Within the field of drug design, there is a great interest in the development of synthetic libraries that mimic the structural complexity of natural product scaffolds. Recent cheminformatic analyses have revealed that 83% of the core ring scaffolds found in natural products are absent among commercially available drug molecules. Spirocycles are one of these cores presumably due to the difficulty found in synthesizing this scaffold. In order to address the limitation in synthetic technology, a novel approach to spiroethers, azaspiro-ring systems, spirocarbocycles, spiroketals, and spiroaminals has been developed using metal carbene initiated cascade reactions. The identification of two novel catalytic systems were critical to the success of synthesizing these varying spirocycles. The first development was identification of Rh2(esp)2 as a catalyst for the efficient insertion of carboxylic acids into acceptor/acceptor diazocarbonyls. The second development was the identification of Rh2(esp)2/PPh3AuOTf as a synergistic catalytic combination for an O–H insertion/Conia-ene cascade for the stereoselective synthesis of tetrahydrofurans and gamma-butyrolactones. These systems were applied to the synthesis of spiroethers using an O–H insertion/Conia-cascade and azaspiro-ring systems using an N–H insertion/Conia-ene cascade. Subsequently, the Rh(II)/Au(I) system was applied to the synthesis of 5-, 6-, and 7-membered oxindole hybridized spirocarbocycles. Lastly, direct access to spiroketals and spiroaminals using a metal carbene initiated cascade reaction dependent on the use of alpha-diazoketones was developed. Within each synthetic effort, valuable mechanistic insights were obtained to justify stereochemistry and applicability to a substrate scope.