Work

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

Year: 2025

Type: article

Abstract: 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.

Source: Green Synthesis and Catalysis

DOI: 10.1016/j.gresc.2025.03.003