Catalytic Enantioselective Michael Addition Reactions of Tertiary Enolates Generated by Detrifluoroacetylation

Abstract

This work describes, for the first time, Michael addition reactions of tertiary fluoro-enolates in situ generated by detrifluoroacetylation with 1-(1-(phenylsulfonyl) vinylsulfonyl)benzene. Excellent enantioselectivity and chemical yields were achieved with application of catalysts (10 mol %) derived from Cu(OTf) and (1S,2S)-1,2-diphenylethane-1,2-diamine. These reactions show a considerable degree of structural generality and allow the preparation of new types of biologically relevant molecules that contain quaternary C-F stereogenic carbon atoms and feature five-, six-, or seven-membered rings as well as heterocyclic 3-fluoro-2,3-dihydrochromen-4-one moieties.

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

“…It should be pointed out that amides 25 represent a combination of two SDE-phoric groups, -CF 3 and -CONH-, leading to strong homo-and heterochiral intermolecular interactions-the foundation of the SDE phenomenon. Considering literature data [87,[123][124][125] and our own experience in the synthesis and properties of fluoro-organic compounds, in particular, catalytic enantioselective reactions [167][168][169][170][171][172][173], we can confidently conclude that practitioners working with -CF 3 -containing compounds should be ready to encounter noticeable magnitudes of the SDEvC (i.e., ∆ee >5%).…”

Divergent Reactivity of gem-Difluoro-enolates toward Nitrogen Electrophiles: Unorthodox Nitroso Aldol Reaction for Rapid Synthesis of α-Ketoamides

“… , They are readily prepared in large quantities and offer convenient access to gem -difluoro-enolates under mild conditions. Currently, aldol, Mannich, halogenation, and sulfenylation processes of these in situ generated fluoro-enolates have been explored. , However, systematic investigation with electrophilic aminating agents that could potentially offer fluorinated α-amino ketones, a high-value synthon and novel structural motif, remains underdeveloped.…”

Detrifluoroacetylative in Situ Generated Cyclic Fluorinated Enolates for the Preparation of Compounds Featuring a C–F Stereogenic Center

“…However, no positive results were obtained in these reactions. 21 Then, (ethene-1,1-diyldisulfonyl)dibenzene ( 23 ) was used as a Michael acceptor to react with hydrates 1 under the Cu-catalyzed conditions. 5 After careful scan of the chiral ligands, (1 S ,2 S )-1,2-diphenylethane-1,2-diamine 24 , bearing a sterically bulky anthracenyl group, was demonstrated to be the best in catalyzing the reaction with 2-fluoro-2-(2,2,2-trifluoro-1,1-dihydroxyethyl)-3,4-dihydronaphthalen-1(2 H )-one ( 1a ).…”