UCLA

Chapter one provides a summary of efforts towards the syntheses of the welwitindolinones with bicyclo[4.3.1]decane cores. Emphasis is given to more recent approaches that have successfully assembled the bicyclic core of the natural products. Chapters two, three, and four present our total syntheses of the welwitindolinone natural products. The enantiospecific total syntheses of N-methylwelwitindolinone C isothiocyanate, N-methylwelwitindolinone D isonitrile, and N-methylwelwitindolinone B isothiocyanate are detailed. The approach to these natural products features an aryne cyclization to construct the bicyclo[4.3.1]decane core of the molecules as well as a C-H nitrene insertion reaction to install the bridgehead nitrogen substituent. In chapter three, a dual C-H functionalization event installs the challenging ether linkage and allows for completion of (-)-N-methylwelwitindolinone D isonitrile. Chapter four details a regio- and diastereoselective chlorinative oxabicyclic opening to enable the first total synthesis of N-methylwelwitindolinone B isothiocyanate.