I am grateful to Jonas for making time to participate in my proposal defense in the middle of his move to MIT. I am especially grateful to Dan for his willingness to meet the "men in the dark suits" as a character reference for my national security clearance.
The Olefin Metathesis Reaction and Its Function in Protic
Therefore, a catalyst that is soluble and stable in water is required to realize this potentially powerful application of olefin metathesis. A variety of ligands can be used to produce water-soluble NHC-containing olefin metathesis catalysts.
A PEG-Displaying Water-Soluble Olefin Metathesis Catalyst
The product was isolated by precipitation of the reaction mixture in diethyl ether (200 mL), followed by vacuum filtration. Outside the box, the reaction mixture was heated to 45 °C and the conversion was followed by 1H NMR spectroscopy.
Initial Efforts to Develop a Small-Molecule Olefin Metathesis
Early research pursuing a water-soluble olefin metathesis catalyst containing an N-heterocyclic carbene (NHC) ligand is reported. This chapter describes early attempts to synthesize such water-soluble NHC-containing olefin metathesis catalysts. Water-soluble groups can be incorporated into NHC ligands or ligands that dissociate during metathesis reactions to produce NHC-containing olefin metathesis catalysts that are water-soluble.
Early efforts to synthesize catalysts with improved stability and activity in water focused on incorporating water-soluble groups onto NHC ligands. As previously mentioned, neither compound 9 nor 10 was ever used to generate a water-soluble olefin metathesis catalyst. Initial efforts focused on the strategy of including water-soluble functional groups on the NHC ligand.
Effect of Water on the Stability and Initiation of Olefin Metathesis
This prompts the study of the decomposition of catalyst 2 and the alkylide/ethylidene (7) and methylidene (8) analogues of 2 in the presence of water. Therefore, experiments were designed to obtain information about the decomposition of methylidene complex 8 in the presence of water. Therefore, examination of the decomposition of 7 in the presence of water should demonstrate the feasibility of this strategy.
These plots represent the decomposition of the 0.023 M ruthenium ethylidene complex 7 at 35 °C in the presence and absence of water.
Water-Soluble Phosphine-Free Olefin Metathesis Catalysts
12 was not sufficiently stable to efficiently mediate ring closure and cross metathesis reactions in water (Chapter 2).26. ROMP of monomer 27 indicates increased activity for catalysts 14 and 15 in water compared to previous water-soluble catalysts. As shown, catalysts 14 and 15 are capable of mediating ROMP in water and are competent catalysts for RCM in an aqueous environment.
Homodimerization of different substrates was used as an initial screening of the ability of catalysts 14 and 15 to perform cross-metathesis in water. The material was dissolved in water (433 mL), followed by the addition of 65 g of Amberlite IRA-400(Cl) resin. Hydrogen chloride gas was produced by slowly dropping sulfuric acid per equivalent (relative to sulfuric acid) of ammonium chloride.) The reaction was allowed to stir for 45 minutes at room temperature.
Research Opportunities in Aqueous Olefin Metathesis
Therefore, metathesis reactions are enhanced by increasing the rate of productive catalysis relative to the rate of catalyst decomposition. The increase in catalyst activity arises from the increase in the ratio of the rate of productive catalysis to the rate of decomposition of the catalyst. Also, the high stability of metathesis catalysts in organic solvents can accommodate a moderate increase in the rate of catalyst decomposition.
Slow dissociation of the ligand trans to NHC is responsible for the poor reactivities observed with catalysts. However, the rate of catalyst initiation increases in more polar solvents,11 and Chapter 4 shows that ruthenium complexes initiate faster in the presence of water.
NMR Spectra for Selected Ruthenium Complexes
Crystal Structure Data for Chapter 5
Because palladium will couple aryl bromides to carbamate nitrogens, 30-32 19's carbamate nitrogen must be methylated with iodomethane prior to the challenging palladium-mediated coupling reaction with ethylenediamine to yield product diamine. 21.33 Cyclization with triethyl orthoformate followed by Boc deprotection with hydrochloric acid yields imidazolium on salt 23, which can be methylated with iodomethane to produce 10 after ion exchange and desalination. Although neither 9 nor 10 led to water-soluble metathesis catalysts, the Boc-protected imidazolium salt 15, which was produced during the synthesis of 9, was used in future research and ultimately used to produce a new water-soluble metathesis catalyst (Chapter 5) .34.35. Imidazolium salt 24, which presents an alcohol from its backbone, can be easily prepared according to procedures from the literature.36 This alcohol provides a synthetic handle for the incorporation of water-soluble functional groups.
Pleasingly, the alcohol of 24 reacts smoothly with the sulfur trioxide pyridine complex to provide the zwitterionic NHC precursor 25 (Scheme 3.3), which displays the water-soluble sulfate group.37.
On the other hand, alkylidene complexes are degraded by bimetallic mechanisms, which is evident from the formation of 3-hexene during the decomposition of the bis(phosphine)propylidene complex.8 The results of this research show that the order of stability of the complex is benzylidene > alkylidene > methylidene. 9. The graph of the decomposition half-life as a function of water concentration for 0.023 M ruthenium methylidene complex 8 at 25 °C is non-linear. Two components of 8 have been identified as likely sources of complex instability—the ruthenium–chloride bonds and the fourteen-electron species produced by phosphine dissociation (Scheme 4.1).
However, in the presence of 4 M water, curvature is observed at the beginning of the collected. As already described, the ruthenium alkylidene and methylidene derivatives of bis(phosphine) complex 1 are known to decompose by very different mechanisms.8 This is also believed to be true for metathesis catalysts containing NHC ligands.7 The decomposition of ruthenium methylidene complexes, such as e.g. complex 8, is known to be first order in the ruthenium methylidene complex.8,13 However, the decomposition of ruthenium benzylidene and alkylidene complexes, such as complexes 2 and 7, is believed to be second order in the phosphine-dissociated fourteen-electron ruthenium complex.8 To determine the kinetic order of ruthenium complex 7 in its degradation under these conditions, the effect of doubling the concentration of 7 on its degradation rate can be investigated in both the presence and absence of 4 M water in THF (Figure 4.6). A cursory examination of the plots for the degradation of ethylidene compound 7 in the presence of 4 M water indicates that it degrades by a different mechanism i.
An examination of the products resulting from the decomposition of 8 reveals several degradation pathways, although most involve the formation of Cy3PMeCl. After ROMP of monomer 27 by 1H NMR spectroscopy provided a measure of the relative activities of catalysts and 15 in water.
From these data, the order of water in the decomposition kinetics of complex 8 is unclear. Cy3PMeCl.21 Therefore, while 1H NMR reveals the presence of multiple decomposition pathways, 31P NMR shows that pathways yielding Cy3PMeCl tend to dominate the decomposition of the ruthenium methylidene complex 8. Therefore, the effect of excess phosphine on the rate of methylidene decomposition 8 ' illuminate the possible role of fourteen-electron species in this decay.
Consistent with this previous research, the formation of Cy3PMeCl is observed for the decomposition of 8 in THF both in the presence and absence of water.
To investigate this possibility, ethyl vinyl ether-based kinetics were performed on compounds 2 and 8 in the presence and absence of water in THF at 25 °C. Water has the same effect on ruthenium methylidene complex 8 , which appears to initiate ∼2 times faster in the presence of water. While 8's initiation appears to roughly double in the presence of 4 M water, the rate of decomposition increases by a factor of ∼5.
The effect of water on the decomposition of 8 can be seen as the combined result of two different causes.
To investigate this possibility, the dissolution of 7 in THF and in 4 M water/THF at 35 °C was investigated. In the absence of water, the decomposition of ethylidene complex 7 is less than first order in 7 itself (Figure 4.6). This observation was also made by Wagener and co-workers when they investigated the decomposition of complex 7 in benzene.
The formation of ruthenium methylidene complex 8 during the decomposition of ethylidene compound 7 is probably indicative of a process such as the one detailed in Scheme 4.5.
The ability of these catalysts to mediate ring-opening metathesis, ring-closing metathesis, and cross-metathesis polymerizations as homogeneous reactions in water is studied. Water-soluble groups can be incorporated into NHC ligands and/or ligands that dissociate during metathesis reactions to produce water-soluble NHC-containing olefinic metathesis catalysts. Nevertheless, the reactions shown in Table 5.4 represent the first examples of successful cross-metathesis in water.
Catalysts 14 and 15 are also able to ring-close α,ω-dienes in water to form five-, six- and seven-membered ring products in good to moderate conversions. The volatiles were removed by rotary evaporation, and the crude material was dissolved in water acidified with hydrochloric acid. Indeed, the development of catalysts 1 and 2 represents significant progress in the ability to perform homogeneous metathesis in water.
Interestingly, catalyst 14 is also produced by mixing styrene 25 with ruthenium bis(pyridine) complex 4 in dry, degassed DMF at 30 °C.
Yet, the ROMP of norbornene monomers in water is one of the oldest reactions for ruthenium-based metathesis. Most previous research on cyclization and cross-metathesis reactions in water with catalysts containing an NHC ligand involved either mixed solvent systems20-23 or heterogeneous systems where catalysis was assumed to occur in organic pores.17,24,25 Therefore, the ability of catalysts 14 and 15 to enable aqueous ring-closing metathesis and cross-metathesis as homogeneous reactions in water are of particular interest. The low concentration of catalyst 14 in water can also increase its stability by decreasing the rate of decomposition pathways involving two metal centers.
The alkylidene derivative of Catalyst 15 will exhibit two water-soluble groups, one from its NHC ligand and that provided by the water-soluble substrate, and is likely completely soluble in water. This inspires the hypothesis that productive cross-metathesis in water requires a coordinating group that can chelate to the ruthenium center and stabilize the ruthenium alkylidene formed during the reaction. Therefore, strategies that increase the stability of the methylidene and alkylidene complexes can produce catalysts with increased activities in water.
