I. [1,2]-Brook rearrangement: Application of silyl glyoxylates in a novel glycolate aldol reaction and in a controlled oligomerization to complete the total synthesis of zaragozic acid C. II. Progress toward the total synthesis of pactamycin

I. Symbiotic reagent activation: Oppenauer oxidation of magnesium alkoxides by silyl glyoxylates triggers second-stage aldolization. The treatment of silyl glyoxylates with magnesium alkoxides leads to a Meerwein-Ponndorf-Verley reduction of the silyl glyoxylate and an Oppenauer oxidation of the alkoxide. The symbiotic transfer of a hydride from the alkoxide to the silyl glyoxylate triggers a [1,2]-Brook rearrangement forming an enolate that undergoes an aldol reaction with the carbonyl oxidation product. The magnesium alkoxide can be generated via deprotonation of primary and secondary alcohols with EtMgBr, Grignard addition to aldehydes or CuI-catalyzed alkylation of epoxides. Moderate levels of anti-diastereoselectivity were observed with primary aliphatic alkoxides. Stereoselective as well as catalytic versions of this reaction were also investigated.*;II. Total synthesis of zaragozic acid C via controlled oligomerization. Tert-butyldimethylsilyl glyoxylate was used as a dipolar glycolic acid synthon to rapidly assemble the core of zaragozic acid C by means of a controlled oligomerization. This new methodology facilitated a rapid, stereocontrolled construction of the carbon skeleton while minimizing the need for functional group and oxidation state manipulation.*;III. Progress toward the total synthesis of pactamycin. A review of literature covering previous synthetic approaches to the core of pactamycin is presented. Work was done on the construction of precursors to an intramolecular cyclization to form the densely functionalized core of pactamycin. The strategies involved using a diazo group to block reactivity and allow installation of core functionality. Subsequent oxidization would reveal the requisite electrophile for the cyclization.*;*Please refer to dissertation for diagrams.