Researchers in China have unveiled a breakthrough synthetic method for creating bicyclo[1.1.1]pentane ketones, a molecular structure with significant potential in pharmaceutical design. The novel technique uses visible light and tert-butyl hydrogen peroxide to generate acyl radicals, enabling the creation of complex molecular structures at room temperature with moderate to high yields.
The research addresses longstanding challenges in medicinal chemistry by providing a streamlined approach to replacing traditional benzene rings with three-dimensional cyclo[n.1.1]alkanes. Since the 1990s, scientists have recognized that such molecular transformations can enhance drug properties like solubility and metabolic stability while circumventing patent restrictions.
Led by researcher Fener Chen, the study demonstrates a metal-free method that successfully synthesizes bicyclo[1.1.1]pentane-ketones under mild conditions. Notably, the technique tolerates oxidation-sensitive chemical groups, including amino, methylthio, and ferrocene substituents, expanding its potential applications in molecular design.
Mechanistic studies confirmed the critical role of tert-butyl hydrogen peroxide in the reaction, with high-resolution mass spectrometry and radical trapping experiments validating the radical-based mechanism. The researchers successfully synthesized a molecule incorporating two bicyclo[1.1.1]pentane rings, a first in the field.
This innovative approach represents a significant advancement in synthetic chemistry, offering researchers a more flexible and efficient method for creating complex molecular structures with potential implications for drug development, materials science, and advanced molecular engineering.
