Initial attempts to open the OBD 18 using Lauten's Nicatalyzed conditions gave a variety of undesired products, while Pd-catalyzed conditions reported by Cheng gave a 99% yield of the exo-alkene 19 (Scheme 3A). Variations on the Cheng conditions (see the Supporting Information for details) still favored isomerization. Thus, we shifted our Scheme 3. A) Pd-catalyzed OBD ring-opening using a model compound. B) Efforts using Sm-mediated OBD ringopening. C) Successful OBD ring-opening with advanced NOG AB ring scaffolds. approach and took inspiration from Molander's reductions of vinyloxiranes to allylic alcohols. We hypothesized that an anionic ring-opening to eliminate the C-O bond of the OBD would circumvent formation of the undesired regioisomer. Applying a modified version of Molander's conditions (Scheme 3B) to 18 gave recovered 18 and the naphthalene 21 in a 6:1 ratio. While the production of 21 was mitigated using H2O as a cosolvent, ligation of H2O to SmI2 generated a mixture of reducing SmI2 species, which gave epoxide 22 and overreduction to 23. Use of unligated SmI2 in THF/MeOH gave no reaction. The Baran group used tris(pyrrolidino)phosphoramide (TPPA) as an alternative to HMPA as a ligand in a SmI2 electroreduction of arenes. Treatment of the actual substrate 16 with TPPA/SmI2 in THF/MeOH still gave competing overreduction and recovered starting material. Given the challenges with opening 18 or 16 in the desired manner, attention was turned to employing the exo-alkene 19 obtained in Scheme 3A as the starting OBD. Gratifyingly, treatment of 19 with TPPA/SmI2 in THF/MeOH (Scheme 3C) gave remaining 19 and the desired 20 in a 1.6:1.0 ratio with no observed overreduction or aromatization. The more functionalized 26 gave no product, likely due to the empty p orbital on B. However, anisole 27 gave a 27% yield of the desired 28, along with 13% of the isomer 29 and 19% remaining 27. Further optimization was not carried out at this point, but will be pursued in the application of this strategy to the synthesis of other anthracycline glycosides and their analogues.