Base-Promoted Diastereoselective Addition of 2-Aryloxy-2-Fluoroketones to N-(tert-Butylsulfinyl)Imines

The asymmetric construction of a quaternary fluorine-containing stereogenic carboncenter is highly valuable for the development of fluoroine-containing bioactive molecules. Herein, a base-promoted, diastereoselective Mannich-type reaction of 2-aryloxy-2-fluoroketones with N-(tert-butylsulfinyl)imines has been developed. A number of the addition products featuring a fluorinated quaternary stereocarbon centre and a beta-fluoroamine structural motif have been readily obtained in good yields with moderate to good diastereoselectivities. The absolute configuration of the major diasteromer was determined by X-ray crystallography analysis, and a closed transition-state mode was proposed to explain the stereochemical outcome of this reaction. In addition, the addition product was efficiently converted into a alpha-fluoro-beta-amino alcohol through desulfinylation followed by reduction of the carbonyl group.