I. Development of a novel nitrogen protection group: Tsoc (triisopropylsilyloxycarbonyl). II. Controlling atropisomerism using a chiral tether in biaryl bond formation. III. Advances in copper hydride chemistry

Nitrogen protection groups are a critical area of peptide synthesis. Although many unique protection groups exist in this field, there are few examples that incorporate silicon, in order to take advantage of the chemospecific unmasking using fluoride. A novel protection group, triisopropylsilyloxycarbonyl (Tsoc), was developed and investigations into its use in peptide chemistry was examined.; The use of transition metals has become a critical area of research in organic synthesis. Stryker's catalyst, (PPh₃)CuH, has long been the preferred method of conjugate reduction of α,β-unsaturated ketones. By using silanes or dialkyl boranes, as the stoichiometric reductant, this process can be made catalytic in copper and the subsequent intermediate (silyl enol ether or boron enolate) used in aldol reactions. When using silanes as the stoichiometric reductant, mixtures of diastereomers are produced in the aldol step, however, when dialkyl boranes are employed diastereoselective aldol reactions can be realized.; In 1956 Eli Lilly discovered what would soon become known as the last defense against S. aureus, vancomycin. Upon elucidation of the precise structure of vancomycin, the task of synthesizing this complex glycopeptide was taken on by several research groups. This molecule presented several challenges to the organic community not only in the synthesis of non-naturally occurring amino acid residues and the presence of eighteen chiral centers, but also in the daunting task of controlling three elements of atropisomerism. Although there has been three total syntheses reported of this compound, no one has been able to form the biaryl portion directly in a stereoselctive fashion to give the S configuration. The use of a chiral tether as a means of controlling axial chirality in biaryl bond formation was investigated and applied toward a model system similar to vancomycin.