Olefin Metathesis

• 1950s – In the presence of various organometallo compounds, olefin metathesis (where the R groups of olefins were swapped with the other) occurred

• 1970s – Chauvin and colleagues proposed mechanism that seemed to fit– Like a dance

• 1980s – Schrock and Grubbs synthesized the first metallo-carbene compounds that were air sensitive and shown to catalyze olefin metathesis

• Three types of olefin metathesis– Ring closing metathesis (RCM)– Ring opening metathesis (ROM)– Cross metathesis (CM)

Image from Greco, G.E. Nobel Chemistry in the Laboratory. J. Chem. Ed. 2007,84(12), 1996

Selectivity Model for CM

• Experiments done by Chatterjee et al showed that the various olefin metathesis substrates could be classified by their relative reactivity– Type I: formed homodimers rapidly

– Type II: formed homodimers slowly

– Type III: didn’t form homodimers, participate in CM

– Type IV: spectator olefin, no CM reaction

• Reacting two olefins from different groups could yield stereospecific, easily predictable products in good yield

• Reactivity of olefins depended on things such as sterics as well as deactivating electron-withdrawing groups

Chatterjee, A. K. A General Model for Selectivity in Olefin Metathesis. J. Am. Chem. Soc. 2003, 125, 11360-11370.

Hypothesis

• In testing out the selectivity model, by reacting a type I (allyl chloride) and type II olefin (4-fluoro-β-nitrostyrene), a predictable product can be obtained.

Olefin Metathesis Catalysts• Schrock and Grubbs

– Air sensitive

– Initially were molybdenum and ruthenium based, respectively

– Both won 2005 Nobel Prize in Chemistry for work in olefin metathesis, along with Chauvin

Images from Pappenfus, T. M. Synthesis and Catalytic Activity of Ruthenium-Indenylidene Complexes for Olefin Metathesis, J. Chem. Ed.

2007, 84 (12), 1998-2000.

Ruthenium Catalysts, continued

• Ruthenium indenylidene complexes– Can be synthesized from commercially available diphenyl propargyl

alcohol, synthetic precursors are all relatively air stable, when not in solution

– Catalytic properties similar to classic Grubbs, if not superior

– Synthesis methods are also relatively simple

Images from Pappenfus, T. M. Synthesis and Catalytic Activity of Ruthenium-Indenylidene Complexes for Olefin Metathesis, J. Chem. Ed.

2007, 84 (12), 1998-2000.

Methods• Synthesis of RuCl2(PPh3)3

– Reflux RuCl3·3H2O with triphenylphosphine under argon in a 1:6 molar ratio for 3 hours, filter out black crystals, wash with anhydrous ether.

• Synthesis of 1a and 1b– 1a:

• Reflux diphenyl propargyl alcohol with RuCl2(PPh3)3 (2:1 equivalents) in a positive argon atmosphere for 2.5 hours, with THF as the solvent. Remove solvent via rotary evaporation, redissolve dark red residue in CH2Cl2, recrystallize with hexanes, slowly. Filter out solid, store in desiccator.

– 1b:• Stir 1a and tricyclohexane in a 1:3.3 equivalent ratio under a positive argon

atmosphere for 1.5 hours, with dichloromethane as the solvent. Remove solvent via rotary evaporation, added hexanes and stir for another 30 minutes. Filter out brown-orange solid, store in desiccator.

• CM reaction– Reflux styrene, allyl chloride and 1b in a 1:1:0.01 ratio overnight.

• Characterization methods– NMR & IR, as well as TM for the RuCl2(PPh3)3

Synthesis methods taken from Parry, R. W. Tris(triphenylphospine)dichlororuthenium(II) Inorganic Syntheses. 1970, XII, 238-239 as well as

Pappenfus, T. M. Synthesis and Catalytic Activity of Ruthenium-Indenylidene Complexes for Olefin Metathesis, J. Chem. Ed. 2007, 84 (12),

1998-2000.

Data: NMR spectra for 1a and 1b, literature

1a in chloroform-d 1b in chloroform-d

All reference spectra obtained from Pappenfus, T. M. Synthesis and Catalytic Activity of Ruthenium-Indenylidene Complexes for Olefin

Metathesis, J. Chem. Ed. 2007, 84 (12), 1998-2000.

Results: NMR spectra of 1a and 1b, experimental

1a in benzene-d 1b in benzene-d

Data: Literature IR spectra of 1a and 1b

Result: Experimental IR spectra of 1a and 1b

1a with nujol 1b with nujol

Data: Allyl Chloride impurities

Used allyl chloride in benzene-d Allyl chloride without impurities, benzene-d

Results: Product vs 1b + reagents

Product in benzene-d 1b + reagents in benzene-d

Results: % Yields

• RuCl2(PPh3)3 (Yield: 0.5059 g)

– RuCl3·H2O used: 0.1658 g (0.641 mmoles, limiting reagent)

– triphenylphosphine used: 0.9986 g (3.807 mmoles)

– % yield: 82.3%

– TM: 130-134˚C, literature indicates 132-134˚C

• 1a (Yield: 0.1944 g)– RuCl2(PPh3)3 used: 0.3621 g (0.378 mmoles, limiting reagent)

– Diphenyl propargyl alcohol used: 0.1513 g (0.727 mmoles)

– % yield: 58.0%

• 1b (Yield: 0.1315 g)– 1a used: 0.1524 g (0.172 mmoles, limiting reagent)

– Tricyclohexylphosphine used: 0.1672 g (0.596 mmoles)

– % yield: 89.9%

Literature value of Tm obtained from Parry, R. W. Tris(triphenylphospine)dichlororuthenium(II) Inorganic Syntheses. 1970, XII, 238-239.

Discussion

• The ruthenium indenylidene complexes synthesized, based on the NMRs, seem to be the desired complexes

• The IRs are less conclusive– Nujol absorptions seem to drown out any

characteristic absorptions (peaks at 2950-2800, 1465-1450 and 1380-1370 cm-1)

Nujol peaks referenced from http://en.wikipedia.org/wiki/Nujol

Did a reaction occur?

• NMR seems to indicate it did• However, it’s also possible that the difference in NMRs is

due to the presence of liquid allyl chloride in the “pre-reaction” NMR taken

• Theoretically, the allyl chloride is highly reactive and should have reacted with the styrene– Normally, styrenes are part of the Type II group, and is also

reactive in CM reactions. However, it’s possible that the presence of the nitro group directly attached to the C=C bond highly reduced its reactivity

Other possible reasons for no reaction

• Many of the intermediates, though fairly air stable, will react with air in the presence of water.

• The purity of the catalyst is unknown, possible that it was much less than 1% molar of the reagents

• Even if the catalyst were pure, it’s possible that 1% molar is insufficient to catalyze the reaction overnight.

• When the CM reaction beaker was refluxed, the solvent evaporated very quickly, had to turn off the heating mantle

• It’s possible that since allyl chloride is fairly volatile, it evaporated before the reaction could take place.

• The effectiveness of the ruthenium indenylidene complexes has only been shown in RCM and ROM.

Conclusions

• Chatterjee et al’s model of CM selectivity is still valid• Although the results of this experiment are not

conclusive, the model is also not disproven• This model of CM selectivity could open paths to new

synthetic routes to important organic compounds, such as various drugs (i.e. epothilones, antitumor agents)

Conclusions: ways to improve

• Find olefins of different reactivities that are both solid– Also, olefins that are not deactivated by electron withdrawing

groups– Product of CM should have distinctive properties from the

reagents, either physical or spectral

• Possibly work with different catalysts which are known to have high reactivity in CM reactions

• Procure correct NMR solvent, to compare with literature

References

• Casey, C. P. 2005 Nobel Prize in Chemistry: Development of the Olefin Metathesis Method in Organic Synthesis. J. Chem. Ed. 2006, 82 (2), 192-195.

• Chatterjee, A. K. A General Model for Selectivity in Olefin Metathesis. J. Am. Chem. Soc. 2003, 125, 11360-11370.

• Fürstner, A. Indenylidene Complexes of Ruthenium: Optimized Synthesis, Structure Elucidation, and Performance as Catalysts for Olefin Metathesis – Application to the Synthesis of the ADE- Ring System of Nakadomarin A. Chem. Eur. J. 2001, 7 (22), 4811- 4820.

• Pappenfus, T. M. Synthesis and Catalytic Activity of Ruthenium-Indenylidene Complexes for Olefin Metathesis, J. Chem. Ed. 2007, 84 (12), 1998-2000.

• Parry, R. W. Tris(triphenylphospine)dichlororuthenium(II) Inorganic Syntheses. 1970, XII, 238-239.