Indole Ring Expansion with TMSCCl3/TMSCBr3

The conventional reaction development wisdom of reactivity speciation frequently perceives reactants as a static supply pool of definitive reactivity-matching reactive units for the deterministic pathway to a specific product, leading to the fixed exposure of severely confined reactivity pattern scope. Reactivity adaptation speciation is proposed herein as a transformative synthetic practice appreciating reactants as a dynamic supply pool of shifting reactive units for opportunistic reactivity-matching diverse-manifold pathways to varied products, allowing for the generative revelation of significantly expanded reactivity pattern scope. Through reactivity adaptation speciation and with indole and TMSCCl3/TMSCBr3 as the reactants, the hitherto elusive reactivity patterns of C2=C3–CCl/CBr insertion ring expansion of indole to quinoline, N1-H–TMS nucleophilic substitution for TMS protection of indole, and N1-H–CCl3 nucleophilic substitution into orthoformamide have been discovered. The C2=C3–CCl/CBr insertion ring expansion endows quinoline with a convenient CCl/CBr synthetic handle for versatile structural elaboration. The synthetic diversity exemplified herein promises reactivity adaptation speciation as a powerful enabling tool for the productive proliferation of reactivity patterns.