Carmela Zappalà

A new versatile fluorinated C4 chiron

Abstract Optically pure 2-(fluoromethyl)-2-[(4-methylphenylsulphinyl)methyl]oxirane has been obtained in good yield and with high d.e. by reacting diazomethane with optically pure 1-fluoro-3-(4-methylphenylsulphinyl)propan-2-one. Regio- and stereo-selective openings of oxirane ring performed with selected nucleophiles afforded several useful derivatives.

Synthesis of fluorinated chirons: Stereoselective oxirane formation by reaction of diazomethane on 1-fluoro-3-arylsulfinyl-2-propanone and ring opening by selected nucleophiles

Abstract (R)-1-fluoro-3-[(4-methylphenyl)sulfinyl]-2-propanone (1) reacts with diazomethane affording (S)-2-(fluoromethyl)-2-[(R)-(4-methylphenyl)sulfinyl]methyl oxirane (2) as the main product. The influence of reaction conditions (solvent, temperature) on the chemo-and stereoselectivity has been studied. Several elaborations of 2, including reactions on the chiral auxiliary and opening of the oxirane ring by carbon, nitrogen, oxygen, phosphorus and halogen nucleophiles, are described. Full structural elucidation of the products is provided.

Introduction of nitrogen functionalities into (R)-1-fluoro-3-(p-tolylsulfinyl)propan-2-one

Abstract Nitrogen functionalities have been introduced on C-2 and C-3 of ( R )-1-fluoro-3-( p - tolylsulfinyl)propan-2-one ( 1 ) through high yield elaborations of the carbonyl and sulfinyl groups, respectively.

Unusual Trifluoroacetic Anhydride Promoted Fragmentation of a γ,γ,γ-Trifluoro-β-(p-methoxyphenyl-amino) Sulfoxide†

The reaction of a γ,γ,γ-trifluoro-β-(p-methoxyphenylamino) sulfoxide with trifluoroacetic anhydride under Pummerer conditions occurs in an abnormal fashion, providing an excellent yield of the cyclic six-membered sulfonium salt arising from intramolecular interception of the usual trifluoroacetoxy-sulfonium intermediate by the electron rich p-methoxyphenyl group.

Synthesis of enantiomerically pure, nitrogen substituted fluoroorganic compounds

Abstract Differently substituted β-keto-t-fluoro-sulfoxides can be easily obtained in enantiomerically and diastereoisomerically pure form through acylation of homochiral alkyl-aryl sulfoxides with the esters or salts of fluorocarboxylic acids. The aminative reduction of the carbonyl group and a properly modified Pummerer rearrangement are the key steps which allow to introduce a nitrogen residue in two different positions of these fluoro-keto-sulfoxides. For instance, starting from the (R)-3- fluoro-1-(4-methylphenyl)sulfinyl acetone 1, these two reactions afford, after further elaboration, the (R)-1-fluoro-2-benzyl- aminopropane 2 and the (R)-3-fluoro-2-benzyloxypropylhydroxyl- amine 3, respectively. Several other examples of similar reactions will be reported. The absolute configuration of the obtained compounds has been assigned in all cases. The diastereoselectivity of processes will be discussed.

Synthesis of an optically pure 2-(fluoromethyl)oxirane by highly diastereoselective transfer of methylene from diazomethane

Abstract As part of a program directed towards developing an asymmetric approach to fluorosubstituted organic molecules 1 , we have observed an efficient transfer of chirality from sulphur to the central carbon atom when chiton 1 is reacted with diazomethane. 2-(Fluoromethyl)-2-[(4- methylphenylsulphinyl)methyl]oxirane 2 was obtained in good yield and with high d.e.: 2-(Fluoromethyl)oxirane 2 , whose crystal and molecular structure will be provided, as well as 2-(chloromcthyl)- and 2-(bromomethyl)- analogs, prepared in the same way, can be considered as a potential carbinols bearing three differently functionalized methylens, each one with a distinct reactivity. Some synthetically useful elaborations of 2 , i.e. transformation of the sulphinyl chiral auxiliary into other functional groups and regioselective opening of the oxirane ring to give derivatives as 3 , will be presented. A possible explanation of the observed diastereoselection, as well as the influence on the reaction outcome of electron-withdrawing groups in α to the carbonyl of the starting ketone will be discussed.