Study On Hydrogen-bonding-promoted Ruthenium-Catalyzed Demanding Ring-closing Metathesis

Sterically demanding metathesis reactions are yet to be developed in the research field of ruthenium-catalyzed olefin metathesis.Due to steric effects,the application of olefin metathesis is often excluded in the synthesis of structurally complex natural products and bioactive drug molecules.Even for the established steric demanding transformations,the slow reaction rates,uses of large amount of expensive ruthenium catalysts and uncontrollable stereochemical outcomes compose significant challenges.Therefore,a general and efficient solution is in high demand.In this thesis,we intended to realize demanding ring-closing metathesis promoted by hydrogen bonding.In the first part,the research progresses in this direction in the last two decades are reviewed.Our research works on the construction of tri-and tetra-substituted olefins by hydrogen-bonding-promoted ring-closing metathesis,and on the removal of ruthenium byproducts are summarized in the result and discussion part.1.Based on our previous work on total synthesis of autolytimycin,an HG-II-catalyzed ring-closing metathesis for constructing the tri-substituted double bond in 5,6-dihydro-a-pyrone system was developed.The reaction condition and substrate scope were explored.A hydrogen bonding-involved reaction mechanism was proposed.2.The hydrogen-bonding-promoted ring-closing metathesis was found able to be used to construct tetra-substituted olefins in further study.The substrate scope of this transformation was explored.3.In the above reactions,several ruthenium-containing byproducts were generated from the decomposition of HG-?,and it was highly difficult to remove these contaminants by column chromatography.After repeated tests,we found that ethylene diamine-type compounds could react with ruthenium byproducts efficiently,thus established a much easier workup procedure.The application of this method for reactions catalyzed by other ruthenium catalysts was also explored.