Catalytic Asymmetric 1,3-Dipolar Cycloaddition of beta-Fluoroalkylated alpha,beta-Unsaturated 2-Pyridylsulfones with Nitrones for Chiral Fluoroalkylated Isoxazolidines and gamma-Amino Alcohols

摘要

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 Ni-II/bis(oxazoline) catalyst. The process was tuned by 4 angstrom 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 -trifluoromethylated -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.