One-pot synthesis and theoretical calculation for trifluoromethylated pyrrolizidines by 1,3-dipolar cycloaddition with azomethine ylides and β-trifluoromethyl acrylamides

•A new one-pot synthesis of trifluoromethylated pyrrolizidines was developed.•High diastereoselectivity (d.r. ≥ 20/1) was observed in most of cases.•The chemoselectivity is overcome by the separate addition of reagents.•The origin of regio- and stereoselectivity were investigated by DFT calculation.

The reaction with β-trifluoromethyl acrylamide 3e and azomethine ylides generated from l-proline and several aldehydes provided the corresponding trifluoromethylated pyrrolizidines with excellent diastereoselectivity (>20/1) in all cases and moderate regioselectivity (up to 1/5.9). A DFT calculation was also examined to reveal the origin of these stereoselectivities.

Graphical abstractThe reaction with β-trifluoromethyl acrylamide 3e and azomethine ylides generated from l-proline and several aldehydes provided the corresponding trifluoromethylated pyrrolizidines with excellent diastereoselectivity (>20/1) in all cases and moderate regioselectivity (up to 1/5.9). A DFT calculation was also examined to reveal the origin of these stereoselectivities.Figure optionsDownload full-size imageDownload as PowerPoint slide