Justin A. M.
Lummiss
a,
Nicholas J.
Beach
a,
Jeffrey C.
Smith
b and
Deryn E.
Fogg
*a
aDepartment of Chemistry and Centre for Catalysis Research & Innovation, University of Ottawa, Ottawa, Ontario, Canada. E-mail: dfogg@uottawa.ca; Tel: 613-562-5800 ext. 6057
bDepartment of Chemistry, Carleton University, Ottawa, Ontario, Canada
First published on 28th May 2012
The first clean, high-yield route is presented to methylidenes RuCl2(L)(PCy3)(CH2) (L = H2IMes or IMes), key vectors for catalysis and deactivation in many olefin metathesis reactions. (H2IMes = N,N′-bis(mesityl)imidazolin-2-ylidene; IMes = N,N′-bis(mesityl)imidazol-2-ylidene).
![]() | ||
Fig. 1 Metathesis catalysts discussed. IMes = N,N′-bis(mesityl)imidazol-2-ylidene; H2IMes = N,N′-bis(mesityl)imidazolin-2-ylidene. |
The literature route to GIICH2 (involving CM of benzylidene GII with ethylene at 50 °C; Scheme 1)4 affords the desired product in <40% yield, the balance being unidentified byproducts. The implied rapidity of decomposition is unexpected. The starting complex GII has a reported half-life of >1 month in benzene at 55 °C,7 and while the 5.7 h half-life found7 for the methylidene target is much shorter, this still exceeds the 1.5 h timescale of the CM reaction by a considerable margin. Of note, however, is the accelerated decomposition observed for various Ru metathesis catalysts in the presence of ethylene.7–10 We suspected that the low yield of GII
CH2 might originate in the vulnerability of intermediates formed during ethylene exchange, particularly four-coordinate RuCl2(H2IMes)(
CH2) (C, Scheme 2), metallacyclobutane B, and – perhaps most susceptible8 – the unsubstituted metallacyclobutane formed via degenerate CM of GII
CH2 with ethylene.
![]() | ||
Scheme 1 Previously reported route to methylidene GII![]() |
![]() | ||
Scheme 2 Details of the synthetic sequence of Scheme 1 (L = H2IMes), highlighting the high-commitment nature of A and C (see text). A parallel sequence involves degenerate exchange of GII![]() |
Kinetics studies by the groups of Grubbs4 and Chen11 indicate that A (L = H2IMes) reacts preferentially with olefin, rather than free PCy3 (a propensity that led Chen to classify the second-generation complexes as “high-commitment” catalysts).11 Indeed, this bias is one factor underlying the exceptional metathesis activity of the N-heterocyclic carbene (NHC) catalysts. In the present context, however, high commitment is detrimental: the bias toward reaction with ethylene results in competitive inhibition of the desired ligand exchange, and prolongs the time that the catalyst spends in its least stable, phosphine-free states. The thermal sensitivity of GII in the presence of ethylene7–9,10c (as in the synthesis shown in Scheme 1) is evidently much greater than that suggested by model studies in the absence of olefin.
The limitations intrinsic to ethenolysis led us to explore an alternative approach to the second-generation methylidene complexes, based on ligand exchange of GICH2 with free NHCs (H2IMes, IMes; Scheme 3). While this synthetic strategy may seem counter-intuitive, given that the half-life of GI
CH2 (40 min at 55 °C in C6D6)2 is much shorter than that of GII, it is designed to exploit the low-commitment nature of the first-generation complex: that is, its propensity for rapid reaction with free PCy34,11 or, potentially, NHC donors. We considered that fast uptake of the Lewis base, coupled with elimination of the vulnerable metallacyclobutane intermediate, could potentially improve reaction rates and yields.
![]() | ||
Scheme 3 Ligand exchange route to second-generation methylidene complexes. |
Access to the first-generation methylidene complex GICH2 in high purity is a prerequisite for the planned approach. In our hands, the reported12 synthesis of GI
CH2via CM with ethylene resulted in persistent contamination by residual GI, consistent with the equilibrium nature of this reaction.13 Essentially quantitative conversions could be readily attained, however, by washing the crude product with pentane to remove styrene, and re-subjecting it to the ethylene treatment. We obtained GI
CH2 free of GI after the second pass, in an overall isolated yield of 85%.
With clean GICH2 in hand, we turned to installation of the H2IMes and IMes ligands. Earlier work described the efficiency with which GII′ can be obtained by treating GI with pure IMes.14–16 Use of isolated IMes, in preference to the in situ-generated carbene, greatly simplified workup and purification, as PCy3 was then the only adventitious species present at the end of reaction. Building on this precedent, we chose to use pure free IMes and H2IMes to synthesize the methylidene complexes of interest. The free carbenes are readily accessible via the established procedures,17,18 and are now also commercially available (Strem).
A potential complication in our intended use of GICH2 as a precursor for ligand exchange is the low room-temperature lability of the PCy3 ligand,4 which necessitates use of elevated temperatures. While both free H2IMes and free IMes show excellent thermal stability,‡ the vulnerability of GI
CH2 is evident from the discussion above. On heating a benzene solution of GI
CH2 and free NHC at 60 °C, however, we found that ligand exchange out-competes decomposition. Thus, NMR-scale experiments in C6D6 revealed rapid formation of GII
CH2 (99% by 22 min; Fig. 2a), with excellent agreement between conversions and in situ yields, as judged from integration against internal standard. Even on increasing reaction times to 45 min, to address any increase in timescale required for preparative-scale experiments, no decomposition was evident. It may be noted that this longer reaction period remains well within the nearly six-hour half-life of the product.7GII
CH2 was obtained in 81% isolated yield, despite some losses incurred by its partial solubility in the cold pentane used to extract the PCy3 co-product. The corresponding reaction with free IMes likewise enables quantitative formation of GII′
CH2 (Fig. 2b), which was isolated in similar yields (78%).
![]() | ||
Fig. 2 Kinetics of ligand exchange of GI![]() ![]() ![]() |
The foregoing describes the first clean, high-yield route to the second-generation Grubbs methylidene complexes GIICH2 and GII′
CH2. A strategy based on ligand exchange of RuCl2(PCy3)2(
CH2) with free H2IMes or IMes eliminates the decomposition that severely limits the yields attainable in metathetical exchange of benzylidene GII with ethylene. Use of the isolated free NHCs (both of which are now commercially available) also contributes to high purity with minimal workup, as the only byproduct in the reaction is readily-removed PCy3. Given the importance of these methylidene resting-state species as vectors for both metathesis and catalyst deactivation, we anticipate that these straightforward, high-yield routes to GII
CH2 and GII′
CH2 will aid significantly in clarifying key reaction pathways in olefin metathesis.
Footnotes |
† Electronic supplementary information (ESI) available: Full experimental details and NMR spectra. See DOI: 10.1039/c2cy20213a |
‡ 1H NMR experiments showed no decomposition of H2IMes or IMes over 10 h at 60 °C in C6D6, as indicated by integration against an internal standard. |
This journal is © The Royal Society of Chemistry 2012 |