Second-generation fluorous chiral (salen) manganese complexes

Article abstract of DOI:10.1039/b007053j

Sterically hindered chiral (salen)manganese complexes bearing long perfluoroalkyl substituents are synthesized and successfully employed as catalysts in the enantioselective (ee = 50-87%) epoxidation of alkenes under fluorous biphasic conditions.

Full text of DOI:10.1039/b007053j

Second-generation fluorous chiral (salen) manganese complexes
Marco Cavazzini, Amedea Manfredi, Fernando Montanari, Silvio Quici and Gianluca Pozzi*
Centro CNR and Dipartimento di Chimica Organica e Industriale dell’Università, Via Golgi 19, I-20133 Milano,
Italy. E-mail: gianluca.pozzi@unimi.it
Received (in Cambridge, UK) 29th August 2000, Accepted 14th September 2000
First published as an Advance Article on the web
Sterically hindered chiral (salen)manganese complexes bear-
ing long perfluoroalkyl substituents are synthesized and
successfully employed as catalysts in the enantioselective (ee
= 50–87%) epoxidation of alkenes under fluorous biphasic
conditions.
to better shield the metal site, the RF substituents in 5,5’-posi-
tions were replaced by perfluoroalkyl-substituted aryl moieties.
Moreover, sterically demanding tert-butyl substituents were
introduced in the key-positions 3,3’ of ligands 3 and 4.
Both salicylaldehydes 7 and 10, the key intermediates for the
synthesis of ligands 3 and 4, were prepared starting from
aldehyde 5,5 as shown in Scheme 1. Pd0-catalyzed cross-
coupling reaction of 5 with boronic acid 6 (yield = 86%),6
followed by O-deprotection (89%) and O-alkylation with
C8F17(CH2)3I (37%), afforded the fluorous salicylaldehyde 7.
Mono- and bis-O-alkylated biaryl compounds were isolated
from the reaction mixture by column chromatography and
reused in following runs.
In the case of salicylaldehyde 10, aldehyde 5 was used as a
precursor of aryl boronic acid 8, whereas perfluoroalkyl-
substituted aryl bromide 9 was prepared by copper-mediated
cross-coupling reaction of 1,3,5-tribromobenzene with 2 equiv.
of C8F17I. The bis(perfluoroalkyl) derivative was obtained as
the main product and isolated in reasonable yields (60%) after
crystallization from CH2Cl2 and then from Et2O. Pd0-catalyzed
cross-coupling reaction of crude aryl boronic acid 8 with 9,
followed by deprotection with BBr3 gave the desired salicyl-
aldehyde 10 in 62% yield.
Following the pioneering work of Horváth and Rábai,1
a
number of reagents and catalysts bearing appropriate per-
fluoroalkyl substituents (‘fluorous compounds’) have been
prepared and used in ‘fluorous biphase chemistry’.2 Catalytic
reactions in fluorous biphasic systems present several advan-
tages over their classical homogeneous counterparts.3 Fluorous
chemistry has also a great potential for enantioselective
transformations, offering both an easy way to recover precious
chiral reagents or catalysts and unusual solvation effects.
Nevertheless, only a few chiral fluorous compounds have been
prepared to date and the actual influence of perfluoroalkyl
substituents (RF) and perfluorocarbon solvents on the outcome
of asymmetric reactions is virtually unknown.4 We have
reported the first example of a fluorous biphasic enantiose-
lective reaction, namely the epoxidation of alkenes in the
presence of the optically active fluorous (salen)MnIII complexes
Mn-1 and Mn-2 (Jacobsen–Katsuki catalysts, Fig. 1).4a Good
chemoselectivity and efficiency were observed in the epoxida-
tion of several substrates, and recycling of the catalysts was also
demonstrated. However, high levels of enantioselectivity were
not attained, except in the epoxidation of indene (ee = 90%).
This behaviour was tentatively ascribed to the low steric
hindrance of the RF groups in the 3,3’- and 5,5’-positions of the
ligands and to the inadequate electronic shielding of the metal
site from the strong electron-withdrawing effect of these
substituents.4c
Condensation of two equivalents of salicylaldehyde 7 or 10
with (1R,2R)-(2)-1,2-diaminocyclohexane in boiling ethanol
afforded the fluorous salen ligands 3 (72%) and 4 (95%),
respectively.7 MnIII complexes Mn-3 and Mn-4 were prepared
by reaction of the corresponding ligand with an excess of
Mn(OAc)2·4H2O in refluxing ethanol under aerobic conditions,
followed by anion exchange with LiCl and then
C7F15COONH4. The exchange of Cl2 for the fluorophilic
Second-generation (salen)MnIII complexes Mn-3 and Mn-4
(Fig. 1) were designed with these assumptions in mind. In order
Scheme 1 Reagents and conditions: i, Pd(OAc)2/PPh3, PriOH, aqueous
Na2CO3, 110 °C; ii, BBr3, CH2Cl2, 0 °C; iii, C8F17(CH2)3I, K2CO3,
CH3CN, 70 °C; iv, (CH3)2SO4, K2CO3, acetone, r.t.; v, HO(CH2)3OH, p-
TsOH, toluene, reflux; vi, BuLi, 278 °C, THF, 45 min, then B(OCH3)3,
278 to 0 °C, aqueous HCl.
Fig. 1 First- (Mn-1, Mn-2) and second-generation (Mn-3, Mn-4) fluorous
chiral (salen)Mn complexes.
DOI: 10.1039/b007053j
Chem. Commun., 2000, 2171–2172
This journal is © The Royal Society of Chemistry 2000
2171

C7F15COO2 anion resulted in the sought preferential solubility
of Mn-3 and Mn-4 in perfluorocarbons, as verified by partition
experiments in biphasic mixtures n-perfluorooctane/organic
solvents. Partition coefficients, determined by UV–Vis spec-
troscopy at 25 °C,8 were found to be quite similar for the two
complexes, ranging from 1.21 for Mn-3 in n-perfluorooctane/
hexane, to > 1000 for Mn-3 and Mn-4 in n-perfluorooctane/
CH3CN and n-perfluorooctane/toluene.
case of triphenylethylene (entries 8–10). Catalytic activity
generally dropped in the fourth run due to the oxidative
decomposition of the catalyst, as evidenced by the progressive
disappearence of the characteristic UV–Vis absorption bands of
the (salen)MnIII in the fluorous phase and by the absence of such
bands in the organic phase. Such behaviour is in agreement with
previous literature reports dealing with (salen)MnIII complexes
immobilised by other techniques.11
First- and second-generation (salen)MnIII complexes were
initially compared in the homogeneous epoxidation of 1,2-dihy-
dronaphthalene in CH2Cl2/benzotrifluoride, using meta-chloro-
perbenzoic acid/ N-methylmorpholine N-oxide (m-CPBA/
NMO) as the oxidant at 250 °C.9 Second-generation catalysts
afforded ee values much higher than those obtained with Mn-1
and Mn-2 (63% vs. 16 and 12%, respectively) and slightly
improved epoxide yields (70% with Mn-3 and Mn-4 vs. 60%
with Mn-1 and Mn-2). Other oxidising agents commonly used
in association with (salen)MnIII complexes were also tested and
the superiority of the new complexes was confirmed.
The use of the second-generation (salen)MnIII complexes
considerably widen the scope of the fluorous biphasic epoxida-
tion reaction, since these catalysts not only afford good epoxide
yields, but also ee ranging from 50 to 87% with several
substrates. This finding strongly supports our aforementioned
hypotheses about the role of RF substituents on the catalytic
activity of (salen)MnIII complexes. The relative importance of
electronic and steric effects in determining the enantioselectiv-
ity of fluorous (salen)MnIII complexes and the design of new
chiral fluorous catalysts are currently investigated in this
laboratory.
PhIO together with small amounts of pyridine N-oxide (PNO)
was used as the oxidising system in the next fluorous biphasic
reactions that were run in n-perfluorooctane/CH3CN (Table 1).†
This set of conditions was chosen taking into account the
favourable partition coefficients of the catalysts and considering
that homogeneous epoxidation reactions with PhIO/PNO are
conveniently carried out in CH3CN at 0–25 °C.10 Both reaction
yield and enantioselectivity rose with temperature under
fluorous biphasic conditions: the best results were obtained at
100 °C, corresponding to the boiling point of n-perfluorooctane
(Table 1, entries 1–5). Blank experiments evidenced that only
traces of epoxide are formed at this temperature in the absence
of the fluorous catalysts. The results obtained in the fluorous
biphasic epoxidation of 1,2-dihydronaphthalene with PhIO/
PNO at 100 °C (entry 5) compare favourably to those reported
for the same reaction in CH3CN in the presence of Jacobsen’s
catalyst, a commercially available, standard (salen)MnIII com-
plex (yield = 70%, ee = 46%).11
We thank the COST Action D12 ‘Fluorous medium: a tool
for environmentally compatible oxidation processes’.
Notes and references
† General procedure for the asymmetric epoxidation of alkenes under
fluorous biphasic conditions: in a 10 ml Schlenk vessel placed in a
thermoregulated bath at 100 °C, 1 ml of a 0.2 M solution of alkene in
CH3CN containing o-dichlorobenzene (0.1 M, internal standard for GC) and
0.2 ml of a 0.25 M solution of pyridine N-oxide (PNO) in CH3CN were
added under nitrogen to 1 ml of a solution of the catalyst in n-
perfluorooctane. PhIO (67 mg, 0.3 mmol) was quickly added under a
nitrogen stream. The two-phase mixture was magnetically stirred at 1300 ±
50 rpm and cooled to room temperature at the end of the reaction. The brown
fluorous layer was separated, washed with CH3CN (2 3 0.5 ml) and reused
in further runs (see Table 1). The combined organic layers were washed
with saturated aqueous Na2SO3 (1 ml), brine (1 ml) and dried (MgSO4).
Epoxide yield and enantiomeric excess were determined by gas-chromato-
graphic analysis of the organic solution.
The fluorous layer, easily separated upon cooling, could be
reused up to three times after the first run as exemplified in the
1 I. T. Horváth and J. Rábai, Science, 1994, 266, 72.
2 I. T. Horváth, Acc. Chem. Res., 1998, 31, 641.
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Rev., 1999, 192, 587; (b) R. H. Fish, Chem. Eur. J., 1999, 5, 1677; (c)
E. De Wolf, G. van Koten and B.-J. Deelman, Chem. Soc. Rev., 1999,
28, 37; (d) M. Cavazzini, F. Montanari, G. Pozzi and S. Quici,
J. Fluorine Chem., 1999, 94, 183; (e) E. G. Hope and A. M. Stuart,
J. Fluorine Chem., 1999, 100, 75.
Table 1 Asymmetric epoxidation of alkenes with PhIO/PNO in CH3CN/
perfluorooctane.a
Entry Catalyst Substrate
T/°C t/h Yieldb(%) Eec(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
Mn-4
Mn-4
Mn-4
Mn-4
Mn-4
Mn-3
Mn-4
1,2-dihydronaphthalene
0
3
3
3
2
1
1
4.5
46
76
74
77
68
8
26
32
42
50
50
87g
85g
83g
71g
80g
68
69
77
70
58
4 (a) G. Pozzi, F. Cinato, F. Montanari and S. Quici, Chem. Commun.,
1998, 877; (b) Y. Takeuchi, Y. Nakamura, Y. Ohgo and D. P. Curran,
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Cinato, F. Montanari and S. Quici, Eur. J. Org. Chem., 1999, 1947; (d)
H. Kleijn, E. Rijnberg, J. T. B. H Jastrzebski and G. van Koten, Org.
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Y. Ohgo and D. P. Curran, Tetrahedron, 2000, 56, 351.
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J. Org. Chem., 1994, 59, 1939.
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E. Hamel, J. N. Lambert, M. F: Mackay, M. E. Reum and J. S. Scoble,
Aust. J. Chem., 1991, 44, 705.
7 (a) W. Zhang, J. L. Loebach, S. R. Wilson and E. N. Jacobsen, J. Am.
Chem. Soc., 1990, 112, 2801; (b) R. Irie, K. Noda, Y. Ito, N. Matsumoto
and T. Katsuki, Tetrahedron Lett., 1990, 31, 7345.
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Org. Chem., 2000, in the press.
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Soc., 1994, 116, 9333.
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Chem., 1998, 136, 47 and references cited therein.
1,2-dihydronaphthalene 20
1,2-dihydronaphthalene 40
1,2-dihydronaphthalene 70
1,2-dihydronaphthalene 100
1,2-dihydronaphthalene 100
triphenylethylene
100 0.5 98
100 0.5 96
100 0.5 92
Mn-4d triphenylethylene
Mn-4e triphenylethylene
Mn-4f
Mn-3
Mn-4
Mn-3
Mn-4
Mn-3
Mn-4
Mn-3
triphenylethylene
triphenylethylene
benzosuberene
benzosuberene
1-methylindene
1-methylindene
1-methylcyclohexene
1-methylcyclohexene
100
1
80
100 0.5 98
100 0.5 92
100 0.5 84
100 0.5 98
100 0.5 96
100 0.5 91
100 0.5 95
52
a See footnote †. b Determined by GC analysis (HP-5 5% phenyl methyl
siloxane column), internal standard method. c Determined by GC analysis
(Cyclodex-B chiral column). d First, e second and f third reuse of the
fluorous layer. g Determined by H NMR spectroscopy in the presence of
1
the chiral shift reagent Eu(hfc)3.
2172
Chem. Commun., 2000, 2171–2172
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