The synthesis of polyfluoroalkyl substituted pyrroles as building blocks for obtaining fluorinated pyrrolidine-containing alkaloids

Abstract

Aim. To study the synthetic potential of cyclization of N-(β-polyfluoroacyl)vinyl derivatives of proline and N-substituted glycines into polyfluoroalkyl pyrroles, which are useful intermediates to fluorinated pyrrolidine alkaloids. Results and discussion. N-(β-Polyfluoroacyl)vinyl derivatives of proline and N-substituted glycines have been obtained and transformed to polyfluoroalkyl-containing pyrroles using acetic or trifluoroacetic anhydride. Experimental part. N-(β-Polyfluoroacyl)vinyl derivatives of proline and N-substituted glycines were obtained from β-alkoxyvinyl polyfluoroalkyl ketones and the corresponding amino acids. The enaminones so obtained were transformed to polyfluoroalkyl-containing pyrroles with acetic or trifluoroacetic anhydride. The structure and composition of the compounds synthesized were proven by the data of 1Н and 19F NMR spectroscopy and elemental analysis. Conclusions. It has been shown that an increase of steric hindrance in N-(β-polyfluoroacyl)vinyl derivatives of proline (the perfluoroethyl group instead of the trifluoromethyl group) and N-substituted glycines (replacement of the N-methyl group with the N-benzyl group) gives mainly polyfluoroacyl pyrrolyl acetates when heating in acetic anhydride. Polyfluoroalkyl-containing pyrroles have been obtained by treatment of N-(β-polyfluoroacyl)vinyl derivatives of proline and glycine with trifluoroacetic anhydride.

Keywords

• enones
• amino acids
• enaminones
• cyclization
• polyfluoroalkyl pyrroles