alpha-Heteroatom Nitriles as Trianion Synthons: Synthesis of Spirocyclic Heterocycles and the Lepadiformine Alkaloids

The first part of the dissertation describes the total synthesis of the lepadiformine alkaloids A, B, and C. The key bond forming reactions involve a one-pot nitrile anion double alkylation and reductive decyanation/cyclization. The double alkylation was exploited to stereoselectively form the cyclohexyl C ring using an achiral aminonitrile and chiral dibromide electrophile. The reductive cyclization was utilized in the diastereoselective construction of the spiropyrrolidine motif. The spirocyclization proceeded by a double SEinv sequence to provide the spiropyrrolidine with overall retention of stereochemistry at the nitrile bearing carbon.;The second portion details the extension of the double alkylation/reductive cyclization approach to the synthesis of various spirocyclic heterocycles. Simple achiral spirocycles of various ring sizes were explored. The construction of chiral substrates was also investigated to determine the diastereoselectivity concerning the double alkylation as well as the reductive cyclization. The diastereoselectivity for the double alkylation was low to moderate. The reductive cyclization proceeded with high diastereoselectivity for six membered nitrile bearing ring systems.;The final chapter tells of the initial findings concerning two separate projects both involving reductive lithiation. The first details the reductive decyanation of decalin and hydrindane substrates that contain a nitrile at the ring junction carbon. The second involves the reductive lithiation and cyclization of tertiary organolithiums onto a pendent fluoride electrophile.