Two different strategies examine intramolecular cyclizations of chiral, metalated nitriles. Cyclizations onto allylic electrophiles through competitive SN2 or SN2' displacements have different trajectories reflecting the different conformations within the forming ring. Deuterium labeling with allylic electrophiles reveals an inherent preference for SN2 displacements reflecting the optimal orbital overlap for the two different geometries. / Bayer School of Natural and Environmental Sciences; / Chemistry and Biochemistry / MS; / Thesis;

This thesis describes new methods of carbon-carbon bond formation using metalated nitriles generated via metal exchange reactions. Sulfinylnitriles undergo a sulfinyl-metal exchange to yield lithiated, magnesiated and zincated nitriles, which can trap a range of electrophiles. The sulfinyl-metal exchange is effective with vinylic, quaternary and tertiary substitution patterns and addresses the long-standing problem of alkylating secondary nitriles. This method was then further extended to other oxidation states of sulfur, namely sulfonyl-metal exchange and relatively unknown sulfide-metal exchange. The sulfide metal exchange overcomes the problem related to the propensity of highly substituted sulfinylnitriles to eliminate. Sulfide-metal exchange is synthetically attractive because of the numerous methods for generating arylsulfides and the high tolerance of arylsulfides to numerous reagents. <br>A copper-catalyzed arylation reaction of aryl iodides and metalated nitriles was developed using catalytic Cu (I) and an amine ligand. A proof of principle has been established, providing a sound basis for developing the reaction. A new strategy has been developed for alkylation of alkenenitrile using LDA as base in presence of catalytic CuCN. Subsequent trapping with an electrophile, affords alkylated alkenenitriles in which the olefin is no longer in conjugation with the nitrile. <br>The distinct structural differences between N- & C-metalated nitriles have been harnessed in a series of chemoselective alkylations. Lithiated nitriles are found to be particularly reactive toward alkyl halides whereas magnesiated nitriles react selectively with oxygenated electrophiles. Using this strategy allows chemoselective alkylation of metalated nitriles. / Bayer School of Natural and Environmental Sciences; / Chemistry and Biochemistry / PhD; / Dissertation;