Gold catalysis in micellar systems

Article abstract of DOI:10.1002/anie.201101396

Micelles to the rescue: Two amphiphiles are shown to afford air-stable aqueous gold catalyst solutions with excellent reactivity and recyclability. Various α-functionalized allenes can be cycloisomerized smoothly and efficiently with this system at room t

Full text of DOI:10.1002/anie.201101396

Communications
DOI: 10.1002/anie.201101396
Gold Catalysis
Gold Catalysis in Micellar Systems**
Stefan R. K. Minkler, Bruce H. Lipshutz,* and Norbert Krause*
Nowadays, preparative transformations are not only judged
by efficiency and stereoselectivity, but also in terms of safety
and economic and environmental sustainability.[1] It is man-
datory to optimize the use of valuable reagents, recycle
precious catalysts, and employ environmentally friendly
reaction media. In this context, water offers many advantages,
but its use is often hampered by the poor solubility of
nonpolar organic substrates and the limited stability and/or
reactivity of many transition-metal or organocatalysts. An
elegant strategy to solve these issues is micellar catalysis.[2]
Micelles formed by addition of amphiphiles to an aqueous
reaction medium allow the solubilization of both unpolar and
polar substrates, reagents, and catalysts as they exhibit a
hydrophilic surface as well as a hydrophobic core. Moreover,
a high local concentration of the reactants in the nanometer-
sized micelles leads to accelerated transformations and
increased selectivities. Compared to traditional “soaps”, the
vitamin E derived amphiphiles PTS and TPGS (Scheme 1)
In homogeneous gold catalysis,[8] recycling of the gold(I)
or gold(III) catalyst is particularly difficult as it is easily
reduced to (catalytically inactive) metallic gold.[9] The few
examples of recyclable gold catalysts take advantage of
stabilization by ionic liquids[10] or a porphyrin ligand.[11] We
now present the first example of gold catalysis in micellar
systems using PTS or TPGS-750-M as the amphiphile, which
afford gold catalysts with excellent reactivity and recycla-
bility.
Based on our interest[12] in the gold-catalyzed cyclo-
isomerization of functionalized allenes,[13] we started our
investigation with the a-hydroxallenes 1a–d. Treatment of
these allenes with 5 mol% of AuBr3 in a 5% aqueous PTS-
solution under air for 1 h at room temperature afforded the
2,5-dihydrofurans 2a–d[14] in 42–88% yield (Table 1,
entries 1–4). Not surprisingly,[15] the unprotected a-amino-
allene 1e was very unreactive under these conditions (Table 1,
entry 5), whereas the tosylated aminoallene 1 f gave pyrroline
2 f in 60% yield (Table 1, entry 6). The former result is due to
deactivation of the gold catalyst by the Lewis basic amine. All
cycloisomerizations took place with full axis-to-center chir-
ality transfer. Under the same conditions, but without PTS,
the yield of dihydrofuran 2d was only 42%, whereas the
cyclization of aminoallene 2 f did not proceed at all. Other
catalysts (AuCl, AgNO3) were less efficient.
Scheme 1. The structures of poly(oxyethyl)-a-tocopheryl sebacate (PTS;
m=4, nꢀ13, R=H) and d-a-tocopherol-polyethyleneglycol-750-succi-
nate monomethyl ether (TPGS-750-M; m=1, nꢀ17, R=Me).
Table 1: The gold-catalyzed cycloisomerization of a-functionalized
allenes 1 in PTS/water.
offer outstanding properties in terms of reactivity, selectivity,
and catalyst recycling in many transition-metal-catalyzed
transformations,[3] including olefin metathesis,[4] Heck reac-
tions,[5] and Suzuki–Miyaura[6] and Negishi couplings.[7]
Entry
1
R1
R2
R3[a]
X
2 (Yield [%])
1
2
3
4
5
6
1a
1b
1c
1d
1e
1 f
iPr
H
H
H
H
nBu
nBu
Bn
Bn
Bn
TBS
TBS
TBS
O
O
O
O
NH
NTs
2a (42)
2b (62)
2c (48)
tBu
nBu
nBu
H
2d (88)[b]
2e (10)[c]
2 f (60)[d]
[*] S. R. K. Minkler, Prof. Dr. N. Krause
Organic Chemistry, Dortmund University of Technology
Otto-Hahn-Strasse 6, 44227 Dortmund (Germany)
Fax: (+49)231-755-3884
E-mail: norbert.krause@tu-dortmund.de
Homepage: chemie.tu-dortmund.de/groups/krause/index.html
H
[a] TBS=tert-butyldimethylsilyl. [b] 42% yield of 2d in the absence of
PTS. [c] Reaction time 24 h. [d] No conversion in the absence of PTS.
Prof. Dr. B. H. Lipshutz
Department of Chemistry & Biochemistry, University of California
Santa Barbara, CA 93106 (USA)
Fax: (+1)805-893-8265
Even though these initial results show the feasibility of
gold catalysis in micellar systems, optimization of the reaction
conditions is required. It is known that the size of PTS-derived
micelles can be strongly increased in the presence of NaCl,
leading to faster reactions in cross-coupling and ring-closing
olefin metathesis.[3] To establish whether this effect can also
be utilized in gold catalysis, dynamic light scattering (DLS)
measurements of a 2% aqueous PTS solution were carried
E-mail: lipshutz@chem.ucsb.edu
[**] We thank Dr. ꢀzge Aksin-Artok (Izmir Institute of Technology,
Turkey) for the ICP-MS analyses and Prof. Dr. Heinz Rehage
(Dortmund University of Technology) for his support in the DLS
measurements.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201101396.
7820
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 7820 –7823

Table 2: The effect of salt concentration on the gold-catalyzed cyclo-
isomerization of allenol 1g in PTS/water.
Entry
AuBr3 (mol%)
[NaCl]
t [min]
Yield [%]
1
2
3
4
5
6
5
5
5
5
2
1
0m
1m
2m
3m
3m
3m
45
30
20
10
20
30
80
88
86
88
88
84
Figure 1. The effect of salt concentration on the average diameter of
PTS-derived micelles according to dynamic light scattering (DLS)
measurements.
out, and they showed a strong effect of NaCl on the
Table 3: Gold-catalyzed cycloisomerization of a-functionalized allenes 1 in the
micelle size (Figure 1). The average diameter
increased from about 10 nm in fresh water to about
100 nm with 3m NaCl.[16] Interestingly, a higher
temperature also leads to larger micelles. This
effect should allow more catalyst and substrate to
migrate into the micellar reaction chamber, resulting
in faster conversions. Indeed, the time required for
complete conversion of allenol 1g to 2,5-dihydro-
furan 2g in 2% aqueous PTS decreases from 45 min
at ambient temperature (no NaCl) to just 10 min
with 3m NaCl (Table 2, entries 1–4). Even with lower
catalyst loadings of 2 or 1 mol% AuBr3, the reactions
are still faster than in the absence of salt (Table 2,
entries 5 and 6 versus 1). High yields (80–88%) were
obtained in all cases.
Under these optimized conditions, various a-
hydroxy- and a-aminoallenes were converted into
the corresponding heterocycles in high yields within
10–80 minutes at room temperature in air (Table 3).
The reaction tolerates the presence of acid-sensitive
TBS ethers (Table 3, entries 1, 4, 7–10) as well as
ester groups (Table 3, entry 3) and sulfonamides
(Table 3, entries 4–6). Compared to the correspond-
presence of PTS or TPGS-750-M and NaCl.
Entry
1
R1
R1
R3
X
AuBr3
Amphiphile t [min] 2 (Yield [%])
[mol%]
1
2
3
4
5
6
7
8
1d nBu
1h Ph
1i tBu
H
H
H
TBS
Bn
Ac
O
O
O
2
2
2
2
2
2
1
1
1
1
1
1
1
1
PTS
PTS
PTS
PTS
PTS
PTS
PTS
30
40
40
60
80
60
70
2d (88)
2h (84)
2i (90)
2 f (76)
2j (82)
2k (87)
2g (82)
2g (88)
2l (86)
2l (92)
2b (84)
2b (85)
2c (83)
2c (78)
1 f
1j
1k
H
H
H
nBu TBS NTs
Ph Bn NTs
iPr Bn NTs
1g Ph
1g Ph
1l iPr
1l iPr
1b tBu
1b tBu
1c nBu
1c nBu
H
H
H
H
H
H
H
H
TBS
TBS
TBS
TBS
Bn
Bn
Bn
Bn
O
O
O
O
O
O
O
O
TPGS-750-M 40
PTS 30
TPGS-750-M 10
PTS 60
TPGS-750-M 60
PTS 80
TPGS-750-M 70
9
10
11
12
13
14
ing allenols, tosylated a-aminoallenes react slower, but give
similar yields (Table 3, entries 4 and 5 versus 1 and 2).
Even though the differences in structure between the
amphiphiles PTS and TPGS-750-M are small (Scheme 1), the
micelles formed in water have a different size and shape.
Cryo-TEM experiments for PTS revealed a mixture of
spherical micelles and wormlike structures, whereas TPGS
give larger particles.[5] Thus, different properties in transition-
metal-catalyzed reactions are expected.[3] Indeed, the cyclo-
isomerization of the allenols 1g and 1l bearing a TBS ether
proceed faster and with higher yield in the presence of TPGS-
750-M (Table 3, entries 8 and 10 versus 7 and 9); in the case of
substrate 1l, only 10 minutes at room temperature were
required to afford product 2l in 92% yield (Table 3, entry 10).
Interestingly, this difference is not observed for the benzyl-
oxy-substituted a-hydroxyallenes 1b and 1c (Table 3,
entries 11–14).
be insoluble in aqueous PTS. To convert this substrate into
dihydrofuran 4, it was stirred strongly in a 2% aqueous PTS
solution containing NaCl (3m) for 30 minutes before AuBr3
(2 mol%) was added. Under these conditions, it took 1 h at
room temperature for complete conversion to afford product
4 in 85% yield (Table 4, entry 1).
With allene 3, we also examined the recyclability of the
micellar gold catalyst. After extraction of the product with n-
hexane, a decreased reactivity was observed; this decrease is
probably due to diffusion of n-hexane into the micelles, which
leaves less room for the substrate. This problem can be solved
either by removal of excess n-hexane under reduced pressure
or (preferably) by extending the time for phase separation. In
the latter case, addition of fresh substrate to the micellar gold
catalyst solution afforded product 4 in high yield and an only
slightly longer reaction time (Table 4, entries 2–4). This result
demonstrates the high stability of the gold catalyst in the PTS
micelles.
Whereas most a-functionalized allenes studied so far are
oily or liquid and seem to have an appreciable solubility in the
aqueous reaction medium, the allenol 3 is solid and appears to
The recyclability of the micellar gold catalyst was further
demonstrated for the acyclic a-hydroxyallene 1g and the
Angew. Chem. Int. Ed. 2011, 50, 7820 –7823
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7821

Communications
Table 4: Recycling of the AuBr3/PTS-catalyst solution in the cycloiso-
merization of allenol 3.
and induces faster reactions. The reaction tolerates the
presence of TBS ethers, ester groups, and sulfonamides. For
certain substrates, TPGS-750-M offers advantages in terms of
reactivity and product yield compared to PTS. The recycling
of the micellar gold catalyst solution is possible without
compromising reactivity and efficiency by extraction of the
product with n-hexane. Moreover, the PTS-derived catalyst
shows a very low leaching of only 0.29% over 4 runs. We are
continuing to study further applications of this environ-
mentally benign and sustainable micellar catalyst system.
Entry
Run
t [min]
Yield [%]
1
2
3
4
1
2
3
4
60
70
70
70
85
86
84
88
Experimental Section
Representative reaction of 1 to 2: In a vial, allene 1l (50.0 mg,
185 mmol) was dissolved in a 2% aqueous TPGS-750-M solution
(1.5 mL) containing NaCl (263 mg, 3m) and treated with AuBr3
(0.8 mg, 1.85 mmol) under air. After complete conversion (10 min,
monitored by TLC), the reaction mixture was extracted with n-
hexane. The solvent was removed under reduced pressure and the
crude product was purified by flash column chromatography (SiO2,
cyclohexane/ethyl acetate = 10:1) to afford 46.2 mg (92%) of 2,5-
dihydrofurane 2l as a yellow oil.
aminoallene 1j (Table 5). For both substrates, consistently
high yields of the heterocycles 2g (88–91%) and 2j (80–83%)
were achieved in 4 runs under air. As for allene 3, a small drop
of the catalyst reactivity was observed after the first run.
Table 5: Recycling of the AuBr3/PTS-catalyst solution in the cycloiso-
merization of allenes 1g/j.
Received: February 24, 2011
Published online: July 1, 2011
Keywords: allenes · gold catalysis · heterocycles · micelles ·
.
sustainability
Entry
Run
1
t [min]
2 (Yield [%])
Leaching[a]
1[a]
2[a]
3[a]
4[a]
5
6
7
8
1
2
3
4
1
2
3
4
1g
1g
1g
1g
1j
1j
1j
1j
40
50
50
50
80
100
100
100
2g (88)
2g (91)
2g (88)
2g (88)
2j (82)
2j (83)
2j (82)
2j (80)
0.08%
0.10%
0.07%
0.04%
–
–
–
–
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