Pd/BINAP/Peroxide‐Enabled Relay Multicomponent Reactions

In recent years, multicomponent reactions have attracted considerable attention due to their efficiency in constructing complex molecules from simple starting materials. Herein, we report a BINAP/peroxide‐controlled Pd‐catalyzed multicomponent reaction involving readily accessible indoles, diazo compounds, and allylic electrophiles, enabling the efficient synthesis of structurally diverse N‐functionalized indoles bearing aza‐quaternary carbon centers, which are prevalent in bioactive molecules and pharmaceuticals. This approach exhibits broad functional group tolerance and excellent regioselectivity for N–H sites, especially applicable to unsubstituted indoles. We have further demonstrated the synthetic utility of the resulting products through various derivatizations, including a concise four‐step synthesis of a mineralocorticoid receptor antagonist to treat aldosterone‐mediated diseases. Mechanistic experiments indicated that this reaction was enabled by a relay catalysis based on Pd^II/Pd^II non‐redox and Pd⁰/Pd^II redox catalytic cycles, which was found to facilitate the activation of carbene and allylic substrates, respectively. The addition of peroxide was found to suppress the premature formation of [Pd⁰(BINAP)] species and keep palladium in the [Pd^II(BINAP)(OAc)₂] form at the beginning of the reaction, thereby avoiding the formation of undesired indole allylation by‐products and significantly increasing the overall yields of the target products.