Olefin metathesis in non-degassed solvent using a recyclable, polymer supported alkylideneruthenium

Article abstract of DOI:10.1039/b007304k

Polystyrene-supported ruthenium complex 8 is a robust procatalyst for olefin metathesis that can be used in non-degassed solvents and recycled without added stabilisers.

Full text of DOI:10.1039/b007304k

Olefin metathesis in non-degassed solvent using a recyclable, polymer
supported alkylideneruthenium†
James Dowden* and Jelena Savovic´
Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath,
Claverton Down, Bath, UK BA2 7AY. E-mail: J.Dowden@bath.ac.uk
Received (in Liverpool, UK) 6th September 2000, Accepted 16th November 2000
First published as an Advance Article on the web 11th December 2000
Polystyrene-supported ruthenium complex 8 is a robust pro-
catalyst for olefin metathesis that can be used in non-
degassed solvents and recycled without added stabilisers.
metathesis.10 This is reflected in the fact that treatment of resin
7 with stoichiometric Grubb’s complex afforded loadings of
only 0.12 mmol g21 (as determined by phosphorus analysis),
while treating the resin with five successive portions of 10
Recent enthusiastic interest in olefin metathesis has been fuelled
by the development of well-defined transition metal catalysts.1
These catalysts have found wide application because they
provide facile alkene exchange, often late in a synthetic
sequence.2 Grubb’s alkylideneruthenium 13 is particularly
mol% of 1 essentially doubled the loading to 0.20 mmol g21
.
Simple filtration and washing of the resin gave 8 as dark brown
beads that could be dried, stored in air and used more than a
month later with no apparent decrease in activity. In all cases no
colour change, or corresponding decomposition was observed
during the loading of the catalyst8 even after extended reaction
times.
Polymer-supported complex 8 was then tested for activity
using representative diene substrates for ring closing metathesis
(Table 1). It is notable that the rates of reaction were somewhat
slower than those reported using homogenous Grubb’s alkyli-
dene 1, so that reaction of benchmark substrates such as diethyl
diallylmalonate (entry 2) was only 42% complete after 90 min.
All of these reactions however, provided good to quantitative
yield of product within 5 h. Preparative scale transformation
(153 mg, 5 mol%, 4 h) of benzyl N,N-diallylcarbamate (entry 1)
gave isolated product in 91% yield after chromatography.
The easy manipulation of 8 is noteworthy. In each case,
general laboratory grade dichloromethane (DCM) was used
without degassing, in an air atmosphere, so that substrates were
simply dissolved and added to the resin in a plastic solid phase
organic synthesis tube fitted with a glass frit. The tube was then
sealed and subjected to agitation by 360° rotation at rt. Filtration
and washing with DCM afforded the product and the remaining
resin used for further transformations.
Recycling of 8 was tested by treatment of the same batch of
resin with equal, successive portions of benzyl N,N-diallyl-
carbamate, without addition of stabilising alkene (Table 2).8
Indeed 8 proved to be remarkably robust providing good yields
over five successive runs at 5 mol% catalyst. In subsequent runs
yields declined steadily and the beads turned from dark brown
to black.
We have also demonstrated the ability of 8 to perform cross
metathesis. Heating a two-fold excess of (Z)-1,4-diacetoxybut-
2-ene13 with 4-allylanisole and 8 in DCM under reflux for 9 h
furnished the cross-coupled product (33%) along with the
anisole homodimer (18%). The recovered resin retained its
brown colouration, rather than turning black. Subsequent ring
popular because it is easy to handle. Undesirable features of
these systems are that they are not amenable to recycling and
that they give rise to high levels of ruthenium contamination.
Recent work has sought to address these problems.4–7 Hoveyda
and co-workers established 56,7 as a remarkably robust complex
that was stable to silica gel chromatography using non-degassed
eluent and could therefore be recovered and recycled. Recently,
Barrett’s group reported a ‘boomerang’ system 38 for sequester-
ing the catalytic species onto vinyl polystyrene. Indeed 3 could
be reused, as long as an alkyl alkene additive was added to
intercept the unstable catalytic methylidene carbene
(Cl2(PCy3)2RuNCH2).8 Complex 2 can be transferred to vinyl
polystyrene in the same way, with corresponding benefits.9
We are interested in developing a robust immobilised catalyst
for olefin metathesis that can be readily modified to operate in
a range of solvent environments. The ability to utilise non-
degassed solvent offers practical simplicity and could widen the
scope of this reaction. The reported stability of 5 was attractive
and we reasoned that a suitably modified version could be
attached to a range of polymer supports. In this communication,
we describe initial studies leading to a recyclable, polystyrene-
supported analogue of complex 5 that promotes olefin met-
athesis in non-degassed solvents.
We envisaged that the isopropyl portion of the phenol ether
could be extended to accommodate some functional handle that
would allow attachment to any chosen support (Scheme 1).
Thus, opening of racemic d-hexanolactone 6 with sodium
methoxide,11 subsequent Mitsunobu reaction with 2-vinylphe-
nol12 and saponification provided 7. Treating the pendant acid
of 7 with aminomethyl polystyrene under standard conditions
afforded the polystyrene supported ligand. Direct formation of
the alkylideneruthenium7 would be expected to be more
efficient but we reasoned that reaction of styrene 7 with 1 would
generate 8 more simply and in sufficient quantities to permit our
initial study. One disadvantage of this approach is that the
accumulation of free phosphine effectively inhibits olefin
Scheme 1 Reagents and conditions: i, sodium methoxide, MeOH, 0 °C to rt,
6 h, 95%; ii, 2-vinylphenol, diisopropyl azodicarboxylate, PPh3, THF, 0 °C
to rt, 14 h, 64%; iii, 1 M NaOH, dioxane, rt, 12 h, 88%; iv, polystyrene-NH2,
DIC, HOBt, CH2Cl2–DMF (1+1), rt, 12 h; v, Cl2(PCy3)2RuNCHPh, DCE, rt,
12 h.
† Electronic supplementary information (ESI) available: experimental
details. See http://www.rsc.org/suppdata/cc/b0/b007304k/
DOI: 10.1039/b007304k
Chem. Commun., 2001, 37–38
This journal is © The Royal Society of Chemistry 2001
37

closing metathesis of benzyl N,N-diallylcarbamate using this
resin afforded the cyclised product in 85% yield over 90 min,
confirming the retention of catalytic activity.
Olefin metathesis using 1 is typically performed in degassed
solvent, for example, previous studies of 5 were performed in
argon-saturated solvent and atmosphere (only chromatography
using non-degassed solvent was reported).7 We believe that this
communication is notable because studies involving non-
degassed solvent have not been widely reported. We also found,
however, that for reactions corresponding to entries 1 and 5
using non-recyclable complex 1 in non-degassed DCM pro-
ceeded in good yield and draw attention to recent discussion
relating to the oxidative decomposition of alkylideneruthen-
iums.14 In the case of Barrett’s boomerang system 3 however, it
is necessary to add 10 mol% hex-1-ene to prevent decomposi-
tion.8 It is therefore interesting that 8 promotes olefin metathesis
for up to five cycles, without added stabiliser.
The ability to perform olefin metathesis in polar protic
solvents is a desirable goal that has so far been addressed by the
development of water-soluble phosphine ligands.14,15 We
therefore investigated the effect of a different polymer support
on the solubility and catalytic activity of the complex. Thus,
amine-functionalised TentaGel (0.3 mmol g21) was converted
into TentaGel-8 and in preliminary experiments we observed
ring-closing metathesis in non-degassed MeOH, although there
was significant variation between batches of resin. The best
reaction proceeded in 31% yield after 6 h of reaction (entry 6)
and the worst gave 18% after overnight reaction with double the
quantity of resin (100 mg). The lower yield of this transforma-
tion presumably reflects the much lower loading offered by this
TentaGel resin but does suggest that modification of the
supporting polymer is a viable strategy.
Table 1 Olefin metathesis using polymer supported complex 8a
In summary, we have reported a novel polymer supported
pro-catalyst for olefin metathesis that is robust and easy to use.
That 8 is stable to non-degassed solvents and can be recycled
without the use of stabilising additives is notable and inter-
esting. An attractive feature of the precursor 7 is that it can be
attached to any solid support.
We are grateful to the University of Bath for a studentship (to
J. S.) and to Professor B. V. L. Potter for helpful advice and
encouragement.
Note added to proof: two notable papers have been published
since the submission of this manuscript: (a) S. B. Garber, J. S.
Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem. Soc.,
2000, 122, 8168; (b) Q. Yao, Angew. Chem., Int. Ed., 2000, 39,
3896.
Notes and references
1 For reviews see: (a) R. H. Grubbs and S. Chang, Tetrahedron, 1998, 54,
4413; (b) S. K. Armstrong, J. Chem. Soc., Perkin Trans. 1, 1998,
371.
2 For examples: (a) R. Roy and S. K. Das, Chem. Commun., 2000, 519;
(b) M. J. Bassindale, A. S. Edwards, P. Hamley, H. Adams and J. P. A.
Harrity, Chem. Commun., 2000, 1035; (c) A. G. M. Barrett, S. D. Baugh,
V. C. Gibson, M. R. Giles, E. L. Marshall and P. A. Procopiou, Chem.
Commun., 1997, 155; (d) S. E. Gibson, V. C. Gibson and S. P. Keen,
Chem. Commun., 1997, 1107.
3 P. Schwab, R. H. Grubbs and J. W. Ziller, J. Am. Chem. Soc., 1996, 118,
100.
4 L. A. Paquette, J. D. Schloss, I. Efremov, F. Fabris, F. Gallou, J.
Mendez-Andino and J. Yang, Org. Lett., 2000, 2, 1259.
5 H. D. Maynard and R. H. Grubbs, Tetrahedron Lett., 1999, 40, 4137.
6 J. P. A. Harrity, D. S. La, D. R. Cefalo, M. S. Visser and A. H. Hoveyda,
J. Am. Chem. Soc., 1998, 120, 2343.
7 J. S. Kingsbury, J. P. A. Harrity, P. J. Bonitatebus and A. H. Hoveyda,
J. Am. Chem. Soc., 1999, 121, 791.
8 M. Ahmed, A. G. M. Barrett, D. C. Braddock, S. M. Cramp and P. A.
Procopiou, Tetrahedron Lett., 1999, 40, 8657.
9 M. Ahmed, T. Arnauld, A. G. M. Barrett, D. C. Braddock and P. A.
Procopiou, Synlett, 2000, 1007.
10 E. L. Dias, S. T. Nguyen and R. H. Grubbs, J. Am. Chem. Soc., 1997,
119, 3887.
11 A. S. Hernandez, A. Thaler, J. Castells and H. Rapoport, J. Org. Chem.,
1996, 61, 314.
12 S. L. Tsaur and R. M. Fitch, J. Colloid Interface Sci., 1987, 115, 450.
13 D. J. O’Leary, H. E. Blackwell, R. A. Washenfelder and R. H. Grubbs,
Tetrahedron Lett., 1998, 39, 7427.
14 D. M. Lynn, B. Mohr, R. H. Grubbs, L. M. Henling and M. W. Day,
J. Am. Chem. Soc., 2000, 122, 6601.
Table 2 Recycling of 8 for the RCM of benzyl N,N-diallylcarbamatea
Conversionb
1
91c
81d
2
81
69
3
68
68
4
67
33
5
63
21
6
46
11
7
40
—
15 T. A. Kirkland, D. M. Lynn and R. H. Grubbs, J. Org. Chem., 1998, 63,
9904.
16 Y. S. Shon and T. R. Lee, Tetrahedron Lett., 1997, 38, 1283.
a All runs performed in non-degassed CH2Cl2 for 90 min. b Relative
integration of 1H NMR. c 5 mol% 8. d 1.5 mol% 8.
38
Chem. Commun., 2001, 37–38