The next challenge of the synthesis was optimization of the key sulfamate-tethered aza-Wacker cyclization reaction. Despite their remarkable utility for site-selective amination, aza-Wacker reactions are rarely used as key steps in the syntheses of complex molecules. Tethered aza-Wacker reactions are particularly powerful because a pre-existing C-N bond is no longer required to form a new one. Our laboratory has a programmatic focus on increasing the prominence of tethered aza-Wacker technology in complex molecule syntheses, and our pursuit of Bactobolin A provided a perfect opportunity to further develop the sulfamate-tethered variant of this chemistry. With 15 mol% of Pd(OAc)2 and 1 equivalent of Cu(OAc)2, cyclized product was isolated in a 20% yield (Figure , Entry 1). Increasing the loading of Pd(OAc)2 to 25 mol% led to an increase in product yield to 45% (Figure , Entry 2). While further [Pd] loading was deleterious (Figure , Entry 3), increasing the reaction time from 16 hours to 24 hours was markedly beneficial (Figure , Entry 4). The reaction yield plateaued at 36 hours (Figure , Entries 5-6).