Transition Metal-Catalyzed Alkyl-Alkyl (sp3-sp3) Cross-Coupling, Its Applications in the Chemistry of N-Boc-Pyrrolidine and Piperidine, and NMR Structural Studies of Organolithiums in Solution

The advent of transition metal-catalyzed cross-coupling involving the formation of new carbon-carbon bonds has led to many great advances in synthetic organic chemistry. The coupling of aryl- or alkenyl- electrophiles with organometallic nucleophiles is commonplace; however, alkyl-alkyl (sp 3-sp3) cross-coupling reactions have been plagued by inherent difficulties. Previously, in the course of investigation of transition metal alkyl intermediates for such processes, a transition metal hydride complex with a rare linear M-H-M linkage was discovered. Using X-ray and neutron crystallography, a structural analysis was performed on that complex, a previously reported non-linear analog, and two new related compounds to determine that inter- and intramolecular interactions play a significant role in the geometry of the M-H-M linkage. In addition, two new transition metal complexes with catalytic potential were generated and characterized crystallographically.;Attempts were made at applying transition metal-catalyzed alkyl-alkyl cross-coupling in 2-alkylations of N-Boc-pyrrolidine and piperidine. A variety of potential organometallic nucleophiles for such processes are accessible through the 2-lithiated species. Several Negishi and Suzuki reactions were performed using RZnCl and RB(OR)2, respectively. There was limited success with the Negishi reactions using bromobenzene electrophiles; however, the Suzuki reactions were unsuccessful.;With the discovery of a rare catalytic dynamic resolution of N-Boc-2-lithiopiperidine in the presence of a chiral auxiliary, focus was shifted to mechanistic understanding. Structural studies of involved species, including the lithiated substrate and chiral auxiliaries, were conducted using 6Li, 15N, and 13C NMR spectroscopy to determine aggregation states.