Abstract

Enabling Divergent Reaction Pathways of R-22 Gas in Continuous Flow

Wai Chung Fu, Assistant Professor, City University of Hong Kong

The difluoromethyl (CF2H) group and other fluoroalkyl moieties are demonstrated to enhance the biological properties for pharmaceuticals and agrochemicals, such as bioavailability, metabolic stability, and lipophilicity.  However, many fluoroalkylation reagents are often toxic, expensive, exhibit low atom economy, or require multiple synthetic steps to prepare.  In this discussion, we explore the use of atom-efficient and cost-effective R-22 gas (ClCF2H) in continuous flow, highlighting flow technologies that enable previously improbable reaction conditions and selectively direct the reaction pathways of ClCF2H.  In the first two studies, unstable difluorinated oxaphosphetane and difluorocarbenes are generated in-line and are immediately consumed to provide diverse classes of CF2D-containing molecules. Recently, we also demonstrated the first gas-to-gas organic synthesis in flow, in which difluoromethyl azide gas (HCF2N3) is generated on-demand from ClCF2H, and is then used in cycloadditions to prepare N-CF2H triazoles.