Studies on the Structure/Reactivity Relationships of Bicyclic Epoxonium Ions and Tethered Nucleophiles. Efforts towards the Total Synthesis of (+)-Lactodehydrothyrsiferol and its Analogs. Multicomponent Approach to the Synthesis of Oxidized Amides through Nitrile Hydrozirconation

摘要

A systematic study on the structure/reactivity relationships of bicyclic epoxonium ions towards tethered nucleophiles has been conducted. The cyclization results show that bicyclo[3.1.0] epoxonium ions have a significant to exclusive preference for exo-cyclizations while bicyclo[4.1.0] epoxonium ions have a strong preference for endo-cyclizations.A convergent approach towards the total synthesis of polycyclic ether natural product (+)-lactodehydrothyrsiferol and its analogs is currently being pursued. This route includes the stereoselective reduction of the bicyclo[3.2.1] ketal which could be prepared from coupling of the functionalized aldehyde and vinyl iodide. Both enantiopure fragments can be obtained from cyclizations of the diepoxide and the monoepoxide, respectively. Key transformations involve two asymmetric epoxidations, a cascade cyclization of diepoxide, a Cr/Ni-mediated coupling reaction and a stereoselective reduction of bicyclo[3.2.1] ketal.An efficient one-pot synthesis of oxidized amides from nitrile hydrozirconation has been developed. From the common acylimine intermediates, acyl aminals can be accessed through alcohol addition, acyl hemiaminals can be accessed through water addition and enamides can be accessed through tautomerization.