Benzyne Platform: A Strategic Approach to Developing Novel Intramolecular Reactions

This paper describes the development of novel “benzyne platform” molecules and their applications in discovering unique intramolecular reactions. Two types of benzyne precursors for silicon tethering were designed to facilitate the assembly of various arynophiles through Si-O bond formation. Using these platforms, we discovered three intramolecular reactions: (1) (4＋2) cycloaddition with phenolates to construct benzovalerene scaffolds, (2) ene reaction with propargyl amides to synthesize allenes and allenamides, and (3) (3＋2) cycloaddition with ynamides to form indoles. The molecular design effectively suppressed undesired side reactions commonly observed in corresponding intermolecular reactions, enabling the discovery of unique reactivities and selectivities specific to intramolecular settings.