Appendage planning should be an important guiding principle for reaction development as without this, the synthetic utility of painstakingly established protocols can be seriously compromised. Indeed, unintended appendages from the directing groups and/or coupling partners have been frequently stuck in the heterocyclic skeletons: they not only are relatively inert to designated transformations but also can completely block the inherent high reactivity of ring atoms. Considering the thoroughly demonstrated enormous synthetic power from the heterocyclic ring atoms, a synthetically useful approach to reaction development is skeleton-oriented synthesis (SOS): SOS refers to a traceless appendage planning synthetic strategy for fabricating molecular skeletons without unintended appendages from the reactivity-assisting groups and using, subsequently, the reactivity of exposed ring atoms for attaching intended appendages.