Immobilized catalysts for iridium-catalyzed allylic amination: Rate enhancement by immobilization

Article abstract of DOI:10.1002/chem.201500382

The first immobilized catalyst for Ir-catalyzed asymmetric allylic aminations is described. The catalyst is a cationic (π-allyl)Ir complex bound by cation exchange to an anionic silica gel support. Preparation of the catalyst is facile, and the supported

Full text of DOI:10.1002/chem.201500382

DOI: 10.1002/chem.201500382
Full Paper
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Asymmetric Catalysis |Hot Paper|
Immobilized Catalysts for Iridium-Catalyzed Allylic Amination:
Rate Enhancement by Immobilization
Chandi C. Malakar and Günter Helmchen*[a]
Dedicated to Professor Lixin Dai, Shanghai Institute of Organic Chemistry, on the occasion of his 90th birthday
Abstract: The first immobilized catalyst for Ir-catalyzed
asymmetric allylic aminations is described. The catalyst is
a cationic (p-allyl)Ir complex bound by cation exchange to
an anionic silica gel support. Preparation of the catalyst is
facile, and the supported catalyst displayed considerably en-
hanced activity compared with the parent homogeneous
catalyst. Up to 43 consecutive amination runs were possible
in recycling experiments.
aminations;[9] however, reaction times of more than 100 h were
required at this loading. In contrast to commonly employed
procedures in which the nucleophile is used in excess, during
the development of an allylic esterification it was necessary to
employ an excess of the allylic component;[10] surprisingly, re-
actions could be completed within a few hours, even with
0.2 mol% catalyst. Nevertheless, in the case of a precious-
metal catalyst, loading of less than 0.1 mol% appears desirable
for applications, even on a multigram scale. An obvious way to
meet this demand is catalyst immobilization. Herein, we are
pleased to report the development of the first immobilized Ir
catalyst for allylic aminations. Allylic aminations have found nu-
merous applications in syntheses of biologically active com-
pounds, in particular alkaloids.[11]
Introduction
The Ir-catalyzed asymmetric allylic substitution (Scheme 1) has
been developed to a useful level of applicability.[1] The current
best catalysts are prepared from complexes [{Ir(cod)Cl}2] (cod=
cycloocta-1,5-diene) or [{Ir(dbcot)Cl}2] (dbcot=dibenzocyclooc-
tatetraene) by reaction with phosphoramidites, for example
L1[2] or L2.[3] Upon treatment with base, cyclometallation[4] is
effected to give complexes that are schematically described in
Scheme 2.[1c,5] Of these, the (p-allyl)Ir complexes C1–C3 are par-
ticularly convenient single-species catalysts that have mainly
been employed in the work leading to this article.
Unfortunately, current catalysts are not very active; typically,
1–4 mol% catalyst is required and catalyst recovery has not
been explored systematically.[6] So far, attempts to reduce the
catalyst loading were only partially successful.[7] In our own
work, a limit of 0.4 mol% was reached for alkylations[8] and
Immobilization often yields a catalyst with low activity, and
special efforts and additional steps in ligand synthesis, as well
as specific expertise in polymer chemistry, are required. These
disadvantages are offset by facile recovery of the catalyst upon
multiple uses.[12] In the area of asymmetric allylic substitution,
a considerable body of work with Pd catalysts has been assem-
bled by the groups of Uozumi and, earlier, Hayashi.[13] These
authors developed chiral phosphanes bound to amphiphilic
polymers as catalysts, which gave rise to very high enantiose-
lectivity with water as solvent at a typical catalyst loading of
5 mol%. However, the number of consecutive runs with
a given catalyst was reported as only three.[13d] Pd complexes
were formed in situ on the polymer. Characterization of such
catalysts is very difficult. In work by our own group with a simi-
lar approach, using polyethyleneglycol-bound PHOX ligands,
we were discouraged by the fact that the maximum number
of consecutive runs was only six, and deactivation of the cata-
lyst could not be prevented.[14]
Scheme 1. Iridium-catalyzed allylic substitution.
[a] Dr. C. C. Malakar, Prof. Dr. G. Helmchen
Organisch-Chemisches Institut
Universität Heidelberg
Our approach to the development of a supported catalyst
for the Ir-catalyzed allylic substitution was guided by the
mechanism of the allylic substitution; the presently accepted
catalytic cycle is summarized in Scheme 2.[1c,15] Of the various
intermediates, cationic (p-allyl)Ir complexes C are excellent cat-
alysts and are readily available.[16] This suggested immobiliza-
Im Neuenheimer Feld 270
69120 Heidelberg (Germany)
E-mail: g.helmchen@oci.uni-heidelberg.de
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201500382.
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by suspending the ammonium
salt in a solution of a crotyl com-
plex
C1–3,
in
acetone
(Scheme 3); upon addition of
water, the silica gel became
yellow within a few minutes,
and the previously light-yellow
supernatant became colorless.
The amount of bound Ir com-
plex was assessed by determin-
ing the amount of crotyl com-
plex recovered from the super-
natant. Samples of silica gel with
contents of 10–70 mmol crotyl
complex per gram were pre-
pared.
Scheme 2. Catalytic cycle of an allylic amination using a cationic (p-allyl)Ir complex (C) as catalyst. Grey areas: spe-
cies bound to a cation exchanger; C1–C3: complexes used in the present investigation.
tion on a cation exchange material, which leads to the follow-
ing scenario (cf. Scheme 2).
Complex C is loaded on to the solid support by ion ex-
change; reaction with a nucleophile is expected to yield
charged olefin complex D, which is deprotonated to give un-
charged complex E, which can leave the solid support and dis-
sociate into product and the putative 16 valence-electron com-
plex F. The reaction of the latter complex with the allylic sub-
strate is fast and reversible.[1c,17] The concentration of F is
small, and this species has so far not been observed experi-
mentally. Complex E constitutes the resting state of the reac-
tion, if the amine nucleophile is used in excess as in usually
employed procedures. Our approach requires binding of a cat-
ionic catalytic species after completion of the reaction. Accord-
ingly, an excess of the allylic component is required to form
(p-allyl)Ir complex C, which has been found by NMR investiga-
tion to be a resting state if the allylic component is used in
excess.[15,16] Note that the charged complex D is not suitable
for capture because it is prone to react back to complex C;
that is, it gives rise to equilibration that finally yields the linear
allylation product.
Work with solid supported catalysts likely requires manipula-
tions under air. For this reason, we chose catalysts containing
dbcot as ancillary ligand (Scheme 2). These are known to allow
allylic substitutions in air, which is not possible with the corre-
Scheme 3. Preparation of supported catalysts by reaction of (p-allyl)Ir com-
plexes with an ammonium salt of a silica gel bound p-ethylbenzenesulfonic
acid (n=amount of complex per gram of supported catalyst).
sponding cod complexes.[18]
Results and Discussion
Determination of the content of Ir complex on the support
after its use as catalyst was carried out by cation exchange,
which involved treatment of the supported catalyst with a solu-
tion of LiOTf, followed by quantitative analysis of liberated C1–
C3 by NMR spectroscopic analysis. Compared with methods
based on the determination of metal content, for example by
ICP-MS,[19] the recovery of the Ir complex is advantageous be-
cause deterioration, for example by oxidation at phosphorus, is
taken into account.
Preparation of the immobilized catalysts
The choice of the support was inspired by the recent work of
Borr› et al. on ring closing metathesis;[19] the authors used
a pyridinium-tagged Ru catalyst in conjunction with a silica
gel-based cation exchanger containing carbon-bound p-ethyl-
phenylsulfonic acid (Si-TsOH “Biotage”, 0.59 mmolgÀ1). We also
used this ion exchanger and first prepared various alkali and
ammonium salts, which were reacted with the Ir complexes.
Optimal results were obtained with a triethylammonium salt,
which is easily available by treatment of the ion exchanger
with triethylamine. Loading of the Ir complex was performed
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Allylic amination under homogeneous conditions
a base (NEt3) that was stronger than aniline to avoid reducing
the regioselectivity through rearrangement of the branched
product 3 into the linear isomer 4.[20] This procedure worked
well in conjunction with 2.32 mol% catalyst; however, it failed
with a loading of 0.42 mol%, which induced preferential for-
mation of the linear isomer (branched/linear (b/l) ratio 15:85).
A representative set of reactants were chosen for testing
(Scheme 4). Results obtained under standard reaction condi-
tions, using either 2.32 or 0.42 mol% catalyst, are presented in
Table 1. Reaction times of 1–3 h were required with 2.32 mol%
Allylic aminations using immobilized catalysts: catalyst ac-
tivity
The reaction of carbonate 1a with N-methyl-benzylamine (2a)
was used as a model in exploratory experiments with immobi-
lized catalysts (Table 2, entries 1–11). To our surprise, reactions
were generally faster than those carried out under homogene-
ous conditions. A catalyst loading of 0.1 mol% sufficed for suc-
cessful preparative amination runs. However, a limit was
reached at a loading of 0.05 mol%, which gave rise to only
19% yield over a period of 36 h (entry 6 in Table 2). The influ-
ence of the following reaction variables was found: 1) The rate
of the amination reaction was slow upon use of a supported
catalyst prepared in situ from
Scheme 4. Ir-catalyzed allylic aminations.
the
triethylammonium
salt
[SiTsO/HNEt3] and complex ent-
C1 (entry 7 in Table 2). 2) A mix-
ture of ent-C1 and unmodified
silica gel gave a catalyst with
low activity (entry 8 in Table 2).
3) At low catalyst loading, the in-
fluence of the solvent on rate as
well as enantioselectivity was
small (cf. entries 3, 9, and 10 in
Table 2); in contrast, under ho-
mogeneous conditions, enantio-
selectivity was found to be
strongly dependent on the sol-
vent (Table 1, entries 2–4). These
observations indicate that the
superiority of the supported cat-
alyst over the homogeneous cat-
alyst at low-catalyst loading is
due to the microenvironment
provided by the support. Fur-
thermore, an effect due to ad-
sorption of a reactant on silica
gel is unlikely, because with the
Table 1. Allylic aminations according to Scheme 4 under homogeneous conditions: influence of catalyst loa-
ding.[a] Bn=benzyl, Tr = trityl.
Entry
R1 of 1
2
Solvent
ent-C1 [mol%]
t [h]
Yield [%][b]
b/l[c]
93:7
93:7
95:5
94:6
96:4
90:10
79:21
97:3
94:6
15:85
98:2
97:3
97:3
70:30
95:5
69:31
ee [%][d]
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH2OTr
CH2OTr
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
H2NCH2Ph
H2NCH2Ph
H2NPh
THF
THF
toluene
iPrOH
THF
THF
THF
THF
THF[f]
THF[f]
THF
THF
THF
THF
THF
2.32
0.42
0.42
0.42
2.32
0.42
2.32
0.42
2.32
0.42
2.32
0.42
2.32
0.42
2.32
0.42
1.2
38
41
38
1.3
47
1.1
49
1.6
43
3
89
63
65
68
88
76
80
80
86
<17[g]
89
35
88
62
75
66
96
98
80
82
91[e]
72[e]
94
74
97
94
97
93
98
97
97
78
9
10
11
12
13
14
15
16
H2NPh
benzimidazole
benzimidazole
HNBn2
HNBn2
HNBn2
55
1.9
53
2
HNBn2
THF
55
[a] Reaction conditions: carbonate 1 (0.65 mmol), nucleophile 2 (0.5 mmol), catalyst, solvent (0.6 mL), stirred,
508C. [b] Isolated yield of the branched product 3. [c] Branched/linear ratio, determined by 1H NMR spectro-
scopic analysis of the crude product. [d] Determined by HPLC analysis. [e] Determined by GC analysis using
a chiral stationary phase. [f] Reaction was performed with NEt3 (1.0 equiv) as additive. [g] Purity ca. 80%.
catalyst; reaction times at low loading of 0.42 mol% were
markedly longer (38–55 h). Selectivities were also lower than
obtained at the higher catalyst loading, except for the regiose-
lectivity of the reaction with benzylamine (entries 7 and 8 in
Table 1). The reactions did not furnish useful results with
0.1 mol% catalyst. The influence of the solvent was tested with
isopropanol, tetrahydrofuran (THF), and toluene at catalyst
loading of 0.42 mol% (entries 2–4 in Table 1). Though there
were no significant differences in reactions times, the enantio-
meric excesses of the product were lower in toluene and iso-
propanol than in THF. Notably, when aniline was used as nucle-
ophile (entries 9 and 10 in Table 1) it was necessary to add
highly polar solvent isopropanol, the reaction rate should de-
crease compared with that obtained with toluene. 4) A sup-
ported catalyst derived from the cod complex C2 gave similar
results to that derived from the dbcot complex C1 (entry 11 in
Table 2).
The substrate scope of the allylic amination promoted by
immobilized catalysts is apparent from Table 2, entries 12–23.
Again, results were generally superior to those achieved under
homogeneous conditions (Table 1). The regioselectivity with
aniline as nucleophile is particularly remarkable. Under other-
wise identical conditions, the homogeneous catalyst gave rise
to the linear product at 0.42 mol% catalyst loading (Table 1,
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with generally high enantiomeric
excess and regioselectivity were
possible in THF (Figure 2A). Re-
gioselectivity is characterized
here by Seebach’s ds value;[21]
that is, the percentage of the
major regioisomer. The first
Table 2. Substrate scope of allylic aminations according to Scheme 4 using immobilized catalysts.[a]
Entry
R1 of 1
2
Solvent
Catalyst [mol%][b] t [min] Yield
(conversion)
[%][c]
b/l[d]
ee [%][e]
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
MeN(H)Bn
H2NCH2Ph
H2NCH2Ph
H2NPh
THF
THF
THF
THF
THF
THF
THF
THF
2.32
0.8
10
66
84
89
84
81 (92)
84
98:2 98
94:6 96
93:7 99
94:6 94
94:6 97
0.42
0.22
0.11
0.05
0.42[f]
0.42[g]
ꢀ20 runs required
a reaction
75
time of only 10 min; up to run
33, conversion was complete
within 3 h, and selectivities were
undiminished, although the yield
of the final run was moderate
(57% of 3a).
180
2200
540
1380
30
60
120
15
72
35
45
40
120
90
150
30
90
40
87
19
81:19
n. d.
87 (100)
59 (69)
87 (96)
83 (88)
84 (98)
91
94:6 95
92:8 98
97:3 97
96:4 91
94:6 94
97:3 92
92:8 93
97:3 97
99:1 86
94:6 97
80:20 97
97:3 98
79:21 69
88:12 98
84:16 98
94:6 97
85:15 94
9
toluene 0.42
10
11
12
13
14
15
16
17
18
19
20
21
22
23
iPrOH
THF[k]
THF
0.42
0.42
2.32
0.42
2.32
0.42
2.32
0.42
2.32
0.42
2.32
0.42
2.32
0.42
Leaching was determined for
aliquots of the supported cata-
lyst; these were treated with
LiOTf to recover the complex C3.
The recovered material was char-
acterized with respect to purity
and amount by 31P NMR spectro-
scopic analysis. The results are
presented in Figure 2B. By using
THF as solvent, the average re-
covery of pure complex C3
along runs 1–30 was 98% per
run. It is apparent that catalyst
loss per run increases slightly
with the number of runs. Thus,
the number of possible consecu-
tive runs is limited by leaching
of the catalytically active Ir com-
plex.
THF
89
82
86
83
73
86
76
83
THF[h]
THF[i]
THF[h]
THF[h]
H2NPh
benzimidazole THF[j]
benzimidazole THF[i]
HNBn2
HNBn2
THF[h]
THF[i]
THF[h]
THF[i]
83
79
73
CH2OTr HNBn2
CH2OTr HNBn2
180
[a] Reaction conditions: carbonate 1 (0.65 mmol), nucleophile 2 (0.5 mmol), catalyst, solvent (0.6 mL), shaken at
508C. [b] [Si-TsO/ent-C1–38.9 mmolgÀ1] and [Si-TsO/ent-C1–10.6 mmolgÀ1] were used in reactions with 2.32 and
1
0.42 mol% catalyst, respectively. [c] Conversion (the sum of 3 and 4) was determined by H NMR spectroscopic
analysis of the crude product by using an internal standard; yield of isolated branched product 3.
[d] Branched/linear ratio, determined by 1H NMR spectroscopic analysis of the crude product. [e] Determined
by chiral HPLC or by GC analysis (entries 12 and 13). [f] Reaction was performed with 1a (0.50 mmol), ent-C1
(0.42 mol%), and [Si-TsO/HNEt3] (200 mg) as additive. [g] Reaction was performed with 1a (0.50 mmol), ent-C1
(0.4 mol%) and silica gel (200 mg) as an additive. [h] Additive NEt3 (1.0 equiv). [i] Additive NEt3 (0.5 equiv).
[j] Additive NEt3 (2.0 equiv). [k] The supported catalyst was prepared from complex C2 to give [Si-TsO/C2-
10.5 mmolgÀ1].
entry 10), whereas the supported catalyst furnished the
branched isomer (Table 2, entry 17). With a view to the catalyt-
ic cycle given in Scheme 2, this result indicates that proton re-
moval from species D is faster at the support than in solution.
Rate profiles are presented in Figure 1. Comparison of reac-
tion times at 50% conversion indicates that, at a loading of
0.42 mol%, the reaction promoted by the supported catalyst is
faster than the reaction under homogeneous conditions by
a factor of 24. Fitting of the curves assuming formation of the
products according to a first order rate equation gave a factor
of 33.
Recycling of immobilized catalysts and catalyst loss
Recyclability is of prime importance for an immobilized cata-
lyst. We have investigated this aspect by using the reaction of
carbonate 1a with N-methyl-benzylamine (2a) (cf. Scheme 4).
Note that although complex C1 is the initial catalyst, during
the reaction C1 is transformed into complex C3, which consti-
tutes the resting state and is recovered (cf. Scheme 2). THF
and toluene were used as solvents. First a high catalyst loading
of 2.4 mol% was employed. Up to 33 consecutive aminations
Figure 1. Kinetic profiles of reactions of 1a with 2a promoted with homoge-
neous and immobilized catalysts (solvent: THF). Reaction conditions: a solu-
tion of carbonate 1a (0.65 mmol), nucleophile 2a (0.5 mmol) and catalyst in
solvent (0.6 mL) was reacted at 508C. Conversion was measured by GC anal-
ysis using hexamethylbenzene as internal standard (see the Supporting In-
formation).
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Figure 2. Yields and selectivities achieved in consecutive reactions of 1a
with 2a; initial catalyst loading: 2.4 mol%, solvent: THF, initial catalyst: [Si-
TsO/ent-C1-39.8 mmolgÀ1]. A) Conversion, yield and selectivities. The ds value
is used as a measure of regioselectivity. B) Amount of catalyst on support
(mmol ent-C3 per gram of support) and loading (mol%) for every third ami-
nation run (solvent THF).
Figure 3. Consecutive reactions of 1a (0.65 mmol) with 2a (0.5 mmol), initial
catalyst loading of 0.42 mol% (solvent: THF, initial catalyst: [Si-TsO/ent-C1–
10.6 mmolgÀ1]). A) Conversion, yield and selectivities. B) Kinetic profiles (con-
version was determined by GC analysis using an internal standard, cf.
Figure 1).
A second recyclability test was performed with a catalyst
loading of 0.42 mol% and THF as solvent. It was possible to
carry out eight consecutive runs without change of regio- or
enantioselectivity (Figure 3). Yields of more than 70% were
achieved up to run seven. In another set of consecutive reac-
tions, 11 runs were achieved with more than 80% yield up to
run 10 (see the Supporting Information). Reaction rate profiles
are given in Figure 3B.
number of runs. This result indicates that several processes
contribute to loss of catalyst.
The “split test”[22] can be used to detect whether a catalytical-
ly active species is present in the solution phase during a reac-
tion catalyzed with a solid catalyst. This test was conducted as
follows. The standard allylic reaction of 1a with 2a was carried
out by using [D8]THF as solvent and catalyst loading of
2.32 mol%. After conversion of 70% had been reached,
a sample of the supernatant was filtered into an NMR tube
and analyzed by 1H NMR spectroscopy. A very slow reaction
was found at 508C (6% conversion over a period of 45 h),
whereas the reaction in the flask with immobilized catalyst
reached 96% conversion within 10 min.[23] This result is inter-
esting with respect to the mechanism of the allylic substitution
(cf. Scheme 2). Allylic amination is usually carried out with an
excess of the amine; in that case, the uncharged olefin com-
plex E is found as resting state. This complex does not bind to
the support and would be lost in consecutive runs. As pointed
Loss of catalyst is expected to be a function of solvent polar-
ity. In case of predominant electrostatic bonding of the catalyst
to the support, loss of the catalyst is expected to decrease
upon lowering of solvent polarity. Accordingly, we have stud-
ied another series of consecutive reactions of carbonate 1a
with amine 2a using toluene as solvent (Figure 4). Indeed,
43 runs were accomplished at catalyst loading of 2.4 mol%;
yields were high up to the 30th run (Figure 4A). Recovery of
98.4% of ent-C3 per run was achieved over 41 runs (Figure 4B).
As with solvent THF, catalyst loss per run increased with the
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played considerably enhanced activity compared with the
parent homogeneous catalysts. Up to 43 consecutive amina-
tion runs were possible in recycling experiments. Preparation
of the catalysts is facile.
Experimental Section
General methods
For spectroscopic and other measurements, as well as chromato-
graphic methods, see the Supporting Information. All reactions
were carried out under an atmosphere of argon in glassware that
was washed several times with demineralized water and dried.
Most reactions were carried out by using complexes C1 or ent-C1.
Only these complexes are included in the general procedures; ex-
periments using C2 or C3 are presented in the tables and the text.
When working with supported catalysts, magnetic stirring was
avoided. The standard reaction vessel was a Schlenk tube with an
externally attached magnet (see the Supporting Information). This
was moved by a magnetic stirrer. Anhydrous THF, diethyl ether, tol-
uene, dichloromethane, and acetonitrile were purchased from
Sigma–Aldrich (Chromasolv) and taken from a solvent purification
system (MBraun, MB SPS-800, filter material: MB-KOL-A, MB-KOL-M;
catalyst: MB-KOL-C). Amine nucleophiles were distilled prior to use.
Silica gel containing carbon-bound p-ethylbenzenesulfonic acid
[ISOLUTE Si-TsOH (SCX-3), 0.59 mmolgÀ1] was purchased from Biot-
age GB Ltd.[24] Ir-complexes C1, C2, and C3 (and enantiomers) were
prepared as reported.[16,5] The syntheses and spectroscopic data of
the following allylic substrates and branched allylic amines have
been reported: 1a,[25] 1b,[25] 1c,[26] 3ab,[4] 3ac,[4] 3ad,[27] and 3ae.[28]
Preparation of [Si-TsO/NHEt3]: general procedure (GP1)
Si-TsOH (“Biotage”, 1.8 g, 0.59 mmolgÀ1) was mixed with excess
NEt3 (15 mL) by slow rotation in a rotary evaporator over a period
of 8 h at RT. The excess of NEt3 was then removed carefully by
using a syringe, and the silica gel was dried under vacuum at RT
for 48 h.
Figure 4. Consecutive reactions of 1a with 2a, initial catalyst loading of
2.4 mol% (solvent: toluene, initial catalyst: [Si-TsO/C1-39.8 mmolgÀ1]).
A) Yield and selectitivities. B) Amount of catalyst on support (mmol ent-
C3per gram of support) and loading (mol%) for every third amination run
(solvent toluene).
Preparation of supported catalysts [Si-TsO/C1-n]: general
procedure (GP2)
out above, we used an excess of the allylic electrophile to
ensure that allyl complex C constitutes the resting state, be-
cause the rate of the steps E!C (via B and C) is higher than
that of the steps C!D!E. The fact that residual catalytic ac-
tivity persists in solution demonstrates that olefin complex E is
present in low concentration. This type of product inhibition is
likely the reason for leaching.
See Scheme 3 for formulas and designation. In an oven-dried
Schlenk tube (washed several times with distilled water to remove
inorganic salts), a suspension of [Si-TsO/NHEt3] (see GP1) in a solu-
tion of C1 in acetone (degassed) was shaken by hand for 3 min
under an atmosphere of argon at RT. Distilled water (degassed)
was then added and shaking was continued for a further 5 min. At
this point, the solid phase became yellow and the supernatant
became colorless. The supernatant was then removed carefully by
using a syringe, and the silica gel was washed successively with de-
gassed acetone (3”2 mL) and degassed n-hexane (3”2 mL). Final-
ly, the silica gel was dried under vacuum at RT overnight to give
the supported catalyst. The combined liquid phases were filtered
through a short silica gel column to recover the excess of C1. The
amount of C1 on the solid support was determined by the differ-
ence between the initial and recovered amounts of C1.
Conclusions
The asymmetric Ir-catalyzed allylic amination is an established
reaction, which has found numerous applications. Still prob-
lematic is the currently employed catalyst loading of 1–
4 mol% of iridium. In an effort to substantially reduce catalyst
loading, we have investigated catalysts immobilized by ionic
bonding. Stable cationic (p-allyl)Ir complexes are readily avail-
able, and they are useful single-species catalysts. The support-
ed catalysts were prepared by binding these species to a modi-
fied silica gel by cation exchange. The supported catalysts dis-
Preparation of [Si-TsO/C1–10.6 mmol per g of support]
According to GP2, [Si-TsO/NHEt3] (1.0 g) was treated with a solution
of C1 (15 mg, 12.5 mmol) in acetone/water (1:2, 5.1 mL). The sup-
ported catalyst was washed with acetone and n-hexane and dried
Chem. Eur. J. 2015, 21, 7127 – 7134
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overnight in high vacuum to obtain [Si-TsO/C1–10.6 mmol per g of
support].
drous Na2SO4, filtered, and the solvent was removed in vacuo.
Quantitative 31P NMR spectroscopic analysis was carried out with
[D8]THF as solvent and C1 as internal standard.
Preparation of [Si-TsO/ent-C1–38.9 mmol per g of support]
According to GP2, [Si-TsO/NHEt3] (1.0 g) was treated with a solution
of ent-C1 (63.3 mg, 52.8 mmol) in acetone/water (1:2, 10 mL). The
supported catalyst was washed with acetone and n-hexane, and
dried overnight in high vacuum to obtain [Si-TsO/ent-C1–38.9 mmol
per g of support].
Acknowledgements
We thank Drs. Mascha Jäkel and Jianping Qu of our group for
samples of the catalysts, Professor Klaus Ditrich (BASF SE) for
enantiomerically pure 1-arylethylamines, and Professor Oliver
Trapp, this institute, for fitting the curves of Figure 1 according
to a first-order rate equation.
Allylic amination using a nonsupported catalyst: general
procedure (GP3)
In a dried Schlenk tube, a solution of C1 (0.42–2.32 mol%) in an
appropriate solvent (0.6 mL) was prepared under an argon atmos-
phere. Carbonate 1 (0.65 mmol), and possibly a base (NEt3, 0.5–
1.0 equiv, unless otherwise indicated) were then added, and the
mixture was stirred for 5 min at RT. Amine 2 (0.5 mmol) and possi-
bly hexamethylbenzene (0.5 mmol) as an internal standard were
added, and the reaction mixture was stirred at 508C. Conversion
was monitored by TLC (petroleum ether/ethyl acetate; KMnO4).
When complete conversion of the nucleophile was reached, the re-
action mixture was concentrated in vacuo. The ratio of regioisom-
ers as well as final conversion were determined by 1H NMR spectro-
scopic analysis of the crude product. The residue was then subject-
ed to flash chromatography on silica gel (petroleum ether/ethyl
acetate) to give the corresponding pure branched and linear prod-
ucts. For the determination of kinetic profiles (Figure 1), samples
were analyzed by GC using hexamethylbenzene as internal stan-
dard (see the Supporting Information for details).
Keywords: allylic compounds
catalysis · iridium · supported catalysts
· amination · asymmetric
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Allylic amination using a supported catalyst [Si-TsO/C1-n]:
general procedure (GP4)
In a heat-gun-dried Schlenk tube (free of soluble inorganic salts),
a suspension of [Si-TsO/C1-n], carbonate 1 (1.3 equiv), and possibly
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washed with anhydrous degassed solvent (4”3 mL) and dried. The
combined liquids were concentrated in vacuo, and the ratio of re-
1
gioisomers as well as final conversion were determined by H NMR
spectroscopic analysis of the crude product. The residue was sub-
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GC using hexamethylbenzene as internal standard (see the Sup-
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Catalyst deactivation was assessed by recovery of a catalytically
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Published online on March 18, 2015
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7134
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