Сherednichenko A. Asymmetric functionalization of N-(tert-butylsulfinyl) polyfluoroalkyl imines

The dissertation is devoted to the synthesis of N-(tert-butylsulfinyl) polyfluoroalkyl imines and investigation of their synthetic potential as building blocks for obtaining optically pure acyclic and heterocyclic compounds. A preparative approach to (R)- and (S)-N-(tert-butylsulfinyl)imines of trifluoropyruvate was developed based on condensation of commercially available methyl trifluoropyruvate with optically pure enantiomers of Ellman's sulfinamide. It was proved that this synthetic method can be scaled up to generate multigram quantities of the imines. A detailed examination of reducing agents for chemo- and stereoselective reduction of the azomethine bond of the obtained N-(tert-butylsulfinyl) trifluoromethyl iminoesters demonstrated that stereochemical outcome of the process depends on the nature of the reductant. It is established that the reaction of N-(tert-butylsulfinyl)imines of trifluoropyruvate with nitromethane is a convenient instrument for the C-C bond construction at the stereogenic azomethine carbon atom, and allows to obtain enantiomerically pure α-trifluoromethyl-substituted β-nitro-α-aminocarboxylates. The efficacy of the aza-Henry reaction in the synthesis of enantiomerically enriched fluorine-containing compounds was also established on the example of the reactions with N-(tert-butylsulfinyl) polyfluoroalkyl aldimines, bearing CF3, C2F5, HC2F4, and BrCF2 groups. The attractiveness of the obtained β-nitroamides as precursors of synthetically interesting optically pure fluorine-containing 1,2-diamines was demonstrated by successful removal of the sulfinyl function and Pd-catalyzed hydrogenation of the nitro group. Cyclization of 1,2-diamines and α,β diaminocarboxylates leads to biologically interesting polyfluoroalkyl imidazolidinones, mono- or disubstituted at the 4-position of the ring. The course of the Mannich reaction of N-trimethylsilyl and N tert butylsulfinyl imines of trifluoropyruvate with acetone was investigated. It is shown that functionalization of N-(tert-butylsulfinyl)imines of trifluoropyruvate with arylmagnesium bromides (Ar = Ph, 4-MeOC6H4) proceeds regio- and stereoselectively, resulting in addition to the azomethine carbon atom and quantitative formation of chiral α-aminocarboxylates. Alternatively, stereoselectivity of the reaction with alkylmagnesium bromides depends on the nature of the solvent, and the best results are achieved while using dichloromethane. Optically pure trifluoromethyl amino esters were easily transformed into corresponding functionalized amino acids under mild conditions – by hydrolysis of the ester group with lithium hydroxide and following removal of the sulfinyl function with solution of hydrogen chloride in diethyl ether. Additionally, the obtained aminocarboxylates were proved to be convenient precursors of enantiomerically pure morpholines, containing a trifluoromethyl group and aryl or alkyl substituents at the 3-position. It is found that addition of push-pull enamines to trifluoromethyl N (tert butylsulfinyl)iminocarboxylates involves only β-position of the enamine. Further cyclization of the addition products occurs at room temperature and leads to non-racemic pyrrolones, isolated with preparative yields.