Substituent‐Controlled Regiodivergent Palladium‐Catalyzed Annulative Dearomatization of Phenols toward Skeletally Diverse Spirocyclohexadienones

Abstract

A palladium‐catalyzed intermolecular dearomative formal [4+2] annulation of phenols with propargyl electrophiles is reported, enabling substituent‐controlled regiodivergent synthesis of a wide range of skeletally diverse spirocyclohexadienones with good yields. The regiodivergence could be precisely controlled by adjusting the steric hindrance of O‐ and N‐substituents from binucleophilic substrates, where substrates with an O‐nucleophilic site were converted into spiro[chromane‐4,1′‐cyclohexane]‐2′,5′‐dien‐4′‐ones with complete regioselectivity and (Z)‐selectivity, whereas N‐nucleophiles enabled a different regiodivergent process to access spiro[cyclohexane‐1,4′‐quinoline]‐2,5‐dien‐4‐ones.

Dearomative spiroannulation of indoles enabled by the diaza-[1,2]-Wittig rearrangement

“…8,9 Among many synthetic methods, intramolecular dearomative cyclization of indole derivatives represents a practical strategy (Scheme 1B), as it can directly develop molecular complexity from planar starting materials. 10–24 Although impressive, this protocol suffers from multi-step synthesis of C3-functionalized indoles and typically relies on metal catalysis and/or external oxidants. In this context, dearomative spiroannulation (DSA) of readily available C3-unfunctionalized indoles is considered a straightforward alternative without laborious multistep synthesis (Scheme 1C).…”