2-dihydronaphthalene and benzo- those obtained with the same oxidizing system and standard
suberene was first studied under homogeneous conditions. It
was shown that the presence of sterically demanding tert-
(salen)manganese complexes under homogeneous condi-
tions. When the reaction was complete, the fluorous layer in
butyl groups and, to a lesser degree, the displacement of the which the catalyst was immobilized was easily recoverable
electron-withdrawing perfluoroalkyl substituents from the li- by simple phase separation at room temperature and could
gand core provide ees higher than those attainable with first be used up to three times before significant decline in yield
generation fluorous chiral (salen)manganese complexes fea- and enantioselectivity was observed.
turing perfluoroalkyl substituents in the key positions (3,3Ј
Introduction
priate perfluoroalkyl substituents RF (‘‘fluorous com-
pounds’’) have been prepared and used in ‘‘fluorous biphase
The use of non-traditional reaction media such as super- chemistry’’,[ an expression used to describe the whole set
10]
[
1]
[2]
critical fluids, ionic liquids, and liquid biphasic systems of stoichiometric and catalytic reactions, phase separations
both aqueous/organic and purely organic)[
3,4]
in synthetic and immobilization techniques that profit from use of per-
(
[5]
[11]
organic chemistry is arousing increasing interest. Investi- fluorinated media.
Principles and applications of
gations in this field have been stimulated by safety and en- fluorous biphase chemistry are described in several re-
vironmental concerns, but also by the search for unusual views.[ Fluorous chemistry has great potential in asym-
selectivities and new catalyst immobilization and recovery metric synthesis, in which solvation effects and effective re-
12]
[
6]
strategies.
covery of precious chiral reagents or catalysts can have crit-
Perfluorocarbons share chemical and physical properties ical importance.[ The asymmetric catalytic epoxidation of
13]
(such as low dielectric constants, chemical inertness, lack of unfunctionalized alkenes is a good benchmark test for this
toxicity, low miscibilities with common organic solvents notion.
and water) that differ quite markedly from those of the cor-
responding hydrogenated compounds.[ These fluids have
7]
Since the discovery of the catalytic activity of chiral (sa-
been found to be very useful in organic reactions involving len)manganese complexes,[
14,15]
a wide variety of cis-disub-
unstable reagents, such as transesterification of polymeriz- stituted and tri- and tetrasubstituted alkenes has been epox-
able alcohols and enamine formation.[ A partially fluorin- idized in the presence of stoichiometric oxidants Ϫ iodosyl-
8]
ated solvent Ϫ benzotrifluoride (α,α,α-trifluorotoluene) Ϫ arenes and m-chloroperbenzoic acid/N-methylmorpholine
has been proposed as a substitute for CH Cl because it has N-oxide (MCPBA/NMO) among them[
16,17]
Ϫ to give en-
2
2
a similar dielectric constant, but lower toxicity.[ In the last antiomerically enriched epoxides in good yields and with
six years, a number of reagents and catalysts bearing appro- moderate to excellent ees. Several approaches towards the
immobilization of (salen)manganese(III) complexes on or-
9]
[
[
a]
b]
Centro CNR Sintesi e Stereochimica di Speciali Sistemi ganic and inorganic supports have been described, with the
Organici,
[18]
aim of recycling the chiral catalysts.
As recently discus-
sed, this strategy still presents some drawbacks, including
poor enantioselectivities due to the inaccessibility of the
Via Golgi 19, 20133 Milano, Italy
Fax: (internat.) ϩ 39-02/2663354
E-mail: gianluca.pozzi@unimi.it
Dipartimento
dell’Universit a` ,
di
Chimica
Organica
e
Industriale
substrate to the catalytic sites and severe leaching of the
complexes.[
19]
Fluorous (salen)manganese(III) complexes
Via Golgi 19, 20133 Milano, Italy
Eur. J. Org. Chem. 2001, 4639Ϫ4649

WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/1224Ϫ4639 $ 17.50ϩ.50/0
4639

M. Cavazzini, A. Manfredi, F. Montanari, S. Quici, G. Pozzi
FULL PAPER
(
Mn-1)Cl Ϫ (Mn-3)Cl (Figure 1) were thus synthesized and diate, which is the actual oxygen-transfer agent in epoxid-
used as catalysts in the aerobic epoxidation of alkenes under ation reactions.[ Although other factors such the con-
fluorous biphase conditions.[ Despite the good chemose- formational flexibility of the ligand and the choice of the
lectivity and efficiency generally observed, these first gen- stoichiometric oxidant might also play important roles, the
eration fluorous catalysts gave promising enantioselectivies results obtained with first generation fluorous (salen)man-
only in the epoxidation of indene (ee ϭ 90%). Later, a few ganese(III) complexes (Figure 1) fitted this picture. The low
other chiral fluorous compounds were described, and some enantioselectivities were tentatively ascribed to a combina-
26]
20]
of these were tested in the fluorous biphase version of reac- tion of low steric hindrance provided by the R substituents
F
tions such as the asymmetric alkylation of aromatic alde- in the 3,3Ј- and 5,5Ј-positions in the ligands and inadequate
hydes with diethylzinc or the asymmetric protonation of electronic shielding of the metal site from the strongly elec-
[
21Ϫ23]
[20b]
enolates.
The results obtained were somewhat encour- tron-withdrawing effect of these substituents.
On these
aging, but further data are required for better understand- grounds, a new set of fluorous chiral catalysts for the asym-
ing of the actual influence of the fluorous environment.
metric epoxidation of alkenes was designed. Second genera-
tion fluorous (salen)manganese(III) complexes (Mn-
4
)Cl Ϫ (Mn-7)X (Figure 2) are all characterized by the
presence of sterically demanding tert-butyl substituents in
the key 3,3Ј-positions. RF substituents are retained in the
5
,5Ј-positions of (Mn-4)Cl and (Mn-5)Cl, but are replaced
by perfluoroalkyl-substituted aryl moieties in the case of
Mn-6)X and (Mn-7)X. A different degree of electronic shi-
(
elding of the metal site within this series of compound is
thus ensured. It should be noted that the biaryl framework
offers additional flexibility in the design of salen ligands.
The overall number of R substituents can be increased to
F
attain the desired preferential solubility in perfluorocarbons
and proper spacers can be inserted between R substituents
F
and the core structure of the ligand in order to achieve fine-
tuning of the electron-withdrawing effect. The biaryl frame-
work was also expected to influence the three-dimensional
structure of the catalyst and to generate more steric hind-
rance, possibly enhancing the enantioselectivity.
Figure 1. First generation fluorous chiral (salen)manganese(III)
complexes
The synthesis of salen ligands is readily accomplished by
condensation of two equivalents of a salicylaldehyde deriv-
ative with a chiral 1,2-diamine. This method also gave good
results in the case of the fluorous ligands 1Ϫ3, but the syn-
thesis of the corresponding perfluoroalkyl-substituted o-hy-
droxybenzaldehydes, especially that of 3,5-disubstituted
compounds, was rather tedious. Since direct perfluoroal-
kylation of benzaldehydes (whether electrophilic, free-rad-
ical or through metal-mediated coupling reactions) affords
only traces of the desired products,[ we fell back on the
perfluoroakylation of a protected 3,5-diiodosalicylic acid
derivative followed by reduction/oxidation of the carb-
In a recent communication, the synthesis of new fluorous,
sterically hindered, chiral (salen)manganese(III) complexes
[
24]
was outlined. Here we describe in detail the preparation
of these compounds and their use as catalysts in the asym-
metric epoxidation of alkenes, under both homogeneous
and fluorous biphase conditions. The improved ligand de-
sign and the careful choice of reaction conditions enabled
the scope of the reaction to be widened considerably.
27]
Results and Discussion
One of the most appealing features of chiral (salen)man- oxylate group and deprotection of the hydroxy group.[20]
ganese(III) complex-catalyzed asymmetric epoxidation of Such a procedure is unsuited for the synthesis of o-hydro-
alkenes is the opportunity to maximize the level of stereoin- xybenzaldehydes bearing tert-butyl groups, due to the diffi-
duction for a given substrate by fine-tuning of the catalyst’s culty of access to the corresponding starting compound.
steric and electronic properties. In many instances, an in- The direct perfluoroalkylation of 5-bromo-3-tert-butylsal-
crease in the steric bulk at the 3,3Ј- and 5,5Ј-positions in icylaldehyde 8 was thus undertaken, in the hope that hydro-
the ligand results in enhanced enantioselectivities. The pres- gen bonding with the hydroxy group and the steric bulk of
ence of bulky substituents (such as tert-butyl groups) is the tert-butyl group would protect the carbonyl group dur-
thought to force the approach of the substrate to the metal ing the reaction (Scheme 1). ortho-Formylation of 2-tert-bu-
site along productive directions, over the chiral diamine tylphenol mediated by SnCl was easily performed accord-
4
backbone, for instance.[ On the other hand, electron-do- ing to the classic procedure of Casiraghi. Bromination of
25]
[28]
nating substituents usually have a positive influence on the the resulting 3-tert-butyl-2-hydroxybenzaldehyde with Br2
enantioselectivity, while the presence of electron-with- in CH COOH afforded 8 in 56% overall yield, which com-
3
drawing substituents results in decreased enantioselectivity pares favourably with the overall yield of 15% obtained by
because of the enhanced reactivity of the Mn-oxo interme- following the reverse order of bromination/formylation as
4640
Eur. J. Org. Chem. 2001, 4639Ϫ4649

Asymmetric Epoxidation of Alkenes in Fluorinated Media
FULL PAPER
Aldehyde 8 is also a convenient starting compound for
the preparation of the fluorous biaryl o-hydroxyaldehydes
1
2 and 18 (Schemes 2 and 3).
Scheme 2. Synthesis of compound 12
Figure 2. Second generation fluorous chiral (salen)manganese(III)
complexes
proposed in the literature.[29] After some unfruitful at-
tempts, the coupling of 8 with C F I was achieved by por-
8
17
tionwise addition of the perfluoroalkylating agent to a sus-
pension of 8 and Cu powder in DMF, the temperature of
which was carefully maintained at 125 °C during the whole
reaction. The fluorous o-hydroxybenzaldehyde 9 was isol-
ated in 75% yield.
Scheme 3. Synthesis of compound 18
It had previously been shown that O-alkylation of hy-
droxy groups with R (CH ) LG (LG ϭ I, OSO C F ) can
F
2 n
2 4 9
profitably be used to insert long R chains into aromatic
F
compounds.[ Accordingly, biaryl aldehyde 10, obtained
from 2,3,4-trimethoxyphenyl boronic acid and aldehyde 8
by a modified Suzuki cross-coupling (yield ϭ 86%) was O-
deprotected (89%) and successively O-alkylated with
C F (CH ) I to give the fluorous salicylaldehyde 12 (37%)
30]
8
17
2 3
31,32]
(
Scheme 2).[
A minor drawback of this otherwise
Scheme 1. Synthesis of compound 9
Eur. J. Org. Chem. 2001, 4639Ϫ4649
straightforward sequence resides in the low-yielding O-al-
4641

M. Cavazzini, A. Manfredi, F. Montanari, S. Quici, G. Pozzi
kylation step. Although the free OH group of the salicyl Table 1. Partition coefficients P for Mn-6(C F COO) between n-
FULL PAPER
7
15
moiety is less accessible to the alkylating agent than those perfluorooctane and an organic solvent
on the other aryl ring, mild reaction conditions were neces-
Entry
Solvent[a]
P
sary if complete O-alkylation of aldehyde 11 was to be
avoided. This resulted in the formation of considerable
amounts of mono- and bis-O-alkylated compounds, which
could nevertheless be isolated and reused in following runs.
The second fluorous biaryl o-hydroxyaldehyde, com-
pound 18, was prepared according to the procedure out-
lined in Scheme 3. In this case, aldehyde 8 was protected by
O-methylation (92%) followed by acid-catalyzed treatment
1
2
3
4
Hexane
Dichloromethane
Toluene
1.21
39
Ͼ100
Ͼ100
Acetonitrile
[a]
Organic solvent (1 mL) was added to a solution of the catalyst
in n-perfluorooctane (0.01 , 1 mL). The mixture was stirred at 20
C for 3 h. The two phases were separated and the concentration
°
with 1,3-propanediol (86%). Cyclic acetal 14 was lithiated of the catalyst in each phase was determined by measurement of
the UV/Vis absorbances at 297 and 441 nm of a sample diluted as
necessary in CF ClCFCl and by comparison of the values ob-
tained with a calibration curve.
1
and quenched with B(OCH ) . H NMR analysis of the
3
3
2
2
crude product obtained after acidic hydrolysis of the reac-
tion mixture showed the presence of boronic acid 15 and of
the corresponding acetal as the main products. Although
1
5 could be isolated by column chromatography, the crude monly used in fluorous biphase chemistry, both complexes
mixture was found to be better used as such for the palla- were confined in n-perfluorooctane (partition coefficient Ͼ
dium(0)-catalyzed cross-coupling reaction with perfluoroal- 100). It should be noted that (Mn-6)C F COO and (Mn-
7
15
kyl-substituted aryl bromide 16. This compound was pre- 7)C F COO strongly absorb in the UV/Vis, and so even
7
15
pared by means of a copper-mediated cross-coupling reac- traces of these complexes should easily be detected in the
tion between 1,3,5-tribromobenzene and two equivalents of organic phase. Other organic solvents, such as chlorinated
C F I. A careful choice of reaction conditions allowed the ones, show a minimal ability to dissolve (Mn-6)C F COO
8
17
7 15
bis(perfluoroalkyl) derivative to be obtained as the main and (Mn-7)C F COO, but only in the case of n-perfluoro-
7
15
product in reasonable yields (60%) after crystallization from octane/hexane mixtures did these fluorous complexes parti-
CH Cl and then Et O. In spite of the use of crude aryl tion significantly between the two layers. The results ob-
2
2
2
boronic acid 15, the cross-coupling reaction afforded alde- tained with (Mn-6)C F COO are summarized in Table 1.
7
15
hyde 17 in good yield (63%); this was then O-deprotected
to give the desired salicylaldehyde 18 in quantitative yield.
First generation fluorous (salen)manganese(III) com-
plexes had primarily been tested as catalysts for the
The fluorous salen ligands 4Ϫ7 were obtained in good fluorous biphase epoxidation of alkenes with molecular
yields (72Ϫ95%) through condensation of two equivalents oxygen in the presence of a sacrificial aldehyde. Indeed, per-
of salicylaldehydes 9, 12, or 18 with the appropriate chiral fluorocarbons dissolve large quantities of O and it was
2
1
(
,2-diamine. The corresponding manganese(III) complexes supposed that this property might favourably influence the
Mn-4)Cl Ϫ (Mn-7)Cl (Figure 1) were prepared by treat- activity of the catalytic system. Second generation fluorous
ment of the ligand with an excess of Mn(OAc) ·4H O in complexes (Mn-4)Cl and (Mn-5)Cl were thus first examined
2
2
refluxing ethanol under aerobic conditions, followed by an- in conjunction with this oxidizing system with the aim of
ion exchange with LiCl. verifying whether the increased steric bulk would have any
As expected, complexes (Mn-4)Cl and (Mn-5)Cl, each of beneficial effect. Benzotrifluoride, which is able to dissolve
which possess a relatively low fluorine load (47.5 and both first and second generation catalysts, was chosen as
4
4.3%, respectively), were found to be soluble in benzotri- the fluorinated medium. The aerobic epoxidation of 1,2-
fluoride and CCl FCF Cl, but only sparingly soluble in dihydronaphthalene and benzosuberene was carried out in
2
2
boiling n-perfluorooctane. Complexes (Mn-6)Cl and (Mn- the dark at 20 °C under atmospheric pressure of O2
)Cl are also soluble in low-fluorinated solvents. More in- (Table 2). A solution of the catalyst in benzotrifluoride was
terestingly, these complexes, richer in fluorine (54.9. and added to a solution of the substrate plus N-hexylimidazole
5.0%, respectively) and bearing multiple R ponytails are dissolved in CH Cl . Pivalaldehyde was gradually added to
7
5
F
2
2
also soluble in n-perfluorooctane, but these solutions are the homogeneous solution, until the aldehyde/starting al-
not stable and aggregation phenomena were observed on kene molar ratio was equal to 3. The degrees of conversion
standing. This behaviour can be explained by mutual inter- observed in blank experiments carried out under the same
actions among the extended organophilic frameworks of conditions, but in the absence of a catalyst, were negligible.
the molecules and by the very low ion-solvating power of
Previous studies had shown that different reaction path-
perfluorocarbons. An exchange of the chloride counterion ways are possible in the presence of O /aldehyde. In particu-
2
Ϫ
of (Mn-6)Cl and (Mn-7)Cl for the fluorophilic C F COO
lar, the partial inversion of the relative configuration during
7
15
anion provided a solution to this problem. Partition coeffi- the epoxidation of cis-stilbene pointed to a free radical
cients between n-perfluorooctane and organic solvents, de- mechanism contribution. This might be deleterious with re-
termined by UV/Vis spectroscopy at 25 °C (see Table 1),[
33]
spect to the enantioselectivity of the catalytic system, as
were found to be quite similar for the resulting (Mn- confirmed by the results obtained with second generation
)C F COO and (Mn-7)C F COO complexes. When the catalysts (ees ϭ 10Ϫ34%). Most interestingly, it appeared
6
7
15
7 15
organic solvent was CH CN or toluene, which are com- that the presence of a tert-butyl group in the 3,3Ј-positions
3
4642
Eur. J. Org. Chem. 2001, 4639Ϫ4649

Asymmetric Epoxidation of Alkenes in Fluorinated Media
FULL PAPER
2
Table 2. Homogeneous epoxidation of 1,2-dihydronaphthalene and benzosuberene with O /pivalaldehyde at 20 °C
Entry
Substrate[a]
Catalyst
t [h]
Yield[b] (%)
ee[c] (%)
1
2
3
4
5
6
7
8
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
Benzosuberene
Benzosuberene
Benzosuberene
(Mn-1)Cl
(Mn-3)Cl
(Mn-4)Cl
(Mn-5)Cl
(Mn-1)Cl
(Mn-3)Cl
(Mn-4)Cl
(Mn-5)Cl
2
2
22
22
2
3
22
22
70
62
44
77
92
91
40
78
10
5
25
10
7
12
34
10
Benzosuberene
[
a]
Conditions. Catalyst: 0.01 mmol; substrate: 0.2 mmol; pivalaldehyde: 0.6 mmol; N-hexylimidazole: 0.02 mmol; solvent: CH
2
Cl
2 3
/PhCF
[
b]
[c]
(
2 mL, 1:1 v/v).
Determined by capillary GC (HP-5 5% phenylmethylsiloxane column, internal standard method). Determined by
capillary GC (Cyclodex-B chiral column).
of the catalyst reduced reaction rates (entries 3 vs. 1, for enced by comparisons between (Mn-1)Cl and (Mn-4)Cl and
example). In many cases this did not result in increased se- between (Mn-3)Cl and (Mn-5)Cl. In the case of 1,2-dihy-
lectivities in epoxide because the incidence of by-products dronaphthalene (entries 1 vs. 3 and 2 vs. 4), substitution of
increased with reaction times. A considerable enhancement the R substituents in 3,3Ј-positions with tert-butyl groups
F
of the level of stereoinduction was observed in reactions produced ∆ees of up to ϩ200%, although the level of ste-
catalyzed by (Mn-4)Cl, in comparison with those carried reoinduction remained rather low. Moderate to good en-
out with the first generation catalyst (Mn-1)Cl derived from antioselectivities were obtained in the epoxidation of benzo-
the same chiral diamine (entries 3 vs. 1 and 7 vs. 5), but a suberene catalyzed by second generation catalysts (Mn-4)Cl
similar comparison between (Mn-5)Cl and (Mn-3)Cl and (Mn-5)Cl (entries 11 and 12), with ∆ees of up to
showed meaningless differences (entries 4 vs. 2 and 8 vs. 6). ϩ125% with respect to those obtained with (Mn-1)Cl and
In order to avoid all interference due to the puzzling na- (Mn-3)Cl (entries 9 and 10).
ture of the O /aldehyde oxidizing system, a second set of
As expected, further improvements in the enantioselectiv-
2
experiments with MCPBA/NMO was undertaken. Jacobsen ities were observed in the epoxidation of 1,2-dihydronaph-
and co-workers had shown that the epoxidation of most thalene catalyzed by (Mn-6)C F COO and (Mn-
7
15
substrates with this combination of oxidants proceeds 7)C F COO. The ees obtained with these complexes were
7
15
smoothly at Ϫ78 °C, to afford high ees.[ Benzotrifluoride almost identical (entries 5 and 7), with ∆ee ϭ ϩ300% relat-
solutions of the fluorous (salen)manganese(III) complexes ive to those obtained in the reaction catalyzed by the first
are not stable at such a low temperature, and so reactions generation catalyst (Mn-1)Cl, the framework of which con-
were carried out at Ϫ50 °C, the lowest temperature compat- tains the same chiral diamine unit (entry 1). It is worth
ible with the solubility of the catalysts, with CH Cl used noting that (Mn-6)C F COO and (Mn-7)C F COO af-
17]
2
2
7
15
7 15
to dissolve the oxidants. The results obtained (Table 3) were forded only a slight improvement (∆ee ϭ ϩ36%) over (Mn-
all in agreement with a positive influence of the higher 4)Cl, still with two R substituents attached at the salycilid-
F
steric bulk of second generation fluorous catalysts, as evid- ene core of the ligand. Given that the epoxidation of 1,2-
Table 3. Homogeneous epoxidation of 1,2-dihydronaphthalene and benzosuberene with MCPBA/NMO at Ϫ50 °C
Entry
Substrate[a]
Catalyst
t [h]
Yield[b] (%)
ee[c] (%)
1
2
3
4
5
6
7
8
9
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
Benzosuberene
Benzosuberene
Benzosuberene
Benzosuberene
Benzosuberene
(Mn-1)Cl
(Mn-3)Cl
(Mn-4)Cl
(Mn-5)Cl
1
1
68
59
84
88
69
65
70
73
83
76
82
72
83
88
16
12
47
33
62
64
63
63
36
28
81
57
63
74
0.5
0.5
0.5
0.5
0.75
0.75
1
(Mn-6)C
(Mn-6)Cl
7
F
F
15COO
15COO
(Mn-7)C
(Mn-7)Cl
(Mn-1)Cl
(Mn-3)Cl
(Mn-4)Cl
(Mn-5)Cl
7
10
11
12
13
14
1
0.5
0.5
0.5
0.5
(Mn-6)C
(Mn-7)C
7
F
F
15COO
15COO
Benzosuberene
7
[
[
a]
Conditions. Catalyst: 0.01 mmol; substrate: 0.2 mmol; MCPBA: 0.4 mmol; NMO: 0.5 mmol; solvent: CH
2
Cl
2
/PhCF
3
(2 mL, 1:1 v/v).
b]
[c]
Determined by capillary GC (HP-5 5% phenyl methyl siloxane column, internal standard method). Determined by capillary GC
Cyclodex-B chiral column).
(
Eur. J. Org. Chem. 2001, 4639Ϫ4649
4643

M. Cavazzini, A. Manfredi, F. Montanari, S. Quici, G. Pozzi
FULL PAPER
dihydronaphthalene catalyzed by (Mn-6)Cl and (Mn-7)Cl fluorous biphase epoxidation of 1,2-dihydronaphthalene
proceeded exactly as in the cases of (Mn-6)C F COO and with PhIO/PNO at 100 °C, the boiling point of n-perfluoro-
7
15
(
Mn-7)C F COO (entries 6 vs. 5 and 8 vs. 7), it is likely octane and the highest operating temperature of the solvent
7 15
that the nature of the counterion does not influence the system, are comparable to those reported for the same reac-
behaviour of the second generation catalysts to any appre- tion in CH CN in the presence of the commercially avail-
3
35]
ciable extent.
able Jacobsen’s catalyst (entry 8).[
On the other hand, the more efficient shielding of the
metal site of the catalysts from the electron-withdrawing ac-
Table 4. Fluorous biphase epoxidation of 1,2-dihydronaphthalene
with PhIO/PNO, catalyzed by Mn-7(C F15COO), at increasing
7
temperatures
tion of the R substituents did not have any positive effect
F
in the case of the epoxidation of benzosuberene, in which
the biaryl catalysts afforded ees even lower than those ob-
tained with (Mn-4)Cl (entries 13 and 14 vs. 11). It should
be also pointed out that removal of two RF substituents
from the 3,3Ј-positions of the ligand without introduction
T[a] [°C]
Yield[b] (%)
ee[c] (%)
Entry
1
t [h]
0
0
20
40
70
100
25
3
3
3
3
2
1
1
24
4.5
3
8
6
[d]
2
3
4
5
6
7
8
46
76
74
77
81
70
26
32
42
50
61
46
of any sterically demanding substituents did not improve
enantioselectivities.[
20b]
The picture emerging from all these
data is coherent with the idea that steric effects play a major
role in determining the level of stereoinduction obtained
with fluorous (salen)manganese(III) complexes in the epox-
idation of alkenes.
The otherwise useful MCPBA/NMO oxidizing system
was not suitable for fluorous biphasic epoxidations in the Determined by capillary GC (Cyclodex-B chiral column). Cata-
[
[
e]
f]
room temp.
[a]
Conditions: see Exp. Sect. [b] Determined by capillary GC (HP-
[c]
5
5% phenylmethylsiloxane column, internal standard method).
[
d]
[
e]
lyst: (Mn-6)C
0
0
7
F15COO.
Homogeneous conditions. Catalyst:
presence of (Mn-6)C F COO and (Mn-7)C F COO, due
7
15
7 15
.01 mmol; substrate: 0.2 mmol; PhIO: 0.3 mmol; PNO:
to the low solubility of these complexes in n-perfluorooct-
ane at the low temperatures at which MCPBA/NMO works
best. Test reactions in CH Cl /benzotrifluoride were thus
2 2 3
.05 mmol; solvent: CH Cl /PhCF
(2 mL, 1:1 v/v). [ See ref.
f]
[35]
Catalyst: Jacobsen’s catalyst.
2
2
carried out with other oxidizing agents commonly used in
Reger and Janda recently described an interesting ap-
association with (salen)manganese(III) complexes. At 25 proach to recoverable, polymer-supported (salen)mangane-
C, PhIO in the presence of small amounts of pyridine N- se(III) complexes.[ They showed that the use of gel-type
19]
°
oxide (PNO) gave results comparable to those obtained resins offers an improvement over earlier immobilization
with MCPBA/NMO at Ϫ50 °C, [for example: epoxide systems, which suffered from poor selectivity and/or recycl-
yield ϭ 81%, ee ϭ 61% in the epoxidation of 1,2-dihydrona- ability of the catalysts, and suggested that their system may
phthalene catalyzed by (Mn-7)C F COO]. This oxidizing find utility in high-throughput organic synthesis. In sum-
7
15
system was thus used in the next fluorous biphase reactions, mary, a catalyst supported on a specific insoluble resin with
which were run in n-perfluorooctane/CH CN. The organic good swelling properties afforded yields ranging between
3
solvent was chosen in view of the favourable partition coef- 71% and 81%, with ees ϭ 51Ϫ88%, in the epoxidation of
ficients of the catalysts and the consideration that homo- three substrates with MCPA/NMO at Ϫ78 °C. This catalyst
geneous epoxidation reactions with PhIO/PNO are conveni- was readily recovered by filtration of the reaction mixture
[34]
ently carried out in CH CN at 0Ϫ25 °C.
and it could be used three times in the epoxidation of styr-
3
Rather unexpectedly, both reaction yield and enantiose- ene and cis-β-methylstyrene without any significant drop in
lectivity rose with temperature under fluorous biphase con- selectivity, but it suddenly lost activity in the fourth run.
ditions (Table 4). Only traces of 1,2-dihydronaphthalene ep- With 1,2-dihydronaphthalene, the catalyst could stand only
oxide were detected at 0 °C in the presence of both catalysts, one recycle. Epoxide yields throughout recycles were not re-
with very low ees (entries 1 and 2). Yields reached their ported.
maximum level at 40 °C, whereas the ees increased regu-
Under the optimized fluorous biphase conditions de-
larly, moving towards the upper value of 60% found under scribed above, reactions catalyzed by second generation (sa-
homogeneous conditions (entry 7). The reasons for this be- len)manganese complexes (Mn-6)C F COO and (Mn-
7
15
haviour, exemplified in the case of (Mn-4)C F COO (Ent- 7)C F COO afforded epoxide yields (68Ϫ98%) and ees
7
15
7 15
ries 3Ϫ6), were not thoroughly investigated, but it is likely (50Ϫ92%) close to those obtained by Reger and Janda
that at low temperature the reaction occurs at the interface (Tables 5 and 6). As had also been found in the case of
of the two phases, where distortion of the catalyst structure homogeneous reactions (Table 3), we did not observe major
[
20b]
could be severe.
Although the biphase mixture we used differences between the two catalysts, although (Mn-
did not become homogeneous even at 100 °C, the miscibil- 7)C F COO usually gave slightly better results. Recycling
7
15
ity of the organic and fluorous component of the system of the fluorous catalysts could be performed quickly by
should be enhanced, thus facilitating both mass transfer simple phase separation at room temperature, and the cata-
and the correct approach of the substrate to the catalytic lytic activity of the fluorous layer significantly dropped in
[
7,12a]
site.
Emergence of temperature-dependent micellar ef- the fourth run. This set of results clearly indicates that the
fects cannot be ruled out either. The results obtained in the fluorous biphase approach is in no way inferior to the im-
4644
Eur. J. Org. Chem. 2001, 4639Ϫ4649

Asymmetric Epoxidation of Alkenes in Fluorinated Media
mobilization of (salen)manganese complexes onto gel-type Table 6. Fluorous biphase epoxidation of alkenes with PhIO/PNO,
FULL PAPER
resins. Some experimental findings, however, deserve a brief catalyzed by Mn-7(C
7
F
15COO), at 100 °C
comment. It is well known that a low-temperature meth-
Entry Substrate[a]
t [h] Yield[b] (%) ee[c] (%)
odology is required for the highly enantioselective epoxid-
ation of styrene derivatives.[ Accordingly, the attempted
36]
1
2
3
4
5
6
7
8
9
0
1
2
3
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
Benzosuberene
Benzosuberene
Benzosuberene
1
1
1
1
77
67
63
19
92
92
83
43
98
99
82
52
50
45
46
40
68
66
64
60
77
77
76
57
92
92
93
79
58
53
40
25
87
85
83
71
fluorous biphase epoxidation of cis-β-methylstyrene at 100
C afforded a mixture of cis- and trans-epoxide (3.6:1 ratio)
[d]
[
[
e]
f]
°
in 68% yield. In this respect, the fluorous biphase approach
still requires some efforts to match the results obtained with
resin-supported catalysts. On the other hand, the fluorous
biphase epoxidation of suitable substrates such as triphenyl-
ethylene (Table 5, entries 17Ϫ20; Table 6, entries 21Ϫ23)
and indene (Table 6, entries 13Ϫ16) did not show any signi-
ficant drop in enantioselectivity and epoxide yield over
three subsequent reaction cycles: the fluorous catalysts were
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
0.25 98
0.25 95
0.25 93
0.5
0.5
0.5
0.5
1
[d]
[e]
[f]
Benzosuberene
1-Methylindene
1-Methylindene
1-Methylindene
1-Methylindene
Indene
Indene
Indene
[
[
[
d]
e]
f]
1
1
1
1
[g]
[g]
[g]
[g]
[
d]
e]
f]
still reasonably active even in the fourth cycle, a result not 14
achieved with resin-supported catalysts.
15[
[
1
1
18
6
7
Indene
76
91
87
76
45
98
96
92
80
1-Methylcyclohexene
1-Methylcyclohexene
1-Methylcyclohexene
1-Methylcyclohexene
Triphenylethylene
Triphenylethylene
Triphenylethylene
Triphenylethylene
[
d]
e]
f]
Table 5. Fluorous biphase epoxidation of alkenes with PhIO/PNO,
19[
catalyzed by Mn-6(C
7
F
15COO), at 100 °C
[
2
0
[
g]
Substrate[a]
Yield[b] (%)
ee[c] (%)
21
0.5
0.5
0.5
1
Entry
1
t [h]
[
[
[
d]
e]
f]
[g]
[g]
[g]
2
2
1
2
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
1,2-Dihydronaphthalene
Benzosuberene
Benzosuberene
Benzosuberene
Benzosuberene
1-Methylindene
1-Methylindene
1-Methylindene
1
1
1
1
68
68
60
30
84
79
75
51
96
95
92
76
95
95
74
50
98
98
95
78
50
48
44
31
69
69
69
54
70
68
66
50
52
50
31
20[
[
[
[
d]
e]
f]
23
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
[
a]
Conditions: see Exp. Sect. [b] Determined by capillary GC (HP-
5% phenyl methyl siloxane column, internal standard method).
Determined by capillary GC (Cyclodex-B chiral column). First
5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
0.5
0.5
0.5
1
[c]
[d]
[
[
[
d]
e]
f]
[e]
reuse of the fluorous layer. Second reuse of the fluorous layer.
[f]
[g]
1
Third reuse of the fluorous layer.
Determined by H NMR
3
spectroscopy in the presence of the chiral shift reagent Eu(hfc) .
[
[
[
d]
e]
f]
1
1
1
1
1
1
1
1
1
1
2
Conclusion
1-Methylindene
1-Methylcyclohexene
1-Methylcyclohexene
1-Methylcyclohexene
1-Methylcyclohexene
Triphenylethylene
Triphenylethylene
Triphenylethylene
Triphenylethylene
[
[
[
d]
e]
f]
The synthesis of new chiral fluorous catalysts and their
evaluation for use in fluorous chemistry is of considerable
interest. We have now demonstrated that sterically encum-
bered chiral (salen)manganese complexes bearing a suitable
g]
0.5
0.5
0.5
1
80
[
[
[
d]
e]
f]
[g]
81
79
number of R substituents can be used as catalysts in the
[g]
F
[g]
asymmetric epoxidation of several substrates, affording re-
sults that compare favourably to those obtained with other
immobilized chiral catalytic systems. Our previous hypo-
theses about the role of steric and electronic effects in deter-
mining the level of stereoinduction of fluorous (salen)man-
ganese(III) complexes have been experimentally confirmed.
The choice of proper reaction conditions is also very im-
portant if satisfactory results are to be achieved. In order
to switch a homogeneous asymmetric catalytic reaction into
66
[
a]
Conditions: see Exp. Sect. [b] Determined by capillary GC (HP-
5
5% phenyl methyl siloxane column, internal standard method).
[
c]
[d]
Determined by capillary GC (Cyclodex-B chiral column). First
[e]
reuse of the fluorous layer. Second reuse of the fluorous layer.
[
f]
[g]
1
Third reuse of the fluorous layer.
Determined by H NMR
spectroscopy in the presence of the chiral shift reagent Eu(hfc)
3
.
Finally, effective recycling of second generation fluorous its fluorous biphase version, many parameters must be ad-
catalysts through a very high number of reaction runs ap- justed, as exemplified here by the striking increase in en-
pears to be mainly hampered by the oxidative decomposi- antioselectivity observed upon raising the temperature.
tion of the catalyst, as evidenced by the progressive disap- Moreover, the solubility of charged fluorous complexes in
pearance of the characteristic UV/Vis absorption bands of perfluorocarbons can be strongly enhanced by choice of a
the (salen)manganese(III) in the fluorous phase and by the fluorinated counterion.
absence of such bands in the organic phase. This is in agree-
We are currently investigating the use of second genera-
ment with previous literature reports dealing with the fate tion fluorous chiral salen ligands in other asymmetric reac-
of immobilized (salen)manganese complexes during oxida- tions, such as the hydrogen-transfer reduction of ketones,[
37]
[
35]
tion reactions,
and also with the behaviour of catalysts with the aim of widening the scope of these versatile li-
attached to gel-type resins.[
19]
gands.
Eur. J. Org. Chem. 2001, 4639Ϫ4649
4645

M. Cavazzini, A. Manfredi, F. Montanari, S. Quici, G. Pozzi
FULL PAPER
methoxyphenyl boronic acid (0.89 g, 4.20 mmol)[31] were dissolved
at room temperature under nitrogen in deaerated 1-propanol (7
Experimental Section
mL) in a Schlenk tube. PPh
3
(9.5 mg, 36 µmol) and Pd(OAc)
2
General Remarks: Solvents were purified by standard methods and
dried if necessary, except for perfluorocarbons, which were used as
received. All commercially available reagents were used as received.
Ϫ TLC was carried out on 60 F254 silica gel. Column chromato-
graphy (CC) was carried out on SI 60 silica gel, mesh size
(
(
2.7 mg, 12 µmol) were then added, followed by aqueous Na CO
1.2 , 4.80 mL). The stirred suspension was warmed in an oil bath
2
3
set at 110 °C. After 2 h the suspension was allowed to cool to room
temperature and water (5 mL) was added. The mixture was stirred
for 1 h and extracted with EtOAc (3 ϫ 20 mL). The combined
0.040Ϫ0.063 mm (Merck, Darmstadt, Germany). Ϫ Melting points
organic layers were washed with 5% aqueous NaHCO
mL) and brine (20 mL), and dried with MgSO . The solvent was
evaporated. and the crude product was purified by CC (silica gel,
light petroleum ether/CH Cl /EtOAc 7:2:1) to give the title com-
3
(2 ϫ 10
(uncorrected) were determined with a Büchi SMP-20 capillary
melting point apparatus. Ϫ Optical rotations were measured using
a PerkinϪElmer 241 polarimeter. Ϫ UV/Vis spectra were measured
4
1
using a Lambda 6 PerkinϪElmer spectrometer. Ϫ H NMR
2
2
1
300 MHz), 13C NMR (75.4 MHz), and F NMR (282 MHz) spec-
tra were recorded on a Bruker AC 300 spectrometer with tetra-
methylsilane (δ ϭ 0), CDCl (δ ϭ 77) and CFCl (δ ϭ 0) as internal
19
pound as a pale yellow solid (1.19 g, 86%); m.p. 74 °C. H NMR
CDCl ): δ ϭ 1.48 [s, 9 H, C(CH ]. 3.74 (s, 3 H, OCH ), 3.93 (s,
H, OCH ), 3.95 (s, 3 H, OCH ), 6.77 (d, J ϭ 8.6 Hz, 1 H), 7.04
d, J ϭ 8.6 Hz, 1 H), 7.56 (d, J ϭ 2.2 Hz, 1 H), 7.72 (d, J ϭ 2.2 Hz,
(
(
3
3
)
3
3
3
3
3
3
3
(
standard respectively, unless otherwise indicated. Ϫ GC analyses
were performed on a HewlettϪPackard 5890 instrument (column:
1
3
1
3
H), 9.93 (s, 1 H, CHO), 11.8 (s, 1 H, OH). C NMR (CDCl ):
δ ϭ 29.7, 35.4, 56.5, 61.3, 61.4, 108.1, 120.9, 124.7, 127.8, 129.6,
32.6, 135.8, 138.3, 143.1, 151.7, 153.7, 160.6, 197.7. C20
344.4): calcd. C 69.75, H 7.02; found C 69.54, H 7.31.
3
0
0 ϫ 0.5 mm RSL-200 polymethylsiloxane or Cyclodex-B, 30 ϫ
.25 mm chiral column). Ϫ Elemental analysis: Redox S.n.C.
1
(
24 5
H O
(Monza, Italy) and Departmental Service of Microanalysis (Uni-
versity of Milano).
3
BBr
-tert-Butyl-2-hydroxy-5-(2,3,4-trihydroxyphenyl)benzaldehyde (11):
(1  in CH Cl , 7 mL, 7 mmol) was added at Ϫ78 °C under
nitrogen to a solution of trimethoxybenzaldehyde 10 (0.69 g,
.01 mmol) in dry CH Cl (8 mL). After 10 min the external tem-
5
-Bromo-3-tert-butyl-2-hydroxybenzaldehyde (8): A solution of Br
0.53 mL, 10.3 mmol) in CH COOH (2 mL) was added dropwise
at room temperature over 15 min to a solution of 3-tert-butyl-2-
hydroxybenzaldehyde (1.78 g, 9.98 mmol) in CH COOH (5 mL).
After 1 h the reaction mixture was diluted with CH Cl (30 mL)
and washed with H O (10 mL), saturated aqueous Na (10
mL), saturated aqueous NaHCO (10 mL), and brine (10 mL). The
organic phase was dried with Na SO and the solvents were evapor-
2
3
2
2
(
3
2
2
2
3
perature was raised to Ϫ18 °C and the solution was stirred for 1 h.
Ice (10 g) was slowly added and the resulting mixture was stirred
until two liquid layers were formed. The aqueous phase was ex-
tracted with Et
washed with brine (15 mL), dried with MgSO
under reduced pressure. Purification by CC (silica gel, CH
MeOH 95:5) afforded the title compound as a pale yellow solid
2
2
2
2 2 5
S O
3
O (3 ϫ 20 mL). The combined organic layers were
and concentrated
Cl
2
2
4
4
ated, to afford the title compound as a yellow solid (2.45 g, 95%,
m.p. 59Ϫ62 °C). The product thus obtained was pure enough for
further reactions as shown by 1H NMR. Crystallization from
MeOH (10 mL, recovery: 60%) afforded an analytically pure
2
2
/
1
(
0.54 g, 89%); m.p.Ͼ200 °C. H NMR (CD
C(CH ], 4.83 (br. s, 3 H, OH),), 6.43 (d, J ϭ 8.4 Hz, 1 H), 6.64
d, J ϭ 8.4 Hz, 1 H), 7.66 (d, J ϭ 2.2 Hz, 1 H), 7.79 (d, J ϭ 2.2 Hz,
3
OD): δ ϭ 1.45 [s, 9 H,
3 3
)
sample; m.p. 63Ϫ64 °C (ref.[ 63.3Ϫ65.5 °C). H NMR (CDCl
29]
1
):
], 7.50 (d, J ϭ 2.5 Hz, 1 H), 7.57 (d, J ϭ
3
(
δ ϭ 1.39 [s, 9 H, C(CH
.5 Hz, 1 H), 9.81 (s, 1 H, CHO), 11.71 (s, 1 H, OH). C NMR
CDCl ): δ ϭ 29.2, 35.4, 121.9, 124.6, 133.8, 137.1, 141.5, 160.3,
95.8. C11 13BrO (257.0): calcd. C 51.38, H 5.10; found C 51.27,
)
3 3
13
1
1
1
H), 9.89 (s, 1 H, CHO). C NMR (CD
08.5, 121.1, 121.9, 132.0, 133.5, 134.6, 136.6, 138.2, 144.7, 146.6,
53.2, 160.4, 199.6. C17 (302.3): calcd. C 67.54, H 6.00; found
3
OD): δ ϭ 29.8, 35.8,
13
2
(
3
18 5
H O
1
H
2
C 66.98, H 6.34.
H 5.23.
3
-tert-Butyl-2-hydroxy-5-[2,3,4-tris(1H,1H,2H,2H,3H,3H-n-per-
3
-tert-Butyl-2-hydroxy-5-n-heptadecafluorooctylbenzaldehyde (9):
fluoroundecyl)phenyl]benzaldehyde (12): A flame-dried Schlenk tube
was charged with compound 11 (0.60 g, 2.00 mmol), anhydrous
K
Copper powder (1.91 g, 30.1 mmol) was added to a solution of o-
hydroxybenzaldehyde 8 (1.54 g, 5.99 mmol) in dry DMF (20 mL)
in a flame-dried Schlenk vessel. The suspension was purged with
nitrogen and warmed whilst stirring to 120 °C. C
1
2
CO
3 3
(1.66 g, 12.0 mmol) and dry CH CN (15 mL). The mixture
was stirred under nitrogen for 10 min at 70 °C, after which
8
F17I (3.20 mL,
8 2 3
C F17(CH )
I (1.76 g, 2.99 mmol)[ was added in three portions
38]
2.1 mmol) was added under nitrogen to the stirred suspension in
over 3 h. The reaction was vigorously stirred at 70 °C overnight.
Evaporation of the solvent under reduced pressure afforded a res-
four 0.80 mL portions, with a pause of 40 min between each addi-
tion. After 3 h the suspension was allowed to cool to room temper-
idue that was taken up in Et
removed by filtration through a Celite pad that was thoroughly
washed with Et O. The clear ether layer was washed with brine (30
mL) and dried with MgSO . Flash CC (silica gel, light petroleum
ether/CH2Cl ϭ 75:25) afforded the title compound (1.24 g, 37%)
as a white solid; m.p. 90Ϫ91 °C. H NMR (CDCl
H, C(CH ], 1.75Ϫ1.82 (m, 2 H), 1.95Ϫ2.20 (m, 8 H), 2.26Ϫ2.41
m, 4 H), 4.09Ϫ4.14 (m, 4 H), 6.75 (d, J ϭ 8.6 Hz), 7.03 (d, J ϭ
2
O (75 mL). The inorganic salts were
ature, treated with H
using a Büchner funnel. The aqueous phase was extracted with
Et O (3 ϫ 15 mL): The combined organic layers were washed with
brine (20 mL) and dried with Na SO . Purification by CC (silica
gel, petroleum ether/Et O 95:5) afforded the title compound as a
white solid (2.72 g. 75%); m.p. 54 °C. H NMR (CDCl
s, 9 H, C(CH ], 7.66 (br. s, 1 H), 9.93 (s, 1 H, CHO), 12.13 (s, 1
H, OH). F NMR (CDCl ): δ ϭ Ϫ81.1 (t, J ϭ 10.0 Hz, 6 F),
Ϫ111.2 (t, J ϭ 13.0 Hz, 4 F), Ϫ121.8 (br. s, 4 F), Ϫ122.3 (br. s, 12
F), Ϫ123.0 (br. s, 4 F), Ϫ126.4 (br. s, 4 F). 13C NMR (CDCl
): δ ϭ
17), 120.1, 131.0, 131.5, 139.8, 163.7,
(596.3): calcd. C 38.20, H 2.20; found C 38.73,
2 2
O (20 mL) and Et O (40 mL), and filtered
2
2
4
2
4
2
2
1
): δ ϭ 1.45 [s, 9
1
3
3
): δ ϭ 1.43
3 3
)
[
3 3
)
(
19
3
8
9
.6 Hz, 1 H), 7.50 (d, J ϭ 2.0 Hz, 1 H), 7.68 (d, J ϭ 2.0 Hz, 1 H),
.90 (s, 1 H, CHO), 11.82 (br. s, 1 H, OH). F (CDCl ): δ ϭ Ϫ82.7
3
1
9
3
(
m, 9 F), Ϫ115.0 (m, 6 F), Ϫ122.5 (br. s, 18 F), Ϫ123.3 (br. s, 6
2
1
8.9, 35.2, 104Ϫ119 (m, C
8
F
1
3
F), Ϫ123.9 (br. s, 62 F), Ϫ126.7 (br. s, 6 F). C NMR (CDCl
δ ϭ 29.7, 35.4, 56.5, 61.3, 61.4, 105Ϫ120 (m, C 17), 105.7, 120.9,
24.7, 127.8, 129.6, 132.6, 135.8, 138.3, 143.1, 151.7, 153.7, 160.6,
3
):
96.5. C19
13 17 2
H F O
8
F
H 2.36.
1
3
-tert-Butyl-2-hydroxy-5-(2,3,4-trimethoxyphenyl)benzaldehyde 197.7. C50
H
33
F
51
O
5
(1682.7): calcd. C 35.69, H 1.98; found C
(10): o-Hydroxybenzaldehyde 8 (1.03 g, 4.01 mmol) and 2,3,4-tri- 35.86, H 1.72.
4646
Eur. J. Org. Chem. 2001, 4639Ϫ4649

Asymmetric Epoxidation of Alkenes in Fluorinated Media
FULL PAPER
5
-Bromo-3-tert-butyl-2-methoxybenzaldehyde (13): Dimethylsulfate with cold Et
1.51 g, 12.0 mmol) was added to a mixture of o-hydroxybenzal- in a Soxhlet apparatus. The combined ethereal extracts were
dehyde 8 (2.57 g, 10.0 mmol) and solid K CO (2.76 g, 20.0 mmol) washed with brine (30 mL) and dried with MgSO . Removal of
in acetone (30 mL). The mixture was stirred at room temperature the solvent under reduced pressure afforded a white solid residue
overnight before being quenched with H O (10 mL) and concen- (8.20 g), which was treated with boiling CH Cl (70 mL). All undis-
trated under reduced pressure. The residue was extracted with solved material was discarded and the warm, clear solution was
CH Cl (3 ϫ 25 mL) and the combined organic layers were washed evaporated to dryness to afford a residue (7.31 g) that was crystal-
with brine (20 mL) and dried with Na SO . Evaporation of the lized twice from Et O (60 mL). The title compound was obtained
solvent afforded the title compound as a pale yellow solid (2.49 g, as a white solid (5.66 g, 60%); m.p. 72 °C. H NMR (CFCl
2 2
O (3 ϫ 50 mL) and then extracted with boiling Et O
(
2
3
4
2
2
2
2
2
2
4
2
1
2
CF
BrF34
), 7.61 (d, J ϭ 2.4 Hz, 1 H), 7.78 (d, J ϭ 2.4 Hz, (993.1): calcd. C 26.61, H 0.30, F 65.04; found C 26.52, H 0.34,
H), 10.24 (s, 1 H, CHO). 13C NMR (CDCl
): δ ϭ 30.9, 35.8, F 64.71.
6.7, 117.6, 130.7, 136.5, 189.3. C12 15BrO (271.0): calcd. C 53.16,
2
Cl,
1
9
3
1
6
2%); m.p. 82 °C Ϫ H NMR (CDCl
3 3 3 3 3
): δ ϭ 1.38 [s, 9 H, C(CH ) ], ext. ref. CDCl ): δ ϭ 7.73 (br. s, 1 H), 7.95 (br. s, 2 H). C22H
.92 (s, 3 H, OCH
3
3
H
2
5
-[3,5-Bis(n-heptadecafluorooctyl)phenyl]-3-tert-butyl-2-methoxy-
benzaldehyde (17): A suspension of crude boronic acid 15 (1.60 g),
(14): aryl bromide 16 (1.23 g, 1.24 mmol), Pd(OAc) (13.8 mg,
O (0.30 mL, 2.39 mmol) was added to a solution of o-me- 61.0 µmol), PPh (48.0 mg, 110 µmol), and Na CO (0.19 g,
thoxybenzaldehyde 13 (2.71 g, 10.0 mmol) and 1,3-propanediol 1.80 mmol) in deaerated 1-propanol (6 mL) was heated to 120 °C
3.80 g, 50.0 mmol) in toluene (5 mL). The yellow solution was in a Schlenk tube under nitrogen. Water (0.6 mL) was added and
H 5.58; found C 53.35, H 5.63.
2
-(5-Bromo-3-tert-butyl-2-methoxyphenyl)-1,3-dioxane
2
BF ·Et
3
2
3
2
3
(
heated to reflux for 4 h, after which it was cooled to room temper-
the mixture was vigorously stirred for 4 h. Cold water (15 mL) was
O (3
(10 mL) and brine (10 mL), and dried ϫ 20 mL). The combined organic layers were washed with 5%
. The solvent was evaporated and the residue was puri- aqueous HCl (2 ϫ 10 mL) and brine (20 mL), and dried with
fied by CC (silica gel, CH Cl /light petroleum ether 1:1) to afford MgSO . The solvent was evaporated to afford a yellow residue
the title compound as a pale yellow oil that slowly solidified on (1.82 g) from which the title compound was isolated by CC (silica
): δ ϭ gel, light petroleum ether/Et O 95:5) as a white solid (0.86 g, 63%);
), m.p. 79Ϫ80 °C. H NMR (CDCl ): δ ϭ 1.48 [s, 9 H, C(CH ],
H, 4.01 (s, 3 H, OCH ), 7.73 (d, J ϭ 2.5 Hz, 1 H), 7.78 (br. s, 1 H),
)], 7.38 (d, J ϭ 2.6 Hz, 1 H), 7.64 (d, J ϭ 2.6 Hz, 1 7.92 (d, J ϭ 2.5 Hz, 1 H), 7.94 (br. s, 2 H), 10.41 (s, 1 H, CHO).
ature and Et
saturated aqueous NaHCO
with MgSO
2 2
O (30 mL) was added. The solution was washed with then added. After 1 h, the suspension was extracted with Et
3
4
2
2
4
1
standing (2.84 g, 86%); m.p. 72.1Ϫ73.5 °C. H NMR (CDCl
3
2
1
1
.35 [s, 9 H, C(CH
.99Ϫ4.01 (m,
)
3 3
], 2.23Ϫ2.41 (m, 2 H), 3.81 (s, 3 H, OCH
3
3
3 3
)
3
2
H), 4.21Ϫ4.27 (m, H), 5.74 [s,
2
1
3
CH(O
2 3 6
C H
H). 13C NMR (CDCl
): δ ϭ 26.1, 31.2, 35.7, 64.1, 68.1, 97.8, 117.5,
29.6, 131.4, 135.0, 145.4, 156.8. C15 21BrO (329.2): calcd. C J ϭ 14.0 Hz, 4 F), Ϫ121.6 (br. s, 4 F), Ϫ122.3 (br. s, 12 F), Ϫ123.2
4.72, H 6.43; found C 54.57, H 6.61.
19
3
3
F NMR (CDCl ): δ ϭ Ϫ81.2 (t, J ϭ 10.0 Hz, 6 F), Ϫ111.4 (t,
1
5
H
3
1
3
(br. s, 4 F), Ϫ126.6 (br. s, 4 F). C NMR (CDCl
6.8, 105Ϫ120 (m, C 17), 124.7 (t, J ϭ 7.0 Hz), 126.9, 129.3 (t,
J ϭ 7.0 Hz), 130.7, 131.5 (t, J ϭ 25.0 Hz), 132.3, 134.1, 142.6,
45.6, 164.5, 190.2. C34 (1104.5): calcd. C 36.97, H 1.64;
found C 36.92, H 1.74.
3
): δ ϭ 31.0, 35.8,
6
8
F
3-tert-Butyl-5-formyl-4-methoxybenzeneboronic Acid (15): A solu-
tion of protected aldehyde 14 (2.63 g, 7.99 mmol) in THF (15 mL)
was cooled to Ϫ78 °C under nitrogen. nBuLi (1.6  in hexanes,
1
18 34 2
H F O
5
.50 mL, 8.80 mmol) was added dropwise over 5 min. The solution
was stirred at Ϫ78 °C for 45 min before being quenched with a
solution of B(OCH
5-[3,5-Bis(n-heptadecafluorooctyl)phenyl]-3-tert-butyl-2-hydroxy-
(2.91 mL, 26.2 mmol) in THF (5 mL). The benzaldehyde (18): A solution of o-methoxybenzaldehyde 17
resulting cloudy suspension was stirred at Ϫ78 °C for 2 h and then (0.50 g, 0.45 mmol) in dry CH Cl (5 mL) was cooled under nitro-
allowed to warm slowly to 0 °C. After 4 h, H O (10 mL) and Et gen to 0 °C. After addition of BBr (1  in CH Cl , 2 mL, 2 mmol),
50 mL) were added. The organic layer was washed three times the solution was stirred at 0 °C for 1 h and then at room temper-
with 10% HCl (20 mL) and once with brine (10 mL), and dried ature for 2 h. The solution was poured into chilled water (5 mL).
with Na SO . The solvent was evaporated and the crude title com- Et O (10 mL) was added and the organic phase was washed with
pound was obtained as a viscous orange oil (1.75 g) that was used O (5 mL), 5% aqueous NaHCO (5 mL), and brine (5 mL), and
as such for further reactions. A sample was purified by CC (silica dried with MgSO . Evaporation of the solvent afforded the title
gel, CH Cl /CH OH 98:2) for analytical purposes. This step re- compound as a white solid (0.49 g, 98%); m.p. 94Ϫ96 °C. H NMR
(CDCl ): δ ϭ 1.48 [s, 9 H, C(CH ], 7.61 (d, J ϭ 2.3 Hz, 1 H),
7.70 (d, J ϭ 2.3 Hz, 1 H), 7.77 (br. s, 1 H), 7.92 (br. s, 2 H), 9.99
3 3
)
2
2
2
2
O
3
2
2
(
2
4
2
H
2
3
4
1
2
2
3
sulted in an appreciable loss of product (yield ϭ 12%) and the
3
3 3
)
crude product was better used as such for the following palla-
dium(0)-catalyzed cross-coupling reaction. H NMR (CDCl
1
19
3
): δ ϭ (s, 1 H, CHO), 11.94 (s, 1 H, OH). F NMR (CDCl
3
): δ ϭ Ϫ81.2
1
.41 [s, 9 H, C(CH
3 3 3
) ], 3.92 (s, 3 H, OCH ), 7.96 (d, J ϭ 1.7 Hz, 1 (t, J ϭ 10.0 Hz, 6 F), Ϫ111.3 (t, J ϭ 14.0 Hz, 4 F), Ϫ121.5 (br. s,
13
H), 8.10 (d, J ϭ 1.7 Hz, 1 H), 10.28 (s, 1 H, CHO). C NMR 4 F), Ϫ122.2 (br. s, 12 F), Ϫ123.2 (br. s, 4 F), Ϫ126.5 (br. s, 4 F).
1
3
(
1
6
CDCl
3
): δ ϭ 31.2, 35.5, 62.4, 129.4, 135.8, 138.9, 142.9, 165.3,
91.2 (C ipso to boron not observed). C12 (236.1): calcd. C 123.9 (t, J ϭ 7.0 Hz), 128.6 (t, J ϭ 7.0 Hz), 129.4, 130.4, 130.8 (t,
1.05, H 7.26; found C 61.37, H 7.14. J ϭ 25.0 Hz), 132.8, 139.9, 142.3, 161.8, 196.9. C33
1090.4): calcd. C 36.35, H 1.48; found C 36.24, H 1.70.
3 8
C NMR (CDCl ): δ ϭ 29.1, 35.2, 105Ϫ120 (m, C F17), 120.9,
H17BO
4
16 34 2
H F O
(
1
-Bromo-3,5-bis(n-heptadecafluorooctyl)benzene (16): Copper pow-
Salen 4: o-Hydroxyaldehyde 9 (1.79 g, 3.00 mmol) was dissolved
benzene (2.99 g, 9.50 mmol) in dry DMF (15 mL) in a flame-dried under nitrogen in hot EtOH (40 mL). (R,R)-1,2-Diaminocyclohex-
Schlenk vessel. The suspension was purged with nitrogen and ane (0.17 g, 1.50 mmol) was added to the stirred solution. The solu-
warmed to 120 °C whilst stirring. C 17I (5.03 mL, 19.0 mmol) was tion was refluxed for 3 h before being cooled to room temperature
added dropwise under nitrogen to the stirred suspension. After 18 h and concentrated under reduced temperature. Purification by flash
the suspension was allowed to cool to room temperature, treated CC (silica gel, light petroleum ether/Et O 98:2) afforded the title
with H O (20 mL) and filtered using a Büchner funnel. The aque- compound (1.60 g, 84%) as a yellow foam. Ϫ [α]
ous phase was extracted with Et O (20 mL). The solid was washed 0.5, Et
der (2.41 g, 38.0 mmol) was added to a solution of 1,3,5-tribromo-
8
F
2
2
0
2
D
ϭ Ϫ165.6 (c ϭ
): δ ϭ 1.38 [s, 18 H, C(CH ],
1
2
2
O). H NMR (CDCl
3
3 3
)
Eur. J. Org. Chem. 2001, 4639Ϫ4649
4647

M. Cavazzini, A. Manfredi, F. Montanari, S. Quici, G. Pozzi
FULL PAPER
1.90Ϫ2.01 (m, 8 H, cC
4
H
8
CHN), 3.31Ϫ3.43 (m, 2 H, cC
4
H
8
CHN), NMR (CDCl
17), 119.2, 123.5, 128.3, 128.7, 128.8, 130.8 (t, J ϭ 25.0 Hz),
139.2, 143.5, 161.7, 165.8. C72 (2259.0) calcd. C 38.28,
J ϭ 10.0 Hz, 6 F), Ϫ111.5 (t, J ϭ 12.0 Hz, 4 F), Ϫ121.6 (br. s, 8 H 1.87, N 1.24; found C 38.36, H 1.90, N 1.18.
3
): δ ϭ 24.7, 29.3, 33.2, 35.3, 72.9, 105Ϫ120 (m,
7
.17 (d, J ϭ 2.3 Hz, 2 H), 7.38 (d, J ϭ 2.3 Hz, 2 H), 8.28 (s, 2 H,
8
C F
19
ArCHϭN), 14.4 (s, 2 H, OH). F NMR (CDCl
3
): δ ϭ Ϫ81.3 (t,
42 68 2 2
H F N O
1
3
F), Ϫ122.3 (br. s, 8 F), Ϫ123.1 (br. s, 4 F), Ϫ126.6 (br. s, 4 F).
NMR (CDCl ): δ ϭ 24.5, 29.3, 33.1, 35.3, 72.5, 105Ϫ120 (m,
17), 118.0, 127.8, 129.0, 138.8, 163.8, 165.4. C44
1270.7): calcd. C 41.59, H 2.86, N 2.06; found C 41.42, H 2.91,
C
Complex (Mn-4)Cl: Solid Mn(OAc)
added under nitrogen in three portions to a solution of ligand 4
1.27 g, 1.00 mmol) in boiling EtOH (40 mL). The brown mixture
was stirred at reflux for 2 h. LiCl (0.12 g, 2.80 mmol) was added
and reflux was continued for 1 h, after which the mixture was al-
lowed to cool to room temperature. The solvent was removed under
2 2
·4H O (0.46 g, 1.90 mmol) was
3
C
(
8
F
36 34 2 2
H F N O
(
N 1.95.
Salen 5: o-Hydroxyaldehyde 9 (1.79 g, 3.00 mmol) and (R,R)-1,2-
diphenylethylenediamine (0.32 g, 1.50 mmol) were condensed ac-
cording to the procedure described for the synthesis of salen 4.
reduced pressure and the residue was dissolved in CH
The solution was washed with water (15 mL) and brine (15 mL),
and dried with Na SO . Evaporation of the solvent under reduced
pressure afforded the title compound as a brown solid (1.29 g,
2 2
Cl (70 mL).
2
Purification by flash CC (silica gel, light petroleum ether/Et O
2
4
9
8:2) afforded the title compound (1.79 g, 87%) as a pale yellow
20
1
foam. Ϫ [α]
D
ϭ Ϫ46.8 (c ϭ 0.5, Et
], 4.75 (s, 2 H, PhCHN), 7.21 (d, J ϭ 2.3 Hz,
H), 7.15Ϫ7.30 (m, 10 H), 7.41 (d, J ϭ 2.3 Hz, 2 H), 8.35 (s, 2 H,
2
O). H NMR (CDCl
3
): δ ϭ
20
Ϫ5
9
5%). Ϫ [α]
CH OH): λmax (lg ε) ϭ 235 nm (4.74). C44
1359.1): calcd. C 38.88, H 2.52, N 2.06; found C 39.15, H 2.41,
N 1.99.
D
ϭ Ϫ188.6 (c ϭ 0.01, CH
3
OH). UV/Vis (1·10 ,
1
2
3 3
.40 [s, 18 H, C(CH )
3
H
34ClF34MnN O
2 2
(
19
ArCHϭN), 14.3 (s, 2 H, OH). F NMR (CDCl
3
): δ ϭ Ϫ81.3 (t,
J ϭ 10.0 Hz, 6 F), Ϫ111.3 (t, J ϭ 14.0 Hz, 4 F), Ϫ121.8 (br. s, 8
1
3
F), Ϫ122.3 (br. s, 8 F), Ϫ123.1 (br. s, 4 F), Ϫ126.6 (br. s, 4 F).
NMR (CDCl3): δ ϭ 28.9, 35.0, 79.8, 105Ϫ120 (m, C
17), 118.0, and subsequent workup were carried out as described for (Mn-
18.2 (t, J ϭ 25.0 Hz), 127.8 (t, J ϭ 6.5 Hz), 127.9, 128.0, 128.6, 4)Cl. The title compound (0.76 g, 52%) was obtained as a brown
C
Complex (Mn-5)Cl: Complexation of ligand 5 (1.37 g, 1.00 mmol)
8
F
1
1
2
0
Ϫ5
28.8 (t, J ϭ 6.5 Hz), 138.5, 163.2, 166.3 Ϫ C52
H
38
F
34
N
2
O
2
solid. Ϫ [α]
D
ϭ Ϫ88.1 (c ϭ 0.01, CH
3
OH). UV/Vis (1·10 ,
(
1368.8): calcd. C 45.63, H 2.80, N 1.92; found C 45.84, H 2.86, CH
3
OH): λmax (lg ε) ϭ 237 nm (4.73). C52
H
36ClF34MnN O
2 2
N 2.07.
(1457.2): calcd. C 42.86, H 2.49, N 1.92; found C 43.11, H 2.60,
N 1.68.
Salen 6: Biaryl aldehyde 12 (1.35 g, 0.80 mmol) was dissolved under
Ar in boiling EtOH (20 mL). (R,R)-1,2-Diaminocyclohexane Complex (Mn-6)Cl: Solid Mn(OAc) ·4H O (245 mg, 1.00 mmol)
2
2
(46.0 mg, 0.40 mmol) was added to the stirred solution, and the
was added under nitrogen in three portions to a solution of ligand
yellow solution was refluxed for 5 h. Evaporation of the solvent 6 (860 mg, 0.25 mmol) in boiling EtOH (20 mL) and benzotrifluor-
afforded a yellow oil that was washed with cold EtOH (5 mL). The ide (5 mL). The brown mixture was stirred at reflux for 4 h. LiCl
residue was redissolved in Et
10 mL) and brine (10 mL). The organic phase was dried with
Na SO and the crude product was further purified by flash chro-
matography (silica gel, light petroleum ether/Et O 95:5) to give the
title compound as a yellow foam (0.91 g, 72%). Ϫ [α]
2
O (40 mL) and washed with water
(85.0 mg, 2.00 mmol) was added and reflux was continued for 1 h,
after which the mixture was allowed to cool to room temperature.
The solvent was removed under reduced pressure and the residue
was extracted with CFCl CF Cl in a Soxhlet apparatus for 6 h. The
(
2
4
2
2
2
2
0
D
ϭ Ϫ13.7
): δ ϭ 1.40 [s, 18 H, C(CH ], further purified by flash CC (silica gel, light petroleum ether/Et O
CHN), 1.67Ϫ1.72 (m, 4 H), 1.94Ϫ2.17
m, 12 H), 2.24Ϫ2.39 (m, 8 H), 3.32Ϫ3.43 (m, 2 H, cC
.59Ϫ3.67 (m, 4 H), 4.04Ϫ4.11 (m, 8 H), 6.67 (d, J ϭ 8.6 Hz, 2
solution obtained was evaporated and the brown solid residue was
1
2
(c ϭ 0.5, Et O) Ϫ H NMR (CDCl
3
3 3
)
2
2
0
1
.45Ϫ2.08 (m, 8 H, cC
4
H
8
4:1) to afford the title compound (565 mg, 64%). Ϫ [α] ϭ Ϫ290
D
Ϫ5
(
4
H
8
CHN), (c ϭ 0.01, CFCl CF Cl). UV/Vis (2·10 , CFCl CF Cl): λ
max
(lg
2
2
2
2
3
74 102 2 8
ε) ϭ 284 nm (4.71), 451 nm (3.63). C106H ClF MnN O
H), 6.89 (d, J ϭ 8.6 Hz, 2 H), 7.10 (d, J ϭ 1.9 Hz, 2 H), 7.45 (d, (3532.0): calcd. C 36.05, H 2.11, N 0.79; found C 36.05, H 2.11,
J ϭ 1.9 Hz, 2 H), 8.32 (s, 2 H, ArCHϭN), 14.21 (br. s, 2 H, OH). N 0.79.
1
9
F NMR (CDCl
J ϭ 14.0 Hz, 12 F), Ϫ121.6 (br. s, 12 F), Ϫ122.3 (br. s, 36 F),
Ϫ123.2 (br. s, 12 F), Ϫ126.6 (br. s, 12 F). 13C NMR (CDCl
): δ ϭ
1.0, 21.5, 21.7, 24.6, 28.2, 29.7, 30.7, 33.4, 35.2, 67.8, 72.2, 72.6,
2.7, 105Ϫ120 (m, C 17), 109.4, 119.2, 125.3, 127.8, 129.6, 130.3,
30.8, 137.4, 142.0, 150.6, 152.0, 160.0, 165.8. C106
3
): δ ϭ Ϫ81.3 (t, J ϭ 10.0 Hz, 18 F), Ϫ111.5 (t,
7
Complex (Mn-6)C F15COO: Complex (Mn-6)Cl (353 mg,
0.10 mmol) was dissolved in Et O (5 mL) and n-perfluorooctane
2
3
(
10 mL) at room temperature.
A large excess of solid
2
7
1
C
7
F
15COONH (1.29 g, 2.99 mmol) was added and the mixture
4
8
F
was vigorously stirred for 24 h under nitrogen. Water (5 mL) was
added and the organic layer was evaporated under reduced pres-
sure. The residue was taken up in n-perfluorooctane (10 mL),
76 102 2 8
H F N O
(
3443.6): calcd. C 36.97, H 2.22, N 0.81; found C 36.90, H 2.25,
N 0.77.
2 4
washed with water (3 ϫ 5 mL) and dried with Na SO . Evapora-
Salen 7: Condensation of biaryl aldehyde 18 (1.09 g, 1.00 mmol)
and (R,R)-1,2-diaminocyclohexane (57.0 mg, 0.50 mmol) in boiling
EtOH (20 mL) and benzotrifluoride (5 mL) and subsequent
workup were carried out according to the procedure described for
the synthesis of salen 3. Evaporation of the solvent under reduced
pressure gave the title compound as a yellow foam (1.08 g, 95%).
tion of the solvent afforded the title compound as a dark brown
20
solid (381 mg, 97%). Ϫ [α]
D
ϭ Ϫ218 (c ϭ 0.01, CFCl
Cl): λmax (lg ε) ϭ 272 nm (4.80), 442 nm
74ClF117MnN 10 (3909.6): calcd. C 35.02, H 1.91, N
.72; found C 35.36, H 1.99, N 0.70.
2 2
CF Cl). UV/
Ϫ5
Vis (3·10 , CFCl
2 2
CF
(
3.74). C114
H
2
O
0
Ϫ [α]2
s, 18 H, C(CH
m, 2 H, cC
.2 Hz, 2 H), 7.67 (br. s, 2 H), 7.76 (br. s, 4 H), 8.38 (s, 2 H, ArCHϭ
0
ϭ Ϫ14.6 (c ϭ 0.5, Et
], 1.45Ϫ2.08 (m, 8 H, cC
CHN), 7.15 (d, J ϭ 2.2 Hz, 2 H), 7.39 (d, J ϭ (35 mL) and benzotrifluoride (5 mL) and subsequent workup were
carried out as described for the synthesis of (Mn-6)Cl. Flash CC
): δ ϭ Ϫ81.3 (t, J ϭ (silica gel, light petroleum ether/Et O 9:1) afforded the title com-
0.0 Hz, 12 F), Ϫ111.5 (t, J ϭ 14.0 Hz, 8 F), Ϫ121.7 (br. s, 8 F), pound (870 mg, 93%) as a dark brown solid. Ϫ [α]
O) Ϫ H NMR (CDCl
1
Complex (Mn-7)Cl: Complexation of ligand 7 (903 mg, 0.40 mmol)
D
2
3
): δ ϭ 1.39
[
(
2
3
)
3
4
H
8
CHN), 3.38Ϫ3.48 with solid Mn(OAc)
2
·4H O (392 mg, 1.60 mmol) in boiling EtOH
2
4 8
H
19
N), 14.21 (br. s, 2 H, OH). F NMR (CDCl
3
2
2
0
1
D
ϭ Ϫ500 (c ϭ
2 2 2 2
0.01, CFCl CF Cl). UV/Vis (2·10 , CFCl CF Cl): λmax (lg ε) ϭ
1
3
Ϫ5
Ϫ122.3 (br. s, 24 F), Ϫ123.2 (br. s, 8 F), Ϫ126.6 (br. s, 8 F).
C
4648
Eur. J. Org. Chem. 2001, 4639Ϫ4649

Asymmetric Epoxidation of Alkenes in Fluorinated Media
FULL PAPER
2
99 nm (4.67), 514 nm (3.12). C72
H
40ClF68MnN
O
2 2
(2347.4):
Montanari, G. Pozzi, S. Quici, J. Fluorine Chem. 1999, 94,
1
83Ϫ193.
calcd. C 36.84, H 1.72, N 1.19; found C 36.05, H 2.11, N 0.79.
[
[
13]
14]
J. A. Gladysz, Science 1994, 266, 55Ϫ56.
E. N. Jacobsen, in: Catalytic Asymmetric Synthesis (Ed.: I.
Ojima), VCH, Weinheim, 1993, pp. 159Ϫ202, and references
therein.
Complex (Mn-7)C
to the procedure described for the synthesis of (Mn-6)C
gave the title compound (270 mg, 99%) as a dark brown solid. Ϫ
7
F
15COO: Anion exchange carried out according
7
F
15COO
[15]
[16]
Y. N. Ito, T. Katsuki, Bull. Chem. Soc. Jpn. 1999, 72, 603Ϫ619,
and references therein.
W. Zhang, E. N. Jacobsen, J. Org. Chem. 1991, 56, 2296Ϫ2298.
M. Palucki, G. J. McCormick, E. N. Jacobsen, Tetrahedron
Lett. 1995, 36, 5457Ϫ5460.
L. Canali, D. C. Sherrington, Chem. Soc. Rev. 1999, 28, 85Ϫ93,
and references therein.
2
0
Ϫ5
[
α]
CFCl
2 4
40ClF83MnN O
D
ϭ Ϫ324 (c ϭ 0.025, CFCl
CF Cl): λmax (lg ε) ϭ 297 nm (4.71), 441 nm (3.53).
(2725.0): calcd. C 35.26, H 1.48, N 1.03;
2
CF
2
Cl). UV/Vis (1.85·10
,
2
2
[
[
[
[
17]
18]
19]
C
80
H
found C 35.01, H 1.52, N 1.20.
General Procedure for the Asymmetric Epoxidation of Alkenes under
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0.25 , 0.20 mL) were added under nitrogen to a solution of the
catalyst in n-perfluorooctane (0.01  1.00 mL). PhIO (67.0 mg,
.30 mmol) was quickly added under a nitrogen stream. The two-
3
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0
[
[
22]
23]
phase mixture was magnetically stirred at 1300Ϯ50 rpm and cooled
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layer was separated, washed with CH
in further runs (see text). The combined organic layers were washed
with saturated aqueous Na SO (1 mL) and brine (1 mL), and
dried (MgSO ). The epoxide yield and enantiomeric excess were
determined by gas chromatographic analysis of the organic solu-
tion. In the case of indene and triphenylethylene, the ees of the
epoxides were determined by H NMR in the presence of the chiral
shift reagent Eu(hfc)
Enantioselective reactions in supercritical CO
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2
, catalyzed by
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