Access to 2-Alkyltropones via Organic Base-Catalyzed Tandem Deamination and Aldol Condensation of Tropinone-Derived Quaternary Ammonium Salts.

ABSTRACT

The tropone skeleton exists in a number of natural products and bioactive substances, and currently, the applications of substituted tropones are significantly limited by their preparative methods. Herein, we report a very convenient method to access 2-alkyltropones via organic base-catalyzed tandem reaction of tropinone-derived quaternary ammonium salts. Tropinone methiodide reacted with a wide variety of aromatic and aliphatic aldehydes in the presence of 1,4-diazabicyclo[2.2.2]octane to afford structurally diverse 2-alkyltropones in moderate to excellent yields with extremely high site selectivity. The reaction employs readily available feedstocks and reagents, is free of transition metals and compatible with water and air, tolerates a variety of functional groups, and can be easily scaled up. Moreover, the products are amenable to various synthetic transformations. Preliminary mechanistic studies revealed that the reaction proceeded via tandem deamination, aldol condensation, and isomerization.