高三化学中国国家集训队上课课件3Metathesis.ppt

Lecture: Transition Metal Catalyzed Complexity Generating Reactions 2 Metathesis,Outline Overview of olefin metathesis Olefin metathesis Ring closing metathesis Ring opening metathesis Cross metathesis Enyne metathesis Diyne metathesis,Reference ACIEE., 2000, 39, 3012 ACIEE., 1997, 36, 2036 JCS. PT1, 1998, 371 Tetrahedron. 1998, 54, 4413 Acc. Chem. Res. 1995, 28, 446,更多资源,Organo-transition Metal Chemistry,Chemistry involves intermediates containing transition metal- carbon bonds,Olefin Metathesis,Olefin Metathesis: metal-catalyzed exchange of olefins.,Metal-carbene Complex,Olefin metathesis catalysts tend to be between Schrock and Fischer carbenes,Representative Catalysts,Development of well-defined metal-carbene complexes as pre-catalysts,Developments in Catalyst,Sigma-donating N-heterocyclic carbene ligands increase general reactivity and thermal stability Arduengo A. et al Acc. Chem. Res. 1999, 32, 913,Attaching Privileged chiral ligand Possible bench top use Hoveyda. A. H. et al Angew. Chem. Int. Ed. 2001, 40, 1452,Still useful for some substrates Air and moisture sensitive (glove box) J. Org. Chem. 1998, 63, 8626,Mechanistic Model of the Metathesis Reaction,Consists of a sequence of reversible formal 2+2 cycloaddition/ cycloreversion processes.,Grubbs. R. H. et al J. Am. Chem. Soc. 1975, 97, 3265,Categories of Metathesis Events,RCM (Ring-closing metathesis) A B C ROM (Ring-opening metathesis) C B A CM (Cross metathesis) A B D ROMP (Ring-opening metathesis polymerization) C B E,Engineering the Direction of the Equilibrium for Ring Closing Metathesis,Ethylene gas generally decreases RCM rate Lower concentration can prevent polymerization and cross metathesis Higher temperature usually promotes RCM process (S gain),Detailed Mechanistic Model of RCM,Dissociative pathway dominates,Grubbs. R. H. et al J. Am. Chem. Soc. 1997, 119, 3887,Factors Affecting RCM,Substitution effects on metal carbene and olefin exchange (sterics and electronics),Grubbs. R. H. et al. Organometallics 1998, 17, 2484,RCM is one of the most useful strategies for ring closure but it cannot be used to make three or four membered rings due to ring strain and the reversibility of the process,Maier. M. E. et al. Angew. Chem. Int. Ed. 2000, 39, 2073,Substitution Effects on RCM: A Comparison of Catalysts,Chemtracts (Org. Chem) 2000, 88,RCM: An Invaluable Tool for Generation of Cyclic Structures in TOS,Remarkable functional group tolerance,Danishesky. S. J. et al J. Am. Chem. Soc. 1997, 119, 10073,Martin. S. F. et al J. Am. Chem. Soc. 1999, 121, 866 Furstner. A. et al J. Org. Chem. 1996, 61, 8746 Hoveyda. A. H et al J. Am. Chem. Soc. 1995, 117, 2943,Clark. J. et al Angew. Chem. Int. Ed. 2000, 39, 372,Double RCM 1,Diastereoselective two-directional RCM,About “Two-directional chain synthesis in TOS” Schreiber. S. L. et al Acc. Chem. Res. 1994, 27, 9,Double RCM 2,Wallace. D. J. et al Tet. Lett. 2000, 41, 2027 Harrity. J. P. et al Tet. Lett. 1999, 40, 3247,Differentiation of diastereotopic olefins,ROM/Double RCM 1,A powerful topology-altering reaction.,Schreiber. S. L. et al, Org. Lett. 2000, 2, 709,Shair M. D. et al, unpublished,ROM/Double RCM or RCM,Schreiber. S. L. et al unpublished,One stereocenter dictates mode of cyclization,ROM/RCM 2,Unstrained cyclic olefin (cyclopentane, cyclohexane). Ethylene gas prevents polymerization. Subtle differences in substrates frequently alter the equilibrium.,Blechert. S. et al Chem. Comm. 2000, 1501,ROM/Double RCM 3,Burke. S. D. et al J. Org. Chem. 1998 63 8826,Difference in reactivity of two catalysts,RCM: Macrocycle Synthesis,Furstner. A. et al, Synthesis 1997 792,En Masse Generation of Macrocycles Using Conformational Analysis,Schreiber. S. L. et al J. Am. Chem. Soc. 1999, 121, 10648.,Expanded six-membered ring leads to higher effective molarity between two reactive termini Minimization of Syn-pentane interaction and A1,3 strain,En Masse Generation of Macrocycles Using Conformational Analysis,Schreiber S. L. et al unpublished,Preference for E-olefin formation due to the conformational bias.,Cross Metathesis 1,In general, lack of control of homo- and hetero-dimerization Employment of an excess of the disubstituted olefin counterpart (preformed homo-dimer) relative to terminal olefin leads to selective formation of hetero-dimer.,Grubbs. R. H. et al. J. Am. Chem. Soc. 2000, 122, 58,Cross Metathesis 2,Grubbs. R. H. et al. J. Am. Chem. Soc. 2000, 122, 3783,Smith III. A. B. et al J. Am. Chem. Soc. 2000, 122, 4984 Also Furstner. A. et al Org. Lett. 2001, 3, 449,CM/Macro-RCM 1,Target product is much lower in energy than other possible products Remarkable robustness of metal carbene species Exploitation of reversible nature of cross-metathesis process,CM-RCM 2 Convergence of Intermediates to Products,Smith III. A. B. et al J. Am. Chem. Soc. 2000, 122, 4984,Enyne Metathesis,Mechanism: Yne-ene type or Ene-yne type,Enyne-RCM gives Type I or Type II diene formation,Grubbs. R. H. et al J. Am. Chem. Soc. 1994, 116, 10802,Tandem Dienyne RCM 1,Tandem Dienyne RCM 2,Boyer. F. D. et al Org. Lett. 2001, 3, 3095,Mori. M. et al Org. Lett. 2001, 3, 1161,ROM/RCM on Enyne Substrate,Without ethylene gas, the reaction does not proceed,Enyne-CM/RCM/DA,Diver. S. et al Tet. Lett. 2001, 42, 171,E/Z selectivity of CM determines RCM,Macro-Enyne-RCM 1 Type II Diene Formation,Shair. M. D. et al, unpublished,Macro-Enyne-RCM 2 Transannular Diels-Alder Reaction,Shair. M. D. et al, unpublished,更多资源,Diyne Metathesis,Alkyne RCM in combination with Lindlar partial hydrogenation is a selective way to generate macrocyclic (Z)-olefins,Catalyst (Schrock alkylidyne complex),D