Synthesis of enantiomerically pure 4-polyfluoromethyl-4-hydroxy-homoprolines by intramolecular cyclization of 6-amino-5-polyfluoromethyl-hex-2-enoic acids

• The first synthesis of racemic and enantiopure 4-polyfluoromethyl-4-hydroxy-homoprolines.
• The synthesis of polyfluoromethyl containing 6-aminoacrylates.
• The example of intramolecular heterocyclization under acidic conditions.

An effective route to racemic and enantiopure 4-polyfluoromethyl-4-hydroxy-homoprolines was developed based on readily available 2-alkoxyvinyl-polyfluoromethyl ketones. Key step of the synthesis was a diastereoselective heterocyclization of 6-amino-5-polyfluoromethyl-hex-2-enoic acids under acidic conditions. The absolute configuration of the stereogenic centers was determined by X-ray.

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