Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

Area of Science:

• Organic Chemistry
• Fluorine Chemistry
• Asymmetric Synthesis

Background:

• Chiral fluorinated compounds are crucial building blocks in pharmaceuticals and materials.
• Efficient methods for constructing chiral centers with fluorine substituents are highly sought after.

Purpose of the Study:

• To develop a novel synthetic route for optically active tetrafluoroethylenated amides.
• To investigate the [1,3]-proton shift reaction for chirality transfer in these systems.

Main Methods:

• Treatment of (R)-N-(2,2,3,3-tetrafluoropent-4-en-1-ylidene)-1-phenylethylamine derivatives with DBU (1,8-Diazabicyclo[5.4.0]undec-7-ene).
• Acid hydrolysis and N-Cbz protection of the rearranged products.
• Analysis of chirality transfer and yields.

Main Results:

• A smooth [1,3]-proton shift reaction occurred with high chirality transfer.
• Optically active tetrafluoroethylenated amides were obtained in moderate three-step yields.
• The reaction proceeded efficiently under mild conditions (room temperature to 50 °C).

Conclusions:

• The developed method provides a viable route to chiral tetrafluoroethylenated amides.
• The [1,3]-proton shift reaction is effective for preserving and transferring chirality.
• This approach offers a valuable tool for accessing complex fluorinated molecules.