Regio- and Stereoselective Hexafluoroisopropoxylation and Trifluoroethoxylation of Allenamides

Abstract

Incorporating fluorinated moieties into organic molecules is an attractive strategy to enhance drug-like properties. Herein, we have developed a simple and self-promoted protocol for hexafluoroisopropoxylation and trifluoroethoxylation of allenamides with fluorinated alcohols such as HFIP and TFE. The reaction provided the fluoroalkoxylated products in a regio-and stereoselective manner in good to moderate yields under mild conditions.

Hexafluoroisopropanol (HFIP)-Mediated Intramolecular Cyclization of Allenamides To Access C1-Vinyl Tetrahydro-β-carbolines

“…The Baidya group recently reported a para -selective allylation of anilines with aryl allenes in combination with Mg(OTf) 2 in HFIP . The Park group implemented the regioselective hydroamination of allenamides promoted by HFIP and NaOAc. , Our group recently achieved the metal-free hexafluoro­isopropoxylation of allenamides . In this work, we report metal-free HFIP-mediated intramolecular cyclization of N-allenyl-tryptamines to access C1-vinyl substituted THβCs (Figure c).…”

“…In a previous study, our group achieved the hexafluoro­isopropoxylation of N-allenamides, wherein HFIP acts as a promotor, solvent, and nucleophile. To our surprise, when tryptamine-derived N-allenamide 1a was subjected to these metal-free conditions ( 1a in HFIP solvent under N 2 at rt), an interesting cyclized product 2a was obtained in 78% NMR yield instead of the expected hexafluoro­isopropoxylated product 3a (Table , entry 1).…”