Catalytic 1,2- and 1,1-Carbocyclization of Alkenes Employing Adamantanols as Tertiary Carbocation Precursors

Catalytic alkene cyclization initiated by carbon electrophiles represents an emerging strategy for constructing valuable and challenging molecular architectures. However, due to reactivity issues, the realization of such reactions with tertiary carbon electrophiles remains a formidable challenge. Herein, we report an efficient Brønsted acid-catalyzed system that overcomes this limitation. Using 1-adamantanols as precursors of tertiary carbocation electrophiles, and through TfOH catalysis, alkenes tethered with carboxyl, sulfonamide, and hydroxyl groups, including those with relatively low reactivity such as alkyl-substituted and terminal alkenes, can be converted into a variety of adamantylated heterocycles in hexafluoroisopropanol with good yields via 1,2-addition or formal 1,1-addition, with high regio- and stereoselectivity. The products serve as versatile synthetic building blocks and can be readily transformed into valuable adamantyl-containing compounds, including derivatives with anti-influenza A activity. Density functional theory (DFT) calculations and control experiments indicate that the moderate electrophilicity of the adamantyl carbocation and the hyperconjugative effect of the adamantyl group in stabilizing carbocations form the basis for achieving the electrophilic cyclization. Additionally, they also reveal that different nucleophilic groups can influence the progression of the reaction. These findings provide references for the design of new electrophilic reactions.