Trisubstituted 2‑Trifluoromethyl Pyrrolidines via Catalytic Asymmetric Michael Addition/Reductive Cyclization

• Published in: Organic letters Vol. 16; no. 9; pp. 2362 - 2365
• Main Authors: Corbett, Michael T., Xu, Qihai, Johnson, Jeffrey S.
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 02.05.2014; Amer Chemical Soc
• Subjects: Catalysis; Chemistry; Chemistry, Organic; Cyclization; Hydrocarbons, Fluorinated - chemical synthesis; Hydrocarbons, Fluorinated - chemistry; Hydrogenation; Letter; Molecular Structure; Physical Sciences; Pyrrolidines - chemical synthesis; Pyrrolidines - chemistry; Science & Technology; KETONES; (S)-ALPHA-TRIFLUOROMETHYL-PROLINE; 1,3-DICARBONYL COMPOUNDS; ENANTIOSELECTIVE CONJUGATE ADDITION; 1,3-DIPOLAR CYCLOADDITION; CONSTRUCTION; AZOMETHINE YLIDES; FLUORINE; NITROALKENES; TRIFLUOROMETHYLATION
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol500679w

The stereoselective synthesis of trisubstituted 2-trifluoromethyl pyrrolidines by asymmetric Michael addition/hydrogenative cyclization is described. The direct organocatalytic addition of 1,1,1-trifluoro­methyl­ketones to nitroolefins proceeds under mild reaction conditions and low catalyst loadings to provide Michael adducts in high yield with excellent diastereo- and enantioselectivity. Catalytic hydrogenation of the Michael adducts stereoselectively generates 2-tri­fluoro­methylated pyrrolidines bearing three contiguous stereocenters. A stereospecific route to epimeric 2-tri­fluoro­methyl pyrrolidines from a common intermediate is described.