NEW VERSATILE FLUORINATED CHIRAL BUILDING-BLOCKS - SYNTHESIS AND REACTIVITY OF OPTICALLY PURE ALPHA-(FLUOROALKYL)-BETA-SULFINYLENAMINES

Efficient synthesis of optically pure alpha-(fluoroalkyl)-beta-sulfiny l enamines has been achieved by aza-Wittig reaction of triphenyliminop hosphoranes with the corresponding alpha-fluorinated-alpha'-sulfinyl k etones. The title compounds 3,4 showed an overwhelming preference for the Z stereochemistry of the enamine form. Their general reactivity ha s been studied. The reaction with some electrophiles (i.e. benzyl chlo roformate and benzyl and allyl bromide) occurs at the nitrogen atom pr oviding the corresponding N,N-disubstituted enamines. Nucleophiles add smoothly to C-2: heteroatom-centered nucleophiles like methanol, ammo nia, and thiophenol afford gem-disubstituted derivatives under thermod ynamic control, while a C-centered nucleophile like nitromethane adds in irreversible fashion. The hydride- and deuteride-promoted reduction of 3,4 to the N-Cbz-protected (14) and N-unprotected (15) alpha-fluor inated-alpha'-sulfinyl amines has been studied. Hydride addition was s tereoselective, while low stereoselection was obtained with the other tested nucleophiles. Desulfurization of the optically pure 1,1,1-trifl uoro-3-sulfinyl amine 15a afforded (R)-1-(trifluoromethyl)ethylamine 1 7. The Pummerer rearrangement of 14 occurs in an unusual nonoxidative way affording the sulfenamide 24, that readily provided (R)-(2-H)- and -(2-D)-3,3,3-trifluoroalaninol (19) and (R)-3,3,3-trifluoroalanine (2 2).