Recent Advances of Alkyne Metathesis. Group Meeting Timothy Chang

Transcription

1 Recent Advances of Alkyne Metathesis Group Meeting Timothy Chang

2 Fischer Carbyne and Schrock Alkylidyne Fischer Doublet LX type 4e Schrock Quartet X 3 type 6e -1-3 lone pair covalent p-back bonding Weak donor L 3 covalents Strong donor L The Organometallic Chemistry of the Transition Metals, 4 th Ed., Crabtree. Organotransition Metal Chemistry, From Bonding to Catalysis, Hartwig.

3 Carbyne Complexes, Fischer et. al. 1988, VCH Group Orbitals of + CR Fragment

4 Carbyne Complexes, Fischer et. al. 1988, VCH MOs of Fischer Carbyne

5 Group Orbitals of L 3 M - Fragment Encyclopedia of Inorganic Chemistry, Electronic Structure of Organometallic Compounds, Albright, T. A.

6 Carbyne Complexes, Fischer et. al. 1988, VCH Molecular Orbitals of L 3 M(CR)

7 A Brief History of Alkyne Metathesis Pennellar, F.; Banks, R. L.; Bailey, G. C. J. Chem. Soc., Chem. Commun. 1968, Mortreux, A.; Blanchard, M. J. Chem. Soc., Chem. Commun. 1974, 786. Katz, T. J.; McGinnis, J. J. Am. Chem. Soc. 1975, 97, For an account, see Schrock, R. R. Polyhedron, 1995, 14, 3177.

8 Catalyst Deactivation by Dimerization and Ring Expansion Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.

9 Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93. Pseudopoisoning Effect

10 Schrock et. al. J. Am. Chem. Soc. 1981, 103, Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93. Preparation of (Me 3 CO) 3 W(CCMe 3 )

11 Application to RCAM Thioether, basic nitrogen containing functional groups are not compatible. Tolerate acidic proton of a secondary amide. Fürstner et. al. Angew. Chem. Int. Ed. 1998, 37, 1734 and J. Am. Chem. Soc. 1999, 121,

12 Curious Effect of Halogenated Solvents Secondary amide is not tolerated. Fürstner et. al. Chem. Eur. J. 2001, 7, 5299 and J. Am. Chem. Soc. 1999, 121, 9453

13 Major Components of the Molybdenum Species Ar = 3,5-xylyl 1 : 2 not active Why is 3 not catalytically active? Why are terminal alkynes not viable substrates? Deprotiometallacyclobutadiene Schrock et. al. J. Am. Chem. Soc. 1985, 107, 5987 Polyhedron 1995, 15, 3177

14 Cross Metathesis 1 Fürstner, A., Mathes, C. Org. Lett. 2001, 3, 221

15 Cross Metathesis 1 Fürstner, A., Mathes, C. Org. Lett. 2001, 3, 221

16 Application of RCM and RCAM to Macrocyclization RCM Schinzer et. al. ACIEE 1997, 36, 523. RCAM Fürstner et. al. Chem. Eur. J. 2003, 7, 5299.

17 Reductive Recycle Strategy for Catalyst Preparation 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. Moore et. al. Org. Syn. 2007, 84, 163.

18 Effects of Alkyl Substituent and Ligand R = Et 5 Ar = 3,5-xylyl Optimal R = Et Optimal Ligand = p-nitrophenol (cheaper) R = Me gives polybutyne Equilibrium ratio of 13:14 = 2:3 (established from both 13 and 14, respectively) Moore et. al. J. Am. Chem. Soc. 2004, 126, 329.

19 Homodimerization Substrate Scope R = Et 5 Ar = 3,5-xylyl 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.

20 Solvent Effect and Precipitation Strategy R = Et 5 Ar = 3,5-xylyl Conversion CHCl 3, Toluene: 100% (0.5 h) CH 3 CN, 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. Moore et. al. J. Am. Chem. Soc. 2004, 126, 329.

21 Preparation of Shape-Persistent Macrocycles by PPT Strategy Zhang, W.; Moore, J. S. J. Am. Chem. Soc. 2004, 126,

22 Catalyst Prepared from Nitrides by Metathesis with Alkynes One major reason that MeCN cannot be used Schrock, Organometallics 1986, 5, 398. Johnson et. al. J. Am. Chem. Soc. 2006, 128, Johnson et. al. Inorg. Chem. 2005, 44, and 38 are preferred thermodynamically. - The formation of 38 is irreversible. - Idea: in situ generation of catalyst by metal nitride/metal alkylidyne interconversion Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.

23 Development Towards a Robust and Practical Precatalyst distorted square pyramidal Fürstner et. al. J. Am. Chem. Soc. 2009, 131, 9468.

24 Scope 11 can be weighed in air and used under dry air (need increased loading) Incompatible: epoxide, aldehyde, acyl chloride Fürstner et. al. J. Am. Chem. Soc. 2009, 131, 9468

25 Improvements on Triphenylsilanolate Bound Mo (Pre)Catalyst Typical Reaction Conditions for Homodimerization, CM, RCAM (A) 15 (10 mol %), MnCl 2 (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 %), MnCl 2 (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. Fürstner et. al. J. Am. Chem. Soc. 2010, 132,

26 Scope Incompatible with aldehyde. Previous stoichiometric experiment showed its conversion to nitrile. Fürstner et. al. J. Am. Chem. Soc. 2010, 132,

27 Roles of Molecular Sieve MS removes butyne MS helps liberate Et 2 O Fürstner et. al. J. Am. Chem. Soc. 2010, 132, Å MS has no sig. effect (i.e. not equilibrium effect of H 2 O)

28 Probing the Active Mo Species 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 o C for days) The hypotheses were tested using 19 and 24. Fürstner et. al. J. Am. Chem. Soc. 2010, 132,

29 Preparation of Molybdenum Alkylidyne Complexes Fürstner et. al. J. Am. Chem. Soc. 2010, 132,

30 An Extraordinary Active Metathesis Catalyst Equilibrium reached at ~ 25 min Fürstner et. al. J. Am. Chem. Soc. 2010, 132,

31 Application of RCAM to the Synthesis of Lactimidomycin Lactimidomycin Seven sp 2 C in a 12-membered lactone Key steps: Ring closing alkyne metathesis and trans-hydrosilylation 1.2 g scale 84% Fürstner et. al. J. Am. Chem. Soc. 2010, 132,

32 Imidazolin-2-iminato Tungsten Catalyst hexane (4.5 mm) 2 h, 95% Tamm et. al. Angew. Chem. Int. Ed. 2007, 46, 8890.

33 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. For reviews on: Alkyne Metathesis, see Zhang, Moore Adv. Synth. Catal. 2007, 349, 93. RCAM, see Fürstner, Davies Chem. Commun. 2005, Carbyne Complexes, Fischer et. al. 1988, VCH Verlagsgesellschaft Handbook of Metathesis: Catalyst Development, Grubbs, Ch 1.11