Small-molecule N-heterocyclic-carbene-containing olefin-metathesis catalysts for use in water

Article abstract of DOI:10.1002/anie.200701258

(Chemical Equation Presented) ROMPing around in water: Two well-defined, small-molecule olefin-metathesis catalysts (1 and 2) are introduced. While they are insufficiently stable to mediate most cross-metathesis reactions in water, these catalysts competently mediate ring-opening metathesis polymerization (ROMP) and ring-closing metathesis reactions in an aqueous environment.

Full text of DOI:10.1002/anie.200701258

Communications
DOI: 10.1002/anie.200701258
Olefin-Metathesis Catalysts
Small-Molecule N-Heterocyclic-Carbene-Containing Olefin-
Metathesis Catalysts for Use in Water**
Jason P. Jordan and Robert H. Grubbs*
Olefin metathesis is a powerful transformation in modern
chemistry.[1] By mediating the exchange of olefin substituents,
metathesis catalysts enable such reactions as ring-closing
metathesis (RCM), cross-metathesis, and ring-opening meta-
thesis polymerization (ROMP) reactions useful for small-
molecule,[1,2] macromolecular,[3] and even supramolecular
chemistry.[4] Because they are stable towards air and moisture
and tolerant of a broad range of functional groups, ruthenium
complexes are particularly useful catalysts for this trans-
formation.[1,5] While olefin metathesis in traditional organic
solvents is now ubiquitous, its potential utility in water is
largely untapped.
Hindering the implementation of aqueous metathesis is a
lack of suitable catalysts. To address this need, our group has
developed water-soluble catalysts 1–4 (PEG: poly(ethylene
glycol)).[6] Other groups have also developed catalysts for use
in aqueous environments though these catalysts require
cosolvents or perform metathesis in the organic pores of a
polymer resin.[7] Catalysts 1, 2, and 3 are quite unstable in
water and only show limited activity for aqueous metathesis
reactions other than ROMP.[6b–c,8] Phosphine-free catalyst 4
demonstrates a greater ability to mediate ring-closing meta-
thesis in an aqueous environment.[6d] However, 4 is a macro-
molecular, polydisperse catalyst that appears to form aggre-
gates in water. Therefore, we describe herein the synthesis of
small-molecule, N-heterocyclic carbene (NHC)-containing
ruthenium complexes 5 and 6 and their activity in aqueous
metathesis.
The syntheses of styrenes 10 and 12 used to produce
catalysts 5 and 6 are shown in Scheme 1. Chloromethylation
followed by Wittig olefination of readily synthesized benzal-
dehyde 7 provides benzyl chloride 9 in moderate yield.
Amination with trimethylamine then yields isopropoxystyr-
ene 10. Amination of 9 with N,N,N’,N’-tetramethylethylene-
diamine followed by methylation and ion exchange gives
isopropoxystyrene 12.
[*] J. P. Jordan, Prof. R. H. Grubbs
Arnold and Mabel Beckman Laboratory of Chemical Synthesis
Division of Chemistry and Chemical Engineering
California Institute of Technology
Pasadena, CA 91125 (USA)
Fax: (+1)626-564-9297
E-mail: rhg@caltech.edu
Scheme 1. Reagents and conditions: a) formaldehyde, HCl(aq),
HCl(g), 508C, 3 h (66%); b) BrCH3PPh3, KOtBu, THF, ꢀ60!158C, 2 h
(78%); c) NMe3, MeCN, 08C!RT, 12 h (81%); d) Me2N(CH2)2NMe2,
[**] We thank Soon H. Hong for the generous donation of substrates 23
MeCN, RT, 24 h, 90%; e) MeI, CH2Cl2, RT, 7 h; f) Amberlite IRA-
and 25 and for helpful discussions, and Dr. Mona Shahgholi for
mass spectroscopic analysis. The National Institutes of Health
(5R01M068647) is acknowledged for funding.
400(Cl), H2O, RT, 12 h (performed three times; 81%, three steps).
The synthesis of the ruthenium complex that displays an
appropriately substituted NHCligand for the production of 6
is straightforward (Scheme 2). Selective protection of the
Supporting information for this article, including full experimental
details and 1Hand 13C NMR spectra, is available on the WWW under
http://www.angewandte.org or from the author.
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primary amine of readily prepared triamine 13 followed by
cyclization gives dihydroimidazolium salt 15. Deprotonation
and ligand exchange with complex 16 yields the desired
ruthenium compound 17, which appears as a mixture of
1
rotational isomers by H and 31P NMR spectroscopy, even at
high temperatures, owing to slow rotation about the ruthe-
nium–NHCbond. [9]
Catalysts 5 and 6 can be synthesized by reacting the
appropriate ruthenium benzylidene with styrenes 10 and 12
(Scheme 3). Mixing 10 and 12 with complexes 17 and 18 in the
presence of copper(I) chloride gives Boc-protected complex
19 and catalyst 5, respectively. Deprotection of 19 with freshly
prepared HCl/benzene solution then produces catalyst 6.
Catalyst 5 is only soluble in water at low concentrations
(< 0.01m) though it is sufficiently soluble to be detected by
1H NMR spectroscopy in deuterium oxide. In contrast,
catalyst 6 readily dissolves in water. Moreover, catalyst 6 is
relatively stable in water with a decomposition half-life of
over a week at ambient temperature under inert conditions.
As reported for other water-soluble catalysts,[6c–d] the
ROMP of challenging endo-norbornene monomer 20[6c,10] was
performed to compare the activities of catalysts 2–6
(Figure 1). Both catalysts 5 and 6 rapidly transform monomer
20 into product polymer. Hence, catalysts 5 and 6 are highly
competent ROMP catalysts, which show activities similar to 4
for this reaction.
Scheme 3. Reagents and conditions: a) 12, CuCl, CH2Cl2, 458C, 1 h
(46%); b) 10, CuCl, CH2Cl2, 458C, 1 h; c) HCl, C6H6, RT, 45 min (67%,
two steps).
Scheme 2. Reagents and conditions: a) Boc2O, DMAP, CH2Cl2, RT, 2 h
(86%); b) HC(OEt)3, NH4Cl, 1208C, 16 h (90%); c) tBuOK, 16, THF,
RT, 17 h (61%). Boc: tert-butyloxycarbonyl; Cy: cyclohexyl.
Figure 1. Conversion versus time profile for polymerization of mono-
mer 20 by catalysts 2–6 as measured by 1HNMR spectroscopy. For
catalysts 2 and 3, the polymerization was run in the presence of one
equivalent of DCl (versus catalyst) for increased activity. (The results
for catalysts 4, 5, and 6 overlap. Data for catalysts 2, 3, and 4 were
obtained from references [6c] and [6d].)
Catalysts 5 and 6 also mediate the RCM of a,w-dienes in
water. This is a challenging transformation in water that, to
date, has only been catalyzed by catalyst 4.[6d] Table 1 lists the
results of the RCM reactions of five different substrates with
catalysts 5 and 6 and provides the reported results with
catalyst 4 for comparison.[6d] The ring-closing of substrates 21
and 23 is readily accomplished by all three catalysts though a
lower conversion of 23 is observed with catalyst 6. However,
the ring-closing of 25 to form a trisubstituted olefin proceeds
in good conversion for catalyst 5 and poor conversion for
catalyst 6—a difference ascribed to the relative stabilities of
the two catalysts under the reaction conditions. Like catalyst
4,[6d] neither 5 nor 6 successfully ring-closed substrate 27. The
RCM of challenging substrate 29 can yield significant
amounts of cycloisomerized side product 31, which is believed
to be produced by ruthenium hydrides generated during
catalyst decomposition.[6d,7c,11] Interestingly, catalyst 5 fully
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Table 1: RCM reactions in water.[a]
apparent lower stability for cata-
lysts 5 and 6 relative to 4 under
these reaction conditions. Attempts
to dimerize other substrates, includ-
ing those based on amino acids,
carbohydrates, and ammonium
salts, failed. Therefore, while cata-
lysts 5 and 6 are unable to make
many aqueous cross-metathesis
reactions practical, along with cata-
lyst 4 they do represent progress in
this area.
Catalyst
Substrate
t [h]
Product
Conversion [%]
4[b]
5
6
12
24
0.5
>95
>95
>95
4
5
6
24
24
4
>95
>95
84
4[b]
5
6
24
24
6
42
70
26
In conclusion, the synthesis of
two small-molecule aqueous meta-
thesis catalysts has been described.
Both catalysts mediate ROMP and
RCM reactions in aqueous media.
While neither catalyst is sufficiently
stable for the practical aqueous
cross-metathesis of many sub-
strates, they do homodimerize allyl
alcohol.
4[b]
5
6
24
24
24
<5
<5
<5
4[b]
5
6
36
24
4
67 (+28)
>95
36 (+59)
[a] Reactions were performed at 308C with 5 mol% catalyst and an initial substrate concentration of
0.2m in D2O. Reaction times are not optimized. Conversions were determined by 1HNMR spectroscopy
and represent the average of two trials. [b] Reactions were performed at room temperature with 5 mol%
catalyst and an initial substrate concentration of 0.2m in D2O or H2O. These data were obtained from
reference [6d].
Received: March 21, 2007
Published online: June 5, 2007
Keywords: metathesis ·
N-heterocyclic carbenes ·
polymerization · ruthenium · water
Table 2: Cross-metathesis reactions in water.[a]
.
Catalyst
Substrate
t [h]
Product
Conversion [%]
E/Z
4[b]
5
6
12
24
6
>95
82 (+4)
69 (+12)
15:1
13:1
19:1
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alcohol in moderate conversions and mediate the cis–trans
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