Visible light induced synthesis of the Benzoyl bioisosteres: bicyclo[1.1.1]pentane-ketone group

Benzoyl groups are commonly found in the structures of various pharmaceuticals, including non-steroidal anti-inflammatory drugs (NSAIDs), central nervous system stimulants, antihyperlipidemic agents, and hypnotics. Bicyclo[1.1.1]pentane-ketone group can serve as bioisostere for benzoyl groups, enhancing 3D spatial complexity, reducing off-target effects, and improving lipophilicity and solubility of the drug molecules. Herein, we present a visible light-induced approach for the synthesis of bicyclo[1.1.1]pentane-ketone, characterized by mild reaction temperature and excellent tolerance to oxidation-sensitive substituents such as -NH 2 , -methylthio and ferrocenyl group. The method delivers all products in moderate to high yields. Mechanistic studies revealed the formation of t Butyl-bicyclo[1.1.1] pentane ether explained the requirement for stoichiometric amounts of t BuOOH rather than catalytic quantities, in despite of the redox-neutral nature of this reaction. An one-step visible light-induced method was developed for the synthesis of acyl bicyclo[1.1.1]pentanes, notable for its mild reaction conditions and excellent compatibility with oxidation-sensitive substituents. Mechanistic studies revealed the formation of a t BuOOH-propellane adduct, highlighting the requirement for stoichiometric amounts of t BuOOH rather than catalytic quantities in the reaction.