Post on 13-Feb-2017
Recent Advances of Alkyne Metathesis
Group Meeting
Timothy Chang
11-09-10
Fischer Carbyne and Schrock Alkylidyne
The Organometallic Chemistry of the Transition Metals, 4th Ed., Crabtree.Organotransition Metal Chemistry, From Bonding to Catalysis, Hartwig.
Fischer Schrock
Doublet Quartet
LX type X3 type
4e 6e
-1 -3
lone paircovalent
p-back bonding
3 covalents
Weak donor L Strong donor L
Group Orbitals of +CR Fragment
Carbyne Complexes, Fischer et. al. 1988, VCH
MOs of Fischer Carbyne
Carbyne Complexes, Fischer et. al. 1988, VCH
Group Orbitals of L3M- Fragment
Encyclopedia of Inorganic Chemistry, Electronic Structure of Organometallic Compounds,
Albright, T. A.
Molecular Orbitals of L3M(CR)
Carbyne Complexes, Fischer et. al. 1988, VCH
A Brief History of Alkyne Metathesis
Pennellar, F.; Banks, R. L.; Bailey, G. C. J. Chem. Soc., Chem. Commun. 1968, 1548.
Mortreux, A.; Blanchard, M. J. Chem. Soc., Chem. Commun. 1974, 786.
Katz, T. J.; McGinnis, J. J. Am. Chem. Soc. 1975, 97, 1592.For an account, see Schrock, R. R. Polyhedron, 1995, 14, 3177.
Catalyst Deactivation by Dimerization and Ring Expansion
Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.
“Pseudopoisoning” Effect
Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.
Preparation of (Me3CO)3W(CCMe3)
Schrock et. al. J. Am. Chem. Soc. 1981, 103, 3932.Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.
Application to RCAM
Fürstner et. al. Angew. Chem. Int. Ed. 1998, 37, 1734 and J. Am. Chem. Soc. 1999, 121, 11108.
Thioether, basic nitrogen containing functional groups are not compatible.Tolerate acidic proton of a secondary amide.
Curious Effect of Halogenated Solvents
Fürstner et. al. Chem. Eur. J. 2001, 7, 5299 and J. Am. Chem. Soc. 1999, 121, 9453
Secondary amide is not tolerated.
Major Components of the Molybdenum Species
Schrock et. al. J. Am. Chem. Soc. 1985, 107, 5987 Polyhedron 1995, 15, 3177
Why is 3 not catalytically active?Why are terminal alkynes not viable substrates?
“Deprotiometallacyclobutadiene”
1 : 2 not activeAr = 3,5-xylyl
Cross Metathesis
Fürstner , A., Mathes, C. Org. Lett. 2001, 3, 221
1
Cross Metathesis
Fürstner , A., Mathes, C. Org. Lett. 2001, 3, 221
1
Application of RCM and RCAM to Macrocyclization
RCM RCAM
Fürstner et. al. Chem. Eur. J. 2003, 7, 5299.
Schinzer et. al. ACIEE 1997, 36, 523.
Reductive Recycle Strategy for Catalyst Preparation
Moore et. al. Org. Syn. 2007, 84, 163.
Ar = 3,5-xylyl
- Active catalyst is generated in the presence of various phenols.- Electron-deficient ligands make the catalysts more active e.g. p-nitrophenol (low cost)- Catalyst is active in MeCN even though it is a coordinating solvent.- Secondary amide and thiophene containing molecules can be used.- Bulky ligand is not required. Apparently electronic factor dominates.- Bulky ligands slows down both dimerization and metathesis presumably.
Effects of Alkyl Substituent and Ligand
Moore et. al. J. Am. Chem. Soc. 2004, 126, 329.
R = Me gives polybutyne
Equilibrium ratio of 13:14 = 2:3 (established from both 13 and 14, respectively)
R = Et
5
Optimal R = Et
Optimal Ligand = p-nitrophenol
(cheaper)
Ar = 3,5-xylyl
Homodimerization Substrate Scope
a Closed system, d8-toluene, 20 °C, t1/2 is the time required for the reaction to reach 50% of final constant ratio of 10 to 12. b Open driven condition, solvent 1,2,4-trichlorobenzene, 30 °C, 22 h, 1 mm Hg, yield based on isolated product. c Ligand A ) R,R,R-trifluoro-o-cresol. d Ligand B ) p-nitrophenol.
R = Et
5Ar = 3,5-xylyl
Solvent Effect and Precipitation Strategy
Conversion CHCl3, Toluene: 100% (0.5 h) CH3CN, THF: 76% (8 h)Acetone: 40% (catalyst decomposition)DMF, MeOH: 0%
Precipitation strategy can be utilized to drive the equilibrium towards desired product such as 7.Aprotic, non-coordinating solvents are preferred.
R = Et
5Ar = 3,5-xylyl
Moore et. al. J. Am. Chem. Soc. 2004, 126, 329.
Preparation of Shape-Persistent Macrocycles by PPT Strategy
Zhang, W.; Moore, J. S. J. Am. Chem. Soc. 2004, 126, 12796.
Catalyst Prepared from Nitrides by Metathesis with Alkynes
Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.
- 36 and 38 are preferred thermodynamically.- The formation of 38 is irreversible.- Idea: in situ generation of catalyst by metal nitride/metal alkylidyne interconversion
One major reason that MeCN cannot be used
Johnson et. al. J. Am. Chem. Soc. 2006, 128, 9614. Johnson et. al. Inorg. Chem. 2005, 44, 9140.
Schrock, Organometallics 1986, 5, 398.
Development Towards a Robust and Practical Precatalyst
Fürstner et. al. J. Am. Chem. Soc. 2009, 131, 9468.
distorted square pyramidal
Scope
Fürstner et. al. J. Am. Chem. Soc.2009, 131, 9468
11 can be weighed in air and used under dry air (need increased loading)
Incompatible: epoxide, aldehyde, acyl chloride
Improvements on Triphenylsilanolate Bound Mo (Pre)Catalyst
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
Typical Reaction Conditions for Homodimerization, CM, RCAM(A) 15 (10 mol %), MnCl2 (10 mol %), MS 5 Å, toluene, 80 °C, 30 min, then
addition of the substrate and reaction at 80 °C or 100 °C (for CM).
(B) 24 (2 mol %), toluene, ambient temperature, MS 5 Å.
(C) 25 (5 mol %), MnCl2 (5 mol %), toluene, 80 °C, 30 min; then addition of the substrate and MS 5 Å, and reaction at ambient temperature.
15 is stable on bench top for storage.
Scope
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
Incompatible with aldehyde. Previous stoichiometric experiment showed its conversion to nitrile.
Roles of Molecular Sieve
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
MS removes butyneMS helps liberate Et2O
3 Å MS has no sig. effect (i.e. not equilibrium effect of H2O)
Probing the Active Mo Species
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
trace
Hypotheses:“The small amounts of alkylidynes, such as 16, formed in the mixture must be superbly active”“12.L acts as a reservoir (slow release) (still show catalytic activity at 80 oC for days)
The hypotheses were tested using 19 and 24.
Preparation of Molybdenum Alkylidyne Complexes
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
An Extraordinary Active Metathesis Catalyst
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
Equilibrium reached at ~ 25 min
Application of RCAM to the Synthesis of Lactimidomycin
1.2 g scale84%
Key steps: Ring closing alkyne metathesis and trans-hydrosilylation
Lactimidomycin
Seven sp2 C in a12-membered lactone
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 14064.
Imidazolin-2-iminato Tungsten Catalyst
Tamm et. al. Angew. Chem. Int. Ed. 2007, 46, 8890.
hexane (4.5 mM)2 h, 95%
Conclusion
- New (pre)catalysts are much more functional group tolerant and efficient.
- Bench top stable pre-catalyst has emerged (silanolate bound Mo complexes).
- The yields of cross-metathesis are generally moderate.
- RCAM and homodimerization are relatively mature.
- Three ways to drive the equilibrium of metathesis:
(1) reduced pressure, (2) precipitation and (3) molecular sieve
- Mechanism of some pre-catalysts is still unknown (tris-amido Mo complex).
- Promising in the area of ADIMET and Shape Persistent Macromolecules.
Alkyne Metathesis, see Zhang, Moore Adv. Synth. Catal. 2007, 349, 93. RCAM, see Fürstner, Davies Chem. Commun. 2005, 2307.Carbyne Complexes, Fischer et. al. 1988, VCH VerlagsgesellschaftHandbook of Metathesis: Catalyst Development, Grubbs, Ch 1.11
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