The first example of transition-metal-mediated transformations of spirodiepoxides and the first general method for carbon-carbon bond formation using the spirodiepoxide functional group are reported. Organocopper-mediated addition to spirodiepoxides gives direct access to densely functionalized hydroxy ketones. The process establishes two noncontiguous stereocenters and installs two oxygen atoms and a new carbon substituent. The utility of the methodology was demonstrated by preparing the stereotetrad of erythromycin in a short, efficient, and stereoselective route.