有机化合物的合成英文培训资料.docx

Alkene/Alkyne MetathesisWuXi AppTecTraining Committee Alkene/Alkyne Metathesis WuXi AppTec Training Committee Jianguang Lei Overview of topics to be discussed: Carbon carbon double bond formation via Alkene or alkyne metathesis reactions Background-Milestones Catalysts  Cp iPr iPr General mechanism R W(CO)5 Ph Cp Ti Cl Al N Ph (F3C)2HCOC Mo (F3C)2HCOC R R1  R3 R2 2 R R (Katz, 1974) R= Ph; OMe 1978 Tebbe reagent 1990 Schrock R1 R 3 N N R [M] R  [M]  [M]  Ph Pcy3  Pcy3 Cy Cy Cl Ru Ph 1 A B R R1 C R2 Cl Ru Ph 3Cl Pcy 3 Cl Ru Ph Cl Pcy Cl Cy N N Cy 3[M] F 5 3 1992 1995 1998 Grubbs 1st generation catalyst R Hermann Pcy3 N Mes R1 R R1 Mes N N Mes Cl Ru N [M] R R3 Cl Ru Ph Cl O Mes Cl Ru R2 4 [M] R2 E R2 D 3 Cl Pcy3 Cl O Grubbs 2nd Hoveyda-Grubbs Catalyst Hoveyda-Grubbs Catalyst generation catalyst 1st Generation 2nd Generation Schrock’s Catalyst Commercially available Air and water sensitive Intolerant of protons on heteroatoms(RCO2H, RSH,ROH, etc.) and some functionalities (eg. RCHO)  Cl Cl Mes N Cl Pcy3 Ru Ph Pcy3 Mes Ligand Effect on Catalyst Activity: Halides: I Br Cl Phosphines: Catalyst activity increases as cone angle and Electron deficient Mo(VI), Cl Ru Ph Pcy3 Eletron donating ability increase iPr iPr 4-e species Ring Closing Metathesis (RCM) N Ph (F3C)2HCOC Mo (F3C)2HCOC NAr ligand, OR ligands, and initial alkylidene,need to be bulky to allow for isolation E l e c t r o n w i t h d r a w i n g  Si O Si  Re2O7/Al2O3-SnBu4 dilute Schrocks catalyst Si O Si 14%  ADMET 86% alkoxides increase reactivity concentrated 95% 5% Grubbs Metathesis Catalyst Commercially available Reasonably stable toward H2O, O2, and minor impurities ease of handling Lower reactivity vs. Molybdenum imido alkylidene catalyst High functional group tolerance Intramolecular metathesis of a diene to form a cyclic olefin Reaction pathway of diene depends on catalyst, dilution, ring size, and substrate Dilution: Intermolecular ADMET can