Metathesis in pure water mediated by supramolecular additives

Article abstract of DOI:10.1002/adsc.200800637

Supramolecular, water-soluble additives based on calix[n] arenes exhibit a beneficial influence on the ring-closing and cross metathesis of non-polar substrates in pure aqueous medium using standard Grubbs-II and Hoveyda-II catalysts. The catalytic activi

Full text of DOI:10.1002/adsc.200800637

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DOI: 10.1002/adsc.200800637
Metathesis in Pure Water Mediated by Supramolecular Additives
Thomas Brendgen,a Tilmann Fahlbusch,a Markus Frank,a Daniel T. Schꢀhle,a
Miriam Seßler,b and Jꢀrgen Schatza,b,*
a
Division of Organic Chemistry 1, University of Ulm, Albert-Einstein-Allee 11, 89018 Ulm, Germany
Organic Chemistry 1, Department of Chemistry and Pharmacy, University of Erlangen-Nꢀrnberg, Henkestr. 42,
b
91054 Erlangen, Germany
Fax : (+49)-9131-85-24707; phone: (+49)-9131-85-25766; e-mail: juergen.schatz@chemie.uni-erlangen.de
Received: October 16, 2008; Published online: February 2, 2009
Abstract: Supramolecular, water-soluble additives
based on calix[n]arenes exhibit a beneficial influ-
ence on the ring-closing and cross metathesis of
non-polar substrates in pure aqueous medium using
standard Grubbs-II and Hoveyda-II catalysts. The
catalytic activity observed in water is virtually the
same as that in pure methanol. Quantitative yields
of metathesis product can be achieved under mild
aerobic conditions in/on water by (micro)solubiliza-
tion of both the catalyst and starting materials by
the macrocycles.
Keywords: calixarenes; green chemistry; metathe-
sis; supramolecular chemistry; water
In recent years, alkene metathesis has developed to a
very valuable, reliable, and widely used methodology,
which has significantly increased the organic chemists
“synthetic tool-box”.[1] Although at a very high stage
of development, there is still a considerable necessity
for improved methods in terms of more efficient cata-
lysts,[2] or novel, sustainable concepts.[3]
Scheme 1. Used catalysts and test reactions.
In a previous study we could show that water-solu-
ble macrocycles can enhance the efficiency of Suzuki
Many target molecules of biological relevance are coupling reactions of aryl chlorides in pure water
mainly soluble in aqueous solution. Therefore, there without hampering preparative features such as ex-
is a substantial interest in methodologies for aqueous traction of organic, non-polar products from the aque-
metal organic chemistry[4] and especially Grubbs-type ous phase. Therefore, we intended to explore this
reactions.[5] Here, previous studies have focused on family of compounds for use in metathesis applica-
the design of water-soluble Grubbs-type catalysts,[6] tions.[15] Especially sulfonato- and imidazolio-calix-
polymer-,[7] or membrane-bound catalytic systems,[8]
ACHTUNGTRENNUNG
Even catalysis in aqueous media is possible just by both the catalysts 1a or 1b, respectively, and the ole-
the use of commercially available Grubbs (1a) and finic substrates.
Hoveyda catalysts (1b) (Scheme 1).[12,13] However,
To test the influence of supramolecular additives
reasonable yields are still only available in those cases onto the RCM of tosylamine 2 under standard condi-
where co-solvents such as DME or acetone are added tions, ammonium calixarene 8, calixarene 12a, the
to a high extent.[14]
non-cyclic compound 11, and sulfonated calix-
Adv. Synth. Catal. 2009, 351, 303 – 307
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Thomas Brendgen et al.
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Table 1. Yields of the RCM of 2 using Grubbs-II catalyst 1a
(5 mol%).[a]
Entry
Solvent
Additive
Yield 3 [%]
1
MeOD
MeOD
MeOD
MeOD
MeOD
MeOD
MeOD/D2O (1:1)
D2O
–
79
<3
<3
54
56
38
36
75
2[b]
3[b]
4[b]
5[b]
6[b]
7
7b
7c
8
11
12a
–
8
–
[a]
Reaction conditions: 4 h and room temperature, 5 mol%
catalyst and additive.
Reaction mixture was shaken hourly for 30 seconds and
was placed directly in an NMR tube to determine the
conversion.
[b]
ments using supramolecular additives in pure water
instead of mixtures.
Pure aqueous solutions, containing 5 mol% addi-
tive, served as reaction media for RCM as well as CM
reactions (Table 2, Figure 1 and Figure 2). In first ex-
periments, it was found that casual shaking of the re-
action vessels yields tend to be somewhat lower than
yields obtained by stirring at rates 1000–1400 minꢀ1.
Therefore, all reactions mixtures were stirred at a
constant stirring rate of 1000 minꢀ1 unless otherwise
stated.
Scheme 2. Used additives for the RCM to yield 3 and 5, re-
spectively (dip=2,6-diisopropylphenyl).
Table 2. Yields and E/Z ratio for metathesis reactions in
water.[a]
Entry Additive Yield 3 [%] Yield 5 [%] E/Z ratio (5)
ACHTUNGTRENNUNG[6,8]arenes 7b, c were added to all reaction compo-
1
2
3
4
5
6
7
8
–
75
n.d.[b]
72
35
99
99
99
90
45
44
60
18
11
12
9
44
31
39
27
26
24
23
37
50
36
30
26
54
24
49
24
14
16:1
17:1
20:1
15:1
12:1
16:1
18:1
14:1
18:1
16:1
13:1
16:1
21:1
15:1
22:1
28:1
11:1
nents in MeOH-d4 as an organic solvent (Scheme 2).
Using the highly active Hoveyda–Grubbs-II catalyst
(1b) nearly no influence on the catalytic activity could
be observed. In all cases after 4 h yields well above
90% were observed. Surprisingly, in case of the stan-
dard Grubbs-II catalyst 1a the RCM of 2 is retarded
by the cationic species 8 and 11 (Table 1, entries 4
and 5) and calixarene 12a (entry 6) and nearly totally
6a
6b
6c
7a
7b
7c
7d[c]
8
9
10
11
12
13
14
15
16
17
9
inhibited using sulfonated calixACTHNUTRGNEUNG[6,8]arenes 7b, c (<3%
10
11
12a
12b
12c
13
14
yield of RCM product, entries 2 and 3)! Here, one
might assume a ligation of the catalytic species by the
sulfonate anion reducing the catalytic ability.
The activity of Grubbs catalyst 1a in different sol-
vent mixtures has been briefly explored as shown in
Table 1 (entries 1, 7, and 8). These observations are in
line with data obtained by Blechert and co-workers
for the metathesis in methanol and methanol/water
mixtures indicating that the catalytic ability is re-
gained with increasing water content.[19] Using water
as sole solvent, basically the same catalytic perfor-
mance can be observed as in pure methanol. These
findings intrigued us to perform all further experi-
30
86
[a]
Reaction conditions: for 3: 4 h, room temperature, cata-
lyst=Grubbs-II (1a); for 5: 24 h, 458C, catalyst=
Hoveda-II (1b); in all cases 5 mol% catalyst and addi-
tive. Errors in yields are usually <2%.
Not detected owing to signal overlap of cyclodextrin and
starting material.
[b]
[c]
30 mol% additive.
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Metathesis in Pure Water Mediated by Supramolecular Additives
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zation of organic compounds, whereas without addi-
tive, only 75% RCM product 3 was observed. The ad-
dition of sulfocalixarenes enhances both the catalytic
activity and solubility of the catalyst in polar media.
This advantageous effect is also visible, because the
reaction is no longer heterogeneous, but becomes
pseudo-homogeneous (Figure 1). It is noteworthy that
because of “cavity effects” sulfocalixarenes are actual-
ly somewhat superior additives than the monomeric
building block, benzenesulfonate 7d. Compared to the
RCM without any additives, we observed that adding
5 mol% of the hydroxyimidazolium 3-oxide salt 14
also led to higher conversions for 2!3 (86%). How-
ever, this positive effect is reversed using the Hovey-
da-II (1b, 14% yield 5) instead of the Grubbs-II cata-
lyst (1a). To the best of our knowledge, this is the first
example where such oxy-imidazolium salts – potential
precursors for N-heterocyclic carbenes – are used in
metathesis reactions.[20] Currently, we are trying to
synthesize Grubbs-type catalysts containing NHCs
based on hydroxyimidazolium 3-oxides to test wheth-
er such ruthenium complexes exhibit inherently
higher catalytic activity and to gain a deeper insight
into these novel NHC precursors.
Figure 1. Reaction vials without any additive (left), with sul-
focalix[6]arene 7b (right).
Surprisingly, we found the highest conversions of
In contrast to RCM reactions, where anionic, sulfo-
99% using sulfocalixarenes 7a–c as additives, possibly nated calix[n]arenes were the additive of choice, the
because of the beneficial influence of (micro)solubili- highest levels of conversion in CM reactions could be
Figure 2. Yields for metathesis reactions.
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Thomas Brendgen et al.
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observed with cationic, imidazolio-substituted calixar- catalyst under very mild, aerobic conditions with high
enes 12a/12c or with the ammonium calixarene 8. The levels of conversion!
achieved higher conversion, when adding 12a or 12c
in comparison to the open-chain compound 11 indi-
cates that cavity effects are not insignificant. This is Experimental Section
also mirrored by the influence of these additives onto
the E/Z ratio. Instead of a ca. 15:1 ratio observed Representative Procedures for Metathesis Reactions
without or with open chain additives 7d, 11 (Table 2, in D2O
entries 8 and 12), imidazoliocalix[4]arenes enhance
the formation of the linear E-isomer up to an E/Z
RCM of 2: A mixture of the catalyst 1a (1.90 mmol, 5
mol%), a supramolecular additive (1.90 mmol, 5 mol% to
ratio of ca. 22:1. Furthermore, it was found that the
formation of homodimer 5 was less favoured when
adding 12b, presumably due to steric effects.
In a search for efficient water-soluble substrates we
have tested the compounds 15–17 (Table 3), mostly
substrate), when applicable, and the substrate 2 (38 mmol) in
850 mL D2O as the solvent was stirred for 4 h at room tem-
perature at a constant stirring rate of 1400 minꢀ1. An aliquot
(150–200 mL) was withdrawn, diluted with MeOD to 600 mL,
1
and directly analyzed by H NMR spectroscopy.
CM of 4: A mixture of the catalyst 1b (6.38 mmol, 5
mol%), a supramolecular additive (6.38 mmol, 5 mol% to
substrate), when applicable, and allylic alcohol (128 mmol)
in 850 mL D2O as the solvent was stirred for 24 h at 458C at
a constant stirring rate of 1000 minꢀ1. After 24 h, the reac-
tion mixture was placed in an NMR tube and the conversion
Table 3. RCM of water-soluble substrates 15, 16 and 17 in
D2O.[a]
1
was determined by H NMR spectroscopy.
All yields and E/Z ratios reported were reproduced 2–5
times and the yields determined by NMR spectroscopy cor-
relate reasonably with yields obtained in conventionally
worked-up runs.
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