Gem-Difluorination of α-Diazo Amides Using (Difluoroiodo)toluene

Abstract

Fluorination chemistry is a branch of study that appeals to the pharmaceutical and agricultural industries. Drawbacks of popular methods of forming carbon-fluorine bonds include high cost or hazardous conditions that are often associated with some of these reagents. A less explored route to organofluorine substrates can be achieved through hypervalent iodine compounds, such as (difluoroiodo)toluene (TolIF2). There is large interest in these compounds because of their mild reactivity, relatively inexpensive production, and environmentally benign by-products. Previously disclosed by the Murphy group is the α-carbonyl difluorination of phenyldiazoacetate compounds using (difluoroiodo)toluene to furnish gem-difluorinated products. Detailed in this report is an extension of the work established by Murphy et al. in the synthesis of 3,3-difluoro-2-oxindole compounds starting from diazo oxindoles. Studies were also performed on tosylhydrazone, hydrazone and dithiane derivatives of oxindole. In addition, the fluorination protocol was used to synthesize N,N-dimethyl-p-nitrophenyldifluoroacetamide from its corresponding α-diazo amide. Finally, strategies towards the synthesis of other phenyldiazoacetamides are discussed in this thesis.