Kinetics Controlled Asymmetric Copper Catalyzed Intramolecular Silicon-oxygen Coupling Reaction

Organosilicon compounds are privileged structural motif found in amounts of biologically active molecules,and silicon-containing compounds are important component of them.Considering the prevalence of this structural unit,there has been considerable interest and challenge in developing methods for accessing1,3-dihydroisobenzofuran structures in organic synthesis and pharmaceutical chemistry,especially for silicon substituted 1,3-dihydroisobenzofuran structures,which may have better efficacy and fewer side effects.However,there are still bottlenecks in the difficulty of introducing silicon atoms and controlling stereospecificities.This thesis mainly focused on the development of Cu-catalyzed intramolecular kinetic resolution of o-silyldiphenylcarbinols to access silicon substituted 1,3-dihydroisobenzofuran with excellent stereospecificities.A kinetic resolution of o-silyldiphenylcarbinols has been developed by CuI/PyrOx-catalyzed intramolecular silicon-carbon bond breaking reaction.This reaction provides a feasible one-step method for the synthesis of silicon substituted1,3-dihydroisobenzofuran with excellent diastereoselectivities and enantioselectivies.Under the optimal reaction conditions,various optically active silicon substituted1,3-dihydroisobenzofuran with two sterogenic centers could be obtained up to 85%enantiomeric excesses with up to 20:1 diastereoselectivities,and the selectivity factor was up to 20.8.In summary,the Intramolecular kinetic resolution reactions of o-silyldiphenylcarbinols have been achieved using a catalytic system composed of copper with different pyridine Oxazoline ligands,providing a practical approach for the facile synthesis of ilicon substituted 1,3-dihydroisobenzofuran with high enantiomeric and diastereoselectivities in most cases.