Charge-transfer interactions: An efficient tool for recycling bis(oxazoline)-copper complexes in asymmetric henry reactions

Article abstract of DOI:10.1002/adsc.201000934

An anthracenyl-modified chiral bis(oxazoline) copper complex has been demonstrated to efficiently promote nitroaldol reactions between structurally varying aldehydes and nitromethane or nitroethane. The catalyst was recovered through formation of a charge transfer complex between the chiral ligand and trinitrofluorenone and its subsequent precipitation with pentane. The efficiency of this procedure was proved through several consecutive catalytic cycles that allowed the sturdy formation of the expected product with a high enantioselectivity. The catalyst′s stability was also put to the test in an original multi-substrate procedure. Following the same recovery concept, a new heterogeneous procedure was tested for which trinitrofluorenone was covalently linked to a silica support. Asymmetric heterogeneous catalysis was performed under these conditions as one of the few examples demonstrating the potential catalyst recycling in nitroaldol reactions through reversible, non-covalent interactions. Copyright

Full text of DOI:10.1002/adsc.201000934

FULL PAPERS
DOI: 10.1002/adsc.201000934
Charge-Transfer Interactions: An Efficient Tool for Recycling
Bis(oxazoline)-Copper Complexes in Asymmetric Henry
Reactions
a
a,b
a,b,
Dorian Didier, Caroline Magnier-Bouvier, and Emmanuelle Schulz *
a
Univ Paris-Sud, Equipe de Catalyse Molꢀculaire, ICMMO, UMR 8182, F-91405 Orsay, France
Fax : (+33)-(0)1-6915-4680; e-mail: emmanuelle.schulz@u-psud.fr
CNRS, F-91405 Orsay, France
b
Received: December 10, 2010; Revised: February 25, 2011; Published online: April 28, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000934.
Abstract: An anthracenyl-modified chiral bis(oxazo- nal multi-substrate procedure. Following the same
line) copper complex has been demonstrated to effi- recovery concept, a new heterogeneous procedure
ciently promote nitroaldol reactions between struc- was tested for which trinitrofluorenone was covalent-
turally varying aldehydes and nitromethane or nitro- ly linked to a silica support. Asymmetric heterogene-
ethane. The catalyst was recovered through forma- ous catalysis was performed under these conditions
tion of a charge transfer complex between the chiral as one of the few examples demonstrating the poten-
ligand and trinitrofluorenone and its subsequent pre- tial catalyst recycling in nitroaldol reactions through
cipitation with pentane. The efficiency of this proce- reversible, non-covalent interactions.
dure was proved through several consecutive catalyt-
ic cycles that allowed the sturdy formation of the ex- Keywords: asymmetric catalysis; bis(oxazolines); cat-
pected product with a high enantioselectivity. The alyst recycling; charge transfer complex; nitroaldol
catalyst’s stability was also put to the test in an origi- reaction
Introduction
chiral salen ligands also recently showed their ability
to promote the asymmetric nitroaldolization with
The Henry (nitroaldol) reaction is a well known high yields and enantioselectivities. Many copper-
access to a wide range of interesting intermediates based asymmetric catalytic systems have been de-
[
10]
starting from easily available aldehydes and nitroal- scribed with chiral diamine-based ligands, salen or
[
1]
[11]
[12]
kane derivatives. The asymmetric version of the re- Schiff base derivatives
and sulfonyldiamines
or
[
13]
action produces enantiomerically enriched b-nitroal- sulfonimidamides.
Chiral bis(oxazolines) as ligand
kanols that can be reduced into b-amino alcohols, or in combination with copper species were first de-
transformed by the Nef reaction to give b-hydroxy scribed by Jørgensen et al. to promote the asymmetric
carbonyl compounds, for instance. Biologically active Henry reaction of a-keto esters with nitrome-
[
14,15]
compounds such as levamisole or propanolol can then thane.
be obtained after few transformations.
The use of copper acetate bis(oxazoline) to
[
2]
catalyze the addition of nitromethane to aldehydes
[
16]
Shibasaki and co-workers reported about twenty was reported by Evans and co-workers. They opti-
years ago the first example of a catalytic asymmetric mized the reaction conditions with different ligands
nitroaldol reaction promoted by lanthanum alkoxide and solvents, and noted the efficiency of
precursors in the presence of (S)-(À)-binaphthol as Cu
ACHTUNGTNERNUNG( OAc) ·H O for both Lewis acid properties and
ligand. Starting from this promising result, other Brønsted base ability. Good activities and enantiose-
asymmetric metal-based catalysts have been report- lectivities were obtained under these conditions in the
2 2
[3]
[4]
ed involving, for instance, zinc complexes in the presence of ligand 1a (Figure 1) in ethanol at room
presence of various ligands derived from semi-aza- temperature. Reactions with a 5 mol% amount of
[
5]
[17]
crown backbones, ferrocenyl-substituted aziridinyl- chiral catalyst were tested by Singh et al. by using
[
6]
methanol compounds or C -symmetrical bis(oxazoli- different metallic salts such as Cu ACHTUNGTRENNUNG( OTf) ,
dine) ligands. Cobalt or chromium salts linked to Zn
2
2
[7]
[8]
[9]
A
H
U
G
R
N
U
(OAc) ·H O or Mg
A
H
U
G
R
N
N
(OAc) ·H O but Cu
A
H
U
G
R
N
U
G
2
2
2
2
2
2
Adv. Synth. Catal. 2011, 353, 1087 – 1095
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Dorian Didier et al.
FULL PAPERS
(
TNF). At the end of the catalytic transformation,
pentane is poured into the reaction mixture, which re-
sults in the precipitation of the catalyst. Products
were then removed for analysis before additional sol-
vent and substrates were added for the reuse of the
catalyst. Complex 1c-TNF depicted in Figure 1 was
thus successfully used 12 times in a Diels–Alder reac-
tion leading to the formation of the expected products
with high yields and enantioselectivities, exactly
matching the results obtained by the corresponding
[
25]
homogeneous system.
The aim of the present work deals with the use of
ligand 1c (Figure 1) under optimized conditions to
obtain various nitroalcohol derivatives in high yields
and enantioselectivities and the fine-tuning of the
procedure allowing its efficient recovery and reuse by
formation of CTC.
Figure 1. Bis(oxazoline) ligands.
led to the best result for the preparation of 2-nitro-1-
phenyl-ethanol with ligand 1b (81% ee).
Results and Discussion
Some efforts have also been devoted towards the
recovery and reuse of those efficient asymmetric cata- Electron-donor bis(oxazoline) ligand 1c has been pre-
lytic systems to follow at best the principles of green viously synthesized by our team, starting from diethyl
[
18]
[25]
chemistry.
nanocrystalline magnesium oxide,
lithium-binaphthol complexes bonded to silica and (1R,2S-aminoindanol) at the first step to obtain
Immobilized (S)-(À)- binaphthol onto malonimidate (route A, Figure 2).
This synthesis
[
19]
or lanthanum- implied the direct introduction of the chiral moiety
[20]
MCM-41,
were able to efficiently carry out the bis(oxazoline) 2, followed by the addition of the an-
asymmetric nitroaldol reaction in several successive thracene moiety (40% yield). The methyl substituent
catalytic runs. Chromium salen derivatives have been on the bridging group was then introduced at the last
electropolymerized giving rise to an efficient insoluble step leading to an overall yield of about 7%. Aiming
catalyst reusable in an original multisubstrate proce- at improving the access to this ligand, a new way was
[9a]
dure. A chiral copper acetate complex tethered to considered (route B), starting with a fragment already
poly(ethylene glycol) was also used in a recycling pro- containing the methyl group. Diethyl 2-
methylmalonimidate 4 was obtained by bubbling HCl
Very recent examples describe the heterogeneization in ethanol in the presence of 2-methylmalononitrile,
[
21]
cedure demonstrating a high activity and stability.
ACHTUNGTRENNUNG
[
22]
[26]
of chiral copper complexes on silica supports. Park prepared according to a reported procedure.
The
et al. demonstrated recently the easy recyclability of same methodology used for route A was pursued to
chiral copper amino complexes when the nitroaldol synthesize chiral bis(oxazoline) 3, by addition of
[
23]
reaction was performed in ionic liquids. Bellemin- (1R,2S)-aminoindanol onto 4. This intermediate bis-
Laponnaz and Gade covalently attached chiral oxazo- (oxazoline) 3 could be recrystallized for analysis in
line ligands to carbosilane dendrimers and used the 46% yield, but it was pure enough as a crude mixture
corresponding copper complexes as immobilized, and to be further used without purification. Ligand 1c was
[
24]
thus recoverable, catalysts in a membrane bag. All thus prepared in 51% yield, in two steps from 2-meth-
these procedures led interestingly to the formation of ylmalonimidate 4, by a nucleophilic substitution on a
the expected products with high enantioselectivity mesylate derivative of anthracene. Thanks to this new
values that remained almost stable along with the suc- route, the overall yield was consequently improved to
cessive catalytic runs. The recycling procedures were 25%.
tested for about a maximum of five runs but were,
Some catalytic tests between benzaldehyde 5a and
however, always accompanied by a non-negligible loss nitromethane 6a were then performed in the presence
of activity leading to diminished isolated yields.
We have previously reported a new efficient immo-
of ligand 1c, to find optimal conditions using Cu-
AHCTUNGTREG(NNUN OAc) ·H O as precatalyst for the nitroaldol reaction
2
2
bilization strategy for the recovery and reuse of asym- (Scheme 1). The procedure described by Evans et al.
metrical bis(oxazoline)-type catalysts based on the was reproduced (10 mol% precatalyst, reaction per-
formation of the corresponding charge-transfer com- formed in ethanol at room temperature in the ab-
[
16]
plex (CTC) arising from an electronic transfer be- sence of additional base) and led to the best results.
tween the anthracene functionality of the new bis(ox- In a typical transformation, the copper bis(oxazoline)
azoline)-type ligand and 2,4,7-trinitrofluorenone complex was formed by mixing ligand 1c with copper
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Charge-Transfer Interactions: An Efficient Tool for Recycling Bis(oxazoline)-Copper Complexes
Figure 2. Different routes towards bis(oxazoline) 1c.
Scheme 1. Nitroaldol reactions catalyzed by ligand 1c-Cu ACTHUNGTERNN(UNG OAc) .
2
acetate in a 1/1 ratio in ethanol and the resulting solu- Table 1. Recycling procedure of 1c-Cu
tion was stirred for 1 h. Nitromethane and the alde- EtOH for the formation of 7a.
A
H
U
G
R
N
N
(OAc) ·H O/TNF in
2
2
hyde were then successively introduced and the reac-
[
a]
[b]
[c]
Run
t [h]
Conv. [%]
Yield 7a [%]
ee 7a [%]
tion mixture was stirred for 24 h. The targeted com-
pound 7a was therefore isolated in high yield (89%)
and excellent enantioselectivity (90% ee, Table 1, run
1
2
3
4
5
6
7
24
36
48
72
72
96
120
>95
93
90
92
80
89
84
83
80
72
63
59
90 (R)
90 (R)
90 (R)
88 (R)
87 (R)
84 (R)
82 (R)
1), indicating that the presence of the additional an-
thracene moiety on 1c was not detrimental to the
enantiofacial discrimination, by comparison to the re-
sults obtained with ligand 1a.
These reaction conditions were then applied to per-
form the recycling procedure. At the end of the first
run, trinitrofluorenone (10 mol%) was added and the
mixture was stirred one additional hour to form the
CTC in solution, as indicated by the immediate colo-
ration to deep red. Pentane was then poured for the
CTC precipitation which was recovered by filtration,
75
66
[
[
[
a]
b]
c]
Determined by NMR spectroscopy.
Isolated yield.
Determined by chiral IB HPLC, for the configuration as-
signment, see Supporting Information.
through removal of the products solution. New sub- perform thus successive catalytic runs. The results are
strates were then added to the resulting catalyst to summarized in Table 1.
Adv. Synth. Catal. 2011, 353, 1087 – 1095
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Dorian Didier et al.
FULL PAPERS
The recovered catalyst was then engaged in the thesis of compounds 7a, 7b and 7d, isolated in 94, 93
[
16]
second run with additional substrates and product 7a and 81% ee, respectively. A non-negligible decrease
could be further isolated but the reaction time had to of the enantioselectivity was only observed for the
be increased to maintain an important isolated yield formation of 7d by using ligand 1c, probably as a
(
Table 1, entry 2). Satisfyingly, however, a similar high result of the competitive non-catalyzed reaction, oc-
enantioselectivity (90%) was obtained for this second curring rapidly with nitromethane in the case of sub-
transformation conducted in the presence of TNF, strate 5d. In our hands, substrates 5c and 5e were en-
showing almost no influence of the formed charge gaged in the Henry reaction with complex 1a-
transfer complex on the selectivity of the catalysis. Cu ACTHUNGTRNEUNG( OAc) ·H O, leading to the expected products 7c
2 2
Catalyst 1c-TNF was further recovered by precipita- and 7e with, respectively, 89 and 87% ees. These
tion and subsequent filtration for five additional con- values are also close to those reported in Table 2, on
secutive catalytic runs showing only a slight decrease using ligand 1c.
in the enantioselectivity values along with the reuses
The use of the anthracene-modified bis(oxazoline)
but the reaction time had to be substantially length- ligand 1c is thus not detrimental, both in terms of ac-
ened in the last cycles. Partial leaching of the catalyst tivity and enantioselectivity, for the formation of
was indeed proved by adding fresh substrate 5a and those nitroalcohol adducts. The reaction with nitro-
nitromethane to the recovered product solution aris- ethane was also studied in the presence of two aro-
ing from the first run. After 24 h stirring, the mixture matic aldehydes 5a and 5e and smoothly led to the
was analyzed indicating that additional 25% conver- preparation of diastereomeric mixtures of compounds
sion occurred to form the expected product with the 7f and 7g with in both cases, the formation of the anti
same enantioselectivity. Although the isolated yield of isomer as major product. This selectivity is in total
the targeted product 7a regularly decreased with the contrast with the one observed through a Brønsted
recycling showing an incomplete recovery of the cata- base catalysis, since the use of Et N afforded mainly
3
[
27]
lyst by precipitation, this procedure is one of the very the syn isomer.
few examples for the use of copper bis(oxazoline) Due to the lower reactivity of nitroethane com-
complexes durably enantioselective, at least for five pared to nitromethane, a complete conversion of the
[
22b,24]
cycles, in the nitroaldol reaction.
The domain of relevance of the complex 1c- targeted products were nevertheless isolated in about
Cu(OAc) ·H O was further demonstrated by the 65% yield. The enantioselectivity of the transforma-
aldehydes could not be reached in one day, but both
ACHTUNGTRENNUNG
2
2
transformation of various aldehydes with either nitro- tion was measured for all compounds and both iso-
methane or nitroethane (Scheme 1). As depicted in mers of 2-nitro-1-phenylpropan-1-ol 7f were prepared
Table 2, the anthracene-modified bis(oxazoline) 1c in 73% ee, by using bis(oxazoline) 1c. This catalytic
proved to be efficient for the formation of nitroalco- system was, however, slightly less selective for the for-
hols arising from aliphatic aldehydes or from substi- mation of 2-nitro-1-(4-trifluoromethylphenyl)-propan-
tuted aromatic ones. The values that were obtained 1-ol 7g, for which the highest enantioselectivity was
matched those reported for the analogous gem-dime- obtained for the formation of the anti (major) isomer
[
28]
thylindanol-derived bis(oxazoline) 1a. Evans indeed (67% ee, Table 2).
described this procedure for the enantioselective syn-
We have therefore employed complex 1c-
Cu(OAc) ·H O in a multi-substrate recycling proce-
AHCTUNGTRENNUNG
2
2
dure (Table 3). This approach consists in introducing
new structurally different substrates at each recycling
of the precipitated CTC-catalyst. Such a procedure
was rarely described in the literature, but may be
Table 2. Nitroaldol reaction between various aldehydes and
nitromethane or nitroethane catalyzed by complex 1c-
[a]
Cu
ACHTUNGTRENNUNG( OAc) ·H O in EtOH.
2 2
[d]
Product Conv.
Yield
[%]
anti/
syn
ee (%) (anti/
syn)
used as a proof for the sturdiness of the reused cata-
[b]
[c]
[b]
[29]
[%]
lytic batch.
As the efficiency of the catalyst was
evaluated with different substrates in homogeneous
conditions, the recycling procedure was thus realized
in the presence of those various aldehydes starting
with the use of nitromethane. The first run of the
transformation involved the selective formation of 2-
nitro-1-phenylethanol 7a. At the end of the transfor-
mation, TNF was added to the reaction mixture fol-
lowed by dilution with pentane which resulted in the
precipitation of the corresponding charge transfer
complex. The product solution was removed through
7
7
7
7
7
7
7
a
b
c
d
e
f
>95
>95
>95
96
91
71
89
79
87
71
83
65
68
–
–
–
–
90 (R)
90 (R)
91 (R)
74 (R)
82 (R)
73/73
–
66/34
65/35
g
76
67/63
[
[
[
[
a]
Reactions were performed for 24 h at 208C.
Determined by NMR spectroscopy.
Isolated yield.
b]
c]
d]
Determined by chiral HPLC, for the configuration as- filtration and 7a could be easily isolated in the expect-
signment, see Supporting Information.
ed yield and enantioselectivity (Table 3, entry 1). At-
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Charge-Transfer Interactions: An Efficient Tool for Recycling Bis(oxazoline)-Copper Complexes
Table 3. Multi-substrates recycling procedure of 1c-Cu ACHTUNGTRENUNG( OAc) ·H O/TNF in EtOH for the formation of various nitroalcohols
2 2
at room temperature.
[b]
[c]
[b]
[d]
Run
Product
t [h]
Conv. [%]
Yield [%]
anti/syn
ee [%] (anti/syn)
1
2
3
4
5
6
7
8
9
7a
7f
7b
7c
7d
7e
7f
7g
7a
24
24
36
48
72
96
60
60
144
>95
<5
80
53
88
89
94
>95
72
90
–
–
–
–
–
–
–
91 (R)
–
69
46
79
82
86
82
61
83 (R)
87 (R)
49 (R)
70 (R)
25/43
4/13
[
[
a]
a]
40/60
41/59
–
80 (R)
[
[
[
[
a]
1
0 mol% Et N was added.
3
b]
c]
d]
Determined by NMR spectroscopy.
Isolated yield.
Determined by chiral HPLC.
tempts to realize a second run in the presence of ben- scribed for analogous copper catalysts in the presence
[
31]
zaldehyde and nitroethane under similar conditions in of a base. Accordingly, the enantioselectivities were
terms of reaction time and temperature failed, howev- drastically diminished (see Table 2 for comparison).
[30]
th
er (entry 2).
Gratifyingly, nevertheless, in a third The same trend occurred for the 8 use of the catalyst
cycle, the recovered complex 1c-TNF could catalyze concerning the preparation of an isomeric mixture of
the formation of 1-cyclohexyl-2-nitroethanol 7b with nitroalcohol 7g. We assume that, in these last two
a high enantioselectivity of 83%. Some catalyst leach- cases, the triethylamine-catalyzed transformation was
ing probably occurred since a slight increase in the re- probably in strong competition with the reaction
action time was necessary to obtain the desired prod- driven by the recovered chiral copper complex 1c,
uct in a valuable yield. This was accompanied with a leading to poor selectivities. Interestingly, however,
th
diminution in the selectivity of the transformation, in the preparation of 7a was attempted in the last 9
comparison to the values obtain with a new catalyst cycle, and after prolonged reaction time this com-
batch (compare Table 3, entry 3 with Table 2, entry 2). pound was isolated with 80% ee, a high value consid-
The subsequent run was associated to the preparation ering both the number of cycles performed with the
of compound 7c which could be isolated with 87% ee, same catalyst batch, and the different conditions that
a value similar to the one obtained in analogous con- were successively used for this recycling strategy.
ditions with a fresh catalyst. The fifth use of the cata-
In order to improve the recycling procedure, the in-
lyst led to the formation of 2-nitro-1-(4-nitrophenyl)- teraction between ligand 1c and TNF grafted on an
ethanol 7d, for which 3 days reaction time were nec- insoluble support was then considered. We indeed
essary to achieve reasonable conversion (Table 3, aimed to avoid the precipitation step by facilitating
entry 5). Some catalyst leaching along the recycling is the filtration procedure and performing the catalytic
here evidenced by the low enantioselectivity value; transformation directly under heterogeneous condi-
that is, 49% instead of 74%, as a proof of the pres- tions.
ence of the competitive racemic non-catalyzed reac-
Activated silica modified by covalently grafted tri-
tion, that can occur in a high rate for this substrate. nitrofluorenone was synthesized as a new material
The catalyst batch was engaged in a next cycle to pre- able to form supported CTC with ligand 1c
pare another structurally different nitroalcohol com- (Scheme 2).
pound and this 6 run led to the preparation of enan- boxylic acid 8 was synthesized in two steps from di-
tioenriched 2-nitro-1-(4-trifluoromethylphenyl)-etha- phenic acid.
2,5,7-Trinitro-9-oxo-9H-fluorene-4-car-
th
[
32]
By coupling with a trimethoxysilane
nol 7e, with up to 70% ee. Attempts to perform the functionalized propylamine in the presence of DCC,
[33]
Henry reaction in the presence of nitroethane were the trimethoxysilyl derivative 9 was obtained
and
then renewed, but the transformation was this time directly grafted on activated silica as a suspension in
[
34]
conducted in the presence of a catalytic amount of refluxing toluene
to yield the modified silica sup-
À1
triethylamine to enhance the reaction rate by activat- port 10 with a 0.191 mmolg loading, as determined
ing nitroethane. Contrary to the previous test by elemental analysis.
(
7
Table 3, entry 2), the expected mixture of isomers for
f was isolated in high yield (Table 3, entry 7) albeit acting 1c and CuACHTGNUTRENNUNG
The heterogeneous catalyst was then formed by re-
(OAc) ·H O followed by addition of
2
2
with a reversed diastereomeric ratio, since the syn the resulting complex as an ethanol solution to sup-
compound was preferentially prepared, as already de- port 10, in an equimolar amount according to grafted
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Dorian Didier et al.
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Scheme 2. Synthesis of the TNF-spport 10.
TNF, to match at best the conditions that were used Table 4. Heterogeneous recycling procedure of 1c-
in the preceding procedure. Tests on the influence of Cu(OAc) ·H O/10 with or without addition of pentane for
the formation of 7a.
A
H
U
G
R
N
N
2
2
the activated silica on the reaction course were firstly
realised using catalyst 1a-Cu(OAc) ·H O (10 mol%)
A
H
U
G
R
N
N
[a]
2
2
Run t
Conv.
h] [%]
Ratio 7a/ Yield 7a
ee 7a
[%]
in the presence of a similar amount of non-modified
support (i.e., simple activated silica) in ethanol. The
transformation afforded 2-nitro-1-phenyl-ethanol 7a
in 58% isolated yield after 24 h reaction in a satisfying
ee of 90%. Its formation was, however, accompanied
by the synthesis in a non-negligible amount of com-
pound 11 (2-nitrovinyl)-benzene, about 10%, arising
from a dehydration step from 7a probably favoured
by the intrinsic acidity of support 10. The heterogene-
[a]
[b]
[c]
[
11
[%]
with addition of pentane
1
2
36 93
72 95
88/12
89/11
74
72
89 (R)
89 (R)
…
5
…
7
72 64
120 64
91/9
54
51
84 (R)
83 (R)
89/11
without addition of pentane
ous asymmetric catalysis was then started in a recy- 1’
cling procedure by successive additions of nitrome- 2’
36 >95
72 95
72 75
72 66
72 56
91/9
84
72
60
55
44
89 (R)
88 (R)
84 (R)
82 (R)
76 (R)
86/14
90/10
88/12
88/12
thane and benzaldehyde on 1c-Cu
A
H
U
G
R
N
N
(OAc) ·H O/10 3’
2
2
4
5
’
’
(
Scheme 3). At the end of each run, pentane was first-
ly added to the reaction mixture and the silica-sup-
ported catalyst was removed from the products in so-
lution by filtration. Results are presented in Table 4.
Compared to the homogeneous procedure in etha-
nol, the reaction time was raised up to 36 h in the
first run (Table 4) to afford good conversions and
[a]
Determined by NMR spectroscopy.
Isolated yield.
Determined by chiral IB HPLC.
[
[
b]
c]
product 7a was satisfyingly isolated in 74% yield and
9% ee. In this case also, a non-negligible amount of
8
unsaturated product 11 was detected.
After the first run, pentane was added in order to
compare the results with the catalytic runs realized
with 1c-Cu ACTHUNGTRNEUNG( OAc) .H O/TNF. The second cycle was
2 2
performed with an increased reaction time that al-
lowed isolating compound 7a with the same yield and
Scheme 3. Nitroaldol reaction in the presence of silica-sup- enantioselectivity. The 7a/11 ratio remained quite
ported TNF 10/1c-Cu(OAc) . stable as did the enantioselectivity along the succes-
AHCTUNGTRENNUNG
2
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Charge-Transfer Interactions: An Efficient Tool for Recycling Bis(oxazoline)-Copper Complexes
sive catalytic cycles. As noticed for the preceding re- Conclusions
cycling procedure, however, the recovery of the cata-
lyst was accompanied with a continuous decrease in Various Henry reactions have thus been performed
activity, but the targeted product was nevertheless in- by using the catalytic system bis(oxazoline) 1c-Cu-
terestingly isolated with a quite stable enantioselectiv-
ity for seven runs.
ACHTUNGTNERNU(GN OAc) affording the expected nitroalcohols with high
yields and enantioselectivities. We have demonstrated
2
This recycling protocol was further simplified and that the chiral complex was recoverable through for-
implied finally the direct recovery of the catalytic sup- mation of charge transfer interactions with trinitro-
port by filtration after each run without addition of fluorenone and it was involved in consecutive catalyt-
pentane (Table 4). In this case, however, the amount ic cycles.
of supported TNF 10 used was two-fold according to
A precipitation procedure by addition of pentane
the initially introduced chiral complex to favour, at proved to be efficient for up to seven reuses of the
best, the charge transfer interaction. Consequently, catalyst in a mono-substrate procedure for the forma-
the reaction mixture was twice diluted. After the cata- tion of 2-nitro-1-phenylethanol. This methodology
lytic reaction, silica was washed once with ethanol to was also employed in an original multi-substrate pro-
recover the most part of the product and reused in a cedure, for which the structure of the substrate was
subsequent cycle.
changed at each reuse of the same catalyst batch, and
As expected, the first run afforded exactly the same the corresponding product was isolated in its pure
results as before, indicating that the dilution was not form, free of any product traces from the preceding
detrimental to the efficiency of the transformation run. A decrease in the product yield was unfortunate-
(
Table 4, run 1’). The second run gave also good re- ly unavoidable along the recycling which is, however,
sults in terms of activity and enantioselectivity (88% frequently reported concerning the Henry reaction,
ee), proving the good stability of the catalyst between whereas the selectivity of the transformation proved
the two first runs under similar reaction conditions as to be more stable. Direct asymmetric heterogeneous
those described previously, and avoiding the use of catalysis could also be performed via covalent linking
the apolar solvent favourable for the formation of the of modified TNF on a silica support, leading to prom-
CTC. At the third run, the activity decreased, howev- ising results in terms of activity and enantioselectivity
er, and compound 7a was isolated in only 60% yield, that were furthermore not decreased compared to
albeit with a good enantioselectivity of 84%. Along those obtained under homogeneous similar condi-
[
23]
the following runs, a regular loss of activity and enan- tions. This procedure is one of the few
for which
tioselectivity was nevertheless observed and at the asymmetric catalysts efficient to promote the enantio-
last run (Table 4, run 5’) product 7a was obtained in selective Henry reaction are recovered through non-
only 44% yield with 76% ee. These results neverthe- covalent, reversible interactions. Work is still in prog-
less prove that chiral bis(oxazoline) copper complexes ress to further stabilize the reversible charge transfer
can be maintained at the surface of a solid silica sup- interaction and minimize, at best, the catalyst leaching
port through non-covalent reversible CTC interac- in an effort to develop continuous asymmetric flow
tions, allowing the production of scalemic nitroalco- procedures.
hols with high enantioselectivity for at least four con-
secutive catalytic runs. To attest for the integrity of
the chiral ligand 1c, the copper complex was recov-
ered from the silica support 10 after these five succes-
Experimental Section
sive catalytic runs. The solid was indeed thoroughly
(
3aR,3a’R,8aS,8a’S)-2,2’-[5-(Anthracen-9-ylmethoxy)-
pentane-2,2-diyl]bis(8,8a-dihydro-3aH-indeno[1,2-d]-
oxazole) (1c)
washed with toluene, as a competitor solvent to disfa-
vour the CTC interactions between anchored-TNF
and the anthracene moiety of the ligand. Copper was
AHCTUNGTRENNUNG
then removed from the resulting mixture by washing In a dried Schlenk tube, TMEDA (174 mL, 1.17 mmol) and
isopropylamine (253 mL, 1.80 mmol) were mixed in 5 mL
with EDTA and 1c was thus isolated in 58% yield. di
ACHTUNGTRENNUNG
The ligand was identical by NMR to a fresh sample. THF and the solution was cooled to À208C. The lithium dii-
sopropylamide solution was then obtained by a slow addi-
It was furthermore submitted again to complexation
tion of n-BuLi (2.26 mL, 1.6M in hexane, 3.61 mmol) during
with Cu ACHTUNGTRENNUNG( OAc) ·H O and involved in a Henry reaction
2 2
3
0 min at À208C. The uncoloured solution was then allowed
between benzaldehyde and nitromethane to yield
compound 7a with the same expected high enantiose-
lectivity (90%).
to stir at room temperature. After 1 h, the solution of LDA
was transferred in a second Schlenk containing 3 (565 mg,
1
.64 mmol) in 15 mL THF and the mixture was stirred at
room temperature during 2 h. 3-(Anthracen-9-ylmethoxy)-
propyl methanesulfonate (1.08 g, 3.28 mmol) in 10 mL THF
was then added to the solution and the mixture was heated
at 608C and stirred during 24 h. Water was added to the so-
Adv. Synth. Catal. 2011, 353, 1087 – 1095
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1093

Dorian Didier et al.
FULL PAPERS
lution and the aqueous layer was extracted with diethyl
ether (3ꢂ30 mL). The organic layer was dried over MgSO4
and then concentrated. The crude product was purified on
silica gel (cyclohexane/ethyl acetate=1:1) to afford the pure
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product as a yellow solid; yield: 479 mg (51%); mp 618C.
1
H NMR (250 MHz, CDCl ): d=1.38 (s, 3H), 1.41–1.45 (m,
3
2
H), 1.88–2.01 (m, 2H), 2.9 (d, 2H, J=18.6 Hz), 3.18–3.33
(
m, 2H), 3.52 (t, 2H, J=6.3 Hz), 5.14–5.25 (m, 2H), 5.29 (s,
2
6
2
H), 5.50 (dd, 2H, J=8.3 Hz, J=3.9 Hz), 7.13–7.25 (m,
H), 7.46–7.51 (m, 6H), 7.99 (d, 2H, J=9.3 Hz), 8.29 (d,
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7373–7375.
1
3
H, J=9.3 Hz), 8.44 (s, 1H); C NMR (62.5 MHz, CDCl ):
3
d=20.7, 24.3, 32.7, 39.6, 64.6, 70.5, 76.4, 83.1, 124.5, 124.9,
1
1
calcd. for C H O N : 592.2720; [a] : +199 (c 1, CHCl );
IR (KBr): n=2935.5, 1646.3, 1090.6, 997.0 cm .
25.0, 125.5, 125.6, 126.0, 127.3, 128.3, 128.9, 130.9, 131.4,
[7] S. Liu, C. Wolf, Org. Lett. 2008, 10, 1831–1834.
39.5, 139.6, 141.8, 168.4; HR-MS (EI): m/z=592.2721,
[
8] Y. Kogami, T. Nakajima, T. Ikeno, T. Yamada, Synthe-
+
2
40
36
3
D
3
sis 2004, 1947–1950.
À1
[
9] a) A. Zulauf, M. Mellah, E. Schulz, J. Org. Chem. 2009,
7
4, 2242–2245; b) R. Kowalczyk, Ł. Sidorowicz, J.
Homogeneous Catalysis and Recovery of the Catalyst
by CTC Formation and Precipitation
Skarzewski, Tetrahedron: Asymmetry 2007, 18, 2581–
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J. Jurczak, J. Org. Chem. 2009, 74, 753–756.
Ligand 1c (33 mg, 0.055 mmol) dissolved in EtOH (1 mL)
[
[
10] a) M. Bandini, F. Piccinelli, S. Tommasi, A. Umani-
Ronchi, C. Ventrici, Chem. Commun. 2007, 616–618;
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was added to Cu ACHTUNGTRENNUNG( OAc) ·H O (10 mg, 0.05 mmol) and the
2 2
blue-green solution was stirred for 1 h at room temperature.
Then, nitroalkane (5.0 mmol) was added drop wise to the
solution and the homogeneous mixture was then stirred for
Metsala, M. Lopp, T. Kanger, J. Org. Chem. 2010, 75,
10 additional minutes. The aldehyde (0.5 mmol) was then in-
[2]
1
313–1316; d) ref.
troduced and the solution was stirred at room temperature
during 24 h. Then, trinitrofluorenone (TNF) (16 mg,
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0.05 mmol) was added to the green mixture to form the
CTC in solution. After 30 min stirring, the catalyst was pre-
cipitated as an insoluble CTC by addition of pentane
6
35–639; d) D. Xin, Y. Ma, F. He, Tetrahedron: Asym-
(
8 mL). The catalyst, recovered by filtration and drying, was
metry 2010, 21, 333–338.
reused in a renewed catalytic run after solubilisation in
EtOH (1 mL). The product-containing solution was then
evaporated under vacuum, the residue was purified by prep-
arative thin layer chromatography (pentane:diethyl ether=
[
[
[
[
12] T. Arai, R. Takashita, Y. Endo, M. Watanabe, A. Yana-
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310.
4
:1) and analyzed by HPLC for the determination of the ee
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15] D.-M. Du, S.-F. Lu, T. Fang, J. Xu, J. Org. Chem. 2005,
(
see below).
1
(
R)-(À)-2-Nitro-1-phenylethanol (7a): H NMR: (CDCl ,
3
2
50 MHz): d=2.99 (br. s, 1H), 4.53 (dd, 1H, J =13.3 Hz
1
7
0, 3712–3715.
and J =3.5 Hz), 4.64 (dd, 1H, J =13.3 Hz and J =9.3 Hz),
2
1
2
1
3
[16] D. A. Evans, D. Seidel, M. Rueping, H. W. Lam, J. T.
Shaw, C. W. Downey, J. Am. Chem. Soc. 2003, 125,
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[17] S. K. Ginotra, V. K. Singh, Org. Biomol. Chem. 2007, 5,
3932–3937.
7
8
.38–7.45 (m, 5H); C NMR: (CDCl , 250 MHz): d=71.1,
3
1.3, 126.1 , 129.0, 129.1, 138.3. HPLC: (IB, hexane/i-
À1
PrOH=9:1, 1.0 mL.min , 210 nm): t (major)=10.13 min,
R
2
0
t =11.73 min; [a] : À48.3 (c 1.00, CHCl ) for 90% ee;
S
D
3
[
9a]
20
Lit [a]D : À30.8 (c 1.00, CHCl ), [62% ee, (R)-isomer].
3
[
18] P. Anastas, N. Eghbali, Chem. Soc. Rev. 2010, 39, 301–
12.
3
[
19] B. M. Choudary, K. V. S. Ranganath, U. Pal, M. L.
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Acknowledgements
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2006, 244, 110–117.
The CNRS, the Ministꢀre de l’Enseignement Supꢁrieur et de
la Recherche and the Program “Chimie et Dꢁveloppement
Durables” du CNRS are acknowledged for financial support.
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1095