Fluorous phase-transfer activation of catalysts: Application of a new rate-enhancement strategy to alkene metathesis

Article abstract of DOI:10.1039/b602428a

Reactions of the bis(pyridine) complex (H₂IMes)(Py) ₂(Cl)₂Ru(=CHPh) and fluorous phosphines P(CH ₂CH₂R_fn)₃ (n = a, 6; b, 8; c, 10; R_fn = (CF₂)_n-1

Full text of DOI:10.1039/b602428a

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COMMUNICATION
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Fluorous phase-transfer activation of catalysts: application of a new
rate-enhancement strategy to alkene metathesis{
Rosenildo Correˆa da Costa and J. A. Gladysz*
Received (in Cambridge, UK) 17th February 2006, Accepted 25th April 2006
First published as an Advance Article on the web 17th May 2006
DOI: 10.1039/b602428a
Reactions of the bis(pyridine) complex (H2IMes)(Py)2-
(Cl)2Ru(LCHPh) and fluorous phosphines P(CH2CH2Rfn)3
(n = a, 6; b, 8; c, 10; Rfn = (CF2)n–1CF3) give (H2IMes)
(P(CH2CH2Rfn)3)(Cl)2Ru(LCHPh) (2a–c, 64–73%), which are
analogs of Grubbs’ second generation catalyst and effective
alkene metathesis catalysts under organic monophasic and
fluorous/organic biphasic conditions. The latter give rate
accelerations, which are believed to arise from phase transfer
of the dissociated fluorous phosphine.
Since the first report in 1994,1 fluorous catalysis has primarily been
regarded as a method for catalyst recovery.2 However, it seemed to
us that fluorous techniques might also be used for catalyst
activation. For example, there are many metal-based catalyst
precursors from which a ligand must first dissociate before the
Scheme 2 Proposed fluorous phase-transfer catalyst activation.
catalytic cycle can be entered. The reverse reaction often slows the
overall rate. Thus, if the ligand could be efficiently scavenged,
Fluorous versions of Grubbs’ catalysts are known,4 but they
faster reactions would occur. Most scavenging strategies involve
have been prepared for purposes of catalyst recovery, and carry
chemical derivatization, but fluorous methodologies could bring
ponytails or tags on either non-dissociating or ‘‘boomerang’’
phase transfer into play.
carbene ligands. Since we wanted to evaluate systems with a
A case in point would be the ruthenium alkene metathesis
catalysts developed by Grubbs.3 As summarized in Scheme 1, the
spectrum of phase properties, the series of fluorous aliphatic
phosphines P(CH2CH2Rfn)3 (n = a, 6; b, 8; c, 10) was selected.5 All
dissociation of a phosphine L (k1 or initiation step) can be followed
exhibit partition coefficients that are highly biased for fluorous
phases (CF3C6F11–toluene: 98.8 : 1.2, >99.7 : ,0.3, >99.7 : ,0.3).5
either by recoordination (k21 step) or alkene binding (k2 step).
Rate studies have identified many catalysts, including the
As shown in Scheme 3, reactions with the ruthenium bis(pyridine)
commercially available first and second generation systems, for
benzylidene complex 16 gave the target complexes 2a–c as
analytically pure pink solids in 64–73% yields. They were
characterized by NMR spectroscopy (1H, 13C, 31P, 19F) and mass
spectrometry, as summarized in the supporting information.{
which k21 > k2.3 We wondered whether rate enhancements might
be realized when catalysts bearing fluorous phosphines were
employed under organic/fluorous liquid/liquid biphasic conditions.
As illustrated in Scheme 2, fluorous phosphines can have high
thermodynamic affinities for fluorous phases, whereas the active
catalyst and alkenes would have high thermodynamic affinities for
organic phases.
Scheme 1 Initiation sequence for a Grubbs-type ruthenium alkene
metathesis catalyst.
Institut fu¨r Organische Chemie, Friedrich-Alexander-Universita¨t
Erlangen-Nu¨rnberg, Henkestraße 42, 91054 Erlangen, Germany
{ Electronic supplementary information (ESI) available: Characterization
of new complexes and procedures for catalytic reactions. See DOI:
10.1039/b602428a
Scheme 3 Synthesis of ruthenium metathesis catalysts with fluorous
phosphines.
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Chem. Commun., 2006, 2619–2621 | 2619

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Complexes 2a, b were soluble in CH2Cl2, benzene, hexane, and
pentane. Paralleling the effect of the Rfn ponytail length in the free
phosphines, 2c was only slightly soluble. The CF3C6F11–toluene
partition coefficients of 2a–c were measured by HPLC.{ The
values, 13.2 : 86.8, 39.6 : 60.4 and 77.6 : 22.4, exhibited the
expected trend. When toluene is replaced by a solvent of greater
polarity (e.g., CH2Cl2), the proportions of 2a, b in the non-
fluorous phase should increase. Since even non-polar alkenes
greatly prefer the non-fluorous phase (CF3C6F11–toluene ,5 : >95
for ¢C10),7 the partitioning of some catalyst precursor into the
fluorous phase is deleterious for the rate. However, the much more
biased partitioning of the fluorous phosphine should often
compensate.
Complexes 2a–c were screened in standard metathesis reactions,
and found to be effective catalyst precursors, as will be detailed in
future publications. To address the theme of this communication,
the ring-closing metathesis of diethyl-2,2-diallylmalonate (3)8 was
investigated under various conditions using 2b (Scheme 4). Two
side-by-side reactions were conducted using 4 mL of CH2Cl2
(0.00125 M in 2b, 0.05 M in 3). In one case, 2 mL of CF3C6F11 was
added. Based upon the partitioning data noted above,7 this should
not affect the concentration of 3 in the CH2Cl2 phase. The
concentration of 2b should be reduced by less than 19.8% (i.e.,
39.6/2 due to the 2 : 1 volume ratio, and still less due to the
substitution of toluene by CH2Cl2). The formation of the
cyclopentene product 4 was monitored by GC in the presence of
an internal standard, and the results are depicted in Fig. 1.
Fig. 1 shows that the initial rate of metathesis was markedly
enhanced in the presence of the fluorous solvent. After 1 and 2 h
the yields of 4 were 23% and 44%, as opposed to 6% and 16% in
CH2Cl2 alone. An analogous experiment was conducted with
perfluoro(2-butyltetrahydrofuran). This solvent is somewhat less
Fig. 1 Rates of formation of 4 in Scheme 4. Solvent systems: ¤ CH2Cl2–
perfluoro(2-butyltetrahydrofuran) (4 mL/2 mL); # CH2Cl2–CF3C6F11
(4 mL/2 mL); & CH2Cl2 only (4 mL).
viscous than CF3C6F11,9 which we imagined might aid diffusion
across the phase boundary. Interestingly, a significantly greater
rate enhancement was observed, with 4 present in 58% and 74%
yields after 1 and 2 h. To confirm that these phenomena were not
unique to a single substrate, diethyl-2-allyl-2-methallylmalonate (5)
and N,N-diallyltosylamide (7) were similarly reacted (Scheme 4).
Analogous rate enhancements were observed for the formation of
6 (Figure 2s,{ CH2Cl2–CF3C6F11) and 8 (Figure 4s,{ CH2Cl2–
perfluoro(2-butyltetrahydrofuran)). The latter was particularly
dramatic (58% vs. 2% and 91% vs. 4% after 1 and 2 h).
Reaction of 5 with the less fluorophilic catalyst 2a gave similar
results (Figure 3s{).
In biphasic fluorous/organic systems, a small amount of
fluorous solvent typically partitions into the organic solvent, and
vice versa. Therefore, there remains some possibility that the
preceding trends might (in part) represent solvent effects. Hence,
analogous experiments were conducted with Grubbs’ second
generation catalyst (H2IMes)(PCy3)(Cl)2Ru(LCHPh)—a non-
fluorous system. As illustrated in the supporting information,
the initial rates of formation of 4 and 8 were virtually
identical in CH2Cl2 and CH2Cl2–perfluoro(2-butyltetrahydro-
furan); that of 4 was only very slightly faster in CH2Cl2–
CF3C6F11 (Figures 5s–7s{). However, the rates of metathesis were
greater than those with 2b (for 4, 44–50% and 77–88% yields in
CH2Cl2 after 15 and 60 min).10
Other additives that might inhibit the k21 step in Scheme 1 have
been investigated. Grubbs,11 Nolan,12 and Blechert13 have
reported various types of copper species and Lewis or Brønsted
acids that are believed to bind the phosphine L and lead to rate
accelerations in certain cases. In a complementary approach, Piers
has developed a novel class of highly active fourteen-valence-
electron catalyst precursors that lack any ligand L.14 Phenol
additives can also have positive effects, but other mechanisms are
thought to be involved.15 Importantly, the dissociated PCy3 ligand
is intimately involved in the decomposition of Grubbs’ second
generation catalyst.16 Therefore, another advantage of the phase
transfer activation in Scheme 2 may be longer-lived catalysts.
Finally, fluorous/organic biphasic conditions have also been
found to give enhanced rates with hetereogenized rhodium
Scheme 4 Test reactions for fluorous phase transfer activation.
2620 | Chem. Commun., 2006, 2619–2621
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hydrogenation catalysts.17 However, another activation mode is
believed operative.
8 M. Scholl, S. Ding, C. W. Lee and R. H. Grubbs, Org. Lett., 1999, 1,
953.
9 S. W. Green, D. S. L. Slinn, R. N. F. Simpson and A. J. Woytek, in
Organofluorine Chemistry Principles and Commercial Applications, ed.
R. E. Banks, B. E. Smart and J. C. Tatlow, Plenum Press, New York,
1994, ch. 4 and Table 9.
In summary, the data presented in this communication are
consistent with a new catalyst activation strategy that uses phase
transfer to fluorous media to remove dissociated ligands that can
compete with substrate molecules for binding to a reactive metal
center. Note that this modus, which we view as ‘‘passive
transport’’, might be coupled with a binding or derivatization
event in the fluorous phase—an enhancement that might be
termed ‘‘active transport’’.18 Hence, there are tantalizing possibi-
lities for future extensions. In any event, experiments are in
progress to further probe the mechanism of activation of 2a, b
under fluorous/organic liquid/liquid biphasic conditions, as well as
their recyclability. These will be detailed in future publications.
We thank the Deutsche Forschungsgemeinschaft (DFG, GL
300/3-3) for support.
10 In Scheme 1, triarylphosphine ligands (L) with electron withdrawing
substituents give greater k1 values.3b The electron withdrawing effects of
the Rfn segments are strongly felt at the phosphorus atoms of a–c
(H. Jiao, S. Le Stang, T. Soo´s, R. Meier, K. Kowski, P. Rademacher,
L. Jafarpour, J.-B. Hamard, S. P. Nolan and J. A. Gladysz, J. Am.
Chem. Soc., 2002, 124, 1516). Hence, 2a–c would be expected to be
faster initiating catalysts than tri-n-alkylphosphine analogs. However,
overall rates are a function of many additional factors3.
11 (a) J. P. Morgan and R. H. Grubbs, Org. Lett., 2000, 2, 3153; (b)
D. M. Lynn, B. Mohr, R. H. Grubbs, L. M. Henling and M. W. Day,
J. Am. Chem. Soc., 2000, 122, 6601; (c) M. S. Sanford, L. M. Henling
and R. H. Grubbs, Organometallics, 1998, 17, 5384; (d) E. L. Dias,
S. T. Nguyen and R. H. Grubbs, J. Am. Chem. Soc., 1997, 119, 3887.
12 J. Huang, H.-J. Schanz, E. D. Stevens and S. P. Nolan, Organometallics,
1999, 18, 5375.
13 M. Rivard and S. Blechert, Eur. J. Org. Chem., 2003, 2225.
14 (a) P. E. Romero, W. E. Piers and R. McDonald, Angew. Chem., Int.
Ed., 2004, 43, 6161, (Angew. Chem., 2004, 116, 6287); (b) P. E. Romero
and W. E. Piers, J. Am. Chem. Soc., 2005, 127, 5032.
15 G. S. Forman, A. E. McConnell, R. P. Tooze, W. J. van Rensburg,
W. H. Meyer, M. M. Kirk, C. L. Dwyer and D. W. Serfontein,
Organometallics, 2005, 24, 4528.
Notes and references
1 I. T. Horva´th and J. Ra´bai, Science, 1994, 266, 72.
2 See relevant chapters in Handbook of Fluorous Chemistry, ed. J. A.
Gladysz, D. P. Curran and I. T. Horva´th, Wiley/VCH, Weinheim, 2004.
3 (a) M. S. Sanford, J. A. Love and R. H. Grubbs, J. Am. Chem. Soc.,
2001, 123, 6543; (b) J. A. Love, M. S. Sanford, M. W. Day and
R. H. Grubbs, J. Am. Chem. Soc., 2003, 125, 10103.
4 (a) Q. Yao and Y. Zhang, J. Am. Chem. Soc., 2004, 126, 74; (b)
M. Matsugi and D. P. Curran, J. Org. Chem., 2005, 70, 5, 1636.
5 L. J. Alvey, D. Rutherford, J. J. J. Juliette and J. A. Gladysz, J. Org.
Chem., 1998, 63, 6302.
6 T. M. Trnka, J. P. Morgan, M. S. Sanford, T. E. Wilhelm, M. Scholl,
T.-L. Choi, S. Ding, M. W. Day and R. H. Grubbs, J. Am. Chem. Soc.,
2003, 125, 2546.
7 J. A. Gladysz, C. Emnet and J. Ra´bai, in Handbook of Fluorous
Chemistry, ed. J. A. Gladysz, D. P. Curran and I. T. Horva´th, Wiley/
VCH, Weinheim, 2004, pp. 56–100.
16 S. H. Hong, M. W. Day and R. H. Grubbs, J. Am. Chem. Soc., 2004,
126, 7414.
17 S. L. Vinson and M. R. Gagne´, Chem. Commun., 2001, 1130.
18 A fluorous dicopper tetracarboxylate of the formula
Cu2(O2CCH(CH2CH2CH2Rf8)2)4 efficiently extracts non-fluorous pyr-
idines into fluorous phases (M. El Bakkari, N. McClenaghan and
J.-M. Vincent, J. Am. Chem. Soc., 2002, 124, 12942). Accordingly,
we have tested pyridine-containing ruthenium metathesis catalysts
such as 1 (Scheme 3) in the presence of this additive under organic/
fluorous biphasic conditions. However, rapid catalyst deactivation was
observed.
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Chem. Commun., 2006, 2619–2621 | 2621