Catalytic Asymmetric 1,3‐Dipolar Cycloaddition of β‐Fluoroalkylated α,β‐Unsaturated 2‐Pyridylsulfones with Nitrones for Chiral Fluoroalkylated Isoxazolidines and γ‐Amino Alcohols

다국어 초록 (Multilingual Abstract)

2‐Pyridylsulfone‐ and fluoroalkylated group‐activated olefins underwent highly efficient diastereo‐ and enantioselective 1,3‐dipolar cycloadditions across various aromatic and aliphatic nitrones in the presence of a chiral NiII/bis(oxazoline) catalyst. The process was tuned by 4 Å molecular sieves, chiral bis(oxazoline) ligands, reaction solvents, and temperature. A wide array of optically pure fluoroalkylated isoxazolidines were obtained, thus facilitating the asymmetric synthesis of an enantioenriched α‐trifluoromethylated γ‐amino alcohol in gram‐scale and a trifluoromethylated derivative of 1,3‐oxazinan‐2‐one with potential pharmaceutical interest. A stereochemical model, based on the absolute configuration of one adduct and some control experiments, was postulated to account for the observed endo‐ and enantioselectivity.
Präparativ wertvoll: Die Ni(ClO4)2/L1‐katalysierte asymmetrische Cycloaddition von Nitronen und β‐fluoralkylierten Vinyl‐2‐pyridylsulfonen wird beschrieben. Enantiomerenangereicherte fluoralkylierte Isoxazolidine wurden in hohen Ausbeuten mit exzellenten Diastereo‐ und Enantionselektivitäten gebildet und anschließend in einen α‐trifluormethylierten γ‐Aminoalkohol und ein 1,3‐Oxazinan‐2‐on umgewandelt.