| During the last two decades, there has been a significant increase in the use of alpha-diazo carbonyl compounds as precursors in C-C bond forming reactions and, in particular, in the generation of quaternary stereocenters. Specifically, the dirhodium(II)-catalyzed decomposition of alpha-diazo carbonyl compounds and the intramolecular insertion of the resulting carbenoid species into unactivated C-H bonds has emerged as a powerful methodology for the construction of both carbocyclic and heterocyclic systems. In the first part of this thesis, the dirhodium(II)-catalyzed intramolecular C-H activation reaction of 2-diazoacetyl-1,3-dioxanes is investigated and utilized for the preparation of the 2,8-dioxabicyclo[3.2.1]octane ring system of zaragozic acids. Zaragozic acids are a family of natural occurring fungal metabolites, which display a nanomolar inhibition of the mammalian squalene synthase, the enzyme that catalyzes the first committed step in the biosynthesis of cholesterol. Their general structure includes an unusual polyoxygenated core, which features six contiguous stereocenters. The chemistry developed in the first part of the thesis is subsequently applied to the asymmetric synthesis of an advanced intermediate for the preparation of zaragozic acid Ax3. Central to our strategy is a regioselective C-H insertion reaction, mediated by a Cu(II) catalyst. In this process, carboxylate groups efficiently direct insertion of the intermediate carbenoid to one of six possible C-H bonds. As an offshoot of these studies, in the third part of the thesis is presented a novel method for the diastereoselective preparation of 4,6-O-pyruvated pyranosides, which play an important role in modulating the physical and biological properties of bacterial cell wall polysaccharides. |
