Combining fluorous and triazole moieties for the tagging of chiral azabis(oxazoline) ligands

Article abstract of DOI:10.1002/adsc.200900129

New fluorous-tagged azabis(oxazoline) ligands were prepared using the copper-catalyzed azide-alkyne cycloaddition as ligation method. The resulting ligands were tested in copper-catalyzed asymmetric benzoylations (up to 99% ee), nitroaldol (up to 90% ee), and Michael reactions (up to 82% ee). The combination of unpolar fluorinated alkyl chains and polar triazole moieties imposes properties that are beneficial for the catalysts with respect to recyclability and selectivity. The scope and limitation of this strategy in comparison to analogous catalysts immobilized on methoxypolyethylene glycol (MeOPEG) or polystyrene is discussed. Moreover, this study shows that the choice of solvent for a given reaction is crucial to arrive at highly recyclable bis(oxazoline) catalysts.

Full text of DOI:10.1002/adsc.200900129

FULL PAPERS
DOI: 10.1002/adsc.200900129
Combining Fluorous and Triazole Moieties for the Tagging of
Chiral Azabis(oxazoline) Ligands
Ramesh Rasappan,a Tobias Olbrich,a and Oliver Reisera,*
a
Institut fꢀr Organische Chemie, Universitꢁt Regensburg, Universitꢁtsstr. 31, 93053 Regensburg, Germany
Fax : (+49)-941-943-4121; phone: (+49)-941-943-4631; e-mail: Oliver.Reiser@chemie.uni-regensburg.de
Received: March 18, 2009; Revised: May 26, 2009; Published online: July 27, 2009
Dedicated to Armin de Meijere on the occasion of his 70th birthday.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900129.
Abstract: New fluorous-tagged azabis(oxazoline) li- of this strategy in comparison to analogous catalysts
gands were prepared using the copper-catalyzed immobilized
on
methoxypolyethylene
glycol
azide-alkyne cycloaddition as ligation method. The (MeOPEG) or polystyrene is discussed. Moreover,
resulting ligands were tested in copper-catalyzed this study shows that the choice of solvent for a
asymmetric benzoylations (up to 99% ee), nitroaldol given reaction is crucial to arrive at highly recyclable
(up to 90% ee), and Michael reactions (up to 82% bis(oxazoline) catalysts.
ee). The combination of unpolar fluorinated alkyl
chains and polar triazole moieties imposes properties Keywords: azabis(oxazolines); click reaction; fluo-
that are beneficial for the catalysts with respect to rous tags; immobilization; kinetic resolution; nitroal-
recyclability and selectivity. The scope and limitation dol reaction
Introduction
As a drawback of this strategy it has been recog-
nized that the ability of the triazole moiety to act as a
Azasemicorrins[1] and bis(oxazolines)[2] are recognized coordination site for metals results in decreased enan-
as privileged classes of chiral ligands, being able to tioselectivities by non-specific coordination of the
form complexes with a broad variety of metals that metal with that moiety rather than with the chiral
are able to catalyze a great number of reactions with ligand in the course of catalyst preparations.[6a,d,7d] For
unparalleled enantioselectivity. Impressive progress example, in the asymmetric benzoylation of diol
has been made in the development of immobilized (Æ)-1, the MeOPEG-bound ligand 6 performed com-
bis(oxazolines)[3] since the first reports on covalent parable to its non-immobilized counterpart 4b, while
immobilization appeared in 2000.[4] Azabis(oxazo- with ligand 5 significantly lower enantioselectivities
ACHTUNGTRENNUNG
lines)[4a,5] have proved to be especially suitable ligands were achieved with respect to 4a (Figure 1). We at-
for attachment onto supports owing to their compara- tributed the loss of selectivity with 5 to copper-com-
tively strong binding to metals resulting in greatly re- plexation with the triazole unit, which might, in addi-
duced leaching when they are used in repeating cycles tion, be assisted through the coordination of adjacent
in catalyses.[6]
ether units from the MeOPEG polymer.
Recent studies on catalyst immobilization by us[6]
Arguably, the most important application of attach-
and other groups[7] revealed that the copper-catalyzed ing perfluoroalkyl moieties to organic compounds is
azide-alkyne cycloaddition (CuAAC) is
a facile to separate the so-tagged compound from a complex
method for grafting catalysts onto polymers or nano- reaction mixture by fluorous biphasic separations, ap-
particles. Using an azido-functionalized support and plying perfluorinated solvent, fluorous silica or per-
an alkyne-substituted ligand or metal-ligand complex, fluorinated tags.[8] This property has provided an at-
high loading of the immobilized derivative close to tractive method for catalyst recovery and recycling
the maximum capacity of the support can be and, consequently, perfluorinated tags were attached
achieved.
to several metal-based catalysts[9] including bis(oxazo-
lines)[10] and organocatalysts.[11]
Adv. Synth. Catal. 2009, 351, 1961 – 1967
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1961

Ramesh Rasappan et al.
FULL PAPERS
of diols[14] the soluble complex CuCl2·11 showed ex-
cellent reactivity and enantioselectivity (Table 1, en-
tries 3–8), being by far superior to the analogous
MeOPEG-supported complex CuCl2·5 (entries 1 and
2). Complete consumption of benzoyl chloride was
Table 1. Copper(II)-catalyzed asymmetric benzoylation of
hydrobenzoin with fluorous tag bound azabis(oxazoline) li-
gands.[a]
Entry Mol% Ligand Run Time
[h]
Yield
[%][b]
ee of 2
[%][c]
1[d]
2[d]
3
4
5
6
7
8
9
1.3
1.3
2
2
2
2
2
2
5
5
5
1
2
1
2
3
4
5
6
1
2
3
4
6
6
2
2
2
2
2
2
6
6
6
6
28
25
45
43
46
26
41
47
42
39
44
43
63
56
>99
>99
99
99
99
99
94
11
11
11
11
11
11
13
13
13
13
Figure 1. Application of azabis(oxazolines) in the asymmet-
ric benzoylation of diol (Æ)-1.
10
11
12
5
5
5
95
94
82
Results and Discussion
[a]
Ligand
(2.2 mol%),
CuCl2
(2 mol%),
PhCOCl
We report here that replacing the MeOPEG back-
bone in 5 with unpolar perfluoroalkyl tags can help to
overcome the limitations outlined above. Besides
greatly improved selectivities rivaling the non-tagged
analogue 4a the solubility profile imposed by a single
perfluorotriazole tag is comparable to that observed
by MeOPEG modification, that is, good solubility in
(0.5 equiv.), DIPEA (1.0 equiv.), CH2Cl2, 08C.
[b]
Isolated yield based on (Æ)-1 (maximum theoretical
yield 50%).
[c]
[d]
Determined by chiral GC.
Taken from ref.[6d]
solvents like dichloromethane, but low solubility in observed within 2 h at 2 mol% of CuCl2·11, giving rise
unpolar solvents like hexanes or diethyl ether, thus al- to (R,R)-2 in ꢀ99% ee. CuCl2·11 showed a compara-
lowing for efficient recovery of ligands and catalysts. ble solubility profile like its MeOPEG-bound ana-
Upon attachment of multiple perfluorotriazole tags, logue CuCl2·5 allowing, after removal of unreacted
the ligands and catalysts become insoluble in most or- (Æ)-1 by filtration, its quantitative precipitation by
ganic solvents (hexanes, diethyl ether, THF, dichloro- the addition of diethyl ether to the reaction mixture.
methane), thus allowing their recovery by simple fil- Thus, CuCl2·11 was reused in six cycles without loss of
tration.
its activity or selectivity (entries 3–8, Table 1), more-
Initial attempts to synthesize a perfluoroalkyl over, no metal leaching is observed. The heterogene-
tagged azabis(oxazoline) in analogy to 6 by direct al- ous three ponytailed complex CuCl2·13 also catalyzed
kylation of deprotonated 7 with 8 were unsuccessful. the benzoylation of (Æ)-1 effectively (entries 9–12),
Nevertheless, propargylation of 7[6d] and chloride/ with greatly improved selectivity compared to the
azide exchange of 8[12] followed by the CuAAC of the polystyrene bound analogue reported by us previous-
resulting 9 and 10 proceeded with high yields to give ly.[6a] CuCl2·13 could be recovered by simple filtration
rise to the monotagged azabis(oxazoline) ligand 11. from the reaction mixture, however, in recycling ex-
Likewise, ligation of 9 with azide 12[13] furnished the periments we noted a drop in selectivity after the
azabis(oxazoline) 13, having three perfluoroalkyl third cycle.
chains and four triazoles incorporated (Scheme 1).
Next we investigated the CuACTHUNGTRENNU(G OAc)2-catalyzed nitro-
The fluorous-tagged ligands 11 and 13 were evalu- aldol reaction for which Evans et al.[15] reported excel-
ated as ligands for metal catalysis. Starting with the lent results with bis(oxazoline) ligands provided that
copper(II)-catalyzed asymmetric monobenzoylation the sterically bulky indabox ligand 14 (Figure 2,
1962
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Fluorous and Triazole Moieties for the Tagging of Chiral Azabis(oxazoline) Ligands
FULL PAPERS
Scheme 1. Synthesis of fluorous-tagged azabis(oxazolines): a) n-BuLi, THF, À788C to room temperature; b) propargyl bro-
mide (4 equiv.), n-BuLi (1.1 equiv), THF, À788C to room temperature, 24 h, 97%; c) NaN3, acetone-H2O (5:1); d) DIPEA
(1.1 equiv.) CuI (6 mol%), THF, room temperature, 12 h, 92%; e) CuI (6 mol%), DIPEA (1.2 equiv.), THF, room tempera-
ture, 70 h, 76%.
Table 2. Copper(II)-catalyzed asymmetric nitroaldol reac-
AHCTUNGTRENNUNG
tion.[a]
Entry Solvent Ligand Run Yield [%][b] ee [%][c]
Figure 2.
1[d]
2
3
4
5
6
7
8
9
EtOH
EtOH
THF
EtOH
THF
THF
THF
THF
THF
THF
THF
THF
14
15
15
4a
4a
11
11
11
11
13
13
13
1
1
1
1
1
1
2
3
4
1
2
3
76
73
75
71
76
68
65
63
65
59
54
57
94 (R)
63
61
86
92
90
90
86
72
Table 2, entry 1) is used. We were pleased to see that
when aza(bisoxazoline) instead of bis(oxazoline) li-
gands are employed the simple valine-derived ligand
4a also performs well, especially when THF is em-
ployed as solvent (Table 2, entries 2–5).
The
single
fluorous
ponytailed
complex
11·Cu(OAc)2 in a homogeneous reaction initially gave
ACHTUNGTRENNUNG
10
11
12
86
82
70
rise to the nitroaldol product 16 with comparable se-
lectivities as observed with 4a (Table 2, entry 6), with
some erosion of enantioselectivity after three reaction
cycles (entries 6–9). Similar results were obtained for
the triple fluorous ponytailed complex 13·CuACTHNUTRGNEUNG(OAc)2
(entries 10–12).
[a]
Ligand (5.5 mol%), Cu
perature, 24 h.
Isolated yield.
ACHTUGNRTEN(NUGN OAc)2·H2O (5 mol%), room tem-
[b]
[c]
[d]
Determined by HPLC.
Taken from ref.[15] 11 and 13 were recovered quantitative-
Finally, we investigated the enantioselective Frie-
del–Crafts alkylation of indoles with benzylidenemal-
ly by addition of hexane and were reused as such.
Adv. Synth. Catal. 2009, 351, 1961 – 1967
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1963

Ramesh Rasappan et al.
FULL PAPERS
onates,[17] which proceeds well with simple bis(oxazo- chloromethane or THF (Table 1 and 2) but not for re-
line) and azabis(oxazoline) ligands, provided that the actions that called for the use of ethanol (Table 3).
metal to ligand ratio is carefully adjusted.[18] However, Nevertheless, experiments showed that also in THF,
both ligands 11 and 13 in combination with various while no ligand leaching was observed, copper leach-
copper salts cannot rival the non-tagged ligand 4a ing was appreciable (approx. 3% in each run). Finally,
(Table 3, entries 1–2, 5–6) in the synthesis of 17. we note that the counteranion in the copper com-
Moreover, attempts to reuse the two complexes plexes can have a large effect on the effectiveness to
11·Cu
ACHTUNGTRENNUNG(OTf)2 or 13·CuACHTUNTGRNE(NUGN OTf)2 were not successful, con- recycle the catalysts. While 13·CuCl2 is largely insolu-
siderably lower enantioselectivities were observed in ble in THF (<0.5 mgmLÀ1; approx. 3% copper leach-
subsequent runs (entries 2–3, 6–7).
ing determined by total reflection X-ray fluorescence
in each reaction cycle) 13·Cu(OAc)2 forms a gel in
AHCTUNGTRENNUNG
that solvent. After removal of THF and addition of
dichloromethane/hexanes 1:5, recovery of the com-
plex therefore by filtration proved to be difficult due
to the morphology of the catalyst (mass recovery
approx. 70% after each cycle).
Table 3. Copper(II)-catalyzed enantioselective 1,4-addition
to benzylidene malonates.[a]
Conclusions
Here we have demonstrated that tagging aza(bisoxa-
zoline) ligands via the copper(I)-catalyzed alkyne-
azide cycloaddition with perfluoroalkyl moieties
opens the possibility to arrive at recyclable cop-
Entry Ligand Run CuX2
Yield [%][b] ee [%][c]
1
2
3
4
5
6
7
4a
11
11
11
11
13
13
1
1
2
1
1
1
2
Cu
Cu(OTf)2
Cu(OTf)2
CuCl2
Cu
Cu(OTf)2
Cu(OTf)2
G
95
86
95
85
50
–
78
AHCTUNGTREGpNNUN er(II)-azabox complexes. Depending on the number
ND[d]
of fluorous tags and triazole moieties, the resulting
copper(II)-azabis(oxazoline) complexes are either
soluble in solvents like dichloromethane, THF or eth-
anol but can be precipitated from diethyl ether or
hexanes (MeOPEG-like properties) or are heteroge-
neous in dichloromethane or THF (polystyrene-like
properties) and can be recovered by direct filtration
from a reaction mixture.
72
68
46
84
76
[a]
Ligand (5.045 mol%), CuX2 (5.0 mol%), EtOH, room
temperature, 8 h.
Isolated yield.
Determined by HPLC.
NR=no reaction.
[b]
[c]
[d]
The perfluoro tag apparently offsets the previously
noted interference of the triazole moiety as an addi-
The difference in performance of the copper cata- tional coordination site in metal catalyses. The success
lysts in combination with ligands 11 and 13 is clearly for efficient recyclability of the metal azabis(oxazo-
attributable to the choice of solvent in which the reac- line) catalysts, however, is greatly dependent on the
tions have to be performed. While complexes with solvent that can be employed for a given reaction.
ligand 11 are soluble in dichloromethane, THF or al- When dichloromethane was used, the reisolated metal
cohols, they can be effectively precipitated from hex- complexes could be reused without observable loss of
anes or diethyl ether, allowing their quantitative re- reactivity and selectivity. THF only allowed the recy-
covery. No appreciable metal or ligand leaching cling of the catalysts approximately three times, while
ACHTUNGTRENNUNG(<0.1%) was observed when copper complexes of 11 for reactions run in ethanol, recycling of the catalysts
were reisolated by precipitation from these solvents. was not possible. The gel-like properties that some of
Nevertheless, for reactions like the asymmetric 1,4-ad- the fluorous tagged catalysts described here adopt in
dition of indoles to malonates (Table 3) that require polar solvents makes efficient recovery and reuse by
alcoholic solvents in order to achieve high selectivi- filtration problematic.
ty,[16] the recovered catalysts while showing the same
activity were inferior in selectivity, indicating the pres-
ence of catalytically active copper centers outside the
chiral environment of the ligand.
Experimental Section
Copper complexes of 13 are insoluble in most or-
ganic solvents but showed appreciable solubility in
ethanol or methanol (approx. 2Æ1 mgmLÀ1). There-
fore, recovery of the catalysts by simple filtration was
Ligand Synthesis
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
only effective for reactions that are carried out in di- THF (10 mL) n-butyllithium (1.1 mmol, 690 mL of 1.6N so-
1964
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Adv. Synth. Catal. 2009, 351, 1961 – 1967

Fluorous and Triazole Moieties for the Tagging of Chiral Azabis(oxazoline) Ligands
FULL PAPERS
lution in hexane) was added slowly at À788C. After stirring
for 10 min, propargyl bromide (4.0 mmol, 274 mL of an 80%
solution in xylene) was added dropwise, and the solution
was slowly warmed to room temperature overnight and
stirred for another 10 h. Aqueous Na2CO3 was added and
the mixture was concentrated. The residue was separated
between CH2Cl2 and aqueous Na2CO3. The aqueous phase
was extracted twice with dichloromethane, and the com-
bined organic phases were dried over MgSO4 concentrated
to give 9 as a light brown liquid; yield: 270 mg (97%).
1H NMR (300 MHz, CDCl3): d=4.58 (d, 2H, J=2.3 Hz),
4.34 (dd, 2H, J=9.2, 8.3 Hz), 4.12 (dd, 2H, J=8.3, 6.7 Hz),
3.86 (ddd, 2H, J=9.2, 6.6, 6.1 Hz), 2.18 (t, 1H, J=2.4 Hz),
1.80–1.66 (m, 2H), 0.88 (d, 6H, J=6.8 Hz), 0.81 (d, 6H, J=
6.8 Hz); 13C NMR (75.5 MHz, CDCl3): d=156.4, 79.1, 71.7,
71.5, 69.7, 39.7, 32.7, 18.6, 17.6; IR: n=3290, 3220, 2965,
sure. Recrystallization from CH2Cl2 gave the complex as
green crystals.
13·CuCl2 complex: Ligand 13 (1.1 mmol) and CuCl2
(1.0 mmol) were stirred in CH2Cl2 (25 mL) for 2 h. The re-
sulting green complex was filtered, washed once with THF
and dried to afford the green complex.
General Procedure for the Catalytic Asymmetric
Benzoylation
1,2-Diol (Æ)-1 (1.0 mmol), diisopropylethylamine (DIPEA,
1.0 mmol) and 0.02 mmol of the fluorous tagged catalyst
were charged in 4 mL of CH2Cl2 and cooled to 08C. Benzoyl
chloride (0.5 mmol) was added and the mixture was stirred
at 08C until the benzoyl chloride disappeared (TLC). After
recovery of the catalyst (see below) the reaction mixture
was poured into water and extracted three times with
CH2Cl2. The combined organic layers were dried over mag-
nesium sulfate. After filtration, the solvent was evaporated
under reduced pressure. The residue was purified by silica
gel column chromatography (hexanes/ethyl acetate).
2915, 2885, 1703, 1640, 1485, 1428, 1273, 1100, 985 cmÀ1
;
[a]2D0: À58.7 (c 1.0, CH3OH); MS (ES-MS): m/z=278.2
(MH+); HR-MS: m/z=278.1875 [MH+], calcd. for
C15H23N3O2: 278.1869.
Single-ponytail perfluorinated azabox 11: To a stirred so-
lution of 9 (830 mg, 2.99 mmol) in degassed dry THF
(15 mL), 1-azido-perfluorodecane (1.46 g, 2.99 mmol), CuI
(34 mg, 0.18 mmol) and DIPEA (606 mL, 3.29 mmol) were
added and the reaction mixture was stirred at room temper-
ature for 12 h. The reaction mixture was quenched with
0.1M EDTA solution, the product was extracted with
CH2Cl2 (thrice). The combined organic layers were washed
with brine and dried over Na2SO4. After removal of the sol-
vent, the crude product was recrystallized from hexane and
ethylacetate to afford 11 as a colorless solid; yield: 2.1 g
(92%); mp 124–1258C. 1H NMR (300 MHz, CDCl3): d=
7.69 (s, 1H), 5.13 (s, 2H), 4.63 (t, 2H, J=7.5 Hz), 4.39 (dd,
2H, J=9.1, 8.5 Hz), 4.13 (dd, 2H, J=8.3, 7.1 Hz) 3.87 (dt,
2H, J=9.1, 6.6 Hz), 2.69–2.86 (m, 2H), 1.77–1.66 (m, 2H),
0.91 (d, 6H, J=6.8 Hz), 0.82 (d, 6H, J=6.8 Hz); 13C NMR
(75.5 MHz, CDCl3): d=155.8, 143.9, 122.5, 70.6, 68.9, 44.1,
31.8, 17.6, 16.7; IR: n=2963, 1750, 1635, 1553, 1485, 1416,
1373, 1333, 1196, 1146, 1095, 1048, 967, 935, 808, 704, 658,
609, 559, 529, 413 cmÀ1; MS (ES): m/z=767 (MH+); HR-
MS: m/z=766.1924 [MH+], calcd. for C25H27F17N6O2:
766.1917.
Catalyst Recovery and Recycling
11·CuCl2 complex (homogeneous): After completion of the
reaction, the reaction mixture was filtered to remove un-
reacted (Æ)-1. Cold diethyl ether (5 mL) was added to the
filtrate to precipitate the complex. The complex was recov-
ered by filtration, dried and directly used for the next reac-
tion.
13·CuCl2 complex (heterogeneous): After completion of
the reaction, the reaction mixture was filtered in order to re-
cover the complex and washed with MeOH (2 mL), dried
and reused directly.
General Procedure for the Copper Acetate-Catalyzed
Direct Nitroaldol Reaction of Nitromethane with
Aldehydes
To
a
Schlenk tube fluorous-tagged azabis(oxazoline)
(OAc)2·H2O (0.05 mmol) were added
(0.055 mmol) and CuAHCTUNGTRENNUNG
Triple-ponytails perfluorinated azabox 13: To a stirred so-
lution of 9 (100 mg, 0.36 mmol) in degassed dry THF
(10 mL), 12 (397 mg, 0.23 mmol), CuI (2.6 mg, 14 mmol) and
DIPEA (45 mL, 0.27 mmol) were added and the reaction
mixture was stirred at room temperature for 70 h. The reac-
tion mixture was quenched with 0.1M EDTA solution, and
the product was filtered and washed with water and ether
and dried under reduced pressure to give 13 as a light
brown solid; yield: 359 mg (76%); mp 153–1558C; IR: n=
3200, 2963, 2104, 1642, 1437, 1327, 1200, 1146, 1112, 972,
705, 657, 530 cmÀ1; MS (ES): m/z (%)=2042 (72), 2041
(MH+, 100), 1931 (38), 1930 (74), 1781 (31), 1764 (47).
under an air atmosphere. THF (2.5 mL) was added and the
mixture was stirred for 1 h at room temperature (20–258C).
To the resulting blue-green solution nitromethane (537 mL,
10 mmol) and benzaldehyde (102 mL, 1 mmol) were added.
After stirring for the time indicated, the catalyst was recov-
ered (see below) and the crude product was purified by
column chromatography (hexanes/EtOAc, 85:15).
Catalyst Recovery and Recycling
11·CuACTHUNTGRNE(NUG OAc)2 complex (homogeneous): After the completion
of reaction, THF was removed; hexanes (5 mL) and di-
chloromethane (1 mL) were added to the reaction mixture
in order to precipitate the complex. The recovered complex
was dried and directly used for the next reaction.
General Procedure for the Preparation of
Copper(II)-Aza(bisoxazoline) Complexes
13·CuACTHUNTGRNE(NUG OAc)2 complex (gel): After the completion of reac-
tion, THF was removed; hexanes (5 mL) and dichlorome-
thane (1 mL) were added to the reaction mixture in order to
precipitate the complex. The recovered complex was dried
and directly used for the next reaction.
11·CuCl2 complex: A solution of ligand 11 (1.1 mmol) and
CuCl2 (1.0 mmol) in CH2Cl2 (25 mL) was stirred for 1 h, fil-
tered, and the filtrate was concentrated under reduced pres-
Adv. Synth. Catal. 2009, 351, 1961 – 1967
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asc.wiley-vch.de
1965

Ramesh Rasappan et al.
FULL PAPERS
General Procedure for the Catalytic Asymmetric
Michael Addition of Indole to Diethyl 2-
BenzyliACHTUNGTRENNUNGdenemalonate
Acknowledgements
This work was supported by the DAAD (fellowship for RR)
and the International Doktorandenkolleg NANOCAT (Elite-
netzwerk Bayern). Dr. Kerstin Leopold, Technical University
Munich, is gratelfully acknowledged for carrying out TXRF
analyses.
To
a
Schlenk tube fluorous-tagged azabis(oxazoline)
(OTf)2 (0.05 mmol) were added under
(0.05 mmol) and CuAHCTUNGTRENNUNG
an air atmosphere. THF (2 mL) was added and the mixture
was stirred for 1 h at room temperature (20–258C). To the
resulting blue-green solution diethyl 2-benzylidenemalonate
(1 mmol, 1.0 equiv.) in EtOH (2 mL) was added and stirring
was continued for 20 min before the indole (1.2 mmol,
1.2 equiv,) was added. After stirring for 8 h at room temper-
ature, the catalyst was recovered (see below) and the crude
product purified by column chromatography (performed
with hexanes/DCM, 1:1, followed by DCM).
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Catalyst Recovery and Recycling
11·CuACHTUNGTRENNUNG(OTf)2 complex (homogeneous): After the completion
of reaction, the solvent was removed under reduced pres-
sure, and the residue was dissolved in CH2Cl2 (0.5 mL) and
diethyl ether was added (5 mL) to the filtrate to precipitate
the complex. The recovered complex was dried and directly
used for the next reaction.
13·CuACHTUNGTRENNUNG(OTf)2 complex (heterogeneous): After the comple-
tion of reaction, the reaction mixture was filtered in order
to recover the complex and washed with EtOH, dried and
reused directly.
Determination of Cu by Means of Total Reflection
X-Ray Fluorescence
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All work was performed in a laminar flow, clean work
space. The solid samples were dissolved in 1 mL of high
purity methanol (analytical grade for chromatography,
Merck, Darmstadt) and an aliquote of 100 mL was mixed
thoroughly with vanadium standard solutions (freshly pre-
pared by dilution of 1000Æ2 mgLÀ1 stock standard solution
in 0.5% HNO3, Merck, Darmstadt). The mixed sample solu-
tions and a blank sample were analyzed for Cu by means of
total reflection X-ray fluorescence (TXRF, Atomika 8010,
Oberschleißheim, Germany). Calibration was performed by
internal vanadium standard addition and investigation of the
blank sample approved contamination-free pre-treatment
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copper only traces of Ta and Co were observed.
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Leaching Experiments
13·CuCl2 (15 mg, copper content=430 mg) was suspended in
1.5 mL of THF. After filtration, the solvent was evaporated,
and the residue was subjected to copper analysis as de-
scribed above. Found: 13.9 mg copper (3% leaching). No ap-
preciable amounts of ligand (<0.5 mg) were observed in the
filtrate.
13·CuCl2 (15 mg, copper content=430 mg) was suspended
in 1.5 mL of MeOH. After filtration, the solvent was evapo-
rated, and the residue was subjected to copper analysis as
described above. Found: 21.3 mg copper (5% leaching).
Approx. 2Æ1 mg of the ligand were observed in the filtrate.
1966
asc.wiley-vch.de
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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